Dynamics of the Extended String-Like Interaction of TFIIE with the p62 Subunit of TFIIH.

PubMed

Okuda, Masahiko; Higo, Junichi; Komatsu, Tadashi; Konuma, Tsuyoshi; Sugase, Kenji; Nishimura, Yoshifumi

2016-09-06

General transcription factor II E (TFIIE) contains an acid-rich region (residues 378-393) in its α-subunit, comprising 13 acidic and two hydrophobic (Phe387 and Val390) residues. Upon binding to the p62 subunit of TFIIH, the acidic region adopts an extended string-like structure on the basic groove of the pleckstrin homology domain (PHD) of p62, and inserts Phe387 and Val390 into two shallow pockets in the groove. Here, we have examined the dynamics of this interaction by NMR and molecular dynamics (MD) simulations. Although alanine substitution of Phe387 and/or Val390 greatly reduced binding to PHD, the binding mode of the mutants was similar to that of the wild-type, as judged by the chemical-shift changes of the PHD. NMR relaxation dispersion profiles of the interaction exhibited large amplitudes for residues in the C-terminal half-string in the acidic region (Phe387, Glu388, Val390, Ala391, and Asp392), indicating a two-site binding mode: one corresponding to the final complex structure, and one to an off-pathway minor complex. To probe the off-pathway complex structure, an atomically detailed free-energy landscape of the binding mode was computed by all-atom multicanonical MD. The most thermodynamically stable cluster corresponded to the final complex structure. One of the next stable clusters was the off-pathway structure cluster, showing the reversed orientation of the C-terminal half-string on the PHD groove, as compared with the final structure. MD calculations elucidated that the C-terminal half-acidic-string forms encounter complexes mainly around the positive groove region with nearly two different orientations of the string, parallel and antiparallel to the final structure. Interestingly, the most encountered complexes exhibit a parallel-like orientation, suggesting that the string has a tendency to bind around the groove in the proper orientation with the aid of Phe387 and/or Val390 to proceed smoothly to the final complex structure. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Transformation of environmental conditions in large former Soviet countries: regional analysis

NASA Astrophysics Data System (ADS)

Bityukova, V. R.; Borovikov, M. S.

2018-01-01

The article studies changes in the structure of environmental conditions of regions in the large former Soviet countries (case study of Russia and Kazakhstan) that have formed considerable contrasts in the placement of industrial complex and population settlement during the previous development stages. The changes related to the transition to market economy have led to essential transformation of environmental conditions. A complex index allowing to assess changes at the regional level in Kazakhstan and Russia and to reveal main similarities and differences between those changes is applied to studying the transformation of regional and industry structure. The article examines both industry-specific and spatial patterns forming environmental conditions at the regional level.

Geophysical-geological studies of possible extensions of the New Madrid Fault Zone. Annual report for 1983. Volume 2

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

Hinze, W.J.; Braile, L.W.; Keller, G.R.

1985-04-01

Recent geophysical investigations have shown that the seismicity of the New Madrid, Missouri seismogenic region is correlative with an ancient rift complex suggesting that the anomalous seismicity is the result of the localization of the regional compressive stress pattern by basement structures. Preliminary evidence indicates that this inferred basement rift complex extends beyond the immediate realm of the intense New Madrid region microseismicity. An integrated geophysical/geological research program is being conducted to evaluate the rift complex hypothesis as an explanation for the earthquake activity in the New Madrid area and its extensions, to refine our knowledge of the structure andmore » physical properties of the rift complex, and to investigate the possible northern extensions of the New Madrid Fault zone, especially the possible northeastern connection to the Anna, Ohio seismic region. Investigation of the northeast extension of the New Madrid Rift Complex into eastern Indiana, north of 39/sup 0/N latitude, has focused upon the acquisition and preparation of arrays of gravity and magnetic anomaly data sets. Another possible arm of the New Madrid Rift Complex, the St. Louis Arm, which extends northwesterly from southern Illinois along the Mississippi River to St. Louis, Missouri, is being studied by an integrated geophysical, seismicity and geological investigation. However, during 1983, special emphasis was placed upon integration of gravity and magnetic anomaly data from the Anna, Ohio seismogenic region with basement lithologic and seismicity information to investigate the possible relationship of basement geology to the seismicity of the Anna area. Interpretation of these data indicate the occurrence of several major lithologic/structural features in the crust of the Anna area. Current seismicity in this region appears to be related to an ancient rift structure and possibly its contact with a low density pluton. 18 refs., 37 figs.« less

Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases

PubMed Central

Xu, Qifang; Malecka, Kimberly L.; Fink, Lauren; Jordan, E. Joseph; Duffy, Erin; Kolander, Samuel; Peterson, Jeffrey; Dunbrack, Roland L.

2016-01-01

Protein kinase autophosphorylation is a common regulatory mechanism in cell signaling pathways. Crystal structures of several homomeric protein kinase complexes have a serine, threonine, or tyrosine autophosphorylation site of one kinase monomer located in the active site of another monomer, a structural complex that we call an “autophosphorylation complex.” We developed and applied a structural bioinformatics method to identify all such autophosphorylation kinase complexes in X-ray crystallographic structures in the Protein Data Bank (PDB). We identified 15 autophosphorylation complexes in the PDB, of which 5 complexes had not previously been described in the publications describing the crystal structures. These 5 consist of tyrosine residues in the N-terminal juxtamembrane regions of colony stimulating factor 1 receptor (CSF1R, Tyr561) and EPH receptor A2 (EPHA2, Tyr594), tyrosine residues in the activation loops of the SRC kinase family member LCK (Tyr394) and insulin-like growth factor 1 receptor (IGF1R, Tyr1166), and a serine in a nuclear localization signal region of CDC-like kinase 2 (CLK2, Ser142). Mutations in the complex interface may alter autophosphorylation activity and contribute to disease; therefore we mutated residues in the autophosphorylation complex interface of LCK and found that two mutations impaired autophosphorylation (T445V and N446A) and mutation of Pro447 to Ala, Gly, or Leu increased autophosphorylation. The identified autophosphorylation sites are conserved in many kinases, suggesting that, by homology, these complexes may provide insight into autophosphorylation complex interfaces of kinases that are relevant drug targets. PMID:26628682

Variability in Rheumatology day care hospitals in Spain: VALORA study.

PubMed

Hernández Miguel, María Victoria; Martín Martínez, María Auxiliadora; Corominas, Héctor; Sanchez-Piedra, Carlos; Sanmartí, Raimon; Fernandez Martinez, Carmen; García-Vicuña, Rosario

To describe the variability of the day care hospital units (DCHUs) of Rheumatology in Spain, in terms of structural resources and operating processes. Multicenter descriptive study with data from a self-completed questionnaire of DCHUs self-assessment based on DCHUs quality standards of the Spanish Society of Rheumatology. Structural resources and operating processes were analyzed and stratified by hospital complexity (regional, general, major and complex). Variability was determined using the coefficient of variation (CV) of the variable with clinical relevance that presented statistically significant differences when was compared by centers. A total of 89 hospitals (16 autonomous regions and Melilla) were included in the analysis. 11.2% of hospitals are regional, 22,5% general, 27%, major and 39,3% complex. A total of 92% of DCHUs were polyvalent. The number of treatments applied, the coordination between DCHUs and hospital pharmacy and the post graduate training process were the variables that showed statistically significant differences depending on the complexity of hospital. The highest rate of rheumatologic treatments was found in complex hospitals (2.97 per 1,000 population), and the lowest in general hospitals (2.01 per 1,000 population). The CV was 0.88 in major hospitals; 0.86 in regional; 0.76 in general, and 0.72 in the complex. there was variability in the number of treatments delivered in DCHUs, being greater in major hospitals and then in regional centers. Nonetheless, the variability in terms of structure and function does not seem due to differences in center complexity. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

The C-terminal region of Ge-1 presents conserved structural features required for P-body localization.

PubMed

Jinek, Martin; Eulalio, Ana; Lingel, Andreas; Helms, Sigrun; Conti, Elena; Izaurralde, Elisa

2008-10-01

The removal of the 5' cap structure by the DCP1-DCP2 decapping complex irreversibly commits eukaryotic mRNAs to degradation. In human cells, the interaction between DCP1 and DCP2 is bridged by the Ge-1 protein. Ge-1 contains an N-terminal WD40-repeat domain connected by a low-complexity region to a conserved C-terminal domain. It was reported that the C-terminal domain interacts with DCP2 and mediates Ge-1 oligomerization and P-body localization. To understand the molecular basis for these functions, we determined the three-dimensional crystal structure of the most conserved region of the Drosophila melanogaster Ge-1 C-terminal domain. The region adopts an all alpha-helical fold related to ARM- and HEAT-repeat proteins. Using structure-based mutants we identified an invariant surface residue affecting P-body localization. The conservation of critical surface and structural residues suggests that the C-terminal region adopts a similar fold with conserved functions in all members of the Ge-1 protein family.

Reinforcing Visual Grouping Cues to Communicate Complex Informational Structure.

PubMed

Bae, Juhee; Watson, Benjamin

2014-12-01

In his book Multimedia Learning [7], Richard Mayer asserts that viewers learn best from imagery that provides them with cues to help them organize new information into the correct knowledge structures. Designers have long been exploiting the Gestalt laws of visual grouping to deliver viewers those cues using visual hierarchy, often communicating structures much more complex than the simple organizations studied in psychological research. Unfortunately, designers are largely practical in their work, and have not paused to build a complex theory of structural communication. If we are to build a tool to help novices create effective and well structured visuals, we need a better understanding of how to create them. Our work takes a first step toward addressing this lack, studying how five of the many grouping cues (proximity, color similarity, common region, connectivity, and alignment) can be effectively combined to communicate structured text and imagery from real world examples. To measure the effectiveness of this structural communication, we applied a digital version of card sorting, a method widely used in anthropology and cognitive science to extract cognitive structures. We then used tree edit distance to measure the difference between perceived and communicated structures. Our most significant findings are: 1) with careful design, complex structure can be communicated clearly; 2) communicating complex structure is best done with multiple reinforcing grouping cues; 3) common region (use of containers such as boxes) is particularly effective at communicating structure; and 4) alignment is a weak structural communicator.

Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

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

Simonetti, Angelita; Marzi, Stefano; Fabbretti, Attilio

2013-06-01

The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2more » is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.« less

Segregating the core computational faculty of human language from working memory.

PubMed

Makuuchi, Michiru; Bahlmann, Jörg; Anwander, Alfred; Friederici, Angela D

2009-05-19

In contrast to simple structures in animal vocal behavior, hierarchical structures such as center-embedded sentences manifest the core computational faculty of human language. Previous artificial grammar learning studies found that the left pars opercularis (LPO) subserves the processing of hierarchical structures. However, it is not clear whether this area is activated by the structural complexity per se or by the increased memory load entailed in processing hierarchical structures. To dissociate the effect of structural complexity from the effect of memory cost, we conducted a functional magnetic resonance imaging study of German sentence processing with a 2-way factorial design tapping structural complexity (with/without hierarchical structure, i.e., center-embedding of clauses) and working memory load (long/short distance between syntactically dependent elements; i.e., subject nouns and their respective verbs). Functional imaging data revealed that the processes for structure and memory operate separately but co-operatively in the left inferior frontal gyrus; activities in the LPO increased as a function of structural complexity, whereas activities in the left inferior frontal sulcus (LIFS) were modulated by the distance over which the syntactic information had to be transferred. Diffusion tensor imaging showed that these 2 regions were interconnected through white matter fibers. Moreover, functional coupling between the 2 regions was found to increase during the processing of complex, hierarchically structured sentences. These results suggest a neuroanatomical segregation of syntax-related aspects represented in the LPO from memory-related aspects reflected in the LIFS, which are, however, highly interconnected functionally and anatomically.

Subsurface structures of buried features in the lunar Procellarum region

NASA Astrophysics Data System (ADS)

Wang, Wenrui; Heki, Kosuke

2017-07-01

The Gravity Recovery and Interior Laboratory (GRAIL) mission unraveled numbers of features showing strong gravity anomalies without prominent topographic signatures in the lunar Procellarum region. These features, located in different geologic units, are considered to have complex subsurface structures reflecting different evolution processes. By using the GRAIL level-1 data, we estimated the free-air and Bouguer gravity anomalies in several selected regions including such intriguing features. With the three-dimensional inversion technique, we recovered subsurface density structures in these regions.

Effector region of the translation elongation factor EF-Tu.GTP complex stabilizes an orthoester acid intermediate structure of aminoacyl-tRNA in a ternary complex.

PubMed Central

Förster, C; Limmer, S; Zeidler, W; Sprinzl, M

1994-01-01

tRNA(Val) from Escherichia coli was aminoacylated with [1-13C]valine and its complex with Thermus thermophilus elongation factor EF-Tu.GTP was analyzed by 13C NMR spectroscopy. The results suggest that the aminoacyl residue of the valyl-tRNA in ternary complex with bacterial EF-Tu and GTP is not attached to tRNA by a regular ester bond to either a 2'- or 3'-hydroxyl group; instead, an intermediate orthoester acid structure with covalent linkage to both vicinal hydroxyls of the terminal adenosine-76 is formed. Mutation of arginine-59 located in the effector region of EF-Tu, a conserved residue in protein elongation factors and the alpha subunits of heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins), abolishes the stabilization of the orthoester acid structure of aminoacyl-tRNA. PMID:8183898

Overlap and Differences in Brain Networks Underlying the Processing of Complex Sentence Structures in Second Language Users Compared with Native Speakers.

PubMed

Weber, Kirsten; Luther, Lisa; Indefrey, Peter; Hagoort, Peter

2016-05-01

When we learn a second language later in life, do we integrate it with the established neural networks in place for the first language or is at least a partially new network recruited? While there is evidence that simple grammatical structures in a second language share a system with the native language, the story becomes more multifaceted for complex sentence structures. In this study, we investigated the underlying brain networks in native speakers compared with proficient second language users while processing complex sentences. As hypothesized, complex structures were processed by the same large-scale inferior frontal and middle temporal language networks of the brain in the second language, as seen in native speakers. These effects were seen both in activations and task-related connectivity patterns. Furthermore, the second language users showed increased task-related connectivity from inferior frontal to inferior parietal regions of the brain, regions related to attention and cognitive control, suggesting less automatic processing for these structures in a second language.

Are Complex Magnetic Field Structures Responsible for the Confined X-class Flares in Super Active Region 12192?

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

Zhang, Jun; Li, Ting; Chen, Huadong, E-mail: zjun@nao.cas.cn, E-mail: hdchen@nao.cas.cn

From 2014 October 19 to 27, six X-class flares occurred in super active region (AR) 12192. They were all confined flares and were not followed by coronal mass ejections. To examine the structures of the four flares close to the solar disk center from October 22 to 26, we firstly employ composite triple-time images in each flare process to display the stratified structure of these flare loops. The loop structures of each flare in both the lower (171 Å) and higher (131 Å) temperature channels are complex, e.g., the flare loops rooting at flare ribbons are sheared or twisted (enwound)more » together, and the complex structures were not destroyed during the flares. For the first flare, although the flare loop system appears as a spindle shape, we can estimate its structures from observations, with lengths ranging from 130 to 300 Mm, heights from 65 to 150 Mm, widths at the middle part of the spindle from 40 to 100 Mm, and shear angles from 16° to 90°. Moreover, the flare ribbons display irregular movements, such as the left ribbon fragments of the flare on October 22 sweeping a small region repeatedly, and both ribbons of the flare on October 26 moved along the same direction instead of separating from each other. These irregular movements also imply that the corresponding flare loops are complex, e.g., several sets of flare loops are twisted together. Although previous studies have suggested that the background magnetic fields prevent confined flares from erupting,based on these observations, we suggest that complex flare loop structures may be responsible for these confined flares.« less

Genetic Structure and Inferences on Potential Source Areas for Bactrocera dorsalis (Hendel) Based on Mitochondrial and Microsatellite Markers

PubMed Central

Shi, Wei; Kerdelhué, Carole; Ye, Hui

2012-01-01

Bactrocera dorsalis (Diptera: Tephritidae) is mainly distributed in tropical and subtropical Asia and in the Pacific region. Despite its economic importance, very few studies have addressed the question of the wide genetic structure and potential source area of this species. This pilot study attempts to infer the native region of this pest and its colonization pathways in Asia. Combining mitochondrial and microsatellite markers, we evaluated the level of genetic diversity, genetic structure, and the gene flow among fly populations collected across Southeast Asia and China. A complex and significant genetic structure corresponding to the geographic pattern was found with both types of molecular markers. However, the genetic structure found was rather weak in both cases, and no pattern of isolation by distance was identified. Multiple long-distance dispersal events and miscellaneous host selection by this species may explain the results. These complex patterns may have been influenced by human-mediated transportation of the pest from one area to another and the complex topography of the study region. For both mitochondrial and microsatellite data, no signs of bottleneck or founder events could be identified. Nonetheless, maximal genetic diversity was observed in Myanmar, Vietnam and Guangdong (China) and asymmetric migration patterns were found. These results provide indirect evidence that the tropical regions of Southeast Asia and southern coast of China may be considered as the native range of the species and the population expansion is northward. Yunnan (China) is a contact zone that has been colonized from different sources. Regions along the southern coast of Vietnam and China probably served to colonize mainly the southern region of China. Southern coastal regions of China may also have colonized central parts of China and of central Yunnan. PMID:22615898

Flattening of Caribbean coral reefs: region-wide declines in architectural complexity

PubMed Central

Alvarez-Filip, Lorenzo; Dulvy, Nicholas K.; Gill, Jennifer A.; Côté, Isabelle M.; Watkinson, Andrew R.

2009-01-01

Coral reefs are rich in biodiversity, in large part because their highly complex architecture provides shelter and resources for a wide range of organisms. Recent rapid declines in hard coral cover have occurred across the Caribbean region, but the concomitant consequences for reef architecture have not been quantified on a large scale to date. We provide, to our knowledge, the first region-wide analysis of changes in reef architectural complexity, using nearly 500 surveys across 200 reefs, between 1969 and 2008. The architectural complexity of Caribbean reefs has declined nonlinearly with the near disappearance of the most complex reefs over the last 40 years. The flattening of Caribbean reefs was apparent by the early 1980s, followed by a period of stasis between 1985 and 1998 and then a resumption of the decline in complexity to the present. Rates of loss are similar on shallow (<6 m), mid-water (6–20 m) and deep (>20 m) reefs and are consistent across all five subregions. The temporal pattern of declining architecture coincides with key events in recent Caribbean ecological history: the loss of structurally complex Acropora corals, the mass mortality of the grazing urchin Diadema antillarum and the 1998 El Nino Southern Oscillation-induced worldwide coral bleaching event. The consistently low estimates of current architectural complexity suggest regional-scale degradation and homogenization of reef structure. The widespread loss of architectural complexity is likely to have serious consequences for reef biodiversity, ecosystem functioning and associated environmental services. PMID:19515663

Comparative genomic analysis of the MHC: the evolution of class I duplication blocks, diversity and complexity from shark to man.

PubMed

Kulski, Jerzy K; Shiina, Takashi; Anzai, Tatsuya; Kohara, Sakae; Inoko, Hidetoshi

2002-12-01

The major histocompatibility complex (MHC) genomic region is composed of a group of linked genes involved functionally with the adaptive and innate immune systems. The class I and class II genes are intrinsic features of the MHC and have been found in all the jawed vertebrates studied so far. The MHC genomic regions of the human and the chicken (B locus) have been fully sequenced and mapped, and the mouse MHC sequence is almost finished. Information on the MHC genomic structures (size, complexity, genic and intergenic composition and organization, gene order and number) of other vertebrates is largely limited or nonexistent. Therefore, we are mapping, sequencing and analyzing the MHC genomic regions of different human haplotypes and at least eight nonhuman species. Here, we review our progress with these sequences and compare the human MHC structure with that of the nonhuman primates (chimpanzee and rhesus macaque), other mammals (pigs, mice and rats) and nonmammalian vertebrates such as birds (chicken and quail), bony fish (medaka, pufferfish and zebrafish) and cartilaginous fish (nurse shark). This comparison reveals a complex MHC structure for mammals and a relatively simpler design for nonmammalian animals with a hypothetical prototypic structure for the shark. In the mammalian MHC, there are two to five different class I duplication blocks embedded within a framework of conserved nonclass I and/or nonclass II genes. With a few exceptions, the class I framework genes are absent from the MHC of birds, bony fish and sharks. Comparative genomics of the MHC reveal a highly plastic region with major structural differences between the mammalian and nonmammalian vertebrates. Additional genomic data are needed on animals of the reptilia, crocodilia and marsupial classes to find the origins of the class I framework genes and examples of structures that may be intermediate between the simple and complex MHC organizations of birds and mammals, respectively.

A Butterfly in the Making: Revealing the Near-Infrared Structure of Hubble 12

NASA Technical Reports Server (NTRS)

Hora, Joseph L.; Latter, William B.

1996-01-01

We present deep narrowband near-IR images and moderate resolution spectra of the young planetary nebula Hubble 12. These data are the first to show clearly the complex structure for this important planetary nebula. Images were obtained at lambda = 2.12, 2.16, and 2.26 micron. The lambda = 2.12 Am image reveals the bipolar nature of the nebula, as well as complex structure near the central star in the equatorial region. The images show an elliptical region of emission, which may indicate a ring or a cylindrical source structure. This structure is possibly related to the mechanism that is producing the bipolar flow. The spectra show the nature of several distinct components. The central object is dominated by recombination lines of H I and He I. The core is not a significant source of molecular hydrogen emission. The east position in the equatorial region is rich in lines of ultraviolet-excited fluorescent H2. A spectrum of part of the central region shows strong [Fe II] emission, which might indicate the presence of shocks.

Crystal structures of the CBS and DRTGG domains of the regulatory region of Clostridiumperfringens pyrophosphatase complexed with the inhibitor, AMP, and activator, diadenosine tetraphosphate.

PubMed

Tuominen, H; Salminen, A; Oksanen, E; Jämsen, J; Heikkilä, O; Lehtiö, L; Magretova, N N; Goldman, A; Baykov, A A; Lahti, R

2010-05-07

Nucleotide-binding cystathionine beta-synthase (CBS) domains serve as regulatory units in numerous proteins distributed in all kingdoms of life. However, the underlying regulatory mechanisms remain to be established. Recently, we described a subfamily of CBS domain-containing pyrophosphatases (PPases) within family II PPases. Here, we express a novel CBS-PPase from Clostridium perfringens (CPE2055) and show that the enzyme is inhibited by AMP and activated by a novel effector, diadenosine 5',5-P1,P4-tetraphosphate (AP(4)A). The structures of the AMP and AP(4)A complexes of the regulatory region of C. perfringens PPase (cpCBS), comprising a pair of CBS domains interlinked by a DRTGG domain, were determined at 2.3 A resolution using X-ray crystallography. The structures obtained are the first structures of a DRTGG domain as part of a larger protein structure. The AMP complex contains two AMP molecules per cpCBS dimer, each bound to a single monomer, whereas in the activator-bound complex, one AP(4)A molecule bridges two monomers. In the nucleotide-bound structures, activator binding induces significant opening of the CBS domain interface, compared with the inhibitor complex. These results provide structural insight into the mechanism of CBS-PPase regulation by nucleotides. Copyright 2010 Elsevier Ltd. All rights reserved.

Segregating the core computational faculty of human language from working memory

PubMed Central

Makuuchi, Michiru; Bahlmann, Jörg; Anwander, Alfred; Friederici, Angela D.

2009-01-01

In contrast to simple structures in animal vocal behavior, hierarchical structures such as center-embedded sentences manifest the core computational faculty of human language. Previous artificial grammar learning studies found that the left pars opercularis (LPO) subserves the processing of hierarchical structures. However, it is not clear whether this area is activated by the structural complexity per se or by the increased memory load entailed in processing hierarchical structures. To dissociate the effect of structural complexity from the effect of memory cost, we conducted a functional magnetic resonance imaging study of German sentence processing with a 2-way factorial design tapping structural complexity (with/without hierarchical structure, i.e., center-embedding of clauses) and working memory load (long/short distance between syntactically dependent elements; i.e., subject nouns and their respective verbs). Functional imaging data revealed that the processes for structure and memory operate separately but co-operatively in the left inferior frontal gyrus; activities in the LPO increased as a function of structural complexity, whereas activities in the left inferior frontal sulcus (LIFS) were modulated by the distance over which the syntactic information had to be transferred. Diffusion tensor imaging showed that these 2 regions were interconnected through white matter fibers. Moreover, functional coupling between the 2 regions was found to increase during the processing of complex, hierarchically structured sentences. These results suggest a neuroanatomical segregation of syntax-related aspects represented in the LPO from memory-related aspects reflected in the LIFS, which are, however, highly interconnected functionally and anatomically. PMID:19416819

Precambrian evolution of the Salalah Crystalline Basement from structural analysis and 40Ar/39Ar geochronology

NASA Astrophysics Data System (ADS)

Al-Doukhi, Hanadi Abulateef

The Salalah Crystalline Basement (SCB) is the largest Precambrian exposure in Oman located on the southern margin of the Arabian Plate at the Arabian Sea shore. This work used remote sensing, detailed structural analysis and the analysis of ten samples using 40Ar/39Ar age dating to establish the Precambrian evolution of the SCB by focusing on its central and southwestern parts. This work found that the SCB evolved through four deformational events that shaped its final architecture: (1) Folding and thrusting event that resulted in the emplacement of the Sadh complex atop the Juffa complex. This event resulted in the formation of possibly N-verging nappe structure; (2) Regional folding event around SE- and SW-plunging axes that deformed the regional fabric developed during the N-verging nappe structure and produced map-scale SE- and SW-plunging antiforms shaping the complexes into a semi-dome structure; (3) Strike-slip shearing event that produced a conjugate set of NE-trending sinistral and NW-trending dextral strike-slip shear zones; and (4) Localized SE-directed gravitational collapse manifested by top-to-the-southeast kinematic indicators. Deformation within the SCB might have ceased by 752.2+/-2.7 Ma as indicated by an age given by an undeformed granite. The thermochron of samples collected throughout the SCB complexes shows a single cooling event that occurred between about 800 and 760 Ma. This cooling event could be accomplished by crustal exhumation resulting in regional collapse following the prolonged period of the contractional deformation of the SCB. This makes the SCB a possible metamorphic core complex.

Structural characterization of POM6 Fab and mouse prion protein complex identifies key regions for prions conformational conversion.

PubMed

Baral, Pravas Kumar; Swayampakula, Mridula; Aguzzi, Adriano; James, Michael N G

2018-05-01

Conversion of the cellular prion protein PrP C into its pathogenic isoform PrP S c is the hallmark of prion diseases, fatal neurodegenerative diseases affecting many mammalian species including humans. Anti-prion monoclonal antibodies can arrest the progression of prion diseases by stabilizing the cellular form of the prion protein. Here, we present the crystal structure of the POM6 Fab fragment, in complex with the mouse prion protein (moPrP). The prion epitope of POM6 is in close proximity to the epitope recognized by the purportedly toxic antibody fragment, POM1 Fab also complexed with moPrP. The POM6 Fab recognizes a larger binding interface indicating a likely stronger binding compared to POM1. POM6 and POM1 exhibit distinct biological responses. Structural comparisons of the bound mouse prion proteins from the POM6 Fab:moPrP and POM1 Fab:moPrP complexes reveal several key regions of the prion protein that might be involved in initiating mis-folding events. The structural data of moPrP:POM6 Fab complex are available in the PDB under the accession number www.rcsb.org/pdb/search/structidSearch.do?structureId=6AQ7. © 2018 Federation of European Biochemical Societies.

Neural Correlates of Verb Argument Structure Processing

PubMed Central

Thompson, Cynthia K.; Bonakdarpour, Borna; Fix, Stephen C.; Blumenfeld, Henrike K.; Parrish, Todd B.; Gitelman, Darren R.; Mesulam, M.-Marsel

2008-01-01

Neuroimaging and lesion studies suggest that processing of word classes, such as verbs and nouns, is associated with distinct neural mechanisms. Such studies also suggest that subcategories within these broad word class categories are differentially processed in the brain. Within the class of verbs, argument structure provides one linguistic dimension that distinguishes among verb exemplars, with some requiring more complex argument structure entries than others. This study examined the neural instantiation of verbs by argument structure complexity: one-, two-, and three-argument verbs. Stimuli of each type, along with nouns and pseudowords, were presented for lexical decision using an event-related functional magnetic resonance imaging design. Results for 14 young normal participants indicated largely overlapping activation maps for verbs and nouns, with no areas of significant activation for verbs compared to nouns, or vice versa. Pseudowords also engaged neural tissue overlapping with that for both word classes, with more widespread activation noted in visual, motor, and peri-sylvian regions. Examination of verbs by argument structure revealed activation of the supramarginal and angular gyri, limited to the left hemisphere only when verbs with two obligatory arguments were compared to verbs with a single argument. However, bilateral activation was noted when both two- and three-argument verbs were compared to one-argument verbs. These findings suggest that posterior peri-sylvian regions are engaged for processing argument structure information associated with verbs, with increasing neural tissue in the inferior parietal region associated with increasing argument structure complexity. These findings are consistent with processing accounts, which suggest that these regions are crucial for semantic integration. PMID:17958479

Deciphering RNA-Recognition Patterns of Intrinsically Disordered Proteins.

