Identification of linker regions and domain borders of the transcription activator protein NtrC from Escherichia coli by limited proteolysis, in-gel digestion, and mass spectrometry.

PubMed

Bantscheff, M; Weiss, V; Glocker, M O

1999-08-24

We have developed a mass spectrometry based method for the identification of linker regions and domain borders in multidomain proteins. This approach combines limited proteolysis and in-gel proteolytic digestions and was applied to the determination of linkers in the transcription factor NtrC from Escherichia coli. Limited proteolysis of NtrC with thermolysin and papain revealed that initial digestion yielded two major bands in SDS-PAGE that were identified by mass spectrometry as the R-domain and the still covalently linked OC-domains. Subsequent steps in limited proteolysis afforded further cleavage of the OC-fragment into the O- and the C-domain at accessible amino acid residues. Mass spectrometric identification of the tryptic/thermolytic peptides obtained after in-gel total proteolysis of the SDS-PAGE-separated domains determined the domain borders and showed that the protease accessible linker between R- and O-domain comprised amino acids Val-131 and Gln-132 within the "Q-linker" in agreement with papain and subtilisin digestion. The region between amino acid residues Thr-389 and Gln-396 marked the hitherto unknown linker sequence that connects the O- with the C-domain. High abundances of proline-, alanine-, serine-, and glutamic acid residues were found in this linker structure (PASE-linker) of related NtrC response regulator proteins. While R- and C-domains remained stable under the applied limited proteolysis conditions, the O-domain was further truncated yielding a core fragment that comprised the sequence from Ile-140 to Arg-320. ATPase activity was lost after separation of the R-domain from the OC-fragment. However, binding of OC- and C- fragments to specific DNA was observed by characteristic band-shifts in migration retardation assays, indicating intact tertiary structures of the C-domain. The outlined strategy proved to be highly efficient and afforded lead information of tertiary structural features necessary for protein design and engineering and for structure-function studies.

An event of alternative splicing affects the expression of the NTRC gene, encoding NADPH-thioredoxin reductase C, in seed plants.

PubMed

Nájera, Victoria A; González, María Cruz; Pérez-Ruiz, Juan Manuel; Cejudo, Francisco Javier

2017-05-01

The NTRC gene encodes a NADPH-dependent thioredoxin reductase with a joint thioredoxin domain, exclusive of photosynthetic organisms. An updated search shows that although most species harbor a single copy of the NTRC gene, two copies were identified in different species of the genus Solanum, Glycine max and the moss Physcomitrella patens. The phylogenetic analysis of NTRCs from different sources produced a tree with the major groups of photosynthetic organisms: cyanobacteria, algae and land plants, indicating the evolutionary success of the NTRC gene among photosynthetic eukaryotes. An event of alternative splicing affecting the expression of the NTRC gene was identified, which is conserved in seed plants but not in algae, bryophytes and lycophytes. The alternative splicing event results in a transcript with premature stop codon, which would produce a truncated form of the enzyme. The standard splicing/alternative splicing (SS/AS) transcripts ratio was higher in photosynthetic tissues from Arabidopsis, Brachypodium and tomato, in line with the higher content of the NTRC polypeptide in these tissues. Moreover, environmental stresses such as cold or high salt affected the SS/AS ratio of the NTRC gene transcripts in Brachypodium seedlings. These results suggest that the alternative splicing of the NTRC gene might be an additional mechanism for modulating the content of NTRC in photosynthetic and non-photosynthetic tissues of seed plants. Copyright © 2017 Elsevier B.V. All rights reserved.

Engagement of Arginine Finger to ATP Triggers Large Conformational Changes in NtrC1 AAA+ ATPase for Remodeling Bacterial RNA Polymerase

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

Chen, Baoyu; Sysoeva, Tatyana A.; Chowdhury, Saikat

The NtrC-like AAA+ ATPases control virulence and other important bacterial activities through delivering mechanical work to {sigma}54-RNA polymerase to activate transcription from {sigma}54-dependent genes. We report the first crystal structure for such an ATPase, NtrC1 of Aquifex aeolicus, in which the catalytic arginine engages the {gamma}-phosphate of ATP. Comparing the new structure with those previously known for apo and ADP-bound states supports a rigid-body displacement model that is consistent with large-scale conformational changes observed by low-resolution methods. First, the arginine finger induces rigid-body roll, extending surface loops above the plane of the ATPase ring to bind {sigma}54. Second, ATP hydrolysismore » permits Pi release and retraction of the arginine with a reversed roll, remodeling {sigma}54-RNAP. This model provides a fresh perspective on how ATPase subunits interact within the ring-ensemble to promote transcription, directing attention to structural changes on the arginine-finger side of an ATP-bound interface.« less

The contribution of NADPH thioredoxin reductase C (NTRC) and sulfiredoxin to 2-Cys peroxiredoxin overoxidation in Arabidopsis thaliana chloroplasts.

PubMed

Puerto-Galán, Leonor; Pérez-Ruiz, Juan M; Guinea, Manuel; Cejudo, Francisco Javier

2015-05-01

Hydrogen peroxide is a harmful by-product of photosynthesis, which also has important signalling activity. Therefore, the level of hydrogen peroxide needs to be tightly controlled. Chloroplasts harbour different antioxidant systems including enzymes such as the 2-Cys peroxiredoxins (2-Cys Prxs). Under oxidizing conditions, 2-Cys Prxs are susceptible to inactivation by overoxidation of their peroxidatic cysteine, which is enzymatically reverted by sulfiredoxin (Srx). In chloroplasts, the redox status of 2-Cys Prxs is highly dependent on NADPH-thioredoxin reductase C (NTRC) and Srx; however, the relationship of these activities in determining the level of 2-Cys Prx overoxidation is unknown. Here we have addressed this question by a combination of genetic and biochemical approaches. An Arabidopsis thaliana double knockout mutant lacking NTRC and Srx shows a phenotype similar to the ntrc mutant, while the srx mutant resembles wild-type plants. The deficiency of NTRC causes reduced overoxidation of 2-Cys Prxs, whereas the deficiency of Srx has the opposite effect. Moreover, in vitro analyses show that the disulfide bond linking the resolving and peroxidatic cysteines protects the latter from overoxidation, thus explaining the dominant role of NTRC on the level of 2-Cys Prx overoxidation in vivo. The overoxidation of chloroplast 2-Cys Prxs shows no circadian oscillation, in agreement with the fact that neither the NTRC nor the SRX genes show circadian regulation of expression. Additionally, the low level of 2-Cys Prx overoxidation in the ntrc mutant is light dependent, suggesting that the redox status of 2-Cys Prxs in chloroplasts depends on light rather than the circadian clock. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Conformational switching upon phosphorylation: a predictive framework based on energy landscape principles.

PubMed

Lätzer, Joachim; Shen, Tongye; Wolynes, Peter G

2008-02-19

We investigate how post-translational phosphorylation modifies the global conformation of a protein by changing its free energy landscape using two test proteins, cystatin and NtrC. We first examine the changes in a free energy landscape caused by phosphorylation using a model containing information about both structural forms. For cystatin the free energy cost is fairly large indicating a low probability of sampling the phosphorylated conformation in a perfectly funneled landscape. The predicted barrier for NtrC conformational transition is several times larger than the barrier for cystatin, indicating that the switch protein NtrC most probably follows a partial unfolding mechanism to move from one basin to the other. Principal component analysis and linear response theory show how the naturally occurring conformational changes in unmodified proteins are captured and stabilized by the change of interaction potential. We also develop a partially guided structure prediction Hamiltonian which is capable of predicting the global structure of a phosphorylated protein using only knowledge of the structure of the unphosphorylated protein or vice versa. This algorithm makes use of a generic transferable long-range residue contact potential along with details of structure short range in sequence. By comparing the results obtained with this guided transferable potential to those from the native-only, perfectly funneled Hamiltonians, we show that the transferable Hamiltonian correctly captures the nature of the global conformational changes induced by phosphorylation and can sample substantially correct structures for the modified protein with high probability.

Role of the σ 54 Activator Interacting Domain in Bacterial Transcription Initiation

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

Siegel, Alexander R.; Wemmer, David E.

Bacterial sigma factors are subunits of RNA polymerase that direct the holoenzyme to specific sets of promoters in the genome and are a central element of regulating transcription. Most polymerase holoenzymes open the promoter and initiate transcription rapidly after binding. However, polymerase containing the members of the σ 54 family must be acted on by a transcriptional activator before DNA opening and initiation occur. A key domain in these transcriptional activators forms a hexameric AAA + ATPase that acts through conformational changes brought on by ATP hydrolysis. Contacts between the transcriptional activator and σ 54 are primarily made through anmore » N-terminal σ 54 activator interacting domain (AID). To better understand this mechanism of bacterial transcription initiation, we characterized the σ 54 AID by NMR spectroscopy and other biophysical methods and show that it is an intrinsically disordered domain in σ 54 alone. In this paper, we identified a minimal construct of the Aquifex aeolicus σ 54 AID that consists of two predicted helices and retains native-like binding affinity for the transcriptional activator NtrC1. Using the NtrC1 ATPase domain, bound with the non-hydrolyzable ATP analog ADP-beryllium fluoride, we studied the NtrC1–σ 54 AID complex using NMR spectroscopy. We show that the σ 54 AID becomes structured after associating with the core loops of the transcriptional activators in their ATP state and that the primary site of the interaction is the first predicted helix. Finally, understanding this complex, formed as the first step toward initiation, will help unravel the mechanism of σ 54 bacterial transcription initiation.« less

Dissecting the role of NtrC and RpoN in the expression of assimilatory nitrate and nitrite reductases in Bradyrhizobium diazoefficiens.

PubMed

López, María F; Cabrera, Juan J; Salas, Ana; Delgado, María J; López-García, Silvina L

2017-04-01

Bradyrhizobium diazoefficiens, a nitrogen-fixing endosymbiont of soybeans, is a model strain for studying rhizobial denitrification. This bacterium can also use nitrate as the sole nitrogen (N) source during aerobic growth by inducing an assimilatory nitrate reductase encoded by nasC located within the narK-bjgb-flp-nasC operon along with a nitrite reductase encoded by nirA at a different chromosomal locus. The global nitrogen two-component regulatory system NtrBC has been reported to coordinate the expression of key enzymes in nitrogen metabolism in several bacteria. In this study, we demonstrate that disruption of ntrC caused a growth defect in B. diazoefficiens cells in the presence of nitrate or nitrite as the sole N source and a decreased activity of the nitrate and nitrite reductase enzymes. Furthermore, the expression of narK-lacZ or nirA-lacZ transcriptional fusions was significantly reduced in the ntrC mutant after incubation under nitrate assimilation conditions. A B. diazoefficiens rpoN 1/2 mutant, lacking both copies of the gene encoding the alternative sigma factor σ 54 , was also defective in aerobic growth with nitrate as the N source as well as in nitrate and nitrite reductase expression. These results demonstrate that the NtrC regulator is required for expression of the B. diazoefficiens nasC and nirA genes and that the sigma factor RpoN is also involved in this regulation.

Chloroplast redox homeostasis is essential for lateral root formation in Arabidopsis.

PubMed

Ferrández, Julia; González, Maricruz; Cejudo, Francisco Javier

2012-09-01

Redox regulation based on dithiol-disulphide interchange is an essential component of the control of chloroplast metabolism. In contrast to heterotrophic organisms, and non-photosynthetic plant tissues, chloroplast redox regulation relies on ferredoxin (Fd) reduced by the photosynthetic electron transport chain, thus being highly dependent on light. The finding of the NADPH-dependent thioredoxin reductase C (NTRC), a chloroplast-localized NTR with a joint thioredoxin domain, showed that NADPH is also used as source of reducing power for chloroplast redox homeostasis. Recently we have found that NTRC is also in plastids of non-photosynthetic tissues. Because these non-green plastids lack photochemical reactions, their redox homeostasis depends exclusively on NADPH produced from sugars and, thus, NTRC may play an essential role maintaining the redox homeostasis in these plastids. The fact that redox regulation occurs in any type of plastids raises the possibility that the functions of chloroplasts and non-green plastids, such as amyloplasts, are integrated to harmonize the growth of the different organs of the plant. To address this question, we generated Arabidopsis plants the redox homeostasis of which is recovered exclusively in chloroplasts, by leaf-specific expression of NTRC in the ntrc mutant, or exclusively in amyloplasts, by root-specific expression of NTRC. The analysis of these plants suggests that chloroplasts exert a pivotal role on plant growth, as expected because chloroplasts constitute the major source of nutrients and energy, derived from photosynthesis, for growth of heterotrophic tissues. However, NTRC deficiency causes impairment of auxin synthesis and lateral root formation. Interestingly, recovery of redox homeostasis of chloroplasts, but not of amyloplasts, was sufficient to restore wild type levels of lateral roots, showing the important signaling function of chloroplasts for the development of heterotrophic organs.

The ntrB and ntrC Genes Are Involved in the Regulation of Poly-3-Hydroxybutyrate Biosynthesis by Ammonia in Azospirillum brasilense Sp7

PubMed Central

Sun, Jun; Peng, Xuan; Van Impe, Jan; Vanderleyden, Jos

2000-01-01

Azospirillum brasilense Sp7 and its ntrA (rpoN), ntrBC, and ntrC mutants have been evaluated for their capabilities of poly-3-hydroxybutyrate (PHB) accumulation in media with high and low ammonia concentrations. It was observed that the ntrBC and ntrC mutants can produce PHB in both low- and high-C/N-ratio media, while no significant PHB production was observed for the wild type or the ntrA mutant in low-C/N-ratio media. Further investigation by fermentation analysis indicated that the ntrBC and ntrC mutants were able to grow and accumulate PHB simultaneously in the presence of a high concentration of ammonia in the medium, while little PHB was produced in the wild type and ntrA (rpoN) mutant during active growth phase. These results provide the first genetic evidence that the ntrB and ntrC genes are involved in the regulation of PHB synthesis by ammonia in A. brasilense Sp7. PMID:10618211

A network of molecular switches controls the activation of the two-component response regulator NtrC

NASA Astrophysics Data System (ADS)

Vanatta, Dan K.; Shukla, Diwakar; Lawrenz, Morgan; Pande, Vijay S.

2015-06-01

Recent successes in simulating protein structure and folding dynamics have demonstrated the power of molecular dynamics to predict the long timescale behaviour of proteins. Here, we extend and improve these methods to predict molecular switches that characterize conformational change pathways between the active and inactive state of nitrogen regulatory protein C (NtrC). By employing unbiased Markov state model-based molecular dynamics simulations, we construct a dynamic picture of the activation pathways of this key bacterial signalling protein that is consistent with experimental observations and predicts new mutants that could be used for validation of the mechanism. Moreover, these results suggest a novel mechanistic paradigm for conformational switching.

Nucleotide-induced asymmetry within ATPase activator ring drives σ54-RNAP interaction and ATP hydrolysis

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

Sysoeva, Tatyana A.; Chowdhury, Saikat; Guo, Liang

2013-12-10

It is largely unknown how the typical homomeric ring geometry of ATPases associated with various cellular activities enables them to perform mechanical work. Small-angle solution X-ray scattering, crystallography, and electron microscopy (EM) reconstructions revealed that partial ATP occupancy caused the heptameric closed ring of the bacterial enhancer-binding protein (bEBP) NtrC1 to rearrange into a hexameric split ring of striking asymmetry. The highly conserved and functionally crucial GAFTGA loops responsible for interacting with σ54–RNA polymerase formed a spiral staircase. We propose that splitting of the ensemble directs ATP hydrolysis within the oligomer, and the ring's asymmetry guides interaction between ATPase andmore » the complex of σ54 and promoter DNA. Similarity between the structure of the transcriptional activator NtrC1 and those of distantly related helicases Rho and E1 reveals a general mechanism in homomeric ATPases whereby complex allostery within the ring geometry forms asymmetric functional states that allow these biological motors to exert directional forces on their target macromolecules.« less

Two distinct redox cascades cooperatively regulate chloroplast functions and sustain plant viability.

PubMed

Yoshida, Keisuke; Hisabori, Toru

2016-07-05

The thiol-based redox regulation system is believed to adjust chloroplast functions in response to changes in light environments. A redox cascade via the ferredoxin-thioredoxin reductase (FTR)/thioredoxin (Trx) pathway has been traditionally considered to serve as a transmitter of light signals to target enzymes. However, emerging data indicate that chloroplasts have a complex redox network composed of diverse redox-mediator proteins and target enzymes. Despite extensive research addressing this system, two fundamental questions are still unresolved: How are redox pathways orchestrated within chloroplasts, and why are chloroplasts endowed with a complicated redox network? In this report, we show that NADPH-Trx reductase C (NTRC) is a key redox-mediator protein responsible for regulatory functions distinct from those of the classically known FTR/Trx system. Target screening and subsequent biochemical assays indicated that NTRC and the Trx family differentially recognize their target proteins. In addition, we found that NTRC is an electron donor to Trx-z, which is a key regulator of gene expression in chloroplasts. We further demonstrate that cooperative control of chloroplast functions via the FTR/Trx and NTRC pathways is essential for plant viability. Arabidopsis double mutants impaired in FTR and NTRC expression displayed lethal phenotypes under autotrophic growth conditions. This severe growth phenotype was related to a drastic loss of photosynthetic performance. These combined results provide an expanded map of the chloroplast redox network and its biological functions.

Two distinct redox cascades cooperatively regulate chloroplast functions and sustain plant viability

PubMed Central

Yoshida, Keisuke; Hisabori, Toru

2016-01-01

The thiol-based redox regulation system is believed to adjust chloroplast functions in response to changes in light environments. A redox cascade via the ferredoxin-thioredoxin reductase (FTR)/thioredoxin (Trx) pathway has been traditionally considered to serve as a transmitter of light signals to target enzymes. However, emerging data indicate that chloroplasts have a complex redox network composed of diverse redox-mediator proteins and target enzymes. Despite extensive research addressing this system, two fundamental questions are still unresolved: How are redox pathways orchestrated within chloroplasts, and why are chloroplasts endowed with a complicated redox network? In this report, we show that NADPH-Trx reductase C (NTRC) is a key redox-mediator protein responsible for regulatory functions distinct from those of the classically known FTR/Trx system. Target screening and subsequent biochemical assays indicated that NTRC and the Trx family differentially recognize their target proteins. In addition, we found that NTRC is an electron donor to Trx-z, which is a key regulator of gene expression in chloroplasts. We further demonstrate that cooperative control of chloroplast functions via the FTR/Trx and NTRC pathways is essential for plant viability. Arabidopsis double mutants impaired in FTR and NTRC expression displayed lethal phenotypes under autotrophic growth conditions. This severe growth phenotype was related to a drastic loss of photosynthetic performance. These combined results provide an expanded map of the chloroplast redox network and its biological functions. PMID:27335455

Nitrogen and Carbon Status Are Integrated at the Transcriptional Level by the Nitrogen Regulator NtrC In Vivo

PubMed Central

Schumacher, Jörg; Behrends, Volker; Pan, Zhensheng; Brown, Dan R.; Heydenreich, Franziska; Lewis, Matthew R.; Bennett, Mark H.; Razzaghi, Banafsheh; Komorowski, Michal; Barahona, Mauricio; Stumpf, Michael P. H.; Wigneshweraraj, Sivaramesh; Bundy, Jacob G.; Buck, Martin

2013-01-01

ABSTRACT Nitrogen regulation in Escherichia coli is a model system for gene regulation in bacteria. Growth on glutamine as a sole nitrogen source is assumed to be nitrogen limiting, inferred from slow growth and strong NtrB/NtrC-dependent gene activation. However, we show that under these conditions, the intracellular glutamine concentration is not limiting but 5.6-fold higher than in ammonium-replete conditions; in addition, α-ketoglutarate concentrations are elevated. We address this glutamine paradox from a systems perspective. We show that the dominant role of NtrC is to regulate glnA transcription and its own expression, indicating that the glutamine paradox is not due to NtrC-independent gene regulation. The absolute intracellular NtrC and GS concentrations reveal molecular control parameters, where NtrC-specific activities were highest in nitrogen-starved cells, while under glutamine growth, NtrC showed intermediate specific activity. We propose an in vivo model in which α-ketoglutarate can derepress nitrogen regulation despite nitrogen sufficiency. PMID:24255125

Expression of the nifA gene of Herbaspirillum seropedicae: role of the NtrC and NifA binding sites and of the -24/-12 promoter element.

PubMed

Souza, E M; Pedrosa, F O; Rigo, L U; Machado, H B; Yates, M G

2000-06-01

The nifA promoter of Herbaspirillum seropedicae contains potential NtrC, NifA and IHF binding sites together with a -12/-24 sigma(N)-dependent promoter. This region has now been investigated by deletion mutagenesis for the effect of NtrC and NifA on the expression of a nifA::lacZ fusion. A 5' end to the RNA was identified at position 641, 12 bp downstream from the -12/-24 promoter. Footprinting experiments showed that the G residues at positions -26 and -9 are hypermethylated, and that the region from -10 to +10 is partially melted under nitrogen-fixing conditions, confirming that this is the active nifA promoter. In H. seropedicae nifA expression from the sigma(N)-dependent promoter is repressed by fixed nitrogen but not by oxygen and is probably activated by the NtrC protein. NifA protein is apparently not essential for nifA expression but it can still bind the NifA upstream activating sequence.

Command, Control, Communications And Intelligence (C3I) Project Book, Fiscal Year 1993

DTIC Science & Technology

1992-10-30

trailers . PM MILSTAR will integrate the GNDCPs into the Army force structure. , . A /" " 1 9S. N/TRC -194 HISTORICAL BACKGROUND: Feb 89 - Army assigns...configuration consists of an S-250 shelter mounted on a truck with a trailer and generator. SCOTT is the ground segment terminal . of the Milstar system...WITH A TRAILER MOUNTED THREE KILOWATT GENERATOR AND ANTENNA. MILSCOTT/11 11-2 PM. MILSTAR (ARMY) SECURE MOBILE ANTI-JAM RELIABLE TACTICAL TERMINAL

Thioredoxins Play a Crucial Role in Dynamic Acclimation of Photosynthesis in Fluctuating Light.

PubMed

Thormählen, Ina; Zupok, Arkadiusz; Rescher, Josephin; Leger, Jochen; Weissenberger, Stefan; Groysman, Julia; Orwat, Anne; Chatel-Innocenti, Gilles; Issakidis-Bourguet, Emmanuelle; Armbruster, Ute; Geigenberger, Peter

2017-01-09

Sunlight represents the energy source for photosynthesis and plant growth. When growing in the field, plant photosynthesis has to manage strong fluctuations in light intensities. Regulation based on the thioredoxin (Trx) system is believed to ensure light-responsive control of photosynthetic reactions in the chloroplast. However, direct evidence for a role of this system in regulating dynamic acclimation of photosynthesis in fluctuating conditions is largely lacking. In this report we show that the ferredoxin-dependent Trxs m1 and m2 as well as the NADPH-dependent NTRC are both indispensable for photosynthetic acclimation in fluctuating light intensities. Arabidopsis mutants with combined deficiency in Trxs m1 and m2 show wild-type growth and photosynthesis under constant light condition, while photosynthetic parameters are strongly modified in rapidly alternating high and low light. Two independent trxm1m2 mutants show lower photosynthetic efficiency in high light, but surprisingly significantly higher photosynthetic efficiency in low light. Our data suggest that a main target of Trx m1 and m2 is the NADP-malate dehydrogenase involved in export of excess reductive power from the chloroplast. The decreased photosynthetic efficiency in the high-light peaks may thus be explained by a reduced capacity of the trxm1m2 mutants in the rapid light activation of this enzyme. In the ntrc mutant, dynamic responses of non-photochemical quenching of excitation energy and plastoquinone reduction state both were strongly attenuated in fluctuating light intensities, leading to a massive decrease in PSII quantum efficiency and a specific decrease in plant growth under these conditions. This is likely due to the decreased ability of the ntrc mutant to control the stromal NADP(H) redox poise. Taken together, our results indicate that NTRC is indispensable in ensuring the full range of dynamic responses of photosynthesis to optimize photosynthesis and maintain growth in fluctuating light, while Trxs m1 and m2 are indispensable for full activation of photosynthesis in the high-light periods but negatively affect photosynthetic efficiency in the low-light periods of fluctuating light. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

NADPH Thioredoxin Reductase C Is Localized in Plastids of Photosynthetic and Nonphotosynthetic Tissues and Is Involved in Lateral Root Formation in Arabidopsis[W

PubMed Central

Kirchsteiger, Kerstin; Ferrández, Julia; Pascual, María Belén; González, Maricruz; Cejudo, Francisco Javier

2012-01-01

Plastids are organelles present in photosynthetic and nonphotosynthetic plant tissues. While it is well known that thioredoxin-dependent redox regulation is essential for leaf chloroplast function, little is known of the redox regulation in plastids of nonphotosynthetic tissues, which cannot use light as a direct source of reducing power. Thus, the question remains whether redox regulation operates in nonphotosynthetic plastid function and how it is integrated with chloroplasts for plant growth. Here, we show that NADPH-thioredoxin reductase C (NTRC), previously reported as exclusive to green tissues, is also expressed in nonphotosynthetic tissues of Arabidopsis thaliana, where it is localized to plastids. Moreover, we show that NTRC is involved in maintaining the redox homeostasis of plastids also in nonphotosynthetic organs. To test the relationship between plastids of photosynthetic and nonphotosynthetic tissues, transgenic plants were obtained with redox homeostasis restituted exclusively in leaves or in roots, through the expression of NTRC under the control of organ-specific promoters in the ntrc mutant. Our results show that fully functional root amyloplasts are not sufficient for root, or leaf, growth, but fully functional chloroplasts are necessary and sufficient to support wild-type rates of root growth and lateral root formation. PMID:22505729

NADPH thioredoxin reductase C is localized in plastids of photosynthetic and nonphotosynthetic tissues and is involved in lateral root formation in Arabidopsis.

PubMed

Kirchsteiger, Kerstin; Ferrández, Julia; Pascual, María Belén; González, Maricruz; Cejudo, Francisco Javier

2012-04-01

Plastids are organelles present in photosynthetic and nonphotosynthetic plant tissues. While it is well known that thioredoxin-dependent redox regulation is essential for leaf chloroplast function, little is known of the redox regulation in plastids of nonphotosynthetic tissues, which cannot use light as a direct source of reducing power. Thus, the question remains whether redox regulation operates in nonphotosynthetic plastid function and how it is integrated with chloroplasts for plant growth. Here, we show that NADPH-thioredoxin reductase C (NTRC), previously reported as exclusive to green tissues, is also expressed in nonphotosynthetic tissues of Arabidopsis thaliana, where it is localized to plastids. Moreover, we show that NTRC is involved in maintaining the redox homeostasis of plastids also in nonphotosynthetic organs. To test the relationship between plastids of photosynthetic and nonphotosynthetic tissues, transgenic plants were obtained with redox homeostasis restituted exclusively in leaves or in roots, through the expression of NTRC under the control of organ-specific promoters in the ntrc mutant. Our results show that fully functional root amyloplasts are not sufficient for root, or leaf, growth, but fully functional chloroplasts are necessary and sufficient to support wild-type rates of root growth and lateral root formation.

Nitrogen stress response and stringent response are coupled in Escherichia coli

PubMed Central

Brown, Daniel R.; Barton, Geraint; Pan, Zhensheng; Buck, Martin; Wigneshweraraj, Sivaramesh

2014-01-01

Assimilation of nitrogen is an essential process in bacteria. The nitrogen regulation stress response is an adaptive mechanism used by nitrogen-starved Escherichia coli to scavenge for alternative nitrogen sources and requires the global transcriptional regulator NtrC. In addition, nitrogen-starved E. coli cells synthesize a signal molecule, guanosine tetraphosphate (ppGpp), which serves as an effector molecule of many processes including transcription to initiate global physiological changes, collectively termed the stringent response. The regulatory mechanisms leading to elevated ppGpp levels during nutritional stresses remain elusive. Here, we show that transcription of relA, a key gene responsible for the synthesis of ppGpp, is activated by NtrC during nitrogen starvation. The results reveal that NtrC couples these two major bacterial stress responses to manage conditions of nitrogen limitation, and provide novel mechanistic insights into how a specific nutritional stress leads to elevating ppGpp levels in bacteria. PMID:24947454

New insights into the reduction systems of plastidial thioredoxins point out the unique properties of thioredoxin z from Arabidopsis.

PubMed

Bohrer, Anne-Sophie; Massot, Vincent; Innocenti, Gilles; Reichheld, Jean-Philippe; Issakidis-Bourguet, Emmanuelle; Vanacker, Hélène

2012-11-01

In plants, thioredoxins (TRX) constitute a large protein disulphide oxidoreductase family comprising 10 plastidial members in Arabidopsis thaliana and subdivided in five types. The f- and m-types regulate enzymes involved mainly in carbon metabolism whereas the x, y, and z types have an antioxidant function. The reduction of TRXm and f in chloroplasts is performed in the light by ferredoxin:thioredoxin reductase (FTR) that uses photosynthetically reduced ferredoxin (Fd) as a reductant. The reduction system of Arabidopsis TRXx, y, and z has never been demonstrated. Recently, a gene encoding an atypical plastidial NADPH-dependent TRX reductase (NTRC) was found. In the present study, gene expression analysis revealed that both reductases are expressed in all organs of Arabidopsis and could potentially serve as electron donors to plastidial TRX. This ability was tested in vitro either with purified NTRC in presence of NADPH or with a light-driven reconstituted system comprising thylakoids and purified Fd and FTR. The results demonstrate that FTR reduces the x and y TRX isoforms but not the recently identified TRXz. Moreover, the results show that NTRC cannot be an efficient alternative reducing system, neither for TRXz nor for the other plastidial TRX. The data reveal that TRXf, m, x, and y, known as redox regulators in the chloroplast, have also the ability to reduce TRXz in vitro. Overall, the present study points out the unique properties of TRXz among plastidial TRX.

The complete nucleotide sequence of the glnALG operon of Escherichia coli K12.

PubMed Central

Miranda-Ríos, J; Sánchez-Pescador, R; Urdea, M; Covarrubias, A A

1987-01-01

The nucleotide sequence of the E. coli glnALG operon has been determined. The glnL (ntrB) and glnG (ntrC) genes present a high homology, at the nucleotide and aminoacid levels, with the corresponding genes of Klebsiella pneumoniae. The predicted aminoacid sequence for glutamine synthetase allowed us to locate some of the enzyme domains. The structure of this operon is discussed. PMID:2882477

ADPase activity of recombinantly expressed thermotolerant ATPases may be caused by copurification of adenylate kinase of Escherichia coli

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

Chen, Baoyu; Sysoeva, Tatyana A.; Chowdhury, Saikat

2009-10-06

Except for apyrases, ATPases generally target only the {gamma}-phosphate of a nucleotide. Some non-apyrase ATPases from thermophilic microorganisms are reported to hydrolyze ADP as well as ATP, which has been described as a novel property of the ATPases from extreme thermophiles. Here, we describe an apparent ADP hydrolysis by highly purified preparations of the AAA+ ATPase NtrC1 from an extremely thermophilic bacterium, Aquifex aeolicus. This activity is actually a combination of the activities of the ATPase and contaminating adenylate kinase (AK) from Escherichia coli, which is present at 1/10 000 of the level of the ATPase. AK catalyzes conversion ofmore » two molecules of ADP into AMP and ATP, the latter being a substrate for the ATPase. We raise concern that the observed thermotolerance of E. coli AK and its copurification with thermostable proteins by commonly used methods may confound studies of enzymes that specifically catalyze hydrolysis of nucleoside diphosphates or triphosphates. For example, contamination with E. coli AK may be responsible for reported ADPase activities of the ATPase chaperonins from Pyrococcus furiosus, Pyrococcus horikoshii, Methanococcus jannaschii and Thermoplasma acidophilum; the ATP/ADP-dependent DNA ligases from Aeropyrum pernix K1 and Staphylothermus marinus; or the reported ATP-dependent activities of ADP-dependent phosphofructokinase of P. furiosus. Purification methods developed to separate NtrC1 ATPase from AK also revealed two distinct forms of the ATPase. One is tightly bound to ADP or GDP and able to bind to Q but not S ion exchange matrixes. The other is nucleotide-free and binds to both Q and S ion exchange matrixes.« less

Center for Transportation Research | The University of Tennessee, Knoxville

Science.gov Websites

Group Tennessee Vans Research CTR Fellows Projects Publications Presentations Education Rail Courses Graders July 9-13, 2018 | 9 a.m. - Noon National Transportation Research Center (NTRC) | 2360 Cherahala -4621. Celebrating CTR's 45th Year (and counting!), 1972-2017 The Center for Transportation Research

Providing Consumers with Web-Based Information on the Environmental Effects of Automobiles

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

Saulsbury, J.W.

The Department of Energy (DOE) and the Environmental Protection Agency (EPA) provide consumers with web-based information on the environmental effects of automobiles so that individuals can make informed choices about the vehicles they use or may purchase. DOE and EPA maintain a web site (www.fueleconomy.gov) that provides users with information about fuel economy [as well as greenhouse gas (GHG) emissions and air pollution emissions] for the cars and trucks they use or may consider purchasing. EPA also maintains a separate web site (www.epa.gov/greenvehicles) that offers similar information, with the focus on air pollution emissions rather than fuel economy. The Americanmore » Council for an Energy-Efficient Economy (ACEEE) (www.greenercars.com) and the California Air Resources Board (CARB) (www.arb.ca.gov/msprog/ccbg/ccbg.htm) also maintain web sites that provide consumers with information on the environmental effects of automobiles. Through the National Transportation Research Center (NTRC) at Oak Ridge National Laboratory, DOE has supported some initial qualitative research with people who are interested in purchasing a new or used vehicle and whose actions identify them as at least somewhat concerned about the environment. The purpose of this research was to explore and understand how these people respond to the different ratings and measurements of environmental effects provided by the four web sites. The goal of the research is to optimize the communication of information provided on the DOE/EPA web site (www.fueleconomy.gov). Working with a private marketing research firm (The Looking Glass Group of Knoxville, Tennessee), NTRC staff initiated this research by meeting with two focus groups in Knoxville on February 27, 2001. To obtain information for comparison, staff from the NTRC and the Looking Glass Group also met with two focus groups in Los Angeles, California, on August 13, 2001.« less

Free energy landscape of activation in a signaling protein at atomic resolution

PubMed Central

Pontiggia, F.; Pachov, D.V.; Clarkson, M.W.; Villali, J.; Hagan, M.F.; Pande, V.S.; Kern, D.

2015-01-01

The interconversion between inactive and active protein states, traditionally described by two static structures, is at the heart of signaling. However, how folded states interconvert is largely unknown due to the inability to experimentally observe transition pathways. Here we explore the free energy landscape of the bacterial response regulator NtrC by combining computation and NMR, and discover unexpected features underlying efficient signaling. We find that functional states are defined purely in kinetic and not structural terms. The need of a well-defined conformer, crucial to the active state, is absent in the inactive state, which comprises a heterogeneous collection of conformers. The transition between active and inactive states occurs through multiple pathways, facilitated by a number of nonnative transient hydrogen bonds, thus lowering the transition barrier through both entropic and enthalpic contributions. These findings may represent general features for functional conformational transitions within the folded state. PMID:26073309

Conformational Transition Pathways in Signaling and Enzyme Catalysis Explored by Computational Methods

NASA Astrophysics Data System (ADS)

Pachov, Dimitar V.

Biomolecules are dynamic in nature and visit a number of states while performing their biological function. However, understanding how they interconvert between functional substates is a challenging task. In this thesis, we employ enhanced computational strategies to reveal in atomistic resolution transition states and molecular mechanism along conformational pathways of the signaling protein Nitrogen Regulatory Protein C (NtrC) and the enzyme Adenylate Kinase (Adk). Targeted Molecular Dynamics (TMD) simulations and NMR experiments have previously found the active/inactive interconversion of NtrC is stabilized by non-native transient contacts. To find where along the conformational pathway they lie and probe the existence of multiple intermediates, a beyond 8mus-extensive mapping of the conformational landscape was performed by a multitude of straightforward MD simulations relaxed from the biased TMD pathway. A number of metastable states stabilized by local interactions was found to underline the conformational pathway of NtrC. Two spontaneous transitions of the last stage of the active-to-inactive conversion were identified and used in path sampling procedures to generate an ensemble of truly dynamic reactive pathways. The transition state ensemble (TSE) and mechanistic descriptors of this transition were revealed in atomic detail and verified by committor analysis. By analyzing how pressure affects the dynamics and function of two homologous Adk proteins - the P.Profundum Adk surviving at 700atm pressure in the deep sea, and the E. coli Adk that lives at ambient pressures - we indirectly obtained atomic information about the TSE of the large-amplitude rate-limiting conformational opening of the Adk lids. Guided by NMR experiments showing significantly decreased activation volumes of the piezophile compared to its mesophilic counterpart, TMD simulations revealed the formation of an extended hydrogen-bonded water network in the transition state of the piezophile that can explain the experimentally measured activation volume differences. The transition state of the conformational change was proposed to lie close to the closed state. Additionally, a number of descriptors were used to characterize the free energy landscape of the mesophile. It was found that the features of landscape are highly sensitive to the binding of different ligands, their protonation states and the presence of magnesium.

Characterization of the orf1glnKamtB operon of Herbaspirillum seropedicae.

PubMed

Noindorf, Lilian; Rego, Fabiane G M; Baura, Valter A; Monteiro, Rose A; Wassem, Roseli; Cruz, Leonardo M; Rigo, Liu U; Souza, Emanuel M; Steffens, Maria B R; Pedrosa, Fabio O; Chubatsu, Leda S

2006-03-01

Herbaspirillum seropedicae is an endophytic nitrogen-fixing bacterium that colonizes economically important grasses. In this organism, the amtB gene is co-transcribed with two other genes: glnK that codes for a PII-like protein and orf1 that codes for a probable periplasmatic protein of unknown function. The expression of the orf1glnKamtB operon is increased under nitrogen-limiting conditions and is dependent on NtrC. An amtB mutant failed to transport methylammonium. Post-translational control of nitrogenase was also partially impaired in this mutant, since a complete switch-off of nitrogenase after ammonium addition was not observed. This result suggests that the AmtB protein is involved in the signaling pathway for the reversible inactivation of nitrogenase in H. seropedicae.

Dynamics of the Escherichia coli proteome in response to nitrogen starvation and entry into the stationary phase.

PubMed

Sanchuki, Heloisa B S; Gravina, Fernanda; Rodrigues, Thiago E; Gerhardt, Edileusa C M; Pedrosa, Fábio O; Souza, Emanuel M; Raittz, Roberto T; Valdameri, Glaucio; de Souza, Gustavo A; Huergo, Luciano F

2017-03-01

Nitrogen is needed for the biosynthesis of biomolecules including proteins and nucleic acids. In the absence of fixed nitrogen prokaryotes such as E. coli immediately ceases growth. Ammonium is the preferred nitrogen source for E. coli supporting the fastest growth rates. Under conditions of ammonium limitation, E. coli can use alternative nitrogen sources to supply ammonium ions and this reprogramming is led by the induction of the NtrC regulon. Here we used label free proteomics to determine the dynamics of E. coli proteins expression in response to ammonium starvation in both the short (30min) and the longer (60min) starvation. Protein abundances and post-translational modifications confirmed that activation of the NtrC regulon acts as the first line of defense against nitrogen starvation. The ribosome inactivating protein Rmf was induced shortly after ammonium exhaustion and this was preceded by induction of other ribosome inactivating proteins such as Hpf and RaiA supporting the hypothesis that ribosome shut-down is a key process during nitrogen limitation stress. The proteomic data revealed that growth arrest due to nitrogen starvation correlates with the accumulation of proteins involved in DNA condensation, RNA and protein catabolism and ribosome hibernation. Collectively, these proteome adaptations will result in metabolic inactive cells which are likely to exhibit multidrug tolerance. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification of the Regulator Gene Responsible for the Acetone-Responsive Expression of the Binuclear Iron Monooxygenase Gene Cluster in Mycobacteria ▿

PubMed Central

Furuya, Toshiki; Hirose, Satomi; Semba, Hisashi; Kino, Kuniki

2011-01-01

The mimABCD gene cluster encodes the binuclear iron monooxygenase that oxidizes propane and phenol in Mycobacterium smegmatis strain MC2 155 and Mycobacterium goodii strain 12523. Interestingly, expression of the mimABCD gene cluster is induced by acetone. In this study, we investigated the regulator gene responsible for this acetone-responsive expression. In the genome sequence of M. smegmatis strain MC2 155, the mimABCD gene cluster is preceded by a gene designated mimR, which is divergently transcribed. Sequence analysis revealed that MimR exhibits amino acid similarity with the NtrC family of transcriptional activators, including AcxR and AcoR, which are involved in acetone and acetoin metabolism, respectively. Unexpectedly, many homologs of the mimR gene were also found in the sequenced genomes of actinomycetes. A plasmid carrying a transcriptional fusion of the intergenic region between the mimR and mimA genes with a promoterless green fluorescent protein (GFP) gene was constructed and introduced into M. smegmatis strain MC2 155. Using a GFP reporter system, we confirmed by deletion and complementation analyses that the mimR gene product is the positive regulator of the mimABCD gene cluster expression that is responsive to acetone. M. goodii strain 12523 also utilized the same regulatory system as M. smegmatis strain MC2 155. Although transcriptional activators of the NtrC family generally control transcription using the σ54 factor, a gene encoding the σ54 factor was absent from the genome sequence of M. smegmatis strain MC2 155. These results suggest the presence of a novel regulatory system in actinomycetes, including mycobacteria. PMID:21856847

An Escherichia coli nitrogen starvation response is important for mutualistic coexistence with Rhodopseudomonas palustris.

PubMed

McCully, Alexandra L; Behringer, Megan G; Gliessman, Jennifer R; Pilipenko, Evgeny V; Mazny, Jeffrey L; Lynch, Michael; Drummond, D Allan; McKinlay, James B

2018-05-04

Microbial mutualistic cross-feeding interactions are ubiquitous and can drive important community functions. Engaging in cross-feeding undoubtedly affects the physiology and metabolism of individual species involved. However, the nature in which an individual's physiology is influenced by cross-feeding and the importance of those physiological changes for the mutualism have received little attention. We previously developed a genetically tractable coculture to study bacterial mutualisms. The coculture consists of fermentative Escherichia coli and phototrophic Rhodopseudomonas palustris In this coculture, E. coli anaerobically ferments sugars into excreted organic acids as a carbon source for R. palustris In return, a genetically-engineered R. palustris constitutively converts N 2 into NH 4 + , providing E. coli with essential nitrogen. Using RNA-seq and proteomics, we identified transcript and protein levels that differ in each partner when grown in coculture versus monoculture. When in coculture with R. palustris , E. coli gene-expression changes resembled a nitrogen starvation response under the control of the transcriptional regulator NtrC. By genetically disrupting E. coli NtrC, we determined that a nitrogen starvation response is important for a stable coexistence, especially at low R. palustris NH 4 + excretion levels. Destabilization of the nitrogen starvation regulatory network resulted in variable growth trends and in some cases, extinction. Our results highlight that alternative physiological states can be important for survival within cooperative cross-feeding relationships. Importance Mutualistic cross-feeding between microbes within multispecies communities is widespread. Studying how mutualistic interactions influence the physiology of each species involved is important for understanding how mutualisms function and persist in both natural and applied settings. Using a bacterial mutualism consisting of Rhodopseudomonas palustris and Escherichia coli growing cooperatively through bidirectional nutrient exchange, we determined that an E. coli nitrogen starvation response is important for maintaining a stable coexistence. The lack of an E. coli nitrogen starvation response ultimately destabilized the mutualism and, in some cases, led to community collapse after serial transfers. Our findings thus inform on the potential necessity of an alternative physiological state for mutualistic coexistence with another species compared to the physiology of species grown in isolation. Copyright © 2018 American Society for Microbiology.

Target Residence Time-Guided Optimization on TTK Kinase Results in Inhibitors with Potent Anti-Proliferative Activity.

PubMed

Uitdehaag, Joost C M; de Man, Jos; Willemsen-Seegers, Nicole; Prinsen, Martine B W; Libouban, Marion A A; Sterrenburg, Jan Gerard; de Wit, Joeri J P; de Vetter, Judith R F; de Roos, Jeroen A D M; Buijsman, Rogier C; Zaman, Guido J R

2017-07-07

The protein kinase threonine tyrosine kinase (TTK; also known as Mps1) is a critical component of the spindle assembly checkpoint and a promising drug target for the treatment of aggressive cancers, such as triple negative breast cancer. While the first TTK inhibitors have entered clinical trials, little is known about how the inhibition of TTK with small-molecule compounds affects cellular activity. We studied the selective TTK inhibitor NTRC 0066-0, which was developed in our own laboratory, together with 11 TTK inhibitors developed by other companies, including Mps-BAY2b, BAY 1161909, BAY 1217389 (Bayer), TC-Mps1-12 (Shionogi), and MPI-0479605 (Myrexis). Parallel testing shows that the cellular activity of these TTK inhibitors correlates with their binding affinity to TTK and, more strongly, with target residence time. TTK inhibitors are therefore an example where target residence time determines activity in in vitro cellular assays. X-ray structures and thermal stability experiments reveal that the most potent compounds induce a shift of the glycine-rich loop as a result of binding to the catalytic lysine at position 553. This "lysine trap" disrupts the catalytic machinery. Based on these insights, we developed TTK inhibitors, based on a (5,6-dihydro)pyrimido[4,5-e]indolizine scaffold, with longer target residence times, which further exploit an allosteric pocket surrounding Lys553. Their binding mode is new for kinase inhibitors and can be classified as hybrid Type I/Type III. These inhibitors have very potent anti-proliferative activity that rivals classic cytotoxic therapy. Our findings will open up new avenues for more applications for TTK inhibitors in cancer treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Control of autogenous activation of Herbaspirillum seropedicae nifA promoter by the IHF protein.

PubMed

Wassem, Roseli; Pedrosa, Fábio O; Yates, Marshall G; Rego, Fabiane G M; Chubatsu, Leda S; Rigo, Liu U; Souza, Emanuel M

2002-07-02

Analysis of the expression of the Herbaspirillum seropedicae nifA promoter in Escherichia coli and Herbaspirillum seropedicae, showed that nifA expression is primarily dependent on NtrC but also required NifA for maximal expression under nitrogen-fixing conditions. Deletion of the IHF (integration host factor)-binding site produced a promoter with two-fold higher activity than the native promoter in the H. seropedicae wild-type strain but not in a nifA strain, indicating that IHF controls NifA auto-activation. IHF is apparently required to prevent overexpression of the NifA protein via auto-activation under nitrogen-fixing conditions in H. seropedicae.

Radio Frequency Sensing of Particulate Matter Accumulation on a Gasoline Particulate Filter

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

Parks, James; Prikhodko, Vitaly Y.; Sappok, Alex

Filter Sensing Technology’s radio frequency (RF) sensor for particulate filter on-board diagnostics (OBD) was studied on a lean gasoline engine at the National Transportation Research Center (NTRC) at Oak Ridge National Laboratory (ORNL). The response of the RF sensor to particulate matter (PM) or “soot” accumulation on the gasoline particulate filter (GPF) installed in the engine exhaust was evaluated. In addition, end plugs of the GPF were purposely removed, and subsequent changes to the RF sensor measured soot loading on the GPF were characterized. Results from the study showed that the RF sensor can accurately measure soot accumulation on amore » GPF; furthermore, the predicted decreased soot accumulation due to plug removal was detected by the RF sensor. Overall, the studies were short and preliminary in nature; however, clearly, the RF sensor demonstrated the capability of measuring GPF soot loading at a level suitable for use in lean gasoline engine emission control OBD and control.« less

Assimilation of Nitrogen from Nitrite and Trinitrotoluene in Pseudomonas putida JLR11

PubMed Central

Caballero, Antonio; Esteve-Núñez, Abraham; Zylstra, Gerben J.; Ramos, Juan L.

2005-01-01

Pseudomonas putida JLR11 releases nitrogen from the 2,4,6-trinitrotoluene (TNT) ring as nitrite or ammonium. These processes can occur simultaneously, as shown by the observation that a nasB mutant impaired in the reduction of nitrite to ammonium grew at a slower rate than the parental strain. Nitrogen from TNT is assimilated via the glutamine syntethase-glutamate synthase (GS-GOGAT) pathway, as evidenced by the inability of GOGAT mutants to use TNT. This pathway is also used to assimilate ammonium from reduced nitrate and nitrite. Three mutants that had insertions in ntrC, nasT, and cnmA, which encode regulatory proteins, failed to grow on nitrite but grew on TNT, although slower than the wild type. PMID:15601726

Unique ATPase site architecture triggers cis-mediated synchronized ATP binding in heptameric AAA+-ATPase domain of flagellar regulatory protein FlrC.

PubMed

Dey, Sanjay; Biswas, Maitree; Sen, Udayaditya; Dasgupta, Jhimli

2015-04-03

Bacterial enhancer-binding proteins (bEBPs) oligomerize through AAA(+) domains and use ATP hydrolysis-driven energy to isomerize the RNA polymerase-σ(54) complex during transcriptional initiation. Here, we describe the first structure of the central AAA(+) domain of the flagellar regulatory protein FlrC (FlrC(C)), a bEBP that controls flagellar synthesis in Vibrio cholerae. Our results showed that FlrC(C) forms heptamer both in nucleotide (Nt)-free and -bound states without ATP-dependent subunit remodeling. Unlike the bEBPs such as NtrC1 or PspF, a novel cis-mediated "all or none" ATP binding occurs in the heptameric FlrC(C), because constriction at the ATPase site, caused by loop L3 and helix α7, restricts the proximity of the trans-protomer required for Nt binding. A unique "closed to open" movement of Walker A, assisted by trans-acting "Glu switch" Glu-286, facilitates ATP binding and hydrolysis. Fluorescence quenching and ATPase assays on FlrC(C) and mutants revealed that although Arg-349 of sensor II, positioned by trans-acting Glu-286 and Tyr-290, acts as a key residue to bind and hydrolyze ATP, Arg-319 of α7 anchors ribose and controls the rate of ATP hydrolysis by retarding the expulsion of ADP. Heptameric state of FlrC(C) is restored in solution even with the transition state mimicking ADP·AlF3. Structural results and pulldown assays indicated that L3 renders an in-built geometry to L1 and L2 causing σ(54)-FlrC(C) interaction independent of Nt binding. Collectively, our results underscore a novel mechanism of ATP binding and σ(54) interaction that strives to understand the transcriptional mechanism of the bEBPs, which probably interact directly with the RNA polymerase-σ(54) complex without DNA looping. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Explosive Characteristics of Carbonaceous Nanoparticles

NASA Astrophysics Data System (ADS)

Turkevich, Leonid; Fernback, Joseph; Dastidar, Ashok

2013-03-01

Explosion testing has been performed on 20 codes of carbonaceous particles. These include SWCNTs (single-walled carbon nanotubes), MWCNTs (multi-walled carbon nanotubes), CNFs (carbon nanofibers), graphene, diamond, fullerene, carbon blacks and graphites. Explosion screening was performed in a 20 L explosion chamber (ASTM E1226-10 protocol), at a (dilute) concentration of 500 g/m3, using a 5 kJ ignition source. Time traces of overpressure were recorded. Samples exhibited overpressures of 5-7 bar, and deflagration index KSt = V1/3 (dp/pt)max ~ 10 - 80 bar-m/s, which places these materials in European Dust Explosion Class St-1 (similar to cotton and wood dust). There was minimal variation between these different materials. The explosive characteristics of these carbonaceous powders are uncorrelated with particle size (BET specific surface area). Additional tests were performed on selected materials to identify minimum explosive concentration [MEC]. These materials exhibit MEC ~ 101 -102 g/m3 (lower than the MEC for coals). The concentration scans confirm that the earlier screening was performed under fuel-rich conditions (i.e. the maximum over-pressure and deflagration index exceed the screening values); e.g. the true fullerene KSt ~ 200 bar-m/s, placing it borderline St-1/St-2. Work supported through the NIOSH Nanotechnology Research Center (NTRC)

Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics

PubMed Central

Pandini, Alessandro; Fornili, Arianna; Fraternali, Franca; Kleinjung, Jens

2012-01-01

Allostery offers a highly specific way to modulate protein function. Therefore, understanding this mechanism is of increasing interest for protein science and drug discovery. However, allosteric signal transmission is difficult to detect experimentally and to model because it is often mediated by local structural changes propagating along multiple pathways. To address this, we developed a method to identify communication pathways by an information-theoretical analysis of molecular dynamics simulations. Signal propagation was described as information exchange through a network of correlated local motions, modeled as transitions between canonical states of protein fragments. The method was used to describe allostery in two-component regulatory systems. In particular, the transmission from the allosteric site to the signaling surface of the receiver domain NtrC was shown to be mediated by a layer of hub residues. The location of hubs preferentially connected to the allosteric site was found in close agreement with key residues experimentally identified as involved in the signal transmission. The comparison with the networks of the homologues CheY and FixJ highlighted similarities in their dynamics. In particular, we showed that a preorganized network of fragment connections between the allosteric and functional sites exists already in the inactive state of all three proteins.—Pandini, A., Fornili, A., Fraternali, F., Kleinjung, J. Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics. PMID:22071506

Peroxiredoxins and NADPH-Dependent Thioredoxin Systems in the Model Legume Lotus japonicus1[W][OA

PubMed Central

Tovar-Méndez, Alejandro; Matamoros, Manuel A.; Bustos-Sanmamed, Pilar; Dietz, Karl-Josef; Cejudo, Francisco Javier; Rouhier, Nicolas; Sato, Shusei; Tabata, Satoshi; Becana, Manuel

2011-01-01

Peroxiredoxins (Prxs), thioredoxins (Trxs), and NADPH-thioredoxin reductases (NTRs) constitute central elements of the thiol-disulfide redox regulatory network of plant cells. This study provides a comprehensive survey of this network in the model legume Lotus japonicus. The aims were to identify and characterize these gene families and to assess whether the NTR-Trx systems are operative in nodules. Quantitative reverse transcription-polymerase chain reaction and immunological and proteomic approaches were used for expression profiling. We identified seven Prx, 14 Trx, and three NTR functional genes. The PrxQ1 gene was found to be transcribed in two alternative spliced variants and to be expressed at high levels in leaves, stems, petals, pods, and seeds and at low levels in roots and nodules. The 1CPrx gene showed very high expression in the seed embryos and low expression in vegetative tissues and was induced by nitric oxide and cytokinins. In sharp contrast, cytokinins down-regulated all other Prx genes, except PrxQ1, in roots and nodules, but only 2CPrxA and PrxQ1 in leaves. Gene-specific changes in Prx expression were also observed in response to ethylene, abscisic acid, and auxins. Nodules contain significant mRNA and protein amounts of cytosolic PrxIIB, Trxh1, and NTRA and of plastidic NTRC. Likewise, they express cytosolic Trxh3, Trxh4, Trxh8, and Trxh9, mitochondrial PrxIIF and Trxo, and plastidic Trxm2, Trxm4, and ferredoxin-Trx reductase. These findings reveal a complex regulation of Prxs that is dependent on the isoform, tissue, and signaling molecule and support that redox NTR-Trx systems are functional in the cytosol, mitochondria, and plastids of nodules. PMID:21562331

Peroxiredoxins and NADPH-dependent thioredoxin systems in the model legume Lotus japonicus.

PubMed

Tovar-Méndez, Alejandro; Matamoros, Manuel A; Bustos-Sanmamed, Pilar; Dietz, Karl-Josef; Cejudo, Francisco Javier; Rouhier, Nicolas; Sato, Shusei; Tabata, Satoshi; Becana, Manuel

2011-07-01

Peroxiredoxins (Prxs), thioredoxins (Trxs), and NADPH-thioredoxin reductases (NTRs) constitute central elements of the thiol-disulfide redox regulatory network of plant cells. This study provides a comprehensive survey of this network in the model legume Lotus japonicus. The aims were to identify and characterize these gene families and to assess whether the NTR-Trx systems are operative in nodules. Quantitative reverse transcription-polymerase chain reaction and immunological and proteomic approaches were used for expression profiling. We identified seven Prx, 14 Trx, and three NTR functional genes. The PrxQ1 gene was found to be transcribed in two alternative spliced variants and to be expressed at high levels in leaves, stems, petals, pods, and seeds and at low levels in roots and nodules. The 1CPrx gene showed very high expression in the seed embryos and low expression in vegetative tissues and was induced by nitric oxide and cytokinins. In sharp contrast, cytokinins down-regulated all other Prx genes, except PrxQ1, in roots and nodules, but only 2CPrxA and PrxQ1 in leaves. Gene-specific changes in Prx expression were also observed in response to ethylene, abscisic acid, and auxins. Nodules contain significant mRNA and protein amounts of cytosolic PrxIIB, Trxh1, and NTRA and of plastidic NTRC. Likewise, they express cytosolic Trxh3, Trxh4, Trxh8, and Trxh9, mitochondrial PrxIIF and Trxo, and plastidic Trxm2, Trxm4, and ferredoxin-Trx reductase. These findings reveal a complex regulation of Prxs that is dependent on the isoform, tissue, and signaling molecule and support that redox NTR-Trx systems are functional in the cytosol, mitochondria, and plastids of nodules.

(Methyl)ammonium Transport in the Nitrogen-Fixing Bacterium Azospirillum brasilense

PubMed Central

Van Dommelen, Anne; Keijers, Veerle; Vanderleyden, Jos; de Zamaroczy, Miklos

1998-01-01

An ammonium transporter of Azospirillum brasilense was characterized. In contrast to most previously reported putative prokaryotic NH4+ transporter genes, A. brasilense amtB is not part of an operon with glnB or glnZ which, in A. brasilense, encode nitrogen regulatory proteins PII and PZ, respectively. Sequence analysis predicts the presence of 12 transmembrane domains in the deduced AmtB protein and classifies AmtB as an integral membrane protein. Nitrogen regulates the transcription of the amtB gene in A. brasilense by the Ntr system. amtB is the first gene identified in A. brasilense whose expression is regulated by NtrC. The observation that ammonium uptake is still possible in mutants lacking the AmtB protein suggests the presence of a second NH4+ transport mechanism. Growth of amtB mutants at low ammonium concentrations is reduced compared to that of the wild type. This suggests that AmtB has a role in scavenging ammonium at low concentrations. PMID:9573149

Topological frustration in βα-repeat proteins: sequence diversity modulates the conserved folding mechanisms of α/β/α sandwich proteins

PubMed Central

Hills, Ronald D.; Kathuria, Sagar V.; Wallace, Louise A.; Day, Iain J.; Brooks, Charles L.; Matthews, C. Robert

2010-01-01

The thermodynamic hypothesis of Anfinsen postulates that structures and stabilities of globular proteins are determined by their amino acid sequences. Chain topology, however, is known to influence the folding reaction, in that motifs with a preponderance of local interactions typically fold more rapidly than those with a larger fraction of non-local interactions. Together, the topology and sequence can modulate the energy landscape and influence the rate at which the protein folds to the native conformation. To explore the relationship of sequence and topology in the folding of βα–repeat proteins, which are dominated by local interactions, a combined experimental and simulation analysis was performed on two members of the flavodoxin-like, α/β/α sandwich fold. Spo0F and the N-terminal receiver domain of NtrC (NT-NtrC) have similar topologies but low sequence identity, enabling a test of the effects of sequence on folding. Experimental results demonstrated that both response-regulator proteins fold via parallel channels through highly structured sub-millisecond intermediates before accessing their cis prolyl peptide bond-containing native conformations. Global analysis of the experimental results preferentially places these intermediates off the productive folding pathway. Sequence-sensitive Gō-model simulations conclude that frustration in the folding in Spo0F, corresponding to the appearance of the off-pathway intermediate, reflects competition for intra-subdomain van der Waals contacts between its N- and C-terminal subdomains. The extent of transient, premature structure appears to correlate with the number of isoleucine, leucine and valine (ILV) side-chains that form a large sequence-local cluster involving the central β-sheet and helices α2, α3 and α4. The failure to detect the off-pathway species in the simulations of NT-NtrC may reflect the reduced number of ILV side-chains in its corresponding hydrophobic cluster. The location of the hydrophobic clusters in the structure may also be related to the differing functional properties of these response regulators. Comparison with the results of previous experimental and simulation analyses on the homologous CheY argues that prematurely-folded unproductive intermediates are a common property of the βα-repeat motif. PMID:20226790

Multiple strategies to prevent oxidative stress in Arabidopsis plants lacking the malate valve enzyme NADP-malate dehydrogenase

PubMed Central

Hebbelmann, Inga; Selinski, Jennifer; Wehmeyer, Corinna; Goss, Tatjana; Voss, Ingo; Mulo, Paula; Kangasjärvi, Saijaliisa; Aro, Eva-Mari; Oelze, Marie-Luise; Dietz, Karl-Josef; Nunes-Nesi, Adriano; Do, Phuc T.; Fernie, Alisdair R.; Talla, Sai K.; Raghavendra, Agepati S.; Linke, Vera; Scheibe, Renate

2012-01-01

The nuclear-encoded chloroplast NADP-dependent malate dehydrogenase (NADP-MDH) is a key enzyme controlling the malate valve, to allow the indirect export of reducing equivalents. Arabidopsis thaliana (L.) Heynh. T-DNA insertion mutants of NADP-MDH were used to assess the role of the light-activated NADP-MDH in a typical C3 plant. Surprisingly, even when exposed to high-light conditions in short days, nadp-mdh knockout mutants were phenotypically indistinguishable from the wild type. The photosynthetic performance and typical antioxidative systems, such as the Beck–Halliwell–Asada pathway, were barely affected in the mutants in response to high-light treatment. The reactive oxygen species levels remained low, indicating the apparent absence of oxidative stress, in the mutants. Further analysis revealed a novel combination of compensatory mechanisms in order to maintain redox homeostasis in the nadp-mdh plants under high-light conditions, particularly an increase in the NTRC/2-Cys peroxiredoxin (Prx) system in chloroplasts. There were indications of adjustments in extra-chloroplastic components of photorespiration and proline levels, which all could dissipate excess reducing equivalents, sustain photosynthesis, and prevent photoinhibition in nadp-mdh knockout plants. Such metabolic flexibility suggests that the malate valve acts in concert with other NADPH-consuming reactions to maintain a balanced redox state during photosynthesis under high-light stress in wild-type plants. PMID:22140244

Response Characteristics of a Stable Mixed Potential Ammonia Sensor in Simulated Diesel Exhaust

DOE PAGES

Ramaiyan, Kannan P.; Pihl, Josh A.; Kreller, Cortney R.; ...

2017-07-15

A mixed potential sensor using Au and Pt dense wire electrodes embedded between tape-casted layers of 8 mol% yttria stabilized zirconia (YSZ) was tested for application toward NH 3, NO, NO 2, C 3H 6 and C 3H 8. In single-gas testing, the sensor exhibited the highest response toward NH 3, while still exhibiting reasonably high sensitivity toward other interferent gases. We tested the sensor in a high-flow reactor at the National Transportation Research Center (NTRC) in order to simulate exhaust gas constituents and flow rates produced by lean-burn vehicles powered by Compression-Ignition Direct-Injection (CIDI), diesel engines. The sensor wasmore » characterized at 525 and 625°C for NH 3, CO, C 3H 6, C 3H 8, and NO x in a base gas composition of 10% O 2, 5% H 2O, and 5% CO 2 flowing at 15 slpm. The sensor exhibited fast response time equal to the response time of the system's switching valve (T90<0.6s). Furthermore, in simulations of overdosing a selective catalytic reduction (SCR) system, the sensor was able to selectively respond to 20ppm injections of NH 3 slip despite the presence of the interferent gas species at combined concentrations ten times higher than that of the NH 3. The laboratory sensor construct was transitioned to a pre-commercial, automotive stick sensor configuration that was demonstrated to retain the advantageous characteristics of the tape-cast device.« less

Poly(3-hydroxybutyrate) hyperproduction by a global nitrogen regulator NtrB mutant strain of Paracoccus denitrificans PD1222

PubMed Central

Olaya-Abril, Alfonso; Luque-Almagro, Víctor M; Manso, Isabel; Gates, Andrew J; Moreno-Vivián, Conrado; Richardson, David J

2017-01-01

Abstract Paracoccus denitrificans PD1222 accumulates short-length polyhydroxyalkanoates, poly(3-hydroxybutyrate), under nitrogen-deficient conditions. Polyhydroxybutyrate metabolism requires the 3-ketoacyl-CoA thiolase PhaA, the acetoacetyl-CoA dehydrogenase/reductase PhaB and the synthase PhaC for polymerization. Additionally, P. denitrificans PD1222 grows aerobically with nitrate as sole nitrogen source. Nitrate assimilation is controlled negatively by ammonium through the two-component NtrBC system. NtrB is a sensor kinase that autophosphorylates a histidine residue under low-nitrogen concentrations and, in turn, transfers a phosphoryl group to an aspartate residue of the response regulator NtrC protein, which acts as a transcriptional activator of the P. denitrificans PD1222 nasABGHC genes. The P. denitrificans PD1222 NtrB mutant was unable to use nitrate efficiently as nitrogen source when compared to the wild-type strain, and it also overproduced poly(3-hydroxybutyrate). Acetyl-CoA concentration in the P. denitrificans PD1222 NtrB mutant strain was higher than in the wild-type strain. The expression of the phaC gene was also increased in the NtrB mutant when compared to the wild-type strain. These results suggest that accumulation of poly(3-hydroxybutyrate) in the NtrB mutant strain of PD1222 responds to the high levels of acetyl-CoA that accumulate in the cytoplasm as consequence of its inability to efficiently use nitrate as nitrogen source. PMID:29228177

Response Characteristics of a Stable Mixed Potential Ammonia Sensor in Simulated Diesel Exhaust

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

Ramaiyan, Kannan P.; Pihl, Josh A.; Kreller, Cortney R.

A mixed potential sensor using Au and Pt dense wire electrodes embedded between tape-casted layers of 8 mol% yttria stabilized zirconia (YSZ) was tested for application toward NH 3, NO, NO 2, C 3H 6 and C 3H 8. In single-gas testing, the sensor exhibited the highest response toward NH 3, while still exhibiting reasonably high sensitivity toward other interferent gases. We tested the sensor in a high-flow reactor at the National Transportation Research Center (NTRC) in order to simulate exhaust gas constituents and flow rates produced by lean-burn vehicles powered by Compression-Ignition Direct-Injection (CIDI), diesel engines. The sensor wasmore » characterized at 525 and 625°C for NH 3, CO, C 3H 6, C 3H 8, and NO x in a base gas composition of 10% O 2, 5% H 2O, and 5% CO 2 flowing at 15 slpm. The sensor exhibited fast response time equal to the response time of the system's switching valve (T90<0.6s). Furthermore, in simulations of overdosing a selective catalytic reduction (SCR) system, the sensor was able to selectively respond to 20ppm injections of NH 3 slip despite the presence of the interferent gas species at combined concentrations ten times higher than that of the NH 3. The laboratory sensor construct was transitioned to a pre-commercial, automotive stick sensor configuration that was demonstrated to retain the advantageous characteristics of the tape-cast device.« less

Initial cloning and sequencing of hydHG, an operon homologous to ntrBC and regulating the labile hydrogenase activity in Escherichia coli K-12.

PubMed Central

Stoker, K; Reijnders, W N; Oltmann, L F; Stouthamer, A H

1989-01-01

To isolate genes from Escherichia coli which regulate the labile hydrogenase activity, a plasmid library was used to transform hydL mutants lacking the labile hydrogenase. A single type of gene, designated hydG, was isolated. This gene also partially restored the hydrogenase activity in hydF mutants (which are defective in all hydrogenase isoenzymes), although the low hydrogenase 1 and 2 levels were not induced. Therefore, hydG apparently regulates, specifically, the labile hydrogenase activity. Restoration of this latter activity in hydF mutants was accompanied by a proportional increase of the H2 uptake activity, suggesting a functional relationship. H2:fumarate oxidoreductase activity was not restored in complemented hydL mutants. These latter strains may therefore lack, in addition to the labile hydrogenase, a second component (provisionally designated component R), possibly an electron carrier coupling H2 oxidation to the anerobic respiratory chain. Sequence analysis showed an open reading frame of 1,314 base pairs for hydG. It was preceded by a ribosome-binding site but apparently lacked a promoter. Minicell experiments revealed a single polypeptide of approximately 50 kilodaltons. Comparison of the predicted amino acid sequence with a protein sequence data base revealed strong homology to NtrC from Klebsiella pneumoniae, a DNA-binding transcriptional activator. The 411 base pairs upstream from pHG40 contained a second open reading frame overlapping hydG by four bases. The deduced amino acid sequence showed considerable homology with the C-terminal part of NtrB. This sequence was therefore assumed to be part of a second gene, encoding the NtrB-like component, and was designated hydH. The labile hydrogenase activity in E. coli is apparently regulated by a multicomponent system analogous to the NtrB-NtrC system. This conclusion is in agreement with the results of Birkmann et al. (A. Birkmann, R. G. Sawers, and A. Böck, Mol. Gen. Genet. 210:535-542, 1987), who demonstrated ntrA dependence for the labile hydrogenase activity. Images PMID:2666400

Co-regulation of Iron Metabolism and Virulence Associated Functions by Iron and XibR, a Novel Iron Binding Transcription Factor, in the Plant Pathogen Xanthomonas

PubMed Central

Pandey, Sheo Shankar; Patnana, Pradeep Kumar; Lomada, Santosh Kumar; Tomar, Archana; Chatterjee, Subhadeep

2016-01-01

Abilities of bacterial pathogens to adapt to the iron limitation present in hosts is critical to their virulence. Bacterial pathogens have evolved diverse strategies to coordinately regulate iron metabolism and virulence associated functions to maintain iron homeostasis in response to changing iron availability in the environment. In many bacteria the ferric uptake regulator (Fur) functions as transcription factor that utilize ferrous form of iron as cofactor to regulate transcription of iron metabolism and many cellular functions. However, mechanisms of fine-tuning and coordinated regulation of virulence associated function beyond iron and Fur-Fe2+ remain undefined. In this study, we show that a novel transcriptional regulator XibR (named X anthomonas iron binding regulator) of the NtrC family, is required for fine-tuning and co-coordinately regulating the expression of several iron regulated genes and virulence associated functions in phytopathogen Xanthomonas campestris pv. campestris (Xcc). Genome wide expression analysis of iron-starvation stimulon and XibR regulon, GUS assays, genetic and functional studies of xibR mutant revealed that XibR positively regulates functions involved in iron storage and uptake, chemotaxis, motility and negatively regulates siderophore production, in response to iron. Furthermore, chromatin immunoprecipitation followed by quantitative real-time PCR indicated that iron promoted binding of the XibR to the upstream regulatory sequence of operon’s involved in chemotaxis and motility. Circular dichroism spectroscopy showed that purified XibR bound ferric form of iron. Electrophoretic mobility shift assay revealed that iron positively affected the binding of XibR to the upstream regulatory sequences of the target virulence genes, an effect that was reversed by ferric iron chelator deferoxamine. Taken together, these data revealed that how XibR coordinately regulates virulence associated and iron metabolism functions in Xanthomonads in response to iron availability. Our results provide insight of the complex regulatory mechanism of fine-tuning of virulence associated functions with iron availability in this important group of phytopathogen. PMID:27902780

Phyletic Distribution and Lineage-Specific Domain Architectures of Archaeal Two-Component Signal Transduction Systems

PubMed Central

Makarova, Kira S.; Wolf, Yuri I.

2017-01-01

ABSTRACT The two-component signal transduction (TCS) machinery is a key mechanism of sensing environmental changes in the prokaryotic world. TCS systems have been characterized thoroughly in bacteria but to a much lesser extent in archaea. Here, we provide an updated census of more than 2,000 histidine kinases and response regulators encoded in 218 complete archaeal genomes, as well as unfinished genomes available from metagenomic data. We describe the domain architectures of the archaeal TCS components, including several novel output domains, and discuss the evolution of the archaeal TCS machinery. The distribution of TCS systems in archaea is strongly biased, with high levels of abundance in haloarchaea and thaumarchaea but none detected in the sequenced genomes from the phyla Crenarchaeota, Nanoarchaeota, and Korarchaeota. The archaeal sensor histidine kinases are generally similar to their well-studied bacterial counterparts but are often located in the cytoplasm and carry multiple PAS and/or GAF domains. In contrast, archaeal response regulators differ dramatically from the bacterial ones. Most archaeal genomes do not encode any of the major classes of bacterial response regulators, such as the DNA-binding transcriptional regulators of the OmpR/PhoB, NarL/FixJ, NtrC, AgrA/LytR, and ActR/PrrA families and the response regulators with GGDEF and/or EAL output domains. Instead, archaea encode multiple copies of response regulators containing either the stand-alone receiver (REC) domain or combinations of REC with PAS and/or GAF domains. Therefore, the prevailing mechanism of archaeal TCS signaling appears to be via a variety of protein-protein interactions, rather than direct transcriptional regulation. IMPORTANCE Although the Archaea represent a separate domain of life, their signaling systems have been assumed to be closely similar to the bacterial ones. A study of the domain architectures of the archaeal two-component signal transduction (TCS) machinery revealed an overall similarity of archaeal and bacterial sensory modules but substantial differences in the signal output modules. The prevailing mechanism of archaeal TCS signaling appears to involve various protein-protein interactions rather than direct transcription regulation. The complete list of histidine kinases and response regulators encoded in the analyzed archaeal genomes is available online at http://www.ncbi.nlm.nih.gov/Complete_Genomes/TCSarchaea.html. PMID:29263101

Phyletic Distribution and Lineage-Specific Domain Architectures of Archaeal Two-Component Signal Transduction Systems.

PubMed

Galperin, Michael Y; Makarova, Kira S; Wolf, Yuri I; Koonin, Eugene V

2018-04-01

The two-component signal transduction (TCS) machinery is a key mechanism of sensing environmental changes in the prokaryotic world. TCS systems have been characterized thoroughly in bacteria but to a much lesser extent in archaea. Here, we provide an updated census of more than 2,000 histidine kinases and response regulators encoded in 218 complete archaeal genomes, as well as unfinished genomes available from metagenomic data. We describe the domain architectures of the archaeal TCS components, including several novel output domains, and discuss the evolution of the archaeal TCS machinery. The distribution of TCS systems in archaea is strongly biased, with high levels of abundance in haloarchaea and thaumarchaea but none detected in the sequenced genomes from the phyla Crenarchaeota , Nanoarchaeota , and Korarchaeota The archaeal sensor histidine kinases are generally similar to their well-studied bacterial counterparts but are often located in the cytoplasm and carry multiple PAS and/or GAF domains. In contrast, archaeal response regulators differ dramatically from the bacterial ones. Most archaeal genomes do not encode any of the major classes of bacterial response regulators, such as the DNA-binding transcriptional regulators of the OmpR/PhoB, NarL/FixJ, NtrC, AgrA/LytR, and ActR/PrrA families and the response regulators with GGDEF and/or EAL output domains. Instead, archaea encode multiple copies of response regulators containing either the stand-alone receiver (REC) domain or combinations of REC with PAS and/or GAF domains. Therefore, the prevailing mechanism of archaeal TCS signaling appears to be via a variety of protein-protein interactions, rather than direct transcriptional regulation. IMPORTANCE Although the Archaea represent a separate domain of life, their signaling systems have been assumed to be closely similar to the bacterial ones. A study of the domain architectures of the archaeal two-component signal transduction (TCS) machinery revealed an overall similarity of archaeal and bacterial sensory modules but substantial differences in the signal output modules. The prevailing mechanism of archaeal TCS signaling appears to involve various protein-protein interactions rather than direct transcription regulation. The complete list of histidine kinases and response regulators encoded in the analyzed archaeal genomes is available online at http://www.ncbi.nlm.nih.gov/Complete_Genomes/TCSarchaea.html. Copyright © 2018 Galperin et al.

Study and analysis of filtering characteristics of 1D photonic crystal

NASA Astrophysics Data System (ADS)

Juyal, Rohan; Suthar, Bhuvneshwer; Kumar, Arun

2018-05-01

Propagation of electromagnetic wave have been studied and analyzed through 1D photonic crystal. 1D photonic band gap material with low and high refractive index material has been chosen for this study. Band structure and reflectivity of this 1D structure has been calculated using transmission matrix method (TMM). Study and analysis of the band structure and reflectivity of this structure shows that this structure may work as an optical filter.