PubMed

Srivastava, Ambuj; Ahmad, Shandar; Gromiha, M Michael

2018-05-29

Intrinsically disordered regions (IDRs) and protein (IDPs) are highly flexible owing to their lack of well-defined structures. A subset of such proteins interacts with various substrates; including RNA; frequently adopting regular structures in the final complex. In this work; we have analysed a dataset of protein⁻RNA complexes undergoing disorder-to-order transition (DOT) upon binding. We found that DOT regions are generally small in size (less than 3 residues) for RNA binding proteins. Like structured proteins; positively charged residues are found to interact with RNA molecules; indicating the dominance of electrostatic and cation-π interactions. However, a comparison of binding frequency shows that interface hydrophobic and aromatic residues have more interactions in only DOT regions than in a protein. Further; DOT regions have significantly higher exposure to water than their structured counterparts. Interactions of DOT regions with RNA increase the sheet formation with minor changes in helix forming residues. We have computed the interaction energy for amino acids⁻nucleotide pairs; which showed the preference of His⁻G; Asn⁻U and Ser⁻U at for the interface of DOT regions. This study provides insights to understand protein⁻RNA interactions and the results could also be used for developing a tool for identifying DOT regions in RNA binding proteins.

An Integrated Geophysical and Tectonic Study of the Structure and Evolution of the Crust in the Snake River Plain Region, Pacific Northwest

NASA Astrophysics Data System (ADS)

Keller, G. R.; Khatiwada, M.

2016-12-01

The Snake River Plain region in the Pacific Northwest of North America has been the target of a number of recent studies that have revealed further complexities in its structure and tectonic evolution. Based on surface morphology and Late Cenozoic volcanic activity, the Snake River Plain consists of an eastern and western arm (ESRP and WSRP) that are similar in many respects but also quite different in other respects. Thus, its origin, evolution, structural complexities, the role of extension and magmatism in its formation, and the tectonic drivers are still subjects of debate. Numerous seismic studies have specifically focused on the structure of the ESRP and Yellowstone area. However, crustal-scale studies of the WSRP are limited. We added new gravity data to the existing coverage in the WSRP region and undertook a regional, integrated analysis approach that included magnetic, seismic reflection and refraction profiling, receiver function results, geological and geospatial data, and interpreted well logs. Our integrated geophysical modeling focused on the structure of the WSRP. We generated two crustal models across it at locations where the most existing geophysical and geological constraints were available. We observed both differences and similarities in the structure of the WSRP and ESRP. Although, the shallow crustal structures are different, a mid-crustal mafic intrusion is a major source of the high gravity anomaly values. Within the context of recent studies in the surrounding region, the intersection of the two arms of the Snake River Plain emerges as a major element of a complex tectonic intersection that includes the High Lava Plains of eastern Oregon, the Northern Nevada Rift, a southwestern extension of the ESRP into northern Nevada, as well as, faulting and volcanism extending northwestward to connect with the Columbia River Basalts region.

Integrative structure and functional anatomy of a nuclear pore complex

NASA Astrophysics Data System (ADS)

Kim, Seung Joong; Fernandez-Martinez, Javier; Nudelman, Ilona; Shi, Yi; Zhang, Wenzhu; Raveh, Barak; Herricks, Thurston; Slaughter, Brian D.; Hogan, Joanna A.; Upla, Paula; Chemmama, Ilan E.; Pellarin, Riccardo; Echeverria, Ignacia; Shivaraju, Manjunatha; Chaudhury, Azraa S.; Wang, Junjie; Williams, Rosemary; Unruh, Jay R.; Greenberg, Charles H.; Jacobs, Erica Y.; Yu, Zhiheng; de La Cruz, M. Jason; Mironska, Roxana; Stokes, David L.; Aitchison, John D.; Jarrold, Martin F.; Gerton, Jennifer L.; Ludtke, Steven J.; Akey, Christopher W.; Chait, Brian T.; Sali, Andrej; Rout, Michael P.

2018-03-01

Nuclear pore complexes play central roles as gatekeepers of RNA and protein transport between the cytoplasm and nucleoplasm. However, their large size and dynamic nature have impeded a full structural and functional elucidation. Here we determined the structure of the entire 552-protein nuclear pore complex of the yeast Saccharomyces cerevisiae at sub-nanometre precision by satisfying a wide range of data relating to the molecular arrangement of its constituents. The nuclear pore complex incorporates sturdy diagonal columns and connector cables attached to these columns, imbuing the structure with strength and flexibility. These cables also tie together all other elements of the nuclear pore complex, including membrane-interacting regions, outer rings and RNA-processing platforms. Inwardly directed anchors create a high density of transport factor-docking Phe-Gly repeats in the central channel, organized into distinct functional units. This integrative structure enables us to rationalize the architecture, transport mechanism and evolutionary origins of the nuclear pore complex.

Integrative structure and functional anatomy of a nuclear pore complex.

PubMed

Kim, Seung Joong; Fernandez-Martinez, Javier; Nudelman, Ilona; Shi, Yi; Zhang, Wenzhu; Raveh, Barak; Herricks, Thurston; Slaughter, Brian D; Hogan, Joanna A; Upla, Paula; Chemmama, Ilan E; Pellarin, Riccardo; Echeverria, Ignacia; Shivaraju, Manjunatha; Chaudhury, Azraa S; Wang, Junjie; Williams, Rosemary; Unruh, Jay R; Greenberg, Charles H; Jacobs, Erica Y; Yu, Zhiheng; de la Cruz, M Jason; Mironska, Roxana; Stokes, David L; Aitchison, John D; Jarrold, Martin F; Gerton, Jennifer L; Ludtke, Steven J; Akey, Christopher W; Chait, Brian T; Sali, Andrej; Rout, Michael P

2018-03-22

Nuclear pore complexes play central roles as gatekeepers of RNA and protein transport between the cytoplasm and nucleoplasm. However, their large size and dynamic nature have impeded a full structural and functional elucidation. Here we determined the structure of the entire 552-protein nuclear pore complex of the yeast Saccharomyces cerevisiae at sub-nanometre precision by satisfying a wide range of data relating to the molecular arrangement of its constituents. The nuclear pore complex incorporates sturdy diagonal columns and connector cables attached to these columns, imbuing the structure with strength and flexibility. These cables also tie together all other elements of the nuclear pore complex, including membrane-interacting regions, outer rings and RNA-processing platforms. Inwardly directed anchors create a high density of transport factor-docking Phe-Gly repeats in the central channel, organized into distinct functional units. This integrative structure enables us to rationalize the architecture, transport mechanism and evolutionary origins of the nuclear pore complex.

Structure of the Repulsive Guidance Molecule (RGM)—Neogenin Signaling Hub

PubMed Central

Bell, Christian H.; Bishop, Benjamin; Tang, Chenxiang; Gilbert, Robert J.C.; Aricescu, A. Radu; Pasterkamp, R. Jeroen; Siebold, Christian

2016-01-01

Repulsive guidance molecule family members (RGMs) control fundamental and diverse cellular processes, including motility and adhesion, immune cell regulation, and systemic iron metabolism. However, it is not known how RGMs initiate signaling through their common cell-surface receptor, neogenin (NEO1). Here, we present crystal structures of the NEO1 RGM-binding region and its complex with human RGMB (also called dragon). The RGMB structure reveals a previously unknown protein fold and a functionally important autocatalytic cleavage mechanism and provides a framework to explain numerous disease-linked mutations in RGMs. In the complex, two RGMB ectodomains conformationally stabilize the juxtamembrane regions of two NEO1 receptors in a pH-dependent manner. We demonstrate that all RGM-NEO1 complexes share this architecture, which therefore represents the core of multiple signaling pathways. PMID:23744777

Observations of peculiar sporadic sodium structures and their relation with wind variations

NASA Astrophysics Data System (ADS)

Sridharan, S.; Prasanth, P. Vishnu; Kumar, Y. Bhavani; Ramkumar, Geetha; Sathishkumar, S.; Raghunath, K.

2009-04-01

Resonance lidar observations of sodium density in the upper mesosphere region over Gadanki (13.5°N, 79.2°E) rarely show complex structures with rapid enhancements of sodium density, completely different from normal sporadic sodium structures. The hourly averaged meteor radar zonal winds over Trivandrum (8.5°N, 76.5°E) show an eastward shear with altitude during the nights, when these events are formed. As suggested by Kane et al. [2001. Joint observations of sodium enhancements and field-aligned ionospheric irregularities. Geophysical Research Letters 28, 1375-1378], our observations show that the complex structures may be formed due to Kelvin-Helmholtz instability, which can occur in the region of strong wind shear.

Infrared Photodissociation Spectroscopy of Metal Ion -WATER Complexes

NASA Astrophysics Data System (ADS)

Bandyopadhyay, B.; Carnegie, P. D.; Duncan, M. A.

2011-06-01

Metal ion-water complexes are produced in a supersonic expansion cluster source via laser vaporization technique. Infrared photodissociation spectroscopy has been performed in the O-H stretch region. DFT calculations have also been carried out to obtain the structures and vibrational frequencies. Infrared spectra show partially resolved rotational structures which will be analyzed.

Cellulose synthase (CesA) genes in the green alga Mesotaenium caldariorum.

PubMed

Roberts, Alison W; Roberts, Eric M; Delmer, Deborah P

2002-12-01

Cellulose, a microfibrillar polysaccharide consisting of bundles of beta-1,4-glucan chains, is a major component of plant and most algal cell walls and is also synthesized by some prokaryotes. Seed plants and bacteria differ in the structures of their membrane terminal complexes that make cellulose and, in turn, control the dimensions of the microfibrils produced. They also differ in the domain structures of their CesA gene products (the catalytic subunit of cellulose synthase), which have been localized to terminal complexes and appear to help maintain terminal complex structure. Terminal complex structures in algae range from rosettes (plant-like) to linear forms (bacterium-like). Thus, algal CesA genes may reveal domains that control terminal complex assembly and microfibril structure. The CesA genes from the alga Mesotaenium caldariorum, a member of the order Zygnematales, which have rosette terminal complexes, are remarkably similar to seed plant CesAs, with deduced amino acid sequence identities of up to 59%. In addition to the putative transmembrane helices and the D-D-D-QXXRW motif shared by all known CesA gene products, M. caldariorum and seed plant CesAs share a region conserved among plants, an N-terminal zinc-binding domain, and a variable or class-specific region. This indicates that the domains that characterize seed plant CesAs arose prior to the evolution of land plants and may play a role in maintaining the structures of rosette terminal complexes. The CesA genes identified in M. caldariorum are the first reported for any eukaryotic alga and will provide a basis for analyzing the CesA genes of algae with different types of terminal complexes.

Structural complexity and molecular heterogeneity of a butterfly ejaculate reflect a complex history of selection

PubMed Central

Cherwin, Tamara S.; Plakke, Melissa S.; Hill, Jason; Small, Brandon S.; Goetz, Breanna J.; Wheat, Christopher W.; Morehouse, Nathan I.

2017-01-01

Male ejaculates are often structurally complex, and this complexity is likely to influence key reproductive interactions between males and females. However, despite its potential evolutionary significance, the molecular underpinnings of ejaculate structural complexity have received little empirical attention. To address this knowledge gap, we sought to understand the biochemical and functional properties of the structurally complex ejaculates of Pieris rapae butterflies. Males in this species produce large ejaculates called spermatophores composed of an outer envelope, an inner matrix, and a bolus of sperm. Females are thought to benefit from the nutrition contained in the soluble inner matrix through increases in longevity and fecundity. However, the indigestible outer envelope of the spermatophore delays female remating, allowing males to monopolize paternity for longer. Here, we show that these two nonsperm-containing spermatophore regions, the inner matrix and the outer envelope, differ in their protein composition and functional properties. We also reveal how these divergent protein mixtures are separately stored in the male reproductive tract and sequentially transferred to the female reproductive tract during spermatophore assembly. Intriguingly, we discovered large quantities of female-derived proteases in both spermatophore regions shortly after mating, which may contribute to spermatophore digestion and hence, female control over remating rate. Finally, we report evidence of past selection on these spermatophore proteins and female proteases, indicating a complex evolutionary history. Our findings illustrate how structural complexity of ejaculates may allow functionally and/or spatially associated suites of proteins to respond rapidly to divergent selective pressures, such as sexual conflict or reproductive cooperation. PMID:28630352

A FUNCTIONAL NEUROIMAGING INVESTIGATION OF THE ROLES OF STRUCTURAL COMPLEXITY AND TASK-DEMAND DURING AUDITORY SENTENCE PROCESSING

PubMed Central

Love, Tracy; Haist, Frank; Nicol, Janet; Swinney, David

2009-01-01

Using functional magnetic resonance imaging (fMRI), this study directly examined an issue that bridges the potential language processing and multi-modal views of the role of Broca’s area: the effects of task-demands in language comprehension studies. We presented syntactically simple and complex sentences for auditory comprehension under three different (differentially complex) task-demand conditions: passive listening, probe verification, and theme judgment. Contrary to many language imaging findings, we found that both simple and complex syntactic structures activated left inferior frontal cortex (L-IFC). Critically, we found activation in these frontal regions increased together with increased task-demands. Specifically, tasks that required greater manipulation and comparison of linguistic material recruited L-IFC more strongly; independent of syntactic structure complexity. We argue that much of the presumed syntactic effects previously found in sentence imaging studies of L-IFC may, among other things, reflect the tasks employed in these studies and that L-IFC is a region underlying mnemonic and other integrative functions, on which much language processing may rely. PMID:16881268

In vivo topography of Rap1p-DNA complex at Saccharomyces cerevisiae TEF2 UAS(RPG) during transcriptional regulation.

PubMed

De Sanctis, Veronica; La Terra, Sabrina; Bianchi, Alessandro; Shore, David; Burderi, Luciano; Di Mauro, Ernesto; Negri, Rodolfo

2002-04-26

We have analyzed in detail the structure of RAP1-UAS(RPG) complexes in Saccharomyces cerevisiae cells using multi-hit KMnO(4), UV and micrococcal nuclease high-resolution footprinting. Three copies of the Rap1 protein are bound to the promoter simultaneously in exponentially growing cells, as shown by KMnO(4) multi-hit footprinting analysis, causing extended and diagnostic changes in the DNA structure of the region containing the UAS(RPG). Amino acid starvation does not cause loss of Rap1p from the complex; however, in vivo UV-footprinting reveals the occurrence of structural modifications of the complex. Moreover, low-resolution micrococcal nuclease digestion shows that the chromatin of the entire region is devoid of positioned nucleosomes but is susceptible to changes in accessibility to the nuclease upon amino acid starvation. The implications of these results for the mechanism of Rap1p action are discussed. (c) 2002 Elsevier Science Ltd.

The Structure of Cognition: Attentional Episodes in Mind and Brain

PubMed Central

Duncan, John

2013-01-01

Cognition is organized in a structured series of attentional episodes, allowing complex problems to be addressed through solution of simpler subproblems. A “multiple-demand” (MD) system of frontal and parietal cortex is active in many different kinds of tasks, and using data from neuroimaging, electrophysiology, neuropsychology, and cognitive studies of intelligence, I propose a core role for MD regions in assembly of the attentional episode. Monkey and human data show dynamic neural coding of attended information across multiple MD regions, with rapid communication within and between regions. Neuropsychological and imaging data link MD function to fluid intelligence, explaining some but not all “executive” deficits after frontal lobe lesions. Cognitive studies link fluid intelligence to goal neglect, and the problem of dividing complex task requirements into focused parts. Like the innate releasing mechanism of ethology, I suggest that construction of the attentional episode provides a core organizational principle for complex, adaptive cognition. PMID:24094101

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

PubMed

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

2016-09-08

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

The structural basis of Arf effector specificity: the crystal structure of ARF6 in a complex with JIP4.

PubMed

Isabet, Tatiana; Montagnac, Guillaume; Regazzoni, Karine; Raynal, Bertrand; El Khadali, Fatima; England, Patrick; Franco, Michel; Chavrier, Philippe; Houdusse, Anne; Ménétrey, Julie

2009-09-16

The JNK-interacting proteins, JIP3 and JIP4, are specific effectors of the small GTP-binding protein ARF6. The interaction of ARF6-GTP with the second leucine zipper (LZII) domains of JIP3/JIP4 regulates the binding of JIPs to kinesin-1 and dynactin. Here, we report the crystal structure of ARF6-GTP bound to the JIP4-LZII at 1.9 A resolution. The complex is a heterotetramer with dyad symmetry arranged in an ARF6-(JIP4)(2)-ARF6 configuration. Comparison of the ARF6-JIP4 interface with the equivalent region of ARF1 shows the structural basis of JIP4's specificity for ARF6. Using site-directed mutagenesis and surface plasmon resonance, we further show that non-conserved residues at the switch region borders are the key structural determinants of JIP4 specificity. A structure-derived model of the association of the ARF6-JIP3/JIP4 complex with membranes shows that the JIP4-LZII coiled-coil should lie along the membrane to prevent steric hindrances, resulting in only one ARF6 molecule bound. Such a heterotrimeric complex gives insights to better understand the ARF6-mediated motor switch regulatory function.

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

Zhang, Jiang; Malmirchegini, G. Reza; Clubb, Robert T.

Native mass spectrometry (MS) has become an invaluable tool for the characterization of proteins and non-covalent protein complexes under near physiological solution conditions. Here we report the structural characterization of human hemoglobin (Hb), a 64 kDa oxygen-transporting protein complex, by high resolution native top-down mass spectrometry using electrospray ionization (ESI) and a 15-Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Native MS preserves the non-covalent interactions between the globin subunits, and electron capture dissociation (ECD) produces fragments directly from the intact Hb complex without dissociating the subunits. Using activated ion ECD, we observe the gradual unfolding process of themore » Hb complex in the gas phase. Without protein ion activation, the native Hb shows very limited ECD fragmentation from the N-termini, suggesting a tightly packed structure of the native complex and therefore low fragmentation efficiency. Precursor ion activation allows steady increase of N-terminal fragment ions, while the C-terminal fragments remain limited (38 c ions and 4 z ions on the α chain; 36 c ions and 2 z ions on the β chain). This ECD fragmentation pattern suggests that upon activation, the Hb complex starts to unfold from the N-termini of both subunits, whereas the C-terminal regions and therefore the potential regions involved in the subunit binding interactions remain intact. ECD-MS of the Hb dimer show similar fragmentation patterns as the Hb tetramer, providing further evidence for the hypothesized unfolding process of the Hb complex in the gas phase. Native top-down ECD-MS allows efficient probing of the Hb complex structure and the subunit binding interactions in the gas phase. Finally, it may provide a fast and effective means to probe the structure of novel protein complexes that are intractable to traditional structural characterization tools.« less

The Disordered C-Terminus of Yeast Hsf1 Contains a Cryptic Low-Complexity Amyloidogenic Region.

PubMed

Pujols, Jordi; Santos, Jaime; Pallarès, Irantzu; Ventura, Salvador

2018-05-06

Response mechanisms to external stress rely on networks of proteins able to activate specific signaling pathways to ensure the maintenance of cell proteostasis. Many of the proteins mediating this kind of response contain intrinsically disordered regions, which lack a defined structure, but still are able to interact with a wide range of clients that modulate the protein function. Some of these interactions are mediated by specific short sequences embedded in the longer disordered regions. Because the physicochemical properties that promote functional and abnormal interactions are similar, it has been shown that, in globular proteins, aggregation-prone and binding regions tend to overlap. It could be that the same principle applies for disordered protein regions. In this context, we show here that a predicted low-complexity interacting region in the disordered C-terminus of the stress response master regulator heat shock factor 1 (Hsf1) protein corresponds to a cryptic amyloid region able to self-assemble into fibrillary structures resembling those found in neurodegenerative disorders.

Upper trophic structure in the Atlantic Patagonian shelf break as inferred from stable isotope analysis

NASA Astrophysics Data System (ADS)

Zhu, Guoping; Zhang, Haiting; Yang, Yang; Wang, Shaoqin; Wei, Lian; Yang, Qingyuan

2017-09-01

The Patagonian Shelf is a very productive region with different ecosystem structures. A long history of fishing in the Southwestern Atlantic Ocean combined with a complex hydrographic structure, with a permanent front over the shelf-break and different coastal frontal regions, and a wide non-frontal area in between have made the food web in this area more complex and have resulted in changes to the spatial-temporal scale. Stable isotopes of carbon and nitrogen were used to determine the trophic structure of the Patagonian shelf break which was previously poorly understood. The results indicated that the average δ15N value of pelagic guild (Illex argentinus) was remarkable lower than those of the other guilds. The δ13C values of almost all species ranged from -17‰ to -18‰, but Stromateus brasiliensis had a significant lower δ13C value. Compared with the southern Patagonian shelf, short food chain length also occurred. The impact of complex oceanographic structures has resulted in food web structure change to the temporal-spatial scale on the Patagonian shelf. The Patagonian shelf break can be considered as a separated ecosystem structure with lower δ15N values.

Photodissociation spectroscopy and ab initio calculations for the Sr +-N 2 complex

NASA Astrophysics Data System (ADS)

Massaouti, Maria; Fanourgakis, George S.; Velegrakis, Michalis

2010-04-01

Electronic vibrationally resolved spectra of the Sr +-N 2 complex have been recorded in two energy regions 20 284-22 988 cm -1 and 15 576-16 380 cm -1. In the high energy region, two progressions are present and they are attributed to the (2) 2Π 3/2,1/2 ← X2Σ+ transitions assuming a linear molecule. This linear configuration is supported from the observed spin-orbit splitting of these excited states as well as from electronic structure calculations. The lower energy spectrum shows a structure, which ends up to a continuum. Considering the complex as an anharmonic oscillator, the spectroscopic constants and the dissociation energies of the corresponding states are determined.

Drainage isolation and climate change-driven population expansion shape the genetic structures of Tuber indicum complex in the Hengduan Mountains region.

PubMed

Feng, Bang; Zhao, Qi; Xu, Jianping; Qin, Jiao; Yang, Zhu L

2016-02-24

The orogenesis of the Qinghai-Tibetan Plateau and the Quaternary climate changes have played key roles in driving the evolution of flora and fauna in Southwest China, but their effects on higher fungi are poorly addressed. In this study, we investigated the phylogeographic pattern of the Tuber indicum species complex, an economically important fungal group distributed in the Hengduan Mountains region. Our data confirmed the existence of two distinct lineages, T. indicum and T. himalayense, within this species complex. Three geographic groups (Groups W, N and C) were revealed within T. indicum, with Group W found in the paleo-Lancang River region, while Groups N and C corresponded to the two banks along the contemporary Jinsha River, suggesting that rivers have acted as barriers for gene flow among populations from different drainages. Historical range expansion resulted from climate changes was inferred in Group C, contributing to the observed gene flow among geographic populations within this group. Although no significant geographic structure was identified in T. himalayense, evidence of drainage isolation for this species was also detected. Our findings demonstrate that both topographic changes and Quaternary climate oscillations have played important roles in driving the genetic structures of the T. indicum species complex.

Uranyl mediated photofootprinting reveals strong E. coli RNA polymerase--DNA backbone contacts in the +10 region of the DeoP1 promoter open complex.

PubMed Central

Jeppesen, C; Nielsen, P E

1989-01-01

Employing a newly developed uranyl photofootprinting technique (Nielsen et al. (1988) FEBS Lett. 235, 122), we have analyzed the structure of the E. coli RNA polymerase deoP1 promoter open complex. The results show strong polymerase DNA backbone contacts in the -40, -10, and most notably in the +10 region. These results suggest that unwinding of the -12 to +3 region of the promoter in the open complex is mediated through polymerase DNA backbone contacts on both sides of this region. The pattern of bases that are hyperreactive towards KMnO4 or uranyl within the -12 to +3 region furthermore argues against a model in which this region is simply unwound and/or single stranded. The results indicate specific protein contacts and/or a fixed DNA conformation within the -12 to +3 region. Images PMID:2503811

Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex

PubMed Central

Tamada, Taro; Honjo, Eijiro; Maeda, Yoshitake; Okamoto, Tomoyuki; Ishibashi, Matsujiro; Tokunaga, Masao; Kuroki, Ryota

2006-01-01

A crystal structure of the signaling complex between human granulocyte colony-stimulating factor (GCSF) and a ligand binding region of GCSF receptor (GCSF-R), has been determined to 2.8 Å resolution. The GCSF:GCSF-R complex formed a 2:2 stoichiometry by means of a cross-over interaction between the Ig-like domains of GCSF-R and GCSF. The conformation of the complex is quite different from that between human GCSF and the cytokine receptor homologous domain of mouse GCSF-R, but similar to that of the IL-6/gp130 signaling complex. The Ig-like domain cross-over structure necessary for GCSF-R activation is consistent with previously reported thermodynamic and mutational analyses. PMID:16492764

Distances, Kinematics, And Structure Of The Orion Complex

NASA Astrophysics Data System (ADS)

Kounkel, Marina; Hartmann, Lee

2018-01-01

I present an analysis of the structure and kinematics of the Orion Molecular Cloud Complex in an effort to better characterize the dynamical state of the closest region of ongoing massive star formation. I measured stellar parallax and proper motions with <5% uncertainty using radio VLBI observations of non-thermally-emitting sources located in various star forming regions within the Orion Complex. This includes the first direct distance measurements for sources that are located outside of the Orion Nebula. I identified a number of binary systems in the VLBI dataset and fitted their orbital motion, which allows for the direct measurement of the masses of the individual components. Additionally, I have identified several stars that have been ejected from the Orion Nebula due to strong gravitational interactions with the most massive members. I complemented the parallax and proper motion measurements with the observations of optical radial velocities of the stars toward the Orion Complex, probing the histories of both dynamic evolution and star formation in the region, providing a 6-dimensional model of the Complex. These observations can serve as a baseline for comparison of the upcoming results from the Gaia space telescope

Anomalous Putamen Volume in Children with Complex Motor Stereotypies

PubMed Central

Mahone, E. Mark; Crocetti, Deana; Tochen, Laura; Kline, Tina; Mostofsky, Stewart H.; Singer, Harvey S.

2016-01-01

Introduction Complex motor stereotypies in children are repetitive, rhythmic movements that have a predictable pattern and location, seem purposeful, but serve no obvious function, tend to be prolonged, and stop with distraction, e.g., arm/hand flapping, waving. They occur in both “primary” (otherwise typically developing) and secondary conditions. These movements are best defined as habitual behaviors and therefore pathophysiologically hypothesized to reside in premotor to posterior putamen circuits. This study sought to clarify the underlying neurobiological abnormality in children with primary complex motor stereotypies using structural neuroimaging, emphasizing brain regions hypothesized to underlie these atypical behaviors. Methods High-resolution anatomical MRI images, acquired at 3.0T, were analyzed in children ages 8–12 years (20 with primary complex motor stereotypies, 20 typically developing). Frontal lobe sub-regions and striatal structures were delineated for analysis. Results Significant reductions (p=0.045) in the stereotypies group were identified in total putamen volume, but not caudate, nucleus accumbens or frontal sub-regions. There were no group differences in total cerebral volume. Conclusion Findings of a smaller putamen provide preliminary evidence suggesting the potential involvement of the habitual pathway as the underlying anatomical site in primary complex motor stereotypies. PMID:27751663

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

Native top-down mass spectrometry for the structural characterization of human hemoglobin

DOE PAGES

Zhang, Jiang; Malmirchegini, G. Reza; Clubb, Robert T.; ...

2015-06-09

Native mass spectrometry (MS) has become an invaluable tool for the characterization of proteins and non-covalent protein complexes under near physiological solution conditions. Here we report the structural characterization of human hemoglobin (Hb), a 64 kDa oxygen-transporting protein complex, by high resolution native top-down mass spectrometry using electrospray ionization (ESI) and a 15-Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Native MS preserves the non-covalent interactions between the globin subunits, and electron capture dissociation (ECD) produces fragments directly from the intact Hb complex without dissociating the subunits. Using activated ion ECD, we observe the gradual unfolding process of themore » Hb complex in the gas phase. Without protein ion activation, the native Hb shows very limited ECD fragmentation from the N-termini, suggesting a tightly packed structure of the native complex and therefore low fragmentation efficiency. Precursor ion activation allows steady increase of N-terminal fragment ions, while the C-terminal fragments remain limited (38 c ions and 4 z ions on the α chain; 36 c ions and 2 z ions on the β chain). This ECD fragmentation pattern suggests that upon activation, the Hb complex starts to unfold from the N-termini of both subunits, whereas the C-terminal regions and therefore the potential regions involved in the subunit binding interactions remain intact. ECD-MS of the Hb dimer show similar fragmentation patterns as the Hb tetramer, providing further evidence for the hypothesized unfolding process of the Hb complex in the gas phase. Native top-down ECD-MS allows efficient probing of the Hb complex structure and the subunit binding interactions in the gas phase. Finally, it may provide a fast and effective means to probe the structure of novel protein complexes that are intractable to traditional structural characterization tools.« less

Internal motions of HII regions and giant HII regions

NASA Technical Reports Server (NTRS)

Chu, You-Hua; Kennicutt, Robert C., Jr.

1994-01-01

We report new echelle observations of the kinematics of 30 HII regions in the Large Magellanic Clouds (LMC), including the 30 Doradus giant HII region. All of the HII regions possess supersonic velocity dispersions, which can be attributed to a combination of turbulent motions and discrete velocity splitting produced by stellar winds and/or embedded supernova remnants (SNRs). The core of 30 Dor is unique, with a complex velocity structure that parallels its chaotic optical morphology. We use our calibrated echelle data to measure the physical properties and energetic requirements of these velocity structures. The most spectacular structures in 30 Dor are several fast expanding shells, which appear to be produced at least partially by SNRs.

Conformational divergence in the HA-33/HA-17 trimer of serotype C and D botulinum toxin complex.

PubMed

Sagane, Yoshimasa; Hayashi, Shintaro; Akiyama, Tomonori; Matsumoto, Takashi; Hasegawa, Kimiko; Yamano, Akihito; Suzuki, Tomonori; Niwa, Koichi; Watanabe, Toshihiro; Yajima, Shunsuke

2016-08-05

Clostridium botulinum produces a large toxin complex (L-TC) comprising botulinum neurotoxin associated with auxiliary nontoxic proteins. A complex of 33- and 17-kDa hemagglutinins (an HA-33/HA-17 trimer) enhances L-TC transport across the intestinal epithelial cell layer via binding HA-33 to a sugar on the cell surface. At least two subtypes of serotype C/D HA-33 exhibit differing preferences for the sugars sialic acid and galactose. Here, we compared the three-dimensional structures of the galactose-binding HA-33 and HA-33/HA-17 trimers produced by the C-Yoichi strain. Comparisons of serotype C/D HA-33 sequences reveal a variable region with relatively low sequence similarity across the C. botulinum strains; the variability of this region may influence the manner of sugar-recognition by HA-33. Crystal structures of sialic acid- and galactose-binding HA-33 are broadly similar in appearance. However, small-angle X-ray scattering revealed distinct solution structures for HA-33/HA-17 trimers. A structural change in the C-terminal variable region of HA-33 might cause a dramatic shift in the conformation and sugar-recognition mode of HA-33/HA-17 trimer. Copyright © 2016 Elsevier Inc. All rights reserved.

Crustal structure of the coastal and marine San Francisco Bay region, California

USGS Publications Warehouse

Parsons, Tom

2002-01-01

In summary, these studies were carried out in an environment where background information on faults in the San Francisco Bay region was sought. Much of the structural information presented here comes from experiments of a style unlikely to be conducted by the USGS in the near future. Together, the chapters in this volume provide a structural framework for a major part of a complex strike-slip fault system.

Structural organization of poliovirus RNA replication is mediated by viral proteins of the P2 genomic region

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

Bienz, K.; Egger, D.; Troxler, M.

1990-03-01

Transcriptionally active replication complexes bound to smooth membrane vesicles were isolated from poliovirus-infected cells. In electron microscopic, negatively stained preparations, the replication complex appeared as an irregularly shaped, oblong structure attached to several virus-induced vesicles of a rosettelike arrangement. Electron microscopic immunocytochemistry of such preparations demonstrated that the poliovirus replication complex contains the proteins coded by the P2 genomic region (P2 proteins) in a membrane-associated form. In addition, the P2 proteins are also associated with viral RNA, and they can be cross-linked to viral RNA by UV irradiation. Guanidine hydrochloride prevented the P2 proteins from becoming membrane bound but didmore » not change their association with viral RNA. The findings allow the conclusion that the protein 2C or 2C-containing precursor(s) is responsible for the attachment of the viral RNA to the vesicular membrane and for the spatial organization of the replication complex necessary for its proper functioning in viral transcription. A model for the structure of the viral replication complex and for the function of the 2C-containing P2 protein(s) and the vesicular membranes is proposed.« less

Structural maintenance of chromosome complexes differentially compact mitotic chromosomes according to genomic context

PubMed Central

Schalbetter, S. A.; Goloborodko, A.; Fudenberg, G.; Belton, J.-M.; Miles, C.; Yu, M.; Dekker, J.; Mirny, L.; Baxter, J.

2017-01-01

Structural Maintenance of Chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modeling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids whilst condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes. PMID:28825700

The Stress-Strain State of Recent Structures in the Northeastern Sector of the Russian Arctic Region

NASA Astrophysics Data System (ADS)

Imaeva, L. P.; Imaev, V. S.; Mel'nikova, V. I.

2018-03-01

Complex research to determine the stress-strain state of the Earth's crust and the types of seismotectonic destruction for the northeastern sector of the Russian Arctic was conducted. The principles of regional ranking of neotectonic structures were developed according to the activity of geodynamic processes, and argumentation for their class differentiation is presented. The structural-tectonic position, the parameters of the deep structure, the system of active faults, and the tectonic stress fields, calculated on the basis of both tectonophysical analysis of discontinuous and folded late Cenozoic deformations and seismological data, were analyzed. This complex of investigations made it possible to determine the directions of the main axes of deformations of the stress-strain state of the Earth's crust and to reveal the regularity in the change of tectonic regimes.

3D structure of the influenza virus polymerase complex: Localization of subunit domains

PubMed Central

Area, Estela; Martín-Benito, Jaime; Gastaminza, Pablo; Torreira, Eva; Valpuesta, José M.; Carrascosa, José L.; Ortín, Juan

2004-01-01

The 3D structure of the influenza virus polymerase complex was determined by electron microscopy and image processing of recombinant ribonucleoproteins (RNPs). The RNPs were generated by in vivo amplification using cDNAs of the three polymerase subunits, the nucleoprotein, and a model virus-associated RNA containing 248 nt. The polymerase structure obtained is very compact, with no apparent boundaries among subunits. The position of specific regions of the PB1, PB2, and PA subunits was determined by 3D reconstruction of either RNP–mAb complexes or tagged RNPs. This structural model is available for the polymerase of a negative-stranded RNA virus and provides a general delineation of the complex and its interaction with the template-associated nucleoprotein monomers in the RNP. PMID:14691253

Dynamics of group II chaperonin and prefoldin probed by 13C NMR spectroscopy.

PubMed

Kurimoto, Eiji; Nishi, Yohei; Yamaguchi, Yoshiki; Zako, Tamotsu; Iizuka, Ryo; Ide, Naoki; Yohda, Masafumi; Kato, Koichi

2008-03-01

Group II chaperonin (CPN) cooperates with prefoldin (PFD), which forms a jellyfish-shaped heterohexameric complex with a molecular mass of 87 kDa. PFD captures an unfolded protein with the tentacles and transfers it to the cavity of CPN. Although X-ray crystal structures of CPN and PFD have been reported, no structural information has been so far available for the terminal regions of the PFD tentacles nor for the C-terminal segments of CPNs, which were regarded to be functionally significant in the previous studies. Here we report 13C NMR analyses on archaeal PFD, CPN, and their complex, focusing on those structurally uncharacterized regions. The PFD and CPN complexes selectively labeled with 13C at methionyl carbonyl carbons were separately and jointly subjected to NMR measurements. 13C NMR spectral data demonstrated that the N-terminal segment of the alpha and beta subunits of PFD as well as the C-terminal segments of the CPN hexadecamer retain significant degrees of freedom in internal motion even in the complex with a molecular mass of 1.1 MDa. 2007 Wiley-Liss, Inc.

Structure of a BMI-1-Ring1B Polycomb Group Ubiquitin Ligase Complex

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

Li,Z.; Cao, R.; Wang, M.

2006-01-01

Polycomb group (PcG) proteins Bmi-1 and Ring1B are core subunits of the PRC1 complex which plays important roles in the regulation of Hox gene expression, X-chromosome inactivation, tumorigenesis and stem cell self-renewal. The RING finger protein Ring1B is an E3 ligase that participates in the ubiquitination of lysine 119 of histone H2A, and the binding of Bmi-1 stimulates the E3 ligase activity. We have mapped the regions of Bmi-1 and Ring1B required for efficient ubiquitin transfer and determined a 2.5 Angstroms structure of the Bmi-1-Ring1B core domain complex. The structure reveals that Ring1B 'hugs' Bmi-1 through extensive RING domain contactsmore » and its N-terminal tail wraps around Bmi-1. The two regions of interaction have a synergistic effect on the E3 ligase activity. Our analyses suggest a model where the Bmi-1-Ring1B complex stabilizes the interaction between the E2 enzyme and the nucleosomal substrate to allow efficient ubiquitin transfer.« less

Architecture and nucleic acids recognition mechanism of the THO complex, an mRNP assembly factor

PubMed Central

Peña, Álvaro; Gewartowski, Kamil; Mroczek, Seweryn; Cuéllar, Jorge; Szykowska, Aleksandra; Prokop, Andrzej; Czarnocki-Cieciura, Mariusz; Piwowarski, Jan; Tous, Cristina; Aguilera, Andrés; Carrascosa, José L; Valpuesta, José María; Dziembowski, Andrzej

2012-01-01

The THO complex is a key factor in co-transcriptional formation of export-competent messenger ribonucleoprotein particles, yet its structure and mechanism of chromatin recruitment remain unknown. In yeast, this complex has been described as a heterotetramer (Tho2, Hpr1, Mft1, and Thp2) that interacts with Tex1 and mRNA export factors Sub2 and Yra1 to form the TRanscription EXport (TREX) complex. In this study, we purified yeast THO and found Tex1 to be part of its core. We determined the three-dimensional structures of five-subunit THO complex by electron microscopy and located the positions of Tex1, Hpr1, and Tho2 C-terminus using various labelling techniques. In the case of Tex1, a β-propeller protein, we have generated an atomic model which docks into the corresponding part of the THO complex envelope. Furthermore, we show that THO directly interacts with nucleic acids through the unfolded C-terminal region of Tho2, whose removal reduces THO recruitment to active chromatin leading to mRNA biogenesis defects. In summary, this study describes the THO architecture, the structural basis for its chromatin targeting, and highlights the importance of unfolded regions of eukaryotic proteins. PMID:22314234

Influence of clamping plate permeability and metal screen structures on three-dimensional magnetic field and eddy current loss in end region of a turbo-generator by numerical analysis

NASA Astrophysics Data System (ADS)

Likun, Wang; Weili, Li; Yi, Xue; Chunwei, Guan

2013-11-01

A significant problem of turbogenerators on complex end structures is overheating of local parts caused by end losses in the end region. Therefore, it is important to investigate the 3-D magnetic field and eddy current loss in the end. In end region of operating large turbogenerator at thermal power plants, magnetic leakage field distribution is complex. In this paper, a 3-D mathematical model used for the calculation of the electromagnetic field in the end region of large turbo-generators is given. The influence of spatial locations of end structures, the actual shape and material of end windings, clamping plate, and copper screen are considered. Adopting the time-step finite element (FE) method and taking the nonlinear characteristics of the core into consideration, a 3-D transient magnetic field is calculated. The objective of this paper is to investigate the influence of clamping plate permeability and metal screen structures on 3-D electromagnetic field distribution and eddy current loss in end region of a turbo-generator. To reduce the temperature of copper screen, a hollow metal screen is proposed. The eddy current loss, which is gained from the 3D transient magnetic field, is used as heat source for the thermal field of end region. The calculated temperatures are compared with test data.

Structure of the glucagon receptor in complex with a glucagon analogue.

PubMed

Zhang, Haonan; Qiao, Anna; Yang, Linlin; Van Eps, Ned; Frederiksen, Klaus S; Yang, Dehua; Dai, Antao; Cai, Xiaoqing; Zhang, Hui; Yi, Cuiying; Cao, Can; He, Lingli; Yang, Huaiyu; Lau, Jesper; Ernst, Oliver P; Hanson, Michael A; Stevens, Raymond C; Wang, Ming-Wei; Reedtz-Runge, Steffen; Jiang, Hualiang; Zhao, Qiang; Wu, Beili

2018-01-03

Class B G-protein-coupled receptors (GPCRs), which consist of an extracellular domain (ECD) and a transmembrane domain (TMD), respond to secretin peptides to play a key part in hormonal homeostasis, and are important therapeutic targets for a variety of diseases. Previous work has suggested that peptide ligands bind to class B GPCRs according to a two-domain binding model, in which the C-terminal region of the peptide targets the ECD and the N-terminal region of the peptide binds to the TMD binding pocket. Recently, three structures of class B GPCRs in complex with peptide ligands have been solved. These structures provide essential insights into peptide ligand recognition by class B GPCRs. However, owing to resolution limitations, the specific molecular interactions for peptide binding to class B GPCRs remain ambiguous. Moreover, these previously solved structures have different ECD conformations relative to the TMD, which introduces questions regarding inter-domain conformational flexibility and the changes required for receptor activation. Here we report the 3.0 Å-resolution crystal structure of the full-length human glucagon receptor (GCGR) in complex with a glucagon analogue and partial agonist, NNC1702. This structure provides molecular details of the interactions between GCGR and the peptide ligand. It reveals a marked change in the relative orientation between the ECD and TMD of GCGR compared to the previously solved structure of the inactive GCGR-NNC0640-mAb1 complex. Notably, the stalk region and the first extracellular loop undergo major conformational changes in secondary structure during peptide binding, forming key interactions with the peptide. We further propose a dual-binding-site trigger model for GCGR activation-which requires conformational changes of the stalk, first extracellular loop and TMD-that extends our understanding of the previously established two-domain peptide-binding model of class B GPCRs.

Bonding in Heavier Group 14 Zero-Valent Complexes-A Combined Maximum Probability Domain and Valence Bond Theory Approach.

PubMed

Turek, Jan; Braïda, Benoît; De Proft, Frank

2017-10-17

The bonding in heavier Group 14 zero-valent complexes of a general formula L 2 E (E=Si-Pb; L=phosphine, N-heterocyclic and acyclic carbene, cyclic tetrylene and carbon monoxide) is probed by combining valence bond (VB) theory and maximum probability domain (MPD) approaches. All studied complexes are initially evaluated on the basis of the structural parameters and the shape of frontier orbitals revealing a bent structural motif and the presence of two lone pairs at the central E atom. For the VB calculations three resonance structures are suggested, representing the "ylidone", "ylidene" and "bent allene" structures, respectively. The influence of both ligands and central atoms on the bonding situation is clearly expressed in different weights of the resonance structures for the particular complexes. In general, the bonding in the studied E 0 compounds, the tetrylones, is best described as a resonating combination of "ylidone" and "ylidene" structures with a minor contribution of the "bent allene" structure. Moreover, the VB calculations allow for a straightforward assessment of the π-backbonding (E→L) stabilization energy. The validity of the suggested resonance model is further confirmed by the complementary MPD calculations focusing on the E lone pair region as well as the E-L bonding region. Likewise, the MPD method reveals a strong influence of the σ-donating and π-accepting properties of the ligand. In particular, either one single domain or two symmetrical domains are found in the lone pair region of the central atom, supporting the predominance of either the "ylidene" or "ylidone" structures having one or two lone pairs at the central atom, respectively. Furthermore, the calculated average populations in the lone pair MPDs correlate very well with the natural bond orbital (NBO) populations, and can be related to the average number of electrons that is backdonated to the ligands. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ligand complex structures of l-amino acid oxidase/monooxygenase from Pseudomonas sp. AIU 813 and its conformational change.

PubMed

Im, Dohyun; Matsui, Daisuke; Arakawa, Takatoshi; Isobe, Kimiyasu; Asano, Yasuhisa; Fushinobu, Shinya

2018-03-01

l-Amino acid oxidase/monooxygenase from Pseudomonas sp. AIU 813 (l-AAO/MOG) catalyzes both the oxidative deamination and oxidative decarboxylation of the α-group of l-Lys to produce a keto acid and amide, respectively. l-AAO/MOG exhibits limited specificity for l-amino acid substrates with a basic side chain. We previously determined its ligand-free crystal structure and identified a key residue for maintaining the dual activities. Here, we determined the structures of l-AAO/MOG complexed with l-Lys, l-ornithine, and l-Arg and revealed its substrate recognition. Asp238 is located at the ceiling of a long hydrophobic pocket and forms a strong interaction with the terminal, positively charged group of the substrates. A mutational analysis on the D238A mutant indicated that the interaction is critical for substrate binding but not for catalytic control between the oxidase/monooxygenase activities. The catalytic activities of the D238E mutant unexpectedly increased, while the D238F mutant exhibited altered substrate specificity to long hydrophobic substrates. In the ligand-free structure, there are two channels connecting the active site and solvent, and a short region located at the dimer interface is disordered. In the l-Lys complex structure, a loop region is displaced to plug the channels. Moreover, the disordered region in the ligand-free structure forms a short helix in the substrate complex structures and creates the second binding site for the substrate. It is assumed that the amino acid substrate enters the active site of l-AAO/MOG through this route. The atomic coordinates and structure factors (codes 5YB6, 5YB7, and 5YB8) have been deposited in the Protein Data Bank (http://wwpdb.org/). 1.4.3.2 (l-amino acid oxidase), 1.13.12.2 (lysine 2-monooxygenase).

Aggregation behavior and complex structure between triblock copolymer and anionic surfactants

NASA Astrophysics Data System (ADS)

Li, Yiming; Bao, Mutai; Wang, Zhining; Zhang, Haixia; Xu, Guiying

2011-01-01

The aggregation behavior and complex structure of ABA triblock copolymer EO 76PO 30EO 76 (F68) with sodium dodecyl sulfate (SDS) and sodium bis(2-ethylhexyl)sulfonate (AOT) in aqueous solution were investigated by surface tension, fluorescence techniques and dynamic light-scattering (DLS) measurements. It is revealed that in certain regions of binding, surfactant/F68 complexes are formed. Structural informations and size of complexes are evaluated. When F68 is present in its nonassociated state, F68/micellar SDS complexes are formed at SDS concentrations above its critical aggregation concentration (cac). The cac is well below the critical micellar concentration (cmc) of pure SDS, and a model suggesting how complexes are formed at the cac in the presence of F68 is described. Experimental results show that SDS interacts with F68 mainly through hydrophobic forces, polypropylene oxide (PPO) groups of F68 are solubilized into SDS micellar cores and poly(ethylene oxide) (PEO) groups interact with SDS micelles. This interaction mechanism results in a "pearl-necklace" complex structure. However, a different structure occurs for F68/AOT complex at lower F68 concentrations, as nonassociated F68 interacts with AOT mainly through ion-dipole interactions. Complexes with a "wrapping" structure at lower F68 concentrations are formed.

On the recognition of complex structures: Computer software using artificial intelligence applied to pattern recognition

NASA Technical Reports Server (NTRS)

Yakimovsky, Y.

1974-01-01

An approach to simultaneous interpretation of objects in complex structures so as to maximize a combined utility function is presented. Results of the application of a computer software system to assign meaning to regions in a segmented image based on the principles described in this paper and on a special interactive sequential classification learning system, which is referenced, are demonstrated.

Kinetic analysis of pre-ribosome structure in vivo

PubMed Central

Swiatkowska, Agata; Wlotzka, Wiebke; Tuck, Alex; Barrass, J. David; Beggs, Jean D.; Tollervey, David

2012-01-01

Pre-ribosomal particles undergo numerous structural changes during maturation, but their high complexity and short lifetimes make these changes very difficult to follow in vivo. In consequence, pre-ribosome structure and composition have largely been inferred from purified particles and analyzed in vitro. Here we describe techniques for kinetic analyses of the changes in pre-ribosome structure in living cells of Saccharomyces cerevisiae. To allow this, in vivo structure probing by DMS modification was combined with affinity purification of newly synthesized 20S pre-rRNA over a time course of metabolic labeling with 4-thiouracil. To demonstrate that this approach is generally applicable, we initially analyzed the accessibility of the region surrounding cleavage site D site at the 3′ end of the mature 18S rRNA region of the pre-rRNA. This revealed a remarkably flexible structure throughout 40S subunit biogenesis, with little stable RNA–protein interaction apparent. Analysis of folding in the region of the 18S central pseudoknot was consistent with previous data showing U3 snoRNA–18S rRNA interactions. Dynamic changes in the structure of the hinge between helix 28 (H28) and H44 of pre-18S rRNA were consistent with recently reported interactions with the 3′ guide region of U3 snoRNA. Finally, analysis of the H18 region indicates that the RNA structure matures early, but additional protection appears subsequently, presumably reflecting protein binding. The structural analyses described here were performed on total, affinity-purified, newly synthesized RNA, so many classes of RNA and RNA–protein complex are potentially amenable to this approach. PMID:23093724

Volumetric data analysis using Morse-Smale complexes

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

Natarajan, V; Pascucci, V

2005-10-13

The 3D Morse-Smale complex is a fundamental topological construct that partitions the domain of a real-valued function into regions having uniform gradient flow behavior. In this paper, we consider the construction and selective presentation of cells of the Morse-Smale complex and their use in the analysis and visualization of scientific datasets. We take advantage of the fact that cells of different dimension often characterize different types of features present in the data. For example, critical points pinpoint changes in topology by showing where components of the level sets are created, destroyed or modified in genus. Edges of the Morse-Smale complexmore » extract filament-like features that are not explicitly modeled in the original data. Interactive selection and rendering of portions of the Morse-Smale complex introduces fundamental data management challenges due to the unstructured nature of the complex even for structured inputs. We describe a data structure that stores the Morse-Smale complex and allows efficient selective traversal of regions of interest. Finally, we illustrate the practical use of this approach by applying it to cryo-electron microscopy data of protein molecules.« less

Structural and Functional Analysis of an mRNP Complex That Mediates the High Stability of Human β-Globin mRNA

PubMed Central

Yu, Jia; Russell, J. Eric

2001-01-01

Human globins are encoded by mRNAs exhibiting high stabilities in transcriptionally silenced erythrocyte progenitors. Unlike α-globin mRNA, whose stability is enhanced by assembly of a specific messenger RNP (mRNP) α complex on its 3′ untranslated region (UTR), neither the structure(s) nor the mechanism(s) that effects the high-level stability of human β-globin mRNA has been identified. The present work describes an mRNP complex assembling on the 3′ UTR of the β-globin mRNA that exhibits many of the properties of the stability-enhancing α complex. The β-globin mRNP complex is shown to contain one or more factors homologous to αCP, a 39-kDa RNA-binding protein that is integral to α-complex assembly. Sequence analysis implicates a specific 14-nucleotide pyrimidine-rich track within its 3′ UTR as the site of β-globin mRNP assembly. The importance of this track to mRNA stability is subsequently verified in vivo using mice expressing human β-globin transgenes that contain informative mutations in this region. In combination, the in vitro and in vivo analyses indicate that the high stabilities of the α- and β-globin mRNAs are maintained through related mRNP complexes that may share a common regulatory pathway. PMID:11486027

Factors influencing efficient structure of fuel and energy complex

NASA Astrophysics Data System (ADS)

Sidorova, N. G.; Novikova, S. A.

2017-10-01

The development of the Russian fuel-energy complex is a priority for the national economic policy, and the Far East is a link between Russia and the Asia-Pacific region. Large-scale engineering of numerous resources of the Far East will force industrial development, increase living standard and strengthen Russia’s position in the global energy market. So, revealing the factors which influence rational structure of the fuel-energy complex is very urgent nowadays. With the use of depth analysis of development tendencies of the complex and its problems the authors show ways of its efficiency improvement.

Segmental Duplication, Microinversion, and Gene Loss Associated with a Complex Inversion Breakpoint Region in Drosophila

PubMed Central

Calvete, Oriol; González, Josefa; Betrán, Esther; Ruiz, Alfredo

2012-01-01

Chromosomal inversions are usually portrayed as simple two-breakpoint rearrangements changing gene order but not gene number or structure. However, increasing evidence suggests that inversion breakpoints may often have a complex structure and entail gene duplications with potential functional consequences. Here, we used a combination of different techniques to investigate the breakpoint structure and the functional consequences of a complex rearrangement fixed in Drosophila buzzatii and comprising two tandemly arranged inversions sharing the middle breakpoint: 2m and 2n. By comparing the sequence in the breakpoint regions between D. buzzatii (inverted chromosome) and D. mojavensis (noninverted chromosome), we corroborate the breakpoint reuse at the molecular level and infer that inversion 2m was associated with a duplication of a ∼13 kb segment and likely generated by staggered breaks plus repair by nonhomologous end joining. The duplicated segment contained the gene CG4673, involved in nuclear transport, and its two nested genes CG5071 and CG5079. Interestingly, we found that other than the inversion and the associated duplication, both breakpoints suffered additional rearrangements, that is, the proximal breakpoint experienced a microinversion event associated at both ends with a 121-bp long duplication that contains a promoter. As a consequence of all these different rearrangements, CG5079 has been lost from the genome, CG5071 is now a single copy nonnested gene, and CG4673 has a transcript ∼9 kb shorter and seems to have acquired a more complex gene regulation. Our results illustrate the complex effects of chromosomal rearrangements and highlight the need of complementing genomic approaches with detailed sequence-level and functional analyses of breakpoint regions if we are to fully understand genome structure, function, and evolutionary dynamics. PMID:22328714

Seismotectonic zoning of Azerbaijan territory

NASA Astrophysics Data System (ADS)

Kangarli, Talat; Aliyev, Ali; Aliyev, Fuad; Rahimov, Fuad

2017-04-01

Studying of the space-time correlation and consequences effect between tectonic events and other geological processes that have created modern earth structure still remains as one of the most important problems in geology. This problem is especially important for the East Caucasus-South Caspian geodynamic zone. Being situated at the eastern part of the Caucasian strait, this zone refers to a center of Alpine-Himalayan active folded belt, and is known as a complex tectonic unit with jointing heterogeneous structural-substantial complexes arising from different branches of the belt (Doburja-Caucasus-Kopetdag from the north and Pyrenean-Alborz from the south with Kura and South Caspian zone). According to GPS and precise leveling data, activity of regional geodynamic processes shows intensive horizontal and vertical movements of the Earth's crust as conditioned by collision of the Arabian and Eurasian continental plates continuing since the end of Miocene. So far studies related to the regional of geology-geophysical data, periodically used for the geological and tectonic modeling of the environment mainly based on the fixing ideology. There still remains a number of uncertainties in solution of issues related to regional geology, tectonics and magmatism, structure and interrelation of different structural zones, space-time interrelations between onshore and offshore complexes, etc. At the same time large dataset produced by surface geological surveys, deep geological mapping of on- and offshore areas with the use of seismic and electrical reconnaissance and geophysical field zoning methods, deep well drilling and remote sensing activities. Conducted new studies produced results including differentiation of formerly unknown nappe complexes of the different ages and scales within the structure of mountain-fold zones, identification of new zones containing ophiolites in their section, outlining of currently active faulting areas, geophysical interpretation of the deep structure of Greater and Lesser Caucasus, detailed description of the deep structure of Caspian zone, Kur and Caspian megadepressions, identification of nappe-folded structure of the Absheron Peninsula and the Absheron threshold at the border of Middle and South Caspian, justification of the possible hydrocarbon concentration at the tectonically stratified substantial complexes of mountain and foothill areas, etc. Based on the outcomes of implemented researches, some general conclusions and schemes were drawn for some parts of the project region within the plate tectonics conceptual frameworks, to include the territories of Lesser Caucasus and South Caspian. Analysis and comparison of these data with macroseismic and instrumental data allowed us to conduct seismotectonic studies in a region and develop a new scheme of seismotectonic map with outlined recent and forecasted seismic activity. There also correlated foci zones of earthquakes with subhorizontal and subvertical borders in earth crust, which shows their structure-dynamic relationship. In the one hand, the earthquake foci zones belong to the faults of the basement which extend to sedimentary cover and their intersection knots. On the other hand, there appearing inner-block seismogenic levels, namely, in seismic generation acts all the earth crust: tectonic stress results on movements along fault zones, as well as lateral displacements along non-stable contacts of the structure-substance complexes of different competency.

Cavitation, Flow Structure and Turbulence in the Tip Region of a Rotor Blade

NASA Technical Reports Server (NTRS)

Wu, H.; Miorini, R.; Soranna, F.; Katz, J.; Michael, T.; Jessup, S.

2010-01-01

Objectives: Measure the flow structure and turbulence within a Naval, axial waterjet pump. Create a database for benchmarking and validation of parallel computational efforts. Address flow and turbulence modeling issues that are unique to this complex environment. Measure and model flow phenomena affecting cavitation within the pump and its effect on pump performance. This presentation focuses on cavitation phenomena and associated flow structure in the tip region of a rotor blade.

Strike-Slip Faulting Processes on Ganymede: Global Morphological Mapping and Structural Interpretation of Grooved and Transitional Terrains

NASA Astrophysics Data System (ADS)

Burkhard, L. M.; Cameron, M. E.; Smith-Konter, B. R.; Seifert, F.; Pappalardo, R. T.; Collins, G. C.

2015-12-01

Ganymede's fractured surface reveals many large-scale, morphologically distinct regions of inferred distributed shear and strike-slip faulting that may be important to the structural development of its surface and in the transition from dark to light (grooved) materials. To better understand the role of strike-slip tectonism in shaping Ganymede's complex icy surface, we perform a detailed mapping of key examples of strike-slip morphologies (i.e., en echelon structures, strike-slip duplexes, laterally offset pre-existing features, and possible strained craters) from Galileo and Voyager images. We focus on complex structures associated with grooved terrain (e.g. Nun Sulcus, Dardanus Sulcus, Tiamat Sulcus, and Arbela Sulcus) and terrains transitional from dark to light terrain (e.g. the boundary between Nippur Sulcus and Marius Regio, including Byblus Sulcus and Philus Sulcus). Detailed structural interpretations suggest strong evidence of strike-slip faulting in some regions (i.e., Nun and Dardanus Sulcus); however, further investigation of additional strike-slip structures is required of less convincing regions (i.e., Byblus Sulcus). Where applicable, these results are synthesized into a global database representing an inferred sense of shear for many of Ganymede's fractures. Moreover, when combined with existing observations of extensional features, these results help to narrow down the range of possible principal stress directions that could have acted at the regional or global scale to produce grooved terrain on Ganymede.

Multi-region statistical shape model for cochlear implantation

NASA Astrophysics Data System (ADS)

Romera, Jordi; Kjer, H. Martin; Piella, Gemma; Ceresa, Mario; González Ballester, Miguel A.

2016-03-01

Statistical shape models are commonly used to analyze the variability between similar anatomical structures and their use is established as a tool for analysis and segmentation of medical images. However, using a global model to capture the variability of complex structures is not enough to achieve the best results. The complexity of a proper global model increases even more when the amount of data available is limited to a small number of datasets. Typically, the anatomical variability between structures is associated to the variability of their physiological regions. In this paper, a complete pipeline is proposed for building a multi-region statistical shape model to study the entire variability from locally identified physiological regions of the inner ear. The proposed model, which is based on an extension of the Point Distribution Model (PDM), is built for a training set of 17 high-resolution images (24.5 μm voxels) of the inner ear. The model is evaluated according to its generalization ability and specificity. The results are compared with the ones of a global model built directly using the standard PDM approach. The evaluation results suggest that better accuracy can be achieved using a regional modeling of the inner ear.