Review of Preliminary Analysis Techniques for Tension Structures.

DTIC Science & Technology

1984-02-01

INTRODUCTION. .. ..... ....... ....... .... 1 1.1 Purpose of Study .. .. ........ ......... 1I 1.2 Motivation for Study . .. ..... ....... ... 2 1.3 Scope...of Study .. .. ....... ........... 5 Chapter 2. MECHANICS OF TENSION STRUCTURES .. ...... ......... 6 2.1 Deployment Phase...Purpose of Study Tension structures are ones in which the main load-carrying members trans- mit applied loads to the foundations or other supporting

"What's in a structure?" The story of biguanides

NASA Astrophysics Data System (ADS)

Kathuria, Deepika; Bankar, Apoorva A.; Bharatam, Prasad V.

2018-01-01

Biguanides are a very interesting class of molecules which have been extensively studied for their medicinal applications. The structural and electronic structural aspects of biguanides have been explored in detail; however, even today, scientific literature continues to represent biguanides incorrectly as 1a. The X-ray crystal structure analysis and various spectroscopic studies such as UV, 1H and 15N NMR have confirmed that biguanide exists as tautomer 1b. Electronic structure analysis also supports the existence of 1b. This review focuses on the structure and electronic structure of biguanides and aims to emphasize the importance of the correct representation of a structure. There is a need to commence the use of 1b for the general representation of biguanides in textbooks and research articles which will ensure a correct perspective for further studies on these molecules.

Structural variability in Cu(I) and Ag(I) coordination polymers with a flexible dithione ligand: Synthesis, crystal structure, microbiological and theoretical studies

NASA Astrophysics Data System (ADS)

Beheshti, Azizolla; Nozarian, Kimia; Babadi, Susan Soleymani; Noorizadeh, Siamak; Motamedi, Hossein; Mayer, Peter; Bruno, Giuseppe; Rudbari, Hadi Amiri

2017-05-01

Two new compounds namely [Cu(SCN)(μ-L)]n (1) and {[Ag (μ2-L)](ClO4)}n (2) have been synthesized at room temperature by one-pot reactions between the 1,1-(1,4-butanediyl)bis(1,3-dihydro-3-methyl-1H-imidazole- 2-thione) (L) and appropriate copper(I) and silver(I) salts. These polymers have been characterized by single crystal X-ray diffraction, XRPD, TGA, elemental analysis, infrared spectroscopy, antibacterial activity and scanning probe microscopy studies. In the crystal structure of 1, copper atoms have a distorted trigonal planar geometry with a CuS2N coordination environment. Each of the ligands in the structure of 1 acting as a bidentate S-bridging ligand to form a 1D chain structure. Additionally, the adjacent 1D chains are interconnected by the intermolecular C-H…S interactions to create a 2D network structure. In contrast to 1, in the cationic 3D structure of 2 each of the silver atoms exhibits an AgS4 tetrahedral geometry with 4-membered Ag2S2 rings. In the structure of 2, the flexible ligand adopts two different conformations; gauche-anti-gauche and anti-anti-anti. The antibacterial studies of these polymers showed that polymer 2 is more potent antibacterial agent than 1. Scanning probe microscopy (SPM) study of the treated bacteria was carried out to investigate the structural changes cause by the interactions between the polymers and target bacteria. Theoretical study of polymer 1 investigated by the DFT calculations indicates that observed transitions at 266 nm and 302 nm in the UV-vis spectrum could be attributed to the π→π* and MLCT transitions, respectively.

Structure change of β-hairpin induced by turn optimization: an enhanced sampling molecular dynamics simulation study.

PubMed

Shao, Qiang; Yang, Lijiang; Gao, Yi Qin

2011-12-21

Our previous study showed that for the tested polypeptides which have similar β-hairpin structures but different sequences, their folding free energy pathways are dominantly determined by the turn conformational propensity. In this study, we study how the turn conformational propensity affects the structure of hairpins. The folding of two mutants of GB1p peptide (GB1m2 and GB1m3), which have the optimized turn sequence ((6)DDATK(11)T → (6)NPATG(11)K) with native structures unsolved, were simulated using integrated tempering sampling molecular dynamics simulations and the predicted stable structures were compared to wild-type GB1p. It was observed that the turn optimization of GB1p generates a more favored 5-residue type I(') turn in addition to the 6-residue type I turn in wild-type GB1p. As a result two distinctly different hairpin structures are formed corresponding to the "misfolded" (M) and the "folded" (F) states. M state is a one-residue-shifted asymmetric β-hairpin structure whereas F state has the similar symmetric hairpin structure as wild-type GB1p. The formation of the favored type I(') turn has a small free energy barrier and leads to the shifted β-hairpin structure, following the modified "zipping" model. The presence of disfavored type I turn structure makes the folding of a β-hairpin consistent with the "hydrophobic-core-centric" model. On the other hand, the folding simulations on other two GB1p mutants (GB1r1 and GBr2), which have the position of the hydrophobic core cluster further away from the turn compared to wild-type GB1p, showed that moving the hydrophobic core cluster away from the turn region destabilizes but does not change the hairpin structure. Therefore, the present study showed that the turn conformational propensity is a key factor in affecting not only the folding pathways but also the stable structure of β-hairpins, and the turn conformational change induced by the turn optimization leads to significant changes of β-hairpin structure.

Molecular Dynamic Simulation of Space and Earth-Grown Crystal Structures of Thermostable T1 Lipase Geobacillus zalihae Revealed a Better Structure.

PubMed

Ishak, Siti Nor Hasmah; Aris, Sayangku Nor Ariati Mohamad; Halim, Khairul Bariyyah Abd; Ali, Mohd Shukuri Mohamad; Leow, Thean Chor; Kamarudin, Nor Hafizah Ahmad; Masomian, Malihe; Rahman, Raja Noor Zaliha Raja Abd

2017-09-25

Less sedimentation and convection in a microgravity environment has become a well-suited condition for growing high quality protein crystals. Thermostable T1 lipase derived from bacterium Geobacillus zalihae has been crystallized using the counter diffusion method under space and earth conditions. Preliminary study using YASARA molecular modeling structure program for both structures showed differences in number of hydrogen bond, ionic interaction, and conformation. The space-grown crystal structure contains more hydrogen bonds as compared with the earth-grown crystal structure. A molecular dynamics simulation study was used to provide insight on the fluctuations and conformational changes of both T1 lipase structures. The analysis of root mean square deviation (RMSD), radius of gyration, and root mean square fluctuation (RMSF) showed that space-grown structure is more stable than the earth-grown structure. Space-structure also showed more hydrogen bonds and ion interactions compared to the earth-grown structure. Further analysis also revealed that the space-grown structure has long-lived interactions, hence it is considered as the more stable structure. This study provides the conformational dynamics of T1 lipase crystal structure grown in space and earth condition.

Studies on the syntheses, structural Characterization, antimicrobial of the CO-CRYSTAL 1,10-phenanthrolin-1-IUM(1,10-phenH+)-caffeine(caf)-hexafluorophosphate

NASA Astrophysics Data System (ADS)

El Hamdani, H.; El Amane, M.; Duhayon, C.

2018-03-01

Co-crystal of 1,10-phenanthrolin-1-ium-caffeine-hexafluorophosphate was synthesized, studied by FTIR, 1H, 13C NMR, DSC and X-ray structure and crystallized in the monoclinic space group C2/c. The unit cell parameters are a = 19.3761 (3), b = 17.9548 (3), c = 13.8074 (3) with β = 117.8132 (10). The final R value is 0.069 for 29,522 measured reflections. The co-crystal structure analysis indicate the 1,10-phenanthroline is protonated by one nitrogen atom and formed the 1,10-phenanthrolin-1-ium cation, which is stabilized by hydrogen bonds N+-H…Odbnd C interaction with carbonyl and imidazol ring in caffeine molecule. The intermolecular hydrogen bonds: Csbnd H...O, Csbnd H...N, Nsbnd H...O, Csbnd H...F and intramolecular hydrogen bond: C1sbnd H12...O14, together play a vital role in stabilizing the structure of co-crystal. The X-ray structural analysis confirm the assignments of the structure from infrared, 1H, 13C NMR, spectroscopic data DSC and molar conductivity analysis. The antimicrobial activity of the co-crystal was studied.

Trade study plan for Graphite Composite Primary Structure (GCPS)

NASA Technical Reports Server (NTRS)

Greenberg, H. S.

1994-01-01

This TA 2 document (with support from TA 1) describes the trade study plan that will identify the most suitable structural configuration for an SSTO winged vehicle capable of delivering 25,000 lbs to a 220 nm circular orbit at 51.6 degree inclination For this most suitable configuration the structural attachment of the wing, and the most suitable GCPS composite materials for intertank, wing, tail and thrust structure are identified. This trade study analysis uses extensive information derived in the TA 1 trade study plan and is identified within the study plan. In view of this, for convenience, the TA 1 study plan is included as an appendix to this document.

Structure and DNA-Binding Sites of the SWI1 AT-rich Interaction Domain (ARID) Suggest Determinants for Sequence-Specific DNA Recognition

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

Kim, Suhkmann; Zhang, Ziming; Upchurch, Sean

2004-04-16

2 ARID is a homologous family of DNA-binding domains that occur in DNA binding proteins from a wide variety of species, ranging from yeast to nematodes, insects, mammals and plants. SWI1, a member of the SWI/SNF protein complex that is involved in chromatin remodeling during transcription, contains the ARID motif. The ARID domain of human SWI1 (also known as p270) does not select for a specific DNA sequence from a random sequence pool. The lack of sequence specificity shown by the SWI1 ARID domain stands in contrast to the other characterized ARID domains, which recognize specific AT-rich sequences. We havemore » solved the three-dimensional structure of human SWI1 ARID using solution NMR methods. In addition, we have characterized non-specific DNA-binding by the SWI1 ARID domain. Results from this study indicate that a flexible long internal loop in ARID motif is likely to be important for sequence specific DNA-recognition. The structure of human SWI1 ARID domain also represents a distinct structural subfamily. Studies of ARID indicate that boundary of the DNA binding structural and functional domains can extend beyond the sequence homologous region in a homologous family of proteins. Structural studies of homologous domains such as ARID family of DNA-binding domains should provide information to better predict the boundary of structural and functional domains in structural genomic studies. Key Words: ARID, SWI1, NMR, structural genomics, protein-DNA interaction.« less

Application of Exploratory Structural Equation Modeling to Evaluate the Academic Motivation Scale

ERIC Educational Resources Information Center

Guay, Frédéric; Morin, Alexandre J. S.; Litalien, David; Valois, Pierre; Vallerand, Robert J.

2015-01-01

In this research, the authors examined the construct validity of scores of the Academic Motivation Scale using exploratory structural equation modeling. Study 1 and Study 2 involved 1,416 college students and 4,498 high school students, respectively. First, results of both studies indicated that the factor structure tested with exploratory…

47 CFR 1.61 - Procedures for handling applications requiring special aeronautical study.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Procedures for handling applications requiring special aeronautical study. (a) Antenna Structure Registration is conducted by the Wireless Telecommunications Bureau as follows: (1) Each antenna structure owner... modified construction, register that antenna structure with the Wireless Telecommunications Bureau using...

5-(1-Aryl-3-(thiophen-2-yl)-1H-pyrazol-4-yl)-1H-tetrazoles: Synthesis, structural characterization, Hirshfeld analysis, anti-inflammatory and anti-bacterial studies

NASA Astrophysics Data System (ADS)

Kumbar, Mahadev N.; Kamble, Ravindra R.; Dasappa, Jagadeesh Prasad; Bayannavar, Praveen K.; Khamees, Hussien Ahmed; Mahendra, M.; Joshi, Shrinivas D.; Dodamani, Suneel; Rasal, V. P.; Jalalpure, Sunil

2018-05-01

A series of novel 5-(1-aryl-3-(thiophen-2-yl)-1H-pyrazol-4-yl)-1H-tetrazoles 7(h-s) were designed and synthesized. Structural characterization was done by spectral and single crystal X-ray studies. The intermolecular interactions of compound 7n were quantified and visualized using Hirshfeld surface analysis. Structures of newly synthesized compounds were docked into active site of COX-2 enzyme PDB:

Perceived Discrimination and Social Relationship Functioning among Sexual Minorities: Structural Stigma as a Moderating Factor

PubMed Central

Doyle, David Matthew; Molix, Lisa

2015-01-01

Work on structural stigma shows how public policy affects health outcomes for members of devalued groups, including sexual minorities. In the current research, structural stigma is proposed as a moderating variable that strengthens deleterious associations between perceived discrimination and social relationship functioning. Hypotheses were tested in two cross-sectional studies, including both online (N = 214; Study 1) and community (N = 94; Study 2) samples of sexual minority men and women residing throughout the United States. Structural stigma was coded from policy related to sexual minority rights within each state. Confirming hypotheses, support for the moderating role of structural stigma was found via multilevel models across studies. Specifically, associations between perceived discrimination and friendship strain, loneliness (Study 1) and familial strain (Study 2) were increased for those who resided in states with greater levels of structural stigma and attenuated for those who resided in states with lesser levels. In Study 1, these results were robust to state-level covariates (conservatism and religiosity), but conservatism emerged as a significant moderator in lieu of structural stigma in Study 2. Results are discussed in the context of the shifting landscape of public policy related to sexual minority rights within the United States. PMID:26807046

Structural variability in Cu(I) and Ag(I) coordination polymers with a flexible dithione ligand: Synthesis, crystal structure, microbiological and theoretical studies

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

Beheshti, Azizolla, E-mail: a.beheshti@scu.ac.ir; Nozarian, Kimia; Babadi, Susan Soleymani

Two new compounds namely [Cu(SCN)(µ-L)]{sub n} (1) and ([Ag (µ{sub 2}-L)](ClO{sub 4})){sub n} (2) have been synthesized at room temperature by one-pot reactions between the 1,1-(1,4-butanediyl)bis(1,3-dihydro-3-methyl-1H-imidazole- 2-thione) (L) and appropriate copper(I) and silver(I) salts. These polymers have been characterized by single crystal X-ray diffraction, XRPD, TGA, elemental analysis, infrared spectroscopy, antibacterial activity and scanning probe microscopy studies. In the crystal structure of 1, copper atoms have a distorted trigonal planar geometry with a CuS{sub 2}N coordination environment. Each of the ligands in the structure of 1 acting as a bidentate S-bridging ligand to form a 1D chain structure. Additionally, themore » adjacent 1D chains are interconnected by the intermolecular C-H…S interactions to create a 2D network structure. In contrast to 1, in the cationic 3D structure of 2 each of the silver atoms exhibits an AgS{sub 4} tetrahedral geometry with 4-membered Ag{sub 2}S{sub 2} rings. In the structure of 2, the flexible ligand adopts two different conformations; gauche-anti-gauche and anti-anti-anti. The antibacterial studies of these polymers showed that polymer 2 is more potent antibacterial agent than 1. Scanning probe microscopy (SPM) study of the treated bacteria was carried out to investigate the structural changes cause by the interactions between the polymers and target bacteria. Theoretical study of polymer 1 investigated by the DFT calculations indicates that observed transitions at 266 nm and 302 nm in the UV–vis spectrum could be attributed to the π→π* and MLCT transitions, respectively. - Graphical abstract: Two new Cu(I) and Ag(I) coordination polymers have been have been synthesized by one-pot reactions. Copper complex has a 2D non-covalent structure, but silver compound is a 3D coordination compound. These compounds have effective antibacterial activity. - Highlights: • Cu(I) and Ag(I) based coordination polymers have different network structures. • Ag(I) polymer has more antibacterial activity than Cu(I) polymer. • DFT calculations of Cu(I) polymer has been investigated. • Cu(I) and Ag(I) polymers can destroy the structure of chromosomal and plasmid DNA.« less

Computational investigation of the human SOD1 mutant, Cys146Arg, that directs familial amyotrophic lateral sclerosis.

PubMed

Srinivasan, E; Rajasekaran, R

2017-07-25

The genetic substitution mutation of Cys146Arg in the SOD1 protein is predominantly found in the Japanese population suffering from familial amyotrophic lateral sclerosis (FALS). A complete study of the biophysical aspects of this particular missense mutation through conformational analysis and producing free energy landscapes could provide an insight into the pathogenic mechanism of ALS disease. In this study, we utilized general molecular dynamics simulations along with computational predictions to assess the structural characterization of the protein as well as the conformational preferences of monomeric wild type and mutant SOD1. Our static analysis, accomplished through multiple programs, predicted the deleterious and destabilizing effect of mutant SOD1. Subsequently, comparative molecular dynamic studies performed on the wild type and mutant SOD1 indicated a loss in the protein conformational stability and flexibility. We observed the mutational consequences not only in local but also in long-range variations in the structural properties of the SOD1 protein. Long-range intramolecular protein interactions decrease upon mutation, resulting in less compact structures in the mutant protein rather than in the wild type, suggesting that the mutant structures are less stable than the wild type SOD1. We also presented the free energy landscape to study the collective motion of protein conformations through principal component analysis for the wild type and mutant SOD1. Overall, the study assisted in revealing the cause of the structural destabilization and protein misfolding via structural characterization, secondary structure composition and free energy landscapes. Hence, the computational framework in our study provides a valuable direction for the search for the cure against fatal FALS.

Detecting molecular features of spectra mainly associated with structural and non-structural carbohydrates in co-products from bioEthanol production using DRIFT with uni- and multivariate molecular spectral analyses.

PubMed

Yu, Peiqiang; Damiran, Daalkhaijav; Azarfar, Arash; Niu, Zhiyuan

2011-01-01

The objective of this study was to use DRIFT spectroscopy with uni- and multivariate molecular spectral analyses as a novel approach to detect molecular features of spectra mainly associated with carbohydrate in the co-products (wheat DDGS, corn DDGS, blend DDGS) from bioethanol processing in comparison with original feedstock (wheat (Triticum), corn (Zea mays)). The carbohydrates related molecular spectral bands included: A_Cell (structural carbohydrates, peaks area region and baseline: ca. 1485-1188 cm(-1)), A_1240 (structural carbohydrates, peak area centered at ca. 1240 cm(-1) with region and baseline: ca. 1292-1198 cm(-1)), A_CHO (total carbohydrates, peaks region and baseline: ca. 1187-950 cm(-1)), A_928 (non-structural carbohydrates, peak area centered at ca. 928 cm(-1) with region and baseline: ca. 952-910 cm(-1)), A_860 (non-structural carbohydrates, peak area centered at ca. 860 cm(-1) with region and baseline: ca. 880-827 cm(-1)), H_1415 (structural carbohydrate, peak height centered at ca. 1415 cm(-1) with baseline: ca. 1485-1188 cm(-1)), H_1370 (structural carbohydrate, peak height at ca. 1370 cm(-1) with a baseline: ca. 1485-1188 cm(-1)). The study shows that the grains had lower spectral intensity (KM Unit) of the cellulosic compounds of A_1240 (8.5 vs. 36.6, P < 0.05), higher (P < 0.05) intensities of the non-structural carbohydrate of A_928 (17.3 vs. 2.0) and A_860 (20.7 vs. 7.6) than their co-products from bioethanol processing. There were no differences (P > 0.05) in the peak area intensities of A_Cell (structural CHO) at 1292-1198 cm(-1) and A_CHO (total CHO) at 1187-950 cm(-1) with average molecular infrared intensity KM unit of 226.8 and 508.1, respectively. There were no differences (P > 0.05) in the peak height intensities of H_1415 and H_1370 (structural CHOs) with average intensities 1.35 and 1.15, respectively. The multivariate molecular spectral analyses were able to discriminate and classify between the corn and corn DDGS molecular spectra, but not wheat and wheat DDGS. This study indicated that the bioethanol processing changes carbohydrate molecular structural profiles, compared with the original grains. However, the sensitivities of different types of carbohydrates and different grains (corn and wheat) to the processing differ. In general, the bioethanol processing increases the molecular spectral intensities for the structural carbohydrates and decreases the intensities for the non-structural carbohydrates. Further study is needed to quantify carbohydrate related molecular spectral features of the bioethanol co-products in relation to nutrient supply and availability of carbohydrates.

Performance evaluation of Arizona's LTPP SPS-1 project : strategic study of flexible pavement structural factors.

DOT National Transportation Integrated Search

2012-01-01

As part of the Long Term Pavement Performance (LTPP) Program, Arizona DOT constructed 16 SPS-1 test : sections on U.S. Route 93 near Kingman. The SPS-1 study was designed to study a variety of structural : sections in new asphalt concrete constructio...

Molecular basis of structural makeup of hulless barley in relation to rumen degradation kinetics and intestinal availability in dairy cattle: A novel approach.

PubMed

Damiran, D; Yu, P

2011-10-01

To date, no study has been done of molecular structures in relation to nutrient degradation kinetics and intestinal availability in dairy cattle. The objectives of this study were to (1) reveal molecular structures of hulless barley affected by structural alteration using molecular spectroscopy (diffuse reflectance infrared Fourier transform) as a novel approach, and (2) quantify structure features on a molecular basis in relation to digestive kinetics and nutritive value in the rumen and intestine in cattle. The modeled feeds in this study were 4 types of hulless barley (HB) cultivars modified in starch traits: (a) normal starch cultivar, (b) zero-amylose waxy, (c) waxy, and (d) high-amylose. The molecular structural features were determined using diffuse reflectance infrared Fourier transform spectroscopy in the mid-infrared region (ca. 4,000-800 cm(-1)) of the electromagnetic spectrum. The items assessed included infrared intensity attributed to protein amide I (ca. 1,715-1,575 cm(-1)), amide II (ca. 1,575-1,490 cm(-1)), α-helix (ca. 1,648-1,660 cm(-1)), β-sheet (ca. 1,625-1,640 cm(-1)), and their ratio, β-glucan (ca. 1,445-1,400 cm(-1)), total carbohydrates (CHO; ca. 1,188-820 cm(-1)) and their 3 major peaks, structural carbohydrates (ca. 1,277-1,190 cm(-1)), and ratios of amide I to II and amide I to CHO. The results show that (1) the zero-amylose waxy was the greatest in amide I and II peak areas, as well as in the ratio of protein amide I to CHO among HB; (2) α-helix-to-β-sheet ratio differed among HB: the high-amylose was the greatest, the zero-amylose waxy and waxy were the intermediate, and the normal starch was the lowest; (3) HB were similar in β-glucan and CHO molecular structural makeup; (4) altered starch HB cultivars were similar to each other, but were different from the normal starch cultivar in protein molecular makeup; and (5) the rate and extent of rumen degradation of starch and protein were highly related to the molecular structural makeup of HB. In conclusion, the molecular structural makeup on a molecular basis was related to rumen degradation kinetics and intestinal availability in dairy cattle. The alteration of starch structure in barley grain affects starch structure and the magnitude of protein and β-glucan contents, as well as the protein molecular structure of HB. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Advanced transportation system study: Manned launch vehicle concepts for two way transportation system payloads to LEO. Work breakdown structure and work breakdown structure dictionary

NASA Technical Reports Server (NTRS)

Duffy, James B.

1992-01-01

The report describes the work breakdown structure (WBS) and its associated WBS dictionary for task area 1 of contract NAS8-39207, advanced transportation system studies (ATSS). This WBS format is consistent with the preliminary design level of detail employed by both task area 1 and task area 4 in the ATSS study and is intended to provide an estimating structure for parametric cost estimates.

Multilayer photosensitive structures based on porous silicon and rare-earth-element compounds: Study of spectral characteristics

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

Kirsanov, N. Yu.; Latukhina, N. V., E-mail: natalat@yandex.ru; Lizunkova, D. A.

2017-03-15

The spectral characteristics of the specular reflectance, photosensitivity, and photoluminescence (PL) of multilayer structures based on porous silicon with rare-earth-element (REE) ions are investigated. It is shown that the photosensitivity of these structures in the wavelength range of 0.4–1.0 μm is higher than in structures free of REEs. The structures with Er{sup 3+} ions exhibit a luminescence response at room temperature in the spectral range from 1.1 to 1.7 μm. The PL spectrum of the erbium impurity is characterized by a fine line structure, which is determined by the splitting of the {sup 4}I{sub 15/2} multiplet of the Er{sup 3+}more » ion. It is shown that the structures with a porous layer on the working surface have a much lower reflectance in the entire spectral range under study (0.2–1.0 μm).« less

The Sla2p/HIP1/HIP1R family: similar structure, similar function in endocytosis?

PubMed

Gottfried, Irit; Ehrlich, Marcelo; Ashery, Uri

2010-02-01

HIP1 (huntingtin interacting protein 1) has two close relatives: HIP1R (HIP1-related) and yeast Sla2p. All three members of the family have a conserved domain structure, suggesting a common function. Over the past decade, a number of studies have characterized these proteins using a combination of biochemical, imaging, structural and genetic techniques. These studies provide valuable information on binding partners, structure and dynamics of HIP1/HIP1R/Sla2p. In general, all suggest a role in CME (clathrin-mediated endocytosis) for the three proteins, though some differences have emerged. In this mini-review we summarize the current views on the roles of these proteins, while emphasizing the unique attributes of each family member.

Study of structural design concepts for an arrow wing supersonic transport configuration, volume 1. Tasks 1 and 2

NASA Technical Reports Server (NTRS)

1976-01-01

A structural design study was made, based on a 1975 level of technology, to assess the relative merits of structural concepts and materials for an advanced supersonic transport cruising at Mach 2.7. Preliminary studies were made to insure compliance of the configuration with general design criteria, to integrate the propulsion system with the airframe, to select structural concepts and materials, and to define an efficient structural arrangement. An advanced computerized structural design system was used, in conjunction with a relatively large, complex finite element model, for detailed analysis and sizing of structural members to satisfy strength and flutter criteria. A baseline aircraft design was developed for assessment of current technology and for use in future studies of aerostructural trades, and application of advanced technology. Criteria, analysis methods, and results are presented.

Identifiability of large-scale non-linear dynamic network models applied to the ADM1-case study.

PubMed

Nimmegeers, Philippe; Lauwers, Joost; Telen, Dries; Logist, Filip; Impe, Jan Van

2017-06-01

In this work, both the structural and practical identifiability of the Anaerobic Digestion Model no. 1 (ADM1) is investigated, which serves as a relevant case study of large non-linear dynamic network models. The structural identifiability is investigated using the probabilistic algorithm, adapted to deal with the specifics of the case study (i.e., a large-scale non-linear dynamic system of differential and algebraic equations). The practical identifiability is analyzed using a Monte Carlo parameter estimation procedure for a 'non-informative' and 'informative' experiment, which are heuristically designed. The model structure of ADM1 has been modified by replacing parameters by parameter combinations, to provide a generally locally structurally identifiable version of ADM1. This means that in an idealized theoretical situation, the parameters can be estimated accurately. Furthermore, the generally positive structural identifiability results can be explained from the large number of interconnections between the states in the network structure. This interconnectivity, however, is also observed in the parameter estimates, making uncorrelated parameter estimations in practice difficult. Copyright © 2017. Published by Elsevier Inc.

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

Synthesis, structural characterization and density functional studies of ethyl 4-(biphenyl-4-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate A non-merohedral twinned structure

NASA Astrophysics Data System (ADS)

Yıdırım, Sema Öztürk; Büyükmumcu, Zeki; Butcher, Ray J.; Çetin, Gökalp; Şimşek, Rahime; Şafak, Cihat

2018-07-01

1,4-Dihydropyridine (1,4-DHP) derivatives have the reducing effect of extracellular Ca2+ ions influx on the L-type calcium channel. Because of this effect many 1,4-DHP derivatives are potent calcium channel blockers and antihypertensive agents. The biphenyl group is present in the structures of the most biologically active compounds and thus is an important group. By introducing this moiety into the structure of various compounds, active compounds are obtained. Thus, pharmacologically active structures can be condensed with the biphenyl structure to achieve novel biologically active compounds or compounds with increased activity. In this study, to achieve an active calcium channel blocker compound, the biphenyl group was introduced into the 1,4-DHP structure. The structure of the compound is proved by IR, 1H NMR, Mass spectroscopy, X-ray crystallography and elemental analysis. The cytotoxic activity assays have continued and positive results have been obtained. The phenyl rings [C16-C21 and C22-C27] make dihedral angles of 84.4 (1) and 87.5 (1)°, respectively, with the 1,4-dihydropyridine ring [N1/C1/C4-C9]. In the crystal, adjacent molecules are linked by Nsbnd H … O and Csbnd H … O hydrogen bonds into chains parallel to [010].

Detecting Molecular Features of Spectra Mainly Associated with Structural and Non-Structural Carbohydrates in Co-Products from BioEthanol Production Using DRIFT with Uni- and Multivariate Molecular Spectral Analyses

PubMed Central

Yu, Peiqiang; Damiran, Daalkhaijav; Azarfar, Arash; Niu, Zhiyuan

2011-01-01

The objective of this study was to use DRIFT spectroscopy with uni- and multivariate molecular spectral analyses as a novel approach to detect molecular features of spectra mainly associated with carbohydrate in the co-products (wheat DDGS, corn DDGS, blend DDGS) from bioethanol processing in comparison with original feedstock (wheat (Triticum), corn (Zea mays)). The carbohydrates related molecular spectral bands included: A_Cell (structural carbohydrates, peaks area region and baseline: ca. 1485–1188 cm−1), A_1240 (structural carbohydrates, peak area centered at ca. 1240 cm−1 with region and baseline: ca. 1292–1198 cm−1), A_CHO (total carbohydrates, peaks region and baseline: ca. 1187–950 cm−1), A_928 (non-structural carbohydrates, peak area centered at ca. 928 cm−1 with region and baseline: ca. 952–910 cm−1), A_860 (non-structural carbohydrates, peak area centered at ca. 860 cm−1 with region and baseline: ca. 880–827 cm−1), H_1415 (structural carbohydrate, peak height centered at ca. 1415 cm−1 with baseline: ca. 1485–1188 cm−1), H_1370 (structural carbohydrate, peak height at ca. 1370 cm−1 with a baseline: ca. 1485–1188 cm−1). The study shows that the grains had lower spectral intensity (KM Unit) of the cellulosic compounds of A_1240 (8.5 vs. 36.6, P < 0.05), higher (P < 0.05) intensities of the non-structural carbohydrate of A_928 (17.3 vs. 2.0) and A_860 (20.7 vs. 7.6) than their co-products from bioethanol processing. There were no differences (P > 0.05) in the peak area intensities of A_Cell (structural CHO) at 1292–1198 cm−1 and A_CHO (total CHO) at 1187–950 cm−1 with average molecular infrared intensity KM unit of 226.8 and 508.1, respectively. There were no differences (P > 0.05) in the peak height intensities of H_1415 and H_1370 (structural CHOs) with average intensities 1.35 and 1.15, respectively. The multivariate molecular spectral analyses were able to discriminate and classify between the corn and corn DDGS molecular spectra, but not wheat and wheat DDGS. This study indicated that the bioethanol processing changes carbohydrate molecular structural profiles, compared with the original grains. However, the sensitivities of different types of carbohydrates and different grains (corn and wheat) to the processing differ. In general, the bioethanol processing increases the molecular spectral intensities for the structural carbohydrates and decreases the intensities for the non-structural carbohydrates. Further study is needed to quantify carbohydrate related molecular spectral features of the bioethanol co-products in relation to nutrient supply and availability of carbohydrates. PMID:21673931

[Does the GHQ-12 scoring system affect its factor structure? An exploratory study of Ibero American students].

PubMed

Urzúa, Alfonso; Caqueo-Urízar, Alejandra; Bargsted, Mariana; Irarrázaval, Matías

2015-06-01

This study aimed to evaluate whether the scoring system of the General Health Questionnaire (GHQ-12) alters the instrument's factor structure. The method considered 1,972 university students from nine Ibero American countries. Modeling was performed with structural equations for 1, 2, and 3 latent factors. The mechanism for scoring the questions was analyzed within each type of structure. The results indicate that models with 2 and 3 factors show better goodness-of-fit. In relation to scoring mechanisms, procedure 0-1-1-1 for models with 2 and 3 factors showed the best fit. In conclusion, there appears to be a relationship between the response format and the number of factors identified in the instrument's structure. The model with the best fit was 3-factor 0-1-1-1-formatted, but 0-1-2-3 has acceptable and more stable indicators and provides a better format for two- and three-dimensional models.

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

Triclinic-monoclinic-orthorhombic (T-M-O) structural transitions in phase diagram of FeVO4-CrVO4 solid solutions

NASA Astrophysics Data System (ADS)

Bera, Ganesh; Reddy, V. R.; Rambabu, P.; Mal, P.; Das, Pradip; Mohapatra, N.; Padmaja, G.; Turpu, G. R.

2017-09-01

Phase diagram of FeVO4-CrVO4 solid solutions pertinent with structural and magnetic phases is presented with unambiguous experimental evidences. Solid solutions Fe1-xCrxVO4 (0 ≤ x ≤ 1.0) were synthesized through the standard solid state route and studied by X-ray diffraction, scanning electron microscopy, energy dispersive spectra of X-rays, Raman spectroscopy, d.c. magnetization, and 57Fe Mössbauer spectroscopic studies. FeVO4 and CrVO4 were found to be in triclinic (P-1 space group) and orthorhombic structures (Cmcm space group), respectively. Cr incorporation into the FeVO4 lattice leads to the emergence of a new monoclinic phase dissimilar to the both end members of the solid solutions. In Fe1-xCrxVO4 up to x = 0.10, no discernible changes in the triclinic structure were found. A new structural monoclinic phase (C2/m space group) emerges within the triclinic phase at x = 0.125, and with the increase in Cr content, it gets stabilized with clear single phase signatures in the range of x = 0.175-0.25 as evidenced by the Rietveld analysis of the structures. Beyond x = 0.33, orthorhombic phase similar to CrVO4 (Cmcm space group) emerges and coexists with a monoclinic structure up to x = 0.85, which finally tends to stabilize in the range of x = 0.90-1.00. The Raman spectroscopic studies also confirm the structural transition. FeVO4 Raman spectra show the modes related to three nonequivalent V ions in the triclinic structure, where up to 42 Raman modes are observed in the present study. With the stabilization of structures having higher symmetry, the number of Raman modes decreases and the modes related to symmetry inequivalent sites collate into singular modes from the doublet structure. A systematic crossover from two magnetic transitions in FeVO4, at 21.5 K and 15.4 K to single magnetic transition in CrVO4, at 71 K (antiferromagnetic transition), is observed in magnetization studies. The intermediate solid solution with x = 0.15 shows two magnetic transitions, whereas in the compound with x = 0.33 one of the magnetic transitions disappears. 57Fe Mössbauer spectroscopic studies show a finger print evidence for disappearance of non-equivalent sites of Fe as the structure changes from Triclinic-Monoclinic-Orthorhombic phases with the increasing Cr content in Fe1-xCrxVO4. Comprehensive studies related to the structural changes in Fe1-xCrxVO4 solid solutions lead us to detailed phase diagrams which shall be characteristic for room temperature structural and temperature dependent magnetic transitions in these solid solutions, respectively.

Molecular basis for TANK recognition by TRAF1 revealed by the crystal structure of TRAF1/TANK complex.

PubMed

Kim, Chang Min; Jeong, Jae-Hee; Son, Young-Jin; Choi, Jun-Hyuk; Kim, Sunghwan; Park, Hyun Ho

2017-03-01

Tumor necrosis factor receptor-associated factor 1 (TRAF1) is a multifunctional adaptor protein involved in important processes of cellular signaling, including innate immunity and apoptosis. TRAF family member-associated NF-kappaB activator (TANK) has been identified as a competitive intracellular inhibitor of TRAF2 function. Although TRAF recognition by various receptors has been studied extensively in the field of TRAF-mediated biology, molecular and functional details of TANK recognition and interaction with TRAF1 have not been studied. In this study, we report the crystal structure of the TRAF1/TANK peptide complex. Quantitative interaction experiments showed that TANK peptide interacts with both TRAF1 and TRAF2 with similar affinity in a micromolar range. Our structural study also reveals that TANK binds TRAF1 using a minor minimal consensus motif for TRAF binding, Px(Q/E)xT. Coordinate and structural factor were deposited in the Protein Data Bank under PDB ID code 5H10. © 2017 Federation of European Biochemical Societies.

Factor Structure and Psychometric Properties of the Injection Phobia Scale-Anxiety

ERIC Educational Resources Information Center

Olatunji, Bunmi O.; Sawchuk, Craig N.; Moretz, Melanie W.; David, Bieke; Armstrong, Thomas; Ciesielski, Bethany G.

2010-01-01

The present investigation examined the factor structure and psychometric properties of the Injection Phobia Scale-Anxiety (IPS-Anx). Principal components analysis of IPS-Anx items in Study 1 (n = 498) revealed a 2-factor structure consisting of Distal Fear and Contact Fear. However, CFA results in Study 2 (n = 567) suggest that a 1-factor…

Invariom based electron density studies on the C/Si analogues haloperidol/sila-haloperidol and venlafaxine/sila-venlafaxine.

PubMed

Luger, Peter; Dittrich, Birger; Tacke, Reinhold

2015-09-14

The subjects of this study are the structures and electron densities of the carbon/silicon analogues haloperidol/sila-haloperidol (1a/1b) and venlafaxine/sila-venlafaxine (2a/2b). The parent carbon compounds 1a (an antipsychotic agent) and 2a (an antidepressant) are both in clinical use. For haloperidol/sila-haloperidol, three published structures were studied in more detail: the structures of haloperidol hydrochloride (1a·HCl), haloperidol hydropicrate (1a·HPic) and sila-haloperidol hydrochloride (1b·HCl). For venlafaxine/sila-venlafaxine, the published structures of venlafaxine (2a), venlafaxine hydrochloride (2a·HCl; as orthorhombic (2a·HCl-ortho) and monoclinic polymorph (2a·HCl-mono)) and sila-venlafaxine hydrochloride (2b·HCl) were investigated. Based on these structures, the molecular electron densities were reconstructed by using the invariom formalism. They were further analysed in terms of Bader's quantum theory of atoms in molecules, electrostatic potentials mapped onto electron density isosurfaces and Hirshfeld surfaces. These studies were performed with a special emphasis on the comparison of the corresponding carbon/silicon analogues.

Molecular structure, interatomic interactions and vibrational analysis of 1,4-diazabicyclo[3.2.1]octane parent ring system

NASA Astrophysics Data System (ADS)

Britvin, Sergey N.; Rumyantsev, Andrey M.; Zobnina, Anastasia E.; Padkina, Marina V.

2017-02-01

Molecular structure of 1,4-diazabicyclo[3.2.1]octane, a parent ring of TAN1251 family of alkaloids, is herein characterized for the first time in comparison with the structure of nortropane (8-azabicyclo[3.2.1]octane), the parent framework of tropane ring system. The methods of study involve X-ray structural analysis, DFT geometry optimizations with infrared frequency calculations followed by natural bond orbital (NBO) analysis, and vibrational analysis of infrared spectrum.

Functional and structural insights into novel DREB1A transcription factors in common wheat (Triticum aestivum L.): A molecular modeling approach.

PubMed

Kumar, Anuj; Kumar, Sanjay; Kumar, Upendra; Suravajhala, Prashanth; Gajula, M N V Prasad

2016-10-01

Triticum aestivum L. known as common wheat is one of the most important cereal crops feeding a large and growing population. Various environmental stress factors including drought, high salinity and heat etc. adversely affect wheat production in a significant manner. Dehydration-responsive element-binding (DREB1A) factors, a class of transcription factors (TF) play an important role in combating drought stress. It is known that DREB1A specifically interacts with the dehydration responsive elements (DRE/CRT) inducing expression of genes involved in environmental stress tolerance in plants. Despite its critical interplay in plants, the structural and functional aspects of DREB1A TF in wheat remain unresolved. Previous studies showed that wheat DREBs (DREB1 and DREB2) were isolated using various methods including yeast two-hybrid screens but no extensive structural models were reported. In this study, we made an extensive in silico study to gain insight into DREB1A TF and reported the location of novel DREB1A in wheat chromosomes. We inferred the three-dimensional structural model of DREB1A using homology modelling and further evaluated them using molecular dynamics(MD) simulations yielding refined modelled structures. Our biochemical function predictions suggested that the wheat DREB1A orthologs have similar biochemical functions and pathways to that of AtDREB1A. In conclusion, the current study presents a structural perspective of wheat DREB1A and helps in understanding the molecular basis for the mechanism of DREB1A in response to environmental stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

MoTe2, A novel anode material for sodium ion battery

NASA Astrophysics Data System (ADS)

Panda, Manas Ranjan; Anish Raj, K.; Bao, Qiaoliang; Mitra, Sagar

2018-04-01

2D layered transition metal dichalcogenides are considered as a potential anode for sodium-ion batteries due to their high specific capacity, structural stability and its well-developed two-dimensional layers. 2D layered structure Molybdenum ditelluride (MoTe2) provides a superior Na-ion storage properties in sodium ion battery due to its comparative more interlayer spacing (0.699 nm). In the current study MoTe2 polycrystalline powder sample has been prepared by solid state reaction process, the structural and morphological studies have been carried out by XRD, FE-SEM and EDS etc. XRD study revealsthe well crystalline structure of the material having hexagonal structure. FE-SEM and EDS studies depict the uniformflakes like structure of the material. When it is tested as sodium-ion battery anode by applying a potential window 0.1-2.5 V, the material demonstrates a high capacity and high power performances. The as prepared MoTe2 shows an initial discharge capacity of 376 mA h g-1 and a corresponding discharge capacity of 303 mA h g-1 after the 50th cycle at a current density of 500 mA g-1.

Alteration of blood clot structures by interleukin-1 beta in association with bone defects healing

PubMed Central

Wang, Xin; Friis, Thor E.; Masci, Paul P.; Crawford, Ross W.; Liao, Wenbo; Xiao, Yin

2016-01-01

The quality of hematomas are crucial for successful early bone defect healing, as the structure of fibrin clots can significantly influence the infiltration of cells, necessary for bone regeneration, from adjacent tissues into the fibrin network. This study investigated if there were structural differences between hematomas from normal and delayed healing bone defects and whether such differences were linked to changes in the expression of IL-1β. Using a bone defect model in rats, we found that the hematomas in the delayed healing model had thinner fibers and denser clot structures. Moreover, IL-1β protein levels were significantly higher in the delayed healing hematomas. The effects of IL-1β on the structural properties of human whole blood clots were evaluated by thrombelastograph (TEG), scanning electronic microscopy (SEM), compressive study, and thrombolytic assays. S-nitrosoglutathione (GSNO) was applied to modulate de novo hematoma structure and the impact on bone healing was evaluated in the delayed healing model. We found that GSNO produced more porous hematomas with thicker fibers and resulted in significantly enhanced bone healing. This study demonstrated that IL-1β and GSNO had opposing effects on clot architecture, the structure of which plays a pivotal role in early bone healing. PMID:27767056

Polarized light microscopy study on the reentrant phase transition in a (Ba 1–xK x)Fe 2As 2 single crystal with x = 0.24

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

Liu, Yong; Tanatar, Makariy A.; Timmons, Erik

In this study, a sequence of structural/magnetic transitions on cooling is reported in the literature for hole-doped iron-based superconductor (Ba 1–xK x)Fe 2As 2 with x = 0.24. By using polarized light microscopy, we directly observe the formation of orthorhombic domains in (Ba 1–xK x)Fe 2As 2 (x = 0.24) single crystal below a temperature of simultaneous structural/magnetic transition T N ~ 80 K. The structural domains vanish below ~30 K, but reappear below T = 15 K. Our results are consistent with reentrance transformation sequence from high-temperature tetragonal (HTT) to low temperature orthorhombic (LTO1) structure at T N ~more » 80 K, LTO1 to low temperature tetragonal (LTT) structure at T c ~ 25 K, and LTT to low temperature orthorhombic (LTO2) structure at T ~ 15 K.« less

Polarized light microscopy study on the reentrant phase transition in a (Ba 1–xK x)Fe 2As 2 single crystal with x = 0.24

DOE PAGES

Liu, Yong; Tanatar, Makariy A.; Timmons, Erik; ...

2016-11-09

In this study, a sequence of structural/magnetic transitions on cooling is reported in the literature for hole-doped iron-based superconductor (Ba 1–xK x)Fe 2As 2 with x = 0.24. By using polarized light microscopy, we directly observe the formation of orthorhombic domains in (Ba 1–xK x)Fe 2As 2 (x = 0.24) single crystal below a temperature of simultaneous structural/magnetic transition T N ~ 80 K. The structural domains vanish below ~30 K, but reappear below T = 15 K. Our results are consistent with reentrance transformation sequence from high-temperature tetragonal (HTT) to low temperature orthorhombic (LTO1) structure at T N ~more » 80 K, LTO1 to low temperature tetragonal (LTT) structure at T c ~ 25 K, and LTT to low temperature orthorhombic (LTO2) structure at T ~ 15 K.« less

Use of Monoclonal Antibodies to Study the Structural Basis of the Function of Nicotinic Acetylcholine Receptors on Electric Organ and Muscle and to Determine the Structure of Nicotinic Acetylcholine Receptors on Neurons

DTIC Science & Technology

1989-03-16

nucleus robustus archistriatalis 1 1 1 nucleus reticularis gigantocellularis 1 3 3 nucleus reticularis lateralis 1 3 3 nucleus ... reticularis pontis caudalis 1 1 3 nucleus reticularis parvocellularis 1 1 2 nucleus rotundus 1 1 1 nucleus tractus solitarii 1 3 3 nucleus semilunaris...Structure a-bungarotoxin mAb 35 inAb 270 nucleus accumbens 1 1 1 nucleus basalis 1 1 1 nucleus cerebelli intermedium 2 3 3

Why don't we find more polymorphs?

PubMed

Price, Sarah L

2013-08-01

Crystal structure prediction (CSP) studies are not limited to being a search for the most thermodynamically stable crystal structure, but play a valuable role in understanding polymorphism, as shown by interdisciplinary studies where the crystal energy landscape has been explored experimentally and computationally. CSP usually produces more thermodynamically plausible crystal structures than known polymorphs. This article illustrates some reasons why: because (i) of approximations in the calculations, particularly the neglect of thermal effects (see §1.1); (ii) of the molecular rearrangement during nucleation and growth (see §1.2); (iii) the solid-state structures observed show dynamic or static disorder, stacking faults, other defects or are not crystalline and so represent more than one calculated structure (see §1.3); (iv) the structures are metastable relative to other molecular compositions (see §1.4); (v) the right crystallization experiment has not yet been performed (see §1.5) or (vi) cannot be performed (see §1.6) and the possibility (vii) that the polymorphs are not detected or structurally characterized (see §1.7). Thus, we can only aspire to a general predictive theory for polymorphism, as this appears to require a quantitative understanding of the kinetic factors involved in all possible multi-component crystallizations. For a specific molecule, analysis of the crystal energy landscape shows the potential complexity of its crystallization behaviour.

Detoxification of aflatoxins on prospective approach: effect on structural, mechanical, and optical properties under pressures.

PubMed

Wei, Yong-Kai; Zhao, Xiao-Miao; Li, Meng-Meng; Yu, Jing-Xin; Gurudeeban, Selvaraj; Hu, Yan-Fei; Ji, Guang-Fu; Wei, Dong-Qing

2018-06-01

Aflatoxins are sequential of derivatives of coumarin and dihydrofuran with similar chemical structures and well-known carcinogenic agent. Many studies performed to detoxify aflatoxins, but the result is not ideal. Therefore, we studied structural, infrared spectrum, mechanical, and optical properties of these compounds in the aim of perspective physics. Mulliken charge distributions and infrared spectral analysis performed to understand the structural difference between the basic types of aflatoxins. In addition, the effect of pressure, different polarized, and incident directions on their structural changes was determined. It is found that AFB 1 is most stable structure among four basic types aflatoxins (AFB 1 , AFB 2 , AFG 1 , and AFG 2 ), and IR spectra are analyzed to exhibit the difference on structures of them. The mechanical properties of AFB 1 indicate that the structure of this toxin can be easily changed by pressure. The real [Formula: see text] and imaginary [Formula: see text] parts of the dielectric function, and the absorption coefficient [Formula: see text] and energy loss spectrum [Formula: see text] were also obtained under different polarized and incident directions. Furthermore, biological experiments needed to support the toxic level of AFB 1 using optical technologies.

Structural phase transitions in GaAs to 108 GPa

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

Weir, S.T.; Vohra, Y.K.; Vanderborgh, C.A.

1989-01-15

The III-V compound GaAs was studied using energy-dispersive x-ray diffraction with a synchro- tron source up to a pressure of 108 GPa. When the pressure was increased to 16.6 GPa, the GaAs sample transformed from the zinc-blende structure to an orthorhombic structure (GaAs(II)), space group Pmm2, consisting of a primitive orthorhombic lattice with a basis of (0,0,0) and (0,(1/2,..cap alpha..), where ..cap alpha.. = 0.35. Upon a further increase of pressure to 24 +- 1 GPa, GaAs(II) transformed to another orthorhombic structure (GaAs(III)), space group Imm2, consisting of a body-centered orthorhombic lattice with a basis of (0,0,0) and (0, (1/2,..delta..),more » where ..delta.. is 0.425 at 28.1 GPa. With increasing pressure, ..delta.. approached (1/2 and the GaAs(III) structure gradually assumed the symmetry of the simple hexagonal structure. The transition to the simple hexagonal structure (GaAs(IV)) was completed in the vicinity of 60--80 GPa. The structure remains simple hexagonal up to at least 108 GPa, the highest pressure reached in this study.« less

Structures of invisible, excited protein states by relaxation dispersion NMR spectroscopy

PubMed Central

Vallurupalli, Pramodh; Hansen, D. Flemming; Kay, Lewis E.

2008-01-01

Molecular function is often predicated on excursions between ground states and higher energy conformers that can play important roles in ligand binding, molecular recognition, enzyme catalysis, and protein folding. The tools of structural biology enable a detailed characterization of ground state structure and dynamics; however, studies of excited state conformations are more difficult because they are of low population and may exist only transiently. Here we describe an approach based on relaxation dispersion NMR spectroscopy in which structures of invisible, excited states are obtained from chemical shifts and residual anisotropic magnetic interactions. To establish the utility of the approach, we studied an exchanging protein (Abp1p SH3 domain)–ligand (Ark1p peptide) system, in which the peptide is added in only small amounts so that the ligand-bound form is invisible. From a collection of 15N, 1HN, 13Cα, and 13CO chemical shifts, along with 1HN-15N, 1Hα-13Cα, and 1HN-13CO residual dipolar couplings and 13CO residual chemical shift anisotropies, all pertaining to the invisible, bound conformer, the structure of the bound state is determined. The structure so obtained is cross-validated by comparison with 1HN-15N residual dipolar couplings recorded in a second alignment medium. The methodology described opens up the possibility for detailed structural studies of invisible protein conformers at a level of detail that has heretofore been restricted to applications involving visible ground states of proteins. PMID:18701719

TED Study of Si(113) Surfaces

NASA Astrophysics Data System (ADS)

Suzuki, T.; Minoda, H.; Tanishiro, Y.; Yagi, K.

A TED study of Si(113) surfaces was carried out. Reflections from the 3 × 2 reconstruction were seen at room temperature, while half-order reflections were very faint. The surface showed the phase transition between the 3 × 1 and the disordered (rough) structures at about 930°C. The (113) surface structure at room temperature was analyzed using TED intensity. Four kinds of structure models proposed previously, including both the 3 × 1 and the 3 × 2 reconstructed structures, were examined. The R-factors calculated using the energy-optimized atomic coordinates are not sufficiently small. After minimization of the R-factors, Dabrowski's 3 × 2 structure model is most agreeable, while Ranke's 3 × 1 and 3 × 2 structure models are not to be excluded. STM observation showed that the surface is composed of small domains of the 3 × 2 structure.

Synthesis and structural investigation of new Co1-xNixTeO4 (x = 0, 0.2, 0.5, 0.8 and 1) compounds

NASA Astrophysics Data System (ADS)

Patel, Akhilesh K.; Singh, Harishchandra; Suresh, K. G.

2018-05-01

The new polycrystalline compounds Co1-xNixTeO4 (x = 0, 0.2, 0.5, 0.8 and 1) were prepared by sol-gel method and their structural properties have been studied. Structural investigation through Rietveld method shows monoclinic structure with space group P21/c for all compounds. All compounds polyhedral structure found to be in octahedral form with cations (M) at the center and six oxygen atoms at corner of octahedral structure. The lattice parameters variation with Ni substitution are found to be decreasing with Ni substitution.

Domain alternation and active site remodeling are conserved structural features of ubiquitin E1.

PubMed

Lv, Zongyang; Yuan, Lingmin; Atkison, James H; Aldana-Masangkay, Grace; Chen, Yuan; Olsen, Shaun K

2017-07-21

E1 enzymes for ubiquitin (Ub) and Ub-like modifiers (Ubls) harbor two catalytic activities that are required for Ub/Ubl activation: adenylation and thioester bond formation. Structural studies of the E1 for the Ubl s mall u biquitin-like mo difier (SUMO) revealed a single active site that is transformed by a conformational switch that toggles its competency for catalysis of these two distinct chemical reactions. Although the mechanisms of adenylation and thioester bond formation revealed by SUMO E1 structures are thought to be conserved in Ub E1, there is currently a lack of structural data supporting this hypothesis. Here, we present a structure of Schizosaccharomyces pombe Uba1 in which the second catalytic cysteine half-domain (SCCH domain) harboring the catalytic cysteine has undergone a 106° rotation that results in a completely different network of intramolecular interactions between the SCCH and adenylation domains and translocation of the catalytic cysteine 12 Å closer to the Ub C terminus compared with previous Uba1 structures. SCCH domain alternation is accompanied by conformational changes within the Uba1 adenylation domains that effectively disassemble the adenylation active site. Importantly, the structural and biochemical data suggest that domain alternation and remodeling of the adenylation active site are interconnected and are intrinsic structural features of Uba1 and that the overall structural basis for adenylation and thioester bond formation exhibited by SUMO E1 is indeed conserved in Ub E1. Finally, the mechanistic insights provided by the novel conformational snapshot of Uba1 presented in this study may guide efforts to develop small molecule inhibitors of this critically important enzyme that is an active target for anticancer therapeutics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Effect of Se concentration on photonic bandgap of 1-D As-S-Se/air multilayers

NASA Astrophysics Data System (ADS)

Singh, Rajpal; Suthar, B.; Bhargava, A.

2018-05-01

The photonic band structure of 1-D chalcogenide photonic crystal consisting of As-S-Se/air multilayered structure is studied. The photonic band structure is calculated using plane wave expansion method. The effect of Se constration on the photonic bandgap is studied. It is found that the photonic bandgap increases with Se-concentration and shows the red shift.

Structure Evolution of BaTiO3 on Co Doping: X-ray diffraction and Raman study

NASA Astrophysics Data System (ADS)

Mansuri, Amantulla; Mishra, Ashutosh

2016-10-01

In the present study, we have synthesize polycrystalline samples of BaTi1-xCoxO3 (x = 0, 0.05 and 0.1) with standard solid state reaction technique. The obtained samples are characterized by X-ray diffraction (XRD) and Raman spectroscopy. The detail structural analysis has been performed by Rietveld refinement using Fullprof program. The structural analysis reveal the samples are chemical pure and crystallize in tetragonal phase with space group Pm3m. We observe an increase in lattice parameters which results due to substitution of Co2+ with large ionic radii (0.9) for smaller ionic radii (0.6) Ti4+. Moreover peak at 45.5° shift to 45° on Co doping, which is due to structure phase transition from tetragonal to cubic. Raman study infers that the intensity of characteristic peaks decreases and linewidth increases with Co doping. The bands linked with the tetragonal structure (307 cm1) decreased due to the tetragonal-towards-cubic phase transition with Co doping. Our structural study reveals the expansion of BTO unit cell and tetragonal-to-cubic phase transformation takes place, results from different characterization techniques are conclusive and show structural evolution with Co doping.

New biochemical insight of conserved water molecules at catalytic and structural Zn2+ ions in human matrix metalloproteinase-I: a study by MD-simulation.

PubMed

Chakrabarti, Bornali; Bairagya, Hridoy R; Mukhopadhyay, Bishnu P; Sekar, K

2017-02-01

Human matrix metalloproteinase (MMP)-1 or collagenase-1 plays a significant role in embryonic development, tissue remodeling, and is also involved in several diseases like arthritis, metastasis, etc. Molecular dynamics simulation studies on hMMP-1 X-ray structures (PDB Id. 1CGE, 1CGF, 1CGL, 1HFC, and 2TCL) suggest that the three conserved water molecules (W H/1 , W I , W S ) are coordinated with catalytic zinc (Zn C ), and one water molecule (W) is associated at structural zinc ion (Zn S ). Transition of the coordination geometry around Zn C from tetrahedral to octahedral and tetrahedral to trigonal bipyramidal at Zn S are also observed during the dynamics. Recognition of two zinc ions through water mediated bridges (Zn C - W H (W 1 )…W 2 ….H 183 - Zn S ) and stabilization of secondary coordination zone around the metal ions indicates the possibility of Zn C …Zn S coupled catalytic mechanism in hMMP-I. This study not only reveals a functionally important role of conserved water molecules in hMMP-I but also highlights the involvement of other non catalytic residues, such as S172 and D170 in the catalytic mechanism. The results obtained in this study could be relevant for importance of conserved water mediated recognition site of the sequence residue id. 202(RWTNNFREY)210, interaction of W(tryptophan)203 to zinc bound histidine, their influence on the water molecules that are involved in bridging between Zn C and Zn S , and structure-based design of specific hMMP inhibitors. Graphical abstract Water mediated recognition of structural and catalytic zinc ions of hMMP-1 structure (MD simulatated conformation).

G2-structures for N  =  1 supersymmetric AdS4 solutions of M-theory

NASA Astrophysics Data System (ADS)

Grigorian, Sergey

2018-04-01

We study the N  =  1 supersymmetric solutions of D  =  11 supergravity obtained as a warped product of four-dimensional anti-de Sitter space with a seven-dimensional Riemannian manifold M. Using the octonion bundle structure on M we reformulate the Killing spinor equations in terms of sections of the octonion bundle on M. The solutions then define a single complexified G 2-structure on M or equivalently two real G 2-structures. We then study the torsion of these G 2-structures and the relationships between them.

Contribution of gravity data and Sentinel-1 image for structural mapping. Case of Beni Mellal Atlas and Beni Moussa plain (Morocco).

NASA Astrophysics Data System (ADS)

Boutirame, Ikram; Boukdir, Ahmed; Akhssas, Ahmed; Boutirame, Fatima; Manar, Ahmed; Aghzzaf, Brahim

2018-05-01

The present work is a combined study of gravity and Sentine-1 data for fracture mapping in the karstic massif of Beni Mellal Atlas and the adjacent plain of Beni Moussa. In order to locate the various faults that contribute to the study area structuring, the gravimetric contacts analysis method, based on the joint use of the horizontal gradient and the upward continuation at different altitudes, has been applied to the gravity data. To optimize the structural mapping in the study area, the gravimetric lineaments obtained were completed and correlated with the lineaments got from Sentinel-1 image. Four faults families of NE-SW; E-O; N-S and NWSE directions have been highlighted. There fault families are perfectly combined with the studied area's surface water network, moreover, they corroborate with the previous geological and structural studies.

Effect of two imidazolium derivatives of ionic liquids on the structure and activity of adenosine deaminase.

PubMed

Ajloo, Davood; Sangian, Masoomeh; Ghadamgahi, Maryam; Evini, Mina; Saboury, Ali Akbar

2013-04-01

The effect of two ionic liquids, 1-allyl 3-methyl-imidazolium (IL1) and 1-octhyl 3-methyl-imidozolium chlorides (IL2), on the structure and activity of adenosine deaminase (ADA) were described by UV-vis and fluorescence spectrophotometry in phosphate buffer and results were compared with docking and molecular dynamics (MD) simulation studies. All results showed that inhibition of activity and reduction of enzyme tertiary structure are more for octhyl than allyl derivative due to the more hydrophobic property of it. Finally structure parameters obtained from MD simulation showed that ionic liquid reduces intermolecular hydrogen bond and unfold enzyme structure. Calculation results are in good agreement with spectrophotometric studies. Copyright © 2013 Elsevier B.V. All rights reserved.

Magnetic structure in Mn1 -xCoxGe compounds

NASA Astrophysics Data System (ADS)

Altynbaev, E.; Siegfried, S.-A.; Strauß, P.; Menzel, D.; Heinemann, A.; Fomicheva, L.; Tsvyashchenko, A.; Grigoriev, S.

2018-04-01

The magnetic system of the pseudobinary compound Mn1 -xCoxGe has been studied using small-angle neutron scattering and susceptibility measurements. It is found that Mn1 -xCoxGe orders magnetically at low temperatures in the whole concentration range of x ∈[0 /0.9 ] . Four different states of the magnetic structure have been found at low temperatures: the long-range-ordered (LRO) short-period helical magnetic structure at x

SFG spectroscopy from 10 -8 to 1000 mbar: less-ordered CO structures and coadsorption on Pd (1 1 1)

NASA Astrophysics Data System (ADS)

Morkel, Matthias; Unterhalt, Holger; Salmeron, Miquel; Rupprechter, Günther; Freund, Hans-Joachim

2003-06-01

Vibrational sum frequency generation spectroscopy was employed to study "less-ordered" phases resulting from low-temperature CO exposure on Pd(1 1 1). Such imperfect structures may also occur under catalytic reaction conditions up to 1000 mbar and originate from the superposition of ordered structures when the CO mobility and flux were insufficient. The effect of coadsorbed hydrogen and water was also examined.

Analyzing The Effect of Skin Postbuckling on General Stresses, Strains and Stability of Composite Structures

NASA Technical Reports Server (NTRS)

Zamula, G. N.; Ierusalimsky, K. M.; Kalmykova, G. S.; Fomin, V. P.

1998-01-01

The present paper is a final technical report within the NCCW-1-233 research program (dated June 1, 1997) accomplished as a part of co-operation between United States' NASA and Russia's Goskomoboronprom in aeronautics, and continues similar NCCW-73 and NCC-1-233 programs accomplished in 1996 and 1997, respectively. The report concludes studies in two domains, "Analyzing the effect of skin postbuckling on general stresses and strains in a composite structure" and "Evaluating the effect of skin postbuckling behavior on general stability of a composite structure"; the work was fulfilled in compliance with NCC-1-233 requirements (as of June 1, 1997). Also, the present studies may be regarded as a partial generalization of efforts in [1, 2] conducted within the above programs in what concerns postbuckling behavior of composite structures.

Controlled synthesis of nanostructured molybdenum oxide electrodes for high performance supercapacitor devices

NASA Astrophysics Data System (ADS)

Maheswari, Nallappan; Muralidharan, Gopalan

2017-09-01

Well defined crystallographic and one dimensional morphological structure of molybdenum oxide were successfully synthesized by adjusting the duration of hydrothermal treatment. The prepared molybdenum oxide was examined through XRD, SEM, FTIR, TEM, BET and electrochemical studies. The XRD patterns illustrate that MoOx prepared by variying the hydrothermal reaction time are in different crystallographic structure of MoyOx (Mo8O23 and MoO3). SEM studies reveal the different morphological structures ranging from flake like morphology to nanorods. TEM images confirm the excellent nanorod structure. The nanorod structure ensures good cyclic behaviour with maximum capacitance of 1080 F g-1 at a current density of 2 A g-1. This large capacity of the MoO3 nanostructures enabled fabrication of symmetric and asymmertic supercapacitor devices. The asymmertic device exhibits a maximum specific capacitance of 145 F g-1 at 2 mV s-1 with highest energy density of 38.6 W h kg-1 at 374.7 W kg-1 power density.

Activator Protein-1: redox switch controlling structure and DNA-binding

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

Yin, Zhou; Machius, Mischa; Nestler, Eric J.

The transcription factor, activator protein-1 (AP-1), binds to cognate DNA under redox control; yet, the underlying mechanism has remained enigmatic. A series of crystal structures of the AP-1 FosB/JunD bZIP domains reveal ordered DNA-binding regions in both FosB and JunD even in absence DNA. However, while JunD is competent to bind DNA, the FosB bZIP domain must undergo a large conformational rearrangement that is controlled by a ‘redox switch’ centered on an inter-molecular disulfide bond. Solution studies confirm that FosB/JunD cannot undergo structural transition and bind DNA when the redox-switch is in the ‘OFF’ state, and show that the mid-pointmore » redox potential of the redox switch affords it sensitivity to cellular redox homeostasis. The molecular and structural studies presented here thus reveal the mechanism underlying redox-regulation of AP-1 Fos/Jun transcription factors and provide structural insight for therapeutic interventions targeting AP-1 proteins.« less

Structural basis of nectin-1 recognition by pseudorabies virus glycoprotein D

PubMed Central

Qi, Jianxun; Wu, Lili; Tian, Kegong; Luo, Tingrong; Shi, Yi

2017-01-01

An early and yet indispensable step in the alphaherpesvirus infection is the engagement of host receptors by the viral envelope glycoprotein D (gD). Of the thus-far identified gD receptors, nectin-1 is likely the most effective in terms of its wide usage by multiple alphaherpesviruses for cell entry. The molecular basis of nectin-1 recognition by the gD protein is therefore an interesting scientific question in the alphaherpesvirus field. Previous studies focused on the herpes simplex virus (HSV) of the Simplexvirus genus, for which both the free gD structure and the gD/nectin-1 complex structure were reported at high resolutions. The structural and functional features of other alphaherpesviral gDs, however, remain poorly characterized. In the current study, we systematically studied the characteristics of nectin-1 binding by the gD of a Varicellovirus genus member, the pseudorabies virus (PRV). We first showed that PRV infects host cells via both human and swine nectin-1, and that its gD exhibits similar binding affinities for nectin-1 of the two species. Furthermore, we demonstrated that removal of the PRV gD membrane-proximal residues could significantly increase its affinity for the receptor binding. The structures of PRV gD in the free and the nectin-1-bound states were then solved, revealing a similar overall 3D fold as well as a homologous nectin-1 binding mode to its HSV counterpart. However, several unique features were observed at the binding interface of PRV gD, enabling the viral ligand to utilize different gD residues (from those of HSV) for nectin-1 engagement. These observed binding characteristics were further verified by the mutagenesis study using the key-residue mutants of nectin-1. The structural and functional data obtained in this study, therefore, provide the basis of receptor recognition by PRV gD. PMID:28542478

Solid-State NMR Studies of Amyloid Materials: A Protocol to Define an Atomic Model of Aβ(1-42) in Amyloid Fibrils.

PubMed

Xiao, Yiling; McElheny, Dan; Hoshi, Minako; Ishii, Yoshitaka

2018-01-01

Intense efforts have been made to understand the molecular structures of misfolded amyloid β (Aβ) in order to gain insight into the pathological mechanism of Alzheimer's disease. Solid-state NMR spectroscopy (SSNMR) is considered a primary tool for elucidating the structures of insoluble and noncrystalline amyloid fibrils and other amyloid assemblies. In this chapter, we describe a detailed protocol to obtain the first atomic model of the 42-residue human Aβ peptide Aβ(1-42) in structurally homogeneous amyloid fibrils from our recent SSNMR study (Nat Struct Mol Biol 22:499-505, 2015). Despite great biological and clinical interest in Aβ(1-42) fibrils, their structural details have been long-elusive until this study. The protocol is divided into four sections. First, the solid-phase peptide synthesis (SPPS) and purification of monomeric Aβ(1-42) is described. We illustrate a controlled incubation method to prompt misfolding of Aβ(1-42) into homogeneous amyloid fibrils in an aqueous solution with fragmented Aβ(1-42) fibrils as seeds. Next, we detail analysis of Aβ(1-42) fibrils by SSNMR to obtain structural restraints. Finally, we describe methods to construct atomic models of Aβ(1-42) fibrils based on SSNMR results through two-stage molecular dynamics calculations.

Association of fluorescein anterior corneal mosaic and corneal K-structures by in vivo laser confocal microscopy in patients with keratoconus.

PubMed

Kobayashi, Akira; Yokogawa, Hideaki; Mori, Natsuko; Masaki, Toshinori; Sugiyama, Kazuhisa

2017-01-01

To report the in vivo laser confocal microscopy findings of corneas with keratoconus, with special attention to abnormality of Bowman's layer and sub-Bowman's fibrous structures (Kobayashi-structures [K-structures]). Sixteen keratoconic eyes in 8 consecutive patients with keratoconus (4 males, 4 females, mean age, 41.1 years) were included in this study. Slit-lamp biomicroscopic photos were taken with or without fluorescein staining. The existence of anterior corneal mosaic (ACM) after eyelid rubbing under fluorescein staining was documented. In vivo laser confocal microscopic examinations were performed for all patients in both the central cone and the peripheral cornea to examine the existence of K-structures. According to the Amsler-Krumeich scale, the eyes were graded as follows: stage 1 (n=3), stage 2 (n=1), stage 3 (n=1), and stage 4 (n=11). ACM was observed in 7 eyes (61.1%) in the cone area and 16 eyes (100%) in the peripheral cornea among all keratoconic eyes enrolled in this study. In addition, K-structures were observed in the 7 eyes (61.1%) and 16 eyes (100%) in the peripheral cornea among all keratoconic eyes. The presence of the K-structures was completely matched (100%) with the presence of ACM in both the central cone and the peripheral cornea. In 11 eyes with stage 4 keratoconus, ACM and K-structure was absent in 9 eyes (81.8%) in the cone area. On the contrary, in 5 eyes with mild-to-moderate keratoconus (grade 1 to 3), ACM and K-structure was present in all eyes (100%) in the cone area. The absent ratio of ACM and K-structures in the cone area was significantly higher in stage 4 severe keratoconus compared to mild-to-moderate keratoconus (grade 1 to 3) (Fisher, P =0.005). The existence of ACM and K-structures in both the central cone and the peripheral cornea showed perfect accord in patients with keratoconus, indicating a strong association of ACM and K-structures in patients with keratoconus. With the progress of the keratoconus, it seemed that ACM and K-structure progressively disappeared, suggesting Bowman's layer abnormalities due to keratoconus. Further study in larger groups of patients with keratoconus is required to fully understand the significance of ACM/K-structures in keratoconic eyes and their association with Bowman's layer.

Effects of Fluid-Structure Interaction on Dynamic Response of Composite Structures: Experimental and Numerical Studies

DTIC Science & Technology

2013-08-01

STRUCTURES: EXPERIMENTAL AND NUMERICAL STUDIES by Young W. Kwon August 1, 2013 Approved for public release; distribution is unlimited Prepared...failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE...AND SUBTITLE Effects of Fluid-Structure Interaction on Dynamic Responses of Composite Structures: Experimental and Numerical Studies 5a. CONTRACT

X-ray and cryo-EM structures of inhibitor-bound cytochrome bc 1 complexes for structure-based drug discovery

PubMed Central

Amporndanai, Kangsa; O’Neill, Paul M.

2018-01-01

Cytochrome bc 1, a dimeric multi-subunit electron-transport protein embedded in the inner mitochondrial membrane, is a major drug target for the treatment and prevention of malaria and toxoplasmosis. Structural studies of cytochrome bc 1 from mammalian homologues co-crystallized with lead compounds have underpinned structure-based drug design to develop compounds with higher potency and selectivity. However, owing to the limited amount of cytochrome bc 1 that may be available from parasites, all efforts have been focused on homologous cytochrome bc 1 complexes from mammalian species, which has resulted in the failure of some drug candidates owing to toxicity in the host. Crystallographic studies of the native parasite proteins are not feasible owing to limited availability of the proteins. Here, it is demonstrated that cytochrome bc 1 is highly amenable to single-particle cryo-EM (which uses significantly less protein) by solving the apo and two inhibitor-bound structures to ∼4.1 Å resolution, revealing clear inhibitor density at the binding site. Therefore, cryo-EM is proposed as a viable alternative method for structure-based drug discovery using both host and parasite enzymes. PMID:29765610

Structural studies of an arabinan from the stems of Ephedra sinica by methylation analysis and 1D and 2D NMR spectroscopy.

PubMed

Xia, Yong-Gang; Liang, Jun; Yang, Bing-You; Wang, Qiu-Hong; Kuang, Hai-Xue

2015-05-05

Plant arabinan has important biological activity. In this study, a water-soluble arabinan (Mw∼6.15kDa) isolated from the stems of Ephedra sinica was found to consist of (1→5)-Araƒ, (1→3,5)-Araƒ, T-Araƒ, (1→3)-Araƒ and (1→2,5)-Araƒ residues at proportions of 10:2:3:2:1. A tentative structure was proposed by methylation analysis, nuclear magnetic resonance (NMR) spectroscopy ((1)H NMR, (13)C NMR, DEPT-135, (1)H-(1)H COSY, HSQC, HMBC and ROESY) and literature. The structure proposed includes a branched (1→5)-α-Araf backbone where branching occurs at the O-2 and O-3 positions of the residues with 7.7% and 15.4% of the 1,5-linked α-Araf substituted at the O-2 and O-3 positions. The presence of a branched structure was further observed by atomic force microscopy. This polymer was characterized as having a much longer linear (1→5)-α-Araf backbone as a repeating unit. In particular, the presence of α-Araf→3)-α-Araf-(1→3)-α-Araf-(1→ attached at the O-2 is a new finding. This study may facilitate a deeper understanding of structure-activity relationships of biological polysaccharides from the stems of E. sinica. Copyright © 2014 Elsevier Ltd. All rights reserved.

Thermostructural analysis of three structural concepts for reusable space vehicles

NASA Technical Reports Server (NTRS)

Taylor, A. H.; Jackson, L. R.

1979-01-01

Three structural concepts are studied: (1) a state-of-the-art insulated aluminum skin-stringer structure; (2) a near-art insulated evacuated aluminum-alloy honeycomb structure; and (3) an advanced evacuated Rene 41 honeycomb hot structure. Each is evaluated for its thermostructural performance for each of the flight profiles (ascent, entry, and a recall or abort). Results indicate that (1) the state-of-the-art structure encounters negligible thermal stress; (2) the near-art structure has acceptable thermal stresses; and (3) the advanced structure will have thermal stress levels above the material allowables.

Style Matching or Ability Building? An Empirical Study on FD Learners' Learning in Well-Structured and Ill-Structured Asynchronous Online Learning Environments

ERIC Educational Resources Information Center

Zheng, Robert Z.; Flygare, Jill A.; Dahl, Laura B.

2009-01-01

The present study investigated (1) the impact of cognitive styles on learner performance in well-structured and ill-structured learning, and (2) scaffolding as a cognitive tool to improve learners' cognitive abilities, especially field dependent (FD) learners' ability to thrive in an ill-structured learning environment. Two experiments were…

Ten-Structure as Strategy of Addition 1-20 by Involving Spatial Structuring Ability for First Grade Students

ERIC Educational Resources Information Center

Salmah, Ummy; Putri, Ratu Ilma Indra; Somakim

2015-01-01

The aim of this study is to design learning activities that can support students to develop strategies for the addition of number 1 to 20 in the first grade by involving students' spatial structuring ability. This study was conducted in Indonesia by involving 27 students. In this paper, one of three activities is discussed namely ten-box activity.…

Computational modeling of Repeat1 region of INI1/hSNF5: An evolutionary link with ubiquitin

PubMed Central

Bhutoria, Savita

2016-01-01

Abstract The structure of a protein can be very informative of its function. However, determining protein structures experimentally can often be very challenging. Computational methods have been used successfully in modeling structures with sufficient accuracy. Here we have used computational tools to predict the structure of an evolutionarily conserved and functionally significant domain of Integrase interactor (INI)1/hSNF5 protein. INI1 is a component of the chromatin remodeling SWI/SNF complex, a tumor suppressor and is involved in many protein‐protein interactions. It belongs to SNF5 family of proteins that contain two conserved repeat (Rpt) domains. Rpt1 domain of INI1 binds to HIV‐1 Integrase, and acts as a dominant negative mutant to inhibit viral replication. Rpt1 domain also interacts with oncogene c‐MYC and modulates its transcriptional activity. We carried out an ab initio modeling of a segment of INI1 protein containing the Rpt1 domain. The structural model suggested the presence of a compact and well defined ββαα topology as core structure in the Rpt1 domain of INI1. This topology in Rpt1 was similar to PFU domain of Phospholipase A2 Activating Protein, PLAA. Interestingly, PFU domain shares similarity with Ubiquitin and has ubiquitin binding activity. Because of the structural similarity between Rpt1 domain of INI1 and PFU domain of PLAA, we propose that Rpt1 domain of INI1 may participate in ubiquitin recognition or binding with ubiquitin or ubiquitin related proteins. This modeling study may shed light on the mode of interactions of Rpt1 domain of INI1 and is likely to facilitate future functional studies of INI1. PMID:27261671

Computational modeling of Repeat1 region of INI1/hSNF5: An evolutionary link with ubiquitin.