X-Ray absorption spectroscopy quantitative analysis of biomimetic copper(II) complexes with tridentate nitrogen ligands mimicking the tris(imidazole) array of protein centres.

PubMed

Borghi, Elena; Casella, Luigi

2010-02-21

In this study copper(ii) complexes with the tridentate nitrogen ligand bis[2-(1-methylbenzimidazol-2-yl)ethyl]amine (2-BB) are considered as model compounds for the Cu-tris(imidazole) array found in several copper proteins. 2-BB chelates copper(ii) forming two six-membered rings and the complexes contain methanol, nitrite, azide and water as ancillary ligands; both the coordination numbers and stereochemistries differ in these complexes. Their key structural features were investigated by using full multiple-scattering theoretical analysis of the copper K-edge X-ray absorption spectrum with the MXAN code. We showed that using cluster sizes large enough to include all atoms of the ligand, the analysis of the XANES region can give both a structural model of the metal centre and map the structure of the 2-BB complexes. Complex [Cu(2-BB)(N(3))](+) provided a critical test through the comparison of the XANES simulation results with crystallographic data, thus permitting the extension of the method to the complex [Cu(2-BB)(H(2)O)(n)](+) (n = 1 or 2), for which crystallographic data are not available but is expected to bear a five-coordinated Cu(3N)(2O) core (n = 2). The structural data of [Cu(2-BB)(MeOH)(ClO(4))](+) and [Cu(2-BB)(NO(2))](+), both with a Cu(3N)(2O) core but with a different stereochemistry, were used as the starting parameters for two independent simulations of the XANES region of the [Cu(2-BB)(H(2)O)(2)](+) cation. The two structural models generated by simulation converge towards a structure for the aqua-cation with a lower coordination number. New calculations, where four-coordinated Cu(3N)(O) cores were considered as the starting structures, validated that the structure of the aqua-complex in the powder state has a copper(ii) centre with a four-coordinated Cu(3N)(O) core and a molecular formula [Cu(2-BB)(H(2)O)](ClO(4)).(H(2)O). A water solvation molecule, presumed to be disordered from the simulations with the two Cu(3N)(2O) cores, is present. The successful treatment of this Cu-2-BB complex system allows the extension of the method to other biomimetic compounds when a structural characterization is lacking.

Structure of the Tropomyosin Overlap Complex from Chicken Smooth Muscle: Insight into the Diversity of N-Terminal Recognition

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

Frye, Jeremiah; Klenchin, Vadim A.; Rayment, Ivan

Tropomyosin is a stereotypical {alpha}-helical coiled coil that polymerizes to form a filamentous macromolecular assembly that lies on the surface of F-actin. The interaction between the C-terminal and N-terminal segments on adjacent molecules is known as the overlap region. We report here two X-ray structures of the chicken smooth muscle tropomyosin overlap complex. A novel approach was used to stabilize the C-terminal and N-terminal fragments. Globular domains from both the human DNA ligase binding protein XRCC4 and bacteriophage {phi}29 scaffolding protein Gp7 were fused to 37 and 28 C-terminal amino acid residues of tropomyosin, respectively, whereas the 29 N-terminal aminomore » acids of tropomyosin were fused to the C-terminal helix bundle of microtubule binding protein EB1. The structures of both the XRCC4 and Gp7 fusion proteins complexed with the N-terminal EB1 fusion contain a very similar helix bundle in the overlap region that encompasses {approx}15 residues. The C-terminal coiled coil opens to allow formation of the helix bundle, which is stabilized by hydrophobic interactions. These structures are similar to that observed in the NMR structure of the rat skeletal overlap complex [Greenfield, N. J., et al. (2006) J. Mol. Biol. 364, 80-96]. The interactions between the N- and C-terminal coiled coils of smooth muscle tropomyosin show significant curvature, which differs somewhat between the two structures and implies flexibility in the overlap complex, at least in solution. This is likely an important attribute that allows tropomyosin to assemble around the actin filaments. These structures provide a molecular explanation for the role of N-acetylation in the assembly of native tropomyosin.« less

Interpretive geologic cross sections for the Death Valley regional flow system and surrounding areas, Nevada and California

USGS Publications Warehouse

Sweetkind, D.S.; Dickerson, R.P.; Blakely, R.J.; Denning, Paul

2001-01-01

This report presents a network of 28 geologic cross sections that portray subsurface geologic relations within the Death Valley regional ground-water system, a ground-water basin that encompasses a 3? x 3? area (approximately 70,000 km2) in southern Nevada and eastern California. The cross sections transect that part of the southern Great Basin that includes Death Valley, the Nevada Test Site, and the potential high-level nuclear waste underground repository at Yucca Mountain. The specific geometric relationships portrayed on the cross sections are discussed in the context of four general sub-regions that have stratigraphic similarities and general consistency of structural style: (1) the Nevada Test Site vicinity; (2) the Spring Mountains, Pahrump Valley and Amargosa Desert region; (3) the Death Valley region; and (4) the area east of the Nevada Test Site. The subsurface geologic interpretations portrayed on the cross sections are based on an integration of existing geologic maps, measured stratigraphic sections, published cross sections, well data, and geophysical data and interpretations. The estimated top of pre-Cenozoic rocks in the cross sections is based on inversion of gravity data, but the deeper parts of the sections are based on geologic conceptual models and are more speculative. The region transected by the cross sections includes part of the southern Basin and Range Province, the northwest-trending Walker Lane belt, the Death Valley region, and the northern Mojave Desert. The region is structurally complex, where a locally thick Tertiary volcanic and sedimentary section unconformably overlies previously deformed Proterozoic through Paleozoic rocks. All of these rocks have been deformed by complex Neogene ex-tensional normal and strike-slip faults. These cross sections form a three-dimensional network that portrays the interpreted stratigraphic and structural relations in the region; the sections form part of the geologic framework that will be incorporated in a complex numerical model of ground-water flow in the Death Valley region.

Dynamic Programming for Structured Continuous Markov Decision Problems

NASA Technical Reports Server (NTRS)

Dearden, Richard; Meuleau, Nicholas; Washington, Richard; Feng, Zhengzhu

2004-01-01

We describe an approach for exploiting structure in Markov Decision Processes with continuous state variables. At each step of the dynamic programming, the state space is dynamically partitioned into regions where the value function is the same throughout the region. We first describe the algorithm for piecewise constant representations. We then extend it to piecewise linear representations, using techniques from POMDPs to represent and reason about linear surfaces efficiently. We show that for complex, structured problems, our approach exploits the natural structure so that optimal solutions can be computed efficiently.

Structural characteristics and tectonics of northeastern Tellus Regio and Meni Tessera

NASA Technical Reports Server (NTRS)

Toermaenen, T.

1992-01-01

The Tellus Regio-Meni Tessera region is an interesting highland area characterized by large areas of complex ridged terrain or tessera terrain. The area was previously studied from the Venera 15/16 data, typical characteristics of complex tessera terrain of Tellus Regio were analyzed, and a formation mechanism was proposed. Apparent depths of compensation of approximately 30-50 km were calculated from Pioneer Venus gravity and topography data. These values indicate predominant Airy compensation for the area. Regional stresses and lithospheric structures were defined from analysis of surface structures, topography, and gravity data. In this work we concentrate on northeastern Tellus Regio and Meni Tessera, which are situated north and west of Tellus Regio. Structural features and relationships are analyzed in order to interpret tectonic history of the area. Study area was divided into three subareas: northeastern Tellus Regio, Meni Tessera, and the deformed plain between them.

An Adaptive Complex Network Model for Brain Functional Networks

PubMed Central

Gomez Portillo, Ignacio J.; Gleiser, Pablo M.

2009-01-01

Brain functional networks are graph representations of activity in the brain, where the vertices represent anatomical regions and the edges their functional connectivity. These networks present a robust small world topological structure, characterized by highly integrated modules connected sparsely by long range links. Recent studies showed that other topological properties such as the degree distribution and the presence (or absence) of a hierarchical structure are not robust, and show different intriguing behaviors. In order to understand the basic ingredients necessary for the emergence of these complex network structures we present an adaptive complex network model for human brain functional networks. The microscopic units of the model are dynamical nodes that represent active regions of the brain, whose interaction gives rise to complex network structures. The links between the nodes are chosen following an adaptive algorithm that establishes connections between dynamical elements with similar internal states. We show that the model is able to describe topological characteristics of human brain networks obtained from functional magnetic resonance imaging studies. In particular, when the dynamical rules of the model allow for integrated processing over the entire network scale-free non-hierarchical networks with well defined communities emerge. On the other hand, when the dynamical rules restrict the information to a local neighborhood, communities cluster together into larger ones, giving rise to a hierarchical structure, with a truncated power law degree distribution. PMID:19738902

Advanced Multivariate Inversion Techniques for High Resolution 3D Geophysical Modeling

DTIC Science & Technology

2010-09-01

crustal structures. But short periods are difficult to measure, especially in tectonically and geologically complex areas. On the other hand, gravity...East Africa Rift System Knowledge of crustal and upper mantle structure is of importance for understanding East Africa’s geodynamic evolution and for...area with less lateral heterogeneity but great tectonic complexity. To increase the effectiveness of the technique in this region, we explore gravity

All-atom molecular dynamics simulation of a photosystem i/detergent complex.

PubMed

Harris, Bradley J; Cheng, Xiaolin; Frymier, Paul

2014-10-09

All-atom molecular dynamics (MD) simulation was used to investigate the solution structure and dynamics of the photosynthetic pigment-protein complex photosystem I (PSI) from Thermosynechococcus elongatus embedded in a toroidal belt of n-dodecyl-β-d-maltoside (DDM) detergent. Evaluation of root-mean-square deviations (RMSDs) relative to the known crystal structure show that the protein complex surrounded by DDM molecules is stable during the 200 ns simulation time, and root-mean-square fluctuation (RMSF) analysis indicates that regions of high local mobility correspond to solvent-exposed regions such as turns in the transmembrane α-helices and flexible loops on the stromal and lumenal faces. Comparing the protein-detergent complex to a pure detergent micelle, the detergent surrounding the PSI trimer is found to be less densely packed but with more ordered detergent tails, contrary to what is seen in most lipid bilayer models. We also investigated any functional implications for the observed conformational dynamics and protein-detergent interactions, discovering interesting structural changes in the psaL subunits associated with maintaining the trimeric structure of the protein. Importantly, we find that the docking of soluble electron mediators such as cytochrome c6 and ferredoxin to PSI is not significantly impacted by the solubilization of PSI in detergent.

Synthesis, crystal structure investigation and magnetism of the complex metal-rich boride series Crx(Rh1-yRuy)7-xB3 (x=0.88-1; y=0-1) with Th7Fe3-type structure

NASA Astrophysics Data System (ADS)

Misse, Patrick R. N.; Mbarki, Mohammed; Fokwa, Boniface P. T.

2012-08-01

Powder samples and single crystals of the new complex boride series Crx(Rh1-yRuy)7-xB3 (x=0.88-1; y=0-1) have been synthesized by arc-melting the elements under purified argon atmosphere on a water-cooled copper crucible. The products, which have metallic luster, were structurally characterized by single-crystal and powder X-ray diffraction as well as EDX measurements. Within the whole solid solution range the hexagonal Th7Fe3 structure type (space group P63mc, no. 186, Z=2) was identified. Single-crystal structure refinement results indicate the presence of chromium at two sites (6c and 2b) of the available three metal Wyckoff sites, with a pronounced preference for the 6c site. An unexpected Rh/Ru site preference was found in the Ru-rich region only, leading to two different magnetic behaviors in the solid solution: The Rh-rich region shows a temperature-independent (Pauli) paramagnetism whereas an additional temperature-dependent paramagnetic component is found in the Ru-rich region.

The Sacred Mountain of Varallo in Italy: seismic risk assessment by acoustic emission and structural numerical models.

PubMed

Carpinteri, Alberto; Lacidogna, Giuseppe; Invernizzi, Stefano; Accornero, Federico

2013-01-01

We examine an application of Acoustic Emission (AE) technique for a probabilistic analysis in time and space of earthquakes, in order to preserve the valuable Italian Renaissance Architectural Complex named "The Sacred Mountain of Varallo." Among the forty-five chapels of the Renaissance Complex, the structure of the Chapel XVII is of particular concern due to its uncertain structural condition and due to the level of stress caused by the regional seismicity. Therefore, lifetime assessment, taking into account the evolution of damage phenomena, is necessary to preserve the reliability and safety of this masterpiece of cultural heritage. A continuous AE monitoring was performed to assess the structural behavior of the Chapel. During the monitoring period, a correlation between peaks of AE activity in the masonry of the "Sacred Mountain of Varallo" and regional seismicity was found. Although the two phenomena take place on very different scales, the AE in materials and the earthquakes in Earth's crust, belong to the same class of invariance. In addition, an accurate finite element model, performed with DIANA finite element code, is presented to describe the dynamic behavior of Chapel XVII structure, confirming visual and instrumental inspections of regional seismic effects.

Interaction with the Src homology (SH3-SH2) region of the Src-family kinase Hck structures the HIV-1 Nef dimer for kinase activation and effector recruitment.

PubMed

Alvarado, John Jeff; Tarafdar, Sreya; Yeh, Joanne I; Smithgall, Thomas E

2014-10-10

HIV-1 Nef supports high titer viral replication in vivo and is essential for AIDS progression. Nef function depends on interactions with multiple host cell effectors, including Hck and other Src-family kinases. Here we describe the x-ray crystal structure of Nef in complex with the Hck SH3-SH2 regulatory region to a resolution of 1.86 Å. The complex crystallized as a dimer of complexes, with the conserved Nef PXXPXR motif engaging the Hck SH3 domain. A new intercomplex contact was found between SH3 Glu-93, and Nef Arg-105. Mutagenesis of Hck SH3 Glu-93 interfered with Nef·Hck complex formation and kinase activation in cells. The Hck SH2 domains impinge on the N-terminal region of Nef to stabilize a dimer conformation that exposes Asp-123, a residue critical for Nef function. Our results suggest that in addition to serving as a kinase effector for Nef, Hck binding may reorganize the Nef dimer for functional interaction with other signaling partners. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Interaction with the Src Homology (SH3-SH2) Region of the Src-family Kinase Hck Structures the HIV-1 Nef Dimer for Kinase Activation and Effector Recruitment*

PubMed Central

Alvarado, John Jeff; Tarafdar, Sreya; Yeh, Joanne I.; Smithgall, Thomas E.

2014-01-01

HIV-1 Nef supports high titer viral replication in vivo and is essential for AIDS progression. Nef function depends on interactions with multiple host cell effectors, including Hck and other Src-family kinases. Here we describe the x-ray crystal structure of Nef in complex with the Hck SH3-SH2 regulatory region to a resolution of 1.86 Å. The complex crystallized as a dimer of complexes, with the conserved Nef PXXPXR motif engaging the Hck SH3 domain. A new intercomplex contact was found between SH3 Glu-93, and Nef Arg-105. Mutagenesis of Hck SH3 Glu-93 interfered with Nef·Hck complex formation and kinase activation in cells. The Hck SH2 domains impinge on the N-terminal region of Nef to stabilize a dimer conformation that exposes Asp-123, a residue critical for Nef function. Our results suggest that in addition to serving as a kinase effector for Nef, Hck binding may reorganize the Nef dimer for functional interaction with other signaling partners. PMID:25122770

Comparative analysis of port tariffs in the ESCAP region

DOT National Transportation Integrated Search

2002-01-01

Ports of the Economic and Social Commission for Asia and the Pacific (ESCAP) region have long-established tariff structures. Some tariffs are extremely complex while others are relatively simple. There is, however, an increasing desire on the part of...

Aromatic Ring Currents Illustrated--NMR Spectra of Tin(IV) Porphyrin Complexes. An Advanced Undergraduate Experiment.

ERIC Educational Resources Information Center

Arnold, Dennis P.

1988-01-01

Attempts to show that in the closed loops of cyclic structures the protons situated in conic regions above and below the ring will be shielded. Uses the diamagnetic and air stable octahedral tin(IV) complexes of porphyrins for study. Notes complexes crystallize easily and offer spectacular purple colors. (MVL)

Heptameric (L12)6/L10 rather than canonical pentameric complexes are found by tandem MS of intact ribosomes from thermophilic bacteria.

PubMed

Ilag, Leopold L; Videler, Hortense; McKay, Adam R; Sobott, Frank; Fucini, Paola; Nierhaus, Knud H; Robinson, Carol V

2005-06-07

Ribosomes are universal translators of the genetic code into protein and represent macromolecular structures that are asymmetric, often heterogeneous, and contain dynamic regions. These properties pose considerable challenges for modern-day structural biology. Despite these obstacles, high-resolution x-ray structures of the 30S and 50S subunits have revealed the RNA architecture and its interactions with proteins for ribosomes from Thermus thermophilus, Deinococcus radiodurans, and Haloarcula marismortui. Some regions, however, remain inaccessible to these high-resolution approaches because of their high conformational dynamics and potential heterogeneity, specifically the so-called L7/L12 stalk complex. This region plays a vital role in protein synthesis by interacting with GTPase factors in translation. Here, we apply tandem MS, an approach widely applied to peptide sequencing for proteomic applications but not previously applied to MDa complexes. Isolation and activation of ions assigned to intact 30S and 50S subunits releases proteins S6 and L12, respectively. Importantly, this process reveals, exclusively while attached to ribosomes, a phosphorylation of L12, the protein located in multiple copies at the tip of the stalk complex. Moreover, through tandem MS we discovered a stoichiometry for the stalk protuberance on Thermus thermophilus and other thermophiles and contrast this assembly with the analogous one on ribosomes from mesophiles. Together with evidence for a potential interaction with the degradosome, these results show that important findings on ribosome structure, interactions, and modifications can be discovered by tandem MS, even on well studied ribosomes from Thermus thermophilus.

Heptameric (L12)6/L10 rather than canonical pentameric complexes are found by tandem MS of intact ribosomes from thermophilic bacteria

PubMed Central

Ilag, Leopold L.; Videler, Hortense; McKay, Adam R.; Sobott, Frank; Fucini, Paola; Nierhaus, Knud H.; Robinson, Carol V.

2005-01-01

Ribosomes are universal translators of the genetic code into protein and represent macromolecular structures that are asymmetric, often heterogeneous, and contain dynamic regions. These properties pose considerable challenges for modern-day structural biology. Despite these obstacles, high-resolution x-ray structures of the 30S and 50S subunits have revealed the RNA architecture and its interactions with proteins for ribosomes from Thermus thermophilus, Deinococcus radiodurans, and Haloarcula marismortui. Some regions, however, remain inaccessible to these high-resolution approaches because of their high conformational dynamics and potential heterogeneity, specifically the so-called L7/L12 stalk complex. This region plays a vital role in protein synthesis by interacting with GTPase factors in translation. Here, we apply tandem MS, an approach widely applied to peptide sequencing for proteomic applications but not previously applied to MDa complexes. Isolation and activation of ions assigned to intact 30S and 50S subunits releases proteins S6 and L12, respectively. Importantly, this process reveals, exclusively while attached to ribosomes, a phosphorylation of L12, the protein located in multiple copies at the tip of the stalk complex. Moreover, through tandem MS we discovered a stoichiometry for the stalk protuberance on Thermus thermophilus and other thermophiles and contrast this assembly with the analogous one on ribosomes from mesophiles. Together with evidence for a potential interaction with the degradosome, these results show that important findings on ribosome structure, interactions, and modifications can be discovered by tandem MS, even on well studied ribosomes from Thermus thermophilus. PMID:15923259

Crystal Structure of a Complex of the Intracellular Domain of Interferon λ Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.

PubMed

Zhang, Di; Wlodawer, Alexander; Lubkowski, Jacek

2016-11-20

The crystal structure of a construct consisting of the FERM and SH2-like domains of the human Janus kinase 1 (JAK1) bound to a fragment of the intracellular domain of the interferon-λ receptor 1 (IFNLR1) has been determined at the nominal resolution of 2.1Å. In this structure, the receptor peptide forms an 85-Å-long extended chain, in which both the previously identified box1 and box2 regions bind simultaneously to the FERM and SH2-like domains of JAK1. Both domains of JAK1 are generally well ordered, with regions not seen in the crystal structure limited to loops located away from the receptor-binding regions. The structure provides a much more complete and accurate picture of the interactions between JAK1 and IFNLR1 than those given in earlier reports, illuminating the molecular basis of the JAK-cytokine receptor association. A glutamate residue adjacent to the box2 region in IFNLR1 mimics the mode of binding of a phosphotyrosine in classical SH2 domains. It was shown here that a deletion of residues within the box1 region of the receptor abolishes stable interactions with JAK1, although it was previously shown that box2 alone is sufficient to stabilize a similar complex of the interferon-α receptor and TYK2. Published by Elsevier Ltd.

Crystal Structure of Arginase from Plasmodium falciparum and Implications for l-Arginine Depletion in Malarial Infection

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

Dowling, Daniel P.; Ilies, Monica; Olszewski, Kellen L.

The 2.15 {angstrom} resolution crystal structure of arginase from Plasmodium falciparum, the parasite that causes cerebral malaria, is reported in complex with the boronic acid inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) (K{sub d} = 11 {micro}M). This is the first crystal structure of a parasitic arginase. Various protein constructs were explored to identify an optimally active enzyme form for inhibition and structural studies and to probe the structure and function of two polypeptide insertions unique to malarial arginase: a 74-residue low-complexity region contained in loop L2 and an 11-residue segment contained in loop L8. Structural studies indicate that the low-complexity region ismore » largely disordered and is oriented away from the trimer interface; its deletion does not significantly compromise enzyme activity. The loop L8 insertion is located at the trimer interface and makes several intra- and intermolecular interactions important for enzyme function. In addition, we also demonstrate that arg- Plasmodium berghei sporozoites show significantly decreased liver infectivity in vivo. Therefore, inhibition of malarial arginase may serve as a possible candidate for antimalarial therapy against liver-stage infection, and ABH may serve as a lead for the development of inhibitors.« less

Redox chemistry of nickel(II) complexes supported by a series of noninnocent β-diketiminate ligands.

PubMed

Takaichi, June; Morimoto, Yuma; Ohkubo, Kei; Shimokawa, Chizu; Hojo, Takayuki; Mori, Seiji; Asahara, Haruyasu; Sugimoto, Hideki; Fujieda, Nobutaka; Nishiwaki, Nagatoshi; Fukuzumi, Shunichi; Itoh, Shinobu

2014-06-16

Nickel complexes of a series of β-diketiminate ligands ((R)L(-), deprotonated form of 2-substituted N-[3-(phenylamino)allylidene]aniline derivatives (R)LH, R = Me, H, Br, CN, and NO2) have been synthesized and structurally characterized. One-electron oxidation of the neutral complexes [Ni(II)((R)L(-))2] by AgSbF6 or [Ru(III)(bpy)3](PF6)3 (bpy = 2,2'-bipyridine) gave the corresponding metastable cationic complexes, which exhibit an EPR spectrum due to a doublet species (S = 1/2) and a characteristic absorption band in near IR region ascribable to a ligand-to-ligand intervalence charge-transfer (LLIVCT) transition. DFT calculations have indicated that the divalent oxidation state of nickel ion (Ni(II)) is retained, whereas one of the β-diketiminate ligands is oxidized to give formally a mixed-valence complex, [Ni(II)((R)L(-))((R)L(•))](+). Thus, the doublet spin state of the oxidized cationic complex can be explained by taking account of the antiferromagnetic interaction between the high-spin nickel(II) ion (S = 1) and the organic radical (S = 1/2) of supporting ligand. A single-crystal structure of one of the cationic complexes (R = H) has been successfully determined to show that both ligands in the cationic complex are structurally equivalent. On the basis of theoretical analysis of the LLIVCT band and DFT calculations as well as the crystal structure, the mixed-valence complexes have been assigned to Robin-Day class III species, where the radical spin is equally delocalized between the two ligands to give the cationic complex, which is best described as [Ni(II)((R)L(0.5•-))2](+). One-electron reduction of the neutral complexes with decamethylcobaltocene gave the anionic complexes when the ligand has the electron-withdrawing substituent (R = CN, NO2, Br). The generated anionic complexes exhibited EPR spectra due to a doublet species (S = 1/2) but showed no LLIVCT band in the near-IR region. Thus, the reduced complexes are best described as the d(9) nickel(I) complexes supported by two anionic β-diketiminate ligands, [Ni(I)((R)L(-))2](-). This conclusion was also supported by DFT calculations. Substituent effects on the electronic structures of the three oxidation states (neutral, cationic, and anionic) of the complexes are systematically evaluated on the basis of DFT calculations.

Structure of the EndoMS-DNA Complex as Mismatch Restriction Endonuclease.

PubMed

Nakae, Setsu; Hijikata, Atsushi; Tsuji, Toshiyuki; Yonezawa, Kouki; Kouyama, Ken-Ichi; Mayanagi, Kouta; Ishino, Sonoko; Ishino, Yoshizumi; Shirai, Tsuyoshi

2016-11-01

Archaeal NucS nuclease was thought to degrade the single-stranded region of branched DNA, which contains flapped and splayed DNA. However, recent findings indicated that EndoMS, the orthologous enzyme of NucS, specifically cleaves double-stranded DNA (dsDNA) containing mismatched bases. In this study, we determined the structure of the EndoMS-DNA complex. The complex structure of the EndoMS dimer with dsDNA unexpectedly revealed that the mismatched bases were flipped out into binding sites, and the overall architecture most resembled that of restriction enzymes. The structure of the apo form was similar to the reported structure of Pyrococcus abyssi NucS, indicating that movement of the C-terminal domain from the resting state was required for activity. In addition, a model of the EndoMS-PCNA-DNA complex was preliminarily verified with electron microscopy. The structures strongly support the idea that EndoMS acts in a mismatch repair pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

How the brain attunes to sentence processing: Relating behavior, structure, and function

PubMed Central

Fengler, Anja; Meyer, Lars; Friederici, Angela D.

2016-01-01

Unlike other aspects of language comprehension, the ability to process complex sentences develops rather late in life. Brain maturation as well as verbal working memory (vWM) expansion have been discussed as possible reasons. To determine the factors contributing to this functional development, we assessed three aspects in different age-groups (5–6 years, 7–8 years, and adults): first, functional brain activity during the processing of increasingly complex sentences; second, brain structure in language-related ROIs; and third, the behavioral comprehension performance on complex sentences and the performance on an independent vWM test. At the whole-brain level, brain functional data revealed a qualitatively similar neural network in children and adults including the left pars opercularis (PO), the left inferior parietal lobe together with the posterior superior temporal gyrus (IPL/pSTG), the supplementary motor area, and the cerebellum. While functional activation of the language-related ROIs PO and IPL/pSTG predicted sentence comprehension performance for all age-groups, only adults showed a functional selectivity in these brain regions with increased activation for more complex sentences. The attunement of both the PO and IPL/pSTG toward a functional selectivity for complex sentences is predicted by region-specific gray matter reduction while that of the IPL/pSTG is additionally predicted by vWM span. Thus, both structural brain maturation and vWM expansion provide the basis for the emergence of functional selectivity in language-related brain regions leading to more efficient sentence processing during development. PMID:26777477

Improved Phase Characterization of Far-Regional Body Wave Arrivals in Central Asia

DTIC Science & Technology

2008-09-30

developing array -based methods that can more accurately characterize far-regional (14*-29*) seismic wavefield structure. Far- regional (14*-29*) seismograms...arrivals with the primary arrivals. These complexities can be region and earthquake specific. The regional seismic arrays that have been built in the last...fifteen years should be a rich data source for the study of far-regional phase behavior. The arrays are composed of high-quality borehole seismometers

Assembly and analysis of eukaryotic Argonaute–RNA complexes in microRNA-target recognition

PubMed Central

Gan, Hin Hark; Gunsalus, Kristin C.

2015-01-01

Experimental studies have uncovered a variety of microRNA (miRNA)–target duplex structures that include perfect, imperfect and seedless duplexes. However, non-canonical binding modes from imperfect/seedless duplexes are not well predicted by computational approaches, which rely primarily on sequence and secondary structural features, nor have their tertiary structures been characterized because solved structures to date are limited to near perfect, straight duplexes in Argonautes (Agos). Here, we use structural modeling to examine the role of Ago dynamics in assembling viable eukaryotic miRNA-induced silencing complexes (miRISCs). We show that combinations of low-frequency, global modes of motion of Ago domains are required to accommodate RNA duplexes in model human and C. elegans Ago structures. Models of viable miRISCs imply that Ago adopts variable conformations at distinct target sites that generate distorted, imperfect miRNA-target duplexes. Ago's ability to accommodate a duplex is dependent on the region where structural distortions occur: distortions in solvent-exposed seed and 3′-end regions are less likely to produce steric clashes than those in the central duplex region. Energetic analyses of assembled miRISCs indicate that target recognition is also driven by favorable Ago-duplex interactions. Such structural insights into Ago loading and target recognition mechanisms may provide a more accurate assessment of miRNA function. PMID:26432829

Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca[superscript 2+]·calmodulins

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

Fallon, Jennifer L.; Baker, Mariah R.; Xiong, Liangwen

2009-11-10

Voltage-dependent calcium channels (Ca(V)) open in response to changes in membrane potential, but their activity is modulated by Ca(2+) binding to calmodulin (CaM). Structural studies of this family of channels have focused on CaM bound to the IQ motif; however, the minimal differences between structures cannot adequately describe CaM's role in the regulation of these channels. We report a unique crystal structure of a 77-residue fragment of the Ca(V)1.2 alpha(1) subunit carboxyl terminus, which includes a tandem of the pre-IQ and IQ domains, in complex with Ca(2+).CaM in 2 distinct binding modes. The structure of the Ca(V)1.2 fragment is anmore » unusual dimer of 2 coiled-coiled pre-IQ regions bridged by 2 Ca(2+).CaMs interacting with the pre-IQ regions and a canonical Ca(V)1-IQ-Ca(2+).CaM complex. Native Ca(V)1.2 channels are shown to be a mixture of monomers/dimers and a point mutation in the pre-IQ region predicted to abolish the coiled-coil structure significantly reduces Ca(2+)-dependent inactivation of heterologously expressed Ca(V)1.2 channels.« less

Regional Population Dynamics

Treesearch

Andrew Birt

2011-01-01

The population dynamics of the southern pine beetle (SPB) exhibit characteristic fluctuations between relatively long endemic and shorter outbreak periods. Populations exhibit complex and hierarchical spatial structure with beetles and larvae aggregating within individual trees, infestations with multiple infested trees, and regional outbreaks that comprise a large...

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

Crustal structure in the Elko-Carlin Region, Nevada, during Eocene gold mineralization: Ruby-East Humboldt metamorphic core complex as a guide to the deep crust

USGS Publications Warehouse

Howard, K.A.

2003-01-01

The deep crustal rocks exposed in the Ruby-East Humboldt metamorphic core complex, northeastern Nevada, provide a guide for reconstructing Eocene crustal structure ~50 km to the west near the Carlin trend of gold deposits. The deep crustal rocks, in the footwall of a west-dipping normal-sense shear system, may have underlain the Pinon and Adobe Ranges about 50 km to the west before Tertiary extension, close to or under part of the Carlin trend. Eocene lakes formed on the hanging wall of the fault system during an early phase of extension and may have been linked to a fluid reservoir for hydrothermal circulation. The magnitude and timing of Paleogene extension remain indistinct, but dikes and tilt axes in the upper crust indicate that spreading was east-west to northwest-southeast, perpendicular to a Paleozoic and Mesozoic orogen that the spreading overprinted. High geothermal gradients associated with Eocene or older crustal thinning may have contributed to hydrothermal circulation in the upper crust. Late Eocene eruptions, upper crustal dike intrusion, and gold mineralization approximately coincided temporally with deep intrusion of Eocene sills of granite and quartz diorite and shallower intrusion of the Harrison Pass pluton into the core-complex rocks. Stacked Mesozoic nappes of metamorphosed Paleozoic and Precambrian rocks in the core complex lay at least 13 to 20 km deep in Eocene time, on the basis of geobarometry studies. In the northern part of the complex, the presently exposed rocks had been even deeper in the late Mesozoic, to >30 km depths, before losing part of their cover by Eocene time. Nappes in the core plunge northward beneath the originally thicker Mesozoic tectonic cover in the north part of the core complex. Mesozoic nappes and tectonic wedging likely occupied the thickened midlevel crustal section between the deep crustal core-complex intrusions and nappes and the overlying upper crust. These structures, as well as the subsequent large-displacement Cenozoic extensional faulting and flow in the deep crust, would be expected to blur the expression of any regional structural roots that could correlate with mineral belts. Structural mismatch of the mineralized upper crust and the tectonically complex middle crust suggests that the Carlin trend relates not to subjacent deeply penetrating rooted structures but to favorable upper crustal host rocks aligned within a relatively coherent regional block of upper crust.

Mononuclear nickel (II) and copper (II) coordination complexes supported by bispicen ligand derivatives: Experimental and computational studies

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

Singh, Nirupama; Niklas, Jens; Poluektov, Oleg

2017-01-01

The synthesis, characterization and density functional theory calculations of mononuclear Ni and Cu complexes supported by the N,N’-Dimethyl-N,N’-bis-(pyridine-2-ylmethyl)-1,2-diaminoethane ligand and its derivatives are reported. The complexes were characterized by X-ray crystallography as well as by UV-visible absorption spectroscopy and EPR spectroscopy. The solid state structure of these coordination complexes revealed that the geometry of the complex depended on the identity of the metal center. Solution phase characterization data are in accord with the solid phase structure, indicating minimal structural changes in solution. Optical spectroscopy revealed that all of the complexes exhibit color owing to d-d transition bands in the visiblemore » region. Magnetic parameters obtained from EPR spectroscopy with other structural data suggest that the Ni(II) complexes are in pseudo-octahedral geometry and Cu(II) complexes are in a distorted square pyramidal geometry. In order to understand in detail how ligand sterics and electronics affect complex topology detailed computational studies were performed. The series of complexes reported in this article will add significant value in the field of coordination chemistry as Ni(II) and Cu(II) complexes supported by tetradentate pyridyl based ligands are rather scarce.« less

Molecular architecture and function of the SEA complex, a modulator of the TORC1 pathway.

PubMed

Algret, Romain; Fernandez-Martinez, Javier; Shi, Yi; Kim, Seung Joong; Pellarin, Riccardo; Cimermancic, Peter; Cochet, Emilie; Sali, Andrej; Chait, Brian T; Rout, Michael P; Dokudovskaya, Svetlana

2014-11-01

The TORC1 signaling pathway plays a major role in the control of cell growth and response to stress. Here we demonstrate that the SEA complex physically interacts with TORC1 and is an important regulator of its activity. During nitrogen starvation, deletions of SEA complex components lead to Tor1 kinase delocalization, defects in autophagy, and vacuolar fragmentation. TORC1 inactivation, via nitrogen deprivation or rapamycin treatment, changes cellular levels of SEA complex members. We used affinity purification and chemical cross-linking to generate the data for an integrative structure modeling approach, which produced a well-defined molecular architecture of the SEA complex and showed that the SEA complex comprises two regions that are structurally and functionally distinct. The SEA complex emerges as a platform that can coordinate both structural and enzymatic activities necessary for the effective functioning of the TORC1 pathway. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Coral reef structural complexity provides important coastal protection from waves under rising sea levels.

PubMed

Harris, Daniel L; Rovere, Alessio; Casella, Elisa; Power, Hannah; Canavesio, Remy; Collin, Antoine; Pomeroy, Andrew; Webster, Jody M; Parravicini, Valeriano

2018-02-01

Coral reefs are diverse ecosystems that support millions of people worldwide by providing coastal protection from waves. Climate change and human impacts are leading to degraded coral reefs and to rising sea levels, posing concerns for the protection of tropical coastal regions in the near future. We use a wave dissipation model calibrated with empirical wave data to calculate the future increase of back-reef wave height. We show that, in the near future, the structural complexity of coral reefs is more important than sea-level rise in determining the coastal protection provided by coral reefs from average waves. We also show that a significant increase in average wave heights could occur at present sea level if there is sustained degradation of benthic structural complexity. Our results highlight that maintaining the structural complexity of coral reefs is key to ensure coastal protection on tropical coastlines in the future.

Coral reef structural complexity provides important coastal protection from waves under rising sea levels

PubMed Central

Harris, Daniel L.; Rovere, Alessio; Casella, Elisa; Power, Hannah; Canavesio, Remy; Collin, Antoine; Pomeroy, Andrew; Webster, Jody M.; Parravicini, Valeriano

2018-01-01

Coral reefs are diverse ecosystems that support millions of people worldwide by providing coastal protection from waves. Climate change and human impacts are leading to degraded coral reefs and to rising sea levels, posing concerns for the protection of tropical coastal regions in the near future. We use a wave dissipation model calibrated with empirical wave data to calculate the future increase of back-reef wave height. We show that, in the near future, the structural complexity of coral reefs is more important than sea-level rise in determining the coastal protection provided by coral reefs from average waves. We also show that a significant increase in average wave heights could occur at present sea level if there is sustained degradation of benthic structural complexity. Our results highlight that maintaining the structural complexity of coral reefs is key to ensure coastal protection on tropical coastlines in the future. PMID:29503866

Multiscale Dynamics of Solar Magnetic Structures

NASA Technical Reports Server (NTRS)

Uritsky, Vadim M.; Davila, Joseph M.

2012-01-01

Multiscale topological complexity of the solar magnetic field is among the primary factors controlling energy release in the corona, including associated processes in the photospheric and chromospheric boundaries.We present a new approach for analyzing multiscale behavior of the photospheric magnetic flux underlying these dynamics as depicted by a sequence of high-resolution solar magnetograms. The approach involves two basic processing steps: (1) identification of timing and location of magnetic flux origin and demise events (as defined by DeForest et al.) by tracking spatiotemporal evolution of unipolar and bipolar photospheric regions, and (2) analysis of collective behavior of the detected magnetic events using a generalized version of the Grassberger-Procaccia correlation integral algorithm. The scale-free nature of the developed algorithms makes it possible to characterize the dynamics of the photospheric network across a wide range of distances and relaxation times. Three types of photospheric conditions are considered to test the method: a quiet photosphere, a solar active region (NOAA 10365) in a quiescent non-flaring state, and the same active region during a period of M-class flares. The results obtained show (1) the presence of a topologically complex asymmetrically fragmented magnetic network in the quiet photosphere driven by meso- and supergranulation, (2) the formation of non-potential magnetic structures with complex polarity separation lines inside the active region, and (3) statistical signatures of canceling bipolar magnetic structures coinciding with flaring activity in the active region. Each of these effects can represent an unstable magnetic configuration acting as an energy source for coronal dissipation and heating.

Structural elements and organization of the ancestral translational machinery

NASA Technical Reports Server (NTRS)

Rein, R.; Srinivasan, S.; Mcdonald, J.; Raghunathan, G.; Shibata, M.

1987-01-01

The molecular mechanisms of the primitive translational apparatus are discussed in the framework of present-day protein biosynthesis. The structural necessities of an early adaptor and the multipoint recognition properties of such an adaptor are investigated on the basis of structure/function relationships found in a contemporary system and a molecular model of the contemporary transpeptidation complex. A model of the tRNA(Tyr)-tyrosyl tRNA synthetase complex including the positioning of the disordered region is proposed; the model is used to illustrate the required recognition properties of the ancestor aminoacyl synthetase.

Solvation-induced σ-complex structure formation in the gas phase: a revisit to the infrared spectroscopy of [C6H6-(CH3OH)2]+.

PubMed

Mizuse, Kenta; Suzuki, Yuta; Mikami, Naohiko; Fujii, Asuka

2011-10-20

Structures of the [C(6)H(6)-(CH(3)OH)(2)](+) cluster cation are investigated with infrared (IR) spectroscopy. While the noncovalent type structure has been confirmed for the n = 1 cluster of [C(6)H(6)-(CH(3)OH)(n)](+), only contradictory interpretations have been given for the spectra of n = 2, in which significant changes have been observed with the Ar tagging. In the present study, we revisit IR spectroscopy of the n = 2 cluster from the viewpoint of the σ-complex structure, which includes a covalent bond formation between the benzene and methanol moieties. The observed spectral range is extended to the lower-frequency region, and the spectrum is measured with and without Ar and N(2) tagging. A strongly hydrogen-bonded OH stretch band, which is characteristic to the σ-complex structure, is newly found with the tagging. The remarkable spectral changes with the tagging are interpreted by the competition between the σ-complex and noncovalent complex structures in the [C(6)H(6)-(CH(3)OH)(2)](+) system. This result shows that the microsolvation only with one methanol molecule can induce the σ-complex structure formation.

Unravelling the shape and structural assembly of the photosynthetic GAPDH-CP12-PRK complex from Arabidopsis thaliana by small-angle X-ray scattering analysis.

PubMed

Del Giudice, Alessandra; Pavel, Nicolae Viorel; Galantini, Luciano; Falini, Giuseppe; Trost, Paolo; Fermani, Simona; Sparla, Francesca

2015-12-01

Oxygenic photosynthetic organisms produce sugars through the Calvin-Benson cycle, a metabolism that is tightly linked to the light reactions of photosynthesis and is regulated by different mechanisms, including the formation of protein complexes. Two enzymes of the cycle, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK), form a supramolecular complex with the regulatory protein CP12 with the formula (GAPDH-CP122-PRK)2, in which both enzyme activities are transiently inhibited during the night. Small-angle X-ray scattering analysis performed on both the GAPDH-CP12-PRK complex and its components, GAPDH-CP12 and PRK, from Arabidopsis thaliana showed that (i) PRK has an elongated, bent and screwed shape, (ii) the oxidized N-terminal region of CP12 that is not embedded in the GAPDH-CP12 complex prefers a compact conformation and (iii) the interaction of PRK with the N-terminal region of CP12 favours the approach of two GAPDH tetramers. The interaction between the GAPDH tetramers may contribute to the overall stabilization of the GAPDH-CP12-PRK complex, the structure of which is presented here for the first time.

SCOWLP classification: Structural comparison and analysis of protein binding regions

PubMed Central

Teyra, Joan; Paszkowski-Rogacz, Maciej; Anders, Gerd; Pisabarro, M Teresa

2008-01-01

Background Detailed information about protein interactions is critical for our understanding of the principles governing protein recognition mechanisms. The structures of many proteins have been experimentally determined in complex with different ligands bound either in the same or different binding regions. Thus, the structural interactome requires the development of tools to classify protein binding regions. A proper classification may provide a general view of the regions that a protein uses to bind others and also facilitate a detailed comparative analysis of the interacting information for specific protein binding regions at atomic level. Such classification might be of potential use for deciphering protein interaction networks, understanding protein function, rational engineering and design. Description Protein binding regions (PBRs) might be ideally described as well-defined separated regions that share no interacting residues one another. However, PBRs are often irregular, discontinuous and can share a wide range of interacting residues among them. The criteria to define an individual binding region can be often arbitrary and may differ from other binding regions within a protein family. Therefore, the rational behind protein interface classification should aim to fulfil the requirements of the analysis to be performed. We extract detailed interaction information of protein domains, peptides and interfacial solvent from the SCOWLP database and we classify the PBRs of each domain family. For this purpose, we define a similarity index based on the overlapping of interacting residues mapped in pair-wise structural alignments. We perform our classification with agglomerative hierarchical clustering using the complete-linkage method. Our classification is calculated at different similarity cut-offs to allow flexibility in the analysis of PBRs, feature especially interesting for those protein families with conflictive binding regions. The hierarchical classification of PBRs is implemented into the SCOWLP database and extends the SCOP classification with three additional family sub-levels: Binding Region, Interface and Contacting Domains. SCOWLP contains 9,334 binding regions distributed within 2,561 families. In 65% of the cases we observe families containing more than one binding region. Besides, 22% of the regions are forming complex with more than one different protein family. Conclusion The current SCOWLP classification and its web application represent a framework for the study of protein interfaces and comparative analysis of protein family binding regions. This comparison can be performed at atomic level and allows the user to study interactome conservation and variability. The new SCOWLP classification may be of great utility for reconstruction of protein complexes, understanding protein networks and ligand design. SCOWLP will be updated with every SCOP release. The web application is available at . PMID:18182098

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.

HotRegion: a database of predicted hot spot clusters.

PubMed

Cukuroglu, Engin; Gursoy, Attila; Keskin, Ozlem

2012-01-01

Hot spots are energetically important residues at protein interfaces and they are not randomly distributed across the interface but rather clustered. These clustered hot spots form hot regions. Hot regions are important for the stability of protein complexes, as well as providing specificity to binding sites. We propose a database called HotRegion, which provides the hot region information of the interfaces by using predicted hot spot residues, and structural properties of these interface residues such as pair potentials of interface residues, accessible surface area (ASA) and relative ASA values of interface residues of both monomer and complex forms of proteins. Also, the 3D visualization of the interface and interactions among hot spot residues are provided. HotRegion is accessible at http://prism.ccbb.ku.edu.tr/hotregion.

Method for the thermal characterization, visualization, and integrity evaluation of conducting material samples or complex structures

DOEpatents

Ortiz, Marcos G.

1992-01-01

A method for modeling a conducting material sample or structure (herein called a system) as at least two regions which comprise an electrical network of resistances, for measuring electric resistance between at least two selected pairs of external leads attached to the surface of the system, wherein at least one external lead is attached to the surface of each of the regions, and, using basic circuit theory, for translating measured resistances into temperatures or thermophysical properties in corresponding regions of the system.

Method for the thermal characterization, visualization, and integrity evaluation of conducting material samples or complex structures

DOEpatents

Ortiz, M.G.

1992-11-24

Disclosed is a method for modeling a conducting material sample or structure (herein called a system) as at least two regions which comprise an electrical network of resistances, for measuring electric resistance between at least two selected pairs of external leads attached to the surface of the system, wherein at least one external lead is attached to the surface of each of the regions, and, using basic circuit theory, for translating measured resistances into temperatures or thermophysical properties in corresponding regions of the system. 16 figs.

CryoEM and image sorting for flexible protein/DNA complexes.

PubMed

Villarreal, Seth A; Stewart, Phoebe L

2014-07-01

Intrinsically disordered regions of proteins and conformational flexibility within complexes can be critical for biological function. However, disorder, flexibility, and heterogeneity often hinder structural analyses. CryoEM and single particle image processing techniques offer the possibility of imaging samples with significant flexibility. Division of particle images into more homogenous subsets after data acquisition can help compensate for heterogeneity within the sample. We present the utility of an eigenimage sorting analysis for examining two protein/DNA complexes with significant conformational flexibility and heterogeneity. These complexes are integral to the non-homologous end joining pathway, and are involved in the repair of double strand breaks of DNA. Both complexes include the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and biotinylated DNA with bound streptavidin, with one complex containing the Ku heterodimer. Initial 3D reconstructions of the two DNA-PKcs complexes resembled a cryoEM structure of uncomplexed DNA-PKcs without additional density clearly attributable to the remaining components. Application of eigenimage sorting allowed division of the DNA-PKcs complex datasets into more homogeneous subsets. This led to visualization of density near the base of the DNA-PKcs that can be attributed to DNA, streptavidin, and Ku. However, comparison of projections of the subset structures with 2D class averages indicated that a significant level of heterogeneity remained within each subset. In summary, image sorting methods allowed visualization of extra density near the base of DNA-PKcs, suggesting that DNA binds in the vicinity of the base of the molecule and potentially to a flexible region of DNA-PKcs. Copyright © 2013 Elsevier Inc. All rights reserved.

Optimal sensor placement for active guided wave interrogation of complex metallic components

NASA Astrophysics Data System (ADS)

Coelho, Clyde K.; Kim, Seung Bum; Chattopadhyay, Aditi

2011-04-01

With research in structural health monitoring (SHM) moving towards increasingly complex structures for damage interrogation, the placement of sensors is becoming a key issue in the performance of the damage detection methodologies. For ultrasonic wave based approaches, this is especially important because of the sensitivity of the travelling Lamb waves to material properties, geometry and boundary conditions that may obscure the presence of damage if they are not taken into account during sensor placement. The framework proposed in this paper defines a sensing region for a pair of piezoelectric transducers in a pitch-catch damage detection approach by taking into account the material attenuation and probability of false alarm. Using information about the region interrogated by a sensoractuator pair, a simulated annealing optimization framework was implemented in order to place sensors on complex metallic geometries such that a selected minimum damage type and size could be detected with an acceptable probability of false alarm anywhere on the structure. This approach was demonstrated on a lug joint to detect a crack and on a large Naval SHM test bed and resulted in a placement of sensors that was able to interrogate all parts of the structure using the minimum number of transducers.

NMR study of xenotropic murine leukemia virus-related virus protease in a complex with amprenavir

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

Furukawa, Ayako; Okamura, Hideyasu; Morishita, Ryo

2012-08-24

Highlights: Black-Right-Pointing-Pointer Protease (PR) of XMR virus (XMRV) was successfully synthesized with cell-free system. Black-Right-Pointing-Pointer Interface of XMRV PR with an inhibitor, amprenavir (APV), was identified with NMR. Black-Right-Pointing-Pointer Structural heterogeneity is induced for two PR protomers in the APV:PR = 1:2 complex. Black-Right-Pointing-Pointer Structural heterogeneity is transmitted even to distant regions from the interface. Black-Right-Pointing-Pointer Long-range transmission of structural change may be utilized for drug discovery. -- Abstract: Xenotropic murine leukemia virus-related virus (XMRV) is a virus created through recombination of two murine leukemia proviruses under artificial conditions during the passage of human prostate cancer cells in athymic nudemore » mice. The homodimeric protease (PR) of XMRV plays a critical role in the production of functional viral proteins and is a prerequisite for viral replication. We synthesized XMRV PR using the wheat germ cell-free expression system and carried out structural analysis of XMRV PR in a complex with an inhibitor, amprenavir (APV), by means of NMR. Five different combinatorially {sup 15}N-labeled samples were prepared and backbone resonance assignments were made by applying Otting's method, with which the amino acid types of the [{sup 1}H, {sup 15}N] HSQC resonances were automatically identified using the five samples (Wu et al., 2006) . A titration experiment involving APV revealed that one APV molecule binds to one XMRV PR dimer. For many residues, two distinct resonances were observed, which is thought to be due to the structural heterogeneity between the two protomers in the APV:XMRV PR = 1:2 complex. PR residues at the interface with APV have been identified on the basis of chemical shift perturbation and identification of the intermolecular NOEs by means of filtered NOE experiments. Interestingly, chemical shift heterogeneity between the two protomers of XMRV PR has been observed not only at the interface with APV but also in regions apart from the interface. This indicates that the structural heterogeneity induced by the asymmetry of the binding of APV to the XMRV PR dimer is transmitted to distant regions. This is in contrast to the case of the APV:HIV-1 PR complex, in which the structural heterogeneity is only localized at the interface. Long-range transmission of the structural change identified for the XMRV PR complex might be utilized for the discovery of a new type of drug.« less

Resonance Raman and surface-enhanced resonance Raman spectra of LH2 antenna complex from Rhodobacter sphaeroides and Ectothiorhodospira sp. excited in the Qx and Qy transitions.

PubMed

Chumanov, G; Picorel, R; Ortiz de Zarate, I; Cotton, T M; Seibert, M

2000-05-01

Well-resolved vibrational spectra of LH2 complex isolated from two photosynthetic bacteria, Rhodobacter sphaeroides and Ectothiorhodospira sp., were obtained using surface-enhanced resonance Raman scattering (SERRS) exciting into the Qx and the Qy transitions of bacteriochlorophyll a. High-quality SERRS spectra in the Qy region were accessible because the strong fluorescence background was quenched near the roughened Ag surface. A comparison of the spectra obtained with 590 nm and 752 nm excitation in the mid- and low-frequency regions revealed spectral differences between the two LH2 complexes as well as between the LH2 complexes and isolated bacteriochlorophyll a. Because peripheral modes of pigments contribute mainly to the low-frequency spectral region, frequencies and intensities of many vibrational bands in this region are affected by interactions with the protein. The results demonstrate that the microenvironment surrounding the pigments within the two LH2 complexes is somewhat different, despite the fact that the complexes exhibit similar electronic absorption spectra. These differences are most probably due to specific pigment-pigment and pigment-protein interactions within the LH2 complexes, and the approach might be useful for addressing subtle static and dynamic structural variances between pigment-protein complexes from different sources or in complexes altered chemically or genetically.

Mapping multivalency and differential affinities within large intrinsically disordered protein complexes with segmental motion analysis.

PubMed

Milles, Sigrid; Lemke, Edward A

2014-07-07

Intrinsically disordered proteins (IDPs) can bind to multiple interaction partners. Numerous binding regions in the IDP that act in concert through complex cooperative effects facilitate such interactions, but complicate studying IDP complexes. To address this challenge we developed a combined fluorescence correlation and time-resolved polarization spectroscopy approach to study the binding properties of the IDP nucleoporin153 (Nup153) to nuclear transport receptors (NTRs). The detection of segmental backbone mobility of Nup153 within the unperturbed complex provided a readout of local, region-specific binding properties that are usually masked in measurements of the whole IDP. The binding affinities of functionally and structurally diverse NTRs to distinct regions of Nup153 can differ by orders of magnitudes-a result with implications for the diversity of transport routes in nucleocytoplasmic transport. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Open-ringed structure of the Cdt1-Mcm2-7 complex as a precursor of the MCM double hexamer.

PubMed

Zhai, Yuanliang; Cheng, Erchao; Wu, Hao; Li, Ningning; Yung, Philip Yuk Kwong; Gao, Ning; Tye, Bik-Kwoon

2017-03-01

The minichromosome maintenance complex (MCM) hexameric complex (Mcm2-7) forms the core of the eukaryotic replicative helicase. During G1 phase, two Cdt1-Mcm2-7 heptamers are loaded onto each replication origin by the origin-recognition complex (ORC) and Cdc6 to form an inactive MCM double hexamer (DH), but the detailed loading mechanism remains unclear. Here we examine the structures of the yeast MCM hexamer and Cdt1-MCM heptamer from Saccharomyces cerevisiae. Both complexes form left-handed coil structures with a 10-15-Å gap between Mcm5 and Mcm2, and a central channel that is occluded by the C-terminal domain winged-helix motif of Mcm5. Cdt1 wraps around the N-terminal regions of Mcm2, Mcm6 and Mcm4 to stabilize the whole complex. The intrinsic coiled structures of the precursors provide insights into the DH formation, and suggest a spring-action model for the MCM during the initial origin melting and the subsequent DNA unwinding.

High-Resolution Seismic Velocity and Attenuation Models of the Caucasus-Caspian Region

DTIC Science & Technology

2009-09-30

region is part of the Alpine-Himalayan collision belt and is an area of complex structure accompanied by large variations in seismic wave velocities...velocity structure is developed using teleseismic receiver functions and surface waves. Joint inversion of surface wave group dispersion curves...Caucasus and the thinnest is in the Arabian Plate. Thin crust is also observed near the Caspian. The lithospheric mantle in the Greater Caucasus and the

Dorso-medial and ventro-lateral functional specialization of the human retrosplenial complex in spatial updating and orienting.

PubMed

Burles, Ford; Slone, Edward; Iaria, Giuseppe

2017-04-01

The retrosplenial complex is a region within the posterior cingulate cortex implicated in spatial navigation. Here, we investigated the functional specialization of this large and anatomically heterogeneous region using fMRI and resting-state functional connectivity combined with a spatial task with distinct phases of spatial 'updating' (i.e., integrating and maintaining object locations in memory during spatial displacement) and 'orienting' (i.e., recalling unseen locations from current position in space). Both spatial 'updating' and 'orienting' produced bilateral activity in the retrosplenial complex, among other areas. However, spatial 'updating' produced slightly greater activity in ventro-lateral portions, of the retrosplenial complex, whereas spatial 'orienting' produced greater activity in a more dorsal and medial portion of it (both regions localized along the parieto-occipital fissure). At rest, both ventro-lateral and dorso-medial subregions of the retrosplenial complex were functionally connected to the hippocampus and parahippocampus, regions both involved in spatial orientation and navigation. However, the ventro-lateral subregion of the retrosplenial complex displayed more positive functional connectivity with ventral occipital and temporal object recognition regions, whereas the dorso-medial subregion activity was more correlated to dorsal activity and frontal activity, as well as negatively correlated with more ventral parietal structures. These findings provide evidence for a dorso-medial to ventro-lateral functional specialization within the human retrosplenial complex that may shed more light on the complex neural mechanisms underlying spatial orientation and navigation in humans.

Structure of an anti-HIV-1 hammerhead ribozyme complex with a 17-mer DNA substrate analog of HIV-1 gag RNA and a mechanism for the cleavage reaction: 750 MHz NMR and computer experiments

NASA Technical Reports Server (NTRS)

Ojha, R. P.; Dhingra, M. M.; Sarma, M. H.; Myer, Y. P.; Setlik, R. F.; Shibata, M.; Kazim, A. L.; Ornstein, R. L.; Rein, R.; Turner, C. J.;

The Ndc80 internal loop is required for recruitment of the Ska complex to establish end-on microtubule attachment to kinetochores.

PubMed

Zhang, Gang; Kelstrup, Christian D; Hu, Xiao-Wen; Kaas Hansen, Mathilde J; Singleton, Martin R; Olsen, Jesper V; Nilsson, Jakob

2012-07-01

The Ndc80 complex establishes end-on attachment of kinetochores to microtubules, which is essential for chromosome segregation. The Ndc80 subunit is characterized by an N-terminal region that binds directly to microtubules, and a long coiled-coil region that interacts with Nuf2. A loop region in Ndc80 that generates a kink in the structure disrupts the long coiled-coil region but the exact function of this loop, has until now, not been clear. Here we show that this loop region is essential for end-on attachment of kinetochores to microtubules in human cells. Cells expressing loop mutants of Ndc80 are unable to align the chromosomes, and stable kinetochore fibers are absent. Through quantitative mass spectrometry and immunofluorescence we found that the binding of the spindle and kinetochore associated (Ska) complex depends on the loop region, explaining why end-on attachment is defective. This underscores the importance of the Ndc80 loop region in coordinating chromosome segregation through the recruitment of specific proteins to the kinetochore.

The Sacred Mountain of Varallo in Italy: Seismic Risk Assessment by Acoustic Emission and Structural Numerical Models

PubMed Central

Carpinteri, Alberto; Invernizzi, Stefano; Accornero, Federico

2013-01-01

We examine an application of Acoustic Emission (AE) technique for a probabilistic analysis in time and space of earthquakes, in order to preserve the valuable Italian Renaissance Architectural Complex named “The Sacred Mountain of Varallo.” Among the forty-five chapels of the Renaissance Complex, the structure of the Chapel XVII is of particular concern due to its uncertain structural condition and due to the level of stress caused by the regional seismicity. Therefore, lifetime assessment, taking into account the evolution of damage phenomena, is necessary to preserve the reliability and safety of this masterpiece of cultural heritage. A continuous AE monitoring was performed to assess the structural behavior of the Chapel. During the monitoring period, a correlation between peaks of AE activity in the masonry of the “Sacred Mountain of Varallo” and regional seismicity was found. Although the two phenomena take place on very different scales, the AE in materials and the earthquakes in Earth's crust, belong to the same class of invariance. In addition, an accurate finite element model, performed with DIANA finite element code, is presented to describe the dynamic behavior of Chapel XVII structure, confirming visual and instrumental inspections of regional seismic effects. PMID:24381511

Individual Differences in the Alignment of Structural and Functional Markers of the V5/MT Complex in Primates

PubMed Central

Large, I.; Bridge, H.; Ahmed, B.; Clare, S.; Kolasinski, J.; Lam, W. W.; Miller, K. L.; Dyrby, T. B.; Parker, A. J.; Smith, J. E. T.; Daubney, G.; Sallet, J.; Bell, A. H.; Krug, K.