PubMed

Bhutoria, Savita; Kalpana, Ganjam V; Acharya, Seetharama A

2016-09-01

The structure of a protein can be very informative of its function. However, determining protein structures experimentally can often be very challenging. Computational methods have been used successfully in modeling structures with sufficient accuracy. Here we have used computational tools to predict the structure of an evolutionarily conserved and functionally significant domain of Integrase interactor (INI)1/hSNF5 protein. INI1 is a component of the chromatin remodeling SWI/SNF complex, a tumor suppressor and is involved in many protein-protein interactions. It belongs to SNF5 family of proteins that contain two conserved repeat (Rpt) domains. Rpt1 domain of INI1 binds to HIV-1 Integrase, and acts as a dominant negative mutant to inhibit viral replication. Rpt1 domain also interacts with oncogene c-MYC and modulates its transcriptional activity. We carried out an ab initio modeling of a segment of INI1 protein containing the Rpt1 domain. The structural model suggested the presence of a compact and well defined ββαα topology as core structure in the Rpt1 domain of INI1. This topology in Rpt1 was similar to PFU domain of Phospholipase A2 Activating Protein, PLAA. Interestingly, PFU domain shares similarity with Ubiquitin and has ubiquitin binding activity. Because of the structural similarity between Rpt1 domain of INI1 and PFU domain of PLAA, we propose that Rpt1 domain of INI1 may participate in ubiquitin recognition or binding with ubiquitin or ubiquitin related proteins. This modeling study may shed light on the mode of interactions of Rpt1 domain of INI1 and is likely to facilitate future functional studies of INI1. © 2016 The Protein Society.

LEED STUDY OF Ag(111)-(√ 7×√ 7)R19.1^o-4Ar

NASA Astrophysics Data System (ADS)

Caragiu, Mellita; Diehl, Renee D.; Leatherman, Gerry S.

2000-03-01

Recent LEED studies of the adsorption geometries of Xe and Kr on metal surfaces have indicated that, contrary to expectations, the low-coordination adsorption sites are generally preferred, even on relatively corrugated surfaces such as Cu(1\\overline 1 0). This study extends the range of this phenomenon to include Ar. On Ag(111), Ar can form a commensurate structure, Ag(111)-(√ 7×√ 7)R19.1^o-4Ar, if the step sites are first blocked by preadsorbing another species such as CO. A dynamical LEED analysis of this structure at 33K indicates that the structure includes one atom per unit cell on a top site and the remaining three on bridge sites. This structure is clearly preferred over ones in which hollow sites are occupied, providing evidence that the preference of noble gases atoms for low-coordination sites on metals extends to Ar.

Accounting for Relatedness in Family Based Genetic Association Studies

PubMed Central

McArdle, P.F.; O’Connell, J.R.; Pollin, T.I.; Baumgarten, M.; Shuldiner, A.R.; Peyser, P.A.; Mitchell, B.D.

2007-01-01

Objective Assess the differences in point estimates, power and type 1 error rates when accounting for and ignoring family structure in genetic tests of association. Methods We compare by simulation the performance of analytic models using variance components to account for family structure and regression models that ignore relatedness for a range of possible family based study designs (i.e., sib pairs vs. large sibships vs. nuclear families vs. extended families). Results Our analyses indicate that effect size estimates and power are not significantly affected by ignoring family structure. Type 1 error rates increase when family structure is ignored, as density of family structures increases, and as trait heritability increases. For discrete traits with moderate levels of heritability and across many common sampling designs, type 1 error rates rise from a nominal 0.05 to 0.11. Conclusion Ignoring family structure may be useful in screening although it comes at a cost of a increased type 1 error rate, the magnitude of which depends on trait heritability and pedigree configuration. PMID:17570925

Biomechanics and Biotensegrity: Study Method and Frequency Response of the Simplex and 3-bar-SVD Tensegrity Configurations

NASA Astrophysics Data System (ADS)

Castro Arenas, C.; Ghersi, I.; Miralles, M. T.

2016-04-01

The purpose of this work is to study the frequency response of 3D tensegrity structures. These are structures that have been used, since the 80’s, to model biological systems of different scales. This fact led to the origin of the field of biotensegrity, which includes biomechanics as a natural field of application. In this work: a) A simple method for the analysis of frequency response of different nodes in 3D tensegrity structures was set up and tuned. This method is based on a video-analysis algorithm, which was applied to the structures, as they were vibrated along their axis of symmetry, at frequencies from 1 Hz to 60 Hz. b) Frequency-response analyses were performed, for the simplest 3D structure, the Simplex module, as well as for two towers, formed by stacking two and three Simplex modules, respectively. Resonant frequencies were detected for the Simplex module at (19.2±0.1) Hz and (50.2±0.1) Hz (the latter being an average of frequencies between homologous nodes). For the towers with two and three modules, each selected node presented a characteristic frequency response, modulated by their spatial placement in each model. Resonances for the two-stage tower were found at: (12±0.1) Hz; (16.2±0.1) Hz; (29.4±0.1) Hz and (37.2±0.1) Hz. For the tower with three Simplex modules, the main resonant frequencies were found at (12.0±0.1) Hz and (21.0±0.1) Hz. Results show that the proposed method is adequate for the study (2D) of any 3D tensegrity structure, with the potential of being generalized to the study of oscillations in three dimensions. A growing complexity and variability in the frequency response of the nodes was observed, as modules were added to the structures. These findings were compared to those found in the available literature.

Solution structure of a DNA mimicking motif of an RNA aptamer against transcription factor AML1 Runt domain.

PubMed

Nomura, Yusuke; Tanaka, Yoichiro; Fukunaga, Jun-ichi; Fujiwara, Kazuya; Chiba, Manabu; Iibuchi, Hiroaki; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Kozu, Tomoko; Sakamoto, Taiichi

2013-12-01

AML1/RUNX1 is an essential transcription factor involved in the differentiation of hematopoietic cells. AML1 binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. In a previous study, we obtained RNA aptamers against the AML1 Runt domain by systematic evolution of ligands by exponential enrichment and revealed that RNA aptamers exhibit higher affinity for the Runt domain than that for RDE and possess the 5'-GCGMGNN-3' and 5'-N'N'CCAC-3' conserved motif (M: A or C; N and N' form Watson-Crick base pairs) that is important for Runt domain binding. In this study, to understand the structural basis of recognition of the Runt domain by the aptamer motif, the solution structure of a 22-mer RNA was determined using nuclear magnetic resonance. The motif contains the AH(+)-C mismatch and base triple and adopts an unusual backbone structure. Structural analysis of the aptamer motif indicated that the aptamer binds to the Runt domain by mimicking the RDE sequence and structure. Our data should enhance the understanding of the structural basis of DNA mimicry by RNA molecules.

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

Katayama, Naoyuki; Onari, Seiichiro; Matsubayashi, Kazuyuki

We report the comprehensive studies between synchrotron X-ray diffraction, electrical resistivity and magnetic susceptibility experiments for the iron arsenides Can(n+1)/2(Fe1-xPtx)(2+3n)Ptn(n -1)/2As(n+1)(n+2)/2 for n=2 and 3. Both structures crystallize in the monoclinic space group P21/m (#11) with three-dimensional FeAs structures. The horizontal FeAs layers are bridged by inclined FeAs planes through edge-sharing FeAs5 square pyramids, resulting in triangular tunneling structures rather than the simple layered structures found in conventional iron arsenides. n=3 system shows a sign of superconductivity with a small volume fraction. Our first-principles calculations of these systems clearly indicate that the Fermi surfaces originate from strong Fe-3d characters andmore » the three-dimensional nature of the electric structures for both systems, thus offering the playgrounds to study the effects of dimensionality on high Tc superconductivity.« less

Secondary structural analyses of ITS1 in Paramecium.

PubMed

Hoshina, Ryo

2010-01-01

The nuclear ribosomal RNA gene operon is interrupted by internal transcribed spacer (ITS) 1 and ITS2. Although the secondary structure of ITS2 has been widely investigated, less is known about ITS1 and its structure. In this study, the secondary structure of ITS1 sequences for Paramecium and other ciliates was predicted. Each Paramecium ITS1 forms an open loop with three helices, A through C. Helix B was highly conserved among Paramecium, and similar helices were found in other ciliates. A phylogenetic analysis using the ITS1 sequences showed high-resolution, implying that ITS1 is a good tool for species-level analyses.

Altered Primary Motor Cortex Structure, Organization, and Function in Chronic Pain: A Systematic Review and Meta-Analysis.

PubMed

Chang, Wei-Ju; O'Connell, Neil E; Beckenkamp, Paula R; Alhassani, Ghufran; Liston, Matthew B; Schabrun, Siobhan M

2018-04-01

Chronic pain can be associated with movement abnormalities. The primary motor cortex (M1) has an essential role in the formulation and execution of movement. A number of changes in M1 function have been reported in studies of people with chronic pain. This review systematically evaluated the evidence for altered M1 structure, organization, and function in people with chronic pain of neuropathic and non-neuropathic origin. Database searches were conducted and a modified STrengthening the Reporting of OBservational studies in Epidemiology checklist was used to assess the methodological quality of included studies. Meta-analyses, including preplanned subgroup analyses on the basis of condition were performed where possible. Sixty-seven studies (2,290 participants) using various neurophysiological measures were included. There is conflicting evidence of altered M1 structure, organization, and function for neuropathic and non-neuropathic pain conditions. Meta-analyses provided evidence of increased M1 long-interval intracortical inhibition in chronic pain populations. For most measures, the evidence of M1 changes in chronic pain populations is inconclusive. This review synthesizes the evidence of altered M1 structure, organization, and function in chronic pain populations. For most measures, M1 changes are inconsistent between studies and more research with larger samples and rigorous methodology is required to elucidate M1 changes in chronic pain populations. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Fracture trends identified by ERTS-1 imagery in Utah and Nevada

NASA Technical Reports Server (NTRS)

Jensen, M. L. (Principal Investigator); Erickson, M. P.; Smith, M. R.

1973-01-01

The author has identified the following significant results. In the Utah-Nevada area, linear structural trends recorded on ERTS-1 imagery conform in part to previously recognized structures. In addition, the ERTS-1 imagery reveals cryptic structures not previously identified and not readily apparent in other imagery. These structures are illustrated by prominent east-west trending structures which appear to be concentrated in pre-volcanic rocks. This suggests that the structures are older than many of those with other trends which are equally prominent in volcanic and non-volcanic terrain. Since the older east-west structures may have controlled early Tertiary emplacement of magma or the ascent of mineralizing fluids, their recognition is important in minerial exploration. Soil-gas sampling and analysis for mercury content is being continued over structures, and projected trends of buried structures which appear, from studies of ERTS-1 imagery, to be favorable to mineralization. Comparison of ERTS-1 and Skylab imagery indicated that ERTS-1 imagery records more previously unrecognized linear structures than the Skylab imagery. In differentiating and identifying different rock types, the Skylab imagery appears to be more effective.

Structure Determination of Mycobacterium tuberculosis Serine Protease Hip1 (Rv2224c)

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

Naffin-Olivos, Jacqueline L.; Daab, Andrew; White, Andre

The Mycobacterium tuberculosis (Mtb) serine protease Hip1 (hydrolase important for pathogenesis; Rv2224c) promotes tuberculosis (TB) pathogenesis by impairing host immune responses through proteolysis of a protein substrate, Mtb GroEL2. The cell surface localization of Hip1 and its immunomodulatory functions make Hip1 a good drug target for new adjunctive immune therapies for TB. Here, we report the crystal structure of Hip1 to a resolution of 2.6 Å and the kinetic studies of the enzyme against model substrates and the protein GroEL2. The structure shows a two-domain protein, one of which contains the catalytic residues that are the signature of a serinemore » protease. Surprisingly, a threonine is located within the active site close enough to hydrogen bond with the catalytic residues Asp463 and His490. Mutation of this residue, Thr466, to alanine established its importance for function. Our studies provide insights into the structure of a member of a novel family of proteases. Knowledge of the Hip1 structure will aid in designing inhibitors that could block Hip1 activity« less

Structure Determination of Mycobacterium tuberculosis Serine Protease Hip1 (Rv2224c).

PubMed

Naffin-Olivos, Jacqueline L; Daab, Andrew; White, Andre; Goldfarb, Nathan E; Milne, Amy C; Liu, Dali; Baikovitz, Jacqueline; Dunn, Ben M; Rengarajan, Jyothi; Petsko, Gregory A; Ringe, Dagmar

2017-05-02

The Mycobacterium tuberculosis (Mtb) serine protease Hip1 (hydrolase important for pathogenesis; Rv2224c) promotes tuberculosis (TB) pathogenesis by impairing host immune responses through proteolysis of a protein substrate, Mtb GroEL2. The cell surface localization of Hip1 and its immunomodulatory functions make Hip1 a good drug target for new adjunctive immune therapies for TB. Here, we report the crystal structure of Hip1 to a resolution of 2.6 Å and the kinetic studies of the enzyme against model substrates and the protein GroEL2. The structure shows a two-domain protein, one of which contains the catalytic residues that are the signature of a serine protease. Surprisingly, a threonine is located within the active site close enough to hydrogen bond with the catalytic residues Asp463 and His490. Mutation of this residue, Thr466, to alanine established its importance for function. Our studies provide insights into the structure of a member of a novel family of proteases. Knowledge of the Hip1 structure will aid in designing inhibitors that could block Hip1 activity.

Resonance assignments for the substrate binding domain of Hsp70 chaperone Ssa1 from Saccharomyces cerevisiae.

PubMed

Hu, Wanhui; Wu, Huiwen; Zhang, Hong; Gong, Weibin; Perrett, Sarah

2015-10-01

Hsp70 chaperone proteins play crucial roles in the cell. Extensive structural and functional studies have been performed for bacterial and mammalian Hsp70s. Ssa1 from Saccharomyces cerevisiae is a member of the Hsp70 family. In vivo and biochemical studies on Ssa1 have revealed that it regulates prion propagation and the cell cycle. However, no structural data has been obtained for Ssa1 up to now. Here we report the almost complete (96 %) (1)H, (13)C, (15)N backbone and side chain NMR assignment of the 18.8 kDa Ssa1 substrate binding domain. The construct includes residues 382-554, which corresponds to the entire substrate binding domain and two following α-helices in homologous structures. The secondary structure predicted from the assigned chemical shifts is consistent with that of homologous Hsp70 substrate binding domains.

Biochemical studies of the Saccharomyces cerevisiae Mph1 helicase on junction-containing DNA structures

PubMed Central

Kang, Young-Hoon; Munashingha, Palinda Ruvan; Lee, Chul-Hwan; Nguyen, Tuan Anh; Seo, Yeon-Soo

2012-01-01

Saccharomyces cerevisiae Mph1 is a 3–5′ DNA helicase, required for the maintenance of genome integrity. In order to understand the ATPase/helicase role of Mph1 in genome stability, we characterized its helicase activity with a variety of DNA substrates, focusing on its action on junction structures containing three or four DNA strands. Consistent with its 3′ to 5′ directionality, Mph1 displaced 3′-flap substrates in double-fixed or equilibrating flap substrates. Surprisingly, Mph1 displaced the 5′-flap strand more efficiently than the 3′ flap strand from double-flap substrates, which is not expected for a 3–5′ DNA helicase. For this to occur, Mph1 required a threshold size (>5 nt) of 5′ single-stranded DNA flap. Based on the unique substrate requirements of Mph1 defined in this study, we propose that the helicase/ATPase activity of Mph1 play roles in converting multiple-stranded DNA structures into structures cleavable by processing enzymes such as Fen1. We also found that the helicase activity of Mph1 was used to cause structural alterations required for restoration of replication forks stalled due to damaged template. The helicase properties of Mph1 reported here could explain how it resolves D-loop structure, and are in keeping with a model proposed for the error-free damage avoidance pathway. PMID:22090425

Crystal structure of TBC1D15 GTPase‐activating protein (GAP) domain and its activity on Rab GTPases

PubMed Central

Chen, Yan‐Na; Gu, Xin; Zhou, X. Edward; Wang, Weidong; Cheng, Dandan; Ge, Yinghua; Ye, Fei

2017-01-01

Abstract TBC1D15 belongs to the TBC (Tre‐2/Bub2/Cdc16) domain family and functions as a GTPase‐activating protein (GAP) for Rab GTPases. So far, the structure of TBC1D15 or the TBC1D15·Rab complex has not been determined, thus, its catalytic mechanism on Rab GTPases is still unclear. In this study, we solved the crystal structures of the Shark and Sus TBC1D15 GAP domains, to 2.8 Å and 2.5 Å resolution, respectively. Shark‐TBC1D15 and Sus‐TBC1D15 belong to the same subfamily of TBC domain‐containing proteins, and their GAP‐domain structures are highly similar. This demonstrates the evolutionary conservation of the TBC1D15 protein family. Meanwhile, the newly determined crystal structures display new variations compared to the structures of yeast Gyp1p Rab GAP domain and TBC1D1. GAP assays show that Shark and Sus GAPs both have higher catalytic activity on Rab11a·GTP than Rab7a·GTP, which differs from the previous study. We also demonstrated the importance of arginine and glutamine on the catalytic sites of Shark GAP and Sus GAP. When arginine and glutamine are changed to alanine or lysine, the activities of Shark GAP and Sus GAP are lost. PMID:28168758

[A structural protein study of the influenza A (H1N1) virus by polyacrylamide gel electrophoresis].

PubMed

Pérez Guevara, M T; Savón Valdés, C; Rivas Arjona, M; Goyenechea Hernández, A

1992-01-01

Influenza is an acute respiratory disease typically appearing as an epidemic. Three immunological types of the influenza virus are known: A, B and C. Continually, antigen changes occur, especially in type A. Therefore, a comparative study was carried out on 4 influenza A(H1N1) virus strains in relation to protein structure (surface antigens), by using polyacrylamide gel electrophoresis by the modified Laemmli method. The objective was to compare the structural proteins of the A/Havana/1292/78 (H1N1) national strain with the proteins of 3 international pattern strains. In all the cases, 6 bands were detected by densitometry. In the 4 strains studied the most abundant protein was M. Great differences between the Cuban strain and the 3 international patterns were not seen.

Hybrid functional study of band structures of GaAs1-xNx and GaSb1-xNx alloys

NASA Astrophysics Data System (ADS)

Virkkala, Ville; Havu, Ville; Tuomisto, Filip; Puska, Martti J.

2012-02-01

Band structures of GaAs1-xNx and GaSb1-xNx alloys are studied in the framework of the density functional theory within the hybrid functional scheme (HSE06). We find that the scheme gives a clear improvement over the traditional (semi)local functionals in describing, in a qualitative agreement with experiments, the bowing of electron energy band gap in GaAs1-xNx alloys. In the case of GaSb1-xNx alloys, the hybrid functional used makes the study of band structures possible ab initio without any empirical parameter fitting. We explain the trends in the band gap reductions in the two materials that result mainly from the positions of the nitrogen-induced states with respect to the bottoms of the bulk conduction bands.

Mutations in the putative calcium-binding domain of polyomavirus VP1 affect capsid assembly

NASA Technical Reports Server (NTRS)

Haynes, J. I. 2nd; Chang, D.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

1993-01-01

Calcium ions appear to play a major role in maintaining the structural integrity of the polyomavirus and are likely involved in the processes of viral uncoating and assembly. Previous studies demonstrated that a VP1 fragment extending from Pro-232 to Asp-364 has calcium-binding capabilities. This fragment contains an amino acid stretch from Asp-266 to Glu-277 which is quite similar in sequence to the amino acids that make up the calcium-binding EF hand structures found in many proteins. To assess the contribution of this domain to polyomavirus structural integrity, the effects of mutations in this region were examined by transfecting mutated viral DNA into susceptible cells. Immunofluorescence studies indicated that although viral protein synthesis occurred normally, infective viral progeny were not produced in cells transfected with polyomavirus genomes encoding either a VP1 molecule lacking amino acids Thr-262 through Gly-276 or a VP1 molecule containing a mutation of Asp-266 to Ala. VP1 molecules containing the deletion mutation were unable to bind 45Ca in an in vitro assay. Upon expression in Escherichia coli and purification by immunoaffinity chromatography, wild-type VP1 was isolated as pentameric, capsomere-like structures which could be induced to form capsid-like structures upon addition of CaCl2, consistent with previous studies. However, although VP1 containing the point mutation was isolated as pentamers which were indistinguishable from wild-type VP1 pentamers, addition of CaCl2 did not result in their assembly into capsid-like structures. Immunogold labeling and electron microscopy studies of transfected mammalian cells provided in vivo evidence that a mutation in this region affects the process of viral assembly.

First-principles studies of the v7×v7R19.1° structure of sulfur on the Pd(1 1 1) surface

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

Alfonso, D.R.

2007-11-01

Density functional theory is used to investigate the v7×v7R19.1° structure of sulfur on the Pd(111) surface. Among the different models that were considered, the densely packed mixed sulfur-metal overlayer structure proposed by Liu et al. [W. Liu, K.A.R. Mitchell, W. Berndt, Surf. Sci. 393 (1997) L119] was found to be the most energetically favorable. This model consists of arrangement of Pd triangles and pentagons on top of Pd(111) with the sulfur atoms at 3/7 monolayer coverage. The dominant mechanism for sulfur interaction with Pd in the overlayer region is the rehybridization of sulfur 3p and metal 4d bands. Simulated scanningmore » tunneling microscopy image for this structure shows some similarity with that obtained from experiment. Our study confirms that surface sulfide with no structural resemblance to its bulk counterparts can form on Pd(111).« less

Local structural distortion and electrical transport properties of Bi(Ni 1/2Ti 1/2)O 3 perovskite under high pressure

DOE PAGES

Zhu, Jinlong; Yang, Liuxiang; Wang, Hsiu -Wen; ...

2015-12-16

Perovskite-structure materials generally exhibit local structural distortions that are distinct from long-range, average crystal structure. The characterization of such distortion is critical to understanding the structural and physical properties of materials. In this work, we combined Pair Distribution Function (PDF) technique with Raman spectroscopy and electrical resistivity measurement to study Bi(Ni 1/2Ti 1/2)O 3 perovskite under high pressure. PDF analysis reveals strong local structural distortion at ambient conditions. As pressure increases, the local structure distortions are substantially suppressed and eventually vanish around 4 GPa, leading to concurrent changes in the electronic band structure and anomalies in the electrical resistivity. Wemore » find, consistent with PDF analysis, Raman spectroscopy data suggest that the local structure changes to a higher ordered state at pressures above 4 GPa.« less

Local structural distortion and electrical transport properties of Bi(Ni1/2Ti1/2)O3 perovskite under high pressure.

PubMed

Zhu, Jinlong; Yang, Liuxiang; Wang, Hsiu-Wen; Zhang, Jianzhong; Yang, Wenge; Hong, Xinguo; Jin, Changqing; Zhao, Yusheng

2015-12-16

Perovskite-structure materials generally exhibit local structural distortions that are distinct from long-range, average crystal structure. The characterization of such distortion is critical to understanding the structural and physical properties of materials. In this work, we combined Pair Distribution Function (PDF) technique with Raman spectroscopy and electrical resistivity measurement to study Bi(Ni1/2Ti1/2)O3 perovskite under high pressure. PDF analysis reveals strong local structural distortion at ambient conditions. As pressure increases, the local structure distortions are substantially suppressed and eventually vanish around 4 GPa, leading to concurrent changes in the electronic band structure and anomalies in the electrical resistivity. Consistent with PDF analysis, Raman spectroscopy data suggest that the local structure changes to a higher ordered state at pressures above 4 GPa.

Comparison of Newly Assembled Full Length HIV-1 Integrase With Prototype Foamy Virus Integrase: Structure-Function Prospective.

PubMed

Dayer, Mohammad Reza

2016-05-01

Drug design against human immunodeficiency virus type 1 (HIV-1) integrase through its mechanistic study is of great interest in the area in biological research. The main obstacle in this area is the absence of the full-length crystal structure for HIV-1 integrase to be used as a model. A complete structure, similar to HIV-1 of a prototype foamy virus integrase in complex with DNA, including all conservative residues, is available and has been extensively used in recent investigations. The aim of this study was to determine whether the above model is precisely representative of HIV-1 integrase. This would critically determine the success of any designed drug using the model in deactivation of integrase and AIDS treatment. Primarily, a new structure for HIV-1 was constructed, using a crystal structure of prototype foamy virus as the starting structure. The constructed structure of HIV-1 integrase was simultaneously simulated with a prototype foamy virus integrase on a separate occasion. Our results indicate that the HIV-1 system behaves differently from the prototype foamy virus in terms of folding, hydration, hydrophobicity of binding site and stability. Based on our findings, we can conclude that HIV-1 integrase is vastly different from the prototype foamy virus integrase and does not resemble it, and the modeling output of the prototype foamy virus simulations could not be simply generalized to HIV-1 integrase. Therefore, our HIV-1 model seems to be more representative and more useful for future research.

Magnetostructural phase transformations in Tb 1-x Mn 2

DOE PAGES

Zou, Junding; Paudyal, Durga; Liu, Jing; ...

2015-01-16

Magnetism and phase transformations in non-stoichiometric Tb 1-xMn 2 (x = 0.056, 0.039) have been studied as functions of temperature and magnetic field using magnetization, heat capacity, and X-ray powder diffraction measurements. Lowering the temperature, the compounds sequentially order ferrimagnetically and antiferromagnetically, and finally, exhibit spin reorientation transitions. Moreover, these structural distortions from room temperature cubic to low temperature rhombohedral structures occur at T N, and are accompanied by large volume changes reaching ~-1.27% and -1.42%, respectively. First principles electronic structure calculations confirm the phase transformation from the ferrimagnetic cubic structure to the antiferromagnetic rhombohedral structure in TbMn 2.

Cocrystal structure of the ICAP1 PTB domain in complex with a KRIT1 peptide

PubMed Central

Liu, Weizhi; Boggon, Titus J.

2013-01-01

Integrin cytoplasmic domain-associated protein-1 (ICAP1) is a suppressor of integrin activation and directly binds to the cytoplasmic tail of β1 integrins; its binding suppresses integrin activation by competition with talin. Krev/Rap1 interaction trapped-1 (KRIT1) releases ICAP1 suppression of integrin activation by sequestering ICAP1 away from integrin cytoplasmic tails. Here, the cocrystal structure of the PTB domain of ICAP1 in complex with a 29-­amino-acid fragment (residues 170–198) of KRIT1 is presented to 1.7 Å resolution [the resolution at which 〈I/σ(I)〉 = 2.9 was 1.83 Å]. In previous studies, the structure of ICAP1 with integrin β1 was determined to 3.0 Å resolution and that of ICAP1 with the N-terminal portion of KRIT1 (residues 1–­198) was determined to 2.54 Å resolution; therefore, this study provides the highest resolution structure yet of ICAP1 and allows further detailed analysis of the interaction of ICAP1 with its minimal binding region in KRIT1. PMID:23695561

In Silico Analysis of the Structural and Biochemical Features of the NMD Factor UPF1 in Ustilago maydis.

PubMed

Martínez-Montiel, Nancy; Morales-Lara, Laura; Hernández-Pérez, Julio M; Martínez-Contreras, Rebeca D

2016-01-01

The molecular mechanisms regulating the accuracy of gene expression are still not fully understood. Among these mechanisms, Nonsense-mediated Decay (NMD) is a quality control process that detects post-transcriptionally abnormal transcripts and leads them to degradation. The UPF1 protein lays at the heart of NMD as shown by several structural and functional features reported for this factor mainly for Homo sapiens and Saccharomyces cerevisiae. This process is highly conserved in eukaryotes but functional diversity can be observed in various species. Ustilago maydis is a basidiomycete and the best-known smut, which has become a model to study molecular and cellular eukaryotic mechanisms. In this study, we performed in silico analysis to investigate the structural and biochemical properties of the putative UPF1 homolog in Ustilago maydis. The putative homolog for UPF1 was recognized in the annotated genome for the basidiomycete, exhibiting 66% identity with its human counterpart at the protein level. The known structural and functional domains characteristic of UPF1 homologs were also found. Based on the crystal structures available for UPF1, we constructed different three-dimensional models for umUPF1 in order to analyze the secondary and tertiary structural features of this factor. Using these models, we studied the spatial arrangement of umUPF1 and its capability to interact with UPF2. Moreover, we identified the critical amino acids that mediate the interaction of umUPF1 with UPF2, ATP, RNA and with UPF1 itself. Mutating these amino acids in silico showed an important effect over the native structure. Finally, we performed molecular dynamic simulations for UPF1 proteins from H. sapiens and U. maydis and the results obtained show a similar behavior and physicochemical properties for the protein in both organisms. Overall, our results indicate that the putative UPF1 identified in U. maydis shows a very similar sequence, structural organization, mechanical stability, physicochemical properties and spatial organization in comparison to the NMD factor depicted for Homo sapiens. These observations strongly support the notion that human and fungal UPF1 could perform equivalent biological activities.

Investigating Effects of Invasive Species on Plant Community Structure

ERIC Educational Resources Information Center

Franklin, Wilfred

2008-01-01

In this article, the author presents a field study project that explores factors influencing forest community structure and lifts the veil off of "plant blindness." This ecological study consists of three laboratories: (1) preliminary field trip to the study site; (2) plant survey; and (3) analyzing plant community structure with descriptive…

The hOGG1 Ser326Cys Gene Polymorphism and Breast Cancer Risk in Saudi Population.

PubMed

Alanazi, Mohammed; Pathan, Akbar Ali Khan; Shaik, Jilani P; Alhadheq, Abdullah; Khan, Zahid; Khan, Wajahatullah; Al Naeem, Abdulrahman; Parine, Narasimha Reddy

2017-07-01

The purpose of this study was to test the association between human 8-oxoguanine glycosylase 1 (hOGG1) gene polymorphisms and susceptibility to breast cancer in Saudi population. We have also aimed to screen the hOGG1 Ser326Cys polymorphism effect on structural and functional properties of the hOGG1 protein using in silico tools. We have analyzed four SNPs of hOGG1 gene among Saudi breast cancer patients along with healthy controls. Genotypes were screened using TaqMan SNP genotype analysis method. Experimental data was analyzed using Chi-square, t test and logistic regression analysis using SPSS software (v.16). In silco analysis was conducted using discovery studio and HOPE program. Genotypic analysis showed that hOGG1 rs1052133 (Ser326Cys) is significantly associated with breast cancer samples in Saudi population, however rs293795 (T >C), rs2072668 (C>G) and rs2075747 (G >A) did not show any association with breast cancer. The hOGG1 SNP rs1052133 (Ser326Cys) minor allele T showed a significant association with breast cancer samples (OR = 1.78, χ2 = 7.86, p = 0.02024). In silico structural analysis was carried out to compare the wild type (Ser326) and mutant (Cys326) protein structures. The structural prediction studies revealed that Ser326Cys variant may destabilize the protein structure and it may disturb the hOGG1 function. Taken together this is the first In silico study report to confirm Ser326Cys variant effect on structural and functional properties of hOGG1 gene and Ser326Cys role in breast cancer susceptibility in Saudi population.

Photoelectron spectroscopy and density functional theory study of TiAlO(y) (-) (y=1-3) and TiAl(2)O(y) (-) (y=2-3) clusters.

PubMed

Zhang, Zeng-Guang; Xu, Hong-Guang; Zhao, Yuchao; Zheng, Weijun

2010-10-21

Small titanium-aluminum oxide clusters, TiAlO(y) (-) (y=1-3) and TiAl(2)O(y) (-) (y=2-3), were studied by using anion photoelectron spectroscopy. The adiabatic detachment energies of TiAlO(y) (-) (y=1-3) were estimated to be 1.11±0.05, 1.70±0.08, and 2.47±0.08eV based on their photoelectron spectra; those of TiAl(2)O(2) (-) and TiAl(2)O(3) (-) were estimated to be 1.17±0.08 and 2.2±0.1eV, respectively. The structures of these clusters were determined by comparison of density functional calculations with the experimental results. The structure of TiAlO(-) is nearly linear with the O atom in the middle. That of TiAlO(2) (-) is a kite-shaped structure. TiAlO(3) (-) has a kite-shaped TiAlO(2) unit with the third O atom attaching to the Ti atom. TiAl(2)O(2) (-) has two nearly degenerate Al-O-Ti-O-Al chain structures that can be considered as cis and trans forms. TiAl(2)O(3) (-) has two low-lying isomers, kite structure and book structure. The structures of these clusters indicate that the Ti atom tends to bind to more O atoms.

Empirical Analysis of Farm Credit Risk under the Structure Model

ERIC Educational Resources Information Center

Yan, Yan

2009-01-01

The study measures farm credit risk by using farm records collected by Farm Business Farm Management (FBFM) during the period 1995-2004. The study addresses the following questions: (1) whether farm's financial position is fully described by the structure model, (2) what are the determinants of farm capital structure under the structure model, (3)…

Biochemical and Structural Characterization of the Human TL1A Ectodomain†¶

PubMed Central

Zhan, Chenyang; Yan, Qingrong; Patskovsky, Yury; Li, Zhenhong; Toro, Rafael; Meyer, Amanda; Cheng, Huiyong; Brenowitz, Michael; Nathenson, Stanley G; Almo, Steven C

2009-01-01

TNF-like 1A (TL1A) is a newly described member of the TNF superfamily that is directly implicated in the pathogenesis of autoimmune diseases, including inflammatory bowel disease, atherosclerosis and rheumatoid arthritis. We report the crystal structure of the human TL1A extracellular domain at a resolution of 2.5 Å, which reveals a jelly-roll fold typical of the TNF superfamily. This structural information, in combination with complementary mutagenesis and biochemical characterization, provides insights into the binding interface and the specificity of the interactions between TL1A and the DcR3 and DR3 receptors. These studies suggest that the mode of interaction between TL1A and DcR3 differs from other characterized TNF ligand/receptor complexes. In addition, we have generated functional TL1A mutants with altered disulfide bonding capability that exhibit enhanced solution properties, which will facilitate the production of materials for future cell-based and whole animal studies. In summary, these studies provide insights into the structure and function of TL1A and provide the basis for the rational manipulation of its interactions with cognate receptors. PMID:19522538

Biochemical and Structural Characterization of the Human TL1A Ectodomain

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

Zhan, C.; Yan, Q; Patskovsky, Y

TNF-like 1A (TL1A) is a newly described member of the TNF superfamily that is directly implicated in the pathogenesis of autoimmune diseases, including inflammatory bowel disease, atherosclerosis, and rheumatoid arthritis. We report the crystal structure of the human TL1A extracellular domain at a resolution of 2.5 {angstrom}, which reveals a jelly-roll fold typical of the TNF superfamily. This structural information, in combination with complementary mutagenesis and biochemical characterization, provides insights into the binding interface and the specificity of the interactions between TL1A and the DcR3 and DR3 receptors. These studies suggest that the mode of interaction between TL1A and DcR3more » differs from other characterized TNF ligand/receptor complexes. In addition, we have generated functional TL1A mutants with altered disulfide bonding capability that exhibit enhanced solution properties, which will facilitate the production of materials for future cell-based and whole animal studies. In summary, these studies provide insights into the structure and function of TL1A and provide the basis for the rational manipulation of its interactions with cognate receptors.« less

Form-Finding Using Nonlinear Analysis Method in Tensioned Fabric Structure in The Form of Handkerchief Surface

NASA Astrophysics Data System (ADS)

Ibrahim, MH Wan; Hadi, MN Abdul; Hooi Min, Yee

2018-04-01

Tensioned fabric structure with different surface form could be realized. Their variations as possible choice form of minimal surface for tensioned fabric structure have been studied. The form of used in TFS is Handkerchief Surface. Handkerchief Surface used in TFS because Handkerchief Surface is the form of minimal surface and Handkerchief Surface has not been studied by other researcher. Besides, no other work on Handkerchief Surface as idea in tensioned fabric structure has been found. The aim of the study is to propose converged shape of Handkerchief Surface with variable u=v=0.4 and u=v=1.0. The method used for Form-Finding is nonlinear analysis method. From the result, the surface of Handkerchief TFS model, u=v=0.4 and u=v=1.0 show the total warp and fill stress deviation is less than 0.01. The initial equilibrium shape of Handkerchief tensioned fabric structure model, u=v=0.4 and u=v=1.0 is corresponding to equal tension surface. Tensioned fabric structure in the form of Handikerchief Surface is a structurally viable surface form to be considered by engineer.

Complexation and Structure Elucidation of the Axial Conformers of Mono- and (±)-trans-1,2-Disubstituted Cyclohexanes by Enantiopure Alleno-Acetylenic Cage Receptors.

PubMed

Gropp, Cornelius; Trapp, Nils

2018-04-25

Single crystal X-ray diffraction is a powerful method to unambiguously characterize the structure of molecules with atomic resolution. Herein, we review the molecular recognition of the (di)axial conformers of Mono- and (±)-trans-1,2-disubstituted cyclohexanes by enantiopure alleno-acetylenic cage receptors in solution and in the solid state. Single crystals of the host-guest complexes suitable for X-ray diffraction allow for the first time to study the dihedral angles of a series of Mono- and (±)-trans-1,2-disubstituted cyclohexanes in their (di)axial chair conformation. Theoretical studies indicate negligible influence of the host structure on the guest conformation, suggesting that the structural information obtained from the host-guest complexes give insight into the innate structures of Mono- and (±)-trans-1,2-disubstituted cyclohexanes. Strong deviation of the dihedral angles a,a(X-C(1)-C(2)-X) from the idealized 180° are observed, accompanied by substantial flattening of the ring dihedral angles ρ(X-C(1)-C(2)-C(3)).

Activator Protein-1: redox switch controlling structure and DNA-binding.

PubMed

Yin, Zhou; Machius, Mischa; Nestler, Eric J; Rudenko, Gabby

2017-11-02

The transcription factor, activator protein-1 (AP-1), binds to cognate DNA under redox control; yet, the underlying mechanism has remained enigmatic. A series of crystal structures of the AP-1 FosB/JunD bZIP domains reveal ordered DNA-binding regions in both FosB and JunD even in absence DNA. However, while JunD is competent to bind DNA, the FosB bZIP domain must undergo a large conformational rearrangement that is controlled by a 'redox switch' centered on an inter-molecular disulfide bond. Solution studies confirm that FosB/JunD cannot undergo structural transition and bind DNA when the redox-switch is in the 'OFF' state, and show that the mid-point redox potential of the redox switch affords it sensitivity to cellular redox homeostasis. The molecular and structural studies presented here thus reveal the mechanism underlying redox-regulation of AP-1 Fos/Jun transcription factors and provide structural insight for therapeutic interventions targeting AP-1 proteins. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Structural basis of dual Ca2+/pH regulation of the endolysosomal TRPML1 channel

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

Li, Minghui; Zhang, Wei K.; Benvin, Nicole M.

The activities of organellar ion channels are often regulated by Ca2+ and H+, which are present in high concentrations in many organelles. Here we report a structural element critical for dual Ca2+/pH regulation of TRPML1, a Ca2+-release channel crucial for endolysosomal function. TRPML1 mutations cause mucolipidosis type IV (MLIV), a severe lysosomal storage disorder characterized by neurodegeneration, mental retardation and blindness. We obtained crystal structures of the 213-residue luminal domain of human TRPML1 containing three missense MLIV-causing mutations. This domain forms a tetramer with a highly electronegative central pore formed by a novel luminal pore loop. Cysteine cross-linking and cryo-EMmore » analyses confirmed that this architecture occurs in the full-length channel. Structure–function studies demonstrated that Ca2+ and H+ interact with the luminal pore and exert physiologically important regulation. The MLIV-causing mutations disrupt the luminal-domain structure and cause TRPML1 mislocalization. Our study reveals the structural underpinnings of TRPML1's regulation, assembly and pathogenesis.« less

Fat emulsions based on structured lipids (1,3-specific triglycerides): an investigation of the in vivo fate.

PubMed

Hedeman, H; Brøndsted, H; Müllertz, A; Frokjaer, S

1996-05-01

Structured lipids (1,3-specific triglycerides) are new chemical entities made by enzymatic transesterification of the fatty acids in the 1,3 positions of the triglyceride. The purpose of this study is to characterize structured lipids with either short chain fatty acids or medium chain fatty acids in the 1,3 positions with regard to their hydrophobicity, and investigate the in vivo fate in order to evaluate the potential of structured lipids as core material in fat emulsions used as parenteral drug delivery system. The lipids were characterized by employing reversed phase high performance liquid chromatography. The biodistribution of radioactively labeled emulsions was studied in rats. By employing high performance liquid chromatography a rank order of the hydrophobicities of the lipids could be given, with the triglycerides containing long chain fatty acids being the most hydrophobic and the structured lipid with short chain fatty acids in the 1,3 positions the least. When formulated as fat emulsions, the emulsion based on structured lipids with short fatty acids in the 1,3 positions was removed slower from the general blood circulation compared to emulsions based on lipids with long chain fatty acids in the 1,3 positions. The type of core material influences the in vivo circulation time of fat emulsions.

A Raman scattering study of the structural ordering in Bi1- x La x FeO3 ceramic ferroelectromagnetics

NASA Astrophysics Data System (ADS)

Teplyakova, N. A.; Titov, S. V.; Verbenko, I. A.; Sidorov, N. V.; Reznichenko, L. A.

2015-09-01

Based on Raman spectra, we have studied structural ordering processes in ceramics of ferroelectromagnetics Bi1- x La x FeO3 ( x = 0.075-0.20). It has been found that the structure of Bi1- x La x FeO3 is close to the structure of the crystal BiFeO3. However, lines in Raman spectra of Bi1- x La x FeO3 are considerably broadened compared to lines in the Raman spectrum of the BiFeO3 single crystal, which indicates that the structure of solid solutions is much more disordered. In Raman spectra of Bi1- x La x FeO3, in the range of librational vibrations of octahedra as a whole (50-90 cm-1), several groups of lines are observed in frequency ranges 59-69, 72-77, and 86-92 cm-1 (depending on the composition of solid solution). This confirms X-ray data that examined solid solutions are not single-phase. At a La content x = 0.120, Raman lines in the low-frequency spectral range narrow, which indicates that the ordering of structural units in cationic sublattices somewhat increases. Upon an increase in the content of La in the Bi1- x La x FeO3 structure, no unambiguous dependence of parameters of spectral lines is observed. It is likely that this is explained by the fact that, as the value of x increases, the character of the incorporation of La into the structure of the solid solution changes.

Structural insight into GRIP1-PDZ6 in Alzheimer's disease: study from protein expression data to molecular dynamics simulations.

PubMed

Chatterjee, Paulami; Roy, Debjani

2017-08-01

Protein-protein interaction domain, PDZ, plays a critical role in efficient synaptic transmission in brain. Dysfunction of synaptic transmission is thought to be the underlying basis of many neuropsychiatric and neurodegenerative disorders including Alzheimer's disease (AD). In this study, Glutamate Receptor Interacting Protein1 (GRIP1) was identified as one of the most important differentially expressed, topologically significant proteins in the protein-protein interaction network. To date, very few studies have analyzed the detailed structural basis of PDZ-mediated protein interaction of GRIP1. In order to gain better understanding of structural and dynamic basis of these interactions, we employed molecular dynamics (MD) simulations of GRIP1-PDZ6 dimer bound with Liprin-alpha and GRIP1-PDZ6 dimer alone each with 100 ns simulations. The analyses of MD simulations of Liprin-alpha bound GRIP1-PDZ6 dimer show considerable conformational differences than that of peptide-free dimer in terms of SASA, hydrogen bonding patterns, and along principal component 1 (PC1). Our study also furnishes insight into the structural attunement of the PDZ6 domains of Liprin-alpha bound GRIP1 that is attributed by significant shift of the Liprin-alpha recognition helix in the simulated peptide-bound dimer compared to the crystal structure and simulated peptide-free dimer. It is evident that PDZ6 domains of peptide-bound dimer show differential movements along PC1 than that of peptide-free dimers. Thus, Liprin-alpha also serves an important role in conferring conformational changes along the dimeric interface of the peptide-bound dimer. Results reported here provide information that may lead to novel therapeutic approaches in AD.

Structural characterization of the Man5 glycoform of human IgG3 Fc

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

Shah, Ishan S.; Lovell, Scott; Mehzabeen, Nurjahan

Immunoglobulin G (IgG) consists of four subclasses in humans: IgG1, IgG2, IgG3 and IgG4, which are highly conserved but have unique differences that result in subclass-specific effector functions. Though IgG1 is the most extensively studied IgG subclass, study of other subclasses is important to understand overall immune function and for development of new therapeutics. When compared to IgG1, IgG3 exhibits a similar binding profile to Fcγ receptors and stronger activation of complement. All IgG subclasses are glycosylated at N297, which is required for Fcγ receptor and C1q complement binding as well as maintaining optimal Fc conformation. We have determined themore » crystal structure of homogenously glycosylated human IgG3 Fc with a GlcNAc2Man5 (Man5) high mannose glycoform at 1.8 Å resolution and compared its structural features with published structures from the other IgG subclasses. Although the overall structure of IgG3 Fc is similar to that of other subclasses, some structural perturbations based on sequence differences were revealed. For instance, the presence of R435 in IgG3 (and H435 in the other IgG subclasses) has been implicated to result in IgG3-specific properties related to binding to protein A, protein G and the neonatal Fc receptor (FcRn). The IgG3 Fc structure helps to explain some of these differences. Additionally, protein-glycan contacts observed in the crystal structure appear to correlate with IgG3 affinity for Fcγ receptors as shown by binding studies with IgG3 Fc glycoforms. Finally, this IgG3 Fc structure provides a template for further studies aimed at engineering the Fc for specific gain of function.« less

Association of fluorescein anterior corneal mosaic and corneal K-structures by in vivo laser confocal microscopy in patients with keratoconus

PubMed Central

Kobayashi, Akira; Yokogawa, Hideaki; Mori, Natsuko; Masaki, Toshinori; Sugiyama, Kazuhisa

2017-01-01

Objective To report the in vivo laser confocal microscopy findings of corneas with keratoconus, with special attention to abnormality of Bowman’s layer and sub-Bowman’s fibrous structures (Kobayashi-structures [K-structures]). Methods Sixteen keratoconic eyes in 8 consecutive patients with keratoconus (4 males, 4 females, mean age, 41.1 years) were included in this study. Slit-lamp biomicroscopic photos were taken with or without fluorescein staining. The existence of anterior corneal mosaic (ACM) after eyelid rubbing under fluorescein staining was documented. In vivo laser confocal microscopic examinations were performed for all patients in both the central cone and the peripheral cornea to examine the existence of K-structures. Results According to the Amsler–Krumeich scale, the eyes were graded as follows: stage 1 (n=3), stage 2 (n=1), stage 3 (n=1), and stage 4 (n=11). ACM was observed in 7 eyes (61.1%) in the cone area and 16 eyes (100%) in the peripheral cornea among all keratoconic eyes enrolled in this study. In addition, K-structures were observed in the 7 eyes (61.1%) and 16 eyes (100%) in the peripheral cornea among all keratoconic eyes. The presence of the K-structures was completely matched (100%) with the presence of ACM in both the central cone and the peripheral cornea. In 11 eyes with stage 4 keratoconus, ACM and K-structure was absent in 9 eyes (81.8%) in the cone area. On the contrary, in 5 eyes with mild-to-moderate keratoconus (grade 1 to 3), ACM and K-structure was present in all eyes (100%) in the cone area. The absent ratio of ACM and K-structures in the cone area was significantly higher in stage 4 severe keratoconus compared to mild-to-moderate keratoconus (grade 1 to 3) (Fisher, P=0.005). Conclusion The existence of ACM and K-structures in both the central cone and the peripheral cornea showed perfect accord in patients with keratoconus, indicating a strong association of ACM and K-structures in patients with keratoconus. With the progress of the keratoconus, it seemed that ACM and K-structure progressively disappeared, suggesting Bowman’s layer abnormalities due to keratoconus. Further study in larger groups of patients with keratoconus is required to fully understand the significance of ACM/K-structures in keratoconic eyes and their association with Bowman’s layer. PMID:28794613

Earth Observatory Satellite system definition study. Report no. 3: Design/cost tradeoff studies. Appendix D: EOS configuration design data. Part 1: Spacecraft configuration

NASA Technical Reports Server (NTRS)

1974-01-01

The results of structural studies of the Earth Observatory Satellite (EOS) which define the member sizes to meet the vehicle design requirements are presented. The most significant requirements in sizing the members are the stiffness required to meet the launch vehicle design frequencies both in the late al and in the longitudinal directions. The selected configurations, both baseline and preferred, for the Delta and Titan launch vehicles were evaluated for stiffness requirements. The structural idealization used to estimate the stiffness of each structural arrangement, was based on an evaluation of primary loads paths, effectivity of structural members, and estimated sizes for the preferred configurations. The study included an evaluation of the following structural materials: (1) aluminum alloys, (2) titanium alloys, (3) beryllium, (4) beryllium/aluminum alloy, and (5) composite materials.

Magnetic structure and local lattice distortion in giant negative thermal expansion material Mn3Cu1-xGexN

NASA Astrophysics Data System (ADS)

Iikubo, S.; Kodama, K.; Takenaka, K.; Takagi, H.; Shamoto, S.

2010-11-01

Magnetic and local structures in an antiperovskite system, Mn3Cu1-xGexN, with a giant negative thermal expansion have been studied by neutron powder diffraction measurement. We discuss (1) an importance of an averaged cubic crystal structure and a ΓG5g antiferromagnetic spin structure for the large magneto-volume effect (MVE) in this itinerant electron system, (2) an unique role of a local lattice distortion well described by the low temperature tetragonal structure of Mn3GeN for the broadening of MVE.

Purifying Properly Folded Cysteine-rich, Zinc Finger Containing Recombinant Proteins for Structural Drug Targeting Studies: the CH1 Domain of p300 as a Case Example

PubMed Central

Kim, Yong Joon; Kaluz, Stefan; Mehta, Anil; Weinert, Emily; Rivera, Shannon; Van Meir, Erwin G.

2017-01-01

The transcription factor Hypoxia-Inducible Factor (HIF) complexes with the coactivator p300, activating the hypoxia response pathway and allowing tumors to grow. The CH1 and CAD domains of each respective protein form the interface between p300 and HIF. Small molecule compounds are in development that target and inhibit HIF/p300 complex formation, with the goal of reducing tumor growth. High resolution NMR spectroscopy is necessary to study ligand interaction with p300-CH1, and purifying high quantities of properly folded p300-CH1 is needed for pursuing structural and biophysical studies. p300-CH1 has 3 zinc fingers and 9 cysteine residues, posing challenges associated with reagent compatibility and protein oxidation. A protocol has been developed to overcome such issues by incorporating zinc during expression and streamlining the purification time, resulting in a high yield of optimally folded protein (120 mg per 4 L expression media) that is suitable for structural NMR studies. The structural integrity of the final recombinant p300-CH1 has been verified to be optimal using onedimensional 1H NMR spectroscopy and circular dichroism. This protocol is applicable for the purification of other zinc finger containing proteins. PMID:28966947

11th Annual Systems Engineering Conference

DTIC Science & Technology

2008-10-23

effectiveness for force structure architecture studies – Problem of interest was Layered Intelligence, Surveillance and Reconnaissance ( LISR ) with Integrated...Cleared for Public Release, Control No. 08-110, dtd. 10-1-0811 LISR CET Typical Products 1 Satellite_A; 1 Satellite_B; 3 VehA; 1 VehB (50%) 2 VehA; 3...the means to support LISR force structure architecture studies: Stand-alone and as a lead-in to detailed work Cleared for Public Release, Control No

Supramolecular architectures constructed through self-assembly of a chalcone and substituted diazo-β-diketones

NASA Astrophysics Data System (ADS)

Prajapati, R.; Mishra, L.; Grabowski, S. J.; Govil, G.; Dubey, S. K.

2008-05-01

Organic compounds namely pyridyl chalcone viz. 3-[4-(3-oxo-3-pyridin-2-yl-propenyl)-phenyl]-1-pyridin-2-yl-propenone (L 1), p-cholorophenyldiazopentane-2,4-dione (L 2) and p-methyl phenyldiazopentane-2,4-dione (L 3) have been characterized by their single-crystal X-ray crystallographic studies. Several structural motifs resulting upon their self-association through probable non-covalent interactions have been discussed. The studies of related motifs found in Cambridge Structural Database are performed and the results are related to the structural data obtained for crystal structures reported here in.

FIBER AND INTEGRATED OPTICS: Photodetector waveguide structures made of epitaxial InGaAs films and intended for integrated circuits manufactured from III-V semiconductor compounds

NASA Astrophysics Data System (ADS)

Shmal'ko, A. V.; Lamekin, V. F.; Smirnov, V. L.; Polyantsev, A. S.; Kogan, Yu I.; Babushkina, T. S.; Kuntsevich, T. S.; Peshkovskaya, O. G.

1990-08-01

Photodetector waveguide structures made of epitaxial InxGa1 - xAs solid-solution films were developed and investigated. These structures were intended for optical integrated circuits manufactured from III-V semiconductor compounds for operation in the wavelength range 1.0-1.5 μm. Two types of photodetector waveguide p-i-n structures were developed. They consisted of a composite waveguide and tunnel-coupled waveguides, respectively. A study was made of structural parameters, responsivity, spectral and time characteristics, and dark currents in photodetectors made of the waveguide structures. This investigation was carried out in the wavelength range 1.0-1.3 μm. The maximum spectral responsivity of one of the types of the waveguide photodetector was ~ 0.5 ± 0.1 A/W and the dark current did not exceed 10 - 7-10 - 8 A.

Crystal structures of inhibitor complexes of human T-cell leukemia virus (HTLV-1) protease

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

Satoh, Tadashi; Li, Mi; Nguyen, Jeffrey-Tri

2010-09-28

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus associated with several serious diseases, such as adult T-cell leukemia and tropical spastic paraparesis/myelopathy. For a number of years, the protease (PR) encoded by HTLV-1 has been a target for designing antiviral drugs, but that effort was hampered by limited available structural information. We report a high-resolution crystal structure of HTLV-1 PR complexed with a statine-containing inhibitor, a significant improvement over the previously available moderate-resolution structure. We also report crystal structures of the complexes of HTLV-1 PR with five different inhibitors that are more compact and more potent. A detailedmore » study of structure-activity relationships was performed to interpret in detail the influence of the polar and hydrophobic interactions between the inhibitors and the protease.« less

Crystal Structures of Inhibitir Complexes of Human T-Cell Leukemia Virus (HTLV-1) Protease

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

Satoh, Tadashi; Li, Mi; Nguyen, Jeffrey-Tri

2010-09-17

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus associated with several serious diseases, such as adult T-cell leukemia and tropical spastic paraparesis/myelopathy. For a number of years, the protease (PR) encoded by HTLV-1 has been a target for designing antiviral drugs, but that effort was hampered by limited available structural information. We report a high-resolution crystal structure of HTLV-1 PR complexed with a statine-containing inhibitor, a significant improvement over the previously available moderate-resolution structure. We also report crystal structures of the complexes of HTLV-1 PR with five different inhibitors that are more compact and more potent. A detailedmore » study of structure-activity relationships was performed to interpret in detail the influence of the polar and hydrophobic interactions between the inhibitors and the protease.« less

Structural, dielectric and impedance spectroscopy studies in Co doped La0.7Te0.3MnO3

NASA Astrophysics Data System (ADS)

Uthaman, Bhagya; Revathy, R.; Job, Rojerce Brown; Varma, Manoj Raama

2018-05-01

The effect of cobalt doping on the structural and dielectric properties of the electron-doped manganite La0.7Te0.3Mn1-xCoxO3 (x=0, 0.1, 0.3 and 0.5) has been investigated. Cobalt substitution induces a structural transition from rhombohedral structure (R-3 c space group) to orthorhombic structure (Pbnm space group). It is observed that, dielectric constant decreases with Co concentration which could be due to suppression of double exchange (DE) interaction between Mn2+ and Mn3+. Also, the effect of the grain and grain boundary density on the dielectric response is studied using Cole-Cole plots.

Insights into the structural/conformational requirements of cytotoxic oxadiazoles as potential chemotherapeutic target binding agents

NASA Astrophysics Data System (ADS)

Alikhani, Radin; Razzaghi-Asl, Nima; Ramazani, Ali; Hosseinzadeh, Zahra

2018-07-01

A few novel previously synthesized 2,5-disubstituted 1,3,4-oxadiazoles with cytotoxic activity (1-17) were subjected to combined docking/quantum mechanical studies against chemotherapeutic targets. Selected macromolecular targets were those that were previously known to be inhibited by 1,3,4-oxadiazoles. Within this work, favorable binding modes/affinities of the oxadiazoles toward validated cancer targets were elucidated. Some oxadiazole structures exhibited ΔGbs comparable to or stronger than crystallographic ligands that were previously demonstrated to inhibit such targets. On the basis of obtained results, a general structure activity/binding relationship (SAR/SBR) was developed and a few 2,5-disubstituted 1,3,4-oxadiazole structures were proposed and virtually validated as potential cytotoxic candidates. To get more insight into structure binding relationship of candidate molecules within best correlated targets, docked conformation of the best in silico in vitro correlated oxadiazole structure was analyzed in terms of intermolecular binding energy components by functional B3LYP in association with split valence basis set using polarization functions (Def2-SVP). We believe that such modeling studies may be complementary to our previous results on the synthesis and cytotoxicity assessment of novel 1,3,4-oxadiazole derivatives through extending the scope of privileged structures toward designing new potential anti-tumor compounds.

Crystal structure of TBC1D15 GTPase-activating protein (GAP) domain and its activity on Rab GTPases.

PubMed

Chen, Yan-Na; Gu, Xin; Zhou, X Edward; Wang, Weidong; Cheng, Dandan; Ge, Yinghua; Ye, Fei; Xu, H Eric; Lv, Zhengbing

2017-04-01

TBC1D15 belongs to the TBC (Tre-2/Bub2/Cdc16) domain family and functions as a GTPase-activating protein (GAP) for Rab GTPases. So far, the structure of TBC1D15 or the TBC1D15·Rab complex has not been determined, thus, its catalytic mechanism on Rab GTPases is still unclear. In this study, we solved the crystal structures of the Shark and Sus TBC1D15 GAP domains, to 2.8 Å and 2.5 Å resolution, respectively. Shark-TBC1D15 and Sus-TBC1D15 belong to the same subfamily of TBC domain-containing proteins, and their GAP-domain structures are highly similar. This demonstrates the evolutionary conservation of the TBC1D15 protein family. Meanwhile, the newly determined crystal structures display new variations compared to the structures of yeast Gyp1p Rab GAP domain and TBC1D1. GAP assays show that Shark and Sus GAPs both have higher catalytic activity on Rab11a·GTP than Rab7a·GTP, which differs from the previous study. We also demonstrated the importance of arginine and glutamine on the catalytic sites of Shark GAP and Sus GAP. When arginine and glutamine are changed to alanine or lysine, the activities of Shark GAP and Sus GAP are lost. © 2017 The Protein Society.

Structural and magnetic properties of non-stoichiometric Fe1-xO thin films

NASA Astrophysics Data System (ADS)

Muhammed Shameem P., V.; Mekala, Laxman; Kumar, M. Senthil

2018-04-01

The Fe1-xO thin films of various iron deficiencies (x) have been grown at ambient temperature by reactive dc magnetron sputtering technique and their structural and magnetic properties are studied. The structural study shows that the films are polycrystalline. As the iron content (1-x) varies from 0.924 to 0.855 a clear consistent change in the preferential orientation of the grains from [111] to the [200] direction is observed. The magnetization measurements show the possible existence of small superparamagnetic defect clusters at 300 K and large spinel-type defect clusters below the Neel temperature.

Pressure induced phase transition in CdTe nanowire: A DFT study

NASA Astrophysics Data System (ADS)

Bhatia, Manjeet; Khan, Md. Shahzad; Srivastava, Anurag

2018-05-01

We have studied structural phase transition and electronic properties of CdTe nanowires in their wurtzite (B4) to rocksalt (B1) phase by first principles density functional calculations using SIESTA code. Nanowires are derived from wurtzite and rocksalt phase of bulk CdTe with growth direction along 100 planes. We observed structural phase transition from B4→B1 at 4.79 GPa. Wurtzite structure is found to have band gap 2.30 eV while rocksalt is metallic in nature. Our calculated lattice constant (4.55 Å for B4 and 5.84 Å for B1), transition pressure (4.79 GPa) and electronic structure results are in close agreement with the previous calculations on bulk and nanostructures.

Structural and functional predictors of regional peak pressures under the foot during walking.

PubMed

Morag, E; Cavanagh, P R

1999-04-01

The objective of this study was to identify structural and functional factors which are predictors of peak pressure underneath the human foot during walking. Peak plantar pressure during walking and eight data sets of structural and functional measures were collected on 55 asymptomatic subjects between 20 and 70 yr. A best subset regression approach was used to establish models which predicted peak regional pressure under the foot. Potential predictor variables were chosen from physical characteristics, anthropometric data, passive range of motion (PROM), measurements from standardized weight bearing foot radiographs, mechanical properties of the plantar soft tissue, stride parameters, foot motion in 3D, and EMG during walking. Peak pressure values under the rearfoot, midfoot, MTH1, and hallux were measured. Heel pressure was a function of linear kinematics, longitudinal arch structure, thickness of plantar soft tissue, and age. Midfoot pressure prediction was dominated by arch structure, while MTH1 pressure was a function of radiographic measurements, talo-crural joint motion, and gastrocnemius activity. Hallux pressure was a function of structural measures and MTP1 joint motion. Foot structure and function predicted only approximately 50% of the variance in peak pressure, although the relative contributions in different anatomical regions varied dramatically. Structure was dominant in predicting peak pressure under the midfoot and MTH1, while both structure and function were important at the heel and hallux. The predictive models developed in this study give insight into potential etiological factors associated with elevated plantar pressure. They also provide direction for future studies designed to reduce elevated pressure in "at-risk" patients.

Electronic structure-sunlight driven water splitting activity correlation of (Zn1-yGay)(O1-zNz).

PubMed

RajaAmbal, Sivaraman; Yadav, A K; Jha, S N; Bhattacharyya, D; Gopinath, Chinnnakonda S

2014-11-21

(Zn1-yGay)(O1-zNz) (y≤ 0.10; z≤ 0.15) solid solutions have been investigated for their electronic structure and visible light photocatalytic activity, and a correlation was found between them. (Zn1-yGay)(O1-zNz) with ZnO as the major component have been synthesized by a solution combustion method in 10 minutes using simple raw materials. The local structures of Zn K edge and Ga K edge, and changes in the chemical environment with the incorporation of Ga and N in ZnO were determined by EXAFS study. EXAFS and XRD results suggested the dissolution of GaN in the ZnO lattice. The homogeneity of the solid solution was demonstrated from HRTEM studies. Photoluminescence studies revealed the creation of a new band at the top of the ZnO valence band (VB), and thus the broadening of the VB of (Zn1-yGay)(O1-zNz) or a decrease in the band gap was attributed to the origin of visible light absorption. UV-Vis spectral studies showed light absorption up to 550 nm, which directly supports the VB broadening. Predominant oxygen vacancies and high photocorrosion observed for ZnO were fully suppressed for (Zn1-yGay)(O1-zNz), indicating the minimization of defects, and thus more sustainability under irradiation conditions. The bare solid solution exhibited reasonable and promising activity for solar hydrogen evolution and photoelectrochemical current generation at 0 V. The present work explained factors such as the preparation method, single phase structure with the stabilization of integral parts, homogeneity in the structure, compensation of oxygen vacancies, and suppression of the density of recombination centres that play a pivotal role in realizing solar energy harvesting.

Structural characterisation of some vanillic Mannich bases: Experimental and theoretical study

NASA Astrophysics Data System (ADS)

Petrović, Vladimir P.; Simijonović, Dušica; Novaković, Sladjana B.; Bogdanović, Goran A.; Marković, Svetlana; Petrović, Zorica D.

2015-10-01

In this paper, synthesis and structural determination of 2-[1-(N-4-fluorophenylamino)-1-(4-hydroxy-3-methoxyphenyl)]methylcyclohexanone (MB-F) is presented. To determine the structure of this new compound, IR and NMR spectral characterisation was performed experimentally and theoretically. Simulation of spectral data was carried out using three functionals: B3LYP, B3LYP-D2, and M06-2X. The results obtained for MB-F were compared to those attained for similar, known compound 2-[1-(N-phenylamino)-1-(4-hydroxy-3-methoxyphenyl)]methylcyclohexanone (MB-H), whose crystal structure is presented here. Taking into account all experimental and theoretical findings, the structure of MB-F was proposed.

Origin of the magnetic transition at 100 K in ɛ-Fe2O3 nanoparticles studied by x-ray absorption fine structure spectroscopy

NASA Astrophysics Data System (ADS)

López-Sánchez, J.; Muñoz-Noval, A.; Castellano, C.; Serrano, A.; del Campo, A.; Cabero, M.; Varela, M.; Abuín, M.; de la Figuera, J.; Marco, J. F.; Castro, G. R.; Rodríguez de la Fuente, O.; Carmona, N.

2017-12-01

The current study unveils the structural origin of the magnetic transition of the ɛ-Fe2O3 polymorph from an incommensurate magnetic order to a collinear ferrimagnetic state at low temperature. The high crystallinity of the samples and the absence of other iron oxide polymorphs have allowed us to carry out temperature-dependent x-ray absorption fine structure spectroscopy experiments out. The deformation of the structure is followed by the Debye-Waller factor for each selected Fe-O and Fe-Fe sub-shell. For nanoparticle sizes between 7 and 15 nm, the structural distortions between the Fete and Fe-D1oc sites are localized in a temperature range before the magnetic transition starts. On the contrary, the inherent interaction between the other sub-shells (named Fe-O1,2 and Fe-Fe1) provokes cooperative magneto-structural changes in the same temperature range. This means that the Fete with Fe-D1oc polyhedron interaction seems to be uncoupled with temperature dealing with these nanoparticle sizes wherein the structural distortions are likely moderate due to surface effects.

Structural hierarchy of chromatin in chicken erythrocyte nuclei based on small-angle neutron scattering: Fractal nature of the large-scale chromatin organization

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

Lebedev, D. V., E-mail: isaev@omrb.pnpi.spb.ru; Filatov, M. V.; Kuklin, A. I.

The chromatin organization in chicken erythrocyte nuclei was studied by small-angle neutron scattering in the scattering-vector range from 1.5 x 10{sup -1} to 10{sup -4} A{sup -1} with the use of the contrast-variation technique. This scattering-vector range corresponds to linear dimensions from 4 nm to 6 {mu}m and covers the whole hierarchy of chromatin structures, from the nucleosomal structure to the entire nucleus. The results of the present study allowed the following conclusions to be drawn: (1) both the chromatin-protein structure and the structure of the nucleic acid component in chicken erythrocyte nuclei have mass-fractal properties, (2) the structure ofmore » the protein component of chromatin exhibits a fractal behavior on scales extending over two orders of magnitude, from the nucleosomal size to the size of an entire nucleus, and (3) the structure of the nucleic acid component of chromatin in chicken erythrocyte nuclei is likewise of a fractal nature and has two levels of organization or two phases with the crossover point at about 300-400 nm.« less

ARE THE FAINT STRUCTURES AHEAD OF SOLAR CORONAL MASS EJECTIONS REAL SIGNATURES OF DRIVEN SHOCKS?

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

Lee, Jae-Ok; Moon, Y.-J.; Lee, Kangjin

2014-11-20

Recently, several studies have assumed that the faint structures ahead of coronal mass ejections (CMEs) are caused by CME-driven shocks. In this study, we have conducted a statistical investigation to determine whether or not the appearance of such faint structures depends on CME speeds. For this purpose, we use 127 Solar and Heliospheric Observatory/Large Angle Spectroscopic COronagraph (LASCO) front-side halo (partial and full) CMEs near the limb from 1997 to 2011. We classify these CMEs into two groups by visual inspection of CMEs in the LASCO-C2 field of view: Group 1 has the faint structure ahead of a CME andmore » Group 2 does not have such a structure. We find the following results. (1) Eighty-seven CMEs belong to Group 1 and 40 CMEs belong to Group 2. (2) Group 1 events have much higher speeds (average = 1230 km s{sup –1} and median = 1199 km s{sup –1}) than Group 2 events (average = 598 km s{sup –1} and median = 518 km s{sup –1}). (3) The fraction of CMEs with faint structures strongly depends on CME speeds (V): 0.93 (50/54) for fast CMEs with V ≥ 1000 km s{sup –1}, 0.65 (34/52) for intermediate CMEs with 500 km s{sup –1} ≤ V < 1000 km s{sup –1}, and 0.14 (3/21) for slow CMEs with V < 500 km s{sup –1}. We also find that the fraction of CMEs with deca-hecto metric type II radio bursts is consistent with the above tendency. Our results indicate that the observed faint structures ahead of fast CMEs are most likely an enhanced density manifestation of CME-driven shocks.« less

Bioinformatic Analysis of Pathogenic Missense Mutations of Activin Receptor Like Kinase 1 Ectodomain

PubMed Central

Scotti, Claudia; Olivieri, Carla; Boeri, Laura; Canzonieri, Cecilia; Ornati, Federica; Buscarini, Elisabetta; Pagella, Fabio; Danesino, Cesare

2011-01-01

Activin A receptor, type II-like kinase 1 (also called ALK1), is a serine-threonine kinase predominantly expressed on endothelial cells surface. Mutations in its ACVRL1 encoding gene (12q11-14) cause type 2 Hereditary Haemorrhagic Telangiectasia (HHT2), an autosomal dominant multisystem vascular dysplasia. The study of the structural effects of mutations is crucial to understand their pathogenic mechanism. However, while an X-ray structure of ALK1 intracellular domain has recently become available (PDB ID: 3MY0), structure determination of ALK1 ectodomain (ALK1EC) has been elusive so far. We here describe the building of a homology model for ALK1EC, followed by an extensive bioinformatic analysis, based on a set of 38 methods, of the effect of missense mutations at the sequence and structural level. ALK1EC potential interaction mode with its ligand BMP9 was then predicted combining modelling and docking data. The calculated model of the ALK1EC allowed mapping and a preliminary characterization of HHT2 associated mutations. Major structural changes and loss of stability of the protein were predicted for several mutations, while others were found to interfere mainly with binding to BMP9 or other interactors, like Endoglin (CD105), whose encoding ENG gene (9q34) mutations are known to cause type 1 HHT. This study gives a preliminary insight into the potential structure of ALK1EC and into the structural effects of HHT2 associated mutations, which can be useful to predict the potential effect of each single mutation, to devise new biological experiments and to interpret the biological significance of new mutations, private mutations, or non-synonymous polymorphisms. PMID:22028876

Structure of Motor Abilities in Children.

ERIC Educational Resources Information Center

Krus, Patricia H.; And Others

1981-01-01

The purpose of this study was to investigate the structure of motor proficiency in a sample of 765 children between the ages of 4 1/2 to 14 1/2 years. The study was conducted as one aspect of the standardization of a motor proficiency scale, the Bruininks-Oseretsky Test of Motor Proficiency. (Author/SJL)

DNA binding mechanism revealed by high resolution crystal structure of Arabidopsis thaliana WRKY1 protein

PubMed Central

Duan, Ming-Rui; Nan, Jie; Liang, Yu-He; Mao, Peng; Lu, Lu; Li, Lanfen; Wei, Chunhong; Lai, Luhua; Li, Yi; Su, Xiao-Dong

2007-01-01

WRKY proteins, defined by the conserved WRKYGQK sequence, are comprised of a large superfamily of transcription factors identified specifically from the plant kingdom. This superfamily plays important roles in plant disease resistance, abiotic stress, senescence as well as in some developmental processes. In this study, the Arabidopsis WRKY1 was shown to be involved in the salicylic acid signaling pathway and partially dependent on NPR1; a C-terminal domain of WRKY1, AtWRKY1-C, was constructed for structural studies. Previous investigations showed that DNA binding of the WRKY proteins was localized at the WRKY domains and these domains may define novel zinc-binding motifs. The crystal structure of the AtWRKY1-C determined at 1.6 Å resolution has revealed that this domain is composed of a globular structure with five β strands, forming an antiparallel β-sheet. A novel zinc-binding site is situated at one end of the β-sheet, between strands β4 and β5. Based on this high-resolution crystal structure and site-directed mutagenesis, we have defined and confirmed that the DNA-binding residues of AtWRKY1-C are located at β2 and β3 strands. These results provided us with structural information to understand the mechanism of transcriptional control and signal transduction events of the WRKY proteins. PMID:17264121

A Water‐Soluble Tetraazaperopyrene Dye as Strong G‐Quadruplex DNA Binder

PubMed Central

Hahn, Lena

2016-01-01

Abstract The interactions of the water‐soluble tetraazaperopyrene dye 1 with ct‐DNA, duplex‐[(dAdT)12 ⋅(dAdT)12], duplex‐[(dGdC)12 ⋅(dGdC)12] as well as with two G‐quadruplex‐forming sequences, namely the human telomeric 22AG and the promotor sequence c‐myc, were investigated by means of UV/visible and fluorescence spectroscopy, isothermal titration calorimetry (ITC) and molecular docking studies. Dye 1 exhibits a high affinity for G‐quadruplex structures over duplex DNA structures. Furthermore, the ligand shows promising G‐quadruplex discrimination, with an affinity towards c‐myc of 2×107  m −1 (i.e., K d=50 nm), which is higher than for 22AG (4×106  m −1). The ITC data reveal that compound 1 interacts with c‐myc in a stoichiometric ratio of 1:1 but also indicate the presence of two identical lower affinity secondary binding sites per quadruplex. In 22AG, there are two high affinity binding sites per quadruplex, that is, one on each side, with a further four weaker binding sites. For both quadruplex structures, the high affinity interactions between compound 1 and the quadruplex‐forming nucleic acid structures are weakly endothermic. Molecular docking studies suggest an end‐stacking binding mode for compound 1 interacting with quadruplex structures, and a higher affinity for the parallel conformation of c‐myc than for the mixed‐hybrid conformation of 22AG. In addition, docking studies also suggest that the reduced affinity for duplex DNA structures is due to the non‐viability of an intercalative binding mode. PMID:26997208

Synthesis, fungicidal activity, structure-activity relationships (SARs) and density functional theory (DFT) studies of novel strobilurin analogues containing arylpyrazole rings.

PubMed

Liu, Yuanyuan; Lv, Kunzhi; Li, Yi; Nan, Qiuli; Xu, Jinyuan

2018-05-18

A series of novel strobilurin analogues (1a-1f, 2a-2e, 3a-3e) containing arylpyrazole rings were synthesized and characterized by NMR spectroscopy. The structures of 1f, 2b and 3b were also determined by single crystal X-ray diffraction analysis. These analogues were collected together with other twenty-eight similar compounds 4a-4f, 5a-5h, 6a-6h and 7a-7f from our previous studies, for in vitro bioassays and thorough structure-activity relationships (SARs) studies. Most compounds exhibited excellent-to-good fungicidal activity against Rhizoctonia solani, especially 5c, 7a, 6c, and 3b with 98.94%, 83.40%, 71.40% and 65.87% inhibition rates at 0.1 μg mL -1 , respectively, better than commercial pyraclostrobin. Comparative molecular field analysis (CoMFA) was employed to study three-dimensional quantitative structure-activity relationships (3D-QSARs). Density functional theory (DFT) calculation was also carried out to provide more information regarding SARs. The present work provided some hints for developing novel strobilurin fungicides.