2016-01-01

Extrastriate visual area V5/MT in primates is defined both structurally by myeloarchitecture and functionally by distinct responses to visual motion. Myelination is directly identifiable from postmortem histology but also indirectly by image contrast with structural magnetic resonance imaging (sMRI). First, we compared the identification of V5/MT using both sMRI and histology in Rhesus macaques. A section-by-section comparison of histological slices with in vivo and postmortem sMRI for the same block of cortical tissue showed precise correspondence in localizing heavy myelination for V5/MT and neighboring MST. Thus, sMRI in macaques accurately locates histologically defined myelin within areas known to be motion selective. Second, we investigated the functionally homologous human motion complex (hMT+) using high-resolution in vivo imaging. Humans showed considerable intersubject variability in hMT+ location, when defined with myelin-weighted sMRI signals to reveal structure. When comparing sMRI markers to functional MRI in response to moving stimuli, a region of high myelin signal was generally located within the hMT+ complex. However, there were considerable differences in the alignment of structural and functional markers between individuals. Our results suggest that variation in area identification for hMT+ based on structural and functional markers reflects individual differences in human regional brain architecture. PMID:27371764

Red/near-infrared luminescence tuning of group-14 element complexes of dipyrrins based on a central atom.

PubMed

Yamamura, Masaki; Albrecht, Marcel; Albrecht, Markus; Nishimura, Yoshinobu; Arai, Tatsuo; Nabeshima, Tatsuya

2014-02-03

A dipyrrin complex has been one of the most utilized fluorescent dyes, and a variety of dipyrrin complexes show intriguing functions based on the various coordination structures of the central element. We now report the synthesis, structure, and photophysical properties of germanium and stannane complexes of the N2O2-type tetradentate dipyrrin, L·Ge and L·Sn, which are heavier analogues of the previously reported dipyrrin silicon complex, L·Si. The central group-14 atoms of the monomeric complexes have geometries close to trigonal bipyramidal (TBP), in which the contribution of the square-pyramidal (SP) character becomes higher as the central atom is heavier. Interestingly, L·Sn formed a dimeric structure in the crystal. All complexes L·Si, L·Ge, and L·Sn showed a fluorescence in the red/NIR region. Fluorescence quantum yields of L·Ge and L·Sn are higher than that of L·Si. These results indicated that the central atom on the dipyrrin complexes contributes not only to the geometry difference but also to tuning the fluorescence properties.

Crystal structure of a shark single-domain antibody V region in complex with lysozyme.

PubMed

Stanfield, Robyn L; Dooley, Helen; Flajnik, Martin F; Wilson, Ian A

2004-09-17

Cartilaginous fish are the phylogenetically oldest living organisms known to possess components of the vertebrate adaptive immune system. Key to their immune response are heavy-chain, homodimeric immunoglobulins called new antigen receptors (IgNARs), in which the variable (V) domains recognize antigens with only a single immunoglobulin domain, akin to camelid heavy-chain V domains. The 1.45 angstrom resolution crystal structure of the type I IgNAR V domain in complex with hen egg-white lysozyme (HEL) reveals a minimal antigen-binding domain that contains only two of the three conventional complementarity-determining regions but still binds HEL with nanomolar affinity by means of a binding interface comparable in size to conventional antibodies.

Lightning Activity Relative to the Microphysical and Kinematic Structure of Storms during a Thunder-Snow Episode on 29-30 November 2006

NASA Astrophysics Data System (ADS)

Emersic, C.; Macgorman, D.; Schuur, T.; Lund, N.; Payne, C.; Bruning, E.

2007-12-01

We have examined lightning activity relative to the microphysical and kinematic structure of a winter thunderstorm complex (a thunder-snow episode) observed east of Norman, Oklahoma during the evening of 29-30 November 2006. Polarimetric radar provided information about the type of particles present in various regions of the storms. The Lightning Mapping Array (LMA) recorded VHF signals produced by developing lightning channels. The times of arrival of these lightning signals across the array were then used to reconstruct the location and structure of lightning, and these reconstructions were overlaid with radar data to examine the relationship between lightning properties and storm particle types. Four storms in this winter complex have been examined. It was inferred from lightning structure that, in their mature stage, all cells we examined had a positive tripole electrical structure (an upper positive charge center, a midlevel negative charge center, and a lower positive charge center). The storms began with lightning activity in the lower dipole (lower positive and midlevel negative regions), but this evolved into lightning activity throughout the tripole structure within approximately 15-20 minutes. In the longer lived storms, the mature stage lasted for approximately 1.5-2 hours. During this stage, the lower positive charge region was situated less than 5 km above ground, the midlevel negative charge region was typically above 5 km, and the upper positive charge region was located at an altitude of less than 10 km in all the storm cells analyzed. The charge regions descended over approximately the last 30 minutes of lightning activity, the lower charge regions eventually reaching ground. This resulted in the loss of the lower positive charge center and the subsequent diminishment of the lower negative charge center. Lightning initiation usually coincided with the edges of regions of high reflectivity and was coincident with the presence of graupel and ice crystals in the lower dipole. Radar data suggest that ice crystals were the dominant charge carriers in the upper positive region.

Digital Sequences and a Time Reversal-Based Impact Region Imaging and Localization Method

PubMed Central

Qiu, Lei; Yuan, Shenfang; Mei, Hanfei; Qian, Weifeng

2013-01-01

To reduce time and cost of damage inspection, on-line impact monitoring of aircraft composite structures is needed. A digital monitor based on an array of piezoelectric transducers (PZTs) is developed to record the impact region of impacts on-line. It is small in size, lightweight and has low power consumption, but there are two problems with the impact alarm region localization method of the digital monitor at the current stage. The first one is that the accuracy rate of the impact alarm region localization is low, especially on complex composite structures. The second problem is that the area of impact alarm region is large when a large scale structure is monitored and the number of PZTs is limited which increases the time and cost of damage inspections. To solve the two problems, an impact alarm region imaging and localization method based on digital sequences and time reversal is proposed. In this method, the frequency band of impact response signals is estimated based on the digital sequences first. Then, characteristic signals of impact response signals are constructed by sinusoidal modulation signals. Finally, the phase synthesis time reversal impact imaging method is adopted to obtain the impact region image. Depending on the image, an error ellipse is generated to give out the final impact alarm region. A validation experiment is implemented on a complex composite wing box of a real aircraft. The validation results show that the accuracy rate of impact alarm region localization is approximately 100%. The area of impact alarm region can be reduced and the number of PZTs needed to cover the same impact monitoring region is reduced by more than a half. PMID:24084123

Lithospheric Velocity Structure of the Anatolain plateau-Caucasus-Caspian Regions

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

Gok, R; Mellors, R J; Sandvol, E

Anatolian Plateau-Caucasus-Caspian region is an area of complex structure accompanied by large variations in seismic wave velocities. Despite the complexity of the region little is known about the detailed lithospheric structure. Using data from 29 new broadband seismic stations in the region, a unified velocity structure is developed using teleseismic receiver functions and surface waves. Love and Rayleigh surface waves dispersion curves have been derived from event-based analysis and ambient-noise correlation. We jointly inverted the receiver functions with the surface wave dispersion curves to determine absolute shear wave velocity and important discontinuities such as sedimentary layer, Moho, lithospheric-asthenospheric boundary. Wemore » combined these new station results with Eastern Turkey Seismic Experiment results (29 stations). Caspian Sea and Kura basin underlained by one of the thickest sediments in the world. Therefore, short-period surface waves are observed to be very slow. The strong crustal multiples in receiver functions and the slow velocities in upper crust indicate the presence of thick sedimentary unit (up to 20 km). Crustal thickness varies from 34 to 52 km in the region. The thickest crust is in Lesser Caucasus and the thinnest is in the Arabian Plate. The lithospheric mantle in the Greater Caucasus and the Kura depression is faster than the Anatolian Plateau and Lesser Caucasus. This possibly indicates the presence of cold lithosphere. The lower crust is slowest in the northeastern part of the Anatolian Plateau where Holocene volcanoes are located.« less

Structural and tectonic setting of the Charleston, South Carolina, region: Evidence from the Tertiary stratigraphic record

USGS Publications Warehouse

Weems, R.E.; Lewis, W.C.

2002-01-01

Eleven upper Eocene through Pliocene stratigraphic units occur in the subsurface of the region surrounding Charleston, South Carolina. These units contain a wealth of information concerning the long-term tectonic and structural setting of that area. These stratigraphic units have a mosaic pattern of distribution, rather than a simple layered pattern, because deposition, erosion, and tectonic warping have interacted in a complex manner through time. By generating separate structure-contour maps for the base of each stratigraphic unit, an estimate of the original basal surface of each unit can be reconstructed over wide areas. Changes in sea level over geologic time generate patterns of deposition and erosion that are geographically unique for the time of each transgression. Such patterns fail to persist when compared sequentially over time. In some areas, however, there has been persistent, repetitive net downward of upward movement over the past 34 m.y. These repetitive patterns of persistent motion are most readily attributable to tectonism. The spatial pattern of these high and low areas is complex, but it appears to correlate well with known tectonic features of the region. This correlation suggests that the tectonic setting of the Charleston region is controlled by scissors-like compression on a crustal block located between the north-trending Adams Run fault and the northwest-trending Charleston fault. Tectonism is localized in the Charleston region because it lies within a discrete hinge zone that accommodates structural movement between the Cape Fear arch and the Southeast Georgia embayment.

Uplifted ophiolitic rocks on Isla Gordon, southernmost Chile: implications for the closure history of the Rocas Verdes marginal basin and the tectonic evolution of the Beagle Channel region

NASA Astrophysics Data System (ADS)

Cunningham, W. D.

1994-04-01

A succession of mafic rocks that includes gabbro, sheeted dikes and deformed pillow basalts has been mapped in detail on Isla Gordon, southernmost Chile and is identified as an upper ophiolitic complex representing the uplifted floor of the Late Jurassic-Early Cretaceous Rocas Verdes marginal basin. The complex was uplifted, deformed, and regionally metamorphosed prior to the intrusion of an undeformed 90 Ma granodiorite that cuts the complex. The complex appears para-autochthonous, is gently tilted to the northeast and is internally sheared by near-vertical foliation zones. No evidence for obduction was observed although the base of the complex is not exposed. The ophiolitic rocks have been regionally metamorphosed to mid-upper greenschist levels. Isla Gordon is bounded by the northwest and southwest arms of the Beagle Channel, two important structural boundaries in the southernmost Andes that are interpreted to have accommodated north-side-up and left-lateral displacements. Directly north of Isla Gordon is the Cordillera Darwin metamorphic complex that exposes the highest grade metamorphic rocks in the Andes south of Peru. On the north coast of Isla Gordon a volcaniclastic turbidite sequence that is interpreted to have been deposited above the mafic floor is metamorphosed to lower greenschist levels in strong metamorphic contrast to amphibolite-grade othogneisses exposed in Cordillera Darwin only 2 km away across the northwest arm of the Beagle Channel. The profound metamorphic break across the northwest arm of the Beagle Channel and the regional northeast tilt of the ophiolitic complex are consistent with the previously proposed hypothesis that Isla Gordon represents the upper plate to an extensional fault that accommodated tectonic unroofing of Cordillera Darwin. However, limited structural evidence for extension was identified in this study to support the model and further work is needed to determine the relative importance of contractional, extensional and strike-slip displacements during the closure of the Rocas Verdes marginal basin and uplift of Cordillera Darwin. The Isla Gordon ophiolitic complex is correlative with other regional occurrences of ophiolitic rocks including the previously studied Tortuga, Sarmiento and Larsen Harbour complexes. The existence of the Isla Gordon ophiolitic complex helps link the known occurrences of the marginal basin floor into a semi-continuous belt that sheds light on the original continuity of the basin.

Structural Mechanism behind Distinct Efficiency of Oct4/Sox2 Proteins in Differentially Spaced DNA Complexes

PubMed Central

Yesudhas, Dhanusha; Anwar, Muhammad Ayaz; Panneerselvam, Suresh; Durai, Prasannavenkatesh; Shah, Masaud; Choi, Sangdun

2016-01-01

The octamer-binding transcription factor 4 (Oct4) and sex-determining region Y (SRY)-box 2 (Sox2) proteins induce various transcriptional regulators to maintain cellular pluripotency. Most Oct4/Sox2 complexes have either 0 base pairs (Oct4/Sox20bp) or 3 base pairs (Oct4/Sox23bp) separation between their DNA-binding sites. Results from previous biochemical studies have shown that the complexes separated by 0 base pairs are associated with a higher pluripotency rate than those separated by 3 base pairs. Here, we performed molecular dynamics (MD) simulations and calculations to determine the binding free energy and per-residue free energy for the Oct4/Sox20bp and Oct4/Sox23bp complexes to identify structural differences that contribute to differences in induction rate. Our MD simulation results showed substantial differences in Oct4/Sox2 domain movements, as well as secondary-structure changes in the Oct4 linker region, suggesting a potential reason underlying the distinct efficiencies of these complexes during reprogramming. Moreover, we identified key residues and hydrogen bonds that potentially facilitate protein-protein and protein-DNA interactions, in agreement with previous experimental findings. Consequently, our results confess that differential spacing of the Oct4/Sox2 DNA binding sites can determine the magnitude of transcription of the targeted genes during reprogramming. PMID:26790000

Structural basis of ligand interaction with atypical chemokine receptor 3

NASA Astrophysics Data System (ADS)

Gustavsson, Martin; Wang, Liwen; van Gils, Noortje; Stephens, Bryan S.; Zhang, Penglie; Schall, Thomas J.; Yang, Sichun; Abagyan, Ruben; Chance, Mark R.; Kufareva, Irina; Handel, Tracy M.

2017-01-01

Chemokines drive cell migration through their interactions with seven-transmembrane (7TM) chemokine receptors on cell surfaces. The atypical chemokine receptor 3 (ACKR3) binds chemokines CXCL11 and CXCL12 and signals exclusively through β-arrestin-mediated pathways, without activating canonical G-protein signalling. This receptor is upregulated in numerous cancers making it a potential drug target. Here we collected over 100 distinct structural probes from radiolytic footprinting, disulfide trapping, and mutagenesis to map the structures of ACKR3:CXCL12 and ACKR3:small-molecule complexes, including dynamic regions that proved unresolvable by X-ray crystallography in homologous receptors. The data are integrated with molecular modelling to produce complete and cohesive experimentally driven models that confirm and expand on the existing knowledge of the architecture of receptor:chemokine and receptor:small-molecule complexes. Additionally, we detected and characterized ligand-induced conformational changes in the transmembrane and intracellular regions of ACKR3 that elucidate fundamental structural elements of agonism in this atypical receptor.

Structural basis of ligand interaction with atypical chemokine receptor 3

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

Gustavsson, Martin; Wang, Liwen; van Gils, Noortje

2017-01-18

Chemokines drive cell migration through their interactions with seven-transmembrane (7TM) chemokine receptors on cell surfaces. The atypical chemokine receptor 3 (ACKR3) binds chemokines CXCL11 and CXCL12 and signals exclusively through β-arrestin-mediated pathways, without activating canonical G-protein signalling. This receptor is upregulated in numerous cancers making it a potential drug target. Here we collected over 100 distinct structural probes from radiolytic footprinting, disulfide trapping, and mutagenesis to map the structures of ACKR3:CXCL12 and ACKR3:small-molecule complexes, including dynamic regions that proved unresolvable by X-ray crystallography in homologous receptors. The data are integrated with molecular modelling to produce complete and cohesive experimentally drivenmore » models that confirm and expand on the existing knowledge of the architecture of receptor:chemokine and receptor:small-molecule complexes. Additionally, we detected and characterized ligand-induced conformational changes in the transmembrane and intracellular regions of ACKR3 that elucidate fundamental structural elements of agonism in this atypical receptor.« less

X-ray absorption near-edge spectroscopy in bioinorganic chemistry: Application to M–O2 systems

PubMed Central

Sarangi, Ritimukta

2012-01-01

Metal K-edge X-ray absorption spectroscopy (XAS) has been extensively applied to bioinorganic chemistry to obtain geometric structure information on metalloprotein and biomimetic model complex active sites by analyzing the higher energy extended X-ray absorption fine structure (EXAFS) region of the spectrum. In recent years, focus has been on developing methodologies to interpret the lower energy K-pre-edge and rising-edge regions (XANES) and using it for electronic structure determination in complex bioinorganic systems. In this review, the evolution and progress of 3d-transition metal K-pre-edge and rising-edge methodology development is presented with particular focus on applications to bioinorganic systems. Applications to biomimetic transition metal–O2 intermediates (M = Fe, Co, Ni and Cu) are reviewed, which demonstrate the power of the method as an electronic structure determination technique and its impact in understanding the role of supporting ligands in tuning the electronic configuration of transition metal–O2 systems. PMID:23525635

Molecular modeling studies of substrate binding by penicillin acylase.

PubMed

Chilov, G G; Stroganov, O V; Svedas, V K

2008-01-01

Molecular modeling has revealed intimate details of the mechanism of binding of natural substrate, penicillin G (PG), in the penicillin acylase active center and solved questions raised by analysis of available X-ray structures, mimicking Michaelis complex, which substantially differ in the binding pattern of the PG leaving group. Three MD trajectories were launched, starting from PDB complexes of the inactive mutant enzyme with PG (1FXV) and native penicillin acylase with sluggishly hydrolyzed substrate analog penicillin G sulfoxide (1GM9), or from the complex obtained by PG docking. All trajectories converged to a similar PG binding mode, which represented the near-to-attack conformation, consistent with chemical criteria of how reactive Michaelis complex should look. Simulated dynamic structure of the enzyme-substrate complex differed significantly from 1FXV, resembling rather 1GM9; however, additional contacts with residues bG385, bS386, and bN388 have been found, which were missing in X-ray structures. Combination of molecular docking and molecular dynamics also clarified the nature of extremely effective phenol binding in the hydrophobic pocket of penicillin acylase, which lacked proper explanation from crystallographic experiments. Alternative binding modes of phenol were probed, and corresponding trajectories converged to a single binding pattern characterized by a hydrogen bond between the phenol hydroxyl and the main chain oxygen of bS67, which was not evident from the crystal structure. Observation of the trajectory, in which phenol moved from its steady bound to pre-dissociation state, mapped the consequence of molecular events governing the conformational transitions in a coil region a143-a146 coupled to substrate binding and release of the reaction products. The current investigation provided information on dynamics of the conformational transitions accompanying substrate binding and significance of poorly structured and flexible regions in maintaining catalytic framework.

Tailored optical vector fields for ultrashort-pulse laser induced complex surface plasmon structuring.

PubMed

Ouyang, J; Perrie, W; Allegre, O J; Heil, T; Jin, Y; Fearon, E; Eckford, D; Edwardson, S P; Dearden, G

2015-05-18

Precise tailoring of optical vector beams is demonstrated, shaping their focal electric fields and used to create complex laser micro-patterning on a metal surface. A Spatial Light Modulator (SLM) and a micro-structured S-waveplate were integrated with a picosecond laser system and employed to structure the vector fields into radial and azimuthal polarizations with and without a vortex phase wavefront as well as superposition states. Imprinting Laser Induced Periodic Surface Structures (LIPSS) elucidates the detailed vector fields around the focal region. In addition to clear azimuthal and radial plasmon surface structures, unique, variable logarithmic spiral micro-structures with a pitch Λ ∼1μm, not observed previously, were imprinted on the surface, confirming unambiguously the complex 2D focal electric fields. We show clearly also how the Orbital Angular Momentum(OAM) associated with a helical wavefront induces rotation of vector fields along the optic axis of a focusing lens and confirmed by the observed surface micro-structures.

Regional interoperability: making systems connect in complex disasters.

PubMed

Briggs, Susan Miller

2009-08-01

Effective use of the Incident Command System (ICS) is the key to regional interoperability. Many different organizations with different command structures and missions respond to a disaster. The ICS allows different kinds of agencies (fire, police, and medical) to work together effectively in response to a disaster. Functional requirements, not titles, determine the organizational hierarchy of the ICS structure. The ICS is a modular/adaptable system for all disasters regardless of etiology and for all organizations regardless of size.

The relationship between the understory shrub component of coastal forests and the conservation of forest carnivores

Treesearch

Keith M. Slauson; William J. Zielinski

2007-01-01

The physical structure of vegetation is an important predictor of habitat for wildlife species. The coastal forests of the Redwood region are highly productive, supporting structurally-diverse forest habitats. The major elements of structural diversity in these forests include trees, shrubs, and herbaceous plants, which together create three-dimensional complexity. In...

Velocity Structure Determination Through Seismic Waveform Modeling and Time Deviations

NASA Astrophysics Data System (ADS)

Savage, B.; Zhu, L.; Tan, Y.; Helmberger, D. V.

2001-12-01

Through the use of seismic waveforms recorded by TriNet, a dataset of earthquake focal mechanisms and deviations (time shifts) relative to a standard model facilitates the investigation of the crust and uppermost mantle of southern California. The CAP method of focal mechanism determination, in use by TriNet on a routine basis, provides time shifts for surface waves and Pnl arrivals independently relative to the reference model. These shifts serve as initial data for calibration of local and regional seismic paths. Time shifts from the CAP method are derived by splitting the Pnl section of the waveform, the first arriving Pn to just before the arrival of the S wave, from the much slower surface waves then cross-correlating the data with synthetic waveforms computed from a standard model. Surface waves interact with the entire crust, but the upper crust causes the greatest effect. Whereas, Pnl arrivals sample the deeper crust, upper mantle, and source region. This natural division separates the upper from lower crust for regional calibration and structural modeling and allows 3-D velocity maps to be created using the resulting time shifts. Further examination of Pnl and other arrivals which interact with the Moho illuminate the complex nature of this boundary. Initial attempts at using the first 10 seconds of the Pnl section to determine upper most mantle structure have proven insightful. Two large earthquakes north of southern California in Nevada and Mammoth Lakes, CA allow the creation of record sections from 200 to 600 km. As the paths swing from east to west across southern California, simple 1-D models turn into complex structure, dramatically changing the waveform character. Using finite difference models to explain the structure, we determine that a low velocity zone is present at the base of the crust and extends to 100 km in depth. Velocity variations of 5 percent of the mantle in combination with steeply sloping edges produces complex waveform variations. Characteristics of this complex propagation appear from the southern Sierra Nevada Mountains, in the west, to Death Valley in the east. The structure does not cross the Garlock fault to the south, but we are unsure of the structures northern extent.

Islands within an island: Population genetic structure of the endemic Sardinian newt, Euproctus platycephalus.

PubMed

Ball, Sarah E; Bovero, Stefano; Sotgiu, Giuseppe; Tessa, Giulia; Angelini, Claudio; Bielby, Jon; Durrant, Christopher; Favelli, Marco; Gazzaniga, Enrico; Garner, Trenton W J

2017-02-01

The identification of historic and contemporary barriers to dispersal is central to the conservation of endangered amphibians, but may be hindered by their complex life history and elusive nature. The complementary information generated by mitochondrial (mtDNA) and microsatellite markers generates a valuable tool in elucidating population structure and the impact of habitat fragmentation. We applied this approach to the study of an endangered montane newt, Euproctus platycephalus . Endemic to the Mediterranean island of Sardinia, it is threatened by anthropogenic activity, disease, and climate change. We have demonstrated a clear hierarchy of structure across genetically divergent and spatially distinct subpopulations. Divergence between three main mountain regions dominated genetic partitioning with both markers. Mitochondrial phylogeography revealed a deep division dating to ca. 1 million years ago (Mya), isolating the northern region, and further differentiation between the central and southern regions ca. 0.5 Mya, suggesting an association with Pleistocene severe glacial oscillations. Our findings are consistent with a model of southward range expansion during glacial periods, with postglacial range retraction to montane habitat and subsequent genetic isolation. Microsatellite markers revealed further strong population structure, demonstrating significant divergence within the central region, and partial differentiation within the south. The northern population showed reduced genetic diversity. Discordance between mitochondrial and microsatellite markers at this scale indicated a further complexity of population structure, in keeping with male-biased dispersal and female philopatry. Our study underscores the need to elucidate cryptic population structure in the ecology and conservation strategies for endangered island-restricted amphibians, especially in the context of disease and climate change.

Block-induced Complex Structures Building the Flare-productive Solar Active Region 12673

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

Yang, Shuhong; Zhang, Jun; Zhu, Xiaoshuai

Solar active region (AR) 12673 produced 4 X-class, 27 M-class, and numerous lower-class flares during its passage across the visible solar disk in 2017 September. Our study is to answer the questions why this AR was so flare-productive and how the X9.3 flare, the largest one of the past decade, took place. We find that there was a sunspot in the initial several days, and then two bipolar regions emerged nearby it successively. Due to the standing of the pre-existing sunspot, the movement of the bipoles was blocked, while the pre-existing sunspot maintained its quasi-circular shaped umbra only with themore » disappearance of a part of penumbra. Thus, the bipolar patches were significantly distorted, and the opposite polarities formed two semi-circular shaped structures. After that, two sequences of new bipolar regions emerged within the narrow semi-circular zone, and the bipolar patches separated along the curved channel. The new bipoles sheared and interacted with the previous ones, forming a complex topological system, during which numerous flares occurred. At the highly sheared region, a great deal of free energy was accumulated. On September 6, one negative patch near the polarity inversion line began to rapidly rotate and shear with the surrounding positive fields, and consequently the X9.3 flare erupted. Our results reveal that the block-induced complex structures built the flare-productive AR and the X9.3 flare was triggered by an erupting filament due to the kink instability. To better illustrate this process, a block-induced eruption model is proposed for the first time.« less

IR-UV double resonance spectroscopic investigation of phenylacetylene-alcohol complexes. Alkyl group induced hydrogen bond switching.

PubMed

Singh, Prashant Chandra; Patwari, G Naresh

2008-06-12

The electronic transitions of phenylacetylene complexes with water and trifluoroethanol are shifted to the blue, while the corresponding transitions for methanol and ethanol complexes are shifted to the red relative to the phenylacetylene monomer. Fluorescence dip infrared (FDIR) spectra in the O-H stretching region indicate that, in all the cases, phenylacetylene is acting as a hydrogen bond acceptor to the alcohols. The FDIR spectrum in the acetylenic C-H stretching region shows Fermi resonance bands for the bare phenylacetylene, which act as a sensitive tool to probe the intermolecular structures. The FDIR spectra reveal that water and trifluoroethanol interact with the pi electron density of the acetylene C-C triple bond, while methanol and ethanol interact with the pi electron density of the benzene ring. It can be inferred that the hydrogen bonding acceptor site on phenylacetylene switches from the acetylene pi to the benzene pi with lowering in the partial charge on the hydrogen atom of the OH group. The most significant finding is that the intermolecular structures of water and methanol complexes are notably distinct, which, to the best of our knowledge, this is first such observation in the case of complexes of substituted benzenes.

Evidence for a complex archean deformational history; southwestern Michipicoten Greenstone Belt, Ontario

NASA Technical Reports Server (NTRS)

Mcgill, George E.; Shrady, Catherine H.

1986-01-01

The Michipicoten Greenstone Belt extends for about 150 km ENE from the northeastern angle of Lake Superior. In common with many other Archean greenstone belts, it is characterized by generally steep bedding dips and a distribution of major lithologic types suggesting a crudely synclinal structure for the belt as a whole. Detailed mapping and determination of structural sequence demonstrates that the structure is much more complex. The Archean history of the belt includes formation of at least three regionally significant cleavages, kilometer-scale overturning, extensive shearing, and diabase intrusion. Most well defined, mappable 'packages' of sedimentary rocks appear to be bounded by faults. These faults were active relatively early in the structural history of the belt, when extensive overturning also occurred. Steepening of dips, NW-SE shortening, development of steep NE cleavage, and pervasive shearing all postdate the early faulting and the regional overturning, obscuring much of the detail needed to define the geometry of the earlier structures. The results obtained so far suggest, however, that the Michipicoten Greenstone Belt underwent an early stage of thrusting and associated isoclinal folding, probably in a convergent tectonic environment.

Pyramidal Cells in Prefrontal Cortex of Primates: Marked Differences in Neuronal Structure Among Species

PubMed Central

Elston, Guy N.; Benavides-Piccione, Ruth; Elston, Alejandra; Manger, Paul R.; DeFelipe, Javier

2010-01-01

The most ubiquitous neuron in the cerebral cortex, the pyramidal cell, is characterized by markedly different dendritic structure among different cortical areas. The complex pyramidal cell phenotype in granular prefrontal cortex (gPFC) of higher primates endows specific biophysical properties and patterns of connectivity, which differ from those in other cortical regions. However, within the gPFC, data have been sampled from only a select few cortical areas. The gPFC of species such as human and macaque monkey includes more than 10 cortical areas. It remains unknown as to what degree pyramidal cell structure may vary among these cortical areas. Here we undertook a survey of pyramidal cells in the dorsolateral, medial, and orbital gPFC of cercopithecid primates. We found marked heterogeneity in pyramidal cell structure within and between these regions. Moreover, trends for gradients in neuronal complexity varied among species. As the structure of neurons determines their computational abilities, memory storage capacity and connectivity, we propose that these specializations in the pyramidal cell phenotype are an important determinant of species-specific executive cortical functions in primates. PMID:21347276

A low-complexity region in the YTH domain protein Mmi1 enhances RNA binding.

PubMed

Stowell, James A W; Wagstaff, Jane L; Hill, Chris H; Yu, Minmin; McLaughlin, Stephen H; Freund, Stefan M V; Passmore, Lori A

2018-06-15

Mmi1 is an essential RNA-binding protein in the fission yeast Schizosaccharomyces pombe that eliminates meiotic transcripts during normal vegetative growth. Mmi1 contains a YTH domain that binds specific RNA sequences, targeting mRNAs for degradation. The YTH domain of Mmi1 uses a noncanonical RNA-binding surface that includes contacts outside the conserved fold. Here, we report that an N-terminal extension that is proximal to the YTH domain enhances RNA binding. Using X-ray crystallography, NMR, and biophysical methods, we show that this low-complexity region becomes more ordered upon RNA binding. This enhances the affinity of the interaction of the Mmi1 YTH domain with specific RNAs by reducing the dissociation rate of the Mmi1-RNA complex. We propose that the low-complexity region influences RNA binding indirectly by reducing dynamic motions of the RNA-binding groove and stabilizing a conformation of the YTH domain that binds to RNA with high affinity. Taken together, our work reveals how a low-complexity region proximal to a conserved folded domain can adopt an ordered structure to aid nucleic acid binding. © 2018 Stowell et al.

Nuclear shapes: Quest for triaxiality in 86Ge and the shape of 98Zr

NASA Astrophysics Data System (ADS)

Werner, V.; Lettmann, M.; Lizarazo, C.; Witt, W.; Cline, D.; Carpenter, M.; Doornenbal, P.; Obertelli, A.; Pietralla, N.; Savard, G.; Söderström, P.-A.; Wu, C.-Y.; Zhu, S.

2018-05-01

The region of neutron-rich nuclei above the N = 50 magic neutron shell closure encompasses a rich variety of nuclear structure, especially shapeevolutionary phenomena. This can be attributed to the complexity of sub-shell closures, their appearance and disappearance in the region, such as the N = 56 sub shell or Z = 40 for protons. Structural effects reach from a shape phase transition in the Zr isotopes, over shape coexistence between spherical, prolate, and oblate shapes, to possibly rigid triaxial deformation. Recent experiments in this region and their main physics viewpoints are summarized.

Structure–function mapping of a heptameric module in the nuclear pore complex

PubMed Central

Fernandez-Martinez, Javier; Phillips, Jeremy; Sekedat, Matthew D.; Diaz-Avalos, Ruben; Velazquez-Muriel, Javier; Franke, Josef D.; Williams, Rosemary; Stokes, David L.; Chait, Brian T.

2012-01-01

The nuclear pore complex (NPC) is a multiprotein assembly that serves as the sole mediator of nucleocytoplasmic exchange in eukaryotic cells. In this paper, we use an integrative approach to determine the structure of an essential component of the yeast NPC, the ∼600-kD heptameric Nup84 complex, to a precision of ∼1.5 nm. The configuration of the subunit structures was determined by satisfaction of spatial restraints derived from a diverse set of negative-stain electron microscopy and protein domain–mapping data. Phenotypic data were mapped onto the complex, allowing us to identify regions that stabilize the NPC’s interaction with the nuclear envelope membrane and connect the complex to the rest of the NPC. Our data allow us to suggest how the Nup84 complex is assembled into the NPC and propose a scenario for the evolution of the Nup84 complex through a series of gene duplication and loss events. This work demonstrates that integrative approaches based on low-resolution data of sufficient quality can generate functionally informative structures at intermediate resolution. PMID:22331846

Synthesis, spectroscopic, thermal and structural properties of [M(3-aminopyridine)2Ni(μ-CN)2(CN)2]n (M(II) = Co and Cu) heteropolynuclear cyano-bridged complexes

NASA Astrophysics Data System (ADS)

Kartal, Zeki

2016-01-01

Two novel cyano-bridged heteropolynuclear complexes, [Co(3-aminopyridine)2Ni(μ-CN)2(CN)2]n and [Cu(3-aminopyridine)2Ni(μ-CN)2(CN)2]n have been synthesized and characterized by elemental, thermal, FT-IR and FT-Raman spectroscopies. The structures of complexes have been determined by X-ray powder diffraction. The FT-IR and FT-Raman spectra of complexes have been recorded in the region of 3500-400 cm-1 and 3500-100 cm-1, respectively. General information was acquired about structural properties of these complexes from FT-IR and FT-Raman spectra by considering changes at characteristic peaks of the cyano group and 3AP. The splitting of the ν(Ctbnd N) stretching bands in the FT-IR spectra for complexes indicates the presence of terminal and bridging cyanides. The thermal behaviors of these complexes have been also investigated in the range of 25-950 °C using TG and DTG methods. Magnetic susceptibility measurements were made at room temperature using Gouy-balance.

Distinct modes of recruitment of the CCR4-NOT complex by Drosophila and vertebrate Nanos.

PubMed

Raisch, Tobias; Bhandari, Dipankar; Sabath, Kevin; Helms, Sigrun; Valkov, Eugene; Weichenrieder, Oliver; Izaurralde, Elisa

2016-05-02

Nanos proteins repress the expression of target mRNAs by recruiting effector complexes through non-conserved N-terminal regions. In vertebrates, Nanos proteins interact with the NOT1 subunit of the CCR4-NOT effector complex through a NOT1 interacting motif (NIM), which is absent in Nanos orthologs from several invertebrate species. Therefore, it has remained unclear whether the Nanos repressive mechanism is conserved and whether it also involves direct interactions with the CCR4-NOT deadenylase complex in invertebrates. Here, we identify an effector domain (NED) that is necessary for the Drosophila melanogaster (Dm) Nanos to repress mRNA targets. The NED recruits the CCR4-NOT complex through multiple and redundant binding sites, including a central region that interacts with the NOT module, which comprises the C-terminal domains of NOT1-3. The crystal structure of the NED central region bound to the NOT module reveals an unanticipated bipartite binding interface that contacts NOT1 and NOT3 and is distinct from the NIM of vertebrate Nanos. Thus, despite the absence of sequence conservation, the N-terminal regions of Nanos proteins recruit CCR4-NOT to assemble analogous repressive complexes. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

The structural, connectomic and network covariance of the human brain.

PubMed

Irimia, Andrei; Van Horn, John D

2013-02-01

Though it is widely appreciated that complex structural, functional and morphological relationships exist between distinct areas of the human cerebral cortex, the extent to which such relationships coincide remains insufficiently appreciated. Here we determine the extent to which correlations between brain regions are modulated by either structural, connectomic or network-theoretic properties using a structural neuroimaging data set of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) volumes acquired from N=110 healthy human adults. To identify the linear relationships between all available pairs of regions, we use canonical correlation analysis to test whether a statistically significant correlation exists between each pair of cortical parcels as quantified via structural, connectomic or network-theoretic measures. In addition to this, we investigate (1) how each group of canonical variables (whether structural, connectomic or network-theoretic) contributes to the overall correlation and, additionally, (2) whether each individual variable makes a significant contribution to the test of the omnibus null hypothesis according to which no correlation between regions exists across subjects. We find that, although region-to-region correlations are extensively modulated by structural and connectomic measures, there are appreciable differences in how these two groups of measures drive inter-regional correlation patterns. Additionally, our results indicate that the network-theoretic properties of the cortex are strong modulators of region-to-region covariance. Our findings are useful for understanding the structural and connectomic relationship between various parts of the brain, and can inform theoretical and computational models of cortical information processing. Published by Elsevier Inc.

Design and Analysis of Complex D-Regions in Reinforced Concrete Structures

ERIC Educational Resources Information Center

Yindeesuk, Sukit

2009-01-01

STM design provisions, such as those in Appendix A of ACI318-08, consist of rules for evaluating the capacity of the load-resisting truss that is idealized to carry the forces through the D-Region. These code rules were primarily derived from test data on simple D-Regions such as deep beams and corbels. However, these STM provisions are taken as…

Dynamics of a developing economy with a remote region: Agglomeration, trade integration and trade patterns

NASA Astrophysics Data System (ADS)

Commendatore, Pasquale; Kubin, Ingrid; Sushko, Iryna

2018-05-01

We consider a three-region developing economy with poor transport infrastructures. Two models are related to different stages of development: in the first all regions are autarkic; in the second two of the regions begin to integrate with the third region still not accessible to trade. The properties of the two models are studied also considering the interplay between industry location and trade patterns. Dynamics of these models are described by two-dimensional piecewise smooth maps, characterized by multistability and complex bifurcation structure of the parameter space. We obtain analytical results related to stability of various fixed points and illustrate several bifurcation structures by means of two-dimensional bifurcation diagrams and basins of coexisting attractors.

Learning Predictive Statistics: Strategies and Brain Mechanisms.

PubMed

Wang, Rui; Shen, Yuan; Tino, Peter; Welchman, Andrew E; Kourtzi, Zoe

2017-08-30

When immersed in a new environment, we are challenged to decipher initially incomprehensible streams of sensory information. However, quite rapidly, the brain finds structure and meaning in these incoming signals, helping us to predict and prepare ourselves for future actions. This skill relies on extracting the statistics of event streams in the environment that contain regularities of variable complexity from simple repetitive patterns to complex probabilistic combinations. Here, we test the brain mechanisms that mediate our ability to adapt to the environment's statistics and predict upcoming events. By combining behavioral training and multisession fMRI in human participants (male and female), we track the corticostriatal mechanisms that mediate learning of temporal sequences as they change in structure complexity. We show that learning of predictive structures relates to individual decision strategy; that is, selecting the most probable outcome in a given context (maximizing) versus matching the exact sequence statistics. These strategies engage distinct human brain regions: maximizing engages dorsolateral prefrontal, cingulate, sensory-motor regions, and basal ganglia (dorsal caudate, putamen), whereas matching engages occipitotemporal regions (including the hippocampus) and basal ganglia (ventral caudate). Our findings provide evidence for distinct corticostriatal mechanisms that facilitate our ability to extract behaviorally relevant statistics to make predictions. SIGNIFICANCE STATEMENT Making predictions about future events relies on interpreting streams of information that may initially appear incomprehensible. Past work has studied how humans identify repetitive patterns and associative pairings. However, the natural environment contains regularities that vary in complexity from simple repetition to complex probabilistic combinations. Here, we combine behavior and multisession fMRI to track the brain mechanisms that mediate our ability to adapt to changes in the environment's statistics. We provide evidence for an alternate route for learning complex temporal statistics: extracting the most probable outcome in a given context is implemented by interactions between executive and motor corticostriatal mechanisms compared with visual corticostriatal circuits (including hippocampal cortex) that support learning of the exact temporal statistics. Copyright © 2017 Wang et al.

Structural insights into the histone H1-nucleosome complex

PubMed Central

Zhou, Bing-Rui; Feng, Hanqiao; Kato, Hidenori; Dai, Liang; Yang, Yuedong; Zhou, Yaoqi; Bai, Yawen

2013-01-01

Linker H1 histones facilitate formation of higher-order chromatin structures and play important roles in various cell functions. Despite several decades of effort, the structural basis of how H1 interacts with the nucleosome remains elusive. Here, we investigated Drosophila H1 in complex with the nucleosome, using solution nuclear magnetic resonance spectroscopy and other biophysical methods. We found that the globular domain of H1 bridges the nucleosome core and one 10-base pair linker DNA asymmetrically, with its α3 helix facing the nucleosomal DNA near the dyad axis. Two short regions in the C-terminal tail of H1 and the C-terminal tail of one of the two H2A histones are also involved in the formation of the H1–nucleosome complex. Our results lead to a residue-specific structural model for the globular domain of the Drosophila H1 in complex with the nucleosome, which is different from all previous experiment-based models and has implications for chromatin dynamics in vivo. PMID:24218562

Conserved tetramer junction in the kinetochore Ndc80 complex

PubMed Central

Valverde, Roberto; Ingram, Jessica; Harrison, Stephen C.

2016-01-01

Summary The heterotetrameric Ndc80 complex establishes connectivity along the principal longitudinal axis of a kinetochore. Its two heterodimeric subcomplexes, each with a globular end and a coiled-coil shaft, connect end-to-end to create a ∼600 Å long rod spanning the gap from centromere-proximal structures to spindle microtubules. Neither subcomplex has a known function on its own, but the heterotetrameric organization and the characteristics of the junction are conserved from yeast to man. We have determined crystal structures of two shortened (“dwarf”) Ndc80 complexes that contain the full tetramer junction and both globular ends. The junction connects two α-helical coiled coils through regions of four-chain and three-chain overlap. The complexity of its structure depends on interactions among conserved amino-acid residues, suggesting a binding site for additional cellular factor(s) not yet identified. PMID:27851957

Photoacoustic microscopy of complex regional pain syndrome type I (CRPS-1) after stellate ganglion blocks in vivo

NASA Astrophysics Data System (ADS)

Zhou, Yong; Yi, Xiaobin; Xing, Wenxin; Hu, Song; Maslov, Konstantin I.; Wang, Lihong V.

2015-03-01

We used photoacoustic microscopy (PAM) to assist diagnoses and monitor the progress and treatment outcome of complex regional pain syndrome type 1 (CRPS-1). Blood vasculature and oxygen saturation (sO2) were imaged by PAM in eight adult patients with CRPS-1. Patients' hands and cuticles were imaged both before and after stellate ganglion block (SGB) for comparison. For all patients, both the vascular structure and sO2 could be assessed by PAM. In addition, more vessels and stronger signals were observed after SGB.

X-ray superbubbles

NASA Technical Reports Server (NTRS)

Cash, W.

1983-01-01

Four regions of the galaxy, the Cygnus Superbubble, the Eta Carina complex, the Orion/Eridanus complex, and the Gum Nebula, are discussed as examples of collective effects in the interstellar medium. All four regions share certain features, indicating a common structure. The selection effects which determine the observable X-ray properties of the superbubbles are discussed, and it is demonstrated that only a very few more in our Galaxy can be detected in X rays. X-ray observation of extragalactic superbubbles is shown to be possible but requires the capabilities of a large, high quality, AXAF class observatory.

T4 AsiA blocks DNA recognition by remodeling σ70 region 4

PubMed Central

Lambert, Lester J; Wei, Yufeng; Schirf, Virgil; Demeler, Borries; Werner, Milton H

2004-01-01

Bacteriophage T4 AsiA is a versatile transcription factor capable of inhibiting host gene expression as an ‘anti-σ′ factor while simultaneously promoting gene-specific expression of T4 middle genes in conjunction with T4 MotA. To accomplish this task, AsiA engages conserved region 4 of Eschericia coli σ70, blocking recognition of most host promoters by sequestering the DNA-binding surface at the AsiA/σ70 interface. The three-dimensional structure of an AsiA/region 4 complex reveals that the C-terminal α helix of region 4 is unstructured, while four other helices adopt a completely different conformation relative to the canonical structure of unbound region 4. That AsiA induces, rather than merely stabilizes, this rearrangement can be realized by comparison to the homologous structures of region 4 solved in a variety of contexts, including the structure of Thermotoga maritima σA region 4 described herein. AsiA simultaneously occupies the surface of region 4 that ordinarily contacts core RNA polymerase (RNAP), suggesting that an AsiA-bound σ70 may also undergo conformational changes in the context of the RNAP holoenzyme. PMID:15257291

Indirect DNA Readout by an H-NS Related Protein: Structure of the DNA Complex of the C-Terminal Domain of Ler

PubMed Central

Cordeiro, Tiago N.; Schmidt, Holger; Madrid, Cristina; Juárez, Antonio; Bernadó, Pau; Griesinger, Christian; García, Jesús; Pons, Miquel

2011-01-01

Ler, a member of the H-NS protein family, is the master regulator of the LEE pathogenicity island in virulent Escherichia coli strains. Here, we determined the structure of a complex between the DNA-binding domain of Ler (CT-Ler) and a 15-mer DNA duplex. CT-Ler recognizes a preexisting structural pattern in the DNA minor groove formed by two consecutive regions which are narrower and wider, respectively, compared with standard B-DNA. The compressed region, associated with an AT-tract, is sensed by the side chain of Arg90, whose mutation abolishes the capacity of Ler to bind DNA. The expanded groove allows the approach of the loop in which Arg90 is located. This is the first report of an experimental structure of a DNA complex that includes a protein belonging to the H-NS family. The indirect readout mechanism not only explains the capacity of H-NS and other H-NS family members to modulate the expression of a large number of genes but also the origin of the specificity displayed by Ler. Our results point to a general mechanism by which horizontally acquired genes may be specifically recognized by members of the H-NS family. PMID:22114557

Indirect DNA readout by an H-NS related protein: structure of the DNA complex of the C-terminal domain of Ler.

PubMed

Cordeiro, Tiago N; Schmidt, Holger; Madrid, Cristina; Juárez, Antonio; Bernadó, Pau; Griesinger, Christian; García, Jesús; Pons, Miquel

2011-11-01

Ler, a member of the H-NS protein family, is the master regulator of the LEE pathogenicity island in virulent Escherichia coli strains. Here, we determined the structure of a complex between the DNA-binding domain of Ler (CT-Ler) and a 15-mer DNA duplex. CT-Ler recognizes a preexisting structural pattern in the DNA minor groove formed by two consecutive regions which are narrower and wider, respectively, compared with standard B-DNA. The compressed region, associated with an AT-tract, is sensed by the side chain of Arg90, whose mutation abolishes the capacity of Ler to bind DNA. The expanded groove allows the approach of the loop in which Arg90 is located. This is the first report of an experimental structure of a DNA complex that includes a protein belonging to the H-NS family. The indirect readout mechanism not only explains the capacity of H-NS and other H-NS family members to modulate the expression of a large number of genes but also the origin of the specificity displayed by Ler. Our results point to a general mechanism by which horizontally acquired genes may be specifically recognized by members of the H-NS family.

All-atom molecular dynamics simulation of a photosystem I/detergent complex

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

Harris, Bradley J.; Cheng, Xiaolin; Frymier, Paul

2014-09-18

All-atom molecular dynamics (MD) simulation was used to investigate the solution structure and dynamics of the photosynthetic pigment protein complex photosystem I (PSI) from Thermosynechococcus elongatus embedded in a toroidal belt of n-dodecyl-β-d-maltoside (DDM) detergent. Evaluation of root-mean-square deviations (RMSDs) relative to the known crystal structure show that the protein complex surrounded by DDM molecules is stable during the 200 ns simulation time, and root-mean-square fluctuation (RMSF) analysis indicates that regions of high local mobility correspond to solvent-exposed regions such as turns in the transmembrane α-helices and flexible loops on the stromal and lumenal faces. Comparing the protein detergent complexmore » to a pure detergent micelle, the detergent surrounding the PSI trimer is found to be less densely packed but with more ordered detergent tails, contrary to what is seen in most lipid bilayer models. We also investigated any functional implications for the observed conformational dynamics and protein detergent interactions, discovering interesting structural changes in the psaL subunits associated with maintaining the trimeric structure of the protein. Moreover, we find that the docking of soluble electron mediators such as cytochrome c 6 and ferredoxin to PSI is not significantly impacted by the solubilization of PSI in detergent.« less

Crystal structure of an FIV/HIV chimeric protease complexed with the broad-based inhibitor, TL-3.

PubMed

Heaslet, Holly; Lin, Ying-Chuan; Tam, Karen; Torbett, Bruce E; Elder, John H; Stout, C David

2007-01-09

We have obtained the 1.7 A crystal structure of FIV protease (PR) in which 12 critical residues around the active site have been substituted with the structurally equivalent residues of HIV PR (12X FIV PR). The chimeric PR was crystallized in complex with the broad-based inhibitor TL-3, which inhibits wild type FIV and HIV PRs, as well as 12X FIV PR and several drug-resistant HIV mutants 1234. Biochemical analyses have demonstrated that TL-3 inhibits these PRs in the order HIV PR > 12X FIV PR > FIV PR, with Ki values of 1.5 nM, 10 nM, and 41 nM, respectively 234. Comparison of the crystal structures of the TL-3 complexes of 12X FIV and wild-typeFIV PR revealed theformation of additinal van der Waals interactions between the enzyme inhibitor in the mutant PR. The 12X FIV PR retained the hydrogen bonding interactions between residues in the flap regions and active site involving the enzyme and the TL-3 inhibitor in comparison to both FIV PR and HIV PR. However, the flap regions of the 12X FIV PR more closely resemble those of HIV PR, having gained several stabilizing intra-flap interactions not present in wild type FIV PR. These findings offer a structural explanation for the observed inhibitor/substrate binding properties of the chimeric PR.

Imaging and three-dimensional reconstruction of chemical groups inside a protein complex using atomic force microscopy

NASA Astrophysics Data System (ADS)

Kim, Duckhoe; Sahin, Ozgur

2015-03-01

Scanning probe microscopes can be used to image and chemically characterize surfaces down to the atomic scale. However, the localized tip-sample interactions in scanning probe microscopes limit high-resolution images to the topmost atomic layer of surfaces, and characterizing the inner structures of materials and biomolecules is a challenge for such instruments. Here, we show that an atomic force microscope can be used to image and three-dimensionally reconstruct chemical groups inside a protein complex. We use short single-stranded DNAs as imaging labels that are linked to target regions inside a protein complex, and T-shaped atomic force microscope cantilevers functionalized with complementary probe DNAs allow the labels to be located with sequence specificity and subnanometre resolution. After measuring pairwise distances between labels, we reconstruct the three-dimensional structure formed by the target chemical groups within the protein complex using simple geometric calculations. Experiments with the biotin-streptavidin complex show that the predicted three-dimensional loci of the carboxylic acid groups of biotins are within 2 Å of their respective loci in the corresponding crystal structure, suggesting that scanning probe microscopes could complement existing structural biological techniques in solving structures that are difficult to study due to their size and complexity.

The complex between a four-way DNA junction and T7 endonuclease I

PubMed Central

Déclais, Anne-Cécile; Fogg, Jonathan M.; Freeman, Alasdair D.J.; Coste, Franck; Hadden, Jonathan M.; Phillips, Simon E.V.; Lilley, David M.J.

2003-01-01

The junction-resolving enzyme endonuclease I is selective for the structure of the DNA four-way (Holliday) junction. The enzyme binds to a four-way junction in two possible orientations, with a 4:1 ratio, opening the DNA structure at the centre and changing the global structure into a 90° cross of approximately coaxial helices. The nuclease cleaves the continuous strands of the junction in each orientation. Binding leads to pronounced regions of protection of the DNA against hydroxyl radical attack. Using all this information together with the known structure of the enzyme and the structure of the BglI–DNA complex, we have constructed a model of the complex of endonuclease I and a DNA junction. This shows how the enzyme is selective for the structure of a four-way junction, such that both continuous strands can be accommodated into the two active sites so that a productive resolution event is possible. PMID:12628932

Molecular Basis for Structural Heterogeneity of an Intrinsically Disordered Protein Bound to a Partner by Combined ESI-IM-MS and Modeling

NASA Astrophysics Data System (ADS)

D'Urzo, Annalisa; Konijnenberg, Albert; Rossetti, Giulia; Habchi, Johnny; Li, Jinyu; Carloni, Paolo; Sobott, Frank; Longhi, Sonia; Grandori, Rita

2015-03-01

Intrinsically disordered proteins (IDPs) form biologically active complexes that can retain a high degree of conformational disorder, escaping structural characterization by conventional approaches. An example is offered by the complex between the intrinsically disordered NTAIL domain and the phosphoprotein X domain (PXD) from measles virus (MeV). Here, distinct conformers of the complex are detected by electrospray ionization-mass spectrometry (ESI-MS) and ion mobility (IM) techniques yielding estimates for the solvent-accessible surface area (SASA) in solution and the average collision cross-section (CCS) in the gas phase. Computational modeling of the complex in solution, based on experimental constraints, provides atomic-resolution structural models featuring different levels of compactness. The resulting models indicate high structural heterogeneity. The intermolecular interactions are predominantly hydrophobic, not only in the ordered core of the complex, but also in the dynamic, disordered regions. Electrostatic interactions become involved in the more compact states. This system represents an illustrative example of a hydrophobic complex that could be directly detected in the gas phase by native mass spectrometry. This work represents the first attempt to modeling the entire NTAIL domain bound to PXD at atomic resolution.

Tectono-stratigraphy and low-grade metamorphism of Late Permian and Early Jurassic accretionary complexes within the Kurosegawa belt, Southwest Japan: Implications for mechanisms of crustal displacement within active continental margin

NASA Astrophysics Data System (ADS)

Hara, Hidetoshi; Kurihara, Toshiyuki; Mori, Hiroshi

2013-04-01

We characterize the tectono-stratigraphic architecture and low-grade metamorphism of the accretionary complex preserved in the Kurosegawa belt of the Kitagawa district in eastern Shikoku, Southwest Japan, in order to understand its internal structure, tectono-metamorphic evolution, and assessments of displacement of continental fragments within the complex. We report the first ever documented occurrence of an Early Jurassic radiolarian assemblage within the accretionary complex of the Kurosegawa belt that has been previously classified as the Late Permian accretionary complex, thus providing a revised age interpretation for these rocks. The accretionary complex is subdivided into four distinct tectono-stratigraphic units: Late Permian mélange and phyllite units, and Early Jurassic mélange and sandstone units. The stratigraphy of these four units is structurally repeated due to an E-W striking, steeply dipping regional fault. We characterized low-grade metamorphism of the accretionary complex via illite crystallinity and Raman spectroscopy of carbonaceous material. The estimated pattern of low-grade metamorphism showed pronounced variability within the complex and revealed no discernible spatial trends. The primary thermal structure in these rocks was overprinted by later tectonic events. Based on geological and thermal structure, we conclude that continental fragments within the Kurosegawa belt were structurally translated into both the Late Permian and Early Jurassic accretionary complexes, which comprise a highly deformed zone affected by strike-slip tectonics during the Early Cretaceous. Different models have been proposed to explain the initial structural evolution of the Kurosegawa belt (i.e., micro-continent collision and klippe tectonic models). Even if we presuppose either model, the available geological evidence requires a new interpretation, whereby primary geological structures are overprinted and reconfigured by later tectonic events.

Phosphorylation-induced conformation of β2-adrenoceptor related to arrestin recruitment revealed by NMR.

PubMed

Shiraishi, Yutaro; Natsume, Mei; Kofuku, Yutaka; Imai, Shunsuke; Nakata, Kunio; Mizukoshi, Toshimi; Ueda, Takumi; Iwaï, Hideo; Shimada, Ichio

2018-01-15

The C-terminal region of G-protein-coupled receptors (GPCRs), stimulated by agonist binding, is phosphorylated by GPCR kinases, and the phosphorylated GPCRs bind to arrestin, leading to the cellular responses. To understand the mechanism underlying the formation of the phosphorylated GPCR-arrestin complex, we performed NMR analyses of the phosphorylated β 2 -adrenoceptor (β 2 AR) and the phosphorylated β 2 AR-β-arrestin 1 complex, in the lipid bilayers of nanodisc. Here we show that the phosphorylated C-terminal region adheres to either the intracellular side of the transmembrane region or lipids, and that the phosphorylation of the C-terminal region allosterically alters the conformation around M215 5.54 and M279 6.41 , located on transemembrane helices 5 and 6, respectively. In addition, we found that the conformation induced by the phosphorylation is similar to that corresponding to the β-arrestin-bound state. The phosphorylation-induced structures revealed in this study propose a conserved structural motif of GPCRs that enables β-arrestin to recognize dozens of GPCRs.

Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization.

PubMed

Gong, Xin; Qian, Hongwu; Shao, Wei; Li, Jingxian; Wu, Jianping; Liu, Jun-Jie; Li, Wenqi; Wang, Hong-Wei; Espenshade, Peter; Yan, Nieng

2016-11-01

Sterol regulatory element-binding protein (SREBP) transcription factors are master regulators of cellular lipid homeostasis in mammals and oxygen-responsive regulators of hypoxic adaptation in fungi. SREBP C-terminus binds to the WD40 domain of SREBP cleavage-activating protein (SCAP), which confers sterol regulation by controlling the ER-to-Golgi transport of the SREBP-SCAP complex and access to the activating proteases in the Golgi. Here, we biochemically and structurally show that the carboxyl terminal domains (CTD) of Sre1 and Scp1, the fission yeast SREBP and SCAP, form a functional 4:4 oligomer and Sre1-CTD forms a dimer of dimers. The crystal structure of Sre1-CTD at 3.5 Å and cryo-EM structure of the complex at 5.4 Å together with in vitro biochemical evidence elucidate three distinct regions in Sre1-CTD required for Scp1 binding, Sre1-CTD dimerization and tetrameric formation. Finally, these structurally identified domains are validated in a cellular context, demonstrating that the proper 4:4 oligomeric complex formation is required for Sre1 activation.

A comparative study of the microstructures observed in statically cast and continuously cast Bi-In-Sn ternary eutectic alloy

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

Sengupta, S.; Soda, H.; McLean, A.

2000-01-01

A ternary eutectic alloy with a composition of 57.2 pct Bi, 24.8 pct In, and 18 pct Sn was continuously cast into wire of 2 mm diameter with casting speeds of 14 and 79 mm/min using the Ohno Continuous Casting (OCC) process. The microstructures obtained were compared with those of statically cast specimens. Extensive segregation of massive Bi blocks, Bi complex structures, and tin-rich dendrites was found in specimens that were statically cast. Decomposition of {radical}Sn by a eutectoid reaction was confirmed based on microstructural evidence. Ternary eutectic alloy with a cooling rate of approximately 1 C/min formed a doublemore » binary eutectic. The double binary eutectic consisted of regions of BiIn and decomposed {radical}Sn in the form of a dendrite cell structure and regions of Bi and decomposed {radical}Sn in the form of a complex-regular cell. The Bi complex-regular cells, which are a ternary eutectic constituent, existed either along the boundaries of the BiIn-decomposed {radical}Sn dendrite cells or at the front of elongated dendrite cell structures. In the continuously cast wires, primary Sn dendrites coupled with a small Bi phase were uniformly distributed within the Bi-In alloy matrix. Neither massive Bi phase, Bi complex-regular cells, no BiIn eutectic dendrite cells were observed, resulting in a more uniform microstructure in contrast to the heavily segregated structures of the statically cast specimens.« less

Stand and cohort structures of old-growth Pinus resinosa-dominated forests of northern Minnesota, USA

Treesearch

Shawn Fraver; Brian J. Palik

2012-01-01

The wide range of stand and age-cohort structures in these old-growth P. resinosa stands depicts pre-settlement forests more complex than those of the single-cohort, post-stand-replacing-fire model that has guided regional forest management. Within-stand patchiness of cohort age structures implies disturbances operating at scales smaller than...