Analysis of Soil Structure Turnover with Garnet Particles and X-Ray Microtomography

PubMed Central

Vogel, Hans-Jörg

2016-01-01

Matter turnover in soil is tightly linked to soil structure which governs the heterogeneous distribution of habitats, reaction sites and pathways in soil. Thereby, the temporal dynamics of soil structure alteration is deemed to be important for essential ecosystem functions of soil but very little is known about it. A major reason for this knowledge gap is the lack of methods to study soil structure turnover directly at microscopic scales. Here we devise a conceptual approach and an image processing workflow to study soil structure turnover by labeling some initial state of soil structure with small garnet particles and tracking their fate with X-ray microtomography. The particles adhere to aggregate boundaries at the beginning of the experiment but gradually change their position relative to the nearest pore as structure formation progresses and pores are destructed or newly formed. A new metric based on the contact distances between particles and pores is proposed that allows for a direct quantification of soil structure turnover rates. The methodology is tested for a case study about soil compaction of a silty loam soil during stepwise increase of bulk density (ρ = {1.1, 1.3, 1.5} g/cm3). We demonstrate that the analysis of mean contact distances provides genuinely new insights about changing diffusion pathways that cannot be inferred neither from conventional pore space attributes (porosity, mean pore size, pore connectivity) nor from deformation analysis with digital image correlation. This structure labeling approach to quantify soil structure turnover provides a direct analogy to stable isotope labeling for the analysis of matter turnover and can be readily combined with each other. PMID:27453995

Interaction of SDS with β-galactosidase. A FT-IR study of the influence of detergent concentration and temperature.

NASA Astrophysics Data System (ADS)

Muga, A.; Castresana, J.; Arrondo, J. L. R.; López, S.; Bernabeu, C.

1988-05-01

The major structure of the enzyme β-galactosidase as studied by FT-IR is β-sheet with maxima in the amide I band at 1639 and 1655 cm -1 in H 2O and 1634 in D 2O. α-helix structure is also present with contribution from β-turns and less-ordered structure. Temperature induces a rearrangement of the structure producing a β-sheet-like conformation. In the presence of the surfactant SDS no big difference in structure is seen at 1% SDS (w:ww) concentration but there is a decrease of 5°C in the midpoint thermal denaturation. In the presence of 10% SDS a different picture is obtained with a higher random structure content.

ERP Evidence for the Activation of Syntactic Structure During Comprehension of Lexical Idiom.

PubMed

Zhang, Meichao; Lu, Aitao; Song, Pingfang

2017-10-01

The present study used event-related potentials to investigate whether the syntactic structure was activated in the comprehension of lexical idioms, and if so, whether it varied as a function of familiarity and semantic transparency. Participants were asked to passively read the "1+2" structural Chinese lexical idioms with each being presented following 3-5 contextual "1+2" (congruent-structure condition) or "2+1" structural Chinese phrases (incongruent-structure condition). The N400 ERP responses showed more positivity in congruent-structure condition relative to incongruent-structure condition in idioms with high familiarity and high semantic transparency, but less positivity in congruent-structure condition in idioms with high familiarity but low semantic transparency, idioms with low familiarity but high semantic transparency, and idioms with low familiarity and low semantic transparency. Our results suggest that syntactic structure, as the unnecessarity of lexical idiomatic words, was nevertheless activated, independent of familiarity and semantic transparency.

Structural determinants of nuclear export signal orientation in binding to exportin CRM1

DOE PAGES

Fung, Ho Yee Joyce; Fu, Szu -Chin; Brautigam, Chad A.; ...

2015-09-08

The Chromosome Region of Maintenance 1 (CRM1) protein mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure. The plasticity of the CRM1-NES interaction is not well understood, as there are many NES sequences that seem incompatible with structures of the NES-bound CRM1 groove. Crystal structures of CRM1 bound to two different NESs with unusual sequences showed the NES peptides binding the CRM1 groove in the opposite orientation (minus) to that of previously studied NESs (plus). A comparison of minus and plus NESs identified structural and sequencemore » determinants for NES orientation. The binding of NESs to CRM1 in both orientations results in a large expansion in NES consensus patterns and therefore a corresponding expansion of potential NESs in the proteome.« less

Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2-P3 ligands: Synthesis, biological evaluation and X-ray structural studies of inhibitor-HIV-1 protease complex

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

Ghosh, Arun K.; Brindisi, Margherita; Nyalapatla, Prasanth R.

Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme Ki of 0.025 nM and antiviral IC50 of 69 nM. An X-ray crystal structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33 Å resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at 1.27 Å resolution. These structures revealed important molecular insight into the inhibitor–HIV-1 protease interactions in the active site.

Structural studies of chromatin and chromosomes. Progress report, March 15--September 15, 1997

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

Bradbury, E.M.

This study focused on the following: (1) the structure of chromatin and chromosomes by neutron and x-ray scatter and atomic force microscope; (2) the architecture of human sperm and the structure of sperm by atomic force microscopy (AFM); (3) genome-architecture and higher-order structures in human sperm nuclei; and (4) the effects of histone modifications on the structure of nucleosomes by protein DNA crosslinking method.

Tuning band gap of monolayer and bilayer SnS2 by strain effect and external electric field: A first principles calculations

NASA Astrophysics Data System (ADS)

Rahman, Abeera; Shin, Young-Han

Recently many efforts have been paid to two-dimensional layered metal dichalcogenides (LMDs). Among them MoS2 has become a prototype LMD, and recent studies show surprising and rich new physics emerging in other van der Waals materials such as layered SnS2 [1-4]. SnS2 is a semiconducting earth-abundant material and Sn is a group IV element replacing the transition metal in MoS2. SnS2 shows new possibilities in various potential applications. However, the knowledge on basic properties of layered SnS2 is still not well understood. In this study, we consider two types of structures; 1T with P 3 m 1 (164) space group and 1H with P63 / mmc (194) space group. Our first principles calculations show that the 1T structure for SnS2 is more stable than the 1H structure whereas latter is more stable for MoS2. Moreover,in contrast to MoS2,SnS2 shows an indirect band gap both for 1T and 1H structures while 1T MoS2 is metallic and 1H has a direct band gap. We also study strain effect in the range of 0-10% on the band structure for monolayer and bilayer SnS2 (both for 1T and 1H structures).We find significant change in their band gaps. We also investigate the bilayer SnS2 with and without out-of-plane stress. This research was supported by Brain Korea 21 Plus Program and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (NRF-2014M3A7B4049367, NRF-2014R1A2A1A1105089).

Interactions of Oxygen and Hydrogen on Pd(111) surface

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

Demchenko, D.O.; Sacha, G.M.; Salmeron, M.

2008-06-25

The coadsorption and interactions of oxygen and hydrogen on Pd(1 1 1) was studied by scanning tunneling microscopy and density functional theory calculations. In the absence of hydrogen oxygen forms a (2 x 2) ordered structure. Coadsorption of hydrogen leads to a structural transformation from (2 x 2) to a ({radical}3 x {radical}3)R30 degree structure. In addition to this transformation, hydrogen enhances the mobility of oxygen. To explain these observations, the interaction of oxygen and hydrogen on Pd(1 1 1) was studied within the density functional theory. In agreement with the experiment the calculations find a total energy minimum formore » the oxygen (2 x 2) structure. The interaction between H and O atoms was found to be repulsive and short ranged, leading to a compression of the O islands from (2 x 2) to ({radical}3 x {radical}3)R30 degree ordered structure at high H coverage. The computed energy barriers for the oxygen diffusion were found to be reduced due to the coadsorption of hydrogen, in agreement with the experimentally observed enhancement of oxygen mobility. The calculations also support the finding that at low temperatures the water formation reaction does not occur on Pd(1 1 1).« less

The Structure and Intensity of Emotional Experiences: Method and Context Convergence.

ERIC Educational Resources Information Center

Mano, Haim

1991-01-01

Structure and intensity of naturally occurring and induced affect were studied with 244 university students and 1 employee in 2 studies using 2 methodological paradigms (dimensionality and classification) and 2 everyday contexts (lecture and television advertising). A circular structure of feeling was experienced during the lecture (naturally…

Self-Study and Evaluation Guide/Revised 1979. Section C-1: Function and Structure.

ERIC Educational Resources Information Center

National Accreditation Council for Agencies Serving the Blind and Visually Handicapped, New York, NY.

The self study guide designed for accreditation of programs serving the blind and visually handicapped covers function and structure standards, standards address five areas: basic characteristics of the organization (legal base, planning, consumer rights), governing authority, the Chief administrator, basic administrative structure (fees for…

Compilation of hydrologic data, Little Elm Creek, Trinity River basin, Texas, 1968

USGS Publications Warehouse

,

1972-01-01

The U.S. Soil Conservation Service is actively engaged in the installation of flood and soil erosion reducing measures in Texas under the authority of "The Flood Control Act ot 1936 and 1944" and ''Watershed Protection and Flood Prevention Act" (Public Law 566), as amended. In June 1968, the Soil Conservation Service estimated approximately 3,500 structures to be physically and economically feasible for installation in Texas. As of September 30, 1968, 1,271 of these structures had been built. This watershed-development program will have varying but important effects on the surface- and ground-water resources of river basins, especially where a large number of the floodwater-retarding structures are built. Basic hydrologic data are needed to appraise the effects of the structures on water yield and the mode of occurrence of runoff. Hydrologic investigations of these small watersheds were begun by the Geological Survey in 1951 and are now being made in 11 areas (fig. 1). These studies are being made in cooperation with t he Texas Water Development Board, the Soil Conservation Service, the San Antonio River Authority, the city of Dallas, and the Tarrant County Water Control and Improvement District No. 1. The 11 study areas were choson to sample watersheds having different rainfall, topography, geology, and soils. In four of the study areas (Mukewater, North, Little Elm, and Pin Oak Creeks), streamflow and rainfall records were collected prior to construction of the floodwater-retarding structures, thus affording the opportunity for analyses to the conditions before and after" development. Structures have now been built in three of these study areas. A summary of the development of the floodwater-retarding structures on each study area as of September 30, 1968, is shown in table 1.

Integration of Inhibition Kinetics and Molecular Dynamics Simulations: A Urea-Mediated Folding Study on Acetaldehyde Dehydrogenase 1.

PubMed

Xu, Yingying; Lee, Jinhyuk; Lü, Zhi-Rong; Mu, Hang; Zhang, Qian; Park, Yong-Doo

2016-07-01

Understanding the mechanism of acetaldehyde dehydrogenase 1 (ALDH1) folding is important because this enzyme is directly involved in several types of cancers and other diseases. We investigated the urea-mediated unfolding of ALDH1 by integrating kinetic inhibition studies with computational molecular dynamics (MD) simulations. Conformational changes in the enzyme structure were also analyzed using intrinsic and 1-anilinonaphthalene-8-sulfonate (ANS)-binding fluorescence measurements. Kinetic studies revealed that the direct binding of urea to ALDH1 induces inactivation of ALDH1 in a manner of mixed-type inhibition. Tertiary structural changes associated with regional hydrophobic exposure of the active site were observed. The urea binding regions on ALDH1 were predicted by docking simulations and were partly shared with active site residues of ALDH1 and with interface residues of the oligomerization domain for tetramer formation. The docking results suggest that urea prevents formation of the ALDH1 normal shape for the tetramer state as well as entrance of the substrate into the active site. Our study provides insight into the structural changes that accompany urea-mediated unfolding of ALDH1 and the catalytic role associated with conformational changes.

The crystal structure of sulfamethoxazole, interaction with DNA, DFT calculation, and molecular docking studies

NASA Astrophysics Data System (ADS)

Das, Dipankar; Sahu, Nilima; Roy, Suman; Dutta, Paramita; Mondal, Sudipa; Torres, Elena L.; Sinha, Chittaranjan

2015-02-01

Sulfamethoxazole (SMX) [4-amino-N-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide] is structurally established by single crystal X-ray diffraction measurement. The crystal packing shows H-bonded 2D polymer through N(7)sbnd H(7A)---O(2), N(7)sbnd H(7B)---O(3), N(1)sbnd H(1)---N(2), C(5)sbnd H(5)---O(3)sbnd S(1) and N(7)sbnd (H7A)---O(2)sbnd S(1). Density Functional Theory (DFT) and Time Dependent-DFT (TD-DFT) computations of optimized structure of SMX determine the electronic structure and has explained the electronic spectral transitions. The interaction of SMX with CT-DNA has been studied by absorption spectroscopy and the binding constant (Kb) is 4.37 × 104 M-1. The in silico test of SMX with DHPS from Escherichia coli and Streptococcus pneumoniae helps to understand drug metabolism and accounts the drug-molecule interactions. The molecular docking of SMX-DNA also helps to predict the interaction feature.

Growth of carbon structured over Pd, Pt and Ni: A comparative DFT study

NASA Astrophysics Data System (ADS)

Quiroga, Matías Abel

2013-03-01

To elucidate the graphene-like structures mechanisms growth over the M(1 1 1) surface (M = Pd, Pt and Ni) we performed ab initio calculus in the frame of density functional theory with the exchange-correlation functional treated according to the Generalized Gradient Approximation (GGA). In order to avoid the problem that represent the complex interaction between the well formed graphene layer and the metallic surface, we recreate the carbon rings formation initial steps, by adding one by one carbon atoms over M(1 1 1) surface. With this strategy, the chemical bonding is always present until the graphene layer is well formed, in which case the GGA neglects van der Waals dispersive forces. We investigate the electronic properties by studying the band structure and the density of states.

Crystallographic Studies of Two Bacterial AntibioticResistance Enzymes: Aminoglycoside Phosphotransferase (2')-Ic and GES-1\\beta-lactamase

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

Brynes, Laura; /Rensselaer Poly.

2007-10-31

Guiana Extended-Spectrum-1 (GES-1) and Aminoglycoside phosphotransferase (2')-Ic (APH(2')-Ic) are two bacteria-produced enzymes that essentially perform the same task: they provide resistance to an array of antibiotics. Both enzymes are part of a growing resistance problem in the medical world. In order to overcome the ever-growing arsenal of antibiotic-resistance enzymes, it is necessary to understand the molecular basis of their action. Accurate structures of these proteins have become an invaluable tool to do this. Using protein crystallography techniques and X-ray diffraction, the protein structure of GES-1 bound to imipenem (an inhibitor) has been solved. Also, APH(2')-Ic has been successfully crystallized, butmore » its structure was unable to be solved using molecular replacement using APH(2')-Ib as a search model. The structure of GES-1, with bound imipenem was solved to a resolution of 1.89A, and though the inhibitor is bound with only moderate occupancy, the structure shows crucial interactions inside the active site that render the enzyme unable to complete the hydrolysis of the {beta}-lactam ring. The APH(2')-Ic dataset could not be matched to the model, APH(2')-Ib, with which it shares 25% sequence identity. The structural information gained from GES-1, and future studies using isomorphous replacement to solve the APH(2')-Ic structure can aid directly to the creation of novel drugs to combat both of these classes of resistance enzymes.« less

Delithiated states of layered cathode materials: doping and dispersion interaction effects on the structure

NASA Astrophysics Data System (ADS)

Eremin, Roman; Zolotarev, Pavel; Bobrikov, Ivan

2018-04-01

Here we present results of density functional theory (DFT) study of delithiated structures of layered LiNiO2 (LNO, Li12Ni12O24 model) cathode material and its doped analogue LiNi0.833Co0.083Al0.083O2 (N10C1A1, Li12Ni10CoAlO24 model). The paper is aimed at independent elucidation of doping and dispersion interaction effects on the structural stability of cathode materials studied. For this purpose, the LNO and N10C1A1 configurational spaces consisting of 87 and 4512 crystallographically independent configurations (obtained starting from 2×2×1 supercell of R-3m structure of LNO) are optimized within a number of DFT models. Based on a comparison of the calculated dependencies for the lattice parameters with the results of in situ neutron diffraction experiments, the most pronounced effect of cathode material stabilization is due to the dispersion interaction. In turn, the doping effect is found to affect cathode structure behavior at the latest stages of delithiation only.

Structure of 1:1 complex of 1-naphthylmethyl ester of monensin A with sodium perchlorate studied by X-ray, FT-IR and ab initio methods

NASA Astrophysics Data System (ADS)

Huczyński, Adam; Janczak, Jan; Brzezinski, Bogumil

2012-12-01

A new crystalline complex formed between 1-naphthylmethyl ester of the naturally occurring antibiotic - monensin A (MON8) with sodium perchlorate has been obtained and studied using X-ray crystallography and FT-IR spectroscopy. The X-ray data of the complex show that MON8 forms a pseudo-cyclic structure stabilised by one weak intramolecular hydrogen bond and the sodium cation co-ordinated by two oxygen atoms of hydroxyl groups and four etheric oxygen atoms in the hydrophilic sphere. Within this structure the oxygen atoms of the ester groups are not involved in the coordination of sodium cation. In contrast to the solid state structure of the complex, in acetonitrile solution an equilibrium between two structures, in which the oxygen atom of the carbonyl ester group is either involved or not involved in the complexation of the sodium cation, is found. In acetonitrile this equilibrium is shifted towards the latter structure i.e. the structure existing in the solid state. The gas-phase structure of [MON8sbnd Na]+ cation as shown the ab initio MO calculations is comparable with the crystal one. Three-dimensional molecular electrostatic potential calculated for the neutral MON8 and [MON8sbnd Na]+ molecules is helpful for understanding the structural aspects of the sodium complex formation.

Multiferroic properties and structural features of M-type Al-substituted barium hexaferrites

NASA Astrophysics Data System (ADS)

Trukhanov, A. V.; Trukhanov, S. V.; Kostishin, V. G.; Panina, L. V.; Salem, M. M.; Kazakevich, I. S.; Turchenko, V. A.; Kochervinskii, V. V.; Krivchenya, D. A.

2017-04-01

Precise studies of the crystal and magnetic structures of M-type substituted barium hexaferrites BaFe12- x Al x O19 (0.1 ≤ x ≤ 1.2) have been performed by powder neutron diffraction in the temperature range 300-730 K. The electric polarization and the magnetization, and also the magnetoelectric effect of the compositions under study have been studied in electric (to 110 kV/m) and magnetic (to 14 T) fields at room temperature. The spontaneous polarization and significant correlation between the dielectric and magnetic subsystems have been observed at room temperature. The magnetoelectric effect value is, on average, about 5%, and it increases slightly with the aluminum cation concentration. The precise structural studies made it possible to reveal the cause and the mechanism of formation of the spontaneous polarization in M-type substituted barium hexaferrites BaFe12- x Al x O19 ( x ≤ 1.2) with a collinear ferromagnetic structure.

Discovery of novel Trypanosoma brucei phosphodiesterase B1 inhibitors by virtual screening against the unliganded TbrPDEB1 crystal structure

PubMed Central

Jansen, Chimed; Wang, Huanchen; Kooistra, Albert J.; de Graaf, Chris; Orrling, Kristina; Tenor, Hermann; Seebeck, Thomas; Bailey, David; de Esch, Iwan J.P.; Ke, Hengming; Leurs, Rob

2013-01-01

Trypanosoma brucei cyclic nucleotide phosphodiesterase B1 (TbrPDEB1) and TbrPDEB2 have recently been validated as new therapeutic targets for human African Trypanosomiasis by both genetic and pharmacological means. In this study we report the crystal structure of the catalytic domain of the unliganded TbrPDEB1 and its use for the in silico screening for new TbrPDEB1 inhibitors with novel scaffolds. The TbrPDEB1 crystal structure shows the characteristic folds of human PDE enzymes, but also contains the parasite-specific P-pocket found in the structures of Leishmania major PDEB1 and Trypanosoma cruzi PDEC. The unliganded TbrPDEB1 X-ray structure was subjected to a structure-based in silico screening approach that combines molecular docking simulations with a protein-ligand interaction fingerprint (IFP) scoring method. This approach identified, six novel TbrPDEB1 inhibitors with IC50 values of 10–80 μM, which may be further optimized as potential selective TbrPDEB inhibitors. PMID:23409953

Gene-Transformation-Induced Changes in Chemical Functional Group Features and Molecular Structure Conformation in Alfalfa Plants Co-Expressing Lc-bHLH and C1-MYB Transcriptive Flavanoid Regulatory Genes: Effects of Single-Gene and Two-Gene Insertion.

PubMed

Heendeniya, Ravindra G; Yu, Peiqiang

2017-03-20

Alfalfa ( Medicago sativa L.) genotypes transformed with Lc-bHLH and Lc transcription genes were developed with the intention of stimulating proanthocyanidin synthesis in the aerial parts of the plant. To our knowledge, there are no studies on the effect of single-gene and two-gene transformation on chemical functional groups and molecular structure changes in these plants. The objective of this study was to use advanced molecular spectroscopy with multivariate chemometrics to determine chemical functional group intensity and molecular structure changes in alfalfa plants when co-expressing Lc-bHLH and C1-MYB transcriptive flavanoid regulatory genes in comparison with non-transgenic (NT) and AC Grazeland (ACGL) genotypes. The results showed that compared to NT genotype, the presence of double genes ( Lc and C1 ) increased ratios of both the area and peak height of protein structural Amide I/II and the height ratio of α-helix to β-sheet. In carbohydrate-related spectral analysis, the double gene-transformed alfalfa genotypes exhibited lower peak heights at 1370, 1240, 1153, and 1020 cm -1 compared to the NT genotype. Furthermore, the effect of double gene transformation on carbohydrate molecular structure was clearly revealed in the principal component analysis of the spectra. In conclusion, single or double transformation of Lc and C1 genes resulted in changing functional groups and molecular structure related to proteins and carbohydrates compared to the NT alfalfa genotype. The current study provided molecular structural information on the transgenic alfalfa plants and provided an insight into the impact of transgenes on protein and carbohydrate properties and their molecular structure's changes.

Low temperature structural transformation in T[Ni(CN){sub 4}].xpyz with x=1,2; T=Mn,Co,Ni,Zn,Cd; pyz=pyrazine

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

Rodriguez-Hernandez, J.; Instituto de Ciencia y Tecnologia de Materiales, Universidad de La Habana; Lemus-Santana, A.A.

2010-01-15

The materials under study are pillared solids T[Ni(CN){sub 4}].xpyz with one and two (x=1,2) pyrazine (pyz) molecules and where T=Mn, Co, Ni, Zn, Cd. Stimulated by their structural features and potential role as prototype of porous solids for hydrogen storage, the structural stability under cryogenic conditions for this series of pillared solids was studied. At low temperature, in the 100-200 K range, the occurrence of a reversible structural transformation was found. For T=Mn, Co, Zn, Cd, with x=2, the structural transformation was observed to occur around 185 K, and the low temperature phase crystallizes with a monoclinic unit cell (spacemore » group Pc). This structure change results from certain charge redistribution on cooling within the involved ligands. For T=Ni with x=1, both the low and high temperature phases crystallize with unit cells of tetragonal symmetry, within the same space group but with a different unit cell volume. In this case the structure change is observed around 120 K. Above that temperature the rotational states for the pyrazine molecule are thermally excited and all the pyrazine molecules in the structure become equivalent. Under this condition the material structure is described using a smaller structural unit. The structural study using X-ray powder diffraction data was complemented with calorimetric and Raman spectroscopy measurements. For the low temperature phases the crystal structures were solved from Patterson methods and then refined using the Rietveld method. - Graphical abstract: Low temperature ordered structure for pyrazine in T[Ni(CN){sub 4}].pyz.« less

Structural investigation of the capsular polysaccharide produced by a novel Klebsiella serotype (SK1). Location of O-acetyl substituents using NMR and MS techniques.

PubMed

Cescutti, P; Ravenscroft, N; Ng, S; Lam, Z; Dutton, G G

1993-06-21

The capsular polysaccharide of Klebsiella SK1 was investigated by methylation analysis, Smith degradation, and 1H NMR spectroscopy. The oligosaccharides (P1 and P2) obtained by bacteriophage phi SK1 degradation of the polymer were studied by methylation analysis, and 1D- and 2D-NMR spectroscopy. The resulting data showed that the parent repeating unit is a branched pentasaccharide having a structure identical to the revised structure recently proposed for Klebsiella serotype K8 capsular polysaccharide. [Formula: see text] The 2D-NMR data showed that one third of the glucuronic acid residues in the SK1 polymer are acetylated at O-2, O-3, or O-4. FABMS studies confirmed the presence of monoacetylated glucuronic acid residues. Thus, the relationship between the Klebsiella K8 and SK1 polymers is akin to that found for Klebsiella polysaccharides K30 and K33, which have been typed as serologically distinct yet their structures differ only in the degree of acetylation.

Crystal structures of ryanodine receptor SPRY1 and tandem-repeat domains reveal a critical FKBP12 binding determinant

NASA Astrophysics Data System (ADS)

Yuchi, Zhiguang; Yuen, Siobhan M. Wong King; Lau, Kelvin; Underhill, Ainsley Q.; Cornea, Razvan L.; Fessenden, James D.; van Petegem, Filip

2015-08-01

Ryanodine receptors (RyRs) form calcium release channels located in the membranes of the sarcoplasmic and endoplasmic reticulum. RyRs play a major role in excitation-contraction coupling and other Ca2+-dependent signalling events, and consist of several globular domains that together form a large assembly. Here we describe the crystal structures of the SPRY1 and tandem-repeat domains at 1.2-1.5 Å resolution, which reveal several structural elements not detected in recent cryo-EM reconstructions of RyRs. The cryo-EM studies disagree on the position of SPRY domains, which had been proposed based on homology modelling. Computational docking of the crystal structures, combined with FRET studies, show that the SPRY1 domain is located next to FK506-binding protein (FKBP). Molecular dynamics flexible fitting and mutagenesis experiments suggest a hydrophobic cluster within SPRY1 that is crucial for FKBP binding. A RyR1 disease mutation, N760D, appears to directly impact FKBP binding through interfering with SPRY1 folding.

Equilibrium geometries, electronic and magnetic properties of small AunNi- (n = 1-9) clusters

NASA Astrophysics Data System (ADS)

Tang, Cui-Ming; Chen, Xiao-Xu; Yang, Xiang-Dong

2014-05-01

Geometrical, electronic and magnetic properties of small AunNi- (n = 1-9) clusters have been investigated based on density functional theory (DFT) at PW91P86 level. An extensive structural search shows that the relative stable structures of AunNi- (n = 1-9) clusters adopt 2D structure for n = 1-5, 7 and 3D structure for n = 6, 8-9. And the substitution of a Ni atom for an Au atom in the Au-n+1 cluster obviously changes the structure of the host cluster. Moreover, an odd-even alternation phenomenon has been found for HOMO-LUMO energy gaps, indicating that the relative stable structures of the AunNi- clusters with odd-numbered gold atoms have a higher relative stability. Finally, the natural population analysis (NPA) and the vertical detachment energies (VDE) are studied, respectively. The theoretical values of VDE are reported for the first time to our best knowledge.

Structure-activity relationship studies of the lipophilic tail region of sphingosine kinase 2 inhibitors.

PubMed

Congdon, Molly D; Childress, Elizabeth S; Patwardhan, Neeraj N; Gumkowski, James; Morris, Emily A; Kharel, Yugesh; Lynch, Kevin R; Santos, Webster L

2015-11-01

Sphingosine-1-phosphate (S1P) is a ubiquitous, endogenous small molecule that is synthesized by two isoforms of sphingosine kinase (SphK1 and 2). Intervention of the S1P signaling pathway has attracted significant attention because alteration of S1P levels is linked to several disease states including cancer, fibrosis, and sickle cell disease. While intense investigations have focused on developing SphK1 inhibitors, only a limited number of SphK2-selective agents have been reported. Herein, we report our investigations on the structure-activity relationship studies of the lipophilic tail region of SLR080811, a SphK2-selective inhibitor. Our studies demonstrate that the internal phenyl ring is a key structural feature that is essential in the SLR080811 scaffold. Further, we show the dependence of SphK2 activity and selectivity on alkyl tail length, suggesting a larger lipid binding pocket in SphK2 compared to SphK1. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Validation of a Japanese version of the Experience in Close Relationship- Relationship Structure].

PubMed

Komura, Kentaro; Murakami, Tatsuya; Toda, Koji

2016-08-01

The purpose of this study was to translate the Experience of Close Relationship-Relationship Structure (ECRRS) and evaluate its validity. In study 1 (N = 982), evidence based internal structure (factor structure, internal consistency, and correlation among sub-scales) and evidence based relations to other variables (depression, reassurance seeking and self-esteem) were confirmed. In study 2 (N = 563), evidence based on internal structure was reconfirmed, and evidence based relations to other variables (IWMS, RQ, and ECR-GO) were confirmed. In study 3 (N = 342), evidence based internal structure (test-retest reliability) was confirmed. Based on these results, we concluded that ECR-RS was valid for measuring adult attachment style.

Differential Interaction of Antimicrobial Peptides with Lipid Structures Studied by Coarse-Grained Molecular Dynamics Simulations.

PubMed

Balatti, Galo E; Ambroggio, Ernesto E; Fidelio, Gerardo D; Martini, M Florencia; Pickholz, Mónica

2017-10-20

In this work; we investigated the differential interaction of amphiphilic antimicrobial peptides with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid structures by means of extensive molecular dynamics simulations. By using a coarse-grained (CG) model within the MARTINI force field; we simulated the peptide-lipid system from three different initial configurations: (a) peptides in water in the presence of a pre-equilibrated lipid bilayer; (b) peptides inside the hydrophobic core of the membrane; and (c) random configurations that allow self-assembled molecular structures. This last approach allowed us to sample the structural space of the systems and consider cooperative effects. The peptides used in our simulations are aurein 1.2 and maculatin 1.1; two well-known antimicrobial peptides from the Australian tree frogs; and molecules that present different membrane-perturbing behaviors. Our results showed differential behaviors for each type of peptide seen in a different organization that could guide a molecular interpretation of the experimental data. While both peptides are capable of forming membrane aggregates; the aurein 1.2 ones have a pore-like structure and exhibit a higher level of organization than those conformed by maculatin 1.1. Furthermore; maculatin 1.1 has a strong tendency to form clusters and induce curvature at low peptide-lipid ratios. The exploration of the possible lipid-peptide structures; as the one carried out here; could be a good tool for recognizing specific configurations that should be further studied with more sophisticated methodologies.

Structure of indazole N1-oxide derivatives studied by X-ray, theoretical methods, 1H, 13C, 15N NMR and EI/MS

NASA Astrophysics Data System (ADS)

Gerpe, Alejandra; Piro, Oscar E.; Cerecetto, Hugo; González, Mercedes

2007-12-01

A series of indazole N1-oxide derivatives has been spectroscopically studied in solution using 1H, 13C, and 15N NMR based on pulsed field gradient selected PFG 1H sbnd X (X = 13C and 15N) gHMQC and gHMBC experiments. Some indazoles were prepared using a new methodology to compare its spectral and structural data with the indazole N1-oxide parent compounds. The 13C resonances of the indazole N1-oxide carbon 3 and 7a demonstrate the N-oxide push-electron capability. The 15N resonances of the indazole N-oxide, nitrogen 1, are near to 30 ppm more shielded than the corresponding values in the indazole heterocycle (deoxygenated form). Moreover, the structures of one indazole and one indazole N-oxide were unambiguously confirmed by X-ray crystallography. The solid state structures were contrasted with the theoretical ones obtained in vacuo at different calculus level. The aromaticity of the derivatives was studied analyzing the H sbnd H coupling constants of indazole's aromatic hydrogens and measuring C sbnd C distances in the solid state. The fragmentation that takes place in EI/MS was gathered for all the indazole N-oxide derivatives and the general fragmentation pattern analyzed.

Crystal structure and theoretical studies of derivative of imidazo-1,2,4-triazine

NASA Astrophysics Data System (ADS)

Dybała, Izabela; Sztanke, Krzysztof

2016-09-01

In this study, we present the result of X-ray structure analysis of methyl [8-(3-chlorophenyl)-4-oxo-2,3,4,6,7,8-heksahydroimidazo[2,1-c][1,2,4]triazin-3-yl]acetate (1). The molecule conformation is flat, with a chlorophenyl substituent and the ester moiety lying in the plain of the heterobicyclic scaffold. Its conformation is stabilized by an intramolecular Nsbnd H…O hydrogen bond. Within the crystalline structure of 1, molecules associate with one another by weak Csbnd H…O, Csbnd H…Cl and Csbnd H…π bonds. The molecular and crystal structure of 1 was compared with the previously described structurally similar compound possessing the same bicyclic rigid core and similar chemical nature of the functional ester moiety. Very interesting differences in molecules geometry and association were observed. Non-covalent bonds within the crystals are additionally visualized by determination of Hirshfeld surfaces. Moreover, the quantum chemical calculation for 1 in the gas phase were carried out. The DFT calculation methods was used to optimize of molecule geometry and obtain molecular energy profiles with respect to selected torsion angles. The quantum chemical conformational analysis that was carried out for compound 1 in the gas phase suggests that in the solid state the molecules adopt the minimum energy conformation.

Structure-activity analysis and biological studies of chensinin-1b analogues.

PubMed

Dong, Weibing; Dong, Zhe; Mao, Xiaoman; Sun, Yue; Li, Fei; Shang, Dejing

2016-06-01

Chensinin-1b shows a potent and broad-spectrum bactericidal activity and no hemolytic activity and thus is a potential therapeutic agent against bacterial infection. The NMR structure of chensinin-1b consists of a partially α-helical region (residues 8-14) in a membrane-mimic environment that is distinct from other common antimicrobial peptides. However, further analysis of the structural features of chensinin-1b is required to better understand its bactericidal activity. In this study, a series of N- and C-terminally truncated or amino acid-substituted chensinin-1b analogues were synthesized. Next, the bactericidal activity and bacterial membrane effects of the analogues were investigated. The results indicated that the N-terminal residues play a more significant role than the C-terminal residues in the antimicrobial activity of chensinin-1b. The removal of five amino acids from the C-terminus of chensinin-1b did not affect its biological properties, but helix disruption significantly decreased bactericidal activity. The substitution of positively charged residues increased the helicity and antimicrobial activity of the peptide. We also identified a novel analogue [R(4),R(10)]C1b(3-13) that exhibited similar bactericidal properties with its parent peptide chensinin-1b. Electrostatic interactions between the selected analogues and lipopolysaccharides or cells were detected using isothermal titration calorimetry or zeta potential. The thermodynamic parameters ΔH and ΔS for [R(4),R(10)]C1b(3-13) were -20.48kcalmol(-1) and -0.0408kcalmol(-1)deg(-1), respectively. Chensinin-1b yielded similar results of -26.36kcalmol(-1) and -0.0559kcalmol(-1)deg(-1) for ΔH and ΔS, respectively. These results are consistence with their antimicrobial activities. Lastly, membrane depolarization studies showed that selected analogues exerted bactericidal activity by damaging the cytoplasmic membrane. Antimicrobial peptide chensinin-1b is a candidate for the development of new drugs and a template for the design of synthetic analogues. It mainly exhibits a random coil conformation in membrane environment, and in this manuscript, we characterized the structure of chensinin-1b using NMR spectroscopy, its structure is different than the structures of magainin 2, which has an α-helical conformation and indolicidin, which has a random coil structure. The structural features of chensinin-1b that are required for its potent bactericidal activity were also elucidated. Based on these data, we can fully understand the structure-activity relationship of such peptide and identified a novel analogue with properties that make it an attractive topic for future therapeutic research. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A DE-1/whistler study of the thermal plasma structure and dynamics in the dusk bulge sector of the magnetosphere

NASA Technical Reports Server (NTRS)

Carpenter, D. L.

1992-01-01

The objective of this research was to obtain new understanding of the thermal plasma structure and dynamics of the plasmasphere bulge region of the magnetosphere, with special emphasis on the erosion process that results in a reduction in plasmasphere size and on the manner in which erosion leads to the presence of patches of dense plasma in the middle and outer afternoon-dusk magnetosphere. Case studies involving data from the DE 1, GEOS 2, and ISEE 1 satellites and from ground whistler stations Siple, Halley, and Kerguelen were used. A copy of the published paper entitled 'A case study of plasma structure in the dusk sector associated with enhanced magnetospheric convection,' is included.

The Vibrio cholerae Colonization Factor GbpA Possesses a Modular Structure that Governs Binding to Different Host Surfaces

PubMed Central

Wong, Edmond; Vaaje-Kolstad, Gustav; Ghosh, Avishek; Hurtado-Guerrero, Ramon; Konarev, Peter V.; Ibrahim, Adel F. M.; Svergun, Dmitri I.; Eijsink, Vincent G. H.; Chatterjee, Nabendu S.; van Aalten, Daan M. F.

2012-01-01

Vibrio cholerae is a bacterial pathogen that colonizes the chitinous exoskeleton of zooplankton as well as the human gastrointestinal tract. Colonization of these different niches involves an N-acetylglucosamine binding protein (GbpA) that has been reported to mediate bacterial attachment to both marine chitin and mammalian intestinal mucin through an unknown molecular mechanism. We report structural studies that reveal that GbpA possesses an unusual, elongated, four-domain structure, with domains 1 and 4 showing structural homology to chitin binding domains. A glycan screen revealed that GbpA binds to GlcNAc oligosaccharides. Structure-guided GbpA truncation mutants show that domains 1 and 4 of GbpA interact with chitin in vitro, whereas in vivo complementation studies reveal that domain 1 is also crucial for mucin binding and intestinal colonization. Bacterial binding studies show that domains 2 and 3 bind to the V. cholerae surface. Finally, mouse virulence assays show that only the first three domains of GbpA are required for colonization. These results explain how GbpA provides structural/functional modular interactions between V. cholerae, intestinal epithelium and chitinous exoskeletons. PMID:22253590

Structural and Thermodynamic Properties of Amyloid-β Peptides: Impact of Fragment Size

NASA Astrophysics Data System (ADS)

Kitahara, T.; Wise-Scira, O.; Coskuner, O.

2010-10-01

Alzheimer's disease is a progressive neurodegenerative disease whose physiological characteristics include the accumulation of amyloid-containing deposits in the brain and consequent synapse and neuron loss. Unfortunately, most widely used drugs for the treatment can palliate the outer symptoms but cannot cure the disease itself. Hence, developing a new drug that can cure it. Most recently, the ``early aggregation and monomer'' hypothesis has become popular and a few drugs have been developed based on this hypothesis. Detailed understanding of the amyloid-β peptide structure can better help us to determine more effective treatment strategies; indeed, the structure of Amyloid has been studied extensively employing experimental and theoretical tools. Nevertheless, those studies have employed different fragment sizes of Amyloid and characterized its conformational nature in different media. Thus, the structural properties might be different from each other and provide a reason for the existing debates in the literature. Here, we performed all-atom MD simulations and present the structural and thermodynamic properties of Aβ1-16, Aβ1-28, and Aβ1-42 in the gas phase and in aqueous solution. Our studies show that the overall structures, secondary structures, and the calculated thermodynamic properties change with increasing peptide size. In addition, we find that the structural properties of those peptides are different from each other in the gas phase and in aqueous solution.

Mechanical design of the first proximal Ig domain of human cardiac titin revealed by single molecule force spectroscopy.

PubMed

Li, Hongbin; Fernandez, Julio M

2003-11-14

The elastic I-band part of muscle protein titin contains two tandem immunoglobulin (Ig) domain regions of distinct mechanical properties. Until recently, the only known structure was that of the I27 module of the distal region, whose mechanical properties have been reported in detail. Recently, the structure of the first proximal domain, I1, has been resolved at 2.1A. In addition to the characteristic beta-sandwich structure of all titin Ig domains, the crystal structure of I1 showed an internal disulfide bridge that was proposed to modulate its mechanical extensibility in vivo. Here, we use single molecule force spectroscopy and protein engineering to examine the mechanical architecture of this domain. In contrast to the predictions made from the X-ray crystal structure, we find that the formation of a disulfide bridge in I1 is a relatively rare event in solution, even under oxidative conditions. Furthermore, our studies of the mechanical stability of I1 modules engineered with point mutations reveal significant differences between the mechanical unfolding of the I1 and I27 modules. Our study illustrates the varying mechanical architectures of the titin Ig modules.

Synthesis, spectroscopic characterizations, crystal structures and DFT studies of nalidixic acid carbonyl hydrazones derivatives

NASA Astrophysics Data System (ADS)

Bergamini, F. R. G.; Ribeiro, M. A.; Lancellotti, M.; Machado, D.; Miranda, P. C. M. L.; Cuin, A.; Formiga, A. L. B.; Corbi, P. P.

2016-09-01

This article describes the synthesis and characterization of the 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbohydrazide (hzd) and six carbonyl hydrazones derivatives of the nalidixic with 1H-pyrrol-2-ylmethylidene (hpyrr), 1H-imidazol-2-ylmethylidene (h2imi), pyridin-2-ylmethylidene (h2py), pyridin-3-ylmethylidene (h3py), pyridin-4-ylmethylidene(h4py) and (2-hydroxyphenyl)methylidene (hsali). The carbonyl hydrazones were characterized by elemental and ESI-QTOF-MS analyses, IR and detailed NMR spectroscopic measurements. The 2D NMR experiments allowed the unambiguous assignment of the hydrogen, carbon and nitrogen atoms, which have not been reported for nalidixic acid carbonyl hydrazone derivatives so far. Crystal structures of hzd and the new carbonyl hydrazones h2imi, hpyrr and h3py were determined by X-ray diffraction studies. Although the synthesis of hzd was reported decades ago, the hzd crystal structure have not been reported yet. Geometric optimizations of all the characterized structures were performed with the aid of DFT studies. Despite the fact that the hydrazones with 2-pyridine carboxylic acid (h2py) and salicyl aldehyde (hsali) were already reported by literature, a detailed spectroscopic study followed by DFT studies are also reported for such compounds in this manuscript. Antimicrobial studies of the compounds are also presented.

Structural and functional insights into the role of the N-terminal Mps1 TPR domain in the SAC (spindle assembly checkpoint).

PubMed

Thebault, Philippe; Chirgadze, Dimitri Y; Dou, Zhen; Blundell, Tom L; Elowe, Sabine; Bolanos-Garcia, Victor M

2012-12-15

The SAC (spindle assembly checkpoint) is a surveillance system that ensures the timely and accurate transmission of the genetic material to offspring. The process implies kinetochore targeting of the mitotic kinases Bub1 (budding uninhibited by benzamidine 1), BubR1 (Bub1 related) and Mps1 (monopolar spindle 1), which is mediated by the N-terminus of each kinase. In the present study we report the 1.8 Å (1 Å=0.1 nm) crystal structure of the TPR (tetratricopeptide repeat) domain in the N-terminal region of human Mps1. The structure reveals an overall high similarity to the TPR motif of the mitotic checkpoint kinases Bub1 and BubR1, and a number of unique features that include the absence of the binding site for the kinetochore structural component KNL1 (kinetochore-null 1; blinkin), and determinants of dimerization. Moreover, we show that a stretch of amino acids at the very N-terminus of Mps1 is required for dimer formation, and that interfering with dimerization results in mislocalization and misregulation of kinase activity. The results of the present study provide an important insight into the molecular details of the mitotic functions of Mps1 including features that dictate substrate selectivity and kinetochore docking.

Characterization of the Microchemical Structure of Seed Endosperm within a Cellular Dimension among Six Barley Varieties with Distinct Degradation Kinetics, Using Ultraspatially Resolved Synchrotron-Based Infrared Synchrotron-Based Infrared

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

Liu, N.; Yu, P

2010-01-01

Barley varieties have similar chemical composition but exhibit different rumen degradation kinetics and nutrient availability. These biological differences may be related to molecular, structural, and chemical makeup among the seed endosperm tissue. No detailed study was carried out. The objectives of this study were: (1) to use a molecular spectroscopy technique, synchrotron-based Fourier transform infrared microspectroscopy (SFTIRM), to determine the microchemical-structural features in seed endosperm tissue of six developed barley varieties; (2) to study the relationship among molecular-structural characteristics, degradation kinetics, and nutrient availability in six genotypes of barley. The results showed that inherent microchemical-structural differences in the endosperm amongmore » the six barley varieties were detected by the synchrotron-based analytical technique, SFTIRM, with the univariate molecular spectral analysis. The SFTIRM spectral profiles differed (P < 0.05) among the barley samples in terms of the peak ratio and peak area and height intensities of amides I (ca. 1650 cm{sup -1}) and II (ca. 1550 cm{sup -1}), cellulosic compounds (ca. 1240 cm{sup -1}), CHO component peaks (the first peak at the region ca. 1184-1132 cm{sup -1}, the second peak at ca. 1132-1066 cm{sup -1}, and the third peak at ca. 1066-950 cm{sup -1}). With the SFTIRM technique, the structural characteristics of the cereal seeds were illuminated among different cultivars at an ultraspatial resolution. The structural differences of barley seeds may be one reason for the various digestive behaviors and nutritive values in ruminants. The results show weak correlations between the functional groups spectral data (peak area, height intensities, and ratios) and rumen biodegradation kinetics (rate and extent of nutrient degradation). Weak correlations may indicate that limited variations of these six barley varieties might not be sufficient to interpret the relationship between spectroscopic information and the nutrient value of barley grain, although significant differences in biodegradation kinetics were observed. In conclusion, the studies demonstrated the potential of ultraspatially resolved synchrotron based technology (SFTIRM) to reveal the structural and chemical makeup within cellular and subcellular dimensions without destruction of the inherent structure of cereal grain tissue.« less

NMR Spectroscopy and Molecular Dynamics Simulation of r(CCGCUGCGG)2 Reveal a Dynamic UU Internal Loop Found in Myotonic Dystrophy Type 1†

PubMed Central

Parkesh, Raman; Fountain, Matthew; Disney, Matthew D.

2011-01-01

The NMR structure of an RNA with a copy of the 5′CUG/3′GUC motif found in the triplet repeating disorder myotonic dystrophy type 1 (DM1) is disclosed. The lowest energy conformation of the UU pair is a single hydrogen bonded structure; however, the UU protons undergo exchange indicating structural dynamics. Molecular dynamics simulations show that the single hydrogen bonded structure is the most populated one but the UU pair interconverts between 0, 1, and 2 hydrogen bonded pairs. These studies have implications for the recognition of the DM1 RNA by small molecules and proteins. PMID:21204525

Aziridinyl-substituted benzo-1,4-quinones: A preliminary investigation on the theoretical and experimental studies of their structure and spectroscopic properties

NASA Astrophysics Data System (ADS)

Šarlauskas, Jonas; Tamulienė, Jelena; Čėnas, Narimantas

2017-05-01

The detailed structure, chemical and spectroscopic properties of the derivatives of the selected 2,5-bis(1-aziridinyl)-benzo-1,4-quinone conformers were studied by applying quantum chemical and experimental methods. The relationship between the structure and chemical activity of the selected 3 bifunctional bioreductive quinonic anticancer agents - aziridinyl benzoquinones (AzBQ compounds) was obtained. The results obtained showed that the position of aziridine rings influenced by the chemical activity of the investigated compound were more significant than the substitutions of the benzene ring of the AzBQ compounds. The solvents influencing this activity were obtained, too.

Transmission electron diffraction determination of the Ge(001)-(2 × 1) surface structure

NASA Astrophysics Data System (ADS)

Collazo-Davila, C.; Grozea, D.; Landree, E.; Marks, L. D.

1997-04-01

The lateral displacements in the Ge(001)-(2 × 1) surface reconstruction have been determined using transmission electron diffraction (TED). The best-fit model includes displacements extending six layers into the bulk. The atomic positions found agree with X-ray studies to within a few hundredths of an ångström. With the positions determined so precisely, it is suggested that the Ge(001)-(2 × 1) surface can now serve as a standard for comparison with theoretical surface structure calculations. The results from the currently available theoretical studies on the surface are compared with the experimentally determined structure.

Glomerular structural-functional relationship models of diabetic nephropathy are robust in type 1 diabetic patients.

PubMed

Mauer, Michael; Caramori, Maria Luiza; Fioretto, Paola; Najafian, Behzad

2015-06-01

Studies of structural-functional relationships have improved understanding of the natural history of diabetic nephropathy (DN). However, in order to consider structural end points for clinical trials, the robustness of the resultant models needs to be verified. This study examined whether structural-functional relationship models derived from a large cohort of type 1 diabetic (T1D) patients with a wide range of renal function are robust. The predictability of models derived from multiple regression analysis and piecewise linear regression analysis was also compared. T1D patients (n = 161) with research renal biopsies were divided into two equal groups matched for albumin excretion rate (AER). Models to explain AER and glomerular filtration rate (GFR) by classical DN lesions in one group (T1D-model, or T1D-M) were applied to the other group (T1D-test, or T1D-T) and regression analyses were performed. T1D-M-derived models explained 70 and 63% of AER variance and 32 and 21% of GFR variance in T1D-M and T1D-T, respectively, supporting the substantial robustness of the models. Piecewise linear regression analyses substantially improved predictability of the models with 83% of AER variance and 66% of GFR variance explained by classical DN glomerular lesions alone. These studies demonstrate that DN structural-functional relationship models are robust, and if appropriate models are used, glomerular lesions alone explain a major proportion of AER and GFR variance in T1D patients. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Rational design, synthesis, biologic evaluation, and structure-activity relationship studies of novel 1-indanone alpha(1)-adrenoceptor antagonists.

PubMed

Li, Minyong; Xia, Lin

2007-11-01

In the present report, a novel series of 1-indanone alpha(1)-adrenoceptor antagonists were designed and synthesized based on 3D-pharmacophore model. Their in vitro alpha(1)-adrenoceptor antagonistic assay showed that three compounds (2a, 2m, and 2o) had similar or improved alpha(1)-adrenoceptor antagonistic activities relative to the positive control prazosin. Based on these results, a three-dimensional quantitative structure-activity relationship study was performed using a Self-Organizing Molecular Field Analysis method to provide insight for the future development of alpha(1)-adrenoceptor antagonists.

Exploring the Structure of Adaptive Behavior: Project Report Number 87-1.

ERIC Educational Resources Information Center

Bruininks, Robert H.; McGrew, Kevin

This report presents results from three research studies that were designed to explore both the definition and the structure of the adaptive behavior construct. The first study investigated the structure of adaptive behavior as a function of age, developmental level, and type of handicap through an exploratory factor analysis of both the…

Theoretical Study of the Structure, Stability and Oxygen Reduction Activity of Ultrathin Platinum Nanowires

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

Matanovic, Ivana; Kent, Paul; Garzon, Fernando

2012-10-10

We use density functional theory to study the difference in the structure, stability and catalytic reactivity between ultrathin, 0.5- 1.0 nm diameter, platinum nanotubes and nanowires. Model nanowires were formed by inserting an inner chain of platinum atoms in small diameter nanotubes. In this way more stable, nonhollow structures were formed. The difference in the electronic structure of platinum nanotubes and nanowires was examined by inspecting the density of surface states and band structure. Furthermore, reactivity towards the oxygen reduction reaction of platinum nanowires was addressed by studying the change in the chemisorption energies of oxygen and hydroxyl groups, inducedmore » by inserting the inner chain of platinum atoms into the hollow nanotubes. Both ultrathin platinum nanotubes and nanowires show distinct properties compared to bulk platinum. Nanotubes with diameters larger than 1 nm show promise for use as oxygen reduction catalysts.« less

Density Functional Study of the Structure, Stability and Oxygen Reduction Activity of Ultrathin Platinum Nanowires

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

Matanovic, Ivana; Kent, Paul; Garzon, Fernando

2013-03-14

We used density functional theory to study the difference in the structure, stability and catalytic reactivity between ultrathin, 0.5–1.0 nm diameter, platinum nanotubes and nanowires. Model nanowires were formed by inserting an inner chain of platinum atoms in small diameter nanotubes. In this way more stable, non-hollow structures were formed. The difference in the electronic structure of platinum nanotubes and nanowires was examined by inspecting the density of surface states and band structure. Furthermore, reactivity toward the oxygen reduction reaction of platinum nanowires was assessed by studying the change in the chemisorption energies of oxygen, hydroxyl, and hydroperoxyl groups, inducedmore » by converting the nanotube models to nanowires. Both ultrathin platinum nanotubes and nanowires show distinct properties compared to bulk platinum. Single-wall nanotubes and platinum nanowires with diameters larger than 1 nm show promise for use as oxygen reduction catalysts.« less

V/STOL tilt-rotor study, task 1. Volume 1: Conceptual design

NASA Technical Reports Server (NTRS)

1972-01-01

A conceptual design study was conducted to define a representative military and/or commercial tilt-propeller aircraft for short takeoff and landing operation. The level of structural technology selected for the operational aircraft was based on aluminum, steel, titanium, and adhesive bonded structures. The data describe the following: (1) aircraft weight, (2) performance and stability, (3) aerodynamic noise, (4) dynamic characteristics, (5) maintainability and reliability, and (6) operating economics.

Endophilin-A1 BAR domain interaction with arachidonyl CoA.

PubMed

Petoukhov, Maxim V; Weissenhorn, Winfried; Svergun, Dmitri I

2014-01-01

Endophilin-A1 belongs to the family of BAR domain containing proteins that catalyze membrane remodeling processes via sensing, inducing and stabilizing membrane curvature. We show that the BAR domain of endophilin-A1 binds arachidonic acid and molds its coenzyme A (CoA) activated form, arachidonyl-CoA into a defined structure. We studied low resolution structures of endophilin-A1-BAR and its complex with arachidonyl-CoA in solution using synchrotron small-angle X-ray scattering (SAXS). The free endophilin-A1-BAR domain is shown to be dimeric at lower concentrations but builds tetramers and higher order complexes with increasing concentrations. Extensive titration SAXS studies revealed that the BAR domain produces a homogenous complex with the lipid micelles. The structural model of the complexes revealed two arachidonyl-CoA micelles bound to the distal arms of an endophilin-A1-BAR dimer. Intriguingly, the radius of the bound micelles significantly decreases compared to that of the free micelles, and this structural result may provide hints on the potential biological relevance of the endophilin-A1-BAR interaction with arachidonyl CoA.

Average and local crystal structures of (Ga 1–xZn x)(N 1–xO x) solid solution nanoparticles

DOE PAGES

Feygenson, Mikhail; Neuefeind, Joerg C.; Tyson, Trevor A.; ...

2015-11-06

We report the comprehensive study of the crystal structure of (Ga 1–xZn x)(N 1–xO x) solid solution nanoparticles by means of neutron and synchrotron x-ray scattering. In our study we used four different types of (Ga 1–xZn x)(N 1–xO x) nanoparticles, with diameters of 10–27 nm and x = 0.075–0.51, which show the narrow energy-band gaps from 2.21 to 2.61 eV. The Rietveld analysis of the neutron diffraction data revealed that the average crystal structure is the hexagonal wurtzite (space group P6 3mc), in agreement with previous reports on similar bulk materials. The pair-distribution function (PDF) analysis of the samemore » data found that the local structure is more disordered than the average one. It is best described by the model with a lower symmetry space group P1, where atoms are quasirandomly distorted from their nominal positions in the hexagonal wurtzite lattice.« less

Solvothermal syntheses, structures, and magnetic properties of three cobalt coordination polymers constructed from naphthalene-1,4-dicarboxylic acid and bis(imidazole) linkers

NASA Astrophysics Data System (ADS)

Dong, Jun-Liang; He, Kun-Huan; Wang, Duo-Zhi; Zhang, Ying-Hui; Wang, Dan-Hong

2018-07-01

Three new Co(II) coordination polymers with formulas of {[Co2(L1)(1,4-NDC)2]·3H2O}n (1), [Co3(L2)2(HCOO)2(1,4-NDC)2]n (2) and [Co2(L2)(μ3-OH)(1,4-NDC)1.5]n (3) (1,4-H2NDC = Naphthalene-1,4-dicarboxylic acid, L1 = di(1H-imidazol-1-yl)methane, L2 = 1,4-di(1H-imidazol-1-yl)benzene) were solvothermal synthesized from 1,4-H2NDC with the aid of three different length-controllable auxiliary ligands and fully characterized. Their structures are determined by single-crystal X-ray diffraction, IR spectra, elemental analysis, powder X-ray diffraction and thermogravimetric analysis. Complexes 1 and 3 display 3D framework structures, corresponding to a 6-connected (412·63) net, a 8-connected (424·5·63) net, respectively. However, it is noteworthy that the complex 1 displays a 2-fold interpenetrating framework structure, complex 3 possesses a self-interpenetrating framework structure. Complex 2 displays 2D 4-connected undulating plane net structure. Moreover, magnetic studies indicate antiferromagnetic interactions between the Co(II) ions in the four complexes.

The synthesis and structures of 1,1'-bis(sulfonyl)ferrocene derivatives.

PubMed

Chanawanno, Kullapa; Holstrom, Cole; Crandall, Laura A; Dodge, Henry; Nemykin, Victor N; Herrick, Richard S; Ziegler, Christopher J

2016-09-28

A series of 1,1'-bis(sulfonyl)ferrocene compounds were produced via the 1,1'-bis(sulfonate)ferrocene ammonium salt. This compound can be readily converted to 1,1' bis(sulfonylchloride)ferrocene. By varying stoichiometry and reaction times, both mono- and bis-sulfonamide derivatives can be synthesized. All new compounds presented in this report have been structurally characterized. The structures of the bis-sulfonamide systems are similar to the well-studied bis(amide) ferrocene compounds. Intermolecular hydrogen bonding is observed, typically between NH and SO groups of neighboring sulfonamides. However in the bis(GABA) derivative, intermolecular NH to CO hydrogen bonding interactions are present.

Photonic structures in diamond based on femtosecond UV laser induced periodic surface structuring (LIPSS).

PubMed

Granados, Eduardo; Martinez-Calderon, Miguel; Gomez, Mikel; Rodriguez, Ainara; Olaizola, Santiago M

2017-06-26

We study the fabrication of photonic surface structures in single crystal diamond by means of highly controllable direct femtosecond UV laser induced periodic surface structuring. By appropriately selecting the excitation wavelength, intensity, number of impinging pulses and their polarization state, we demonstrate emerging high quality and fidelity diamond grating structures with surface roughness below 1.4 nm. We characterize their optical properties and study their potential for the fabrication of photonic structure anti-reflection coatings for diamond Raman lasers in the near-IR.

Structural Basis of Wee Kinases Functionality and Inactivation by Diverse Small Molecule Inhibitors.

PubMed

Zhu, Jin-Yi; Cuellar, Rebecca A; Berndt, Norbert; Lee, Hee Eun; Olesen, Sanne H; Martin, Mathew P; Jensen, Jeffrey T; Georg, Gunda I; Schönbrunn, Ernst

2017-09-28

Members of the Wee family of kinases negatively regulate the cell cycle via phosphorylation of CDK1 and are considered potential drug targets. Herein, we investigated the structure-function relationship of human Wee1, Wee2, and Myt1 (PKMYT1). Purified recombinant full-length proteins and kinase domain constructs differed substantially in phosphorylation states and catalytic competency, suggesting complex mechanisms of activation. A series of crystal structures reveal unique features that distinguish Wee1 and Wee2 from Myt1 and establish the structural basis of differential inhibition by the widely used Wee1 inhibitor MK-1775. Kinome profiling and cellular studies demonstrate that, in addition to Wee1 and Wee2, MK-1775 is an equally potent inhibitor of the polo-like kinase PLK1. Several previously unrecognized inhibitors of Wee kinases were discovered and characterized. Combined, the data provide a comprehensive view on the catalytic and structural properties of Wee kinases and a framework for the rational design of novel inhibitors thereof.

Structural and functional characterization of a cell cycle associated HDAC1/2 complex reveals the structural basis for complex assembly and nucleosome targeting

PubMed Central

Itoh, Toshimasa; Fairall, Louise; Muskett, Frederick W.; Milano, Charles P.; Watson, Peter J.; Arnaudo, Nadia; Saleh, Almutasem; Millard, Christopher J.; El-Mezgueldi, Mohammed; Martino, Fabrizio; Schwabe, John W.R.

2015-01-01

Recent proteomic studies have identified a novel histone deacetylase complex that is upregulated during mitosis and is associated with cyclin A. This complex is conserved from nematodes to man and contains histone deacetylases 1 and 2, the MIDEAS corepressor protein and a protein called DNTTIP1 whose function was hitherto poorly understood. Here, we report the structures of two domains from DNTTIP1. The amino-terminal region forms a tight dimerization domain with a novel structural fold that interacts with and mediates assembly of the HDAC1:MIDEAS complex. The carboxy-terminal domain of DNTTIP1 has a structure related to the SKI/SNO/DAC domain, despite lacking obvious sequence homology. We show that this domain in DNTTIP1 mediates interaction with both DNA and nucleosomes. Thus, DNTTIP1 acts as a dimeric chromatin binding module in the HDAC1:MIDEAS corepressor complex. PMID:25653165

Effect of dissolved LiCl on the ionic liquid-Au(111) interface: an in situ STM study

NASA Astrophysics Data System (ADS)

Borisenko, Natalia; Atkin, Rob; Lahiri, Abhishek; Zein El Abedin, Sherif; Endres, Frank

2014-07-01

The structure of the electrolyte/electrode interface plays a significant role in electrochemical processes. To date, most studies are focusing on understanding the interfacial structure in pure ionic liquids. In this paper in situ scanning tunnelling microscopy (STM) has been employed to elucidate the structure of the charged Au(111)-ionic liquid (1-butyl-1-methylpyrrolidinium tris(pentafluoroethyl)trifluorophosphate, [Py1,4]FAP) interface in the presence of 0.1 M LiCl. The addition of the Li salt to the ionic liquid has a strong influence on the interfacial structure. In the first STM scan in situ measurements reveal that Au(111) undergoes the (22 \\times \\surd 3) ‘herringbone’ reconstruction in a certain potential regime, and there is strong evidence that the gold surface dissolves at negative electrode potentials in [Py1,4]FAP containing LiCl. Bulk deposition of Li is obtained at -2.9 V in the second STM scan.

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

Kennedy, R.P.; Kincaid, R.H.; Short, S.A.

This report presents the results of part of a two-task study on the engineering characterization of earthquake ground motion for nuclear power plant design. Task I of the study, which is presented in NUREG/CR-3805, Vol. 1, developed a basis for selecting design response spectra taking into account the characteristics of free-field ground motion found to be significant in causing structural damage. Task II incorporates additional considerations of effects of spatial variations of ground motions and soil-structure interaction on foundation motions and structural response. The results of Task II are presented in four parts: (1) effects of ground motion characteristics onmore » structural response of a typical PWR reactor building with localized nonlinearities and soil-structure interaction effects; (2) empirical data on spatial variations of earthquake ground motion; (3) soil-structure interaction effects on structural response; and (4) summary of conclusions and recommendations based on Tasks I and II studies. This report presents the results of the first part of Task II. The results of the other parts will be presented in NUREG/CR-3805, Vols. 3 to 5.« less

Identification and preliminary structure-activity relationships of 1-Indanone derivatives as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors.

PubMed

Gao, Dingding; Li, Yingxia

2017-07-15

Indoleamine 2,3-dioxygenase 1 (IDO1) plays a vital role in the catabolism of tryptophan along with the kynurenine pathway which is involved in many human diseases including cancer, Alzheimer's disease, etc. In this study, compound 1 bearing a 1-Indanone scaffold was identified as a novel IDO1 inhibitor by structure-based virtual screening, with moderate to good enzymatic and cellular inhibitory activities. Also, surface plasmon resonance analysis validated the direct interaction between compound 1 and IDO1 protein. The preliminary SAR was further explored and the binding mode with IDO1 protein was predicted by experiment along with molecular docking. Subsequent ADME properties of these active compounds were analyzed in silico, and the results showed good pharmacokinetic efficiencies. We believe this study contributes a lot to the structural diversity for the future development of highly potent IDO1 inhibitors. Copyright © 2017. Published by Elsevier Ltd.

Active large structures

NASA Technical Reports Server (NTRS)

Soosaar, K.

1982-01-01

Some performance requirements and development needs for the design of large space structures are described. Areas of study include: (1) dynamic response of large space structures; (2) structural control and systems integration; (3) attitude control; and (4) large optics and flexibility. Reference is made to a large space telescope.

Bioinformatics approaches for structural and functional analysis of proteins in secondary metabolism in Withania somnifera.

PubMed

Sanchita; Singh, Swati; Sharma, Ashok

2014-11-01

Withania somnifera (Ashwagandha) is an affluent storehouse of large number of pharmacologically active secondary metabolites known as withanolides. These secondary metabolites are produced by withanolide biosynthetic pathway. Very less information is available on structural and functional aspects of enzymes involved in withanolides biosynthetic pathways of Withiana somnifera. We therefore performed a bioinformatics analysis to look at functional and structural properties of these important enzymes. The pathway enzymes taken for this study were 3-Hydroxy-3-methylglutaryl coenzyme A reductase, 1-Deoxy-D-xylulose-5-phosphate synthase, 1-Deoxy-D-xylulose-5-phosphate reductase, farnesyl pyrophosphate synthase, squalene synthase, squalene epoxidase, and cycloartenol synthase. The prediction of secondary structure was performed for basic structural information. Three-dimensional structures for these enzymes were predicted. The physico-chemical properties such as pI, AI, GRAVY and instability index were also studied. The current information will provide a platform to know the structural attributes responsible for the function of these protein until experimental structures become available.

Crystal Structure of Streptococcus pyogenes Cas1 and Its Interaction with Csn2 in the Type II CRISPR-Cas System.

PubMed

Ka, Donghyun; Lee, Hasup; Jung, Yi-Deun; Kim, Kyunggon; Seok, Chaok; Suh, Nayoung; Bae, Euiyoung

2016-01-05

CRISPRs and Cas proteins constitute an RNA-guided microbial immune system against invading nucleic acids. Cas1 is a universal Cas protein found in all three types of CRISPR-Cas systems, and its role is implicated in new spacer acquisition during CRISPR-mediated adaptive immunity. Here, we report the crystal structure of Streptococcus pyogenes Cas1 (SpCas1) in a type II CRISPR-Cas system and characterize its interaction with S. pyogenes Csn2 (SpCsn2). The SpCas1 structure reveals a unique conformational state distinct from type I Cas1 structures, resulting in a more extensive dimerization interface, a more globular overall structure, and a disruption of potential metal-binding sites for catalysis. We demonstrate that SpCas1 directly interacts with SpCsn2, and identify the binding interface and key residues for Cas complex formation. These results provide structural information for a type II Cas1 protein, and lay a foundation for studying multiprotein Cas complexes functioning in type II CRISPR-Cas systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Homology modeling, binding site identification and docking study of human angiotensin II type I (Ang II-AT1) receptor.

PubMed

Vyas, Vivek K; Ghate, Manjunath; Patel, Kinjal; Qureshi, Gulamnizami; Shah, Surmil

2015-08-01

Ang II-AT1 receptors play an important role in mediating virtually all of the physiological actions of Ang II. Several drugs (SARTANs) are available, which can block the AT1 receptor effectively and lower the blood pressure in the patients with hypertension. Currently, there is no experimental Ang II-AT1 structure available; therefore, in this study we modeled Ang II-AT1 receptor structure using homology modeling followed by identification and characterization of binding sites and thereby assessing druggability of the receptor. Homology models were constructed using MODELLER and I-TASSER server, refined and validated using PROCHECK in which 96.9% of 318 residues were present in the favoured regions of the Ramachandran plots. Various Ang II-AT1 receptor antagonist drugs are available in the market as antihypertensive drug, so we have performed docking study with the binding site prediction algorithms to predict different binding pockets on the modeled proteins. The identification of 3D structures and binding sites for various known drugs will guide us for the structure-based drug design of novel compounds as Ang II-AT1 receptor antagonists for the treatment of hypertension. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Discovery of novel inhibitors for DHODH via virtual screening and X-ray crystallographic structures

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

McLean, Larry R.; Zhang, Ying; Degnen, William

2010-10-28

Amino-benzoic acid derivatives 1-4 were found to be inhibitors for DHODH by virtual screening, biochemical, and X-ray crystallographic studies. X-ray structures showed that 1 and 2 bind to DHODH as predicted by virtual screening, but 3 and 4 were found to be structurally different from the corresponding compounds initially identified by virtual screening.

Structural and functional characterization of an arylamine N-acetyltransferase from the pathogen Mycobacterium abscessus: differences from other mycobacterial isoforms and implications for selective inhibition.

PubMed

Cocaign, Angélique; Kubiak, Xavier; Xu, Ximing; Garnier, Guillaume; Li de la Sierra-Gallay, Inès; Chi-Bui, Linh; Dairou, Julien; Busi, Florent; Abuhammad, Areej; Haouz, Ahmed; Dupret, Jean Marie; Herrmann, Jean Louis; Rodrigues-Lima, Fernando

2014-11-01

Mycobacterium abscessus is the most pathogenic rapid-growing mycobacterium and is one of the most resistant organisms to chemotherapeutic agents. However, structural and functional studies of M. abscessus proteins that could modify/inactivate antibiotics remain nonexistent. Here, the structural and functional characterization of an arylamine N-acetyltransferase (NAT) from M. abscessus [(MYCAB)NAT1] are reported. This novel prokaryotic NAT displays significant N-acetyltransferase activity towards aromatic substrates, including antibiotics such as isoniazid and p-aminosalicylate. The enzyme is endogenously expressed and functional in both the rough and smooth M. abscessus morphotypes. The crystal structure of (MYCAB)NAT1 at 1.8 Å resolution reveals that it is more closely related to Nocardia farcinica NAT than to mycobacterial isoforms. In particular, structural and physicochemical differences from other mycobacterial NATs were found in the active site. Peculiarities of (MYCAB)NAT1 were further supported by kinetic and docking studies showing that the enzyme was poorly inhibited by the piperidinol inhibitor of mycobacterial NATs. This study describes the first structure of an antibiotic-modifying enzyme from M. abscessus and provides bases to better understand the substrate/inhibitor-binding specificities among mycobacterial NATs and to identify/optimize specific inhibitors. These data should also contribute to the understanding of the mechanisms that are responsible for the pathogenicity and extensive chemotherapeutic resistance of M. abscessus.

A (1)H-NMR study on the effect of high pressures on beta-lactoglobulin.

PubMed

Belloque, J; López-Fandiño, R; Smith, G M

2000-09-01

1H NMR was used to study the effect of high pressure on changes in the structure of beta-lactoglobulin (beta-Lg), particularly the strongly bonded regions, the "core". beta-Lg was exposed to pressures ranging from 100 to 400 MPa at neutral pH. After depressurization and acidification to pH 2.0, (1)H NMR spectra were taken. Pressure-induced unfolding was studied by deuterium exchange. Refolding was also evaluated. Our results showed that the core was unaltered at 100 MPa but increased its conformational flexibility at >/=200 MPa. Even though the core was highly flexible at 400 MPa, its structure was found to be identical to the native structure after equilibration back to atmospheric pressure. It is suggested that pressure-induced aggregates are formed by beta-Lg molecules maintaining most of their structure, and the intermolecular -SS- bonds, formed by -SH/-SS- exchange reaction, are likely to involve C(66)-C(160) rather than C(106)-C(119). In addition, the beta-Lg variants A and B could be distinguished in a (1)H NMR spectrum from a solution made with the AB mixed variant, by the differences in chemical shifts of M(107) and C(106); structural implications are discussed. Under pressure, the core of beta-Lg A seemed to unfold faster than that of beta-LgB. The structural recovery of the core was full for both variants.

Effects of Cannabis Use on Human Brain Structure in Psychosis: A Systematic Review Combining In Vivo Structural Neuroimaging and Post Mortem Studies

PubMed Central

Rapp, Charlotte; Bugra, Hilal; Riecher-Rössler, Anita; Tamagni, Corinne; Borgwardt, Stefan

2012-01-01

It is unclear yet whether cannabis use is a moderating or causal factor contributing to grey matter alterations in schizophrenia and the development of psychotic symptoms. We therefore systematically reviewed structural brain imaging and post mortem studies addressing the effects of cannabis use on brain structure in psychosis. Studies with schizophrenia (SCZ) and first episode psychosis (FEP) patients as well as individuals at genetic (GHR) or clinical high risk for psychosis (ARMS) were included. We identified 15 structural magnetic resonance imaging (MRI) (12 cross sectional / 3 longitudinal) and 4 post mortem studies. The total number of subjects encompassed 601 schizophrenia or first episode psychosis patients, 255 individuals at clinical or genetic high risk for psychosis and 397 healthy controls. We found evidence for consistent brain structural abnormalities in cannabinoid 1 (CB1) receptor enhanced brain areas as the cingulate and prefrontal cortices and the cerebellum. As these effects have not consistently been reported in studies examining non-psychotic and healthy samples, psychosis patients and subjects at risk for psychosis might be particularly vulnerable to brain volume loss due to cannabis exposure PMID:22716152

Structure, Dynamics, and Interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 Examined by Molecular Modeling, Simulation, and Electrostatic Studies

PubMed Central

Bhutani, Isha; Loharch, Saurabh; Gupta, Pawan; Madathil, Rethi; Parkesh, Raman

2015-01-01

The enzymes decaprenylphosphoryl-β-D-ribose oxidase (DprE1) and decaprenylphosphoryl-β-D-ribose-2-epimerase (DprE2) catalyze epimerization of decaprenylphosporyl ribose (DPR) todecaprenylphosporyl arabinose (DPA) and are critical for the survival of Mtb. Crystal structures of DprE1 so far reported display significant disordered regions and no structural information is known for DprE2. We used homology modeling, protein threading, molecular docking and dynamics studies to investigate the structural and dynamic features of Mtb DprE1 and DprE2 and DprE1-DprE2 complex. A three-dimensional model for DprE2 was generated using the threading approach coupled with ab initio modeling. A 50 ns simulation of DprE1 and DprE2 revealed the overall stability of the structures. Principal Component Analysis (PCA) demonstrated the convergence of sampling in both DprE1 and DprE2. In DprE1, residues in the 269–330 area showed considerable fluctuation in agreement with the regions of disorder observed in the reported crystal structures. In DprE2, large fluctuations were detected in residues 95–113, 146–157, and 197–226. The study combined docking and MD simulation studies to map and characterize the key residues involved in DprE1-DprE2 interaction. A 60 ns MD simulation for DprE1-DprE2 complex was also performed. Analysis of data revealed that the docked complex is stabilized by H-bonding, hydrophobic and ionic interactions. The key residues of DprE1 involved in DprE1-DprE2 interactions belong to the disordered region. We also examined the docked complex of DprE1-BTZ043 to investigate the binding pocket of DprE1 and its interactions with the inhibitor BTZ043. In summary, we hypothesize that DprE1-DprE2 interaction is crucial for the synthesis of DPA and DprE1-DprE2 complex may be a new therapeutic target amenable to pharmacological validation. The findings have important implications in tuberculosis (TB) drug discovery and will facilitate drug development efforts against TB. PMID:25789990

Structure, dynamics, and interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 examined by molecular modeling, simulation, and electrostatic studies.

PubMed

Bhutani, Isha; Loharch, Saurabh; Gupta, Pawan; Madathil, Rethi; Parkesh, Raman

2015-01-01

The enzymes decaprenylphosphoryl-β-D-ribose oxidase (DprE1) and decaprenylphosphoryl-β-D-ribose-2-epimerase (DprE2) catalyze epimerization of decaprenylphosporyl ribose (DPR) todecaprenylphosporyl arabinose (DPA) and are critical for the survival of Mtb. Crystal structures of DprE1 so far reported display significant disordered regions and no structural information is known for DprE2. We used homology modeling, protein threading, molecular docking and dynamics studies to investigate the structural and dynamic features of Mtb DprE1 and DprE2 and DprE1-DprE2 complex. A three-dimensional model for DprE2 was generated using the threading approach coupled with ab initio modeling. A 50 ns simulation of DprE1 and DprE2 revealed the overall stability of the structures. Principal Component Analysis (PCA) demonstrated the convergence of sampling in both DprE1 and DprE2. In DprE1, residues in the 269-330 area showed considerable fluctuation in agreement with the regions of disorder observed in the reported crystal structures. In DprE2, large fluctuations were detected in residues 95-113, 146-157, and 197-226. The study combined docking and MD simulation studies to map and characterize the key residues involved in DprE1-DprE2 interaction. A 60 ns MD simulation for DprE1-DprE2 complex was also performed. Analysis of data revealed that the docked complex is stabilized by H-bonding, hydrophobic and ionic interactions. The key residues of DprE1 involved in DprE1-DprE2 interactions belong to the disordered region. We also examined the docked complex of DprE1-BTZ043 to investigate the binding pocket of DprE1 and its interactions with the inhibitor BTZ043. In summary, we hypothesize that DprE1-DprE2 interaction is crucial for the synthesis of DPA and DprE1-DprE2 complex may be a new therapeutic target amenable to pharmacological validation. The findings have important implications in tuberculosis (TB) drug discovery and will facilitate drug development efforts against TB.

Candidate configuration trade study, Stellar-inertial Measurement Systems (SIMS) for an Earth Observation Satellite (EOS)

NASA Technical Reports Server (NTRS)

Ogletree, G.; Coccoli, J.; Mckern, R.; Smith, M.; White, R.

1972-01-01

The results of analytical and simulation studies of the stellar-inertial measurement system (SIMS) for an earth observation satellite are presented. Subsystem design analyses and sensor design trades are reported. Three candidate systems are considered: (1) structure-mounted gyros with structure-mounted star mapper, (2) structure-mounted gyros with gimbaled star tracker, and (3) gimbaled gyros with structure-mounted star mapper. The purpose of the study is to facilitate the decisions pertaining to gimbaled versus structure-mounted gyros and star sensors, and combinations of systems suitable for the EOS satellite.

G-rich telomeric and ribosomal DNA sequences from the fission yeast genome form stable G-quadruplex DNA structures in vitro and are unwound by the Pfh1 DNA helicase

PubMed Central

Wallgren, Marcus; Mohammad, Jani B.; Yan, Kok-Phen; Pourbozorgi-Langroudi, Parham; Ebrahimi, Mahsa; Sabouri, Nasim

2016-01-01

Certain guanine-rich sequences have an inherent propensity to form G-quadruplex (G4) structures. G4 structures are e.g. involved in telomere protection and gene regulation. However, they also constitute obstacles during replication if they remain unresolved. To overcome these threats to genome integrity, organisms harbor specialized G4 unwinding helicases. In Schizosaccharomyces pombe, one such candidate helicase is Pfh1, an evolutionarily conserved Pif1 homolog. Here, we addressed whether putative G4 sequences in S. pombe can adopt G4 structures and, if so, whether Pfh1 can resolve them. We tested two G4 sequences, derived from S. pombe ribosomal and telomeric DNA regions, and demonstrated that they form inter- and intramolecular G4 structures, respectively. Also, Pfh1 was enriched in vivo at the ribosomal G4 DNA and telomeric sites. The nuclear isoform of Pfh1 (nPfh1) unwound both types of structure, and although the G4-stabilizing compound Phen-DC3 significantly enhanced their stability, nPfh1 still resolved them efficiently. However, stable G4 structures significantly inhibited adenosine triphosphate hydrolysis by nPfh1. Because ribosomal and telomeric DNA contain putative G4 regions conserved from yeasts to humans, our studies support the important role of G4 structure formation in these regions and provide further evidence for a conserved role for Pif1 helicases in resolving G4 structures. PMID:27185885

pH-Dependent reversible crystal transformation of 1-carboxymethyl-1-methyl-pyrrolidinium bromides and their spectroscopic fingerprint

NASA Astrophysics Data System (ADS)

Tong, Ya-yan; Zhang, Heng; Chang, Liang-liang; Xuan, Xiao-peng

2018-03-01

In this work, two 1-carboxymethyl-1-methyl-pyrrolidinium bromides (N-methylpyrrolidine betaine hydrobromides) with the stoichiometry of betaine:hydrobromic acid as 1:1 and 2:1, denoted as CMPRHBr-I and CMPRHBr-II, respectively, were prepared and crystallographically determined. The large difference in these two structures is the type of hydrogen bonds, resulting in the different thermal stability. A strong Osbnd H ⋯ Br hydrogen bond was observed in CMPRHBr-I, whereas O ⋯ H ⋯ O hydrogen bond in CMPRHBr-II. Both these two crystals can mutually transform by changing the pH value of the aqueous solution. Vibrational spectroscopic studies shows that these two structures can be easily distinguished by the characteristic bands such as νCdbnd O stretching vibration and the D-type bands. Our studies indicate that it should be cautious of the structural change as this type of organic salts was purified and recrystallized.

Ways and Means of Adapting Culture and Structure: Case Studies. Support Document 1

ERIC Educational Resources Information Center

Clayton, Berwyn; Fisher, Thea; Harris, Roger; Bateman, Andrea; Brown, Mike

2008-01-01

The resource in this support document is a set of small case studies, offering insights into how a range of organisations have gone about adapting their organisational structure and/or culture to enhance their capability. Key elements of each case are presented with a particular emphasis on: (1) the principles that have underpinned each approach…

Structural Studies on Varicella Zoster Virus

DTIC Science & Technology

1990-08-20

TABLE OF CONTENTS INTRODUCTION 1 The VZV Genome , 8 VZV Proteins 12 VZV Transcription 14 The Structure of HSV 15 Herpesvirus Expression 16...VZV virion . . . 4 Figure 2. A drawing of the VZV nucleocapsid 6 Figure 3. A comparison of the structure of the genomes of HSV - 1 and VZV 9 Figure 4...VZV, and purified VZ virions probed with antibody against VZV IE62 (the HSV - 1 ICP4 equivalent) . . . 154 xii Figure 48. Autoradiograph of VZV IE62

Does reading in shallow L1 orthography slow attrition of language-specific morphological structures?

PubMed

Zaretsky, Elena; Bar-Shalom, Eva G

2010-01-01

This study looks at the relationship between L1 (Russian) attrition and L1 reading ability in Russian-English-speaking bilingual children. Ten Russian-English bilingual children and 10 adults participated in this study. Nine out of 10 children participants were born in the US and used L1 as their primary language of interaction within the family, but the intensity and the length of uninterrupted L1 exposure differed for each child. All participants were tested on perception (grammaticality judgement) and production (narrative) tasks to assess their sensitivity to and retention of the morphosyntactic structure of L1. All children showed some attrition of grammatical morphemes, specifically in the Russian systems of declension and conjugation; however, the degree of attrition correlated with reading ability in L1, i.e. children with L1 reading skills showed a lesser degree of attrition for some language-specific morphosyntactic structures. This finding shows interdependence of oral and reading skills and points to the role reading in language with shallow orthography may play in preservation of L1 grammatical structures in oral language. The implications for the clinical applications are also discussed.

The structure of transcription termination factor Nrd1 reveals an original mode for GUAA recognition

PubMed Central

Franco-Echevarría, Elsa; González-Polo, Noelia; Zorrilla, Silvia; Martínez-Lumbreras, Santiago; Santiveri, Clara M.; Campos-Olivas, Ramón; Sánchez, Mar; Calvo, Olga

2017-01-01

Abstract Transcription termination of non-coding RNAs is regulated in yeast by a complex of three RNA binding proteins: Nrd1, Nab3 and Sen1. Nrd1 is central in this process by interacting with Rbp1 of RNA polymerase II, Trf4 of TRAMP and GUAA/G terminator sequences. We lack structural data for the last of these binding events. We determined the structures of Nrd1 RNA binding domain and its complexes with three GUAA-containing RNAs, characterized RNA binding energetics and tested rationally designed mutants in vivo. The Nrd1 structure shows an RRM domain fused with a second α/β domain that we name split domain (SD), because it is formed by two non-consecutive segments at each side of the RRM. The GUAA interacts with both domains and with a pocket of water molecules, trapped between the two stacking adenines and the SD. Comprehensive binding studies demonstrate for the first time that Nrd1 has a slight preference for GUAA over GUAG and genetic and functional studies suggest that Nrd1 RNA binding domain might play further roles in non-coding RNAs transcription termination. PMID:28973465

Seeking structure in social organization: compensatory control and the psychological advantages of hierarchy.

PubMed

Friesen, Justin P; Kay, Aaron C; Eibach, Richard P; Galinsky, Adam D

2014-04-01

Hierarchies are a ubiquitous form of human social organization. We hypothesized that 1 reason for the prevalence of hierarchies is that they offer structure and therefore satisfy the core motivational needs for order and control relative to less structured forms of social organization. This hypothesis is rooted in compensatory control theory, which posits that (a) individuals have a basic need to perceive the world as orderly and structured, and (b) personal and external sources of control are capable of satisfying this need because both serve the comforting belief that the world operates in an orderly fashion. Our first 2 studies confirmed that hierarchies were perceived as more structured and orderly relative to egalitarian arrangements (Study 1) and that working in a hierarchical workplace promotes a feeling of self-efficacy (Study 2). We threatened participants' sense of personal control and measured perceptions of and preferences for hierarchy in 5 subsequent experiments. Participants who lacked control perceived more hierarchy occurring in ambiguous social situations (Study 3) and preferred hierarchy more strongly in workplace contexts (Studies 4-5). We also provide evidence that hierarchies are indeed appealing because of their structure: Preference for hierarchy was higher among individuals high in Personal Need for Structure and a control threat increased preference for hierarchy even among participants low in Personal Need for Structure (Study 5). Framing a hierarchy as unstructured reversed the effect of control threat on hierarchy (Study 6). Finally, hierarchy-enhancing jobs were more appealing after control threat, even when they were low in power and status (Study 7). (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Hybrid density functional study of structural, bonding, and electronic properties of the manganite series La1-xCaxMnO3 (x =0,1/4,1)

NASA Astrophysics Data System (ADS)

Korotana, R.; Mallia, G.; Gercsi, Z.; Liborio, L.; Harrison, N. M.

2014-05-01

Hybrid-exchange density functional theory calculations are carried out to determine the effects of A-site doping on the electronic and magnetic properties of the manganite series La1-xCaxMnO3. This study focuses on the ground state of an ordered Ca occupancy in a periodic structure. It is shown that the hybrid-exchange functional, Becke three-parameter Lee-Yang-Parr (B3LYP), provides an accurate and consistent description of the electronic structure for LaMnO3, CaMnO3, and La0.75Ca0.25MnO3. We have quantified the relevant structural, magnetic, and electronic energy contributions to the stability of the doped compound. An insight into the exchange coupling mechanism for the low hole density region of the phase diagram, where a polaron (anti-Jahn-Teller) forms, is also provided. This study completes a microscopic description of the lightly doped insulator with an antiferromagnetic-to-ferromagnetic and metal-to-insulator transition.

Correlation between the conformational states of F1-ATPase as determined from its crystal structure and single-molecule rotation

PubMed Central

Okuno, Daichi; Fujisawa, Ryo; Iino, Ryota; Hirono-Hara, Yoko; Imamura, Hiromi; Noji, Hiroyuki

2008-01-01

F1-ATPase is a rotary molecular motor driven by ATP hydrolysis that rotates the γ-subunit against the α3β3 ring. The crystal structures of F1, which provide the structural basis for the catalysis mechanism, have shown essentially 1 stable conformational state. In contrast, single-molecule studies have revealed that F1 has 2 stable conformational states: ATP-binding dwell state and catalytic dwell state. Although structural and single-molecule studies are crucial for the understanding of the molecular mechanism of F1, it remains unclear as to which catalytic state the crystal structure represents. To address this issue, we introduced cysteine residues at βE391 and γR84 of F1 from thermophilic Bacillus PS3. In the crystal structures of the mitochondrial F1, the corresponding residues in the ADP-bound β (βDP) and γ were in direct contact. The βE190D mutation was additionally introduced into the β to slow ATP hydrolysis. By incorporating a single copy of the mutant β-subunit, the chimera F1, α3β2β(E190D/E391C)γ(R84C), was prepared. In single-molecule rotation assay, chimera F1 showed a catalytic dwell pause in every turn because of the slowed ATP hydrolysis of β(E190D/E391C). When the mutant β and γ were cross-linked through a disulfide bond between βE391C and γR84C, F1 paused the rotation at the catalytic dwell angle of β(E190D/E391C), indicating that the crystal structure represents the catalytic dwell state and that βDP is the catalytically active form. The former point was again confirmed in experiments where F1 rotation was inhibited by adenosine-5′-(β,γ-imino)-triphosphate and/or azide, the most commonly used inhibitors for the crystallization of F1. PMID:19075235

Compliant Robotic Structures. Part 2

DTIC Science & Technology

1986-07-01

Nonaxially Homogeneous Stresses and Strains 44 Parametric Studies 52 % References 65 III. LARGE DEFLECTIONS OF CONTINUOUS ELASTIC ’- STRUCTURES 66...APPENDIX C: Computer Program for the Element String 133 -° SUMMARY This is the second year report which is a part of a three- year study on compliant...ratios as high as 10/1 for laboratory-scale models and up to 3/1 for full-scale prototype arms. The first two years of this study have involved the

Reconstruction of low-index graphite surfaces

NASA Astrophysics Data System (ADS)

Thinius, Sascha; Islam, Mazharul M.; Bredow, Thomas

2016-07-01

The low-index graphite surfaces (10 1 -0), (10 1 -1), (11 2 -0) and (11 2 - 1) have been studied by density functional theory (DFT) including van-der-Waals (vdW) corrections. Different from the (0001) surface which has been extensively investigated both experimentally and theoretically, there is no comprehensive study on the (10 1 -0)- (10 1 -1)-, (11 2 -0)- and (11 2 - 1)-surfaces available, although they are of relevance for Li insertion processes, e.g. in Li-ion batteries. In this study the structure and stability of all non-(0001) low-index surfaces were calculated with RPBE-D3 and converged slab models. In all cases reconstruction involving bond formation between unsaturated carbon atoms of two neighboring graphene sheets reduces the surface energy dramatically. Two possible reconstruction patterns have been considered. The first possibility leads to formation of oblong nanotubes. Alternatively, the graphene sheets form bonds to different neighboring sheets at the upper and lower sides and sinusoidal structures are formed. Both structure types have similar stabilities. Based on the calculated surface energies the Gibbs-Wulff theorem was applied to construct the macroscopic shape of graphite single crystals.

Structural Enhancement of Learning

ERIC Educational Resources Information Center

Trumpower, David L.; Goldsmith, Timothy E.

2004-01-01

Structural learning aids, such as interactive overviews (IOs), have previously been shown to facilitate text comprehension and recall. In this study, we examined the effects of structural aids on learners' structural knowledge and their performance on a procedural transfer task. In Experiment 1, 90 college students were presented definitions of…

Structural studies of MFE-1: the 1.9 A crystal structure of the dehydrogenase part of rat peroxisomal MFE-1.

PubMed

Taskinen, Jukka P; Kiema, Tiila R; Hiltunen, J Kalervo; Wierenga, Rik K

2006-01-27

The 1.9 A structure of the C-terminal dehydrogenase part of the rat peroxisomal monomeric multifunctional enzyme type 1 (MFE-1) has been determined. In this construct (residues 260-722 and referred to as MFE1-DH) the N-terminal hydratase part of MFE-1 has been deleted. The structure of MFE1-DH shows that it consists of an N-terminal helix, followed by a Rossmann-fold domain (domain C), followed by two tightly associated helical domains (domains D and E), which have similar topology. The structure of MFE1-DH is compared with the two known homologous structures: human mitochondrial 3-hydroxyacyl-CoA dehydrogenase (HAD; sequence identity is 33%) (which is dimeric and monofunctional) and with the dimeric multifunctional alpha-chain (alphaFOM; sequence identity is 28%) of the bacterial fatty acid beta-oxidation alpha2beta2-multienzyme complex. Like MFE-1, alphaFOM has an N-terminal hydratase part and a C-terminal dehydrogenase part, and the structure comparisons show that the N-terminal helix of MFE1-DH corresponds to the alphaFOM linker helix, located between its hydratase and dehydrogenase part. It is also shown that this helix corresponds to the C-terminal helix-10 of the hydratase/isomerase superfamily, suggesting that functionally it belongs to the N-terminal hydratase part of MFE-1.

Role of Thermal Process on Self-Assembled Structures of 4′-([2,2′:6′,2″-Terpyridin]-4′-Yl)-[1,1′-Biphenyl]-4-Carboxylic Acid on Au(III)

PubMed Central

Liu, Xiaoqing; Wang, Yongli; Song, Xin; Chen, Feng; Ouyang, Hongping; Zhang, Xueao; Cai, Yingxiang; Liu, Xiaoming; Wang, Li

2013-01-01

The role of dynamic processes on self-assembled structures of 4′-([2,2′:6′, 2″-terpyridin]-4′-yl)-[1,1′-biphenyl]-4-carboxylic acid (l) molecules on Au(III) has been studied by scanning tunneling microscopy. The as-deposited monolayer is closed-packed and periodic in a short-range due to dipole forces. A thermal annealing process at 110 degrees drives such disordered monolayer into ordered chain-like structures, determined by the combination of the dipole forces and hydrogen bonding. Further annealing at 130 degrees turns the whole monolayer into a bowknot-like structure in which hydrogen bonding plays the dominant role in the formation of assembled structures. Such dependence of an assembled structure on the process demonstrates that an assembled structure can be regulated and controlled not only by the molecular structure but also by the thermal process to form the assembled structure. PMID:23478440

Mechanistic Insights into the Specificity of Human Cytosolic Sulfotransferase 2A1 (hSULT2A1) for Hydroxylated Polychlorinated Biphenyls Through the Use of Fluoro-tagged Probes

PubMed Central

Ekuase, E.J.; van ’t Erve, T.J.; Rahaman, A.; Robertson, L.W.; Duffel, M.W.; Luthe, G.

2015-01-01

Determining the relationships between the structures of substrates and inhibitors and their interactions with drug-metabolizing enzymes is of prime importance in predicting the toxic potential of new and legacy xenobiotics. Traditionally, quantitative structure activity relationship (QSAR) studies are performed with many distinct compounds. Based on the chemical properties of the tested compounds, complex relationships can be established so that models can be developed to predict toxicity of novel compounds. In this study, the use of fluorinated analogues as supplemental QSAR compounds was investigated. Substituting fluorine induces changes in electronic and steric properties of the substrate without substantially changing the chemical backbone of the substrate. In vitro assays were performed using purified human cytosolic sulfotransferase hSULT2A1 as a model enzyme. A mono-hydroxylated polychlorinated biphenyl (4-OH PCB 14) and its four possible mono-fluoro analogues were used as test compounds. Remarkable similarities were found between this approach and previously published QSAR studies for hSULT2A1. Both studies implicate the importance of dipole moment and dihedral angle as being important to PCB structure in respect to being substrates for hSULT2A1. We conclude that mono-fluorinated analogues of a target substrate can be a useful tool to study the structure activity relationships for enzyme specificity. PMID:26165989

Special Features of Structure Formation in an Explosion-Welded Magnesium-Aluminum Composite Under Deformation and Subsequent Heat Treatment

NASA Astrophysics Data System (ADS)

Gurevich, L. M.; Arisova, V. N.; Trykov, Yu. P.; Ponomareva, I. A.; Trudov, A. F.

2016-07-01

The effect of bending deformation and subsequent heat treatment on the variation of microhardness and structure of explosion-welded magnesium-aluminum layered composite material MA2-1 - AD1 is studied.

Polarized neutron scattering study of the multiple order parameter system NdB 4 [Polarized neutron scattering study on multiple order parameter system NdB 4

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

Metoki, Naoto; Yamauchi, Hiroki; Matsuda, Masaaki

Neutron polarization analysis has been carried out in order to clarify the magnetic structures of multiple order parameter f-electron system NdB 4. We confirmed the noncollinear “all-in all-out” structure (Γ 4) of the in-plane moment, which is in good agreement with our previous neutron powder diffraction study. We found that the magnetic moment along the c-axis m c showed diagonally antiferromagnetic structure (Γ 10), inconsistent with previously reported “vortex” structure (Γ 2). The microscopic mixture of these two structures with →q 0=(0,0,0) appears in phase II and remains stable in phases III and IV, where an incommensurate modulation coexists. Themore » unusual magnetic ordering is phenomenologically understood via Landau theory with the primary order parameter Γ 4 coupled with higher-order secondary order parameter Γ 10. The magnetic moments were estimated to be 1.8 ± 0.2 and 0.2 ± 0.05μ B at T = 7.5K for Γ 4 and Γ 10, respectively. We also found a long-period incommensurate modulation of the →q 1=(0,0,1/2) antiferromagnetic structure of mc with the propagation →q s1=(0.14,0.14,0.1) and →q s2=(0.2,0,0.1) in phase III and IV, respectively. The amplitude of sinusoidal modulation was about m c=1.0 ± 0.2μ B at T=1.5 K. The local (0,0,1/2) structure consists of in-plane ferromagnetic and out-of-plane antiferromagnetic coupling of m c, opposite to the coexisting Γ 10. The mc of Γ 10 is significantly enhanced up to 0.6μ B at T=1.5 K, which is accompanied by the incommensurate modulations. As a result, the Landau phenomenological approach indicates that the higher-order magnetic and/or multipole interactions based on the pseudoquartet f-electron state play important roles.« less

Polarized neutron scattering study of the multiple order parameter system NdB 4 [Polarized neutron scattering study on multiple order parameter system NdB 4

DOE PAGES

Metoki, Naoto; Yamauchi, Hiroki; Matsuda, Masaaki; ...

2018-05-17

Neutron polarization analysis has been carried out in order to clarify the magnetic structures of multiple order parameter f-electron system NdB 4. We confirmed the noncollinear “all-in all-out” structure (Γ 4) of the in-plane moment, which is in good agreement with our previous neutron powder diffraction study. We found that the magnetic moment along the c-axis m c showed diagonally antiferromagnetic structure (Γ 10), inconsistent with previously reported “vortex” structure (Γ 2). The microscopic mixture of these two structures with →q 0=(0,0,0) appears in phase II and remains stable in phases III and IV, where an incommensurate modulation coexists. Themore » unusual magnetic ordering is phenomenologically understood via Landau theory with the primary order parameter Γ 4 coupled with higher-order secondary order parameter Γ 10. The magnetic moments were estimated to be 1.8 ± 0.2 and 0.2 ± 0.05μ B at T = 7.5K for Γ 4 and Γ 10, respectively. We also found a long-period incommensurate modulation of the →q 1=(0,0,1/2) antiferromagnetic structure of mc with the propagation →q s1=(0.14,0.14,0.1) and →q s2=(0.2,0,0.1) in phase III and IV, respectively. The amplitude of sinusoidal modulation was about m c=1.0 ± 0.2μ B at T=1.5 K. The local (0,0,1/2) structure consists of in-plane ferromagnetic and out-of-plane antiferromagnetic coupling of m c, opposite to the coexisting Γ 10. The mc of Γ 10 is significantly enhanced up to 0.6μ B at T=1.5 K, which is accompanied by the incommensurate modulations. As a result, the Landau phenomenological approach indicates that the higher-order magnetic and/or multipole interactions based on the pseudoquartet f-electron state play important roles.« less

Zero-n gap in one dimensional photonic crystal

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

Chobey, Mahesh K., E-mail: mahesh01chobey@gmail.com; Suthar, B.

2016-05-06

We study a one-dimensional (1-D) photonic crystal composed of Double Positive (DPS) and Double Negative (DNG) material. This structure shows omnidirectional photonic bandgap, which is insensitive with angle of incidence and polarization. To study the effect of structural parameters on the photonic band structure, we have calculated photonic band gap at various thicknesses of DPS and DNG.

Reliability, Validity, and Factor Structure of the Imaginative Capability Scale

ERIC Educational Resources Information Center

Liang, Chaoyun; Chia, Tsorng-Lin

2014-01-01

Three studies were combined to test the reliability, validity, and factor structure of the imaginative capability scale (ICS). The ICS was a new self-report measure, which was developed to be empirically valid and easy to administer. Study 1 consisted in an exploratory factor analysis to determine the most appropriate structure of the ICS in a…

Stability and Change in Social Goals as Related to Goal Structures and Engagement in School

ERIC Educational Resources Information Center

Madjar, Nir

2017-01-01

The current studies explored (a) the extended external validity of social-goal-orientation framework; (b) the mediating role of social goals between classroom goal structures and students' engagement; and (c) whether changes in social goals can be explained by classroom goal structures and engagement. Study 1 was cross-sectional (N = 317), and…

Cycle 0(CY1991) NLS trade studies and analyses report. Book 1: Structures and core vehicle

NASA Technical Reports Server (NTRS)

1992-01-01

This report (SR-1: Structures, Trades, and Analysis), documents the Core Tankage Trades and analyses performed in support of the National Launch System (NLS) Cycle 0 preliminary design activities. The report covers trades that were conducted on the Vehicle Assembly, Fwd Skirt, LO2 Tank, Intertank, LH2 Tank, and Aft Skirt of the NLS Core Tankage. For each trade study, a two page executive summary and the detail trade study are provided. The trade studies contain study results, recommended changes to the Cycle 0 Baselines, and suggested follow on tasks to be performed during Cycle 1.

Growth, structural, optical, thermal and laser damage threshold studies of an organic single crystal: 1,3,5 – triphenylbenzene (TPB)

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

Raja, R. Subramaniyan; Babu, G. Anandha; Ramasamy, P., E-mail: E-mail-ramasamyp@ssn.edu.in

2016-05-23

Good quality single crystals of pure hydrocarbon 1,3,5-Triphenylbenzene (TPB) have been successfully grown using toluene as a solvent using controlled slow cooling solution growth technique. TPB crystallizes in orthorhombic structure with the space group Pna2{sub 1}. The structural perfection of the grown crystal has been analysed by high resolution X-ray diffraction measurements. The range and percentage of the optical transmission are ascertained by recording the UV-vis spectrum. Thermo gravimetric analysis (TGA) and differential thermal analysis (DTA) were used to study its thermal properties. Powder second harmonic generation studies were carried out to explore its NLO properties. Laser damage threshold valuemore » has been determined using Nd:YAG laser operating at 1064 nm.« less

Comparative study of synthesis, structural and magnetic properties of Cu2+ substituted Co-Ni, Co-Zn and Co-Mg nano ferrites

NASA Astrophysics Data System (ADS)

Ramakrishna, A.; Murali, N.; Margarette, S. J.; Samatha, K.; Veeraiah, V.

2018-02-01

Mixed ferrites of the form Co0.5M0.1Cu0.4Fe2O4 (M = Ni, Zn and Mg) have been synthesized using the sol-gel auto combustion technique. Structural analyses are carried out using powder X-ray diffraction to idntify pure ferrite phases. SEM analysis revealed clear crystal morphology with relatively uniform grain sizes with polygonal structures. The FT-IR studies also confirm the bond formation and cation vibrations at low (365-392 cm-1) and high (579-587 cm-1) bands that correspond to the tetrahedral and octahedral sites, respectively. The magnetic properties studied through vibrating sample magnetometer showed that the Ni substituted sample has more magnetic character by exhibiting the highest saturation magnetization.

Structural analysis of fructans from Agave americana grown in South Africa for spirit production.

PubMed

Ravenscroft, Neil; Cescutti, Paola; Hearshaw, Meredith A; Ramsout, Ronica; Rizzo, Roberto; Timme, Elizabeth M

2009-05-27

Fructans isolated from Agave americana grown in South Africa are currently used for spirit production. Structural studies on water-soluble fructans were performed to facilitate the development of other applications including its use as a prebiotic. Acid hydrolysis followed by HPAEC-PAD analysis confirmed that the fructan was composed of glucose and fructose, and size analysis by HPAEC-PAD and size exclusion chromatography indicated that the saccharides have a DP range from 6 to 50. An average DP of 14 was estimated by (1)H NMR analysis. Linkage analysis and ESI-MS studies suggest that A. americana has a neofructan structure consisting of a central sucrose to which (2 → 1)- and (2 → 6)-linked β-D-Fruf chains are attached. The (2 → 1)-linked units extend from C-1 of Fru and C-6 of glucose, whereas the (2 → 6)-linked β-D-Fruf units are attached to C-6 of the central Fru. This structure accounts for the presence of equimolar amounts of 1,6-linked Glu and 1,2,6-linked Fru found in linkage analysis and the multiplicity of the NMR signals observed. Detailed ESI-MS studies were performed on fructan fractions: native, periodate oxidized/reduced, and permethylated oligomers. These derivatizations introduced mass differences between Glc and Fru following oxidation and between 1,2-, 1,6-, 2,6-, and 1,2,6-linked units after methylation. Thus, ESI-MS showed the presence of a single Glc per fructan chain and that it is predominantly internal, rather than terminal as found in inulin. These structural features were confirmed by the use of 1D and 2D NMR experiments.

Co-evolution of payoff strategy and interaction strategy in prisoner's dilemma game

NASA Astrophysics Data System (ADS)

Zhang, Kangjie; Cheng, Hongyan

2016-11-01

Co-evolutionary dynamical models, providing a realistic paradigm for investigating complex system, have been extensively studied. In this paper, the co-evolution of payoff strategy and interaction strategy is studied. Starting with an initial Gaussian distribution of payoff strategy r with the mean u and the variance q, we focus on the final distribution of the payoff strategy. We find that final distribution of the payoff strategy may display different structures depending on parameters. In the ranges u < - 1 and u > 3, the distribution displays a single-peak structure which is symmetric about r = u. The distribution manifests itself as a double-peak structure in the range - 1 < u < 3 although a fake three-peak structure shows up in range 1 < u < 2. The explanations on the formation of different types of payoff strategy distributions are presented.

Structural characterization of an all-aminosugar-containing capsular polysaccharide from Colwellia psychrerythraea 34H

PubMed Central

Casillo, Angela; Ståhle, Jonas; Parrilli, Ermenegilda; Sannino, Filomena; Mitchell, Daniel E.; Pieretti, Giuseppina; Gibson, Matthew I.; Marino, Gennaro; Lanzetta, Rosa; Parrilli, Michelangelo; Widmalm, Göran; Tutino, Maria L.; Corsaro, Maria M.

2017-01-01

Colwellia psychrerythraea strain 34H, a Gram-negative bacterium isolated from Arctic marine sediments, is considered a model to study the adaptation to cold environments. Recently, we demonstrated that C. psychrerythraea 34H produces two different extracellular polysaccharides, a capsular polysaccharide and a medium released polysaccharide, which confer cryoprotection to the bacterium. In this study, we report the structure of an additional capsular polysaccharide produced by Colwellia grown at a different temperature. The structure was determined using chemical methods, and one- and two-dimensional NMR spectroscopy. The results showed a trisaccharide repeating unit made up of only amino-sugar residues: N-acetyl-galactosamine, 2,4-diacetamido-2,4,6-trideoxy-glucose (bacillosamine), and 2-acetamido-2-deoxyglucuronic acid with the following structure: →4)-β-d-GlcpNAcA-(1→3)-β-d-QuipNAc4NAc-(1→3)-β-d-GalpNAc-(1→. The 3D model, generated in accordance with 1H,1H-NOE NMR correlations and consisting of ten repeating units, shows a helical structure. In contrast with the other extracellular polysaccharides produced from Colwellia at 4 °C, this molecule displays only a low ice recrystallization inhibition activity. PMID:28161737

Unveiling the molecular mechanism of brassinosteroids: Insights from structure-based molecular modeling studies.

PubMed

Lei, Beilei; Liu, Jiyuan; Yao, Xiaojun

2015-12-01

Brassinosteroid (BR) phytohormones play indispensable roles in plant growth and development. Brassinolide (BL) and 24-epibrassinolide (24-epiBL) are the most active ones among the BRs reported thus far. Unfortunately, the extremely low natural content and intricate synthesis process limit their popularization in agricultural production. Earlier reports to discover alternative compounds have resulted in molecules with nearly same scaffold structure and without diversity in chemical space. In the present study, receptors structure based BRs regulation mechanism was analyzed. First, we examined the detailed binding interactions and their dynamic stability between BL and its receptor BRI1 and co-receptor BAK1. Then, the binding modes and binding free energies for 24-epiBL and a series of representative BRs binding with BRI1 and BRI1-BAK1 were carried out by molecular docking, energy minimization and MM-PBSA free energy calculation. The obtained binding structures and energetic results provided vital insights into the structural factors affecting the activity from both receptors and BRs aspects. Subsequently, the obtained knowledge will serve as valuable guidance to build pharmacophore models for rational screening of new scaffold alternative BRs. Copyright © 2015 Elsevier Inc. All rights reserved.

The Experiences in Close Relationship Scale (ECR)-short form: reliability, validity, and factor structure.

PubMed

Wei, Meifen; Russell, Daniel W; Mallinckrodt, Brent; Vogel, David L

2007-04-01

We developed a 12-item, short form of the Experiences in Close Relationship Scale (ECR; Brennan, Clark, & Shaver, 1998) across 6 studies. In Study 1, we examined the reliability and factor structure of the measure. In Studies 2 and 3, we cross-validated the reliability, factor structure, and validity of the short form measure; whereas in Study 4, we examined test-retest reliability over a 1-month period. In Studies 5 and 6, we further assessed the reliability, factor structure, and validity of the short version of the ECR when administered as a stand-alone instrument. Confirmatory factor analyses indicated that 2 factors, labeled Anxiety and Avoidance, provided a good fit to the data after removing the influence of response sets. We found validity to be equivalent for the short and the original versions of the ECR across studies. Finally, the results were comparable when we embedded the short form within the original version of the ECR and when we administered it as a stand-alone measure.

Structural analysis of N-linked glycans in Caenorhabditis elegans.

PubMed

Natsuka, Shunji; Adachi, Jiro; Kawaguchi, Masahumi; Nakakita, Shin-ichi; Hase, Sumihiro; Ichikawa, Akira; Ikura, Koji

2002-06-01

Caenorhabditis elegans is an excellent model for morphogenetic research. However, little information is available on the structure of cell-surface glycans in C. elegans, although several lines of evidence have suggested a role for these glycans in cell-cell interactions during development. In this study, we analyzed N-glycan structures. Oligosaccharides liberated by hydrazinolysis from a total membrane fraction were labeled by pyridylamination, and around 90% of the N-glycans were detected as neutral oligosaccharides. The most dominant structure was Man(alpha)1-6(Man(alpha)1-3)Man(beta)1-4GlcNAc(beta)1-4GlcNAc, which is commonly found in insects. Branching structures of major oligomannose-type glycans were the same as those found in mammals. Structures that had a core fucose or non-reducing end N-acetylglucosamine were also identified, but ordinary complex-type glycans with N-acetyllactosamine were not detected as major components.

Anomalous diffusion on a random comblike structure

NASA Astrophysics Data System (ADS)

Havlin, Shlomo; Kiefer, James E.; Weiss, George H.

1987-08-01

We have recently studied a random walk on a comblike structure as an analog of diffusion on a fractal structure. In our earlier work, the comb was assumed to have a deterministic structure, the comb having teeth of infinite length. In the present paper we study diffusion on a one-dimensional random comb, the length of whose teeth are random variables with an asymptotic stable law distribution φ(L)~L-(1+γ) where 0<γ<=1. Two mean-field methods are used for the analysis, one based on the continuous-time random walk, and the second a self-consistent scaling theory. Both lead to the same conclusions. We find that the diffusion exponent characterizing the mean-square displacement along the backbone of the comb is dw=4/(1+γ) for γ<1 and dw=2 for γ>=1. The probability of being at the origin at time t is P0(t)~t-ds/2 for large t with ds=(3-γ)/2 for γ<1 and ds=1 for γ>1. When a field is applied along the backbone of the comb the diffusion exponent is dw=2/(1+γ) for γ<1 and dw=1 for γ>=1. The theoretical results are confirmed using the exact enumeration method.

Novel aldehyde and thiosemicarbazone derivatives: Synthesis, spectroscopic characterization, structural studies and molecular docking studies

NASA Astrophysics Data System (ADS)

Karakurt, Tuncay; Tahtaci, Hakan; Subasi, Nuriye Tuna; Er, Mustafa; Ağar, Erbil

2016-12-01

In this study our purpose is that, synthesis and characterization of compounds containing the aldehyde and thiosemicarbazone groups and comparison of the theoretical results with the experimental results. The structures of all synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, elemental analyses techniques. The structure of compound (4) (C9H8N4O2S) was also elucidated by X-ray diffraction analysis. In addition, the theoretical IR spectrum, 1H NMR and 13C NMR chemical shift values, frontier molecular orbital values (FMO) of these molecules were analyzed by using Becke-3- Lee-Yang-Parr (B3LYP) method with LanL2DZ basis set. Finally, molecular docking studies were performed on synthesized compounds using the 4DKI beta-lactam protein structure to determine the potential binding mode of inhibitors.

UV-Vis spectroscopy of tyrosine side-groups in studies of protein structure. Part 1: basic principles and properties of tyrosine chromophore.

PubMed

Antosiewicz, Jan M; Shugar, David

Spectroscopic properties of tyrosine residues may be employed in structural studies of proteins. Here we discuss several different types of UV-Vis spectroscopy, like normal, difference and second-derivative UV absorption spectroscopy, fluorescence spectroscopy, linear and circular dichroism spectroscopy, and Raman spectroscopy, and corresponding optical properties of the tyrosine chromophore, phenol, which are used to study protein structure.

UV-Vis spectroscopy of tyrosine side-groups in studies of protein structure. Part 1: basic principles and properties of tyrosine chromophore.

PubMed

Antosiewicz, Jan M; Shugar, David

2016-06-01

Spectroscopic properties of tyrosine residues may be employed in structural studies of proteins. Here we discuss several different types of UV-Vis spectroscopy, like normal, difference and second-derivative UV absorption spectroscopy, fluorescence spectroscopy, linear and circular dichroism spectroscopy, and Raman spectroscopy, and corresponding optical properties of the tyrosine chromophore, phenol, which are used to study protein structure.

The Effect of Terminal Substitution on the Helical Carbon Structure of Fluoro-Alkane Chains: a Pure Rotational Study of CH2OH-Cn-1F2n-1 (n = 4, 5,& 6)

NASA Astrophysics Data System (ADS)

Schwartz, Aaron Z. A.; Maturo, Mark P.; Obenchain, Daniel A.; Cooke, S. A.

2016-06-01

Continuing a series of studies to investigate the change in structure of hydrocarbons as the amount of fluorination is increased to varying degrees of substitution, we present a survey on the change in the helical nature of the fluorinated carbon backbone when a -CH2OH group is substituted for a terminal - CF3 group. Spectra for 1H,1H-heptafluorobutan-1-ol, 1H,1H-nonafluoropentan-1-ol, and 1H,1H-undecafluorohexan-1-ol were collected separately using a chirped-pulse FTMW spectrometer in the range of 7-13 GHz. Only one conformation was observed for each molecule. Additional measurements of the 1H,1H-heptafluorobutan-1-ol were completed using a Balle-Flygare cavity instrument. Assignments of the singly-substituted 13C isotopologues of the 1H,1H-heptafluorobutan-1-ol were also measured. A comparison of both ab initio and experimental structures will be presented.

Computational Prediction of the Heterodimeric and Higher-Order Structure of gpE1/gpE2 Envelope Glycoproteins Encoded by Hepatitis C Virus.

PubMed

Freedman, Holly; Logan, Michael R; Hockman, Darren; Koehler Leman, Julia; Law, John Lok Man; Houghton, Michael

2017-04-15

Despite the recent success of newly developed direct-acting antivirals against hepatitis C, the disease continues to be a global health threat due to the lack of diagnosis of most carriers and the high cost of treatment. The heterodimer formed by glycoproteins E1 and E2 within the hepatitis C virus (HCV) lipid envelope is a potential vaccine candidate and antiviral target. While the structure of E1/E2 has not yet been resolved, partial crystal structures of the E1 and E2 ectodomains have been determined. The unresolved parts of the structure are within the realm of what can be modeled with current computational modeling tools. Furthermore, a variety of additional experimental data is available to support computational predictions of E1/E2 structure, such as data from antibody binding studies, cryo-electron microscopy (cryo-EM), mutational analyses, peptide binding analysis, linker-scanning mutagenesis, and nuclear magnetic resonance (NMR) studies. In accordance with these rich experimental data, we have built an in silico model of the full-length E1/E2 heterodimer. Our model supports that E1/E2 assembles into a trimer, which was previously suggested from a study by Falson and coworkers (P. Falson, B. Bartosch, K. Alsaleh, B. A. Tews, A. Loquet, Y. Ciczora, L. Riva, C. Montigny, C. Montpellier, G. Duverlie, E. I. Pecheur, M. le Maire, F. L. Cosset, J. Dubuisson, and F. Penin, J. Virol. 89:10333-10346, 2015, https://doi.org/10.1128/JVI.00991-15). Size exclusion chromatography and Western blotting data obtained by using purified recombinant E1/E2 support our hypothesis. Our model suggests that during virus assembly, the trimer of E1/E2 may be further assembled into a pentamer, with 12 pentamers comprising a single HCV virion. We anticipate that this new model will provide a useful framework for HCV envelope structure and the development of antiviral strategies. IMPORTANCE One hundred fifty million people have been estimated to be infected with hepatitis C virus, and many more are at risk for infection. A better understanding of the structure of the HCV envelope, which is responsible for attachment and fusion, could aid in the development of a vaccine and/or new treatments for this disease. We draw upon computational techniques to predict a full-length model of the E1/E2 heterodimer based on the partial crystal structures of the envelope glycoproteins E1 and E2. E1/E2 has been widely studied experimentally, and this provides valuable data, which has assisted us in our modeling. Our proposed structure is used to suggest the organization of the HCV envelope. We also present new experimental data from size exclusion chromatography that support our computational prediction of a trimeric oligomeric state of E1/E2. Copyright © 2017 American Society for Microbiology.

Computational Prediction of the Heterodimeric and Higher-Order Structure of gpE1/gpE2 Envelope Glycoproteins Encoded by Hepatitis C Virus

PubMed Central

Logan, Michael R.; Hockman, Darren; Koehler Leman, Julia; Law, John Lok Man

2017-01-01

ABSTRACT Despite the recent success of newly developed direct-acting antivirals against hepatitis C, the disease continues to be a global health threat due to the lack of diagnosis of most carriers and the high cost of treatment. The heterodimer formed by glycoproteins E1 and E2 within the hepatitis C virus (HCV) lipid envelope is a potential vaccine candidate and antiviral target. While the structure of E1/E2 has not yet been resolved, partial crystal structures of the E1 and E2 ectodomains have been determined. The unresolved parts of the structure are within the realm of what can be modeled with current computational modeling tools. Furthermore, a variety of additional experimental data is available to support computational predictions of E1/E2 structure, such as data from antibody binding studies, cryo-electron microscopy (cryo-EM), mutational analyses, peptide binding analysis, linker-scanning mutagenesis, and nuclear magnetic resonance (NMR) studies. In accordance with these rich experimental data, we have built an in silico model of the full-length E1/E2 heterodimer. Our model supports that E1/E2 assembles into a trimer, which was previously suggested from a study by Falson and coworkers (P. Falson, B. Bartosch, K. Alsaleh, B. A. Tews, A. Loquet, Y. Ciczora, L. Riva, C. Montigny, C. Montpellier, G. Duverlie, E. I. Pecheur, M. le Maire, F. L. Cosset, J. Dubuisson, and F. Penin, J. Virol. 89:10333–10346, 2015, https://doi.org/10.1128/JVI.00991-15). Size exclusion chromatography and Western blotting data obtained by using purified recombinant E1/E2 support our hypothesis. Our model suggests that during virus assembly, the trimer of E1/E2 may be further assembled into a pentamer, with 12 pentamers comprising a single HCV virion. We anticipate that this new model will provide a useful framework for HCV envelope structure and the development of antiviral strategies. IMPORTANCE One hundred fifty million people have been estimated to be infected with hepatitis C virus, and many more are at risk for infection. A better understanding of the structure of the HCV envelope, which is responsible for attachment and fusion, could aid in the development of a vaccine and/or new treatments for this disease. We draw upon computational techniques to predict a full-length model of the E1/E2 heterodimer based on the partial crystal structures of the envelope glycoproteins E1 and E2. E1/E2 has been widely studied experimentally, and this provides valuable data, which has assisted us in our modeling. Our proposed structure is used to suggest the organization of the HCV envelope. We also present new experimental data from size exclusion chromatography that support our computational prediction of a trimeric oligomeric state of E1/E2. PMID:28148799

Vibrational spectroscopy of the silicate mineral plumbotsumite Pb5(OH)10Si4O8 - An assessment of the molecular structure

NASA Astrophysics Data System (ADS)

López, Andrés; Frost, Ray L.; Scholz, Ricardo; Gobac, Željka Žigovečki; Xi, Yunfei

2013-12-01

We have used scanning electron microscopy with energy dispersive X-ray analysis to determine the precise formula of plumbotsumite, a rare lead silicate mineral of formula Pb5(OH)10Si4O8. This study forms the first systematic study of plumbotsumite from the Bigadic deposits, Turkey. Vibrational spectroscopy was used to assess the molecular structure of plumbotsumite as the structure is not known. The mineral is characterized by sharp Raman bands at 1047, 1055 and 1060 cm-1 assigned to SiO stretching vibrational modes and sharp Raman bands at 673, 683 and 697 cm-1 assigned to OSiO bending modes. The observation of multiple bands offers support for a layered structure with variable SiO3 structural units. Little information may be obtained from the infrared spectra because of broad spectral profiles. Intense Raman bands at 3510, 3546 and 3620 cm-1 are ascribed to OH stretching modes. Evidence for the presence of water in the plumbotsumite structure was inferred from the infrared spectra.

Structural social support and cardiovascular disease risk factors in Hispanic/Latino adults with diabetes: results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

PubMed

Hernandez, Rosalba; Carnethon, Mercedes; Giachello, Aida L; Penedo, Frank J; Wu, Donghong; Birnbaum-Weitzman, Orit; Giacinto, Rebeca Espinoza; Gallo, Linda C; Isasi, Carmen R; Schneiderman, Neil; Teng, Yanping; Zeng, Donglin; Daviglus, Martha L

2017-02-23

Cross-sectional and longitudinal studies have yielded inconsistent findings on the associations of social support networks with cardiovascular health in Hispanic/Latino adults with diabetes. We examined the cross-sectional associations of structural social support and traditional cardiovascular disease (CVD) risk factors in a diverse sample of Hispanic/Latino adults with diabetes. This analysis included 2994 adult participants ages 18-74 with diabetes from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL - 2008-2011). Select items from the Social Network Inventory (SNI) were used to assess indices of structural social support, i.e. network size (number of children, parents, and in-laws) and frequency of familial contact. Standardized methods were used to measure abdominal obesity, BMI, hypertension, hypercholesterolemia, and smoking status. Multivariate regression was used to examine associations of structural support with individual CVD risk factors with demographics, acculturation, physical health, and psychological ill-being (depressive symptoms and anxiety) included as covariates. There were no significant cross-sectional associations of structural support indices with abdominal obesity, hypertension, hypercholesterolemia, or smoking status. There was a marginally significant (OR: 1.05; 95%CI 0.99-1.11) trend toward higher odds of obesity in participants reporting a larger family unit (including children, parents, and in-laws) and those with closer ties with extended family relatives (OR: 1.04; 95%CI 0.99-1.09). Structural social support was marginally associated with higher odds of obesity in Hispanic/Latino adults with diabetes. Alternate forms of social support (e.g. healthcare professionals, friends, peers) should be further explored as potential markers of cardiac risk in Hispanics/Latinos with diabetes.

Synthesis, crystal structure and DFT studies of a Zinc(II) complex of 1,3-diaminopropane (Dap), [Zn(Dap)(NCS)2][Zn(Dap)(NCS)2]n. The additional stabilizing role of S⋯π chalcogen bond

NASA Astrophysics Data System (ADS)

Alotaibi, Mshari A.; Alharthi, Abdulrahman I.; Zierkiewicz, Wiktor; Akhtar, Muhammad; Tahir, Muhammad Nawaz; Mazhar, Muhammad; Isab, Anvarhusein A.; Ahmad, Saeed

2017-04-01

A zinc(II) complex of 1,3-diaminopropane (Dap), [Zn(Dap)(NCS)2][Zn(Dap)(NCS)2]n (1) has been prepared and characterized by elemental analysis, IR, 1H &13C NMR spectroscopy, and its crystal structure was determined by X-ray crystallography. The crystal structure of 1 consists of two types of molecules, a discrete monomer and a polymeric one. In the monomeric unit, the zinc atom is bound to one terminal Dap molecule and to two N-bound thiocyanate ions, while in the polymeric unit, Dap acts as a bridging ligand forming a linear chain. The Zn(II) ions in both assume a slightly distorted tetrahedral geometry. The structures of two systems: the [Zn(Dap)(NCS)2][Zn(Dap)(NCS)2]3 complex as a model of 1 and [Zn(Dap)(NCS)2]4 as a simple polymeric structure were optimized with the B3LYP-D3 method. The DFT results support that the experimentally determined structure (1) is more stable in comparison to a simple polymeric structure, [Zn(Dap)(NCS)2]n (2). The interaction energies (ΔE) for NCS anions obtained by B3LYP-D3 method are about -145 kcal mol-1, while the calculated ΔE values for neutral organic ligands are about twice smaller. The X-ray structure of 1 shows that the complex is stabilized mainly by hydrogen bonds. We also found that weak chalcogen bonds play an additional role in stabilization of compound 1. Some of the intermolecular S⋯N distances are smaller than the sum of the van der Waals radii of the corresponding atoms. To the best of our knowledge, this is the first study that shows the structure where the trivalent sulfur is involved in formation of a S⋯π chalcogen bond. The NBO and NCI analyses confirm the existence of this kind of interactions.

Correlation of physical properties with molecular structure for some dicyclic hydrocarbons having high thermal-energy release per unit volume

NASA Technical Reports Server (NTRS)

Wise, P H; Serijan, K T; Goodman, I A

1951-01-01

As part of a program to study the correlation between molecular structure and physical properties of high-density hydrocarbons, the net heats of combustion, melting points, boiling points, densities, and kinematic viscosities of some hydrocarbons in the 2-n-alkylbiphenyl, 1,1-diphenylalkane, diphenylalkane, 1,1-dicyclohexylalkane, and dicyclohexylalkane series are presented.

Structural basis of ligand binding modes at the neuropeptide Y Y1 receptor.

PubMed

Yang, Zhenlin; Han, Shuo; Keller, Max; Kaiser, Anette; Bender, Brian J; Bosse, Mathias; Burkert, Kerstin; Kögler, Lisa M; Wifling, David; Bernhardt, Guenther; Plank, Nicole; Littmann, Timo; Schmidt, Peter; Yi, Cuiying; Li, Beibei; Ye, Sheng; Zhang, Rongguang; Xu, Bo; Larhammar, Dan; Stevens, Raymond C; Huster, Daniel; Meiler, Jens; Zhao, Qiang; Beck-Sickinger, Annette G; Buschauer, Armin; Wu, Beili

2018-04-01

Neuropeptide Y (NPY) receptors belong to the G-protein-coupled receptor superfamily and have important roles in food intake, anxiety and cancer biology 1,2 . The NPY-Y receptor system has emerged as one of the most complex networks with three peptide ligands (NPY, peptide YY and pancreatic polypeptide) binding to four receptors in most mammals, namely the Y 1 , Y 2 , Y 4 and Y 5 receptors, with different affinity and selectivity 3 . NPY is the most powerful stimulant of food intake and this effect is primarily mediated by the Y 1 receptor (Y 1 R) 4 . A number of peptides and small-molecule compounds have been characterized as Y 1 R antagonists and have shown clinical potential in the treatment of obesity 4 , tumour 1 and bone loss 5 . However, their clinical usage has been hampered by low potency and selectivity, poor brain penetration ability or lack of oral bioavailability 6 . Here we report crystal structures of the human Y 1 R bound to the two selective antagonists UR-MK299 and BMS-193885 at 2.7 and 3.0 Å resolution, respectively. The structures combined with mutagenesis studies reveal the binding modes of Y 1 R to several structurally diverse antagonists and the determinants of ligand selectivity. The Y 1 R structure and molecular docking of the endogenous agonist NPY, together with nuclear magnetic resonance, photo-crosslinking and functional studies, provide insights into the binding behaviour of the agonist and for the first time, to our knowledge, determine the interaction of its N terminus with the receptor. These insights into Y 1 R can enable structure-based drug discovery that targets NPY receptors.

Novel recombinant insulin analogue with flexible C-terminus in B chain. NMR structure of biosynthetic engineered A22G-B31K-B32R human insulin monomer in water/acetonitrile solution.

PubMed

Borowicz, Piotr; Bocian, Wojciech; Sitkowski, Jerzy; Bednarek, Elżbieta; Mikiewicz-Syguła, Diana; Błażej-Sosnowska, Sylwia; Bogiel, Monika; Rusek, Dorota; Kurzynoga, Dariusz; Kozerski, Lech

2011-11-01

A tertiary structure of recombinant A22(G)-B31(K)-B32(R)-human insulin monomer (insulin GKR) has been characterized by (1)H, (13)C NMR at natural isotopic abundance using NOESY, TOCSY, (1)H/(13)C-GHSQC, and (1)H/(13)C-GHSQC-TOCSY spectra. Translational diffusion studies indicate the monomer structure in water/acetonitrile (65/35vol.%). CSI analysis confirms existence of secondary structure motifs present in human insulin standard (HIS). Both techniques allow to establish that in this solvent recombinant insulin GKR exists as a monomer. Starting from structures calculated by the program CYANA, two different refinement protocols used molecular dynamics simulated annealing with the program AMBER; in vacuum (AMBER_VC), and including a generalized Born solvent model (AMBER_GB). From these calculations an ensemble of 20 structures of lowest energy was chosen which represents the tertiary structure of studied insulin. Here we present novel insulin with added A22(G) amino acid which interacts with β-turn environment resulting in high flexibility of B chain C-terminus. Copyright © 2011 Elsevier B.V. All rights reserved.

High-speed atomic force microscopy reveals structural dynamics of amyloid β1–42 aggregates

PubMed Central

Watanabe-Nakayama, Takahiro; Ono, Kenjiro; Itami, Masahiro; Takahashi, Ryoichi; Teplow, David B.; Yamada, Masahito

2016-01-01

Aggregation of amyloidogenic proteins into insoluble amyloid fibrils is implicated in various neurodegenerative diseases. This process involves protein assembly into oligomeric intermediates and fibrils with highly polymorphic molecular structures. These structural differences may be responsible for different disease presentations. For this reason, elucidation of the structural features and assembly kinetics of amyloidogenic proteins has been an area of intense study. We report here the results of high-speed atomic force microscopy (HS-AFM) studies of fibril formation and elongation by the 42-residue form of the amyloid β-protein (Aβ1–42), a key pathogenetic agent of Alzheimer's disease. Our data demonstrate two different growth modes of Aβ1–42, one producing straight fibrils and the other producing spiral fibrils. Each mode depends on initial fibril nucleus structure, but switching from one growth mode to another was occasionally observed, suggesting that fibril end structure fluctuated between the two growth modes. This switching phenomenon was affected by buffer salt composition. Our findings indicate that polymorphism in fibril structure can occur after fibril nucleation and is affected by relatively modest changes in environmental conditions. PMID:27162352

Reflections on protein splicing: structures, functions and mechanisms

PubMed Central

Anraku, Yasuhiro; Satow, Yoshinori

2009-01-01

Twenty years ago, evidence that one gene produces two enzymes via protein splicing emerged from structural and expression studies of the VMA1 gene in Saccharomyces cerevisiae. VMA1 consists of a single open reading frame and contains two independent genetic information for Vma1p (a catalytic 70-kDa subunit of the vacuolar H+-ATPase) and VDE (a 50-kDa DNA endonuclease) as an in-frame spliced insert in the gene. Protein splicing is a posttranslational cellular process, in which an intervening polypeptide termed as the VMA1 intein is self-catalytically excised out from a nascent 120-kDa VMA1 precursor and two flanking polypeptides of the N- and C-exteins are ligated to produce the mature Vma1p. Subsequent studies have demonstrated that protein splicing is not unique to the VMA1 precursor and there are many operons in nature, which implement genetic information editing at protein level. To elucidate its structure-directed chemical mechanisms, a series of biochemical and crystal structural studies has been carried out with the use of various VMA1 recombinants. This article summarizes a VDE-mediated self-catalytic mechanism for protein splicing that is triggered and terminated solely via thiazolidine intermediates with tetrahedral configurations formed within the splicing sites where proton ingress and egress are driven by balanced protonation and deprotonation. PMID:19907126

An Examination of the Structure of Leisure Interests of College Students, Working-Age Adults, and Retirees

ERIC Educational Resources Information Center

Hansen, Jo-Ida C.; Dik, Bryan J.; Zhou, Shuangmei

2008-01-01

In this study, the authors investigated the extent to which factor and spatial structures of leisure interests (a) are similar to or distinct from the structure of vocational interests and (b) differ across 3 cohorts: college students (M[subscript age] = 19.6 years, SD = 1.23), working-age adults (M[subscript age] = 29.7, SD = 1.18), and retirees…

Structural optimization and structure-functional selectivity relationship studies of G protein-biased EP2 receptor agonists.

PubMed

Ogawa, Seiji; Watanabe, Toshihide; Moriyuki, Kazumi; Goto, Yoshikazu; Yamane, Shinsaku; Watanabe, Akio; Tsuboi, Kazuma; Kinoshita, Atsushi; Okada, Takuya; Takeda, Hiroyuki; Tani, Kousuke; Maruyama, Toru

2016-05-15

The modification of the novel G protein-biased EP2 agonist 1 has been investigated to improve its G protein activity and develop a better understanding of its structure-functional selectivity relationship (SFSR). The optimization of the substituents on the phenyl ring of 1, followed by the inversion of the hydroxyl group on the cyclopentane moiety led to compound 9, which showed a 100-fold increase in its G protein activity compared with 1 without any increase in β-arrestin recruitment. Furthermore, SFSR studies revealed that the combination of meta and para substituents on the phenyl moiety was crucial to the functional selectivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Electron diffraction and high-resolution electron microscopy studies on layered Li{sub 2−δ}(Mn{sub 1−x}Co{sub x}){sub 1+δ}O{sub 3}

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

Fujii, Hiroki, E-mail: fujii.hiroki@nims.go.jp; Ozawa, Kiyoshi; Mochiku, Takashi

2013-07-15

The structure of Li{sub 2}MnO{sub 3}–LiCoO{sub 2} solid solutions or Li{sub 2−δ}(Mn{sub 1−x}Co{sub x}){sub 1+δ}O{sub 3} (LMCO) which are promising lithium-battery cathodes was studied by high-resolution electron microscopy (HREM). X-ray diffraction (XRD) analyses indicate that Li{sub 1.6}Mn{sub 0.2}Co{sub 1.2}O{sub 3} and Li{sub 1.7}Mn{sub 0.4}Co{sub 0.9}O{sub 3} take a rhombohedral (R3-bar m space group) structure, whereas Li{sub 1.85}Mn{sub 0.7}Co{sub 0.45}O{sub 3} and Li{sub 1.95}Mn{sub 0.9}Co{sub 0.15}O{sub 3} take a monoclinic (C2/m) superstructure. HREM studies on those samples reveal that all of the observed crystallites in sample Li{sub 1.95}Mn{sub 0.9}Co{sub 0.15}O{sub 3} contain sharp stripe structures due to the planar defects alongmore » the c{sub h}-axis (stacking direction of the hexagonal close-packed planes) of parent rhombohedral R3-bar m cell. Such stripe structures become faint with increasing x, Co content. The origin of the planar defects is mainly attributed not to the different structures but to the different local orientations of the monoclinic LMCO. Local disordering of Li and (Mn,Co) in (Li,Mn,Co) planes is developed with increasing x and the structures are transformed from C2/m to R3-bar m. The alternative (Li,Mn,Co)-plane stacking structure, trigonal P3{sub 1}12 LMCO, was occasionally observed. However, only P3{sub 1}12 LMCO platelets with a thickness of a single unit cell were detected. - Graphical abstract: An HREM image for Li{sub 1.95}(Mn{sub 0.9}Co{sub 0.15})O{sub 3} and schematic drawings of C2/m and P3{sub 1}12 Li{sub 2}MnO{sub 3} projected along the various zone axes. Each projected unit cell is indicated by rectangles and parallelograms . - Highlights: • Li{sub 2−δ}(Mn{sub 1−x}Co{sub x}){sub 1+δ}O{sub 3} was studied by high-resolution electron microscopy (HREM). • HREM studies revealed a large amount of planar defects in C2/m Li{sub 1.95}Mn{sub 0.9}Co{sub 0.15}O{sub 3}. • The origin of the defects is the different local orientations of the C2/m platelets. • P3{sub 1}12 platelets with only single unit cell sequence were detected.« less

Soft X-ray photoemission study of Co2(Cr1-xFex)Ga Heusler compounds

NASA Astrophysics Data System (ADS)

Tsunekawa, Masanori; Hattori, Yoshiro; Sekiyama, Akira; Fujiwara, Hidenori; Suga, Shigemasa; Muro, Takayuki; Kanomata, Takeshi; Imada, Shin

2015-08-01

We have performed soft X-ray photoemission spectroscopy (SXPES) and X-ray absorption spectroscopy (XAS) of the Co-based Heusler compounds Co2(Cr1-xFex)Ga (x = 0.0, 0.4, and 1.0) in order to study their electronic structures. Band-structure calculation was carried out and compared with the experimental results. SXPES spectra show hν-dependence, revealing the contributions of the Co, Cr, and Fe 3d electronic states in the valence band. The band width observed by the SXPES seems to be narrower than that predicted by the band-structure calculation. XAS spectra depend strongly on the the value of x in Co2(Cr1-xFex)Ga. The electron correlation effects are found to be stronger as x changes from 0.0 to 1.0.

Evaluating models of object-decision priming: evidence from event-related potential repetition effects.

PubMed

Soldan, Anja; Mangels, Jennifer A; Cooper, Lynn A

2006-03-01

This study was designed to differentiate between structural description and bias accounts of performance in the possible/impossible object-decision test. Two event-related potential (ERP) studies examined how the visual system processes structurally possible and impossible objects. Specifically, the authors investigated the effects of object repetition on a series of early posterior components during structural (Experiment 1) and functional (Experiment 2) encoding and the relationship of these effects to behavioral measures of priming. In both experiments, the authors found repetition enhancement of the posterior N1 and N2 for possible objects only. In addition, the magnitude of the N1 repetition effect for possible objects was correlated with priming for possible objects. Although the behavioral results were more ambiguous, these ERP results fail to support bias models that hold that both possible and impossible objects are processed similarly in the visual system. Instead, they support the view that priming is supported by a structural description system that encodes the global 3-dimensional structure of an object.

Synthesis, characterization of (3E)-1-(6-chloro-2-methyl-4-phenyl quinolin-3-Yl)-3-aryl prop-2-en-1-ones through IR, NMR, single crystal X-ray diffraction and insights into their electronic structure using DFT calculations

NASA Astrophysics Data System (ADS)

Sarveswari, S.; Srikanth, A.; Arul Murugan, N.; Vijayakumar, V.; Jasinski, Jerry P.; Beauchesne, Hanna C.; Jarvis, Ethan E.

2015-02-01

3E-1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)-3-arylprop-2-en-1-ones were synthesized and characterized by FTIR, 1H NMR, 13C NMR, HSQC, DEPT-135. In addition the compound 3E-1-(6-chloro-2-methyl-4-phenylquinolin-3-yl)-3-(2,5-dimethoxyphenyl)prop-2-en-1-one was subjected to the single crystal X-ray diffraction studies. Density functional theory calculations were carried out for this chalcone and its derivatives to investigate into their electronic structure, chemical reactivity, linear and non-linear optical properties. The structure predicted from DFT for chalcone is in good agreement with the structure from XRD measurement.

Murine Leukemia Virus Reverse Transcriptase: Structural Comparison with HIV-1 Reverse Transcriptase

PubMed Central

Coté, Marie L.; Roth, Monica J.

2008-01-01

Recent X-ray crystal structure determinations of Moloney murine leukemia virus reverse transcriptase (MoMLV RT) have allowed for more accurate structure/function comparisons to HIV-1 RT than were formerly possible. Previous biochemical studies of MoMLV RT in conjunction with knowledge of sequence homologies to HIV-1 RT and overall fold similarities to RTs in general, provided a foundation upon which to build. In addition, numerous crystal structures of the MoMLV RT fingers/palm subdomain had also shed light on one of the critical functions of the enzyme, specifically polymerization. Now in the advent of new structural information, more intricate examination of MoMLV RT in its entirety can be realized, and thus the comparisons with HIV-1 RT may be more critically elucidated. Here, we will review the similarities and differences between MoMLV RT and HIV-1 RT via structural analysis, and propose working models for the MoMLV RT based upon that information. PMID:18294720

Cutting Edge: Molecular Structure of the IL-1R-Associated Kinase-4 Death Domain and Its Implications for TLR Signaling

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

Lasker, Michael V.; Gajjar, Mark M.; Nair, Satish K.

2010-07-19

IL-1R-associated kinase (IRAK) 4 is an essential component of innate immunity. IRAK-4 deficiency in mice and humans results in severe impairment of IL-1 and TLR signaling. We have solved the crystal structure for the death domain of Mus musculus IRAK-4 to 1.7 {angstrom} resolution. This is the first glimpse of the structural details of a mammalian IRAK family member. The crystal structure reveals a six-helical bundle with a prominent loop, which among IRAKs and Pelle, a Drosophila homologue, is unique to IRAK-4. This highly structured loop contained between helices two and three, comprises an 11-aa stretch. Although innate immune domainmore » recognition is thought to be very similar between Drosophila and mammals, this structural component points to a drastic difference. This structure can be used as a framework for future mutation and deletion studies and potential drug design.« less

Using Synchrotron Radiation-Based Infrared Microspectroscopy to Reveal Microchemical Structure Characterization: Frost Damaged Wheat vs. Normal Wheat

PubMed Central

Xin, Hangshu; Zhang, Xuewei; Yu, Peiqiang

2013-01-01

This study was conducted to compare: (1) protein chemical characteristics, including the amide I and II region, as well as protein secondary structure; and (2) carbohydrate internal structure and functional groups spectral intensities between the frost damaged wheat and normal wheat using synchrotron radiation-based Fourier transform infrared microspectroscopy (SR-FTIRM). Fingerprint regions of specific interest in our study involved protein and carbohydrate functional group band assignments, including protein amide I and II (ca. 1774–1475 cm−1), structural carbohydrates (SCHO, ca. 1498–1176 cm−1), cellulosic compounds (CELC, ca. 1295–1176 cm−1), total carbohydrates (CHO, ca. 1191–906 cm−1) and non-structural carbohydrates (NSCHO, ca. 954–809 cm−1). The results showed that frost did cause variations in spectral profiles in wheat grains. Compared with healthy wheat grains, frost damaged wheat had significantly lower (p < 0.05) spectral intensities in height and area ratios of amide I to II and almost all the spectral parameters of carbohydrate-related functional groups, including SCHO, CHO and NSCHO. Furthermore, the height ratio of protein amide I to the third peak of CHO and the area ratios of protein amide (amide I + II) to carbohydrate compounds (CHO and SCHO) were also changed (p < 0.05) in damaged wheat grains. It was concluded that the SR-FTIR microspectroscopic technique was able to examine inherent molecular structure features at an ultra-spatial resolution (10 × 10 μm) between different wheat grains samples. The structural characterization of wheat was influenced by climate conditions, such as frost damage, and these structural variations might be a major reason for the decreases in nutritive values, nutrients availability and milling and baking quality in wheat grains. PMID:23949633

Disulfide-stabilized Helical Hairpin Structure and Activity of a Novel Antifungal Peptide EcAMP1 from Seeds of Barnyard Grass (Echinochloa crus-galli)*

PubMed Central

Nolde, Svetlana B.; Vassilevski, Alexander A.; Rogozhin, Eugene A.; Barinov, Nikolay A.; Balashova, Tamara A.; Samsonova, Olga V.; Baranov, Yuri V.; Feofanov, Alexey V.; Egorov, Tsezi A.; Arseniev, Alexander S.; Grishin, Eugene V.

2011-01-01

This study presents purification, activity characterization, and 1H NMR study of the novel antifungal peptide EcAMP1 from kernels of barnyard grass Echinochloa crus-galli. The peptide adopts a disulfide-stabilized α-helical hairpin structure in aqueous solution and thus represents a novel fold among naturally occurring antimicrobial peptides. Micromolar concentrations of EcAMP1 were shown to inhibit growth of several fungal phytopathogens. Confocal microscopy revealed intensive EcAMP1 binding to the surface of fungal conidia followed by internalization and accumulation in the cytoplasm without disturbance of membrane integrity. Close spatial structure similarity between EcAMP1, the trypsin inhibitor VhTI from seeds of Veronica hederifolia, and some scorpion and cone snail toxins suggests natural elaboration of different functions on a common fold. PMID:21561864

Poor structural social support is associated with an increased risk of Type 2 diabetes mellitus: findings from the MONICA/KORA Augsburg cohort study.

PubMed

Altevers, J; Lukaschek, K; Baumert, J; Kruse, J; Meisinger, C; Emeny, R T; Ladwig, K H

2016-01-01

Several psychosocial factors have been shown to increase the risk of Type 2 diabetes mellitus. This study investigated the association between structural social support and incidence of Type 2 diabetes mellitus in men and women. Data were derived from three population-based MONICA/KORA surveys conducted in 1984-1995 in the Augsburg region (southern Germany) and followed up by 2009. The study population comprised 8952 participants (4669 men/4283 women) aged 30-74 years without diabetes at baseline. Structural social support was assessed using the Social Network Index. Sex-specific hazard ratios were estimated from Cox proportional hazard models. Within follow-up, 904 incident Type 2 diabetes mellitus cases (558 men, 346 women) were observed. Crude incidence rates for Type 2 diabetes mellitus per 10 000 person-years were substantially higher in poor compared with good structural social support (men: 94 vs. 69, women: 58 vs. 43). After adjustment for age, survey, parental history of diabetes, smoking status, alcohol intake, physical activity, hypertension, dyslipidaemia, BMI, education, sleep complaints and depressed mood, risk of Type 2 diabetes mellitus for participants with poor compared with good structural social support was 1.31 [95% confidence interval (CI) = 1.11-1.55] in men and 1.10 (95% CI = 0.88-1.37) in women. Stratified analyses revealed a hazard ratio of 1.50 (95% CI = 1.23-1.83) in men with a low level of education and 0.87 (95% CI = 0.62-1.22) in men with a high level of education (P for interaction: 0.0082). Poor structural social support is associated with Type 2 diabetes mellitus in men. This association is independent of risk factors at baseline and is particularly pronounced in men with a low level of education. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Structural, dielectric and magnetic studies of (x) Ni0.7Co0.1Cu0.2Fe2O4 + (1-x) BaTiO3 magnetoelectric composites

NASA Astrophysics Data System (ADS)

Khader, S. Abdul; Parveez, Asiya; Giridharan, N. V.; Sankarappa, T.

2016-05-01

The Magneto-electric composites (x) Ni0.7Co0.1Cu0.2Fe2O4 + (1-x) BaTiO3 (x=10%, 20% and 30%) were synthesized by sintering mixtures of highly ferroelectric BaTiO3 (BT) and highly magneto-strictive component Ni0.7Co0.1Cu0.2Fe2O4 (NCCF). The presences of constituent phases in magneto-electric composites were probed by X-ray diffraction (XRD) studies. The peaks observed in the XRD spectrum indicated spinel cubic structure for NCCF ferrite phase and tetragonal perovskite structure for BT and, both spinel and pervoskite structures for synthesized ME composites. Surface morphology of the samples has been investigated using Field Emission Scanning Electron Microscope (FESEM). Frequency and composition dependent dielectric properties of synthesized composites were measured from 100 Hz to 1 MHz at room temperature using Hioki LCR Hi-TESTER. The dielectric dispersion is observed at lower frequencies for the synthesized ME composites. The hysteresis behavior was studied to understand the magnetic ordering in the synthesized composites using a Vibrating Sample Magnetometer (VSM). It is observed that the values of saturation magnetization increases along with the ferrite content.

Structure Activity Relationship Studies of Flavonoids as Potent Inhibitors of Human Platelet 12-hLO, Reticulocyte 15-hLO-1 and Prostate Epithelial 15-hLO-2

PubMed Central

Vasquez-Martinez, Yesseny; Ohri, Rachana V.; Kenyon, Victor; Holman, Theodore R.; Sepúlveda-Boza, Silvia

2007-01-01

Human lipoxygenase (hLO) isozymes have been implicated in a number of disease states and have attracted much attention with respect to their inhibition. One class of inhibitors, the flavonoids, have been shown to be potent lipoxygenase inhibitors but their study has been restricted to those compounds found in nature, which have limited structural variability. We have therefore carried out a comprehensive study to determine the structural requirements for flavonoid potency and selectivity against platelet 12-hLO, reticulocyte 15-hLO-1 and prostate epithelial 15-hLO-2. We conclude from this study that catechols are essential for high potency, that isoflavones and isoflavanones tend to select against 12-hLO, that isoflavans tend to select against 15-hLO-1, but few flavonoids target 15-hLO-2. PMID:17869117

Recent structural studies on Dom34/aPelota and Hbs1/aEF1α: important factors for solving general problems of ribosomal stall in translation

PubMed Central

Kobayashi, Kan; Ishitani, Ryuichiro; Nureki, Osamu

2013-01-01

In the translation process, translating ribosomes usually move on an mRNA until they reach the stop codon. However, when ribosomes translate an aberrant mRNA, they stall. Then, ribosomes are rescued from the aberrant mRNA, and the aberrant mRNA is subsequently degraded. In eukaryotes, Pelota (Dom34 in yeast) and Hbs1 are responsible for solving general problems of ribosomal stall in translation. In archaea, aPelota and aEF1α, homologous to Pelota and Hbs1, respectively, are considered to be involved in that process. In recent years, great progress has been made in determining structures of Dom34/aPelota and Hbs1/aEF1α. In this review, we focus on the functional roles of Dom34/aPelota and Hbs1/aEF1α in ribosome rescue, based on recent structural studies of them. We will also present questions to be answered by future work. PMID:27493551

Synthesis, crystal structure and study of magnetocaloric effect and single molecular magnetic behaviour in discrete lanthanide complexes.

PubMed

Adhikary, Amit; Sheikh, Javeed Ahmad; Biswas, Soumava; Konar, Sanjit

2014-06-28

The synthesis, crystal structure and magnetic properties of four polynuclear lanthanide coordination complexes having molecular formulae, [Gd3(2)(1)L(H2O)8(Cl)](Cl)4·10H2O (1), [Dy3L(2)(1)(H2O)9](Cl)5·6H2O (2) [Gd6L(2)(2)(HCO2)4(μ3-OH)4(DMF)6(H2O)2](Cl)2·4H2O (3) and [Dy6L(2)(2)(HCO2)4(μ3-OH)4(DMF)6(H2O)2](Cl)2·4H2O (4) (where H2L(1) = bis[(2-pyridyl)methylene]pyridine-2,6-dicarbohydrazide and H4L(2) = bis[2-hydroxy-benzylidene]pyridine-2,6-dicarbohydrazide) are reported. Structural investigation by X-ray crystallography reveals similar structural features for complexes 1 and 2 and they exhibit butterfly like shapes of the molecules. Non-covalent interactions between the molecules create double helical arrangements for both molecules. Complexes 3 and 4 are isostructural and the core structures feature four distorted hemi-cubanes connected by vertex sharing. Magnetic studies unveil significant magnetic entropy changes for complexes 1, 3 and slow relaxation of magnetization for both dysprosium analogues 2 and 4.

The structure of neuronal calcium sensor-1 in solution revealed by molecular dynamics simulations.

PubMed

Bellucci, Luca; Corni, Stefano; Di Felice, Rosa; Paci, Emanuele

2013-01-01

Neuronal calcium sensor-1 (NCS-1) is a protein able to trigger signal transduction processes by binding a large number of substrates and re-shaping its structure depending on the environmental conditions. The X-ray crystal structure of the unmyristoilated NCS-1 shows a large solvent-exposed hydrophobic crevice (HC); this HC is partially occupied by the C-terminal tail and thus elusive to the surrounding solvent. We studied the native state of NCS-1 by performing room temperature molecular dynamics (MD) simulations starting from the crystal and the solution structures. We observe relaxation to a state independent of the initial structure, in which the C-terminal tail occupies the HC. We suggest that the C-terminal tail shields the HC binding pocket and modulates the affinity of NCS-1 for its natural targets. By analyzing the topology and nature of the inter-residue potential energy, we provide a compelling description of the interaction network that determines the three-dimensional organization of NCS-1.

Crystal Structure of the Complex Between Programmed Death-1 (PD-1) and its Ligand PD-L2

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

Lazar-Molnar,E.; Yan, Q.; Cao, E.

2008-01-01

Programmed death-1 (PD-1) is a member of the CD28/B7 superfamily that delivers negative signals upon interaction with its two ligands, PD-L1 or PD-L2. The high-resolution crystal structure of the complex formed by the complete ectodomains of murine PD-1 and PD-L2 revealed a 1:1 receptor:ligand stoichiometry and displayed a binding interface and overall molecular organization distinct from that observed in the CTLA-4/B7 inhibitory complexes. Furthermore, our structure also provides insights into the association between PD-1 and PD-L1 and highlights differences in the interfaces formed by the two PD-1 ligands (PD-Ls) Mutagenesis studies confirmed the details of the proposed PD-1/PD-L binding interfacesmore » and allowed for the design of a mutant PD-1 receptor with enhanced affinity. These studies define spatial and organizational constraints that control the localization and signaling of PD-1/PD-L complexes within the immunological synapse and provide a basis for manipulating the PD-1 pathways for immunotherapy.« less

A Mixed Methods Study Exploring the Factors and Behaviors That Affect Glycemic Control Following a Structured Education Program: The Irish DAFNE Study

ERIC Educational Resources Information Center

Casey, Dympna; O'Hara, Mary Clare; Meehan, Ben; Byrne, Molly; Dinneen, Sean F.; Murphy, Kathy

2016-01-01

Aim: To explain the factors affecting glycemic control (measured by HbA1c) following the Dose Adjustment for Normal Eating (DAFNE) program. Background: DAFNE is a structured education program designed to assist persons with type 1 diabetes mellitus achieve optimal glycemic control. However, not all participants reach this goal. Few studies…

A Taxometric Investigation of the Latent Structure of Worry: Dimensionality and Associations with Depression, Anxiety, and Stress

ERIC Educational Resources Information Center

Olatunji, Bunmi O.; Broman-Fulks, Joshua J.; Bergman, Shawn M.; Green, Bradley A.; Zlomke, Kimberly R.

2010-01-01

Worry has been described as a core feature of several disorders, particularly generalized anxiety disorder (GAD). The present study examined the latent structure of worry by applying 3 taxometric procedures (MAXEIG, MAMBAC, and L-Mode) to data collected from 2 large samples. Worry in the first sample (Study 1) of community participants (n = 1,355)…

Combined PDF and Rietveld studies of ADORable zeolites and the disordered intermediate IPC-1P.

PubMed

Morris, Samuel A; Wheatley, Paul S; Položij, Miroslav; Nachtigall, Petr; Eliášová, Pavla; Čejka, Jiří; Lucas, Tim C; Hriljac, Joseph A; Pinar, Ana B; Morris, Russell E

2016-09-28

The disordered intermediate of the ADORable zeolite UTL has been structurally confirmed using the pair distribution function (PDF) technique. The intermediate, IPC-1P, is a disordered layered compound formed by the hydrolysis of UTL in 0.1 M hydrochloric acid solution. Its structure is unsolvable by traditional X-ray diffraction techniques. The PDF technique was first benchmarked against high-quality synchrotron Rietveld refinements of IPC-2 (OKO) and IPC-4 (PCR) - two end products of IPC-1P condensation that share very similar structural features. An IPC-1P starting model derived from density functional theory was used for the PDF refinement, which yielded a final fit of Rw = 18% and a geometrically reasonable structure. This confirms the layers do stay intact throughout the ADOR process and shows PDF is a viable technique for layered zeolite structure determination.

The hemagglutinin structure of an avian H1N1 influenza A virus

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

Lin, Tianwei; Wang, Gengyan; Li, Anzhang

2009-09-15

The interaction between hemagglutinin (HA) and receptors is a kernel in the study of evolution and host adaptation of H1N1 influenza A viruses. The notion that the avian HA is associated with preferential specificity for receptors with Sia{alpha}2,3Gal glycosidic linkage over those with Sia{alpha}2,6Gal linkage is not all consistent with the available data on H1N1 viruses. By x-ray crystallography, the HA structure of an avian H1N1 influenza A virus, as well as its complexes with the receptor analogs, was determined. The structures revealed no preferential binding of avian receptor analogs over that of the human analog, suggesting that the HA/receptormore » binding might not be as stringent as is commonly believed in determining the host receptor preference for some subtypes of influenza viruses, such as the H1N1 viruses. The structure also showed difference in glycosylation despite the preservation of related sequences, which may partly contribute to the difference between structures of human and avian origin.« less

The NMR Structure of Human Obestatin in Membrane-Like Environments: Insights into the Structure-Bioactivity Relationship of Obestatin

PubMed Central

Gurriarán-Rodríguez, Uxía; Mosteiro, Carlos S.; Álvarez-Pérez, Juan C.; Otero-Alén, María; Camiña, Jesús P.; Gallego, Rosalía; García-Caballero, Tomás; Martín-Pastor, Manuel; Casanueva, Felipe F.; Jiménez-Barbero, Jesús; Pazos, Yolanda

2012-01-01

The quest for therapeutic applications of obestatin involves, as a first step, the determination of its 3D solution structure and the relationship between this structure and the biological activity of obestatin. On this basis, we have employed a combination of circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy, and modeling techniques to determine the solution structure of human obestatin (1). Other analogues, including human non-amidated obestatin (2) and the fragment peptides (6–23)-obestatin (3), (11–23)-obestatin (4), and (16–23)-obestatin (5) have also been scrutinized. These studies have been performed in a micellar environment to mimic the cell membrane (sodium dodecyl sulfate, SDS). Furthermore, structural-activity relationship studies have been performed by assessing the in vitro proliferative capabilities of these peptides in the human retinal pigmented epithelial cell line ARPE-19 (ERK1/2 and Akt phosphorylation, Ki67 expression, and cellular proliferation). Our findings emphasize the importance of both the primary structure (composition and size) and particular segments of the obestatin molecule that posses significant α-helical characteristics. Additionally, details of a species-specific role for obestatin have also been hypothesized by comparing human and mouse obestatins (1 and 6, respectively) at both the structural and bioactivity levels. PMID:23056203

The NMR structure of human obestatin in membrane-like environments: insights into the structure-bioactivity relationship of obestatin.

PubMed

Alén, Begoña O; Nieto, Lidia; Gurriarán-Rodríguez, Uxía; Mosteiro, Carlos S; Álvarez-Pérez, Juan C; Otero-Alén, María; Camiña, Jesús P; Gallego, Rosalía; García-Caballero, Tomás; Martín-Pastor, Manuel; Casanueva, Felipe F; Jiménez-Barbero, Jesús; Pazos, Yolanda

2012-01-01

The quest for therapeutic applications of obestatin involves, as a first step, the determination of its 3D solution structure and the relationship between this structure and the biological activity of obestatin. On this basis, we have employed a combination of circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy, and modeling techniques to determine the solution structure of human obestatin (1). Other analogues, including human non-amidated obestatin (2) and the fragment peptides (6-23)-obestatin (3), (11-23)-obestatin (4), and (16-23)-obestatin (5) have also been scrutinized. These studies have been performed in a micellar environment to mimic the cell membrane (sodium dodecyl sulfate, SDS). Furthermore, structural-activity relationship studies have been performed by assessing the in vitro proliferative capabilities of these peptides in the human retinal pigmented epithelial cell line ARPE-19 (ERK1/2 and Akt phosphorylation, Ki67 expression, and cellular proliferation). Our findings emphasize the importance of both the primary structure (composition and size) and particular segments of the obestatin molecule that posses significant α-helical characteristics. Additionally, details of a species-specific role for obestatin have also been hypothesized by comparing human and mouse obestatins (1 and 6, respectively) at both the structural and bioactivity levels.

Structural characterization of lignin from grape stalks (Vitis vinifera L.).

PubMed

Prozil, Sónia O; Evtuguin, Dmitry V; Silva, Artur M S; Lopes, Luísa P C

2014-06-18

The chemical structure of lignin from grape stalks, an abundant waste of winemaking, has been studied. The dioxane lignin was isolated from extractive- and protein-free grape stalks (Vitis vinifera L.) by modified acidolytic procedure and submitted to a structural analysis by wet chemistry (nitrobenzene and permanganate oxidation (PO)) and spectroscopic techniques. The results obtained suggest that grape stalk lignin is an HGS type with molar proportions of p-hydroxyphenyl (H), guaiacyl (G) and syringyl (S) units of 3:71:26. Structural analysis by (1)H and (13)C NMR spectroscopy and PO indicates the predominance of β-O-4' structures (39% mol) in grape stalk lignin together with moderate amounts of β-5', β-β, β-1', 5-5', and 4-O-5' structures. NMR studies also revealed that grape lignin should be structurally associated with tannins. The condensation degree of grape stalks lignin is higher than that of conventional wood lignins and lignins from other agricultural residues.

The early years of retroviral protease crystal structures.

PubMed

Miller, Maria

2010-01-01

Soon after its discovery, the attempts to develop anti-AIDS therapeutics focused on the retroviral protease (PR)-an enzyme used by lentiviruses to process the precursor polypeptide into mature viral proteins. An urgent need for the three-dimensional structure of PR to guide rational drug design prompted efforts to produce milligram quantities of this enzyme. However, only minute amounts of PR were present in the HIV-1 and HIV-2 viruses, and initial attempts to express this protein in bacteria were not successful. This review describes X-ray crystallographic studies of the retroviral proteases carried out at NCI-Frederick in the late 1980s and early 1990s and puts into perspective the crucial role that the total protein chemical synthesis played in unraveling the structure, mechanism of action, and inhibition of HIV-1 PR. Notably, the first fully correct structure of HIV-1 PR and the first cocrystal structure of its complex with an inhibitor (a substrate-derived, reduced isostere hexapeptide MVT-101) were determined using chemically synthesized protein. Most importantly, these sets of coordinates were made freely available to the research community and were used worldwide to solve X-ray structures of HIV-1 PR complexes with an array of inhibitors and set in motion a variety of theoretical studies. Publication of the structure of chemically synthesized HIV-1 PR complexed with MVT-101 preceded only by six years the approval of the first PR inhibitor as an anti-AIDS drug. Copyright (c) 2010 Wiley Periodicals, Inc.

Conformational Sampling and Binding Site Assessment of Suppression of Tumorigenicity 2 Ectodomain

PubMed Central

Yang, Chao-Yie; Delproposto, James; Chinnaswamy, Krishnapriya; Brown, William Clay; Wang, Shuying; Stuckey, Jeanne A.; Wang, Xinquan

2016-01-01

Suppression of Tumorigenicity 2 (ST2), a member of the interleukin-1 receptor (IL-1R) family, activates type 2 immune responses to pathogens and tissue damage via binding to IL-33. Dysregulated responses contribute to asthma, graft-versus-host and autoinflammatory diseases and disorders. To study ST2 structure for inhibitor development, we performed the principal component (PC) analysis on the crystal structures of IL1-1R1, IL1-1R2, ST2 and the refined ST2 ectodomain (ST2ECD) models, constructed from previously reported small-angle X-ray scattering data. The analysis facilitates mapping of the ST2ECD conformations to PC subspace for characterizing structural changes. Extensive coverage of ST2ECD conformations was then obtained using the accelerated molecular dynamics simulations started with the IL-33 bound ST2ECD structure as instructed by their projected locations on the PC subspace. Cluster analysis of all conformations further determined representative conformations of ST2ECD ensemble in solution. Alignment of the representative conformations with the ST2/IL-33 structure showed that the D3 domain of ST2ECD (containing D1-D3 domains) in most conformations exhibits no clashes with IL-33 in the crystal structure. Our experimental binding data informed that the D1-D2 domain of ST2ECD contributes predominantly to the interaction between ST2ECD and IL-33 underscoring the importance of the D1-D2 domain in binding. Computational binding site assessment revealed one third of the total detected binding sites in the representative conformations may be suitable for binding to potent small molecules. Locations of these sites include the D1-D2 domain ST2ECD and modulation sites conformed to ST2ECD conformations. Our study provides structural models and analyses of ST2ECD that could be useful for inhibitor discovery. PMID:26735493

Determining earthquake recurrence intervals from deformational structures in young lacustrine sediments

USGS Publications Warehouse

Sims, John D.

1975-01-01

Examination of the silty sediments in the lower Van Normal reservoir after the 1971 San Fernando, California earthquake revealed three zones of deformational structures in the 1-m-thick sequence of sediments exposed over about 2 km2 of the reservoir bottom. These zones are correlated with moderate earthquakes that shook the San Fernando area in 1930, 1952, and 1971. The success of this study, coupled with the experimental formation of deformational structures similar to those of the Van Norman reservoir, led to a search for similar structures in Pleistocene and Holocene lakes and lake sediments in other seismically active areas. Thus, studies have been started in Pleistocene and Holocene silty and sandy lake sediments in the Imperial Valley, southeastern California; Clear Lake, in northern California; and the Puget Sound area of Washington. The Imperial Valley study has yielded spectacular results: five zones of structures in the upper 10 m of Late Holocene sediments near Brawley have been correlated over an area of approximately 100 km2, using natural outcrops. These structures are similar to those of the Van Norman reservoir and are interpreted to represent at least five moderate to large earthquakes that affected the southern Imperial Valley area during Late Holocene time. The Clear Lake study has provided ambiguous results with respect to determination of earthquake recurrence intervals because the cores studied are in clayey rich in organic material sediments that have low liquefaction potential. A study of Late Pleistocene varved glacio-lacustrine sediments has been started in the Puget Sound area of Washington, and thirteen sites have been examined. One has yielded 18.75 m of sediments that contains 1,804 varves and fourteen deformed zones interpreted as being caused by earthquake, because they are identical to structures formed experimentally by simulated seismic shaking. Correlation of deformational structures with seismic events is based on:(1) proximity to presently active seismic zones;(2) presence of potentially liquefiable sediments;(3) similarity to structures formed experimentally;(4) small-scale internal structures within deformed zones that suggest liquefaction;(5) structures restricted to single stratigraphic intervals;(6) zones of structures correlatable over large areas; and(7) absence of detectable influence by slopes, slope failures, or other sedimentological, biological, or deformational processes.

Structural studies of TiC{sub 1−x}O{sub x} solid solution by Rietveld refinement and first-principles calculations

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

Jiang, Bo, E-mail: youqin5912@yahoo.com.cn; Hou, Na; Huang, Shanyan

2013-08-15

The lattice parameters, structural stability and electronic structure of titanium oxycarbides (TiC{sub 1−x}O{sub x}, 0≤x≤1) solid solution were investigated by Rietveld refinement and first-principles calculations. Series of TiC{sub 1−x}O{sub x} were precisely synthesized by sintering process under the vacuum. Rietveld refinement results of XRD patterns show the properties of continuous solid solution in TiC{sub 1−x}O{sub x} over the whole composition range. The lattice parameters vary from 0.4324 nm to 0.4194 nm decreasing with increasing oxygen concentration. Results of first-principles calculations reveal that the disorder C/O structure is stable than the order C/O structure. Further investigations of the vacancy in Ti{submore » 1−Va}(C{sub 1−x}O{sub x}){sub 1−Va} solid solution present that the structure of vacancy segregated in TiO-part is more stable than the disorder C/O structure, which can be ascribed to the Ti–Ti bond across O-vacancy and the charge redistributed around Ti-vacancy via the analysis of the electron density difference plots and PDOS. - Graphical abstract: XRD of series of titanium oxycarbides (TiC{sub 1−x}O{sub x}, 0≤x≤1) solid solution prepared by adjusting the proportion of TiO in the starting material. Highlights: • Titanium oxycarbides were obtained by sintering TiO and TiC under carefully controlled conditions. • Rietveld refinement results show continuous solid solution with FCC structure in TiC{sub 1−x}O{sub x}. • The disorder C/O structure is stable than the order C/O structure. • Introduction of vacancy segregated in TiO-part is more stable than disorder C/O structure. • Ti–Ti bond across O-vacancy and the charge redistributed around Ti-vacancy enhance structural stability.« less

Structural, magnetic and magnetocaloric properties of EuMnO3 perovskite manganite: A comprehensive MCE study

NASA Astrophysics Data System (ADS)

Phebe Kokila, I.; Kanagaraj, M.; Sathish Kumar, P.; Peter, Sebastian C.; Sekar, C.; Annal Therese, Helen

2018-02-01

Pervoskite manganite EuMnO3 synthesized by solid-state route was studied for their structural and magnetocaloric properties. EuMnO3 formed a single phase compound in orthorhombic crystal structure with a space group of Pbnm. The zero field cooling and field cooling magnetic responses exhibit an optimal Neel temperature (TN) of 57 K. A stronger magnetic coupling between the EuMnO3 particles are observed by a delay in reaching TN. The magnetocaloric effect analyzed extensively from the negative entropy (-ΔSm) change of 15.23 JKg-1K-1 for EuMnO3, exhibited a Relative Cooling Power (RCP) of ˜211 JKg-1 at 1.2 T proposing EuMnO3 as a potential magnetic refrigerant.

Structural insights into the interaction of IL-33 with its receptors.

PubMed

Liu, Xi; Hammel, Michal; He, Yanfeng; Tainer, John A; Jeng, U-Ser; Zhang, Linqi; Wang, Shuying; Wang, Xinquan

2013-09-10

Interleukin (IL)-33 is an important member of the IL-1 family that has pleiotropic activities in innate and adaptive immune responses in host defense and disease. It signals through its ligand-binding primary receptor ST2 and IL-1 receptor accessory protein (IL-1RAcP), both of which are members of the IL-1 receptor family. To clarify the interaction of IL-33 with its receptors, we determined the crystal structure of IL-33 in complex with the ectodomain of ST2 at a resolution of 3.27 Å. Coupled with structure-based mutagenesis and binding assay, the structural results define the molecular mechanism by which ST2 specifically recognizes IL-33. Structural comparison with other ligand-receptor complexes in the IL-1 family indicates that surface-charge complementarity is critical in determining ligand-binding specificity of IL-1 primary receptors. Combined crystallography and small-angle X-ray-scattering studies reveal that ST2 possesses hinge flexibility between the D3 domain and D1D2 module, whereas IL-1RAcP exhibits a rigid conformation in the unbound state in solution. The molecular flexibility of ST2 provides structural insights into domain-level conformational change of IL-1 primary receptors upon ligand binding, and the rigidity of IL-1RAcP explains its inability to bind ligands directly. The solution architecture of IL-33-ST2-IL-1RAcP complex from small-angle X-ray-scattering analysis resembles IL-1β-IL-1RII-IL-1RAcP and IL-1β-IL-1RI-IL-1RAcP crystal structures. The collective results confer IL-33 structure-function relationships, supporting and extending a general model for ligand-receptor assembly and activation in the IL-1 family.

Structured triglycerides were well tolerated and induced increased whole body fat oxidation compared with long-chain triglycerides in postoperative patients.

PubMed

Sandström, R; Hyltander, A; Körner, U; Lundholm, K

1995-01-01

It has been proposed, on the basis of animal experiments, that medium-chain triglycerides (MCT) may exert more favorable effects on whole body metabolism of injured animals than long-chain triglycerides (LCT). Therefore, the present study was designed to evaluate whether structured triglycerides are associated with increased whole body fat oxidation without promotion of ketogenesis in postoperative patients. A structured lipid emulsion (73403 Pharmacia, Sweden) containing medium- and long-chain fatty acids, esterified randomly to glycerol in a triglyceride structure, was used. Whole body fat oxidation was determined by indirect calorimetry in the postoperative period. Patients were randomized to receive structured lipids 1 day followed by LCT (Intralipid, Pharmacia) the next day or vice versa during 6 postoperative days. In part 1 of the study patients received fat at 1.0 g/kg per day in the presence of 80% of the basal requirement of nonprotein calories. In part 2 patients received fat at 1.5 g/kg per day in the presence of 120% of the nonprotein caloric requirement. Amino acids were always provided at 0.15 g N/kg per day. Structured lipids were not associated with any side effects, were rapidly cleared from the plasma compartment, and were rapidly oxidized without any significant hyperlipidemia or ketosis. Provision of structured lipids in the presence of excess of nonprotein calories (part 2) caused a significantly higher whole body fat oxidation (2.4 +/- 0.05 g/kg per day) compared with LCT provision (1.9 +/- 0.06 g/kg per day) (p < .0001) examined in the same patients. The results demonstrated for the first time in man that provision of structured triglycerides were associated with increased whole body fat oxidation in stressed postoperative patients, which is in line with the original metabolic and biochemical concept for structured triglycerides. The study provided evidence to support that structured lipids may represent a next generation of IV fat emulsions that may be clinically advantageous compared with conventional LCT emulsions in certain clinical conditions.

The CSM testbed matrix processors internal logic and dataflow descriptions

NASA Technical Reports Server (NTRS)

Regelbrugge, Marc E.; Wright, Mary A.

1988-01-01

This report constitutes the final report for subtask 1 of Task 5 of NASA Contract NAS1-18444, Computational Structural Mechanics (CSM) Research. This report contains a detailed description of the coded workings of selected CSM Testbed matrix processors (i.e., TOPO, K, INV, SSOL) and of the arithmetic utility processor AUS. These processors and the current sparse matrix data structures are studied and documented. Items examined include: details of the data structures, interdependence of data structures, data-blocking logic in the data structures, processor data flow and architecture, and processor algorithmic logic flow.

A computational study of the chemokine receptor CXCR1 bound with interleukin-8

NASA Astrophysics Data System (ADS)

Wang, Yang; Severin Lupala, Cecylia; Wang, Ting; Li, Xuanxuan; Yun, Ji-Hye; Park, Jae-hyun; Jin, Zeyu; Lee, Weontae; Tan, Leihan; Liu, Haiguang

2018-03-01

CXCR1 is a G-protein coupled receptor, transducing signals from chemokines, in particular the interleukin-8 (IL8) molecules. This study combines homology modeling and molecular dynamics simulation methods to study the structure of CXCR1-IL8 complex. By using CXCR4-vMIP-II crystallography structure as the homologous template, CXCR1-IL8 complex structure was constructed, and then refined using all-atom molecular dynamics simulations. Through extensive simulations, CXCR1-IL8 binding poses were investigated in detail. Furthermore, the role of the N-terminal of CXCR1 receptor was studied by comparing four complex models differing in the N-terminal sequences. The results indicate that the receptor N-terminal affects the binding of IL8 significantly. With a shorter N-terminal domain, the binding of IL8 to CXCR1 becomes unstable. The homology modeling and simulations also reveal the key receptor-ligand residues involved in the electrostatic interactions known to be vital for complex formation. Project supported by the National Natural Science Foundation of China (Grant Nos. 11575021, U1530401, and U1430237) and the National Research Foundation of Korea (Grant Nos. NRF-2017R1A2B2008483 and NRF-2016R1A6A3A04010213).

Application of amphipols for structure-functional analysis of TRP channels.

PubMed

Huynh, Kevin W; Cohen, Matthew R; Moiseenkova-Bell, Vera Y

2014-10-01

Amphipathic polymers (amphipols), such as A8-35 and SApol, are a new tool for stabilizing integral membrane proteins in detergent-free conditions for structural and functional studies. Transient receptor potential (TRP) ion channels function as tetrameric protein complexes in a diverse range of cellular processes including sensory transduction. Mammalian TRP channels share ~20 % sequence similarity and are categorized into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPA (ankyrin), TRPM (melastatin), TRPP (polycystin), and TRPML (mucolipin). Due to the inherent difficulties in purifying eukaryotic membrane proteins, structural studies of TRP channels have been limited. Recently, A8-35 was essential in resolving the molecular architecture of the nociceptor TRPA1 and led to the determination of a high-resolution structure of the thermosensitive TRPV1 channel by cryo-EM. Newly developed maltose-neopentyl glycol (MNG) detergents have also proven to be useful in stabilizing TRP channels for structural analysis. In this review, we will discuss the impacts of amphipols and MNG detergents on structural studies of TRP channels by cryo-EM. We will compare how A8-35 and MNG detergents interact with the hydrophobic transmembrane domains of TRP channels. In addition, we will discuss what these cryo-EM studies reveal on the importance of screening different types of surfactants toward determining high-resolution structures of TRP channels.

Application of amphipols for structure-functional analysis of TRP channels

PubMed Central

Huynh, Kevin W.; Cohen, Matthew R.; Moiseenkova-Bell, Vera Y.

2014-01-01

Amphipathic polymers (amphipols), such as A8-35 and SApol, are a new tool for stabilizing integral membrane proteins in detergent-free conditions for structural and functional studies. Transient receptor potential (TRP) ion channels function as tetrameric protein complexes in a diverse range of cellular processes including sensory transduction. Mammalian TRP channels share ~20% sequence similarity and are categorized into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPA (ankyrin), TRPM (melastatin), TRPP (polycystin), and TRPML (mucolipin). Due to the inherent difficulties in purifying eukaryotic membrane proteins, structural studies of TRP channels have been limited. Recently, A8-35 was essential in resolving the molecular architecture of the nociceptor TRPA1 and led to the determination of a high resolution structure of the thermosensitive TRPV1 channel by cryo-EM. Newly developed maltose-neopentyl glycol (MNG) detergents have also proven useful in stabilizing TRP channels for structural analysis. In this review, we will discuss the impact of amphipols and MNG detergents on structural studies of TRP channels by cryo-EM. We will compare how A8-35 and MNG detergents interact with the hydrophobic transmembrane (TM) domains of TRP channels. In addition, we will discuss what these cryo-EM studies reveal on the importance of screening different types of surfactants towards determining high resolution structures of TRP channels. PMID:24894720

Multivariate pattern analysis reveals subtle brain anomalies relevant to the cognitive phenotype in neurofibromatosis type 1.

PubMed

Duarte, João V; Ribeiro, Maria J; Violante, Inês R; Cunha, Gil; Silva, Eduardo; Castelo-Branco, Miguel

2014-01-01

Neurofibromatosis Type 1 (NF1) is a common genetic condition associated with cognitive dysfunction. However, the pathophysiology of the NF1 cognitive deficits is not well understood. Abnormal brain structure, including increased total brain volume, white matter (WM) and grey matter (GM) abnormalities have been reported in the NF1 brain. These previous studies employed univariate model-driven methods preventing detection of subtle and spatially distributed differences in brain anatomy. Multivariate pattern analysis allows the combination of information from multiple spatial locations yielding a discriminative power beyond that of single voxels. Here we investigated for the first time subtle anomalies in the NF1 brain, using a multivariate data-driven classification approach. We used support vector machines (SVM) to classify whole-brain GM and WM segments of structural T1 -weighted MRI scans from 39 participants with NF1 and 60 non-affected individuals, divided in children/adolescents and adults groups. We also employed voxel-based morphometry (VBM) as a univariate gold standard to study brain structural differences. SVM classifiers correctly classified 94% of cases (sensitivity 92%; specificity 96%) revealing the existence of brain structural anomalies that discriminate NF1 individuals from controls. Accordingly, VBM analysis revealed structural differences in agreement with the SVM weight maps representing the most relevant brain regions for group discrimination. These included the hippocampus, basal ganglia, thalamus, and visual cortex. This multivariate data-driven analysis thus identified subtle anomalies in brain structure in the absence of visible pathology. Our results provide further insight into the neuroanatomical correlates of known features of the cognitive phenotype of NF1. Copyright © 2012 Wiley Periodicals, Inc.

Ti K-edge EXAFS and XANES study on tektites from different strewnfields

NASA Astrophysics Data System (ADS)

Wang, L.; Furuta, T.; Okube, M.; Yoshiasa, A.

2011-12-01

The concentration and local structure of each element may have various kinds of information about the asteroid impact and mass extinction. Farges and Brown have discussed about the Ti local structure by XANES, and concluded that Ti in tektite occupies 4-coordinated site. EXAFS can be analyzed to give precise information about the distance from Ti to near neighbors. The XAFS measurement of Ti local structure was preformed at the beamline 9C of the Photon Factory in KEK, Tsukuba, Japan. The specimens of tektites are from different strewnfields, they are: indochinite, bediasite, hainanite, philippinite, australite and moldavite. Sample for comparison are Libya desert glass and suevite. The k3χ(k) function was transformed into the radial structure function (RSF) for Ti K-edge of six tektites. The RSF for the Ti atom in indochinite and bediasite are similar; hainanite, australite and philippinite are similar; and moldavite is discriminated from others. It indicates that they have the same local atomic environmental around the Ti atoms and extended structure respectively. Coordination numbers and radial structure function are determined by EXAFS analyses (Table 1). We classified the tektites in three types: in indochinite and bediasite, Ti occupies 4-coordinated tetrahedral site and Ti-O distances are 1.84-1.81 Å; in hainanite, australite and philippinite, Ti occupies 5-coordinated trigonal bi-pyramidal or tetragonal pyramidal site and Ti-O distances are 1.92-1.87 Å; in moldavite, Ti occupies the 6-coordinated octahedral site and Ti-O distance is 2.00-1.96 Å. Formation of tektites is related to the impact process. It is generally recognized that tektites were formed under higher temperature and high pressure. But through this study, local structures of Ti are differing in three strewnfields and even different locations of the same strewnfield. What caused the various local structures will be another topic of tektite studies. Local structure of Ti may be changed in the impact event and the following stage. Tektites splashed to the space and travel in several kinds of processes and routes, which lead to different temperature and pressure history. Local structure of Ti should be related with the temperature, pressure, quenching rate, sizes of impact meteorite and size of falling melts. [1] Koeberl. Ann.Rev.Earth Planet.Sci. 14, 323-350 (1986) [2] François Farges & Gordon E. Brown Jr Geochim. Cosmo. Acta.61, 1863-1870 (1997). [3]Paris, E., Dingwell, D., Seifert, F., Mottana, A. & Romano, C. (1994). Phys. Chem. Miner. 21, 520-525.
Table 1 Structure parameters determined by EXAFS

Structural Arrangement Trade Study. Volume 1: Reusable Hydrogen Composite Tank System (RHCTS) and Graphite Composite Primary Structures (GCPS). Executive summary

NASA Astrophysics Data System (ADS)

1995-03-01

This volume is the first of a three volume set that discusses the structural arrangement trade study plan that will identify the most suitable configuration for an SSTO winged vehicle capable of delivering 25,000 lbs to a 220 nm circular orbit at 51.6 deg inclination. The Reusable Hydrogen Composite Tank System (RHCTS), and Graphite Composite Primary Structures most suitable for intertank, wing and thrust structures are identified. This executive summary presents the trade study process, the selection process, requirements used, analysis performed and data generated. Conclusions and recommendations are also presented.

Structural Arrangement Trade Study. Volume 1: Reusable Hydrogen Composite Tank System (RHCTS) and Graphite Composite Primary Structures (GCPS). Executive summary

NASA Technical Reports Server (NTRS)

1995-01-01

This volume is the first of a three volume set that discusses the structural arrangement trade study plan that will identify the most suitable configuration for an SSTO winged vehicle capable of delivering 25,000 lbs to a 220 nm circular orbit at 51.6 deg inclination. The Reusable Hydrogen Composite Tank System (RHCTS), and Graphite Composite Primary Structures most suitable for intertank, wing and thrust structures are identified. This executive summary presents the trade study process, the selection process, requirements used, analysis performed and data generated. Conclusions and recommendations are also presented.

Estimation of population structure in coastal Douglas-fir [Pseudotsuga menziesii (Mirb.) Franco var. menziesii] using allozyme and microsatellite markers

Treesearch

Konstantin V. Krutovsky; John Bradley St. Clair; Robert Saich; Valerie D. Hipkins; David B. Neale

2009-01-01

Characterizing population structure using neutral markers is an important first step in association genetic studies in order to avoid false associations between phenotypes and genotypes that may arise from nonselective demographic factors. Population structure was studied in a wide sample of approximately 1,300 coastal Douglas-fir [Pseudotsuga menziesii...

Securing the Future: Retention Models in Community Colleges--Study of Community College Structures for Student Success (SCCSSS)

ERIC Educational Resources Information Center

College Board Advocacy & Policy Center, 2012

2012-01-01

The Study of Community College Structures for Student Success (SCCSSS) was launched in 2010 with three goals at its center: (1) To explore a set of promising institutional practices and organizational structures identified through theory and research as having the potential to support community college student success; (2) To present a synthesized…

Structures of EccB 1 and EccD 1 from the core complex of the mycobacterial ESX-1 type VII secretion system

DOE PAGES

Wagner, Jonathan M.; Chan, Sum; Evans, Timothy J.; ...

2016-02-27

The ESX-1 type VII secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. Despite its important role in disease very little is known about the molecular architecture of the ESX-1 secretion system. This study characterizes the structures of the soluble domains of two conserved core ESX-1 components – EccB 1 and EccD 1. The periplasmic domain of EccB 1 consists of 4 repeat domains and a central domain, which together form a quasi 2-fold symmetrical structure. Themore » repeat domains of EccB 1 are structurally similar to a known peptidoglycan binding protein suggesting a role in anchoring the ESX-1 system within the periplasmic space. The cytoplasmic domain of EccD 1 has a ubiquitin-like fold and forms a dimer with a negatively charged groove. In conclusion, these structures represent a major step towards resolving the molecular architecture of the entire ESX-1 assembly and may contribute to ESX-1 targeted tuberculosis intervention strategies.« less

Structures of EccB 1 and EccD 1 from the core complex of the mycobacterial ESX-1 type VII secretion system

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

Wagner, Jonathan M.; Chan, Sum; Evans, Timothy J.

The ESX-1 type VII secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. Despite its important role in disease very little is known about the molecular architecture of the ESX-1 secretion system. This study characterizes the structures of the soluble domains of two conserved core ESX-1 components – EccB 1 and EccD 1. The periplasmic domain of EccB 1 consists of 4 repeat domains and a central domain, which together form a quasi 2-fold symmetrical structure. Themore » repeat domains of EccB 1 are structurally similar to a known peptidoglycan binding protein suggesting a role in anchoring the ESX-1 system within the periplasmic space. The cytoplasmic domain of EccD 1 has a ubiquitin-like fold and forms a dimer with a negatively charged groove. In conclusion, these structures represent a major step towards resolving the molecular architecture of the entire ESX-1 assembly and may contribute to ESX-1 targeted tuberculosis intervention strategies.« less

Contribution of the mu loop to the structure and function of rat glutathione transferase M1-1

PubMed Central

Hearne, Jennifer L.; Colman, Roberta F.

2006-01-01

The “mu loop,” an 11-residue loop spanning amino acid residues 33–43, is a characteristic structural feature of the mu class of glutathione transferases. To assess the contribution of the mu loop to the structure and function of rat GST M1-1, amino acid residues 35–44 (35GDAPDYDRSQ44) were excised by deletion mutagenesis, resulting in the “Deletion Enzyme.” Kinetic studies reveal that the Km values of the Deletion Enzyme are markedly increased compared with those of the wild-type enzyme: 32-fold for 1-chloro-2,4-dinitrobenzene, 99-fold for glutathione, and 880-fold for monobromobimane, while the Vmax value for each substrate is increased only modestly. Results from experiments probing the structure of the Deletion Enzyme, in comparison with that of the wild-type enzyme, suggest that the secondary and quaternary structures have not been appreciably perturbed. Thermostability studies indicate that the Deletion Enzyme is as stable as the wild-type enzyme at 4°C and 10°C, but it rapidly loses activity at 25°C, unlike the wild-type enzyme. In the temperature range of 4°C through 25°C, the loss of activity of the Deletion Enzyme is not the result of a change in its structure, as determined by circular dichroism spectroscopy and sedimentation equilibrium centrifugation. Collectively, these results indicate that the mu loop is not essential for GST M1-1 to maintain its structure nor is it required for the enzyme to retain some catalytic activity. However, it is an important determinant of the enzyme's affinity for its substrates. PMID:16672236

Rationale and Design of the Echocardiographic Study of Hispanics/Latinos (ECHO-SOL).

PubMed

Rodriguez, Carlos J; Dharod, Ajay; Allison, Matthew A; Shah, Sanjiv J; Hurwitz, Barry; Bangdiwala, Shrikant I; Gonzalez, Franklyn; Kitzman, Dalane; Gillam, Linda; Spevack, Daniel; Dadhania, Rupal; Langdon, Sarah; Kaplan, Robert

2015-01-01

Information regarding the prevalence and determinants of cardiac structure and function (systolic and diastolic) among the various Hispanic background groups in the United States is limited. The Echocardiographic Study of Latinos (ECHO-SOL) ancillary study recruited 1,824 participants through a stratified-sampling process representative of the population-based Hispanic Communities Health Study - Study of Latinos (HCHS-SOL) across four sites (Bronx, NY; Chicago, Ill; San Diego, Calif; Miami, Fla). The HCHS-SOL baseline cohort did not include an echo exam. ECHO-SOL added the echocardiographic assessment of cardiac structure and function to an array of existing HCHS-SOL baseline clinical, psychosocial, and socioeconomic data and provides sufficient statistical power for comparisons among the Hispanic subgroups. Standard two-dimensional (2D) echocardiography protocol, including M-mode, spectral, color and tissue Doppler study was performed. The main objectives were to: 1) characterize cardiac structure and function and its determinants among Hispanics and Hispanic subgroups; and 2) determine the contributions of specific psychosocial factors (acculturation and familismo) to cardiac structure and function among Hispanics. We describe the design, methods and rationale of currently the largest and most comprehensive study of cardiac structure and function exclusively among US Hispanics. ECHO-SOL aims to enhance our understanding of Hispanic cardiovascular health as well as help untangle the relative importance of Hispanic subgroup heterogeneity and sociocultural factors on cardiac structure and function.

Structure of fructose bisphosphate aldolase from Bartonella henselae bound to fructose 1,6-bisphosphate.

PubMed

Gardberg, Anna; Abendroth, Jan; Bhandari, Janhavi; Sankaran, Banumathi; Staker, Bart

2011-09-01

Fructose bisphosphate aldolase (FBPA) enzymes have been found in a broad range of eukaryotic and prokaryotic organisms. FBPA catalyses the cleavage of fructose 1,6-bisphosphate into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. The SSGCID has reported several FBPA structures from pathogenic sources, including the bacterium Brucella melitensis and the protozoan Babesia bovis. Bioinformatic analysis of the Bartonella henselae genome revealed an FBPA homolog. The B. henselae FBPA enzyme was recombinantly expressed and purified for X-ray crystallographic studies. The purified enzyme crystallized in the apo form but failed to diffract; however, well diffracting crystals could be obtained by cocrystallization in the presence of the native substrate fructose 1,6-bisphosphate. A data set to 2.35 Å resolution was collected from a single crystal at 100 K. The crystal belonged to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a=72.39, b=127.71, c=157.63 Å. The structure was refined to a final free R factor of 22.2%. The structure shares the typical barrel tertiary structure and tetrameric quaternary structure reported for previous FBPA structures and exhibits the same Schiff base in the active site.

Recovery and fine structure variability of RGII sub-domains in wine (Vitis vinifera Merlot)

PubMed Central

Buffetto, F.; Ropartz, D.; Zhang, X. J.; Gilbert, H. J.; Guillon, F.; Ralet, M.-C.

2014-01-01

Background and Aims Rhamnogalacturonan II (RGII) is a structurally complex pectic sub-domain composed of more than 12 different sugars and 20 different linkages distributed in five side chains along a homogalacturonan backbone. Although RGII has long been described as highly conserved over plant evolution, recent studies have revealed variations in the structure of the polysaccharide. This study examines the fine structure variability of RGII in wine, focusing on the side chains A and B obtained after sequential mild acid hydrolysis. Specifically, this study aims to differentiate intrinsic structural variations in these RGII side chains from structural variations due to acid hydrolysis. Methods RGII from wine (Vitis vinifera Merlot) was sequentially hydrolysed with trifluoroacetic acid (TFA) and the hydrolysis products were separated by anion-exchange chromatography (AEC). AEC fractions or total hydrolysates were analysed by MALDI-TOF mass spectrometry. Key Results The optimal conditions to recover non-degraded side chain B, side chain A and RGII backbone were 0·1 m TFA at 40 °C for 16 h, 0·48 m TFA at 40 °C for 16 h (or 0·1 m TFA at 60 °C for 8 h) and 0·1 m TFA at 60 °C for 16 h, respectively. Side chain B was particularly prone to acid degradation. Side chain A and the RGII GalA backbone were partly degraded by 0·1 m TFA at 80 °C for 1–4 h. AEC allowed separation of side chain B, methyl-esterified side chain A and non-methyl-esterified side chain A. The structure of side chain A and the GalA backbone were highly variable. Conclusions Several modifications to the RGII structure of wine were identified. The observed dearabinosylation and deacetylation were primarily the consequence of acidic treatment, while variation in methyl-esterification, methyl-ether linkages and oxidation reflect natural diversity. The physiological significance of this variability, however, remains to be determined. PMID:24908680

X-ray structure of imidazolonepropionase from Agrobacterium tumefaciens at 1.87 Å resolution

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

Tyagi, Rajiv; Kumaran, Desigan; Burley, Stephen K.

2010-01-12

Histidine degradation in Agrobacterium tumefaciens involves four enzymes, including histidase (EC 4.3.1.3), urocanase (EC 4.2.1.49), imidazolonepropionase (EC 3.5.2.7), and N-formylglutamate amidohydrolase (EC 3.5.3.8). The third enzyme of the pathway, imidazolone-propionase, a 45.6 kDa protein, catalyzes conversion of imidazolone-5-propanoate to N-forminio-L-glutamate. Initial studies of the role of imidazolonepropionase in histidine degradation were published in 1953. Subsequent publications have been limited to enzyme kinetics, crystallization, and a recently reported structure determination. The imidazolonepropionases are members of metallodepenent-hydrolases (or amidohydroase) superfamily, which includs ureases, adenosine deaminases, phosphotriesterases, dihydroorotases, allantoinases, hydantoinases, adenine and cytosine deaminases, imidazolonepropionases, aryldial-kylphosphatases, chlorohydrolases, and formylmethanofuran dehydroases. Proteins belonging tomore » this large group share a common three-dimensional structural motif (an eightfold {alpha}/{beta} or TIM barrel) with similar active sites. Most superfamily members also share a conserved metal binding site, involving four histidine residues and one aspartic acid. Imidazolonepropionase is one of the targets selected for X-ray crystallpgrahpic structure determination by the New York Structural GenomiX Research Consortium (NYSGXRC) Target ID: 9252b to correlate the structure function relationship of poorly studied by important enzyme. Here they report the crystal structure of imidazolonepropionase from Agrobacterium tumefaciens determined at 1.87 {angstrom} resolution.« less

Structural studies of the polysaccharides from the lipopolysaccharides of Azospirillum brasilense Sp246 and SpBr14.

PubMed

Sigida, Elena N; Fedonenko, Yuliya P; Shashkov, Alexander S; Grinev, Vyacheslav S; Zdorovenko, Evelina L; Konnova, Svetlana A; Ignatov, Vladimir V; Knirel, Yuriy A

2014-10-29

Lipopolysaccharides from closely related Azospirillum brasilense strains, Sp246 and SpBr14, were obtained by phenol-water extraction. Mild acid hydrolysis of the lipopolysaccharides followed by GPC on Sephadex G-50 resulted in polysaccharide mixtures. On the basis of sugar and methylation analyses, Smith degradation and (1)H and (13)C NMR spectroscopy data, it was concluded that both bacteria possess the same two distinct polysaccharides having structures 1 and 2: [structure: see text]. Structure 1 has been reported earlier for a polysaccharide of A. brasilense 54 [Fedonenko et al., 2011] whereas to our knowledge structure 2 has not been hitherto found in bacterial polysaccharides. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structural variations of single and tandem mismatches in RNA duplexes: a joint MD simulation and crystal structure database analysis.

PubMed

Halder, Sukanya; Bhattacharyya, Dhananjay

2012-10-04

Internal loops within RNA duplex regions are formed by single or tandem basepairing mismatches with flanking canonical Watson-Crick basepairs on both sides. They are the most common motif observed in RNA secondary structures and play integral functional and structural roles. In this report, we have studied the structural features of 1 × 1, 2 × 2, and 3 × 3 internal loops using all-atom molecular dynamics (MD) simulation technique with explicit solvent model. As MD simulation is intricately dependent on the choice of force-field and these are often rather approximate, we have used both the most popular force-fields for nucleic acids-CHARMM27 and AMBER94-for a comparative analysis. We find that tandem noncanonical basepairs forming 2 × 2 and 3 × 3 internal loops are considerably more stable than the single mismatches forming 1 × 1 internal loops, irrespective of the force field. We have also analyzed crystal structure database to study the conservation of these helical fragments in the corresponding sets of RNA structures. We observe that the nature of stability in MD simulations mimic their fluctuating natures in crystal data sets also, probably indicating reliable natures of both the force fields to reproduce experimental results. We also notice significant structural changes in the wobble G:U basepairs present in these double helical stretches, leading to a biphasic stability for these wobble pairs to release the deformational strains introduced by internal loops within duplex regions.

Thiobenzamide: Structure of a free molecule as studied by gas electron diffraction and quantum chemical calculations

NASA Astrophysics Data System (ADS)

Kolesnikova, Inna N.; Putkov, Andrei E.; Rykov, Anatolii N.; Shishkov, Igor F.

2018-06-01

The equilibrium (re) molecular structure of thiobenzamide along with rh1 structure has been determined in gas phase using gas electron-diffraction (GED) at about 127 °C and quantum-chemical calculations (QC). Rovibrational distance corrections to the thermal averaged GED structure have been computed with anharmonic force constants obtained at the MP2/cc-pVTZ level of theory. According to the results of GED and QC thiobenzamide exists as mixture of two non-planar enantiomers of C1 symmetry. The selected equilibrium geometrical parameters of thiobenzamide (re, Å and ∠e, deg) are the following: (Cdbnd S) = 1.641(4), (Csbnd N) = 1.352(2), (Csbnd C) = 1.478(9), (Cdbnd C)av = 1.395(2), CCN = 114.7(5), CCS = 123.4(5), C2C1C7S = 31(4), C6C1C7N = 29(4). The structure of thiobenzamide in the gas phase is markedly different to that in the literature for the single crystal. The differences between the gas and the solid structures are ascribed to the presence of intermolecular hydrogen bonding in the solid phase.

Structural studies of series HIV-1 nonnucleoside reverse transcriptase inhibitors 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-benzimidazoles with different 4-substituents

NASA Astrophysics Data System (ADS)

Ziółkowska, Natasza E.; Michejda, Christopher J.; Bujacz, Grzegorz D.

2010-03-01

Over the past 10 years, several anti-viral drugs have become available to fight the HIV infection. Antiretroviral treatment reduces the mortality of AIDS. Nonnucleoside inhibitors of HIV-1 reverse transcriptase are specific and potentially nontoxic drugs against AIDS. The crystal structures of five nonnucleoside inhibitors of HIV-1 reverse transcriptase are presented here. The structural parameters, especially those describing the angular orientation of the π-electron systems and influencing biological activity, were determined for all of the investigated inhibitors. The chemical character and orientation of the substituent at C4 position of the benzimidazole moiety substantially influences the anti-viral activity. The structural data of the investigated inhibitors is a good basis for modeling enzyme-inhibitor interactions for structure-assisted drug design.

Effects of Mutations on Structure-Function Relationships of Matrix Metalloproteinase-1.

PubMed

Singh, Warispreet; Fields, Gregg B; Christov, Christo Z; Karabencheva-Christova, Tatyana G

2016-10-14

Matrix metalloproteinase-1 (MMP-1) is one of the most widely studied enzymes involved in collagen degradation. Mutations of specific residues in the MMP-1 hemopexin-like (HPX) domain have been shown to modulate activity of the MMP-1 catalytic (CAT) domain. In order to reveal the structural and conformational effects of such mutations, a molecular dynamics (MD) study was performed of in silico mutated residues in the X-ray crystallographic structure of MMP-1 complexed with a collagen-model triple-helical peptide (THP). The results indicate an important role of the mutated residues in MMP-1 interactions with the THP and communication between the CAT and the HPX domains. Each mutation has a distinct impact on the correlated motions in the MMP-1•THP. An increased collagenase activity corresponded to the appearance of a unique anti-correlated motion and decreased correlated motions, while decreased collagenase activity corresponded both to increased and decreased anti-correlated motions.

Solid-state NMR studies of metal-free SOD1 fibrillar structures.

PubMed

Banci, Lucia; Blaževitš, Olga; Cantini, Francesca; Danielsson, Jens; Lang, Lisa; Luchinat, Claudio; Mao, Jiafei; Oliveberg, Mikael; Ravera, Enrico

2014-06-01

Copper-zinc superoxide dismutase 1 (SOD1) is present in the protein aggregates deposited in motor neurons of amyotrophic lateral sclerosis (ALS) patients. ALS is a neurodegenerative disease that can be either sporadic (ca. 90%) or familial (fALS). The most widely studied forms of fALS are caused by mutations in the sequence of SOD1. Ex mortuo SOD1 aggregates are usually found to be amorphous. In vitro SOD1, in its immature reduced and apo state, forms fibrillar aggregates. Previous literature data have suggested that a monomeric SOD1 construct, lacking loops IV and VII, (apoSODΔIV-VII), shares the same fibrillization properties of apoSOD1, both proteins having the common structural feature of the central β-barrel. In this work, we show that structural information can be obtained at a site-specific level from solid-state NMR. The residues that are sequentially assignable are found to be located at the putative nucleation site for fibrillar species formation in apoSOD, as detected by other experimental techniques.

Characterization of KCNE1 inside Lipodisq Nanoparticles for EPR Spectroscopic Studies of Membrane Proteins.

PubMed

Sahu, Indra D; Zhang, Rongfu; Dunagan, Megan M; Craig, Andrew F; Lorigan, Gary A

2017-06-01

EPR spectroscopic studies of membrane proteins in a physiologically relevant native membrane-bound state are extremely challenging due to the complexity observed in inhomogeneity sample preparation and dynamic motion of the spin-label. Traditionally, detergent micelles are the most widely used membrane mimetics for membrane proteins due to their smaller size and homogeneity, providing high-resolution structure analysis by solution NMR spectroscopy. However, it is often difficult to examine whether the protein structure in a micelle environment is the same as that of the respective membrane-bound state. Recently, lipodisq nanoparticles have been introduced as a potentially good membrane mimetic system for structural studies of membrane proteins. However, a detailed characterization of a spin-labeled membrane protein incorporated into lipodisq nanoparticles is still lacking. In this work, lipodisq nanoparticles were used as a membrane mimic system for probing the structural and dynamic properties of the integral membrane protein KCNE1 using site-directed spin labeling EPR spectroscopy. The characterization of spin-labeled KCNE1 incorporated into lipodisq nanoparticles was carried out using CW-EPR titration experiments for the EPR spectral line shape analysis and pulsed EPR titration experiment for the phase memory time (T m ) measurements. The CW-EPR titration experiment indicated an increase in spectral line broadening with the addition of the SMA polymer which approaches close to the rigid limit at a lipid to polymer weight ratio of 1:1, providing a clear solubilization of the protein-lipid complex. Similarly, the T m titration experiment indicated an increase in T m values with the addition of SMA polymer and approaches ∼2 μs at a lipid to polymer weight ratio of 1:2. Additionally, CW-EPR spectral line shape analysis was performed on six inside and six outside the membrane spin-label probes of KCNE1 in lipodisq nanoparticles. The results indicated significant differences in EPR spectral line broadening and a corresponding inverse central line width between spin-labeled KCNE1 residues located inside and outside of the membrane for lipodisq nanoparticle samples when compared to lipid vesicle samples. These results are consistent with the solution NMR structure of KCNE1. This study will be beneficial for researchers working on studying the structural and dynamic properties of membrane proteins.

Aromatase inhibitory activity of 1,4-naphthoquinone derivatives and QSAR study

PubMed Central

Prachayasittikul, Veda; Pingaew, Ratchanok; Worachartcheewan, Apilak; Sitthimonchai, Somkid; Nantasenamat, Chanin; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong

2017-01-01

A series of 2-amino(chloro)-3-chloro-1,4-naphthoquinone derivatives (1-11) were investigated for their aromatase inhibitory activities. 1,4-Naphthoquinones 1 and 4 were found to be the most potent compounds affording IC50 values 5.2 times lower than the reference drug, ketoconazole. A quantitative structure-activity relationship (QSAR) model provided good predictive performance (R2CV = 0.9783 and RMSECV = 0.0748) and indicated mass (Mor04m and H8m), electronegativity (Mor08e), van der Waals volume (G1v) and structural information content index (SIC2) descriptors as key descriptors governing the activity. To investigate the effects of structural modifications on aromatase inhibitory activity, the model was employed to predict the activities of an additional set of 39 structurally modified compounds constructed in silico. The prediction suggested that the 2,3-disubstitution of 1,4-naphthoquinone ring with halogen atoms (i.e., Br, I and F) is the most effective modification for potent activity (1a, 1b and 1c). Importantly, compound 1b was predicted to be more potent than its parent compound 1 (11.90-fold) and the reference drug, letrozole (1.03-fold). The study suggests the 1,4-naphthoquinone derivatives as promising compounds to be further developed as a novel class of aromatase inhibitors. PMID:28827987

Z = 50 core stability in 110Sn from magnetic-moment and lifetime measurements

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

Kumbartzki, G. J.; Benczer-Koller, N.; Speidel, K. -H.

2016-04-18

In this study, the structure of the semimagic Sn50 isotopes were previously studied via measurements of B(E2;2 1 + → 0 1 +) and g factors of 2 1 + states. The values of the B(E2;2 1 +) in the isotopes below midshell at N = 66 show an enhancement in collectivity, contrary to predictions from shell-model calculations. This work presents the first measurement of the 2 1 + and 4 1 + states' magnetic moments in the unstable neutron-deficient 110Sn. The g factors provide complementary structure information to the interpretation of the observed B(E2) values.

Understanding the structural and energetic basis of PD-1 and monoclonal antibodies bound to PD-L1: A molecular modeling perspective.

PubMed

Shi, Danfeng; Zhou, Shuangyan; Liu, Xuewei; Zhao, Chenxi; Liu, Huanxiang; Yao, Xiaojun

2018-03-01

The inhibitors blocking the interaction between programmed cell death protein 1(PD-1) and programmed death-ligand 1(PD-L1) can activate the immune response of T cell and eliminate cancer cells. The crystallographic studies have provided structural insights of the interactive interfaces between PD-L1 and its protein ligands. However, the hotspot residues on PD-L1 as well as structural and energetic basis for different protein ligands still need to be further investigated. Molecular modeling methods including molecular dynamics simulation, per-residue free energy decomposition, virtual alanine scanning mutagenesis and residue-residue contact analysis were used to qualitatively and quantitatively analyze the interactions between PD-L1 and different protein ligands. The results of virtual alanine scanning mutagenesis suggest that Y56, Q66, M115, D122, Y123, R125 are the hotspot residues on PD-L1. The residue-residue contact analysis further shows that PD-1 interacts with PD-L1 mainly by F and G strands while monoclonal antibodies like avelumab and BMS-936559 mainly interact with PD-L1 by CDR2 and CDR3 loops of the heavy chain. A structurally similar β-hairpin peptide with 13 or 14 residues was extracted from each protein ligand and these β-hairpin peptides were found tightly binding to the putative hotspot residues on PD-L1. This study recognizes the hotspot residues on PD-L1 and uncovers the common structural and energetic basis of different protein ligands binding to PD-L1. These results will be valuable for the design of small molecule or peptide inhibitors targeting on PD-L1. Copyright © 2017 Elsevier B.V. All rights reserved.

X-ray diffraction of solid tin to 1.2 TPa

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

Lazicki, A.; Rygg, J. R.; Coppari, F.

2015-08-12

In this study, we report direct in situ measurements of the crystal structure of tin between 0.12 and 1.2 TPa, the highest stress at which a crystal structure has ever been observed. Using angle-dispersive powder x-ray diffraction, we find that dynamically compressed Sn transforms to the body-centered-cubic (bcc) structure previously identified by ambient-temperature quasistatic-compression studies and by zero-kelvin density-functional theory predictions between 0.06 and 0.16 TPa. However, we observe no evidence for the hexagonal close-packed (hcp) phase found by those studies to be stable above 0.16 TPa. Instead, our results are consistent with bcc up to 1.2 TPa. We conjecturemore » that at high temperature bcc is stabilized relative to hcp due to differences in vibrational free energy.« less

Crystallographic and magnetic structure of the novel compound ErGe 1.83

NASA Astrophysics Data System (ADS)

Oleksyn, O.; Schobinger-Papamantellos, P.; Ritter, C.; de Groot, C. H.; Buschow, K. H. J.

1997-02-01

The crystal structure and the magnetic ordering of the novel orthorhombic compound ErGe 2-x has been studied by neutron powder diffraction and magnetic measurements. The crystal structure belongs to the DyGe 1.85-type (space group Cmc2 1)·ErGe 2-x ( x = 0.17 (2)) orders antiferromagnetically below TN = 6 K and displays a metamagnetic behaviour. The magnetic cell has the same size as the chemical unit cell ( q = 0 ). The magnetic space group is Cmc2 1 (Sh 36173). At T = 1.5 K the magnetic moments of the two erbium sites have the same ordered magnetic moment values of 7.63 (6) μB/Er and are antiferromagnetically coupled leading to an uniaxial structure along the a direction.

A partially folded structure of amyloid-beta(1-40) in an aqueous environment.

PubMed

Vivekanandan, Subramanian; Brender, Jeffrey R; Lee, Shirley Y; Ramamoorthy, Ayyalusamy

2011-07-29

Aggregation of the Aβ(1-40) peptide is linked to the development of extracellular plaques characteristic of Alzheimer's disease. While previous studies commonly show the Aβ(1-40) is largely unstructured in solution, we show that Aβ(1-40) can adopt a compact, partially folded structure. In this structure (PDB ID: 2LFM), the central hydrophobic region of the peptide forms a 3(10) helix from H13 to D23 and the N- and C-termini collapse against the helix due to the clustering of hydrophobic residues. Helical intermediates have been predicted to be crucial on-pathway intermediates in amyloid fibrillogenesis, and the structure presented here presents a new target for investigation of early events in Aβ(1-40) fibrillogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

Polarized neutron scattering study of the multiple order parameter system NdB4

NASA Astrophysics Data System (ADS)

Metoki, N.; Yamauchi, H.; Matsuda, M.; Fernandez-Baca, J. A.; Watanuki, R.; Hagihala, M.

2018-05-01

Neutron polarization analysis has been carried out in order to clarify the magnetic structures of multiple order parameter f -electron system NdB4. We confirmed the noncollinear "all-in all-out" structure (Γ4) of the in-plane moment, which is in good agreement with our previous neutron powder diffraction study. We found that the magnetic moment along the c -axis mc showed diagonally antiferromagnetic structure (Γ10), inconsistent with previously reported "vortex" structure (Γ2). The microscopic mixture of these two structures with q⃗0=(0 ,0 ,0 ) appears in phase II and remains stable in phases III and IV, where an incommensurate modulation coexists. The unusual magnetic ordering is phenomenologically understood via Landau theory with the primary order parameter Γ4 coupled with higher-order secondary order parameter Γ10. The magnetic moments were estimated to be 1.8 ±0.2 and 0.2 ±0.05 μB at T =7.5 K for Γ4 and Γ10, respectively. We also found a long-period incommensurate modulation of the q⃗1=(0 ,0 ,1 /2 ) antiferromagnetic structure of mc with the propagation q⃗s 1=(0.14 ,0.14 ,0.1 ) and q⃗s 2=(0.2 ,0 ,0.1 ) in phase III and IV, respectively. The amplitude of sinusoidal modulation was about mc=1.0 ±0.2 μB at T =1.5 K. The local (0 ,0 ,1 /2 ) structure consists of in-plane ferromagnetic and out-of-plane antiferromagnetic coupling of mc, opposite to the coexisting Γ10. The mc of Γ10 is significantly enhanced up to 0.6 μB at T =1.5 K, which is accompanied by the incommensurate modulations. The Landau phenomenological approach indicates that the higher-order magnetic and/or multipole interactions based on the pseudoquartet f -electron state play important roles.

Study of cobalt effect on structural and optical properties of Dy doped ZnO nanoparticles

NASA Astrophysics Data System (ADS)

Kumar, Pawan; Pandey, Praveen C.

2018-05-01

The present study has been carried out to investigate the effect of Co doping on structural and optical properties of Dy doped ZnO nanoparticles. We have prepared pure Zinc oxide, Dy (1%) doped ZnO and Dy (1%) doped ZnO co-doped with Co(2%) with the help of simple sol-gel combustion method. The structural analysis carried out using X-ray diffraction spectra (XRD) indicates substitution of Dy and Co at Zn site of ZnO crystal structure and hexagonal crystal structure without any secondary phase formation in all the samples. The surface morphology was analyzed by transmission electron microscopy (TEM). Absorption study indicates that Dy doping causes a small shift in band edge, while Co co-doping results significant change is absorption edge as well as introduce defect level absorption in the visible region. The band gap of samples decreases due to Dy and Co doping, which can be attributed to defect level formation below the conduction band in the system.

1-Pentyl-3-(4-methoxy-1-naphthoyl)indole and 2-(2-methoxy-phenyl)-1-(1-pentyl-1 H-indol-3-yl)-ethanone: X-ray structures and computational studies

NASA Astrophysics Data System (ADS)

Nycz, Jacek E.; Malecki, Grzegorz; Zawiazalec, Marcin; Pazdziorek, Tadeusz; Skop, Patrycja

2010-12-01

1-Pentyl-3-(4-methoxy-1-naphthoyl)indole (shortly named JWH-081) ( 1) and 2-(2-methoxy-phenyl)-1-(1-pentyl-1 H-indol-3-yl)-ethanone (shortly named JWH-250) ( 2), are examples of cannabinoids which were characterized by FTIR, UV-Vis, multinuclear NMR spectroscopy and single crystal X-ray diffraction method. The geometries of the studied compounds were optimized in singlet states using the density functional theory (DFT) method with B3LYP functional. Electronic spectra were calculated by TDDFT method. In general, the predicted bond lengths and angles are in a good agreement with the values based on the X-ray crystal structure data.

Two rhodamine 6G derivative compounds: a structural and fluorescence single-crystal study.

PubMed

Di Paolo, Matias; Bossi, Mariano L; Baggio, Ricardo; Suarez, Sebastián A

2016-10-01

The synthesis, characterization, structural analysis and fluorescence properties of two rhodamine 6G derivatives are described, namely a propargylamine derivative, 3',6'-bis(ethylamino)-2',7'-dimethyl-2-(methylcyanide)spiro[isoindole-1,9'-xanthen]-3(2H)-one (I), and a γ-aminobutyric acid (GABA) derivative, 3',6'-bis(ethylamino)-2',7'-dimethyl-3-oxospiro[isoindole-1,9'-xanthen]-2(3H)-yl)butyricacid (II). Both structures are compared with four similar ones from the Cambridge Structural Database (CSD), and the interactions involved in the stabilization are analyzed using the atoms in molecules (AIM) theory. Finally, a single-crystal in-situ reaction study is presented, carried out by fluorescence methods, which enabled the `opening' of the spirolactam ring in the solid phase.

Electronic structure studies of a clock-reconstructed Al/Pd(1 0 0) surface alloy

NASA Astrophysics Data System (ADS)

Kirsch, Janet E.; Tainter, Craig J.

We have employed solid-state Fenske-Hall band structure calculations to examine the electronic structure of Al/Pd(1 0 0), a surface alloy that undergoes a reconstruction, or rearrangement, of the atoms in the top few surface layers. Surface alloys are materials that consist primarily of a single elemental metal, but which have a bimetallic surface composition that is only a few atomic layers in thickness. The results of this study indicate that reconstruction into a clock configuration simultaneously optimizes the intralayer bonding within the surface plane and the bonding between the first and second atomic layers. These results also allow us to examine the fundamental relationship between the electronic and physical structures of this reconstructed surface alloy.

Electron holography study of magnetization behavior in the writer pole of a perpendicular magnetic recording head by a 1 MV transmission electron microscope.

PubMed

Hirata, Kei; Ishida, Yoichi; Akashi, Tetsuya; Shindo, Daisuke; Tonomura, Akira

2012-01-01

The magnetic domain structure of the writer poles of perpendicular magnetic recording heads was studied using electron holography. Although the domain structure of a 100-nm-thick writer pole could be observed with a 300 kV transmission electron microscope, that of the 250-nm-thick writer pole could not be analyzed due to the limited transmission capability of the instrument. On the other hand, the detailed domain structure of the 250-nm-thick writer pole was successfully analyzed by a 1 MV electron microscope using its high transmission capability. The thickness and material dependency of the domain structure of a writer pole were discussed.

Chemical construction and structural permutation of neurotoxic natural product, antillatoxin: importance of the three-dimensional structure of the bulky side chain

PubMed Central

INOUE, Masayuki

2014-01-01

Antillatoxin 1 is a unique natural product that displays potent neurotoxic and neuritogenic activities through activation of voltage-gated sodium channels. The peptidic macrocycle of 1 was attached to a side chain with an exceptionally high degree of methylation. In this review, we discuss the total synthesis and biological evaluation of 1 and its analogues. First we describe an efficient synthetic route to 1. This strategy enabled the unified preparation of nine side chain analogues. Structure-activity relationship studies of these analogues revealed that subtle side chain modification leads to dramatic changes in activity, and detailed structural analyses indicated the importance of the overall size and three dimensional shape of the side chain. Based on these data, we designed and synthesized a photoresponsive analogue, proving that the activity of 1 was modulated via a photochemical reaction. The knowledge accumulated through these studies will be useful for the rational design of new tailor-made molecules to control the function and behavior of ion channels. PMID:24522155

Inferring mechanisms of copy number change from haplotype structures at the human DEFA1A3 locus.

PubMed

Black, Holly A; Khan, Fayeza F; Tyson, Jess; Al Armour, John

2014-07-21

The determination of structural haplotypes at copy number variable regions can indicate the mechanisms responsible for changes in copy number, as well as explain the relationship between gene copy number and expression. However, obtaining spatial information at regions displaying extensive copy number variation, such as the DEFA1A3 locus, is complex, because of the difficulty in the phasing and assembly of these regions. The DEFA1A3 locus is intriguing in that it falls within a region of high linkage disequilibrium, despite its high variability in copy number (n = 3-16); hence, the mechanisms responsible for changes in copy number at this locus are unclear. In this study, a region flanking the DEFA1A3 locus was sequenced across 120 independent haplotypes with European ancestry, identifying five common classes of DEFA1A3 haplotype. Assigning DEFA1A3 class to haplotypes within the 1000 Genomes project highlights a significant difference in DEFA1A3 class frequencies between populations with different ancestry. The features of each DEFA1A3 class, for example, the associated DEFA1A3 copy numbers, were initially assessed in a European cohort (n = 599) and replicated in the 1000 Genomes samples, showing within-class similarity, but between-class and between-population differences in the features of the DEFA1A3 locus. Emulsion haplotype fusion-PCR was used to generate 61 structural haplotypes at the DEFA1A3 locus, showing a high within-class similarity in structure. Structural haplotypes across the DEFA1A3 locus indicate that intra-allelic rearrangement is the predominant mechanism responsible for changes in DEFA1A3 copy number, explaining the conservation of linkage disequilibrium across the locus. The identification of common structural haplotypes at the DEFA1A3 locus could aid studies into how DEFA1A3 copy number influences expression, which is currently unclear.

Structures and biosynthesis of the N- and O-glycans of recombinant human oviduct-specific glycoprotein expressed in human embryonic kidney cells.

PubMed

Yang, Xiaojing; Tao, Shujuan; Orlando, Ron; Brockhausen, Inka; Kan, Frederick W K

2012-09-01

Oviduct-specific glycoprotein (OVGP1) is a major mucin-like glycoprotein synthesized and secreted exclusively by non-ciliated secretory cells of mammalian oviduct. In vitro functional studies showed that OVGP1 plays important roles during fertilization and early embryo development. We have recently produced recombinant human oviduct-specific glycoprotein (rhOVGP1) in human embryonic kidney 293 (HEK293) cells. The present study was undertaken to characterize the structures and determine the biosynthetic pathways of the N- and O-glycans of rhOVGP1. Treatment of the stable rhOVGP1-expressing HEK293 cells with either GalNAcα-Bn to block O-glycan extension, tunicamycin to block N-glycosylation, or neuraminidase increased the electrophoretic mobility of rhOVGP1. A detailed analysis of O- and N-linked glycans of rhOVGP1 by mass spectrometry showed a broad range of many simple and complex glycan structures. In order to identify the enzymes involved in the glycosylation of rhOVGP1, we assayed glycosyltransferase activities involved in the assembly of O- and N-glycans in HEK293 cells, and compared these to those from the immortalized human oviductal cells (OE-E6/E7). Our results demonstrate that HEK293 and OE-E6/E7 cells exhibit a similar spectrum of glycosyltransferase activities that can synthesize elongated and sialylated O-glycans with core 1 and 2 structures, as well as complex multiantennary N-glycans. It is anticipated that the knowledge gained from the present study will facilitate future studies of the role of the glycans of human OVGP1 in fertilization and early embryo development. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

Crystallographic analysis of NHERF1–PLCβ3 interaction provides structural basis for CXCR2 signaling in pancreatic cancer

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

Jiang, Yuanyuan; Wang, Shuo; Holcomb, Joshua

2014-04-04

Highlights: • CXCR2–NHERF1–PLCβ3 complex regulates CXCR2 signaling in pancreatic cancer. • The crystal structure of the NHERF1 PDZ1 domain in complex with PLCβ3. • The structure reveals specificity determinants of PDZ1–PLCβ3 interaction. • Endogenous PLCβ3 in pancreatic cancer cells interacts with both PDZ1 and PDZ2. • Structural basis of the PDZ1–PLCβ3 interaction is valuable in selective drug design. - Abstract: The formation of CXCR2–NHERF1–PLCβ3 macromolecular complex in pancreatic cancer cells regulates CXCR2 signaling activity and plays an important role in tumor proliferation and invasion. We previously have shown that disruption of the NHERF1-mediated CXCR2–PLCβ3 interaction abolishes the CXCR2 signaling cascademore » and inhibits pancreatic tumor growth in vitro and in vivo. Here we report the crystal structure of the NHERF1 PDZ1 domain in complex with the C-terminal PLCβ3 sequence. The structure reveals that the PDZ1–PLCβ3 binding specificity is achieved by numerous hydrogen bonds and hydrophobic contacts with the last four PLCβ3 residues contributing to specific interactions. We also show that PLCβ3 can bind both NHERF1 PDZ1 and PDZ2 in pancreatic cancer cells, consistent with the observation that the peptide binding pockets of these PDZ domains are highly structurally conserved. This study provides an understanding of the structural basis for the PDZ-mediated NHERF1–PLCβ3 interaction that could prove valuable in selective drug design against CXCR2-related cancers.« less

Novel pyrazolyl-s-triazine derivatives, molecular structure and antimicrobial activity

NASA Astrophysics Data System (ADS)

Sharma, Anamika; Ghabbour, Hazem; Khan, Shams Tabrez; de la Torre, Beatriz G.; Albericio, Fernando; El-Faham, Ayman

2017-10-01

A new series of pyrazole-containing s-triazine derivatives were synthesized by reaction of the corresponding s-triazinyl hydrazine derivatives with acetylacetone in the presence of HClO4 or DMF/TEA. The former method allowed the preparation of the target products with higher yields. All compounds were fully characterized. X-ray single crystal diffraction for two representative compounds (4-(4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-yl)morpholine and N-benzyl-4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-(piperidin-1-yl)-1,3,5-triazin-2-amine) was studied and the molecular structures were optimized using the DFT/B3LYP method. The structures were found to be in agreement with X-ray structures. The antimicrobial and antifungal activity of the prepared compounds were tested against the growth of several microorganisms.

Quaternary schematics for property engineering of CdSe thin films

NASA Astrophysics Data System (ADS)

Chavan, G. T.; Pawar, S. T.; Prakshale, V. M.; Sikora, A.; Pawar, S. M.; Chaure, N. B.; Kamble, S. S.; Maldar, N. N.; Deshmukh, L. P.

2017-12-01

The synthesis of quaternary Cd1-xZnxSySe1-y (0 ≤ x = y ≤ 0.35) thin films was done through indigenously developed chemical solution growth process. As-obtained thin films were subjected to the physical, chemical, structural and optical characterizations. The nearly hydrophobic nature of the as-deposited films except binary CdSe was observed through the wettability studies. The colorimetric studies supported a change in physical color attributes. The elemental analysis done confirmed the formation of Cd(Zn, S)Se and the chemical states of constituent elements as Cd2+, Zn2+, S2- and Se2-. Structural assessment suggested the formation of the polycrystalline quaternary phase of the hexagonal wurtzite structure. The Raman spectroscopy was also employed for the confirmation studies on Cd1-xZnxSySe1-y thin films. Morphological observations indicated microstructural transformation from an aggregated bunch of nano-sized globular grains into a rhomboid network of petal/flakes like crystallites. The atomic force micrographs (AFM) revealed the enhancement in the hillock structures. From advanced AFM characterizations, we observed that the CdSe thin film has leptokurtic (Sku = 3.23) surface, whereas, quaternary Cd(Zn, S)Se films have platykurtic (Sku < 3) surface. The orientation of the surface morphology was observed through the angular spectrum studies. The optical absorption studies revealed direct allowed transition for the films with a continuous modulation of the energy bandgap from 1.8 eV to 2.31 eV.

Comparative structural analysis of cytidine, ethenocytidine and their protonated salts III. 1H, 13C and 15N NMR studies at natural isotope abundance.

PubMed Central

Kozerski, L; Sierzputowska-Gracz, H; Krzyzosiak, W; Bratek-Wiewiórowska, M; Jaskólski, M; Wiewiórowski, M

1984-01-01

The 1H, 13C, 15N NMR spectra of cytidine /Cyd/, ethenocytidine /epsilon Cyd/ and their hydrochlorides /Cyd X HC1/ and /epsilon Cyd X HC1/ have been analysed to compare structural differences observed in solution with those existing in the crystalline state. The effects of ethenobridging and protonation of the hertero-aromatic base on the intramolecular stereochemistry, intermolecular interactions and electronic structure of the whole molecule are discussed on the basis of the NMR studies in DMSO solutions. Particular interest is devoted to the discussion of the conformation of the ribose ring, the presence of the intramolecular C-5'-0...H-6-C hydrogen bond, unambiguous assignment of the site of protonation, the mechanism of the 5C-H deuterium exchange in Cyd X HC1, and the intermolecular interactions in solution. PMID:6701098

Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases.

PubMed

Triki, Dhoha; Billot, Telli; Visseaux, Benoit; Descamps, Diane; Flatters, Delphine; Camproux, Anne-Claude; Regad, Leslie

2018-04-10

HIV-2 protease (PR2) is naturally resistant to most FDA (Food and Drug Administration)-approved HIV-1 protease inhibitors (PIs), a major antiretroviral class. In this study, we compared the PR1 and PR2 binding pockets extracted from structures complexed with 12 ligands. The comparison of PR1 and PR2 pocket properties showed that bound PR2 pockets were more hydrophobic with more oxygen atoms and fewer nitrogen atoms than PR1 pockets. The structural comparison of PR1 and PR2 pockets highlighted structural changes induced by their sequence variations and that were consistent with these property changes. Specifically, substitutions at residues 31, 46, and 82 induced structural changes in their main-chain atoms that could affect PI binding in PR2. In addition, the modelling of PR1 mutant structures containing V32I and L76M substitutions revealed a cooperative mechanism leading to structural deformation of flap-residue 45 that could modify PR2 flexibility. Our results suggest that substitutions in the PR1 and PR2 pockets can modify PI binding and flap flexibility, which could underlie PR2 resistance against PIs. These results provide new insights concerning the structural changes induced by PR1 and PR2 pocket variation changes, improving the understanding of the atomic mechanism of PR2 resistance to PIs.

Patterns of structural dynamics in RACK1 protein retained throughout evolution: A hydrogen-deuterium exchange study of three orthologs

PubMed Central

Tarnowski, Krzysztof; Fituch, Kinga; Szczepanowski, Roman H; Dadlez, Michal; Kaus-Drobek, Magdalena

2014-01-01

RACK1 is a member of the WD repeat family of proteins and is involved in multiple fundamental cellular processes. An intriguing feature of RACK1 is its ability to interact with at least 80 different protein partners. Thus, the structural features enabling such interactomic flexibility are of great interest. Several previous studies of the crystal structures of RACK1 orthologs described its detailed architecture and confirmed predictions that RACK1 adopts a seven-bladed β-propeller fold. However, this did not explain its ability to bind to multiple partners. We performed hydrogen-deuterium (H-D) exchange mass spectrometry on three orthologs of RACK1 (human, yeast, and plant) to obtain insights into the dynamic properties of RACK1 in solution. All three variants retained similar patterns of deuterium uptake, with some pronounced differences that can be attributed to RACK1's divergent biological functions. In all cases, the most rigid structural elements were confined to B-C turns and, to some extent, strands B and C, while the remaining regions retained much flexibility. We also compared the average rate constants for H-D exchange in different regions of RACK1 and found that amide protons in some regions exchanged at least 1000-fold faster than in others. We conclude that its evolutionarily retained structural architecture might have allowed RACK1 to accommodate multiple molecular partners. This was exemplified by our additional analysis of yeast RACK1 dimer, which showed stabilization, as well as destabilization, of several interface regions upon dimer formation. PMID:24591271

Structural interactions between lipids, water and S1-S4 voltage-sensing domains.

PubMed

Krepkiy, Dmitriy; Gawrisch, Klaus; Swartz, Kenton J

2012-11-02

Membrane proteins serve crucial signaling and transport functions, yet relatively little is known about their structures in membrane environments or how lipids interact with these proteins. For voltage-activated ion channels, X-ray structures suggest that the mobile voltage-sensing S4 helix would be exposed to the membrane, and functional studies reveal that lipid modification can profoundly alter channel activity. Here, we use solid-state NMR to investigate structural interactions of lipids and water with S1-S4 voltage-sensing domains and to explore whether lipids influence the structure of the protein. Our results demonstrate that S1-S4 domains exhibit extensive interactions with lipids and that these domains are heavily hydrated when embedded in a membrane. We also find evidence for preferential interactions of anionic lipids with S1-S4 domains and that these interactions have lifetimes on the timescale of ≤ 10(-3)s. Arg residues within S1-S4 domains are well hydrated and are positioned in close proximity to lipids, exhibiting local interactions with both lipid headgroups and acyl chains. Comparative studies with a positively charged lipid lacking a phosphodiester group reveal that this lipid modification has only modest effects on the structure and hydration of S1-S4 domains. Taken together, our results demonstrate that Arg residues in S1-S4 voltage-sensing domains reside in close proximity to the hydrophobic interior of the membrane yet are well hydrated, a requirement for carrying charge and driving protein motions in response to changes in membrane voltage. Published by Elsevier Ltd.

TGF-β1 induces the formation of vascular-like structures in embryoid bodies derived from human embryonic stem cells.

PubMed

Wang, Yan; Qian, DE-Jian; Zhong, Wen-Yu; Lu, Jun-Hong; Guo, Xiang-Kai; Cao, Yi-Lin; Liu, Ju

2014-07-01

Human embryonic stem cells (ESCs) can differentiate into endothelial cells in response to stimuli from extracellular cytokines. Transforming growth factor (TGF)-β1 signaling is involved in stem cell renewal and vascular development. Previously, human ESCs were isolated from inner cell mass and a stable ESC line was developed. In the present study, the effects of extracellular TGF-β1 were investigated on human ESC-derived embryoid bodies (EB) in suspension. The structures of the EBs were analyzed with light and electron microscopy, while the cellular composition of the EBs was examined via the expression levels of specific markers. Vascular-like tubular structures and cardiomyocyte-like beating cells were observed in the EBs at day 3 and 8, respectively. The frequencies of vascular-like structures and beating cells in the TGF-β1 treated group were significantly higher compared with the control group (84.31 vs. 12.77%; P<0.001; 37.25 vs. 8.51%; P<0.001, respectively). Electron microscopy revealed the presence of lumens and gap junctions in the sections of the tubular structures. Semiquantitative polymerase chain reaction revealed elevated expression levels of CD31 and fetal liver kinase-1 in EBs cultured with TGF-β1. In addition, extensive staining of von Willebrand factor was observed in the vascular-like structures of TGF-β1-treated EBs. Therefore, the results of the present study may aid the understanding of the underlying mechanisms of human ESC differentiation and improve the methods of propagating specific cell types for the clinical therapy of cardiovascular diseases.

Structural interactions between lipids, water and S1-S4 voltage-sensing domains

PubMed Central

Krepkiy, Dmitriy; Gawrisch, Klaus; Swartz, Kenton J.

2012-01-01

Membrane proteins serve crucial signaling and transport functions, yet relatively little is known about their structures in membrane environments or how lipids interact with these proteins. For voltage-activated ion channels, X-ray structures suggest that the mobile voltage-sensing S4 helix would be exposed to the membrane, and functional studies reveal that lipid modification can profoundly alter channel activity. Here we use solid-state NMR to investigate structural interactions of lipids and water with S1-S4 voltage-sensing domains, and to explore whether lipids influence the structure of the protein. Our results demonstrate that S1-S4 domains exhibit extensive interactions with lipids, and that these domains are heavily hydrated when embedded in a membrane. We also find evidence for preferential interactions of anionic lipids with S1-S4 domains, and that these interactions have lifetimes on the timescale of 10−3s. Arg residues within S1-S4 domains are well-hydrated and are positioned in close proximity to lipids, exhibiting local interactions with both lipid head groups and acyl chains. Comparative studies with a positively charged lipid lacking a phosphodiester group reveal that this lipid modification has only modest effects on the structure and hydration of S1-S4 domains. Taken together, our results demonstrate that Arg residues in S1-S4 voltage-sensing domains reside in close proximity to the hydrophobic interior of the membrane, yet are well-hydrated, a requirement for carrying charge and driving protein motions in response to changes in membrane voltage. PMID:22858867

The optical spectrum of ternary alloy BBi1-xAsx

NASA Astrophysics Data System (ADS)

Yalcin, Battal G.; Aslan, M.; Ozcan, M. H.; Rahnamaye Aliabad, H. A.

2016-06-01

Among the III-V semiconductors, boron BBi and BAs as well as their alloys have attracted both scientific and technological interest in recent years. We present a calculation of the structural, electronic and optical properties of ternary alloy BBi1-xAsx by means of the WIEN2k software package. The exchange-correlation potential is treated by the generalized gradient approximation (GGA) within the schema of Wu and Cohen. Also, we have used the modified Becke-Johnson (mBJ) formalism to improve the band gap results. All the calculations have been performed after geometry optimization. In this study, we have investigated structural properties such as the lattice constant (a0), bulk modulus (B0) and its pressure derivative (B‧), and calculated the electronic band structures of the studied materials. Accurate calculation of linear optical properties, such as real (ɛ 1) and imaginary (ɛ 2) dielectric functions, reflectivity (R), electron energy loss spectrum, absorption coefficient (α), refractive index (n) and sum rule (Neff) are investigated. Our obtained results for studied binary compounds, BBi and BAs, fairly coincide with other theoretical calculations and experimental measurements. According to the best of our knowledge, no experimental or theoretical data are presently available for the studied ternary alloy BBi1-xAsx (0 < x < 1). The role of electronic band structure calculation with regards to the linear optical properties of BBi1-xAsx is discussed. The effect of the spin-orbit interaction (SOI) is also investigated and found to be quite small.

Band gap characterization of ternary BBi1-xNx (0≤x≤1) alloys using modified Becke-Johnson (mBJ) potential

NASA Astrophysics Data System (ADS)

Yalcin, Battal G.

2015-04-01

The semi-local Becke-Johnson (BJ) exchange-correlation potential and its modified form proposed by Tran and Blaha have attracted a lot of interest recently because of the surprisingly accurate band gaps they can deliver for many semiconductors and insulators (e.g., sp semiconductors, noble-gas solids, and transition-metal oxides). The structural and electronic properties of ternary alloys BBi1-xNx (0≤x≤1) in zinc-blende phase have been reported in this study. The results of the studied binary compounds (BN and BBi) and ternary alloys BBi1-xNx structures are presented by means of density functional theory. The exchange and correlation effects are taken into account by using the generalized gradient approximation (GGA) functional of Wu and Cohen (WC) which is an improved form of the most popular Perdew-Burke-Ernzerhof (PBE). For electronic properties the modified Becke-Johnson (mBJ) potential, which is more accurate than standard semi-local LDA and PBE calculations, has been chosen. Geometric optimization has been implemented before the volume optimization calculations for all the studied alloys structure. The obtained equilibrium lattice constants of the studied binary compounds are in coincidence with experimental works. And, the variation of the lattice parameter of ternary alloys BBi1-xNx almost perfectly matches with Vegard's law. The spin-orbit interaction (SOI) has been also considered for structural and electronic calculations and the results are compared to those of non-SOI calculations.

NMR Study Reveals the Receiver Domain of Arabidopsis ETHYLENE RESPONSE1 Ethylene Receptor as an Atypical Type Response Regulator.

PubMed

Hung, Yi-Lin; Jiang, Ingjye; Lee, Yi-Zong; Wen, Chi-Kuang; Sue, Shih-Che

2016-01-01

The gaseous plant hormone ethylene, recognized by plant ethylene receptors, plays a pivotal role in various aspects of plant growth and development. ETHYLENE RESPONSE1 (ETR1) is an ethylene receptor isolated from Arabidopsis and has a structure characteristic of prokaryotic two-component histidine kinase (HK) and receiver domain (RD), where the RD structurally resembles bacteria response regulators (RRs). The ETR1 HK domain has autophosphorylation activity, and little is known if the HK can transfer the phosphoryl group to the RD for receptor signaling. Unveiling the correlation of the receptor structure and phosphorylation status would advance the studies towards the underlying mechanisms of ETR1 receptor signaling. In this study, using the nuclear magnetic resonance technique, our data suggested that the ETR1-RD is monomeric in solution and the rigid structure of the RD prevents the conserved aspartate residue phosphorylation. Comparing the backbone dynamics with other RRs, we propose that backbone flexibility is critical to the RR phosphorylation. Besides the limited flexibility, ETR1-RD has a unique γ loop conformation of opposite orientation, which makes ETR1-RD unfavorable for phosphorylation. These two features explain why ETR1-RD cannot be phosphorylated and is classified as an atypical type RR. As a control, phosphorylation of the ETR1-RD was also impaired when the sequence was swapped to the fragment of the bacterial typical type RR, CheY. Here, we suggest a molecule insight that the ETR1-RD already exists as an active formation and executes its function through binding with the downstream factors without phosphorylation.

Drug-drug cocrystals of antituberculous 4-aminosalicylic acid: Screening, crystal structures, thermochemical and solubility studies.

PubMed

Drozd, Ksenia V; Manin, Alex N; Churakov, Andrei V; Perlovich, German L

2017-03-01

Experimental multistage cocrystal screening of the antituberculous drug 4-aminosalicylic acid (PASA) has been conducted with a number of coformers (pyrazinamide (PYR), nicotinamide (NAM), isonicotinamide (iNAM), isoniazid (INH), caffeine (CAF) and theophylline (TPH)). The crystal structures of 4-aminosalicylic acid cocrystals with isonicotinamide ([PASA+iNAM] (2:1)) and methanol solvate with caffeine ([PASA+CAF+MeOH] (1:1:1)) have been determined by single X-ray diffraction experiments. For the first time for PASA cocrystals it has been found that the structural unit of the [PASA+iNAM] cocrystal (2:1) is formed by 2 types of heterosynthons: acid-pyridine and acid-amide. The desolvation study of the [PASA+CAF+MeOH] cocrystal solvate (1:1:1) has been conducted. The correlation models linking the melting points of the cocrystals with the melting points of the coformers used in this paper have been developed. The thermochemical and solubility properties for all the obtained cocrystals have been studied. Cocrystallization has been shown to lead not only to PASA solubility improving but also to its higher stability against the chemical decomposition. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis, spectral characterization, molecular structure and pharmacological studies of N'-(1, 4-naphtho-quinone-2yl) isonicotinohyWdrazide

NASA Astrophysics Data System (ADS)

Kavitha Rani, P. R.; Fernandez, Annette; George, Annie; Remadevi, V. K.; Sudarsanakumar, M. R.; Laila, Shiny P.; Arif, Muhammed

2015-01-01

A simple and efficient procedure was employed for the synthesis of N'-(1,4-naphtho-quinone-2-yl) isonicotinohydrazide (NIH) by the reaction of 2-hydroxy-1,4-naphthaquinone (lawsone) and isonicotinoyl hydrazine in methanol using ultrasonic irradiation. Lawsone is the principal dye, isolated from the leaves of henna (Lawsonia inermis). Structural modification was done on the molecule aiming to get a more active derivative. The structure of the parent compound and the derivative was characterized by elemental analyses, infrared, electronic, 1H, 13C NMR and GC-MS spectra. The fluorescence spectral investigation of the compound was studied in DMSO and ethanol. Single crystal X-ray diffraction studies reveal that NIH crystallizes in monoclinic space group. The DNA cleavage study was monitored by gel electrophoresis method. The synthesized compound was found to have significant antioxidant activity against DPPH radical (IC50 = 58 μM). The in vitro cytotoxic studies of the derivative against two human cancer cell lines MCF-7 (human breast cancer) and HCT-15 (human colon carcinoma cells) using MTT assay revealed that the compound exhibited higher cytotoxic activity with a lower IC50 value indicating its efficiency in killing the cancer cells even at low concentrations. These results suggest that the structural modifications performed on lawsone could be considered a good strategy to obtain a more active drug.

Growth of thermophilic and hyperthermophilic Fe(III)-reducing microorganisms on a ferruginous smectite as the sole electron acceptor.

PubMed

Kashefi, Kazem; Shelobolina, Evgenya S; Elliott, W Crawford; Lovley, Derek R

2008-01-01

Recent studies have suggested that the structural Fe(III) within phyllosilicate minerals, including smectite and illite, is an important electron acceptor for Fe(III)-reducing microorganisms in sedimentary environments at moderate temperatures. The reduction of structural Fe(III) by thermophiles, however, has not previously been described. A wide range of thermophilic and hyperthermophilic Archaea and Bacteria from marine and freshwater environments that are known to reduce poorly crystalline Fe(III) oxides were tested for their ability to reduce structural (octahedrally coordinated) Fe(III) in smectite (SWa-1) as the sole electron acceptor. Two out of the 10 organisms tested, Geoglobus ahangari and Geothermobacterium ferrireducens, were not able to conserve energy to support growth by reduction of Fe(III) in SWa-1 despite the fact that both organisms were originally isolated with solid-phase Fe(III) as the electron acceptor. The other organisms tested were able to grow on SWa-1 and reduced 6.3 to 15.1% of the Fe(III). This is 20 to 50% less than the reported amounts of Fe(III) reduced in the same smectite (SWa-1) by mesophilic Fe(III) reducers. Two organisms, Geothermobacter ehrlichii and archaeal strain 140, produced copious amounts of an exopolysaccharide material, which may have played an active role in the dissolution of the structural iron in SWa-1 smectite. The reduction of structural Fe(III) in SWa-1 by archaeal strain 140 was studied in detail. Microbial Fe(III) reduction was accompanied by an increase in interlayer and octahedral charges and some incorporation of potassium and magnesium into the smectite structure. However, these changes in the major element chemistry of SWa-1 smectite did not result in the formation of an illite-like structure, as reported for a mesophilic Fe(III) reducer. These results suggest that thermophilic Fe(III)-reducing organisms differ in their ability to reduce and solubilize structural Fe(III) in SWa-1 smectite and that SWa-1 is not easily transformed to illite by these organisms.

Growth of Thermophilic and Hyperthermophilic Fe(III)-Reducing Microorganisms on a Ferruginous Smectite as the Sole Electron Acceptor▿

PubMed Central

Kashefi, Kazem; Shelobolina, Evgenya S.; Elliott, W. Crawford; Lovley, Derek R.

2008-01-01

Recent studies have suggested that the structural Fe(III) within phyllosilicate minerals, including smectite and illite, is an important electron acceptor for Fe(III)-reducing microorganisms in sedimentary environments at moderate temperatures. The reduction of structural Fe(III) by thermophiles, however, has not previously been described. A wide range of thermophilic and hyperthermophilic Archaea and Bacteria from marine and freshwater environments that are known to reduce poorly crystalline Fe(III) oxides were tested for their ability to reduce structural (octahedrally coordinated) Fe(III) in smectite (SWa-1) as the sole electron acceptor. Two out of the 10 organisms tested, Geoglobus ahangari and Geothermobacterium ferrireducens, were not able to conserve energy to support growth by reduction of Fe(III) in SWa-1 despite the fact that both organisms were originally isolated with solid-phase Fe(III) as the electron acceptor. The other organisms tested were able to grow on SWa-1 and reduced 6.3 to 15.1% of the Fe(III). This is 20 to 50% less than the reported amounts of Fe(III) reduced in the same smectite (SWa-1) by mesophilic Fe(III) reducers. Two organisms, Geothermobacter ehrlichii and archaeal strain 140, produced copious amounts of an exopolysaccharide material, which may have played an active role in the dissolution of the structural iron in SWa-1 smectite. The reduction of structural Fe(III) in SWa-1 by archaeal strain 140 was studied in detail. Microbial Fe(III) reduction was accompanied by an increase in interlayer and octahedral charges and some incorporation of potassium and magnesium into the smectite structure. However, these changes in the major element chemistry of SWa-1 smectite did not result in the formation of an illite-like structure, as reported for a mesophilic Fe(III) reducer. These results suggest that thermophilic Fe(III)-reducing organisms differ in their ability to reduce and solubilize structural Fe(III) in SWa-1 smectite and that SWa-1 is not easily transformed to illite by these organisms. PMID:17981937

Structure and reactivity studies of CoHNO{sup +} in the gas phase

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

Chen, H.; Jacobson, D.B.; Freiser, B.S.

1999-12-16

The structure and energetics of three CoHNO{sup +} isomers [HCo(NO){sup +} (1), Co(HNO){sup +} (2), Co(NOH){sup +} (3)] were probed by using density functional theory (DFT). Theory predicts that 2 is the most stable structure with 1 and 3 14.1 and 15.4 kcal/mol less stable. The transition states for 2 {yields} 1 and 2 {yields} 3 conversions were not located. DFT calculations predict D{degree}(CoH{sup +}-NO) = 34.6 kcal/mol and D{degree}(Co{sup +}-HNO) = 45.5 kcal/mol. The gas-phase ion chemistry of CoHNO{sup +} was also studied by using Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. CID and SORI-CID of CoHNO{sup +}more » yield competitive formation of Co{sup +}, CoH{sup +}, and CoNO{sup +}. These results suggest that the barrier for 2 {yields} 1 conversion is less than 45.5 kcal/mol. Reactions with simple molecules were dominated by NO and HNO displacements. Potential energy surface diagrams are presented to explain these displacement reactions. Surprisingly, CoHNO{sup +} reacts with methane by dehydrogenation to yield CoCH{sub 3}NO{sup +}. Studies suggest CH{sub 3}CoNO{sup +} rather than Co(CH{sub 3}NO){sup +}as the structure for this ion.« less

The deformation twin in lamellar Ti 3Al/TiAl structure

NASA Astrophysics Data System (ADS)

Zhang, J. X.; Ye, H. Q.

2003-04-01

A Ti-48Al-2Cr (at.%) alloy consisting of γ+α 2 lamellar structure was deformed in compression at room temperature. Study by high resolution electron microscopy was carried out on the characteristic of induced γ T/α 2 interface. During deformation the γ T/α 2 interface presents a stepped structure and the γ/α 2 interface remains straight. The formation mechanism of γ T associated with misfit dislocations is proposed. 1/2[01 1¯] γ interfacial dislocation in the γ/α 2 interface can dissociate into a 1/6[ 1¯1 2¯] γ partial dislocation which glides on the ( 1¯11) γ plane and causes γ T to form.

Electronic structure and magnetic anisotropy of L1{sub 0}-FePt thin film studied by hard x-ray photoemission spectroscopy and first-principles calculations

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

Ueda, S.; Synchrotron X-ray Station at SPring-8, National Institute for Materials Science, Sayo, Hyogo 679-5148; Mizuguchi, M.

2016-07-25

We have studied the electronic structure of the L1{sub 0} ordered FePt thin film by hard x-ray photoemission spectroscopy (HAXPES), cluster model, and first-principles calculations to investigate the relationship between the electronic structure and perpendicular magneto-crystalline anisotropy (MCA). The Fe 2p core-level HAXPES spectrum of the ordered film revealed the strong electron correlation in the Fe 3d states and the hybridization between the Fe 3d and Pt 5d states. By comparing the experimental valence band structure with the theoretical density of states, the strong electron correlation in the Fe 3d states modifies the valence band electronic structure of the L1{submore » 0} ordered FePt thin film through the Fe 3d-Pt 5d hybridization. These results strongly suggest that the strong electron correlation effect in the Fe 3d states and the Fe 3d-Pt 5d hybridization as well as the spin-orbit interaction in the Pt 5d states play important roles in the perpendicular MCA for L1{sub 0}-FePt.« less

Synthesis, characterization, crystal structure and theoretical study of a compound with benzodiazole ring: antimicrobial activity and DNA binding.

PubMed

Latha, P; Kodisundaram, P; Sundararajan, M L; Jeyakumar, T

2014-08-14

2-(Thiophen-2-yl)-1-((thiophen-2-yl)methyl)-1H-1,3-benzodiazole (HL) is synthesized and characterized by elemental analysis, UV-Vis, FT-IR, (1)H, (13)C NMR, mass spectra, scanning electron microscope (SEM) and single crystal X-ray diffraction. The crystal structure is stabilized by intermolecular CH⋯N and CH⋯π interactions. The molecular structure is also optimized at the B3LYP/6-31G level using density functional theory (DFT). The structural parameters from the theory are nearer to those of crystal, the calculated total energy of coordination is -1522.814a.u. The energy of HOMO-LUMO and the energy gap are -0.20718, -0.04314, 0.16404a.u, respectively. All data obtained from the spectral studies support the structural properties of the compound HL. The benzimidazole ring is essentially planar. The in vitro biological screening effects of the synthesized compound is tested against four bacterial and four fungal strains by well diffusion method. Antioxidant property and DNA binding behaviour of the compound has been investigated using spectrophotometric method. Copyright © 2014 Elsevier B.V. All rights reserved.

Structural confirmation of oligosaccharides newly isolated from sugar beet molasses.

PubMed

Abe, Tatsuya; Horiuchi, Kenichi; Kikuchi, Hiroto; Aritsuka, Tsutomu; Takata, Yusuke; Fukushi, Eri; Fukushi, Yukiharu; Kawabata, Jun; Ueno, Keiji; Onodera, Shuichi; Shiomi, Norio

2012-08-27

Sugar beet molasses is a viscous by-product of the processing of sugar beets into sugar. The molasses is known to contain sucrose and raffinose, a typical trisaccharide, with a well-established structure. Although sugar beet molasses contains various other oligosaccharides as well, the structures of those oligosaccharides have not been examined in detail. The purpose of this study was isolation and structural confirmation of these other oligosaccharides found in sugar beet molasses. Four oligosaccharides were newly isolated from sugar beet molasses using high-performance liquid chromatography (HPLC) and carbon-Celite column chromatography. Structural confirmation of the saccharides was provided by methylation analysis, matrix-assisted laser desorption/ionaization time of flight mass spectrometry (MALDI-TOF-MS), and nuclear magnetic resonance (NMR) measurements. The following oligosaccharides were identified in sugar beet molasses: β-D-galactopyranosyl-(1- > 6)-β-D-fructofuranosyl-(2 <-> 1)-α-D-glucopyranoside (named β-planteose), α-D-galactopyranosyl-(1- > 1)-β-D-fructofuranosyl-(2 <-> 1)-α-D-glucopyranoside (named1-planteose), α-D-glucopyranosyl-(1- > 6)-α-D-glucopyranosyl-(1 <-> 2)-β-D-fructofuranoside (theanderose), and β-D-glucopyranosyl-(1- > 3)-α-D-glucopyranosyl-(1 <-> 2)-β-D-fructofuranoside (laminaribiofructose). 1-planteose and laminaribiofructose were isolated from natural sources for the first time.

Structure of RDE-4 dsRBDs and mutational studies provide insights into dsRNA recognition in the Caenorhabditis elegans RNAi pathway.

PubMed

Chiliveri, Sai Chaitanya; Deshmukh, Mandar V

2014-02-15

The association of RDE-4 (RNAi defective 4), a protein containing two dsRBDs (dsRNA-binding domains), with long dsRNA and Dcr-1 (Dicer1 homologue) initiates the siRNA pathway in Caenorhabditis elegans. Unlike its homologues in higher eukaryotes, RDE-4 dsRBDs possess weak (micromolar) affinity for short dsRNA. With increasing length of dsRNA, RDE-4 exhibits enhanced affinity due to co-operativity. The linker and dsRBD2 are indispensable for RDE-4's simultaneous interaction with dsRNA and Dcr-1. In the present study, we have determined the solution structures of RDE-4 constructs that contain both dsRBDs and the linker region. In addition to the canonical dsRBD fold, both dsRBDs of RDE-4 show modified structural features such as truncation in the β1-β2 loop that rationalize RDE-4's relatively weak dsRNA affinity. Structure and binding studies demonstrate that dsRBD2 plays a decisive role in the RDE-4-dsRNA interaction; however, in contrast with previous findings, we found ephemeral interaction of RDE-4 dsRBD1 with dsRNA. More importantly, mutations in two tandem lysine residues (Lys217 and Lys218) in dsRBD2 impair RDE-4's dsRNA-binding ability and could obliterate RNAi initiation in C. elegans. Additionally, we postulate a structural basis for the minimal requirement of linker and dsRBD2 for RDE-4's association with dsRNA and Dcr-1.

Two proteins for the price of one: Structural studies of the dual-destiny protein preproalbumin with sunflower trypsin inhibitor-1.

PubMed

Franke, Bastian; James, Amy M; Mobli, Mehdi; Colgrave, Michelle L; Mylne, Joshua S; Rosengren, K Johan

2017-07-28

Seed storage proteins are both an important source of nutrition for humans and essential for seedling establishment. Interestingly, unusual napin-type 2S seed storage albumin precursors in sunflowers contain a sequence that is released as a macrocyclic peptide during post-translational processing. The mechanism by which such peptides emerge from linear precursor proteins has received increased attention; however, the structural characterization of intact precursor proteins has been limited. Here, we report the 3D NMR structure of the Helianthus annuus PawS1 ( p repro a lbumin w ith s unflower trypsin inhibitor- 1 ) and provide new insights into the processing of this remarkable dual-destiny protein. In seeds, PawS1 is matured by asparaginyl endopeptidases (AEPs) into the cyclic peptide SFTI-1 ( s un f lower t rypsin i nhibitor- 1 ) and a heterodimeric 2S albumin. The structure of PawS1 revealed that SFTI-1 and the albumin are independently folded into well-defined domains separated by a flexible linker. PawS1 was cleaved in vitro with recombinant sunflower HaAEP1 and in situ using a sunflower seed extract in a way that resembled the expected in vivo cleavages. Recombinant HaAEP1 cleaved PawS1 at multiple positions, and in situ , its flexible linker was removed, yielding fully mature heterodimeric albumin. Liberation and cyclization of SFTI-1, however, was inefficient, suggesting that specific seed conditions or components may be required for in vivo biosynthesis of SFTI-1. In summary, this study has revealed the 3D structure of a macrocyclic precursor protein and provided important mechanistic insights into the maturation of sunflower proalbumins into an albumin and a macrocyclic peptide. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Crystal structure of an orthomyxovirus matrix protein reveals mechanisms for self-polymerization and membrane association.

PubMed

Zhang, Wenting; Zheng, Wenjie; Toh, Yukimatsu; Betancourt-Solis, Miguel A; Tu, Jiagang; Fan, Yanlin; Vakharia, Vikram N; Liu, Jun; McNew, James A; Jin, Meilin; Tao, Yizhi J

2017-08-08

Many enveloped viruses encode a matrix protein. In the influenza A virus, the matrix protein M1 polymerizes into a rigid protein layer underneath the viral envelope to help enforce the shape and structural integrity of intact viruses. The influenza virus M1 is also known to mediate virus budding as well as the nuclear export of the viral nucleocapsids and their subsequent packaging into nascent viral particles. Despite extensive studies on the influenza A virus M1 (FLUA-M1), only crystal structures of its N-terminal domain are available. Here we report the crystal structure of the full-length M1 from another orthomyxovirus that infects fish, the infectious salmon anemia virus (ISAV). The structure of ISAV-M1 assumes the shape of an elbow, with its N domain closely resembling that of the FLUA-M1. The C domain, which is connected to the N domain through a flexible linker, is made of four α-helices packed as a tight bundle. In the crystal, ISAV-M1 monomers form infinite 2D arrays with a network of interactions involving both the N and C domains. Results from liposome flotation assays indicated that ISAV-M1 binds membrane via electrostatic interactions that are primarily mediated by a positively charged surface loop from the N domain. Cryoelectron tomography reconstruction of intact ISA virions identified a matrix protein layer adjacent to the inner leaflet of the viral membrane. The physical dimensions of the virion-associated matrix layer are consistent with the 2D ISAV-M1 crystal lattice, suggesting that the crystal lattice is a valid model for studying M1-M1, M1-membrane, and M1-RNP interactions in the virion.

Interactions of DNA binding proteins with G-Quadruplex structures at the single molecule level

NASA Astrophysics Data System (ADS)

Ray, Sujay

Guanine-rich nucleic acid (DNA/RNA) sequences can form non-canonical secondary structures, known as G-quadruplex (GQ). Numerous in vivo and in vitro studies have demonstrated formation of these structures in telomeric and non-telomeric regions of the genome. Telomeric GQs protect the chromosome ends whereas non-telomeric GQs either act as road blocks or recognition sites for DNA metabolic machinery. These observations suggest the significance of these structures in regulation of different metabolic processes, such as replication and repair. GQs are typically thermodynamically more stable than the corresponding Watson-Crick base pairing formed by G-rich and C-rich strands, making protein activity a crucial factor for their destabilization. Inside the cell, GQs interact with different proteins and their enzymatic activity is the determining factor for their stability. We studied interactions of several proteins with GQs to understand the underlying principles of protein-GQ interactions using single-molecule FRET and other biophysical techniques. Replication Protein-A (RPA), a single stranded DNA (ssDNA) binding protein, is known to posses GQ unfolding activity. First, we compared the thermal stability of three potentially GQ-forming DNA sequences (PQS) to their stability against RPA-mediated unfolding. One of these sequences is the human telomeric repeat and the other two, located in the promoter region of tyrosine hydroxylase gene, are highly heterogeneous sequences that better represent PQS in the genome. The thermal stability of these structures do not necessarily correlate with their stability against protein-mediated unfolding. We conclude that thermal stability is not necessarily an adequate criterion for predicting the physiological viability of GQ structures. To determine the critical structural factors that influence protein-GQ interactions we studied two groups of GQ structures that have systematically varying loop lengths and number 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. Finally, we studied another protein-GQ system where a protein complex works synergistically with a GQ to suppress DNA damage signals by preventing RPA to bind to telomeric DNA. Human telomeres that terminate with a single-stranded 3' G-overhang can be recognized as a DNA damage site by RPA. The protection of telomere-1 (POT1) and POT1-interacting protein (TPP1) heterodimer, binds specifically to telomeric DNA and protects it against RPA binding. Using model telomeric DNA, we studied the competition between POT1/TPP1 and RPA to access telomeric GQs in vitro. Under physiological salt and pH conditions, POT1/TPP1 stably load to a minimal DNA sequence adjacent to a folded GQ and unfolds the anti-parallel GQ as the parallel conformation remains folded. We showed that GQ formation of telomeres enhances the ability of POT1/TPP1 to block RPA's access to telomeres by two orders of magnitude and contributes to suppress DNA damage signals.

Fluid-Structure Interaction in a Fluid-Filled Composite Structure Subjected to Low Velocity Impact

DTIC Science & Technology

2016-06-01

for creating an E-glass composite cubic structure and a pendulum was designed and built to provide a repeatable low velocity impact. The behavior of...structure and a pendulum was designed and built to provide a repeatable low velocity impact. The behavior of the composite structure was studied at various...SET-UP .......................................................31  1.  Impact Pendulum

Structural Studies of CH_3SiF_2-X (x = Nco, Cl) by Microwave Spectroscopy

NASA Astrophysics Data System (ADS)

Guirgis, Gamil A.; Gause, Korreda K.; Seifert, Nathan A.; Zaleski, Daniel P.; Pate, Brooks H.; Palmer, Michael H.; Peebles, Rebecca A.; Peebles, Sean A.; Elmuti, Lena F.; Obenchain, Daniel A.

2012-06-01

The structures of CH_3SiF_2-NCO and CH_3SiF_2-Cl have been studied by molecular rotational spectroscopy in the 6.5-18 GHz band. The rotational spectrum was measured by cavity Fourier transform microwave (FTMW) and chirped-pulse FTMW spectroscopy. The experiment targeted the study of CH_3SiF_2-NCO, but CH_3SiF_2-Cl was also observed as an impurity. Due to the dynamic range achieved on these spectra, all isotopologs with natural abundance ≥0.2% were assigned, which includes two doubly-substituted isotopologs for the chloride (29Si/37Cl and 30Si/37Cl). Strategies for obtaining the molecular structure for these two molecules using either a Kraitchman analysis (to obtain a partial substitution structure) or r_0 analysis (with additional constraints on the structure supplied by the theoretical structure) will be discussed. Derived structural parameters for the CH_3-SiF_2-X base structure are the same for the two compounds. The hyperfine and internal rotation effects in the spectra have been analyzed for all isotopologs and the Hamiltonian parameters are in very good agreement with ab initio results. The barriers to methyl group internal rotation for the two compounds 446(50) cm-1 and 463(3) cm-1 and are independent of the isotopic structure of the heavy atom frame.

1-D Metal Nanobead Arrays within Encapsulated Nanowires via a Red-Ox-Induced Dewetting: Mechanism Study by Atom-Probe Tomography.

PubMed

Sun, Zhiyuan; Tzaguy, Avra; Hazut, Ori; Lauhon, Lincoln J; Yerushalmi, Roie; Seidman, David N

2017-12-13

Metal nanoparticle arrays are excellent candidates for a variety of applications due to the versatility of their morphology and structure at the nanoscale. Bottom-up self-assembly of metal nanoparticles provides an important complementary alternative to the traditional top-down lithography method and makes it possible to assemble structures with higher-order complexity, for example, nanospheres, nanocubes, and core-shell nanostructures. Here we present a mechanism study of the self-assembly process of 1-D noble metal nanoparticles arrays, composed of Au, Ag, and AuAg alloy nanoparticles. These are prepared within an encapsulated germanium nanowire, obtained by the oxidation of a metal-germanium nanowire hybrid structure. The resulting structure is a 1-D array of equidistant metal nanoparticles with the same diameter, the so-called nanobead (NB) array structure. Atom-probe tomography and transmission electron microscopy were utilized to investigate the details of the morphological and chemical evolution during the oxidation of the encapsulated metal-germanium nanowire hybrid-structures. The self-assembly of nanoparticles relies on the formation of a metal-germanium liquid alloy and the migration of the liquid alloy into the nanowire, followed by dewetting of the liquid during shape-confined oxidation where the liquid column breaks-up into nanoparticles due to the Plateau-Rayleigh instability. Our results demonstrate that the encapsulating oxide layer serves as a structural scaffold, retaining the overall shape during the eutectic liquid formation and demonstrates the relationship between the oxide mechanical properties and the final structural characteristics of the 1-D arrays. The mechanistic details revealed here provide a versatile tool-box for the bottom-up fabrication of 1-D arrays nanopatterning that can be modified for multiple applications according to the RedOx properties of the material system components.

Oxidized crystalline (3 × 1)-O surface phases of InAs and InSb studied by high-resolution photoelectron spectroscopy

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

Tuominen, M., E-mail: tmleir@utu.fi, E-mail: pekka.laukkanen@utu.fi; Lång, J.; Dahl, J.

2015-01-05

The pre-oxidized crystalline (3×1)-O structure of InAs(100) has been recently found to significantly improve insulator/InAs junctions for devices, but the atomic structure and formation of this useful oxide layer are not well understood. We report high-resolution photoelectron spectroscopy analysis of (3×1)-O on InAs(100) and InSb(100). The findings reveal that the atomic structure of (3×1)-O consists of In atoms with unexpected negative (between −0.64 and −0.47 eV) and only moderate positive (In{sub 2}O type) core-level shifts; highly oxidized group-V sites; and four different oxygen sites. These fingerprint shifts are compared to those of previously studied oxides of III-V to elucidate oxidation processes.

Development of a truss joint for robotic assembly of space structures

NASA Technical Reports Server (NTRS)

Parma, George F.

1992-01-01

This report presents the results of a detailed study of mechanical fasteners which were designed to facilitate robotic assembly of structures. Design requirements for robotic structural assembly were developed, taking into account structural properties and overall system design, and four candidate fasteners were designed to meet them. These fasteners were built and evaluated in the laboratory, and the Hammer-Head joint was chosen as superior overall. It had a high reliability of fastening under misalignments of 2.54 mm (0.1 in) and 3 deg, the highest end fixity (2.18), the simplest end effector, an integral capture guide, good visual verification, and the lightest weight (782 g, 1.72 lb). The study found that a good design should incorporate chamfers sliding on chamfers, cylinders sliding on chamfers, and hard surface finishes on sliding surfaces. The study also comments on robot flexibility, sag, hysteresis, thermal expansion, and friction which were observed during the testing.

Exploring structural properties of small carbon clusters Cn (n = 1, 2, 3) using molecular mechanics and energy minimization

NASA Astrophysics Data System (ADS)

Miswan, M. A.; Gopir, G.; Anas, M. M.

2016-11-01

Geometry optimization is one of the most widely used methods to study in carbon cluster Cn to understand its structural properties. The total energy for each of the structures was calculated using Octopus software with conjugate gradient Broyden-Fletcher-Goldfarb-Shanno (CG-BFGS). Our calculation and other studies indicate that the linear forms are the most stable structures. However, the C3 isomers have equal probability to form, as the differences in our calculation of total energy are statistically insignificant. Despite there are two cohort of total energy, the calculations are acceptable due to the energy ratio between C3 to C2 and C2 to C1 are comparable to others work. Meanwhile, the bond properties of the C2 and C3 bonds also gives significant difference between our work and previous study.

Rapid identification of Keap1-Nrf2 small-molecule inhibitors through structure-based virtual screening and hit-based substructure search.

PubMed

Zhuang, Chunlin; Narayanapillai, Sreekanth; Zhang, Wannian; Sham, Yuk Yin; Xing, Chengguo

2014-02-13

In this study, rapid structure-based virtual screening and hit-based substructure search were utilized to identify small molecules that disrupt the interaction of Keap1-Nrf2. Special emphasis was placed toward maximizing the exploration of chemical diversity of the initial hits while economically establishing informative structure-activity relationship (SAR) of novel scaffolds. Our most potent noncovalent inhibitor exhibits three times improved cellular activation in Nrf2 activation than the most active noncovalent Keap1 inhibitor known to date.

Comparative modeling of InP solar cell structures

NASA Technical Reports Server (NTRS)

Jain, R. K.; Weinberg, I.; Flood, D. J.

1991-01-01

The comparative modeling of p(+)n and n(+)p indium phosphide solar cell structures is studied using a numerical program PC-1D. The optimal design study has predicted that the p(+)n structure offers improved cell efficiencies as compared to n(+)p structure, due to higher open-circuit voltage. The various cell material and process parameters to achieve the maximum cell efficiencies are reported. The effect of some of the cell parameters on InP cell I-V characteristics was studied. The available radiation resistance data on n(+)p and p(+)p InP solar cells are also critically discussed.

Effect of Annealing Temperature on Structural, Optical, and Electrical Properties of Sol-Gel Spin-Coating-Derived Cu2ZnSnS4 Thin Films

NASA Astrophysics Data System (ADS)

Hosseinpour, Rabie; Izadifard, Morteza; Ghazi, Mohammad Ebrahim; Bahramian, Bahram

2018-02-01

The effect of annealing temperature on structural, optical, and electrical properties of Cu2ZnSnS4 (CZTS) thin films grown on a glass substrate by spin coating sol-gel technique has been studied. Structural study showed that all samples had kesterite crystalline structure. Scanning electron microscopy images showed that the crystalline quality of the samples was improved by heat treatment. Optical study showed that the energy gap values for the samples ranged from 1.55 eV to 1.78 eV. Moreover, good optical conductivity values (1012 S-1 to 1014 S-1) were obtained for the samples. Investigation of the electrical properties of the CZTS thin films showed that the carrier concentration increased significantly with the annealing temperature. The photoelectrical behavior of the samples revealed that the photocurrent under light illumination increased significantly. Overall, the results show that the CZTS thin films annealed at 500°C had better structural, optical, and electrical properties and that such CZTS thin films are desirable for use as absorber layers in solar cells. The photovoltaic properties of the CZTS layer annealed at 500°C were also investigated and the associated figure of merit calculated. The results showed that the fabricated ZnS-CZTS heterojunction exhibited good rectifying behavior but rather low fill factor.

Imidazole derivatives as angiotensin II AT1 receptor blockers: Benchmarks, drug-like calculations and quantitative structure-activity relationships modeling

NASA Astrophysics Data System (ADS)

Alloui, Mebarka; Belaidi, Salah; Othmani, Hasna; Jaidane, Nejm-Eddine; Hochlaf, Majdi

2018-03-01

We performed benchmark studies on the molecular geometry, electron properties and vibrational analysis of imidazole using semi-empirical, density functional theory and post Hartree-Fock methods. These studies validated the use of AM1 for the treatment of larger systems. Then, we treated the structural, physical and chemical relationships for a series of imidazole derivatives acting as angiotensin II AT1 receptor blockers using AM1. QSAR studies were done for these imidazole derivatives using a combination of various physicochemical descriptors. A multiple linear regression procedure was used to design the relationships between molecular descriptor and the activity of imidazole derivatives. Results validate the derived QSAR model.

Effect of Heat Treatment on the Structure and Properties of Explosion Welded Bimetal Kh20N80 + AD1

NASA Astrophysics Data System (ADS)

Shmorgun, V. G.; Arisova, V. N.; Slautin, O. V.; Taube, A. O.; Bakuntseva, V. M.

2017-05-01

Results of a study of the effect of heat treatment on the microhardness, structure and phase composition of diffusion zone in explosion-welded `refractory nickel alloy Kh20N80 + aluminum alloy AD1' bimetal are presented.

Real-time testing of titanium sheet and extrusion coupon specimens subjected to Mach 2.7 supersonic cruise aircraft wing stresses and temperatures

NASA Technical Reports Server (NTRS)

Lunde, T.

1977-01-01

The accuracy of three accelerated flight-by-flight test methods for material selection, and fatigue substantiation of supersonic cruise aircraft structure was studied. The real time stresses and temperatures applied to the specimens were representative of the service conditions in the lower surface of a Mach 2.7 supersonic cruise aircraft wing root structure. Each real time flight lasted about 65 minutes, including about one hour at (500 F) in the cruise condition. Center notched coupon specimens from six titanium materials were tested: mill-annealed, duplex-annealed, and triplex-annealed Ti-8Al-1Mo-1V sheets; mill-annealed Ti-8Al-1Mo-1V extrusion; mill-annealed Ti-6Al-4V sheet; and solution-treated and aged Ti-6Al-4V extrusion. For duplex-annealed Ti-8Al-1Mo-1V sheet, specimens with single spotweld were also tested. The test results were studied in conjunction with other related data from the literature for: material selection, structural fabrication, fatigue resistance of supersonic cruise aircraft structure, and fatigue test acceleration procedures for supersonic cruise aircraft.

Fermi arc electronic structure and Chern numbers in the type-II Weyl semimetal candidate Mo x W 1 - x Te 2

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

Belopolski, Ilya; Xu, Su-Yang; Ishida, Yukiaki

2016-08-15

It has recently been proposed that electronic band structures in crystals can give rise to a previously overlooked type of Weyl fermion, which violates Lorentz invariance and, consequently, is forbidden in particle physics. It was further predicted that Mo x W 1 - x Te 2 may realize such a type-II Weyl fermion. Here, we first show theoretically that it is crucial to access the band structure above the Fermi level ε F to show a Weyl semimetal in Mo x W 1 - x Te 2 . Then, we study Mo x W 1 - x Te 2 bymore » pump-probe ARPES and we directly access the band structure > 0.2 eV above ε F in experiment. By comparing our results with ab initio calculations, we conclude that we directly observe the surface state containing the topological Fermi arc. We propose that a future study of Mo x W 1 - x Te 2 by pump-probe ARPES may directly pinpoint the Fermi arc. Our work sets the stage for the experimental discovery of the first type-II Weyl semimetal in Mo x W 1 - x Te 2 .« less

The Mitosis and Neurodevelopment Proteins NDE1 and NDEL1 Form Dimers, Tetramers, and Polymers with a Folded Back Structure in Solution*

PubMed Central

Soares, Dinesh C.; Bradshaw, Nicholas J.; Zou, Juan; Kennaway, Christopher K.; Hamilton, Russell S.; Chen, Zhuo A.; Wear, Martin A.; Blackburn, Elizabeth A.; Bramham, Janice; Böttcher, Bettina; Millar, J. Kirsty; Barlow, Paul N.; Walkinshaw, Malcolm D.; Rappsilber, Juri; Porteous, David J.

2012-01-01

Paralogs NDE1 (nuclear distribution element 1) and NDEL1 (NDE-like 1) are essential for mitosis and neurodevelopment. Both proteins are predicted to have similar structures, based upon high sequence similarity, and they co-complex in mammalian cells. X-ray diffraction studies and homology modeling suggest that their N-terminal regions (residues 8–167) adopt continuous, extended α-helical coiled-coil structures, but no experimentally derived information on the structure of their C-terminal regions or the architecture of the full-length proteins is available. In the case of NDE1, no biophysical data exists. Here we characterize the structural architecture of both full-length proteins utilizing negative stain electron microscopy along with our established paradigm of chemical cross-linking followed by tryptic digestion, mass spectrometry, and database searching, which we enhance using isotope labeling for mixed NDE1-NDEL1. We determined that full-length NDE1 forms needle-like dimers and tetramers in solution, similar to crystal structures of NDEL1, as well as chain-like end-to-end polymers. The C-terminal domain of each protein, required for interaction with key protein partners dynein and DISC1 (disrupted-in-schizophrenia 1), includes a predicted disordered region that allows a bent back structure. This facilitates interaction of the C-terminal region with the N-terminal coiled-coil domain and is in agreement with previous results showing N- and C-terminal regions of NDEL1 and NDE1 cooperating in dynein interaction. It sheds light on recently identified mutations in the NDE1 gene that cause truncation of the encoded protein. Additionally, analysis of mixed NDE1-NDEL1 complexes demonstrates that NDE1 and NDEL1 can interact directly. PMID:22843697

Characterization and membrane organization of beta 1----3- and beta 1----4-galactosyltransferases from human colonic adenocarcinoma cell lines Colo 205 and SW403: basis for preferential synthesis of type 1 chain lacto-series carbohydrate structures.

PubMed

Holmes, E H

1989-05-01

Evidence indicates that activation of a beta 1----3N-acetylglucosaminyltransferase is responsible for accumulation of large quantities of lacto-series tumor-associated antigens in human colonic adenocarcinomas. Expression of type 1 and 2 core chain derivatives characterize human colonic adenocarcinomas, whereas normal adult colonic epithelial cells express detectable quantities of only type 1 chain derivatives. The basis for preferential synthesis of type 1 chain lacto-series carbohydrate structures characteristic of normal colonic mucosa and human colonic adenocarcinoma Colo 205 cells has been studied. The beta 1----3- and beta 1----4galactosyltransferase enzymes associated with synthesis of type 1 and 2 core chain structures, respectively, have been separated from a Triton X-100 solubilized membrane fraction of Colo 205 cells by chromatography on an alpha-lactalbumin-Sepharose column and their properties studied. Optimal transfer of beta 1----3-linked galactose to acceptor Lc3 occurred in the presence of 0.1% Triton CF-54 with Triton X-100 providing 75% of maximal activity. The enzyme was active over a broad pH range from 6.5 to 7.5 and had a near absolute requirement for Mn2+. The Km values for donor UDPgalactose and acceptor Lc3 were determined to be 48 and 13 microM, respectively. In contrast, the beta 1----4galactosyltransferase required taurodeoxycholate for maximal activity and the Km for Lc3 was found to be 20-fold higher than that for the beta 1----3-specific enzyme under the same assay conditions. Studies with membrane-bound beta 1----3- and beta 1----4galactosyltransferases as found in Golgi-rich membrane fractions of SW403 and Colo 205 adenocarcinoma cells showed that preferential synthesis of type 1 chain structures occurs under conditions similar to those in vivo for biosynthesis of lacto-series core chains. The results suggest that both the higher affinity of the beta 1----3galactosyltransferase for acceptor Lc3 and the membrane organizational features result in preferential synthesis of type 1 chain structures.

An overview of recent nucleon spin structure measurements at Jefferson Lab

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

Allada, Kalyan

2016-02-01

Jefferson Lab have made significant contributions to improve our knowledge of the longitudinal spin structure by measuring polarized structure functions, g1 and g2, down to Q2 = 0.02 GeV2. The low Q2 data is especially useful in testing the Chiral Perturbation theory (cPT) calculations. The spin-dependent sum rules and the spin polarizabilities, constructed from the moments of g1 and g2, provide an important tool to study the longitudinal spin structure. We will present an overview of the experimental program to measure these structure functions at Jefferson Lab, and present some recent results on the neutron polarizabilities, proton g1 at lowmore » Q2, and proton and neutron d2 measurement. In addition to this, we will discuss the transverse spin structure of the nucleon which can be accessed using chiral-odd transversity distribution (h1), and show some results from measurements done on polarized 3He target in Hall A.« less

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

Madrak, R.; Wildman, D.

The key elements have been constructed for a fast chopper system capable of removing single 2.5 MeV proton bunches spaced at 325 MHz. The average chopping rate is ~ 1 MHz. The components include a pulse delaying microstrip structure for deflecting the beam, high voltage (1.2 kV) fast (ns rise time) pulsers, and an associated wideband combiner. Various designs for the deflecting structures have been studied. Measurements of the microstrip structures' coverage factors and pulse shapes are presented.

Structural Priming in Spanish as Evidence of Implicit Learning

ERIC Educational Resources Information Center

Gámez, Perla B.; Shimpi, Priya M.

2016-01-01

This study uses a structural priming technique with young Spanish speakers to test whether exposure to a rare syntactic form in Spanish ("fue"-passive) would increase the production and comprehension of that form. In Study 1, 14 six-year-old Spanish speakers described pictures of transitive scenes. This baseline study revealed that…

Extensions of PDZ domains as important structural and functional elements.

PubMed

Wang, Conan K; Pan, Lifeng; Chen, Jia; Zhang, Mingjie

2010-08-01

'Divide and conquer' has been the guiding strategy for the study of protein structure and function. Proteins are divided into domains with each domain having a canonical structural definition depending on its type. In this review, we push forward with the interesting observation that many domains have regions outside of their canonical definition that affect their structure and function; we call these regions 'extensions'. We focus on the highly abundant PDZ (PSD-95, DLG1 and ZO-1) domain. Using bioinformatics, we find that many PDZ domains have potential extensions and we developed an openly-accessible website to display our results ( http://bcz102.ust.hk/pdzex/ ). We propose, using well-studied PDZ domains as illustrative examples, that the roles of PDZ extensions can be classified into at least four categories: 1) protein dynamics-based modulation of target binding affinity, 2) provision of binding sites for macro-molecular assembly, 3) structural integration of multi-domain modules, and 4) expansion of the target ligand-binding pocket. Our review highlights the potential structural and functional importance of domain extensions, highlighting the significance of looking beyond the canonical boundaries of protein domains in general.

Structural studies of G protein-coupled receptors.

PubMed

Lu, Mengjie; Wu, Beili

2016-11-01

G protein-coupled receptors (GPCRs) comprise the largest membrane protein family. These receptors sense a variety of signaling molecules, activate multiple intracellular signal pathways, and act as the targets of over 40% of marketed drugs. Recent progress on GPCR structural studies provides invaluable insights into the structure-function relationship of the GPCR superfamily, deepening our understanding about the molecular mechanisms of GPCR signal transduction. Here, we review recent breakthroughs on GPCR structure determination and the structural features of GPCRs, and take the structures of chemokine receptor CCR5 and purinergic receptors P2Y 1 R and P2Y 12 R as examples to discuss the importance of GPCR structures on functional studies and drug discovery. In addition, we discuss the prospect of GPCR structure-based drug discovery. © 2016 IUBMB Life, 68(11):894-903, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Structure of the GH1 domain of guanylate kinase-associated protein from Rattus norvegicus

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

Tong, Junsen; Yang, Huiseon; Eom, Soo Hyun

2014-09-12

Graphical abstract: - Highlights: • The crystal structure of GKAP homology domain 1 (GH1) was determined. • GKAP GH1 is a three-helix bundle connected by short flexible loops. • The predicted helix α4 associates weakly with the helix α3, suggesting dynamic nature of the GH1 domain. - Abstract: Guanylate-kinase-associated protein (GKAP) is a scaffolding protein that links NMDA receptor-PSD-95 to Shank–Homer complexes by protein–protein interactions at the synaptic junction. GKAP family proteins are characterized by the presence of a C-terminal conserved GKAP homology domain 1 (GH1) of unknown structure and function. In this study, crystal structure of the GH1 domainmore » of GKAP from Rattus norvegicus was determined in fusion with an N-terminal maltose-binding protein at 2.0 Å resolution. The structure of GKAP GH1 displays a three-helix bundle connected by short flexible loops. The predicted helix α4 which was not visible in the crystal structure associates weakly with the helix α3 suggesting dynamic nature of the GH1 domain. The strict conservation of GH1 domain across GKAP family members and the lack of a catalytic active site required for enzyme activity imply that the GH1 domain might serve as a protein–protein interaction module for the synaptic protein clustering.« less

Probing the Structures and Electronic Properties of Dual-Phosphorus-Doped Gold Cluster Anions (AunP-2, n = 1–8): A Density functional Theory Investigation

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

Xu, Kang-Ming; Huang, Teng; Liu, Yi-Rong

2015-07-29

The geometries of gold clusters doped with two phosphorus atoms, (AunP-2, n = 1–8) were investigated using density functional theory (DFT) methods. Various two-dimensional (2D) and three-dimensional (3D) structures of the doped clusters were studied. The results indicate that the structures of dual-phosphorus-doped gold clusters exhibit large differences from those of pure gold clusters with small cluster sizes. In our study, as for Au6P-2, two cis–trans isomers were found. The global minimum of Au8P-2 presents a similar configuration to that of Au-20, a pyramid-shaped unit, and the potential novel optical and catalytic properties of this structure warrant further attention. Themore » higher stability of AunP-2 clusters relative to Au-n+2 (n = 1–8) clusters was verified based on various energy parameters, and the results indicate that the phosphorus atom can improve the stabilities of the gold clusters. We then explored the evolutionary path of (n = 1–8) clusters. We found that AunP-2 clusters exhibit the 2D–3D structural transition at n = 6, which is much clearer and faster than that of pure gold clusters and single-phosphorus-doped clusters. The electronic properties of AunP-2 (n = 1–8) were then investigated. The photoelectron spectra provide additional fundamental information on the structures and molecular orbitals shed light on the evolution of AunP-2 (n = 1–8). Natural bond orbital (NBO) described the charge distribution in stabilizing structures and revealed the strong relativistic effects of the gold atoms.« less

Prevalent Exon-Intron Structural Changes in the APETALA1/FRUITFULL, SEPALLATA, AGAMOUS-LIKE6, and FLOWERING LOCUS C MADS-Box Gene Subfamilies Provide New Insights into Their Evolution

PubMed Central

Yu, Xianxian; Duan, Xiaoshan; Zhang, Rui; Fu, Xuehao; Ye, Lingling; Kong, Hongzhi; Xu, Guixia; Shan, Hongyan

2016-01-01

AP1/FUL, SEP, AGL6, and FLC subfamily genes play important roles in flower development. The phylogenetic relationships among them, however, have been controversial, which impedes our understanding of the origin and functional divergence of these genes. One possible reason for the controversy may be the problems caused by changes in the exon-intron structure of genes, which, according to recent studies, may generate non-homologous sites and hamper the homology-based sequence alignment. In this study, we first performed exon-by-exon alignments of these and three outgroup subfamilies (SOC1, AG, and STK). Phylogenetic trees reconstructed based on these matrices show improved resolution and better congruence with species phylogeny. In the context of these phylogenies, we traced evolutionary changes of exon-intron structures in each subfamily. We found that structural changes have occurred frequently following gene duplication and speciation events. Notably, exons 7 and 8 (if present) suffered more structural changes than others. With the knowledge of exon-intron structural changes, we generated more reasonable alignments containing all the focal subfamilies. The resulting trees showed that the SEP subfamily is sister to the monophyletic group formed by AP1/FUL and FLC subfamily genes and that the AGL6 subfamily forms a sister group to the three abovementioned subfamilies. Based on this topology, we inferred the evolutionary history of exon-intron structural changes among different subfamilies. Particularly, we found that the eighth exon originated before the divergence of AP1/FUL, FLC, SEP, and AGL6 subfamilies and degenerated in the ancestral FLC-like gene. These results provide new insights into the origin and evolution of the AP1/FUL, FLC, SEP, and AGL6 subfamilies. PMID:27200066

The effect of classroom structure on verbal and physical aggression among peers: a short-term longitudinal study.

PubMed

Bergsmann, Evelyn M; Van De Schoot, Rens; Schober, Barbara; Finsterwald, Monika; Spiel, Christiane

2013-04-01

Teachers promote student learning and well-being in school by establishing a supportive classroom structure. The term classroom structure refers to how teachers design tasks, maintain authority, and evaluate student achievement. Although empirical studies have shown the relation of classroom structure to student motivation, achievement, and well-being, no prior investigations have examined the influence of classroom structure on aggression among peers. The present study examined whether a supportive classroom structure has an impact on verbal and physical aggression. At two points in time, data were collected from 1680 students in Grades 5 to 7 using self-report questionnaires. The results of structural equation modeling revealed that a supportive classroom structure at Time 1 was associated with less perpetrated verbal aggression at Time 2, 9months later. This finding has practical relevance for teacher training as well as for aggression prevention and intervention among children. Copyright © 2012 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Essential Parameters for Structural Analysis and Dereplication by 1H NMR Spectroscopy

PubMed Central

2015-01-01

The present study demonstrates the importance of adequate precision when reporting the δ and J parameters of frequency domain 1H NMR (HNMR) data. Using a variety of structural classes (terpenoids, phenolics, alkaloids) from different taxa (plants, cyanobacteria), this study develops rationales that explain the importance of enhanced precision in NMR spectroscopic analysis and rationalizes the need for reporting Δδ and ΔJ values at the 0.1–1 ppb and 10 mHz level, respectively. Spectral simulations paired with iteration are shown to be essential tools for complete spectral interpretation, adequate precision, and unambiguous HNMR-driven dereplication and metabolomic analysis. The broader applicability of the recommendation relates to the physicochemical properties of hydrogen (1H) and its ubiquity in organic molecules, making HNMR spectra an integral component of structure elucidation and verification. Regardless of origin or molecular weight, the HNMR spectrum of a compound can be very complex and encode a wealth of structural information that is often obscured by limited spectral dispersion and the occurrence of higher order effects. This altogether limits spectral interpretation, confines decoding of the underlying spin parameters, and explains the major challenge associated with the translation of HNMR spectra into tabulated information. On the other hand, the reproducibility of the spectral data set of any (new) chemical entity is essential for its structure elucidation and subsequent dereplication. Handling and documenting HNMR data with adequate precision is critical for establishing unequivocal links between chemical structure, analytical data, metabolomes, and biological activity. Using the full potential of HNMR spectra will facilitate the general reproducibility for future studies of bioactive chemicals, especially of compounds obtained from the diversity of terrestrial and marine organisms. PMID:24895010

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

Masubuchi, Tsugunosuke; Iwasa, Takeshi; JST, ERATO, Nakajima Designer Nanocluster Assembly Project, 3-2-1 Sakado, Takatsu-ku, Kawasaki 213-0012

One end open V{sub n}Bz{sub n}{sup −} (n = 1–5; Bz = benzene) and both ends open V{sub n}Bz{sub n−1}{sup −} (n = 2–5) vanadium–benzene cluster anions were studied using anion photoelectron spectroscopy and density functional calculations. The smaller (n ≤ 3) V{sub n}Bz{sub n} and V{sub n}Bz{sub n−1} clusters and corresponding anions were found to have structural isomers, whereas full-sandwiched V{sub n}Bz{sub n+1} clusters preferred to form multiple-decker sandwich structures. Several isomeric V{sub 2}Bz{sub 2} structures were identified theoretically and the anion photoelectron spectra of V{sub 2}Bz{sub 2}{sup 0/−} were explained well by the coexistence of two isomeric structures:more » (1) a V{sub 2}-core structure sandwiched between benzene molecules and (2) an alternating sandwich structure with the spin state strongly dependent on the structure. The adiabatic electron affinity of both V{sub n}Bz{sub n} and V{sub n}Bz{sub n−1} was found to increase with the cluster size at larger sizes (n = 4 or 5) and approaches to that of V{sub n}Bz{sub n+1}. The evolution of the structural and electronic properties of V{sub n}Bz{sub m} and V{sub n}Bz{sub m}{sup −} (m = n and n − 1) with size is discussed in comparison with V{sub n}Bz{sub n+1} and V{sub n}Bz{sub n+1}{sup −}.« less

Structure of the intact ATM/Tel1 kinase

NASA Astrophysics Data System (ADS)

Wang, Xuejuan; Chu, Huanyu; Lv, Mengjuan; Zhang, Zhihui; Qiu, Shuwan; Liu, Haiyan; Shen, Xuetong; Wang, Weiwu; Cai, Gang

2016-05-01

The ataxia-telangiectasia mutated (ATM) protein is an apical kinase that orchestrates the multifaceted DNA-damage response. Normally, ATM kinase is in an inactive, homodimer form and is transformed into monomers upon activation. Besides a conserved kinase domain at the C terminus, ATM contains three other structural modules, referred to as FAT, FATC and N-terminal helical solenoid. Here we report the first cryo-EM structure of ATM kinase, which is an intact homodimeric ATM/Tel1 from Schizosaccharomyces pombe. We show that two monomers directly contact head-to-head through the FAT and kinase domains. The tandem N-terminal helical solenoid tightly packs against the FAT and kinase domains. The structure suggests that ATM/Tel1 dimer interface and the consecutive HEAT repeats inhibit the binding of kinase substrates and regulators by steric hindrance. Our study provides a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents.

Ab initio study on structural stability of uranium carbide

NASA Astrophysics Data System (ADS)

Sahoo, B. D.; Joshi, K. D.; Gupta, Satish C.

2013-06-01

First principles calculations have been performed using plane wave pseudopotential and full potential linearized augmented plane wave (FP-LAPW) methods to analyze structural, elastic and dynamic stability of UC under hydrostatic compression. Our calculations within pseudopotential method suggest that the rocksalt (B1) structure will transform to body centered orthorhombic (bco) structure at ˜21.5 GPa. The FP-LAPW calculations put this transition at 23 GPa. The transition pressures determined from our calculations though agree reasonably with the experimental value of 27 GPa, the high pressure bco structure suggested by theory differs slightly from the experimentally reported pseudo bco phase. The elastic stability analysis of B1 phase suggests that the B1 to bco transition is driven by the failure of C44 modulus. This finding is further substantiated by the lattice dynamic calculations which demonstrate that the B1 phase becomes dynamically unstable around the transition pressure and the instability is of long wavelength nature.

All-atom ab initio native structure prediction of a mixed fold (1FME): A comparison of structural and folding characteristics of various ββα miniproteins

NASA Astrophysics Data System (ADS)

Kim, Eunae; Jang, Soonmin; Pak, Youngshang

2009-11-01

We performed an all-atom ab initio native structure prediction of 1FME, which is one of the computationally challenging mixed fold ββα miniproteins, by combining a novel conformational search algorithm (multiplexed Q-replica exchange molecular dynamics scheme) with a well-balanced all-atom force field employing a generalized Born implicit solvation model (param99MOD5/GBSA). The nativelike structure of 1FME was identified from the lowest free energy minimum state and in excellent agreement with the NMR structure. Based on the interpretation of the free energy landscape, the structural properties as well as the folding behaviors of 1FME were compared with other ββα miniproteins (1FSD, 1PSV, and BBA5) that we have previously studied with the same force field. Our simulation showed that the 28-residue ββα miniproteins (1FME, 1FSD, and 1PSV) share a common feature of the free energy topography and exhibit the three local minimum states on each computed free energy map, but the 23-residue miniprotein (BBA5) follows a downhill folding with a single minimum state. Also, the structure and stability changes resulting from the two point mutation (Gln1→Glu1 and Ile7→Tyr7) of 1FSD were investigated in details for direct comparison with the experiment. The comparison shows that upon mutation, the experimentally observed turn type switch from an irregular turn (1FSD) to type I' turn (1FME) was well reproduced with the present simulation.

Magnetic properties of nano-multiferroic materials

NASA Astrophysics Data System (ADS)

Ramam, Koduri; Diwakar, Bhagavathula S.; Varaprasad, Kokkarachedu; Swaminadham, Veluri; Reddy, Venu

2017-11-01

Latent magnetization in the multiferroics can be achieved via the structural distortion with respect to particle size and destroying the spiral spin structure, which plays the vital role in high-performance applications. In this investigation, multifunctional single phase Bi1-xLaxFe1-yCoyO3 nanomaterials were synthesized by co-precipitation technique. The chemical composition, phase genesis, morphology and thermal characteristics of the Bi1-xLaxFe1-yCoyO3 were studied by FTIR, XRD, SEM/EDS, TEM and TGA. XRD studies confirmed single phase distorted rhombohedral structure in Bi1-xLaxFe1-yCoyO3. The novelty in magnetic behavior of the Bi0.85La0.15Fe0.75Co0.25O3 multiferroic at room temperature showed both ferro and anti-ferromagnetic nature with higher order remanent magnetization among other nanocomposites in this study. This magnetic anomaly in Bi0.85La0.15Fe0.75Co0.25O3 is due to doping and size effects on the crystal structure that leads to spin-orbit interactions. Besides, Bi0.85La0.15Fe0.75Co0.25O3 integrated graphene oxide (GO) nanocomposite has shown the change in the magnetic hysteresis that indicates the effect of the semiconducting behavior of GO on the ordered magnetic moments in the multiferroic. This kind of magnetic anomaly could form advanced multiferroic devices.

Structural characterization of new Schiff bases of sulfamethoxazole and sulfathiazole, their antibacterial activity and docking computation with DHPS protein structure.

PubMed

Mondal, Sudipa; Mandal, Santi M; Mondal, Tapan Kumar; Sinha, Chittaranjan

2015-01-01

New Schiff bases (1, 2) of substituted salicylaldehydes and sulfamethoxazole (SMX)/sulfathiazole (STZ) are synthesized and characterized by elemental analysis and spectroscopic data. Single crystal X-ray structure of one of the compounds (E)-4-((3,5-dichloro-2-hydroxybenzylidene)amino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide (1c) has been determined. Antimicrobial activities of the Schiff bases and parent sulfonamides (SMX, STZ) have been examined against several Gram-positive and Gram-negative bacteria and sulfonamide resistant pathogens; the lowest MIC is observed for (E)-4-((3,5-dichloro-2-hydroxybenzylidene)amino)-N-(thiazol-2-yl)benzene sulfonamide (2c) (8.0 μg mL(-1)) and (E)-4-((3,5-dichloro-2-hydroxybenzylidene)amino)-N-(5-methylisoxazol-3-yl)benzene sulfonamide (1c) (16.0 μg mL(-1)) against sulfonamide resistant pathogens. DFT optimized structures of the Schiff bases have been used to carry out molecular docking studies with DHPS (dihydropteroate synthase) protein structure (downloaded from Protein Data Bank) using Discovery Studio 3.5 to find the most preferred binding mode of the ligand inside the protein cavity. The theoretical data have been well correlated with the experimental results. Cell viability assay and ADMET studies predict that 1c and 2c have good drug like characters. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of self-assembled monolayer structural order, surface homogeneity and surface energy on pentacene morphology and thin film transistor device performance.

PubMed

Hutchins, Daniel Orrin; Weidner, Tobias; Baio, Joe; Polishak, Brent; Acton, Orb; Cernetic, Nathan; Ma, Hong; Jen, Alex K-Y

2013-01-04

A systematic study of six phosphonic acid (PA) self-assembled monolayers (SAMs) with tailored molecular structures is performed to evaluate their effectiveness as dielectric modifying layers in organic field-effect transistors (OFETs) and determine the relationship between SAM structural order, surface homogeneity, and surface energy in dictating device performance. SAM structures and surface properties are examined by near edge X-ray absorption fine structure (NEXAFS) spectroscopy, contact angle goniometry, and atomic force microscopy (AFM). Top-contact pentacene OFET devices are fabricated on SAM modified Si with a thermally grown oxide layer as a dielectric. For less ordered methyl- and phenyl-terminated alkyl ~(CH 2 ) 12 PA SAMs of varying surface energies, pentacene OFETs show high charge carrier mobilities up to 4.1 cm 2 V -1 s -1 . It is hypothesized that for these SAMs, mitigation of molecular scale roughness and subsequent control of surface homogeneity allow for large pentacene grain growth leading to high performance pentacene OFET devices. PA SAMs that contain bulky terminal groups or are highly crystalline in nature do not allow for a homogenous surface at a molecular level and result in charge carrier mobilities of 1.3 cm 2 V -1 s -1 or less. For all molecules used in this study, no causal relationship between SAM surface energy and charge carrier mobility in pentacene FET devices is observed.

Effects of self-assembled monolayer structural order, surface homogeneity and surface energy on pentacene morphology and thin film transistor device performance

PubMed Central

Hutchins, Daniel Orrin; Weidner, Tobias; Baio, Joe; Polishak, Brent; Acton, Orb; Cernetic, Nathan; Ma, Hong; Jen, Alex K.-Y.

2013-01-01

A systematic study of six phosphonic acid (PA) self-assembled monolayers (SAMs) with tailored molecular structures is performed to evaluate their effectiveness as dielectric modifying layers in organic field-effect transistors (OFETs) and determine the relationship between SAM structural order, surface homogeneity, and surface energy in dictating device performance. SAM structures and surface properties are examined by near edge X-ray absorption fine structure (NEXAFS) spectroscopy, contact angle goniometry, and atomic force microscopy (AFM). Top-contact pentacene OFET devices are fabricated on SAM modified Si with a thermally grown oxide layer as a dielectric. For less ordered methyl- and phenyl-terminated alkyl ~(CH2)12 PA SAMs of varying surface energies, pentacene OFETs show high charge carrier mobilities up to 4.1 cm2 V−1 s−1. It is hypothesized that for these SAMs, mitigation of molecular scale roughness and subsequent control of surface homogeneity allow for large pentacene grain growth leading to high performance pentacene OFET devices. PA SAMs that contain bulky terminal groups or are highly crystalline in nature do not allow for a homogenous surface at a molecular level and result in charge carrier mobilities of 1.3 cm2 V−1 s−1 or less. For all molecules used in this study, no causal relationship between SAM surface energy and charge carrier mobility in pentacene FET devices is observed. PMID:24086795

High-resolution crystal structure and IgE recognition of the major grass pollen allergen Phl p 3.

PubMed

Devanaboyina, S C; Cornelius, C; Lupinek, C; Fauland, K; Dall'Antonia, F; Nandy, A; Hagen, S; Flicker, S; Valenta, R; Keller, W

2014-12-01

Group 2 and 3 grass pollen allergens are major allergens with high allergenic activity and exhibit structural similarity with the C-terminal portion of major group 1 allergens. In this study, we aimed to determine the crystal structure of timothy grass pollen allergen, Phl p 3, and to study its IgE recognition and cross-reactivity with group 2 and group 1 allergens. The three-dimensional structure of Phl p 3 was solved by X-ray crystallography and compared with the structures of group 1 and 2 grass pollen allergens. Cross-reactivity was studied using a human monoclonal antibody which inhibits allergic patients' IgE binding and by IgE inhibition experiments with patients' sera. Conformational Phl p 3 IgE epitopes were predicted with the algorithm SPADE, and Phl p 3 variants containing single point mutations in the predicted IgE binding sites were produced to analyze allergic patients' IgE binding. Phl p 3 is a globular β-sandwich protein showing structural similarity to Phl p 2 and the Phl p 1-C-terminal domain. Phl p 3 showed IgE cross-reactivity with group 2 allergens but not with group 1 allergens. SPADE identified two conformational IgE epitope-containing areas, of which one overlaps with the epitope defined by the monoclonal antibody. The mutation of arginine 68 to alanine completely abolished binding of the blocking antibody. This mutation and a mutation of D13 in the predicted second IgE epitope area also reduced allergic patients' IgE binding. Group 3 and group 2 grass pollen allergens are cross-reactive allergens containing conformational IgE epitopes. They lack relevant IgE cross-reactivity with group 1 allergens and therefore need to be included in diagnostic tests and allergen-specific treatments in addition to group 1 allergens. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nickel superoxide dismutase: structural and functional roles of His1 and its H-bonding network

DOE PAGES

Maroney, Michael J.; Cabelli, Diane E.; Ryan, Kelly C.; ...

2015-01-21

Crystal structures of nickel-dependent superoxide dismutases (NiSODs) reveal the presence of a H-bonding network formed between the NH group of the apical imidazole ligand from His1 and the Glu17 carboxylate from a neighboring subunit in the hexameric enzyme. This interaction is supported by another intrasubunit H-bond between Glu17 and Arg47. In this study, four mutant NiSOD proteins were produced to experimentally evaluate the roles of this H-bonding network and compare the results with prior predictions from density functional theory calculations. The X-ray crystal structure of H1A-NiSOD, which lacks the apical ligand entirely, reveals that in the absence of the Glu17-His1more » H-bond, the active site is disordered. Characterization of this variant using X-ray absorption spectroscopy (XAS) shows that Ni(II) is bound in the expected N₂S₂ planar coordination site. Despite these structural perturbations, the H1A-NiSOD variant retains 4% of wild-type (WT) NiSOD activity. Three other mutations were designed to preserve the apical imidazole ligand but perturb the H-bonding network: R47A-NiSOD, which lacks the intramolecular H-bonding interaction; E17R/R47A-NiSOD, which retains the intramolecular H-bond but lacks the intermolecular Glu17-His1 H-bond; and E17A/R47ANiSOD, which lacks both H-bonding interactions. These variants were characterized by a combination of techniques, including XAS to probe the nickel site structure, kinetic studies employing pulse-radiolytic production of superoxide, and electron paramagnetic resonance to assess the Ni redox activity. The results indicate that in addition to the roles in redox tuning suggested on the basis of previous computational studies, the Glu17-His1 H-bond plays an important structural role in the proper folding of the “Ni-hook” motif that is a critical feature of the active site.« less

Systems definition study for shuttle demonstration flights of large space structures. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1979-01-01

The development of large space structure technology is discussed, with emphasis on space fabricated structures which are automatically manufactured in space from sheet-strip materials and assembled on-orbit. Definition of a flight demonstration involving an Automated Beam Builder and the building and assembling of large structures is presented.

Brain and behaviour phenotyping of a mouse model of neurofibromatosis type-1: an MRI/DTI study on social cognition.

PubMed

Petrella, L I; Cai, Y; Sereno, J V; Gonçalves, S I; Silva, A J; Castelo-Branco, M

2016-09-01

Neurofibromatosis type-1 (NF1) is a common neurogenetic disorder and an important cause of intellectual disability. Brain-behaviour associations can be examined in vivo using morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to study brain structure. Here, we studied structural and behavioural phenotypes in heterozygous Nf1 mice (Nf1(+/-) ) using T2-weighted imaging MRI and DTI, with a focus on social recognition deficits. We found that Nf1(+/-) mice have larger volumes than wild-type (WT) mice in regions of interest involved in social cognition, the prefrontal cortex (PFC) and the caudate-putamen (CPu). Higher diffusivity was found across a distributed network of cortical and subcortical brain regions, within and beyond these regions. Significant differences were observed for the social recognition test. Most importantly, significant structure-function correlations were identified concerning social recognition performance and PFC volumes in Nf1(+/-) mice. Analyses of spatial learning corroborated the previously known deficits in the mutant mice, as corroborated by platform crossings, training quadrant time and average proximity measures. Moreover, linear discriminant analysis of spatial performance identified 2 separate sub-groups in Nf1(+/-) mice. A significant correlation between quadrant time and CPu volumes was found specifically for the sub-group of Nf1(+/-) mice with lower spatial learning performance, suggesting additional evidence for reorganization of this region. We found strong evidence that social and spatial cognition deficits can be associated with PFC/CPu structural changes and reorganization in NF1. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Molecular and crystal structure and the Hirshfeld surface analysis of 1-amino-1-deoxy-α-D-sorbopyranose and 1-amino-1-deoxy-α-D-psicopyranose ("D-sorbosamine" and "D-psicosamine") derivatives

NASA Astrophysics Data System (ADS)

Mossine, Valeri V.; Barnes, Charles L.; Mawhinney, Thomas P.

2018-05-01

Sorbosamine and psicosamine are the last two 1-amino-1-deoxy-hexuloses for which no structural data were available. We report on a13C NMR and a single crystal X-ray diffraction study of 1-deoxy-1-(N-methylphenylamino)-D-sorbose (1) and 1-deoxy-1-(N-methylphenylamino)-D-psicose (2). In solutions, both aminosugars are conformationally unstable and establish equilibria, with 90.7% α-pyranose, 3.8% α-furanose, 1.0% β-pyranose, 0.5% β-furanose, and 4.0% acyclic keto form for 1 and 32.4% α-furanose, 27.2% α-pyranose, 21.0% β-pyranose, 9.1% β-furanose, and 11.0% acyclic keto form for 2. X-ray diffraction data provided detailed structural information on 1 and 2 in the α-pyranose form. Both molecules adopt the 5C2 ring conformations, the bond distances and valence angles compare well with respective pyranose structures. All hydroxyl groups in crystal structures of both 1 and 2 participate in two-dimensional hydrogen bonding networks, the H-bonding pattern in 1 is dominated by co-crystallized water molecules. The Hirshfeld surface analysis revealed a significant contribution of non- or weakly polar interactions to the packing forces for both molecules, with crystal structure of 2 featuring short H⋯H contacts. Other structural features found in 2 are a significant planarity of the tertiary amino group (the pyramid heights are 0.127 Å in 2 vs 0.231 Å in 1), a concomitant non-involvement of the amine nitrogen in heteroatom contacts, and a unique anti-periplanar conformation around the C1sbnd C2 bond.

Propensities of Aromatic Amino Acids versus Leucine and Proline to Induce Residual Structure in the Denatured State Ensemble of Iso-1-cytochrome c

PubMed Central

Finnegan, Michaela L.; Bowler, Bruce E.

2010-01-01

Histidine-heme loop formation in the denatured state of a protein is a sensitive means to probe for residual structure under unfolding conditions. In this study, we use a host-guest approach to investigate the relative tendencies of different amino acids to promote residual structure under denaturing conditions. The host for this work is a 6 amino acid insert of five alanines followed by a lysine engineered immediately following a unique histidine near the N-terminus of yeast iso-1-cytochrome c. We substitute the 4th alanine in this sequence, HAAAXAK, with X = Trp, Phe, Tyr and Leu. The effects of proline are tested with substitutions at positions 1 and 5 in the insert, HPAAAAK and HAAAAPK, respectively. Thermodynamic studies on His-heme loop formation in 3 M guanidine hydrochloride reveal significant stabilization of residual structure by aromatic amino acids, particularly, Trp and Phe, and minimal stabilization of residual structure by Leu. Prolines disfavor His-heme loop formation slightly, presumably due to enhanced chain stiffness. Kinetic studies reveal that much of the change in His-heme loop stability for the aromatic amino acids is caused by a slowing of the rate of His-heme loop breakage, indicating that residual structure is preferentially stabilized in the closed-loop form of the denatured state. PMID:20850458

Integrating aeromagnetic and Landsat™ 8 data into subsurface structural mapping of Precambrian basement complex

NASA Astrophysics Data System (ADS)

Kayode, John Stephen; Nawawi, M. N. M.; Abdullah, Khiruddin B.; Khalil, Amin E.

2017-01-01

The integration of Aeromagnetic data and remotely sensed imagery with the intents of mapping the subsurface geological structures in part of the South-western basement complex of Nigeria was developed using the PCI Geomatica Software. 2013. The data obtained from the Nigerian Geological Survey Agency; was corrected using Regional Residual Separation of the Total Magnetic field anomalies enhanced, and International Geomagnetic Reference Field removed. The principal objective of this study is, therefore, to introduce a rapid and efficient method of subsurface structural depth estimate and structural index evaluation through the incorporation of the Euler Deconvolution technique into PCI Geomatica 2013 to prospect for subsurface geological structures. The shape and depth of burial helped to define these structures from the regional aeromagnetic map. The method enabled various structural indices to be automatically delineated for an index of between 0.5 SI and 3.0 SI at a maximum depth of 1.1 km that clearly showed the best depths estimate for all the structural indices. The results delineate two major magnetic belts in the area; the first belt shows an elongated ridge-like structure trending mostly along the NorthNortheast-SouthSouthwest and the other anomalies trends primarily in the Northeast, Northwest, Northeast-Southwest parts of the study area that could be attributed to basement complex granitic intrusions from the tectonic history of the area. The majority of the second structures showed various linear structures different from the first structure. Basically, a significant offset was delineated at the core segment of the study area, suggesting a major subsurface geological feature that controls mineralisation in this area.

Domain analyses of Usher syndrome causing Clarin-1 and GPR98 protein models.

PubMed

Khan, Sehrish Haider; Javed, Muhammad Rizwan; Qasim, Muhammad; Shahzadi, Samar; Jalil, Asma; Rehman, Shahid Ur

2014-01-01

Usher syndrome is an autosomal recessive disorder that causes hearing loss, Retinitis Pigmentosa (RP) and vestibular dysfunction. It is clinically and genetically heterogeneous disorder which is clinically divided into three types i.e. type I, type II and type III. To date, there are about twelve loci and ten identified genes which are associated with Usher syndrome. A mutation in any of these genes e.g. CDH23, CLRN1, GPR98, MYO7A, PCDH15, USH1C, USH1G, USH2A and DFNB31 can result in Usher syndrome or non-syndromic deafness. These genes provide instructions for making proteins that play important roles in normal hearing, balance and vision. Studies have shown that protein structures of only seven genes have been determined experimentally and there are still three genes whose structures are unavailable. These genes are Clarin-1, GPR98 and Usherin. In the absence of an experimentally determined structure, homology modeling and threading often provide a useful 3D model of a protein. Therefore in the current study Clarin-1 and GPR98 proteins have been analyzed for signal peptide, domains and motifs. Clarin-1 protein was found to be without any signal peptide and consists of prokar lipoprotein domain. Clarin-1 is classified within claudin 2 super family and consists of twelve motifs. Whereas, GPR98 has a 29 amino acids long signal peptide and classified within GPCR family 2 having Concanavalin A-like lectin/glucanase superfamily. It was found to be consists of GPS and G protein receptor F2 domains and twenty nine motifs. Their 3D structures have been predicted using I-TASSER server. The model of Clarin-1 showed only α-helix but no beta sheets while model of GPR98 showed both α-helix and β sheets. The predicted structures were then evaluated and validated by MolProbity and Ramachandran plot. The evaluation of the predicted structures showed 78.9% residues of Clarin-1 and 78.9% residues of GPR98 within favored regions. The findings of present study has resulted in the three dimensional structure prediction and conserved domain analysis which will be quite beneficial in better understanding of molecular components, protein-protein interaction, clinical heterogeneity and pathophysiology of Usher syndrome.

Domain analyses of Usher syndrome causing Clarin-1 and GPR98 protein models

PubMed Central

Khan, Sehrish Haider; Javed, Muhammad Rizwan; Qasim, Muhammad; Shahzadi, Samar; Jalil, Asma; Rehman, Shahid ur

2014-01-01

Usher syndrome is an autosomal recessive disorder that causes hearing loss, Retinitis Pigmentosa (RP) and vestibular dysfunction. It is clinically and genetically heterogeneous disorder which is clinically divided into three types i.e. type I, type II and type III. To date, there are about twelve loci and ten identified genes which are associated with Usher syndrome. A mutation in any of these genes e.g. CDH23, CLRN1, GPR98, MYO7A, PCDH15, USH1C, USH1G, USH2A and DFNB31 can result in Usher syndrome or non-syndromic deafness. These genes provide instructions for making proteins that play important roles in normal hearing, balance and vision. Studies have shown that protein structures of only seven genes have been determined experimentally and there are still three genes whose structures are unavailable. These genes are Clarin-1, GPR98 and Usherin. In the absence of an experimentally determined structure, homology modeling and threading often provide a useful 3D model of a protein. Therefore in the current study Clarin-1 and GPR98 proteins have been analyzed for signal peptide, domains and motifs. Clarin-1 protein was found to be without any signal peptide and consists of prokar lipoprotein domain. Clarin-1 is classified within claudin 2 super family and consists of twelve motifs. Whereas, GPR98 has a 29 amino acids long signal peptide and classified within GPCR family 2 having Concanavalin A-like lectin/glucanase superfamily. It was found to be consists of GPS and G protein receptor F2 domains and twenty nine motifs. Their 3D structures have been predicted using I-TASSER server. The model of Clarin-1 showed only α-helix but no beta sheets while model of GPR98 showed both α-helix and β sheets. The predicted structures were then evaluated and validated by MolProbity and Ramachandran plot. The evaluation of the predicted structures showed 78.9% residues of Clarin-1 and 78.9% residues of GPR98 within favored regions. The findings of present study has resulted in the three dimensional structure prediction and conserved domain analysis which will be quite beneficial in better understanding of molecular components, protein-protein interaction, clinical heterogeneity and pathophysiology of Usher syndrome. PMID:25258483

SL1 revisited: functional analysis of the structure and conformation of HIV-1 genome RNA.

PubMed

Sakuragi, Sayuri; Yokoyama, Masaru; Shioda, Tatsuo; Sato, Hironori; Sakuragi, Jun-Ichi

2016-11-11

The dimer initiation site/dimer linkage sequence (DIS/DLS) region of HIV is located on the 5' end of the viral genome and suggested to form complex secondary/tertiary structures. Within this structure, stem-loop 1 (SL1) is believed to be most important and an essential key to dimerization, since the sequence and predicted secondary structure of SL1 are highly stable and conserved among various virus subtypes. In particular, a six-base palindromic sequence is always present at the hairpin loop of SL1 and the formation of kissing-loop structure at this position between the two strands of genomic RNA is suggested to trigger dimerization. Although the higher-order structure model of SL1 is well accepted and perhaps even undoubted lately, there could be stillroom for consideration to depict the functional SL1 structure while in vivo (in virion or cell). In this study, we performed several analyses to identify the nucleotides and/or basepairing within SL1 which are necessary for HIV-1 genome dimerization, encapsidation, recombination and infectivity. We unexpectedly found that some nucleotides that are believed to contribute the formation of the stem do not impact dimerization or infectivity. On the other hand, we found that one G-C basepair involved in stem formation may serve as an alternative dimer interactive site. We also report on our further investigation of the roles of the palindromic sequences on viral replication. Collectively, we aim to assemble a more-comprehensive functional map of SL1 on the HIV-1 viral life cycle. We discovered several possibilities for a novel structure of SL1 in HIV-1 DLS. The newly proposed structure model suggested that the hairpin loop of SL1 appeared larger, and genome dimerization process might consist of more complicated mechanism than previously understood. Further investigations would be still required to fully understand the genome packaging and dimerization of HIV.

Structure-activity relationship investigation for benzonaphthyridinone derivatives as novel potent Bruton's tyrosine kinase (BTK) irreversible inhibitors.

PubMed

Wang, Beilei; Deng, Yuanxin; Chen, Yongfei; Yu, Kailin; Wang, Aoli; Liang, Qianmao; Wang, Wei; Chen, Cheng; Wu, Hong; Hu, Chen; Miao, Weili; Hur, Wooyoung; Wang, Wenchao; Hu, Zhenquan; Weisberg, Ellen L; Wang, Jinhua; Ren, Tao; Wang, Yinsheng; Gray, Nathanael S; Liu, Qingsong; Liu, Jing

2017-09-08

Through a structure-based drug design approach, a tricyclic benzonaphthyridinone pharmacophore was used as a starting point for carrying out detailed medicinal structure-activity relationhip (SAR) studies geared toward characterization of a panel of proposed BTK inhibitors, including 6 (QL-X-138), 7 (BMX-IN-1) and 8 (QL47). These studies led to the discovery of the novel potent irreversible BTK inhibitor, compound 18 (CHMFL-BTK-11). Kinetic analysis of compound 18 revealed an irreversible binding efficacy (k inact /K i ) of 0.01 μM -1 s -1 . Compound 18 potently inhibited BTK kinase Y223 auto-phosphorylation (EC 50  < 100 nM), arrested cell cycle in G0/G1 phase, and induced apoptosis in Ramos, MOLM13 and Pfeiffer cells. We believe these features would make 18 a good pharmacological tool for studying BTK-related pathologies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Evidence for monoclinic distortion in the ground state phase of underdoped La 1.95Sr 0.05CuO 4: A single crystal neutron diffraction study

DOE PAGES

Singh, Anar; Schefer, Jurg; Sura, Ravi; ...

2016-03-24

The existing controversy about the symmetry of the crystal structure of the ground state of the critical doped La 1.95Sr 0.05CuO 4 has been resolved by analyzing the single crystal neutron diffraction data collected between 5 and 730 K. We observed small but significant intensities for "forbidden" reflections given by extinction rules of the orthorhombic Bmab space group at low temperatures. A careful investigation of neutron diffraction data reveals that the crystal structure of La 1.95Sr 0.05CuO 4 at 5 K is monoclinic with B2/m (2/m 1 1) space group. The monoclinic structure emerges from the orthorhombic structure in amore » continuous way; however, the structure is stable below similar to 120K which agrees with other observed phenomena. Lastly, our results on symmetry changes are crucial for the interpretation of physical properties also in other high temperature superconductors with similar structures.« less

Evidence for monoclinic distortion in the ground state phase of underdoped La{sub 1.95}Sr{sub 0.05}CuO{sub 4}: A single crystal neutron diffraction study

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

Singh, Anar, E-mail: singhanar@gmail.com; Schefer, Jürg; Frontzek, Matthias

2016-03-28

The existing controversy about the symmetry of the crystal structure of the ground state of the critical doped La{sub 1.95}Sr{sub 0.05}CuO{sub 4} has been resolved by analyzing the single crystal neutron diffraction data collected between 5 and 730 K. We observed small but significant intensities for “forbidden” reflections given by extinction rules of the orthorhombic Bmab space group at low temperatures. A careful investigation of neutron diffraction data reveals that the crystal structure of La{sub 1.95}Sr{sub 0.05}CuO{sub 4} at 5 K is monoclinic with B2/m (2/m 1 1) space group. The monoclinic structure emerges from the orthorhombic structure in a continuous way;more » however, the structure is stable below ∼120 K which agrees with other observed phenomena. Our results on symmetry changes are crucial for the interpretation of physical properties also in other high temperature superconductors with similar structures.« less

Protein–Mineral Interactions: Molecular Dynamics Simulations Capture Importance of Variations in Mineral Surface Composition and Structure

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

Andersen, Amity; Reardon, Patrick N.; Chacon, Stephany S.

Molecular dynamics simulations, conventional and metadynamics, were performed to determine the interaction of model protein Gb1 over kaolinite (001), Na+-montmorillonite (001), Ca2+-montmorillonite (001), goethite (100), and Na+-birnessite (001) mineral surfaces. Gb1, a small (56 residue) protein with a well-characterized solution-state nuclear magnetic resonance (NMR) structure and having α-helix, four-fold β-sheet, and hydrophobic core features, is used as a model protein to study protein soil mineral interactions and gain insights on structural changes and potential degradation of protein. From our simulations, we observe little change to the hydrated Gb1 structure over the kaolinite, montmorillonite, and goethite surfaces relative to its solvatedmore » structure without these mineral surfaces present. Over the Na+-birnessite basal surface, however, the Gb1 structure is highly disturbed as a result of interaction with this birnessite surface. Unraveling of the Gb1 β-sheet at specific turns and a partial unraveling of the α-helix is observed over birnessite, which suggests specific vulnerable residue sites for oxidation or hydrolysis possibly leading to fragmentation.« less

Implicit transfer of reversed temporal structure in visuomotor sequence learning.

PubMed

Tanaka, Kanji; Watanabe, Katsumi

2014-04-01

Some spatio-temporal structures are easier to transfer implicitly in sequential learning. In this study, we investigated whether the consistent reversal of triads of learned components would support the implicit transfer of their temporal structure in visuomotor sequence learning. A triad comprised three sequential button presses ([1][2][3]) and seven consecutive triads comprised a sequence. Participants learned sequences by trial and error, until they could complete it 20 times without error. Then, they learned another sequence, in which each triad was reversed ([3][2][1]), partially reversed ([2][1][3]), or switched so as not to overlap with the other conditions ([2][3][1] or [3][1][2]). Even when the participants did not notice the alternation rule, the consistent reversal of the temporal structure of each triad led to better implicit transfer; this was confirmed in a subsequent experiment. These results suggest that the implicit transfer of the temporal structure of a learned sequence can be influenced by both the structure and consistency of the change. Copyright © 2013 Cognitive Science Society, Inc.

Structural properties of a family of hydrogen-bonded co-crystals formed between gemfibrozil and hydroxy derivatives of t-butylamine, determined directly from powder X-ray diffraction data

NASA Astrophysics Data System (ADS)

Cheung, Eugene Y.; David, Sarah E.; Harris, Kenneth D. M.; Conway, Barbara R.; Timmins, Peter

2007-03-01

We report the formation and structural properties of co-crystals containing gemfibrozil and hydroxy derivatives of t-butylamine H 2NC(CH 3) 3-n(CH 2OH) n, with n=0, 1, 2 and 3. In each case, a 1:1 co-crystal is formed, with transfer of a proton from the carboxylic acid group of gemfibrozil to the amino group of the t-butylamine derivative. All of the co-crystal materials prepared are polycrystalline powders, and do not contain single crystals of suitable size and/or quality for single crystal X-ray diffraction studies. Structure determination of these materials has been carried out directly from powder X-ray diffraction data, using the direct-space Genetic Algorithm technique for structure solution followed by Rietveld refinement. The structural chemistry of this series of co-crystal materials reveals well-defined structural trends within the first three members of the family ( n=0, 1, 2), but significantly contrasting structural properties for the member with n=3.

Crystal structure of a putative exo-β-1,3-galactanase from Bifidobacterium bifidum S17

PubMed Central

Godoy, Andre S.; de Lima, Mariana Z. T.; Camilo, Cesar M.; Polikarpov, Igor

2016-01-01

Given the current interest in second-generation biofuels, carbohydrate-active enzymes have become the most important tool to overcome the structural recalcitrance of the plant cell wall. While some glycoside hydrolase families have been exhaustively described, others remain poorly characterized, especially with regard to structural information. The family 43 glycoside hydrolases are a diverse group of inverting enzymes; the available structure information on these enzymes is mainly from xylosidases and arabinofuranosidase. Currently, only one structure of an exo-β-1,3-galactanase is available. Here, the production, crystallization and structure determination of a putative exo-β-1,3-galactanase from Bifidobacterium bifidum S17 (BbGal43A) are described. BbGal43A was successfully produced and showed activity towards synthetic galactosides. BbGal43A was subsequently crystallized and data were collected to 1.4 Å resolution. The structure shows a single-domain molecule, differing from known homologues, and crystal contact analysis predicts the formation of a dimer in solution. Further biochemical studies are necessary to elucidate the differences between BbGal43A and its characterized homologues. PMID:27050262

Electrical characterization of gold-DNA-gold structures in presence of an external magnetic field by means of I-V curve analysis.

PubMed

Khatir, Nadia Mahmoudi; Banihashemian, Seyedeh Maryam; Periasamy, Vengadesh; Ritikos, Richard; Abd Majid, Wan Haliza; Abdul Rahman, Saadah

2012-01-01

This work presents an experimental study of gold-DNA-gold structures in the presence and absence of external magnetic fields with strengths less than 1,200.00 mT. The DNA strands, extracted by standard method were used to fabricate a Metal-DNA-Metal (MDM) structure. Its electric behavior when subjected to a magnetic field was studied through its current-voltage (I-V) curve. Acquisition of the I-V curve demonstrated that DNA as a semiconductor exhibits diode behavior in the MDM structure. The current versus magnetic field strength followed a decreasing trend because of a diminished mobility in the presence of a low magnetic field. This made clear that an externally imposed magnetic field would boost resistance of the MDM structure up to 1,000.00 mT and for higher magnetic field strengths we can observe an increase in potential barrier in MDM junction. The magnetic sensitivity indicates the promise of using MDM structures as potential magnetic sensors.

Electrical Characterization of Gold-DNA-Gold Structures in Presence of an External Magnetic Field by Means of I–V Curve Analysis

PubMed Central

Khatir, Nadia Mahmoudi; Banihashemian, Seyedeh Maryam; Periasamy, Vengadesh; Ritikos, Richard; Majid, Wan Haliza Abd; Rahman, Saadah Abdul

2012-01-01

This work presents an experimental study of gold-DNA-gold structures in the presence and absence of external magnetic fields with strengths less than 1,200.00 mT. The DNA strands, extracted by standard method were used to fabricate a Metal-DNA-Metal (MDM) structure. Its electric behavior when subjected to a magnetic field was studied through its current-voltage (I–V) curve. Acquisition of the I–V curve demonstrated that DNA as a semiconductor exhibits diode behavior in the MDM structure. The current versus magnetic field strength followed a decreasing trend because of a diminished mobility in the presence of a low magnetic field. This made clear that an externally imposed magnetic field would boost resistance of the MDM structure up to 1,000.00 mT and for higher magnetic field strengths we can observe an increase in potential barrier in MDM junction. The magnetic sensitivity indicates the promise of using MDM structures as potential magnetic sensors. PMID:22737025

TEM study of the (SbS){sub 1+δ}(NbS{sub 2}){sub n}, (n=1, 2, 3; δ~1.14, 1.20) misfit layer phases

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

Gómez-Herrero, A., E-mail: adriangh@pdi.ucm.es; Landa-Cánovas, A.R.; Otero-Díaz, L.C.

In the Sb–Nb–S system four new misfit layer phases have been found and carefully investigated via Transmission Electron Microscopy (TEM). Their structures are of composite modulated structure type with stoichiometries that can be formulated as (SbS){sub 1+δ}(NbS{sub 2}){sub n}; for n=1, δ~1.14 and 1.19; for n=2, δ~1.18 and for n=3, δ~1.19. Selected Area Electron Diffraction (SAED) patterns show an almost commensurate fit between the pseudo-tetragonal (SbS) and the pseudo-orthohexagonal (NbS{sub 2}){sub n} subcells along the misfit direction a, with 3(SbS)≈5(NbS{sub 2}), being b the same for both sub-lattices and c the stacking direction. For n=1, a commensurate phase with 4a{submore » SbS}=7a{sub NbS2} has also been observed. In addition to the characteristic misfit and associated modulation of the two sub-structures, a second modulation is also present which appears to be primarily associated with the (SbS) sub-structure of both the n=1 and n=2 phases. High Resolution Transmission Electron Microscopy (HRTEM) images show ordered stacking sequences between the (SbS) and (NbS{sub 2}){sub n} lamellae for each of the four phases, however, disordered intergrowths were also occasionally found. Most of the crystals showed different kinds of twinning defects on quite a fine scale. Many crystals showed curled up edges. In some cases the lamellar crystals were entirely folded giving rise to similar diffraction patterns as found for cylindrical crystals. - Graphical abstract: Idealized structure models of the first three members of the homologous series (SbS){sub 1+δ}(NbS{sub 2}){sub n}. - Highlights: • Transmission Electron Microscopy study of misfit layer sulfides (SbS){sub 1+δ}(NbS{sub 2}){sub n}. • The structures consist of a (SbS) layer interleaved between n (NbS{sub 2}) layers. • Two different members n=1, one n=2 and one n=3 have been studied. • Twinning, intergrowths and different modulations in the (SbS) substructure.« less

Structural and biochemical changes induced by pulsed electric field treatments on Cabernet Sauvignon grape berry skins: impact on cell wall total tannins and polysaccharides.

PubMed

Cholet, Céline; Delsart, Cristèle; Petrel, Mélina; Gontier, Etienne; Grimi, Nabil; L'hyvernay, Annie; Ghidossi, Remy; Vorobiev, Eugène; Mietton-Peuchot, Martine; Gény, Laurence

2014-04-02

Pulsed electric field (PEF) treatment is an emerging technology that is arousing increasing interest in vinification processes for its ability to enhance polyphenol extraction performance. The aim of this study was to investigate the effects of PEF treatment on grape skin histocytological structures and on the organization of skin cell wall polysaccharides and tannins, which, until now, have been little investigated. This study relates to the effects of two PEF treatments on harvested Cabernet Sauvignon berries: PEF1 (medium strength (4 kV/cm); short duration (1 ms)) and PEF2 (low intensity (0.7 kV/cm); longer duration (200 ms)). Histocytological observations and the study of levels of polysaccharidic fractions and total amounts of tannins allowed differentiation between the two treatments. Whereas PEF1 had little effect on the polyphenol structure and pectic fraction, PEF2 profoundly modified the organization of skin cell walls. Depending on the PEF parameters, cell wall structure was differently affected, providing variable performance in terms of polyphenol extraction and wine quality.

Nanotwinning and structural phase transition in CdS quantum dots

NASA Astrophysics Data System (ADS)

Kumar, Pragati; Saxena, Nupur; Chandra, Ramesh; Gupta, Vinay; Agarwal, Avinash; Kanjilal, Dinakar

2012-10-01

Nanotwin structures are observed in high-resolution transmission electron microscopy studies of cubic phase CdS quantum dots in powder form by chemical co-precipitation method. The deposition of thin films of nanocrystalline CdS is carried out on silicon, glass, and TEM grids keeping the substrates at room temperature (RT) and 200°C by pulsed laser ablation. These films are then subjected to thermal annealing at different temperatures. Glancing angle X-ray diffraction results confirm structural phase transitions after thermal annealing of films deposited at RT and 200°C. The variation of average particle size and ratio of intensities in Raman peaks I 2LO/ I 1LO with annealing temperature are studied. It is found that electron-phonon interaction is a function of temperature and particle size and is independent of the structure. Besides Raman modes LO, 2LO and 3LO of CdS at approximately 302, 603, and 903 cm-1 respectively, two extra Raman modes at approximately 390 and 690 cm-1 are studied for the first time. The green and orange emissions observed in photoluminescence are correlated with phase transition.

Nanotwinning and structural phase transition in CdS quantum dots.

PubMed

Kumar, Pragati; Saxena, Nupur; Chandra, Ramesh; Gupta, Vinay; Agarwal, Avinash; Kanjilal, Dinakar

2012-10-23

Nanotwin structures are observed in high-resolution transmission electron microscopy studies of cubic phase CdS quantum dots in powder form by chemical co-precipitation method. The deposition of thin films of nanocrystalline CdS is carried out on silicon, glass, and TEM grids keeping the substrates at room temperature (RT) and 200°C by pulsed laser ablation. These films are then subjected to thermal annealing at different temperatures. Glancing angle X-ray diffraction results confirm structural phase transitions after thermal annealing of films deposited at RT and 200°C. The variation of average particle size and ratio of intensities in Raman peaks I2LO/I1LO with annealing temperature are studied. It is found that electron-phonon interaction is a function of temperature and particle size and is independent of the structure. Besides Raman modes LO, 2LO and 3LO of CdS at approximately 302, 603, and 903 cm-1 respectively, two extra Raman modes at approximately 390 and 690 cm-1 are studied for the first time. The green and orange emissions observed in photoluminescence are correlated with phase transition.

Study of novel junctionless Ge n-Tunneling Field-Effect Transistors with lightly doped drain (LDD) region

NASA Astrophysics Data System (ADS)

Liu, Xiangyu; Hu, Huiyong; Wang, Bin; Wang, Meng; Han, Genquan; Cui, Shimin; Zhang, Heming

2017-02-01

In this paper, a novel junctionless Ge n-Tunneling Field-Effect Transistors (TFET) structure is proposed. The simulation results show that Ion = 5.5 × 10-5A/μm is achieved. The junctionless device structure enhances Ion effectively and increases the region where significant BTBT occurs, comparing with the normal Ge-nTEFT. The impact of the lightly doped drain (LDD) region is investigated. A comparison of Ion and Ioff of the junctionless Ge n-TFET with different channel doping concentration ND and LDD doping concentration NLDD is studied. Ioff is reduced 1 order of magnitude with the optimized ND and NLDD are 1 × 1018cm-3 and 1 × 1017 cm-3, respectively. To reduce the gate induced drain leakage (GIDL) current, the impact of the sloped gate oxide structure is also studied. By employing the sloped gate oxide structure, the below 60 mV/decade subthreshold swing S = 46.2 mV/decade is achieved at Ion = 4.05 × 10-5A/μm and Ion/Ioff = 5.7 × 106.

Structural integrity test and assessment.

NASA Technical Reports Server (NTRS)

Suggs, F.; Poe, R.; Sannicandro, R.

1972-01-01

The feasibility of using an ultrasonic system on board the Space Shuttle Orbiter to facilitate structural evaluation and assessment was studied. Two factors are considered that could limit the capability of an ultrasonic system: (1) the effect of structure configuration and (2) the noise generated during vehicle launch. Results of the study indicate that although the structural configuration has direct bearing on sound propagation, strategic location of transducers will still permit flaw detection. The ultrasonic response data show that a severe acoustic environment does not interfere significantly with either propagation and reflection of surface waves or detection of crack-like flaws in the structure.

[Reparative and neoplastic spheroid cellular structures and their mathematical model].

PubMed

Kogan, E A; Namiot, V A; Demura, T A; Faĭzullina, N M; Sukhikh, G T

2014-01-01

Spheroid cell structures in the cell cultures have been described and are used for studying cell-cell and cell- matrix interactions. At the same time, spheroid cell structure participation in the repair and development of cancer in vivo remains unexplored. The aim of this study was to investigate the cellular composition of spherical structures and their functional significance in the repair of squamous epithelium in human papilloma virus-associated cervical pathology--chronic cervicitis and cervical intraepithelial neoplasia 1-3 degree, and also construct a mathematical model to explain the development and behavior of such spheroid cell structure.

A study on micro-structural and optical parameters of InxSe1-x thin film

NASA Astrophysics Data System (ADS)

Patel, P. B.; Desai, H. N.; Dhimmar, J. M.; Modi, B. P.

2018-04-01

Thin film of Indium Selenide (InSe) has been deposited by thermal evaporation technique onto pre cleaned glass substrate under high vacuum condition. The micro-structural and optical properties of InxSe1-x (x = 0.6, 1-x = 0.4) thin film have been characterized by X-ray diffractrometer (XRD) and UV-Visible spectrophotometer. The XRD spectra showed that InSe thin film has single phase hexagonal structure with preferred orientation along (1 1 0) direction. The micro-structural parameters (crystallite size, lattice strain, dislocation density, domain population) for InSe thin film have been calculated using XRD spectra. The optical parameters (absorption, transmittance, reflectance, energy band gap, Urbach energy) of InSe thin film have been evaluated from absorption spectra. The direct energy band gap and Urbach energy of InSe thin film is found to be 1.90 eV and 235 meV respectively.

Thermodynamics of Nucleic Acid ‘Shape Readout’ by an Aminosugar†

PubMed Central

Xi, Hongjuan; Davis, Erik; Ranjan, Nihar; Xue, Liang; Hyde-Volpe, David; Arya, Dev P.

2012-01-01

Recognition of nucleic acids is important for our understanding of nucleic acid structure as well as for our understanding of nucleic acid-protein interactions. In addition to the direct readout mechanisms of nucleic acids such as H-bonding, shape recognition of nucleic acids is being increasingly recognized to play an equally important role in DNA recognition. Competition Dialysis, UV, Flourescent Intercalator displacement (FID), Computational Docking, and calorimetry studies were conducted to study the interaction of neomycin with a variety of nucleic acid conformations (shapes). At pH 5.5, these results suggest: (1) Neomycin binds three RNA structures (16S A site rRNA, poly(rA)•poly(rA), and poly(rA)•poly(rU)) with high affinities, Ka~107M−1. (2) The binding of neomycin to A-form GC-rich oligomer d(A2G15C15T2)2 has comparable affinity to RNA structures. (3) The binding of neomycin to DNA•RNA hybrids shows a three-fold variance attributable to their structural differences (poly(dA) •poly(rU), Ka=9.4×106M−1 and poly(rA)•poly(dT), Ka=3.1×106M−1). (4) The interaction of neomycin with DNA triplex poly(dA)•2poly(dT) yields a binding affinity of Ka=2.4×105M−1. (5) Poly(dA-dT)2 showed the lowest association constant for all nucleic acids studied (Ka=<105). (6) Neomycin binds to G-quadruplexes with Ka~104-105M−1. (7) Computational studies show that the decrease in major groove width in the B to A transition correlates with increasing neomycin affinity. Neomycin’s affinity for various nucleic acid structures can be ranked as follows, RNAs and GC-rich d(A2G15C15T2)2 structures > poly(dA)•poly(rU) > poly(rA)•poly(dT) > T•A-T triplex , G-quadruplexes, B-form AT-rich or GC-rich DNA sequences. The results illustrate the first example of a small molecule based ‘shape readout’ of different nucleic acid conformations. PMID:21863895

Metal Ion Dependence of the Matrix Metalloproteinase-1 Mechanism.

PubMed

Yang, Hao; Makaroff, Katherine; Paz, Nicholas; Aitha, Mahesh; Crowder, Michael W; Tierney, David L

2015-06-16

Matrix metalloproteinase-1 (MMP-1) plays crucial roles in disease-related physiologies and pathological processes in the human body. We report here solution studies of MMP-1, including characterization of a series of mutants designed to bind metal in either the catalytic site or the structural site (but not both). Circular dichroism and fluorescence spectroscopy of the mutants demonstrate the importance of the structural Zn(II) in maintaining both secondary and tertiary structure, while UV-visible, nuclear magnetic resonance, electron paramagnetic resonance, and extended X-ray absorption fine structure show its presence influences the catalytic metal ion's coordination number. The mutants allow us to demonstrate convincingly the preparation of a mixed-metal analogue, Co(C)Zn(S)-MMP-1, with Zn(II) in the structural site and Co(II) in the catalytic site. Stopped-flow fluorescence of the native form, Zn(C)Zn(S)-MMP-1, and the mixed-metal Co(C)Zn(S)-MMP-1 analogue shows that the internal fluorescence of a nearby Trp residue is modulated with catalysis and can be used to monitor reactivity under a number of conditions, opening the door to substrate profiling.

Structure of the ThDP-dependent enzyme benzaldehyde lyase refined to 1.65 Å resolution

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

Maraite, Andy; Schmidt, Thomas; Ansörge-Schumacher, Marion B.

2007-07-01

The X-ray crystal structure of the ThDP-dependent enzyme benzaldehyde lyase has been refined to 1.65 Å. Benzaldehyde lyase (BAL; EC 4.1.2.38) is a thiamine diphosphate (ThDP) dependent enzyme that catalyses the enantioselective carboligation of two molecules of benzaldehyde to form (R)-benzoin. BAL has hence aroused interest for its potential in the industrial synthesis of optically active benzoins and derivatives. The structure of BAL was previously solved to a resolution of 2.6 Å using MAD experiments on a selenomethionine derivative [Mosbacher et al. (2005 ▶), FEBS J.272, 6067–6076]. In this communication of parallel studies, BAL was crystallized in an alternative spacemore » group (P2{sub 1}2{sub 1}2{sub 1}) and its structure refined to a resolution of 1.65 Å, allowing detailed observation of the water structure, active-site interactions with ThDP and also the electron density for the co-solvent 2-methyl-2,4-pentanediol (MPD) at hydrophobic patches of the enzyme surface.« less

Core-Level Photoemission Investigations of the CADMIUM-TELLURIDE(100) and INDIUM-ANTIMONY(100) Surface and Interfacial Structures.

NASA Astrophysics Data System (ADS)

John, Peter James

1988-12-01

Photoemission techniques, utilizing a synchrotron light source, were used to analyze the clean (100) surfaces of the zinc-blende semiconductor materials CdTe and InSb. Several interfacial systems involving the surfaces of these materials were also studied, including the CdTe(100)-Ag interface, the CdTe(100)-Sb system, and the InSb(100)-Sn interface. High -energy electron diffraction was also employed to acquire information about of surface structure. A one-domain (2x1) structure was observed for the CdTe(100) surface. Analysis of photoemission spectra of the Cd 4d core level for this surface structure revealed two components resulting from Cd surface atoms. The total intensity of these components accounts for a full monolayer of Cd atoms on the surface. A structural model is discussed commensurate with these results. Photoemission spectra of the Cd and Te 4d core levels indicate that Ag or Sb deposited on the CdTe(100)-(2x1) surface at room temperature do not bound strongly to the surface Cd atoms. The room temperature growth characteristics for these two elements on the CdTe(100)-(2x1) are discussed. The growth at elevated substrate temperatures was also studied for Sb deposition. The InSb(100) surface differed from the CdTe(100) surface. Using molecular beam epitaxy, several structures could be generated for the InSb(100) surface, including a c(8x2), a c(4x4), an asymmetric (1x3), a symmetric (1x3), and a (1x1). Analysis of photoemission intensities and line shapes indicates that the c(4x4) surface is terminated with 1{3 over 4} monolayers of Sb atoms. The c(8x2) surface is found to be terminated with {3over 4} monolayer of In atoms. Structural models for both of these surfaces are proposed based upon the photoemission results and upon models of the similar GaAs(100) structures. The room temperature growth characteristics of grey Sn on the InSb(100)-c(4x4) and InSb(100)-c(8x2) surfaces were studied with photoemission. The discontinuity in the valence band maximum for this semiconductor heterojunction system is measured to be 0.40 eV, independent of the starting surface structure and stoichiometry. This result is reconciled with theoretical predictions for heterostructure behavior.

Design and Synthesis of a Series of l-trans-4-Substituted Prolines as Selective Antagonists for the Ionotropic Glutamate Receptors Including Functional and X-ray Crystallographic Studies of New Subtype Selective Kainic Acid Receptor Subtype 1 (GluK1) Antagonist (2S,4R)-4-(2-Carboxyphenoxy)pyrrolidine-2-carboxylic Acid.

PubMed

Krogsgaard-Larsen, Niels; Delgar, Claudia G; Koch, Karina; Brown, Patricia M G E; Møller, Charlotte; Han, Liwei; Huynh, Tri H V; Hansen, Stinne W; Nielsen, Birgitte; Bowie, Derek; Pickering, Darryl S; Kastrup, Jette Sandholm; Frydenvang, Karla; Bunch, Lennart

2017-01-12

Ionotropic glutamate receptor antagonists are valuable tool compounds for studies of neurological pathways in the central nervous system. On the basis of rational ligand design, a new class of selective antagonists, represented by (2S,4R)-4-(2-carboxyphenoxy)pyrrolidine-2-carboxylic acid (1b), for cloned homomeric kainic acid receptors subtype 1 (GluK1) was attained (K i = 4 μM). In a functional assay, 1b displayed full antagonist activity with IC 50 = 6 ± 2 μM. A crystal structure was obtained of 1b when bound in the ligand binding domain of GluK1. A domain opening of 13-14° was seen compared to the structure with glutamate, consistent with 1b being an antagonist. A structure-activity relationship study showed that the chemical nature of the tethering atom (C, O, or S) linking the pyrrolidine ring and the phenyl ring plays a key role in the receptor selectivity profile and that substituents on the phenyl ring are well accommodated by the GluK1 receptor.

Efficacy of Human Immunodeficiency Virus/Sexually Transmitted Infection Prevention Interventions Targeting Female Entertainment Workers: A Systematic Review and Meta-analysis.

PubMed

Lim, Raymond Boon Tar; Tham, Dede Kam Tyng; Cheung, Olive N Y; Wong, Mee Lian

2017-08-01

Female entertainment workers (FEWs) working in karaoke lounges, bars, pubs, nightclubs, discotheques, dance halls, massage parlours, restaurants (as hostesses or singers) and beer gardens are at high risk for human immunodeficiency virus (HIV)/sexually transmitted infection (STI). The aim of the systematic review and meta-analysis is to evaluate the efficacy of HIV/STI intervention programmes targeting FEWs. Among the 14 included studies, majority were in Asia and targeted native FEWs. Most studies were quasi-experimental and the overall quality was relatively low. While most studies employed only behavioural strategies, structural interventions were the least common. In studies with structural interventions, there was a preference for behavioural and biomedical-based outcome measurements rather than structural-related indicators. FEWs in the intervention group were significantly more likely to report condom use with paying (odds ratio OR 1.7; 95% CI 1.0-2.9, p 0.04), but not with regular (OR 1.0; 95% CI 0.8-1.3, p 0.84) partner than the control/comparison group post-intervention.

System technology analysis of aeroassisted orbital transfer vehicles: Moderate lift/drag (0.75-1.5). Volume 3: Cost estimates and work breakdown structure/dictionary, phase 1 and 2

NASA Technical Reports Server (NTRS)

1985-01-01

Technology payoffs of representative ground based (Phase 1) and space based (Phase 2) mid lift/drag ratio aeroassisted orbit transfer vehicles (AOTV) were assessed and prioritized. A narrative summary of the cost estimates and work breakdown structure/dictionary for both study phases is presented. Costs were estimated using the Grumman Space Programs Algorithm for Cost Estimating (SPACE) computer program and results are given for four AOTV configurations. The work breakdown structure follows the standard of the joint government/industry Space Systems Cost Analysis Group (SSCAG). A table is provided which shows cost estimates for each work breakdown structure element.

Synthesis, crystal structure and luminescent properties of a new pyrochlore type tungstate CsGa0.333W1.667O6

NASA Astrophysics Data System (ADS)

Zhao, Dan; Zhao, Ji; Fan, Yun-Chang; Ma, Zhao; Zhang, Rui-Juan; Liu, Bao-Zhong

2018-06-01

High temperature solution reaction leads to a new tungstate compound CsGa0.333W1.667O6, whose structure was determined by single-crystal X-ray diffraction analysis. The results show that it crystallizes in pyrochlore structure with cubic space group Fd-3m and a = 10.2529 (13) Å. In this structure, Ga and W atoms are in a statistical disorder manner. The self-activated luminescent properties CsGa0.333W1.667O6 were studied. Under the excitation of 323 nm, the emission spectrum exhibits a blue emission centered at 466 nm with the chromaticity coordinates (0.1838, 0.1814).

Nuclear structure studies with gamma-ray beams

DOE PAGES

Tonchev, Anton; Bhatia, Chitra; Kelley, John; ...

2015-05-28

In stable and weakly bound neutron-rich nuclei, a resonance-like concentration of dipole states has been observed for excitation energies below the neutron-separation energy. This clustering of strong dipole states has been named the Pygmy Dipole Resonance (PDR) in contrast to the Giant Dipole Resonance (GDR) that dominates the E1 response. Understanding the PDR is presently of great interest in nuclear structure and nuclear astrophysics. High-sensitivity studies of E1 and M1 transitions in closed-shell nuclei using monoenergetic and 100% linearly-polarized photon beams are presented.

Nuclear Structure Studies with Gamma-Ray Beams

NASA Astrophysics Data System (ADS)

Tonchev, Anton; Bhatia, Chitra; Kelley, John; Raut, Rajarshi; Rusev, Gencho; Tornow, Werner; Tsoneva, Nadia

2015-05-01

In stable and weakly bound neutron-rich nuclei, a resonance-like concentration of dipole states has been observed for excitation energies below the neutron-separation energy. This clustering of strong dipole states has been named the Pygmy Dipole Resonance (PDR) in contrast to the Giant Dipole Resonance (GDR) that dominates the E1 response. Understanding the PDR is presently of great interest in nuclear structure and nuclear astrophysics. High-sensitivity studies of E1 and M1 transitions in closed-shell nuclei using monoenergetic and 100% linearly-polarized photon beams are presented.

Protein structure and interactions in the solid state studied by small-angle neutron scattering.

PubMed

Curtis, Joseph E; McAuley, Arnold; Nanda, Hirsh; Krueger, Susan

2012-01-01

Small-angle neutron scattering (SANS) is uniquely qualified to study the structure of proteins in liquid and solid phases that are relevant to food science and biotechnological applications. We have used SANS to study a model protein, lysozyme, in both the liquid and water ice phases to determine its gross-structure, interparticle interactions and other properties. These properties have been examined under a variety of solution conditions before, during, and after freezing. Results for lysozyme at concentrations of 50 mg mL(-1) and 100 mg mL(-1), with NaCl concentrations of 0.4 M and 0 M, respectively, both in the liquid and frozen states, are presented and implications for food science are discussed.

The structure of the coding and 5'-flanking region of the type 1 iodothyronine deiodinase (dio1) gene is normal in a patient with suspected congenital dio1 deficiency.

PubMed

Toyoda, N; Kleinhaus, N; Larsen, P R

1996-06-01

We analyzed the exon-intron structure of the human type 1 deiodinase gene (dio1) and compared it with that of a patient with suspected congenital type 1 deiodinase (D1) deficiency. The hdio1 gene is identical in exon-intron arrangement to the mouse gene, with coding sequences and a selenocysteine insertion sequence (SECIS) element contained in four exons. There were no mutations in the sequences of exons 1-4 of the patient's genomic DNA. Functional studies by transient expression techniques showed no difference in basal promoter activity or T3 responsiveness between the patient's and the normal dio1 gene. A structural abnormality in the dio1 gene is not a likely explanation for this patient's D1-deficient phenotype.

Chromosomal abnormalities in human sperm

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

Martin, R.H.

1985-01-01

The ability to analyze human sperm chromosome complements after penetration of zona pellucida-free hamster eggs provides the first opportunity to study the frequency and type of chromosomal abnormalities in human gametes. Two large-scale studies have provided information on normal men. We have studied 1,426 sperm complements from 45 normal men and found an abnormality rate of 8.9%. Brandriff et al. (5) found 8.1% abnormal complements in 909 sperm from 4 men. The distribution of numerical and structural abnormalities was markedly dissimilar in the 2 studies. The frequency of aneuploidy was 5% in our sample and only 1.6% in Brandriff's, perhapsmore » reflecting individual variability among donors. The frequency of 24,YY sperm was low: 0/1,426 and 1/909. This suggests that the estimates of nondisjunction based on fluorescent Y body data (1% to 5%) are not accurate. We have also studied men at increased risk of sperm chromosomal abnormalities. The frequency of chromosomally unbalanced sperm in 6 men heterozygous for structural abnormalities varied dramatically: 77% for t11;22, 32% for t6;14, 19% for t5;18, 13% for t14;21, and 0% for inv 3 and 7. We have also studied 13 cancer patients before and after radiotherapy and demonstrated a significant dose-dependent increase of sperm chromosome abnormalities (numerical and structural) 36 months after radiation treatment.« less

Design Rules for Tailoring Antireflection Properties of Hierarchical Optical Structures

DOE PAGES

Leon, Juan J. Diaz; Hiszpanski, Anna M.; Bond, Tiziana C.; ...

2017-05-18

Hierarchical structures consisting of small sub-wavelength features stacked atop larger structures have been demonstrated as an effective means of reducing the reflectance of surfaces. However, optical devices require different antireflective properties depending on the application, and general unifying guidelines on hierarchical structures' design to attain a desired antireflection spectral response are still lacking. The type of reflectivity (diffuse, specular, or total/hemispherical) and its angular- and spectral-dependence are all dictated by the structural parameters. Through computational and experimental studies, guidelines have been devised to modify these various aspects of reflectivity across the solar spectrum by proper selection of the features ofmore » hierarchical structures. In this wavelength regime, micrometer-scale substructures dictate the long-wavelength spectral response and effectively reduce specular reflectance, whereas nanometer-scale substructures dictate primarily the visible wavelength spectral response and reduce diffuse reflectance. Coupling structures having these two length scales into hierarchical arrays impressively reduces surfaces' hemispherical reflectance across a broad spectrum of wavelengths and angles. Furthermore, such hierarchical structures in silicon are demonstrated having an average total reflectance across the solar spectrum of 1.1% (average weighted reflectance of 1% in the 280–2500 nm range of the AM 1.5 G spectrum) and specular reflectance <1% even at angles of incidence as high as 67°.« less

The crystal structure of the secreted aspartic protease 1 from Candida parapsilosis in complex with pepstatin A

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

Dostál, Jiří; Brynda, Jiří; Hrušková-Heidingsfeldová, Olga

2010-09-01

Opportunistic pathogens of the genus Candida cause infections representing a major threat to long-term survival of immunocompromised patients. Virulence of the Candida pathogens is enhanced by production of extracellular proteolytic enzymes and secreted aspartic proteases (Saps) are therefore studied as potential virulence factors and possible targets for therapeutic drug design. Candida parapsilosis is less invasive than C. albicans, however, it is one of the leading causative agents of yeast infections. We report three-dimensional crystal structure of Sapp1p from C. parapsilosis in complex with pepstatin A, the classical inhibitor of aspartic proteases. The structure of Sapp1p was determined from protein isolatedmore » from its natural source and represents the first structure of Sap from C. parapsilosis. Overall fold and topology of Sapp1p is very similar to the archetypic fold of monomeric aspartic protease family and known structures of Sap isoenzymes from C. albicans and Sapt1p from C. tropicalis. Structural comparison revealed noticeable differences in the structure of loops surrounding the active site. This resulted in differential character, shape, and size of the substrate binding site explaining divergent substrate specificities and inhibitor affinities. Determination of structures of Sap isoenzymes from various species might contribute to the development of new Sap-specific inhibitors.« less

Quantum molecular dynamics study on the structures and dc conductivity of warm dense silane

NASA Astrophysics Data System (ADS)

Sun, Huayang; Kang, Dongdong; Dai, Jiayu; Zeng, Jiaolong; Yuan, Jianmin

2014-02-01

The ionic and electronic structures of warm dense silane at the densities of 1.795, 2.260, 3.382, and 3.844 g/cm3 have been studied with temperatures from 1000 K to 3 eV using quantum molecular dynamics simulations. At all densities, the structures are melted above 1000 K. The matter states are characterized as polymeric from 1000 to 4000 K and become dense plasma states with further increasing temperature to 1 eV. At two lower densities of 1.795 and 2.260 g/cm3, silane first dissociates and then becomes the polymeric state via a chain state from the initial crystalline structure. At higher densities, however, no dissociation stage was found. These findings can help us understand how the warm dense matter forms. A rise is found for the direct current electric conductivity at T ˜1000 K, indicating the nonmetal-to-metal transition. The conductivity decreases slightly with the increase of temperature, which is due to the more disordered structures at higher temperatures.

Molecular phylogeny of 21 tropical bamboo species reconstructed by integrating non-coding internal transcribed spacer (ITS1 and 2) sequences and their consensus secondary structure.

PubMed

Ghosh, Jayadri Sekhar; Bhattacharya, Samik; Pal, Amita

2017-06-01

The unavailability of the reproductive structure and unpredictability of vegetative characters for the identification and phylogenetic study of bamboo prompted the application of molecular techniques for greater resolution and consensus. We first employed internal transcribed spacer (ITS1, 5.8S rRNA and ITS2) sequences to construct the phylogenetic tree of 21 tropical bamboo species. While the sequence alone could grossly reconstruct the traditional phylogeny amongst the 21-tropical species studied, some anomalies were encountered that prompted a further refinement of the phylogenetic analyses. Therefore, we integrated the secondary structure of the ITS sequences to derive individual sequence-structure matrix to gain more resolution on the phylogenetic reconstruction. The results showed that ITS sequence-structure is the reliable alternative to the conventional phenotypic method for the identification of bamboo species. The best-fit topology obtained by the sequence-structure based phylogeny over the sole sequence based one underscores closer clustering of all the studied Bambusa species (Sub-tribe Bambusinae), while Melocanna baccifera, which belongs to Sub-Tribe Melocanneae, disjointedly clustered as an out-group within the consensus phylogenetic tree. In this study, we demonstrated the dependability of the combined (ITS sequence+structure-based) approach over the only sequence-based analysis for phylogenetic relationship assessment of bamboo.

Spectral and quantum chemical studies on 1,3-bis(N(1)-4-amino-6-methoxypyrimidinebenzenesulfonamide-2,2,4,4-ethane-1,2-dithiol)-2,4-dichlorocyclodiphosph(V)azane and its erbium complex.

PubMed

Al-Mogren, Muneerah M; Alaghaz, Abdel-Nasser M A; El-Gogary, Tarek M

2014-01-24

Novel 1,3-bis(N(1)-4-amino-6-methoxypyrimidine-benzenesulfonamide-2,2,4,4-ethane-1,2-dithiol)-2,4-dichlorocyclodiphosph(V)azane (L), was prepared and their coordinating behavior towards the lanthanide ion Er(III) was studied. The structures of the isolated products are proposed based on elemental analyses, IR, UV-VIS., (1)H NMR, (13)C NMR, (31)P NMR, SEM, XRD, mass spectra, effective magnetic susceptibility measurements and thermogravimetric analysis (TGA). Computational studies have been carried out at the DFT-B3LYP/6-31G(d) level of theory on the structural and spectroscopic properties of L and its binuclear Er(III) complex. Different tautomers of the ligand were optimized at the ab initio DFT level. Keto-form structure is about 17.7 kcal/mol more stable than the enol form (taking zpe correction into account). Simulated IR frequencies were scaled and compared with that experimentally measured. TD-DFT method was used to compute the UV-VIS spectra which compared by the measured electronic spectra. Copyright © 2013 Elsevier B.V. All rights reserved.

Homology modeling study toward identifying structural properties in the HA2 B-loop that would influence the HA1 receptor-binding site.

PubMed

Cueno, Marni E; Imai, Kenichi; Shimizu, Kazufumi; Ochiai, Kuniyasu

2013-07-01

Influenza hemagglutinin (HA) consists of a fibrous globular stem (HA2) inserted into the viral membrane supporting a globular head (HA1). HA1 receptor-binding has been hypothesized to be structurally correlated to the HA2 B-loop, however, this was never fully understood. Here, we elucidated the structural relationship between the HA2 B-loop and the HA1 receptor-binding site (RBS). Throughout this study, we analyzed 2486 H1N1 HA homology models obtained from human, swine and avian strains during 1976-2012. Quality of all homology models were verified before further analyses. We established that amino acid residue 882 is putatively strain-conserved and differs in the human (K882), swine (H882) and avian (N882) strains. Moreover, we observed that the amino acid at residue 882 and, similarly, its orientation has the potential to influence the HA1 RBS diameter measurements which we hypothesize may consequentially affect influenza H1N1 viral infectivity, immune escape, transmissibility, and evolution. Copyright © 2013 Elsevier Inc. All rights reserved.

Local and Average Structures in Ferroelectrics under Perturbing Fields

NASA Astrophysics Data System (ADS)

Usher, Tedi-Marie

Ferroelectric and dielectric ceramics are used in a multitude of applications including sonar, micro-positioning, actuators, transducers, and capacitors. The most widely used compositions are lead (Pb)-based, however there is an ongoing effort to reduce lead-based materials in consumer applications. Many lead-free compositions are under investigation; some are already in production and others have been identified as suitable for certain applications. For any such material system, there is a need to thoroughly characterize the structure in order to develop robust structure-property relationships, particularly during in situ application of different stimuli (e.g. electric field and mechanical stress). This work investigates two lead-free material systems of interest, (1-x)Na1/2Bi1/2TiO3 - (x)BaTiO3 (NBT-xBT) and (1-x)BaTiO3 - (x)Bi(Zn1/2Ti1/2)O3 (BT-xBZT), as well as the constituent compounds Na1/2Bi1/2TiO3 and BaTiO3. Both systems exhibit compositional boundaries between unique phases exhibiting different functional properties. Advanced scattering techniques are used to characterize the atomic structures and how they change during in situ application of different stimuli. The long-range, average structures are probed using high-resolution X-ray diffraction (HRXRD) and neutron diffraction (ND) and local scale structures are probed using X-ray or neutron total scattering, which are converted to pair distribution functions (PDFs). First, two in situ ND experiments which investigate structural changes to NBT-xBT in response to uniaxial stresses and electric fields are presented. In response to stresses, different crystallographic directions strain differently. The elastic anisotropy, (i.e., the orientation-dependence of elastic stiffness) for the studied compositions is characterized. A general inverse relationship between elastic anisotropy and piezoelectric anisotropy is demonstrated for three common ferroelectric point groups. In response to electric fields, different crystallographic directions respond by either domain reorientation or lattice strain, as governed by the material's symmetry. The composition at the phase boundary responds at a lower field and undergoes a phase transition. Next, the PDF method is described and then applied to a structural study of BT-xBZT in combination with HRXRD and ND studies. For BZT >9%, the structure is pseudocubic at the long-range with short-range tetragonal distortions. This structural length-scale dependence is characterized with a box-car fitting method and suggests that with sufficient BZT content, local tetragonal distortions are disrupted at length scales > 40 A. By combining long- and short-range studies, structural variations from the sub-nm to long-range are characterized and enhance the understanding of this and similar material systems. In the final chapters, the local-scale responses of ferroelectric and dielectric materials to electric fields are investigated by PDFs. The novel methodology of measuring X-ray total scattering during in situ application of electric fields is presented and results are shown for piezoelectric (BT), relaxor-ferroelectric (NBT), and dielectric materials (SrTiO3 and HfO2), as well as for NBT-xBT. Local-scale cation reorientation in NBT is evidenced and corresponds to an electric-field-induced phase transition. The ability to quantify local-scale atomic rearrangements during field application is unique to in situ PDF studies; it is not possible through in situ diffraction methods like those presented earlier. This method is extended to neutron-PDFs and ex situ results for NBT are shown. In order to interpret the local scale-changes observed in the in situ PDF studies, the local structures of a series of models with different real, physical effects (strains, polarization, changes in thermal motion, etc) are analyzed and characterized. Finally, the samples used are characterized in terms of grain size/appearance and piezoelectric and ferroelectric properties. In summary, this research demonstrates the use of detailed and in situ structural studies that contribute new knowledge to structure-property relationships for several ferroelectric and dielectric material systems. Additionally, the novel technique of in situ PDFs with electric fields is evidenced to provide unique information on atomic rearrangements caused by in situ stimuli.

N-benzoylimido complexes of palladium. Synthesis, structural characterisation and structure-reactivity relationship.

PubMed

Besenyei, Gábor; Párkányi, László; Szalontai, Gábor; Holly, Sándor; Pápai, Imre; Keresztury, Gábor; Nagy, Andrea

2004-07-07

Benzoyl azides, ArC(O)N3, 2, (Ar = phenyl or substituted phenyl), react with [Pd2Cl2(dppm)2], 1, [dppm = bis(diphenylphosphino)methane] with the formation of novel [Pd2Cl2(mu-NC(O)Ar)(dppm)2], 3, benzoylnitrene complexes that were structurally characterised by multinuclear magnetic resonance and IR spectroscopy and, in several instances, by single crystal X-ray diffraction. As shown by crystallographic studies, the C2P4Pd2 rings adopt extended twist-boat conformations with methylene groups bending towards the bridging benzoylimido moieties. X-ray diffraction studies have revealed the chiral nature of the imido complexes, the chiral element being the propeller-like C2P4Pd2 ring. Structural data accumulated on complexes 3 such as short C-N distances (1.32 A), elongated C=O bonds (1.30 A) as well as the outstandingly high barrier to internal rotation around the N-C(O) linkage (88.3 kJ mol(-1)) are in line with extensive ppi-ppi interaction between the bridging nitrogen and the carbonyl carbon atoms. Theoretical calculations indicate an electron shift from the dimer towards the apical nitrogen atom, which, in turn, facilitates the donation of electrons towards the carbonyl moiety. To elucidate the structure-reactivity relationship of benzoyl azides towards 1, crystallographic and solution IR spectroscopic studies were carried out on a series of para-substituted benzoyl azides. The reaction obeys the Hammett equation. The large positive value of the reaction constant indicates that the azides act as electrophiles in the reaction studied. The enhanced reactivity of 2-nitrobenzoyl azide has been attributed to a decreased conjugation of the phenyl and carbonyl moieties in this reagent.

Structural and Biochemical Basis for the Binding Selectivity of Peroxisome Proliferator-activated Receptor [gamma] to PGC-1[alpha

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

Li, Yong; Kovach, Amanda; Suino-Powell, Kelly

2008-07-23

The functional interaction between the peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and its coactivator PGC-1{alpha} is crucial for the normal physiology of PPAR{gamma} and its pharmacological response to antidiabetic treatment with rosiglitazone. Here we report the crystal structure of the PPAR{gamma} ligand-binding domain bound to rosiglitazone and to a large PGC-1{alpha} fragment that contains two LXXLL-related motifs. The structure reveals critical contacts mediated through the first LXXLL motif of PGC-1{alpha} and the PPAR{gamma} coactivator binding site. Through a combination of biochemical and structural studies, we demonstrate that the first LXXLL motif is the most potent among all nuclear receptor coactivator motifsmore » tested, and only this motif of the two LXXLL-related motifs in PGC-1{alpha} is capable of binding to PPAR{gamma}. Our studies reveal that the strong interaction of PGC-1{alpha} and PPAR{gamma} is mediated through both hydrophobic and specific polar interactions. Mutations within the context of the full-length PGC-1{alpha} indicate that the first PGC-1{alpha} motif is necessary and sufficient for PGC-1{alpha} to coactivate PPAR{gamma} in the presence or absence of rosiglitazone. These results provide a molecular basis for specific recruitment and functional interplay between PPAR{gamma} and PGC-1{alpha} in glucose homeostasis and adipocyte differentiation.« less

Structure of the SPRY domain of the human RNA helicase DDX1, a putative interaction platform within a DEAD-box protein

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

Kellner, Julian N.; Meinhart, Anton, E-mail: anton.meinhart@mpimf-heidelberg.mpg.de

The structure of the SPRY domain of the human RNA helicase DDX1 was determined at 2.0 Å resolution. The SPRY domain provides a putative protein–protein interaction platform within DDX1 that differs from other SPRY domains in its structure and conserved regions. The human RNA helicase DDX1 in the DEAD-box family plays an important role in RNA processing and has been associated with HIV-1 replication and tumour progression. Whereas previously described DEAD-box proteins have a structurally conserved core, DDX1 shows a unique structural feature: a large SPRY-domain insertion in its RecA-like consensus fold. SPRY domains are known to function as protein–proteinmore » interaction platforms. Here, the crystal structure of the SPRY domain of human DDX1 (hDSPRY) is reported at 2.0 Å resolution. The structure reveals two layers of concave, antiparallel β-sheets that stack onto each other and a third β-sheet beneath the β-sandwich. A comparison with SPRY-domain structures from other eukaryotic proteins showed that the general β-sandwich fold is conserved; however, differences were detected in the loop regions, which were identified in other SPRY domains to be essential for interaction with cognate partners. In contrast, in hDSPRY these loop regions are not strictly conserved across species. Interestingly, though, a conserved patch of positive surface charge is found that may replace the connecting loops as a protein–protein interaction surface. The data presented here comprise the first structural information on DDX1 and provide insights into the unique domain architecture of this DEAD-box protein. By providing the structure of a putative interaction domain of DDX1, this work will serve as a basis for further studies of the interaction network within the hetero-oligomeric complexes of DDX1 and of its recruitment to the HIV-1 Rev protein as a viral replication factor.« less

Synthesis and characterization of a prominent NLO active MOF of lead with 1,5-naphthalenedisulfonic acid

NASA Astrophysics Data System (ADS)

Prasad, S. Shibu; Sudarsanakumar, M. R.; Dhanya, V. S.; Suma, S.; Kurup, M. R. Prathapachandra

2018-09-01

A new metal-organic framework of lead, [Pb(1,5-nds)(H2O)3]n (1,5-nds = 1,5-naphthalenedisulfonate) having prominent nonlinear optical property has been prepared by single gel diffusion technique at ambient condition using sodium metasilicate. The second harmonic generation efficiency was analyzed using Kurtz and Perry powder method and was found to be 30 times as large as potassium dihydrogen phosphate (KDP). Single crystal X-ray diffraction studies reveal the crystal structure. The grown crystals were further characterized by elemental analysis, powder XRD study, thermogravimetry, FT-IR and UV-visible spectral studies. The Pb2S2O4 rings in the crystal structure form a 1D channel. Hydrogen bonding and π-π interactions provide additional stability to the compound. Photoluminescence studies were also carried out.

Effect of crystal structure and cationic order on phonon modes across ferroelectric phase transformation in Pb(Fe{sub 0.5-x}Sc{sub x}Nb{sub 0.5})O{sub 3} bulk ceramics

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

Mallesham, B.; Ranjith, R., E-mail: ranjith@iith.ac.in; Viswanath, B.

Pb(Fe{sub 0.5-x}Sc{sub x}Nb{sub 0.5})O{sub 3} [(PFSN) (0 ≤ x ≤ 0.5)] multiferroic relaxors were synthesized and the temperature dependence of phonon modes across ferroelectric to paraelectric transition was studied. With varying Sc content from x = 0 to 0.25 the structure remains monoclinic and with further addition (x = 0.3 - 0.5) the structure transforms into rhombohedral symmetry. Structural refinement studies showed that the change in crystal structure from monoclinic to rhombohedral symmetry involves a volume increment of 34-36%. Associated changes in the tolerance factor (1.024 ≤ t ≤ 0.976) and bond angles were observed. Structure assisted B′-B″ cation orderingmore » was confirmed through the superlattice reflections in selected area electron diffraction (SAED) pattern of Pb(Sc{sub 0.5}Nb{sub 0.5})O{sub 3} (x = 0.5). Cation ordering is also evident from the evolution of Pb-O phonon mode in Raman spectra of compositions with rhombohedral symmetry (x ≥ 0.3). The high temperature Raman scattering studies show that the B-localized mode [F{sub 1u}, ∼250 cm{sup −1}] and BO{sub 6} octahedral rotational mode [F{sub 1g}, ∼200 cm{sup −1}], both originating from polar nano regions (PNRs) behave like coupled phonon modes in rhombohedral symmetry. However, in monoclinic symmetry they behave independently across the transition. Softening of B localized mode across the transition followed by the hardening for all compositions confirms the diffusive nature of the ferroelectric transformation. The presence of correlation between the B localized and BO{sub 6} rotational modes introduces a weak relaxor feature for systems with rhombohedral symmetry in PFSN ceramics, which was confirmed from the macroscopic dielectric studies.« less

Elongated fibrillar structure of a streptococcal adhesin assembled by the high-affinity association of [alpha]- and PPII-helices

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

Larson, Matthew R.; Rajashankar, Kanagalaghatta R.; Patel, Manisha H.

2010-08-18

Streptococcus mutans antigen I/II (AgI/II) is a cell surface-localized protein adhesin that interacts with salivary components within the salivary pellicle. AgI/II contributes to virulence and has been studied as an immunological and structural target, but a fundamental understanding of its underlying architecture has been lacking. Here we report a high-resolution (1.8 {angstrom}) crystal structure of the A{sub 3}VP{sub 1} fragment of S. mutans AgI/II that demonstrates a unique fibrillar form (155 {angstrom}) through the interaction of two noncontiguous regions in the primary sequence. The A{sub 3} repeat of the alanine-rich domain adopts an extended {alpha}-helix that intertwines with the P{submore » 1} repeat polyproline type II (PPII) helix to form a highly extended stalk-like structure heretofore unseen in prokaryotic or eukaryotic protein structures. Velocity sedimentation studies indicate that full-length AgI/II that contains three A/P repeats extends over 50 nanometers in length. Isothermal titration calorimetry revealed that the high-affinity association between the A{sub 3} and P{sub 1} helices is enthalpically driven. Two distinct binding sites on AgI/II to the host receptor salivary agglutinin (SAG) were identified by surface plasmon resonance (SPR). The current crystal structure reveals that AgI/II family proteins are extended fibrillar structures with the number of alanine- and proline-rich repeats determining their length.« less

Structural basis for controlling the dimerization and stability of the WW domains of an atypical subfamily

PubMed Central

Ohnishi, Satoshi; Tochio, Naoya; Tomizawa, Tadashi; Akasaka, Ryogo; Harada, Takushi; Seki, Eiko; Sato, Manami; Watanabe, Satoru; Fujikura, Yukiko; Koshiba, Seizo; Terada, Takaho; Shirouzu, Mikako; Tanaka, Akiko; Kigawa, Takanori; Yokoyama, Shigeyuki

2008-01-01

The second WW domain in mammalian Salvador protein (SAV1 WW2) is quite atypical, as it forms a β-clam-like homodimer. The second WW domain in human MAGI1 (membrane associated guanylate kinase, WW and PDZ domain containing 1) (MAGI1 WW2) shares high sequence similarity with SAV1 WW2, suggesting comparable dimerization. However, an analytical ultracentrifugation study revealed that MAGI1 WW2 (Leu355–Pro390) chiefly exists as a monomer at low protein concentrations, with an association constant of 1.3 × 102 M−1. We determined its solution structure, and a structural comparison with the dimeric SAV1 WW2 suggested that an Asp residue is crucial for the inhibition of the dimerization. The substitution of this acidic residue with Ser resulted in the dimerization of MAGI1 WW2. The spin-relaxation data suggested that the MAGI1 WW2 undergoes a dynamic process of transient dimerization that is limited by the charge repulsion. Additionally, we characterized a longer construct of this WW domain with a C-terminal extension (Leu355–Glu401), as the formation of an extra α-helix was predicted. An NMR structural determination confirmed the formation of an α-helix in the extended C-terminal region, which appears to be independent from the dimerization regulation. A thermal denaturation study revealed that the dimerized MAGI1 WW2 with the Asp-to-Ser mutation gained apparent stability in a protein concentration-dependent manner. A structural comparison between the two constructs with different lengths suggested that the formation of the C-terminal α-helix stabilized the global fold by facilitating contacts between the N-terminal linker region and the main body of the WW domain. PMID:18562638

Structural basis for controlling the dimerization and stability of the WW domains of an atypical subfamily.

PubMed

Ohnishi, Satoshi; Tochio, Naoya; Tomizawa, Tadashi; Akasaka, Ryogo; Harada, Takushi; Seki, Eiko; Sato, Manami; Watanabe, Satoru; Fujikura, Yukiko; Koshiba, Seizo; Terada, Takaho; Shirouzu, Mikako; Tanaka, Akiko; Kigawa, Takanori; Yokoyama, Shigeyuki

2008-09-01

The second WW domain in mammalian Salvador protein (SAV1 WW2) is quite atypical, as it forms a beta-clam-like homodimer. The second WW domain in human MAGI1 (membrane associated guanylate kinase, WW and PDZ domain containing 1) (MAGI1 WW2) shares high sequence similarity with SAV1 WW2, suggesting comparable dimerization. However, an analytical ultracentrifugation study revealed that MAGI1 WW2 (Leu355-Pro390) chiefly exists as a monomer at low protein concentrations, with an association constant of 1.3 x 10(2) M(-1). We determined its solution structure, and a structural comparison with the dimeric SAV1 WW2 suggested that an Asp residue is crucial for the inhibition of the dimerization. The substitution of this acidic residue with Ser resulted in the dimerization of MAGI1 WW2. The spin-relaxation data suggested that the MAGI1 WW2 undergoes a dynamic process of transient dimerization that is limited by the charge repulsion. Additionally, we characterized a longer construct of this WW domain with a C-terminal extension (Leu355-Glu401), as the formation of an extra alpha-helix was predicted. An NMR structural determination confirmed the formation of an alpha-helix in the extended C-terminal region, which appears to be independent from the dimerization regulation. A thermal denaturation study revealed that the dimerized MAGI1 WW2 with the Asp-to-Ser mutation gained apparent stability in a protein concentration-dependent manner. A structural comparison between the two constructs with different lengths suggested that the formation of the C-terminal alpha-helix stabilized the global fold by facilitating contacts between the N-terminal linker region and the main body of the WW domain.

Structure and dynamics of zymogen human blood coagulation factor X.

PubMed

Venkateswarlu, Divi; Perera, Lalith; Darden, Tom; Pedersen, Lee G

2002-03-01

The solution structure and dynamics of the human coagulation factor X (FX) have been investigated to understand the key structural elements in the zymogenic form that participates in the activation process. The model was constructed based on the 2.3-A-resolution x-ray crystallographic structure of active-site inhibited human FXa (PDB:1XKA). The missing gamma-carboxyglutamic acid (GLA) and part of epidermal growth factor 1 (EGF1) domains of the light chain were modeled based on the template of GLA-EGF1 domains of the tissue factor (TF)-bound FVIIa structure (PDB:1DAN). The activation peptide and other missing segments of FX were introduced using homology modeling. The full calcium-bound model of FX was subjected to 6.2 ns of molecular dynamics simulation in aqueous medium using the AMBER6.0 package. We observed significant reorientation of the serine-protease (SP) domain upon activation leading to a compact multi-domain structure. The solution structure of zymogen appears to be in a well-extended conformation with the distance between the calcium ions in the GLA domain and the catalytic residues estimated to be approximately 95 A in contrast to approximately 83 A in the activated form. The latter is in close agreement with fluorescence studies on FXa. The S1-specificity residues near the catalytic triad show significant differences between the zymogen and activated structures.

Unusual folded structures for a tethered squaraine-cholesterol derivative in Langmuir-Blodgett films

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

Stanescu, M.; Samha, H.; Perlstein, J.

2000-01-11

A squaraine-cholesterol diad, 1, which has been found to be a good gelator, has been studied in films at the air-water interface and in supported Langmuir-Blodgett films. Both experimental observations and simulations are consistent with a low-energy folded structure in which there are attractive noncovalent interactions between the squaraine chromophore and the steroid. Although different structures seem likely for 1 in both the crystal and organogels, the present studies suggest that the folded structure exists in both uncompressed and compressed films at the air-water interface and in supported LB films. In both environments the squaraine chromophore shows evidence of squaraine-squarainemore » aggregation; both J and H aggregates are indicated depending upon the conditions imposed upon the film.« less

Cubic-to-tetragonal structural phase transition in Rb1-xCsxCaF3 solid solutions: Thermal expansion and EPR studies

NASA Astrophysics Data System (ADS)

Lahoz, F.; Villacampa, B.; Alcalá, R.; Marquina, C.; Ibarra, M. R.

1997-04-01

The influence of crystal mixing on the structural phase transitions in Rb1-xCsxCaF3 (0=0.44. This transition shows a weak first-order component in the x=0 and 0.1 samples, which is progressively smeared out for x>0.1, indicating a spatial distribution of the critical temperature in those crystals with high ionic substitution rate. In RbCaF3 , another structural phase transition was observed at 20 K with a thermal hysteresis between 20 and 40 K. This transition has not been found in any of the mixed crystals.

Insights into intermediate phases of human intestinal fluids visualized by atomic force microscopy and cryo-transmission electron microscopy ex vivo.

PubMed

Müllertz, Anette; Fatouros, Dimitrios G; Smith, James R; Vertzoni, Maria; Reppas, Christos

2012-02-06

The current work aims to study at the ultrastructural level the morphological development of colloidal intermediate phases of human intestinal fluids (HIFs) produced during lipid digestion. HIFs were aspirated near the ligament of Treitz early (30 min), Aspirate(early), and 1 h, Aspirate(1h)(ave,comp), after the administration of a heterogeneous liquid meal into the antrum. The composition of the sample aspirated 1 h after meal administration was similar to the average lumenal composition 1 h after meal administration (Aspirate(1h)(ave,comp)). The colloidal structures of individual aspirates and supernatants of aspirates after ultracentrifugation (micellar phase) were characterized by means of atomic force microscopy (AFM) and cryogenic transmission electron microscopy (Cryo-TEM). AFM revealed domain-like structures in Aspirate(early) and both vesicles and large aggregates Aspirate(1h)(ave,comp). Rough surfaces and domains varying in size were frequently present in the micellar phase of both Aspirate(early) and Aspirate(1h)(ave,comp). Cryo-TEM revealed an abundance of spherical micelles and occasionally presented worm-like micelles coexisting with faceted and less defined vesicles in Aspirate(early) and Aspirate(1h)(ave,comp). In Aspirate(1h)(ave,comp) oil droplets were visualized with bilayers closely located to their surface suggesting lipolytic product phases accumulated on the surface of the oil droplet. In the micellar phase of Aspirate(early), Cryo-TEM revealed the presence of spherical micelles, small vesicles, membrane fragments, oil droplets and plate-like structures. In the micellar phase of Aspirate(1h)(ave,comp) the only difference was the absence of oil droplets. Visualization studies previously performed with biorelevant media revealed structural features with many similarities as presented in the current investigation. The impression of the complexity and diversion of these phases has been reinforced with the excessive variation of structural features visualized ex vivo in the current study offering insights at the ultrastuctural level of intermediate phases which impact drug solubilization.