Dense Regions in Supersonic Isothermal Turbulence

NASA Astrophysics Data System (ADS)

Robertson, Brant; Goldreich, Peter

2018-02-01

The properties of supersonic isothermal turbulence influence a variety of astrophysical phenomena, including the structure and evolution of star-forming clouds. This work presents a simple model for the structure of dense regions in turbulence in which the density distribution behind isothermal shocks originates from rough hydrostatic balance between the pressure gradient behind the shock and its deceleration from ram pressure applied by the background fluid. Using simulations of supersonic isothermal turbulence and idealized waves moving through a background medium, we show that the structural properties of dense, shocked regions broadly agree with our analytical model. Our work provides a new conceptual picture for describing the dense regions, which complements theoretical efforts to understand the bulk statistical properties of turbulence and attempts to model the more complex features of star-forming clouds like magnetic fields, self-gravity, or radiative properties.

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.

Complex network analysis of resting-state fMRI of the brain.

PubMed

Anwar, Abdul Rauf; Hashmy, Muhammad Yousaf; Imran, Bilal; Riaz, Muhammad Hussnain; Mehdi, Sabtain Muhammad Muntazir; Muthalib, Makii; Perrey, Stephane; Deuschl, Gunther; Groppa, Sergiu; Muthuraman, Muthuraman

2016-08-01

Due to the fact that the brain activity hardly ever diminishes in healthy individuals, analysis of resting state functionality of the brain seems pertinent. Various resting state networks are active inside the idle brain at any time. Based on various neuro-imaging studies, it is understood that various structurally distant regions of the brain could be functionally connected. Regions of the brain, that are functionally connected, during rest constitutes to the resting state network. In the present study, we employed the complex network measures to estimate the presence of community structures within a network. Such estimate is named as modularity. Instead of using a traditional correlation matrix, we used a coherence matrix taken from the causality measure between different nodes. Our results show that in prolonged resting state the modularity starts to decrease. This decrease was observed in all the resting state networks and on both sides of the brain. Our study highlights the usage of coherence matrix instead of correlation matrix for complex network analysis.

Structure-function analysis of RBP-J-interacting and tubulin-associated (RITA) reveals regions critical for repression of Notch target genes.

PubMed

Tabaja, Nassif; Yuan, Zhenyu; Oswald, Franz; Kovall, Rhett A

2017-06-23

The Notch pathway is a cell-to-cell signaling mechanism that is essential for tissue development and maintenance, and aberrant Notch signaling has been implicated in various cancers, congenital defects, and cardiovascular diseases. Notch signaling activates the expression of target genes, which are regulated by the transcription factor CSL (CBF1/RBP-J, Su(H), Lag-1). CSL interacts with both transcriptional corepressor and coactivator proteins, functioning as both a repressor and activator, respectively. Although Notch activation complexes are relatively well understood at the structural level, less is known about how CSL interacts with corepressors. Recently, a new RBP-J (mammalian CSL ortholog)-interacting protein termed RITA has been identified and shown to export RBP-J out of the nucleus, thereby leading to the down-regulation of Notch target gene expression. However, the molecular details of RBP-J/RITA interactions are unclear. Here, using a combination of biochemical/cellular, structural, and biophysical techniques, we demonstrate that endogenous RBP-J and RITA proteins interact in cells, map the binding regions necessary for RBP-J·RITA complex formation, and determine the X-ray structure of the RBP-J·RITA complex bound to DNA. To validate the structure and glean more insights into function, we tested structure-based RBP-J and RITA mutants with biochemical/cellular assays and isothermal titration calorimetry. Whereas our structural and biophysical studies demonstrate that RITA binds RBP-J similarly to the RAM (RBP-J-associated molecule) domain of Notch, our biochemical and cellular assays suggest that RITA interacts with additional regions in RBP-J. Taken together, these results provide molecular insights into the mechanism of RITA-mediated regulation of Notch signaling, contributing to our understanding of how CSL functions as a transcriptional repressor of Notch target genes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Stress- and structure-controlled anisotropy in a region of complex faulting—Yuha Desert, California

USGS Publications Warehouse

Cochran, Elizabeth S.; Kroll, Kayla A.

2015-01-01

We examine shear velocity anisotropy in the Yuha Desert, California using aftershocks of the 2010 M7.2 El Mayor-Cucapah earthquake. The Yuha Desert is underlain by a complex network of right- and left-lateral conjugate faults, some of which experienced triggered slip during the El Mayor-Cucapah earthquake. An automated method that implements multiple measurement windows and a range of bandpass filters is used to estimate the fast direction (ϕ) and delay time (δt) of the split shear waves. We find an average ϕ oriented approximately north–south suggesting it is primarily controlled by the regional maximum compressive stress direction. However, the spatial variability in ϕ reveals that the fault structures that underlie the Yuha Desert also influence the measured splitting parameters. We infer that the northeast- and northwest-oriented ϕ reflect shear fabric subparallel to the conjugate fault structures. We do not observe a simple correlation between δt and hypocentral distance. Instead, the observed spatial variation in δt suggests that near-source variation in anisotropic strength may be equal to or more important than effects local to the station. No temporal variation in splitting parameters is observed during the 70-day period following the main shock. In this region of complex faulting, we observe a spatially variable pattern of anisotropy that is both stress- and structure-controlled. This study suggests that shear fabric can form even along short, discontinuous fault strands with minimal offset.                   

Hydrothermal synthesis, crystal structure, luminescent and magnetic properties of a new mononuclear GdIII coordination complex

NASA Astrophysics Data System (ADS)

Coban, Mustafa Burak

2018-06-01

A new GdIII coordination complex, {[Gd(2-stp)2(H2O)6].2(4,4'-bipy).4(H2O)}, complex 1, (2-stp = 2-sulfoterephthalate anion and 4,4'-bipy = 4,4'-bipyridine), has been synthesized by hydrothermal method and characterized by elemental analysis, solid state UV-Vis and FT-IR spectroscopy, single-crystal X-ray diffraction, solid state photoluminescence and variable-temperature magnetic measurements. The crystal structure determination shows that GdIII ions are eight coordinated and adopt a distorted square-antiprismatic geometry. Molecules interacting through intra- and intermolecular (O-H⋯O, O-H⋯N) hydrogen bonds in complex 1, give rise to 3D hydrogen bonded structure and the discrete lattice 4,4'-bipy molecules occupy the channel of the 3D structure. π-π stacking interactions also exist 4,4'-bipy-4,4'-bipy and 4,4'-bipy-2-stp molecule rings in 3D structures. Additionally, solid state photoluminescence properties of complex 1 at room temperature have been investigated. Under the excitation of UV light (at 349 nm), the complex 1 exhibited green emissions (at 505 nm) of GdIII ion in the visible region. Furthermore, Variable-temperature magnetic susceptibility and isothermal magnetization as function of external magnetic field studies reveal that complex 1 displays possible antiferromagnetic interaction.

Identifying structural styles in Colombia

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

Wilson, W.P.; Van Nieuwenhuise, R.E.; Steuer, M.R.

1996-08-01

Much of our understanding of the Earth is from the study of surface geology and seismic, but many surface structures are responses to deformation which occurred below sedimentary layers. The practice within the petroleum industry is to use top-down processes of analyzing the surface to understand the subsurface, and observed surface structural styles tend to influence seismic interpretations. Yet many conditions which influenced the structural styles seen at the surface are different at depth. Since seismic is a time representation of the Earth, many interpretation pitfalls may exist within areas of complex geology. Also, its reliability decreases with depth andmore » with increasing geologic complexity. Forward modeling and pre-stack depth migration technologies are used to provide true depth images of the seismic data. Even with these advances in seismic imaging technology, the interpreter needs to incorporate additional data into the interpretation. Accurate structural identification requires the interpreter to integrate seismic with surface geology, remote sensing, gravity, magnetic data, geochemistry, fault-plane solutions from earthquakes, and regional tectonic studies. Incorporating these types of data into the interpretation will help us learn how basement is involved in the deformation of overlying sediments. A study of the Eastern Cordillera of Colombia shows the deformation to be dominantly transpressional in style. Euler deconvolution of the areomagnetic data shows a highly fractured basement, steep fault lineaments, en echelon structures, and complex fault patterns, all of which would be typical of wrench-type deformation. Available surface geology, regional studies, earthquake data, and forward modeling support this interpretation.« less

X-ray Intermolecular Structure Factor (XISF): separation of intra- and intermolecular interactions from total X-ray scattering data

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

Mou, Q.; Benmore, C. J.; Yarger, J. L.

2015-06-01

XISF is a MATLAB program developed to separate intermolecular structure factors from total X-ray scattering structure factors for molecular liquids and amorphous solids. The program is built on a trust-region-reflective optimization routine with the r.m.s. deviations of atoms physically constrained. XISF has been optimized for performance and can separate intermolecular structure factors of complex molecules.

X-ray Intermolecular Structure Factor ( XISF ): separation of intra- and intermolecular interactions from total X-ray scattering data

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

Mou, Q.; Benmore, C. J.; Yarger, J. L.

2015-05-09

XISFis a MATLAB program developed to separate intermolecular structure factors from total X-ray scattering structure factors for molecular liquids and amorphous solids. The program is built on a trust-region-reflective optimization routine with the r.m.s. deviations of atoms physically constrained.XISFhas been optimized for performance and can separate intermolecular structure factors of complex molecules.

Collagen Organization in Facet Capsular Ligaments Varies With Spinal Region and With Ligament Deformation.

PubMed

Ban, Ehsan; Zhang, Sijia; Zarei, Vahhab; Barocas, Victor H; Winkelstein, Beth A; Picu, Catalin R

2017-07-01

The spinal facet capsular ligament (FCL) is primarily comprised of heterogeneous arrangements of collagen fibers. This complex fibrous structure and its evolution under loading play a critical role in determining the mechanical behavior of the FCL. A lack of analytical tools to characterize the spatial anisotropy and heterogeneity of the FCL's microstructure has limited the current understanding of its structure-function relationships. Here, the collagen organization was characterized using spatial correlation analysis of the FCL's optically obtained fiber orientation field. FCLs from the cervical and lumbar spinal regions were characterized in terms of their structure, as was the reorganization of collagen in stretched cervical FCLs. Higher degrees of intra- and intersample heterogeneity were found in cervical FCLs than in lumbar specimens. In the cervical FCLs, heterogeneity was manifested in the form of curvy patterns formed by collections of collagen fibers or fiber bundles. Tensile stretch, a common injury mechanism for the cervical FCL, significantly increased the spatial correlation length in the stretch direction, indicating an elongation of the observed structural features. Finally, an affine estimation for the change of correlation length under loading was performed which gave predictions very similar to the actual values. These findings provide structural insights for multiscale mechanical analyses of the FCLs from various spinal regions and also suggest methods for quantitative characterization of complex tissue patterns.

Variation of telencephalon morphology of the threespine stickleback (Gasterosteus aculeatus) in relation to inferred ecology.

PubMed

Park, Peter J; Bell, M A

2010-06-01

We tested the hypothesis that increased telencephalon size has evolved in threespine stickleback fish (Gasterosteus aculeatus) from structurally complex habitats using field-caught samples from one sea-run (ancestral) and 18 ecologically diverse freshwater (descendant) populations. Freshwater habitats ranged from shallow, structurally complex lakes with benthic-foraging stickleback (benthics), to deeper, structurally simple lakes in which stickleback depend more heavily on plankton for prey (generalists). Contrary to our expectations, benthics had smaller telencephala than generalists, but the shape of the telencephalon of the sea-run and benthic populations were more convex laterally. Convex telencephalon shape may indicate enlargement of the dorsolateral region, which is homologous with the tetrapod hippocampus. Telencephalon morphology is also sexually dimorphic, with larger, less convex telencephala in males. Freshwater stickleback from structurally complex habitats have retained the ancestral telencephalon morphology, but populations that feed more in open habitats on plankton have evolved larger, laterally concave telencephala.

Structure of the Rigor Actin-Tropomyosin-Myosin Complex

PubMed Central

Behrmann, Elmar; Müller, Mirco; Penczek, Pawel A.; Mannherz, Hans Georg; Manstein, Dietmar J.; Raunser, Stefan

2014-01-01

The interaction of myosin with actin filaments is the central feature of muscle contraction and cargo movement along actin filaments of the cytoskeleton. Myosin converts the chemical energy stored in ATP into force and movement along actin filaments. Myosin binding to actin induces conformational changes that are coupled to the nucleotide-binding pocket and amplified by a specialized region of the motor domain for efficient force generation. Tropomyosin plays a key role in regulating the productive interaction between myosins and actin. Here, we report the 8 Å resolution structure of the actin-tropomyosin-myosin complex determined by cryo electron microscopy. The pseudo-atomic model of the complex obtained from fitting crystal structures into the map defines the large actin-myosin-tropomyosin interface and the molecular interactions between the proteins in detail and allows us to propose a structural model for tropomyosin dependent myosin binding to actin and actin-induced nucleotide release from myosin. PMID:22817895

Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration.

PubMed

Matysiak, Julien; Lesbats, Paul; Mauro, Eric; Lapaillerie, Delphine; Dupuy, Jean-William; Lopez, Angelica P; Benleulmi, Mohamed Salah; Calmels, Christina; Andreola, Marie-Line; Ruff, Marc; Llano, Manuel; Delelis, Olivier; Lavigne, Marc; Parissi, Vincent

2017-07-28

Insertion of retroviral genome DNA occurs in the chromatin of the host cell. This step is modulated by chromatin structure as nucleosomes compaction was shown to prevent HIV-1 integration and chromatin remodeling has been reported to affect integration efficiency. LEDGF/p75-mediated targeting of the integration complex toward RNA polymerase II (polII) transcribed regions ensures optimal access to dynamic regions that are suitable for integration. Consequently, we have investigated the involvement of polII-associated factors in the regulation of HIV-1 integration. Using a pull down approach coupled with mass spectrometry, we have selected the FACT (FAcilitates Chromatin Transcription) complex as a new potential cofactor of HIV-1 integration. FACT is a histone chaperone complex associated with the polII transcription machinery and recently shown to bind LEDGF/p75. We report here that a tripartite complex can be formed between HIV-1 integrase, LEDGF/p75 and FACT in vitro and in cells. Biochemical analyzes show that FACT-dependent nucleosome disassembly promotes HIV-1 integration into chromatinized templates, and generates highly favored nucleosomal structures in vitro. This effect was found to be amplified by LEDGF/p75. Promotion of this FACT-mediated chromatin remodeling in cells both increases chromatin accessibility and stimulates HIV-1 infectivity and integration. Altogether, our data indicate that FACT regulates HIV-1 integration by inducing local nucleosomes dissociation that modulates the functional association between the incoming intasome and the targeted nucleosome.

Decreased centrality of cortical volume covariance networks in autism spectrum disorders.

PubMed

Balardin, Joana Bisol; Comfort, William Edgar; Daly, Eileen; Murphy, Clodagh; Andrews, Derek; Murphy, Declan G M; Ecker, Christine; Sato, João Ricardo

2015-10-01

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions characterized by atypical structural and functional brain connectivity. Complex network analysis has been mainly used to describe altered network-level organization for functional systems and white matter tracts in ASD. However, atypical functional and structural connectivity are likely to be also linked to abnormal development of the correlated structure of cortical gray matter. Such covariations of gray matter are particularly well suited to the investigation of the complex cortical pathology of ASD, which is not confined to isolated brain regions but instead acts at the systems level. In this study, we examined network centrality properties of gray matter networks in adults with ASD (n = 84) and neurotypical controls (n = 84) using graph theoretical analysis. We derived a structural covariance network for each group using interregional correlation matrices of cortical volumes extracted from a surface-based parcellation scheme containing 68 cortical regions. Differences between groups in closeness network centrality measures were evaluated using permutation testing. We identified several brain regions in the medial frontal, parietal and temporo-occipital cortices with reductions in closeness centrality in ASD compared to controls. We also found an association between an increased number of autistic traits and reduced centrality of visual nodes in neurotypicals. Our study shows that ASD are accompanied by atypical organization of structural covariance networks by means of a decreased centrality of regions relevant for social and sensorimotor processing. These findings provide further evidence for the altered network-level connectivity model of ASD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aberrant Global and Regional Topological Organization of the Fractional Anisotropy-weighted Brain Structural Networks in Major Depressive Disorder

PubMed Central

Chen, Jian-Huai; Yao, Zhi-Jian; Qin, Jiao-Long; Yan, Rui; Hua, Ling-Ling; Lu, Qing

2016-01-01

Background: Most previous neuroimaging studies have focused on the structural and functional abnormalities of local brain regions in major depressive disorder (MDD). Moreover, the exactly topological organization of networks underlying MDD remains unclear. This study examined the aberrant global and regional topological patterns of the brain white matter networks in MDD patients. Methods: The diffusion tensor imaging data were obtained from 27 patients with MDD and 40 healthy controls. The brain fractional anisotropy-weighted structural networks were constructed, and the global network and regional nodal metrics of the networks were explored by the complex network theory. Results: Compared with the healthy controls, the brain structural network of MDD patients showed an intact small-world topology, but significantly abnormal global network topological organization and regional nodal characteristic of the network in MDD were found. Our findings also indicated that the brain structural networks in MDD patients become a less strongly integrated network with a reduced central role of some key brain regions. Conclusions: All these resulted in a less optimal topological organization of networks underlying MDD patients, including an impaired capability of local information processing, reduced centrality of some brain regions and limited capacity to integrate information across different regions. Thus, these global network and regional node-level aberrations might contribute to understanding the pathogenesis of MDD from the view of the brain network. PMID:26960371

The characteristics of dissolved organic matter (DOM) in storm sewer sediments and the binding interaction with Cu(II) in four typical regions in Beijing, China.

PubMed

Zhang, Ziyang; Li, Kun; Zhang, Xiaoran; Li, Haiyan

2017-07-01

In this work, dissolved organic matter (DOM) was extracted from storm sewer sediments collected in four typical regions (residential, campus, traffic and business regions) in Beijing, China. The basic characteristics of DOM were analyzed by UV-visible spectroscopy (UV-Vis), excitation-emission matrix Fluorescence Spectroscopy and Fourier Transform Infrared Spectroscopy. Furthermore, the complexation between DOM and Cu(II) were investigated. The results showed that there were large amount of aromatic structure in the DOM extracted from storm sewer sediments. The microbial activities had also made a contribution to the DOM in storm sewer sediments. The composition of DOM influenced the complexing capacity of Cu(II) greatly, which may be attributed to the protein-like and humic-like substances in storm sewer sediments. This study demonstrated valuable information on the structure present in the DOM of storm sewer sediments and provided new insight for exploring the relationship between DOM and co-existing heavy metals in storm sewer sediments.

Probing the Energetics of Dynactin Filament Assembly and the Binding of Cargo Adaptor Proteins Using Molecular Dynamics Simulation and Electrostatics-Based Structural Modeling.

PubMed

Zheng, Wenjun

2017-01-10

Dynactin, a large multiprotein complex, binds with the cytoplasmic dynein-1 motor and various adaptor proteins to allow recruitment and transportation of cellular cargoes toward the minus end of microtubules. The structure of the dynactin complex is built around an actin-like minifilament with a defined length, which has been visualized in a high-resolution structure of the dynactin filament determined by cryo-electron microscopy (cryo-EM). To understand the energetic basis of dynactin filament assembly, we used molecular dynamics simulation to probe the intersubunit interactions among the actin-like proteins, various capping proteins, and four extended regions of the dynactin shoulder. Our simulations revealed stronger intersubunit interactions at the barbed and pointed ends of the filament and involving the extended regions (compared with the interactions within the filament), which may energetically drive filament termination by the capping proteins and recruitment of the actin-like proteins by the extended regions, two key features of the dynactin filament assembly process. Next, we modeled the unknown binding configuration among dynactin, dynein tails, and a number of coiled-coil adaptor proteins (including several Bicaudal-D and related proteins and three HOOK proteins), and predicted a key set of charged residues involved in their electrostatic interactions. Our modeling is consistent with previous findings of conserved regions, functional sites, and disease mutations in the adaptor proteins and will provide a structural framework for future functional and mutational studies of these adaptor proteins. In sum, this study yielded rich structural and energetic information about dynactin and associated adaptor proteins that cannot be directly obtained from the cryo-EM structures with limited resolutions.

Divergent population structure and climate associations of a chromosomal inversion polymorphism across the Mimulus guttatus species complex

PubMed Central

Oneal, Elen; Lowry, David B.; Wright, Kevin M.; Zhu, Zhirui; Willis, John H.

2014-01-01

Chromosomal rearrangement polymorphisms are common and increasingly found to be associated with adaptive ecological divergence and speciation. Rearrangements, such as inversions, reduce recombination in heterozygous individuals and thus can protect favourable allelic combinations at linked loci, facilitating their spread in the presence of gene flow. Recently, we identified a chromosomal inversion polymorphism that contributes to ecological adaptation and reproductive isolation between annual and perennial ecotypes of the yellow monkeyflower, Mimulus guttatus. Here we evaluate the population genetic structure of this inverted region in comparison with the collinear regions of the genome across the M. guttatus species complex. We tested whether annual and perennial M. guttatus exhibit different patterns of divergence for loci in the inverted and noninverted regions of the genome. We then evaluated whether there are contrasting climate associations with these genomic regions through redundancy analysis. We found that the inversion exhibits broadly different patterns of divergence among annual and perennial M. guttatus and is associated with environmental variation across population accessions. This study is the first widespread population genetic survey of the diversity of the M. guttatus species complex. Our findings contribute to a greater understanding of morphological, ecological, and genetic evolutionary divergence across this highly diverse group of closely related ecotypes and species. Finally, understanding species relationships among M. guttatus sp. has hitherto been stymied by accumulated evidence of substantial gene flow among populations as well as designated species. Nevertheless, our results shed light on these relationships and provide insight into adaptation in life history traits within the complex. PMID:24796267

Identification of the interaction region between hemagglutinin components of the botulinum toxin complex.

PubMed

Suzuki, Tomonori; Miyashita, Shin-Ichiro; Hayashi, Shintaro; Miyata, Keita; Inui, Ken; Kondo, Yosuke; Miyazaki, Satoru; Ohyama, Tohru; Niwa, Koichi; Watanabe, Toshihiro; Sagane, Yoshimasa

2014-04-01

The large toxin complex (L-TC) produced by Clostridium botulinum is formed from the M-TC (BoNT/NTNHA complex) by conjugation of M-TC with HA-33/HA-17 trimer consists of two HA-33 proteins and a single HA-17 protein. This association is mediated by HA-70, which interacts with HA-17. The current study aims to identify the regions of the HA-70 molecule that adhere to the HA-33/HA-17 complex. Products from limited proteolysis of HA-70 were resolved by SDS-PAGE and transferred onto PVDF membranes, where they were probed with HA-33/HA-17 in a far-western blot. Among the HA-70 fragments, HA-33/HA-17 bound to those containing at least the C-terminal half of the HA-70 molecule, but not those carrying the N-terminal half. Additional docking simulation analysis indicated that the HA-70 region Gln420-Tyr575 is responsible for binding to HA-17, which is consistent with the far-western blot data. The findings here reveal additional details concerning the three-dimensional structure of the functional HA sub-complex in the botulinum toxin complex. Copyright © 2014 Elsevier B.V. All rights reserved.

Mesozoic Crustal Thickening of the Longmenshan Belt (NE Tibet, China) by Imbrication of Basement Slices: Insights From Structural Analysis, Petrofabric and Magnetic Fabric Studies, and Gravity Modeling

NASA Astrophysics Data System (ADS)

Xue, Zhenhua; Martelet, Guillaume; Lin, Wei; Faure, Michel; Chen, Yan; Wei, Wei; Li, Shuangjian; Wang, Qingchen

2017-12-01

This work first presents field structural analysis, anisotropy of magnetic susceptibility (AMS) measurements, and kinematic and microstructural studies on the Neoproterozoic Pengguan complex located in the middle segment of the Longmenshan thrust belt (LMTB), NE Tibet. These investigations indicate that the Pengguan complex is a heterogeneous unit with a ductilely deformed NW domain and an undeformed SE domain, rather than a single homogeneous body as previously thought. The NW part of the Pengguan complex is constrained by top-to-the-NW shearing along its NW boundary and top-to-the-SE shearing along its SE boundary, where it imbricates and overrides the SE domain. Two orogen-perpendicular gravity models not only support the imbricated shape of the Pengguan complex but also reveal an imbrication of high-density material hidden below the Paleozoic rocks on the west of the LMTB. Regionally, this suggests a basement-slice-imbricated structure that developed along the margin of the Yangtze Block, as shown by the regional gravity anomaly map, together with the published nearby seismic profile and the distribution of orogen-parallel Neoproterozoic complexes. Integrating the previously published ages of the NW normal faulting and of the SE directed thrusting, the locally fast exhumation rate, and the lithological characteristics of the sediments in the LMTB front, we interpret the basement-slice-imbricated structure as the result of southeastward thrusting of the basement slices during the Late Jurassic-Early Cretaceous. This architecture makes a significant contribution to the crustal thickening of the LMTB during the Mesozoic, and therefore, the Cenozoic thickening of the Longmenshan belt might be less important than often suggested.

The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation

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

Xu, Kai; Olsen, Olav; Tzvetkova-Robev, Dorothea

The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6 ectodomain in complex with the E2 domain of APP and show that it supports a model for APP-induced dimerization and activation of cell surface DR6.

The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation

DOE PAGES

Xu, Kai; Olsen, Olav; Tzvetkova-Robev, Dorothea; ...

2015-04-02

The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6 ectodomain in complex with the E2 domain of APP and show that it supports a model for APP-induced dimerization and activation of cell surface DR6.

Structural basis for recognition of the central conserved region of RSV G by neutralizing human antibodies.

PubMed

Jones, Harrison G; Ritschel, Tina; Pascual, Gabriel; Brakenhoff, Just P J; Keogh, Elissa; Furmanova-Hollenstein, Polina; Lanckacker, Ellen; Wadia, Jehangir S; Gilman, Morgan S A; Williamson, R Anthony; Roymans, Dirk; van 't Wout, Angélique B; Langedijk, Johannes P; McLellan, Jason S

2018-03-01

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants and the elderly, and yet there remains no effective treatment or vaccine. The surface of the virion is decorated with the fusion glycoprotein (RSV F) and the attachment glycoprotein (RSV G), which binds to CX3CR1 on human airway epithelial cells to mediate viral attachment and subsequent infection. RSV G is a major target of the humoral immune response, and antibodies that target the central conserved region of G have been shown to neutralize both subtypes of RSV and to protect against severe RSV disease in animal models. However, the molecular underpinnings for antibody recognition of this region have remained unknown. Therefore, we isolated two human antibodies directed against the central conserved region of RSV G and demonstrated that they neutralize RSV infection of human bronchial epithelial cell cultures in the absence of complement. Moreover, the antibodies protected cotton rats from severe RSV disease. Both antibodies bound with high affinity to a secreted form of RSV G as well as to a peptide corresponding to the unglycosylated central conserved region. High-resolution crystal structures of each antibody in complex with the G peptide revealed two distinct conformational epitopes that require proper folding of the cystine noose located in the C-terminal part of the central conserved region. Comparison of these structures with the structure of fractalkine (CX3CL1) alone or in complex with a viral homolog of CX3CR1 (US28) suggests that RSV G would bind to CX3CR1 in a mode that is distinct from that of fractalkine. Collectively, these results build on recent studies demonstrating the importance of RSV G in antibody-mediated protection from severe RSV disease, and the structural information presented here should guide the development of new vaccines and antibody-based therapies for RSV.

Structural basis for recognition of the central conserved region of RSV G by neutralizing human antibodies

PubMed Central

Jones, Harrison G.; Brakenhoff, Just P. J.; Furmanova-Hollenstein, Polina; Wadia, Jehangir S.; Gilman, Morgan S. A.; Roymans, Dirk

2018-01-01

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants and the elderly, and yet there remains no effective treatment or vaccine. The surface of the virion is decorated with the fusion glycoprotein (RSV F) and the attachment glycoprotein (RSV G), which binds to CX3CR1 on human airway epithelial cells to mediate viral attachment and subsequent infection. RSV G is a major target of the humoral immune response, and antibodies that target the central conserved region of G have been shown to neutralize both subtypes of RSV and to protect against severe RSV disease in animal models. However, the molecular underpinnings for antibody recognition of this region have remained unknown. Therefore, we isolated two human antibodies directed against the central conserved region of RSV G and demonstrated that they neutralize RSV infection of human bronchial epithelial cell cultures in the absence of complement. Moreover, the antibodies protected cotton rats from severe RSV disease. Both antibodies bound with high affinity to a secreted form of RSV G as well as to a peptide corresponding to the unglycosylated central conserved region. High-resolution crystal structures of each antibody in complex with the G peptide revealed two distinct conformational epitopes that require proper folding of the cystine noose located in the C-terminal part of the central conserved region. Comparison of these structures with the structure of fractalkine (CX3CL1) alone or in complex with a viral homolog of CX3CR1 (US28) suggests that RSV G would bind to CX3CR1 in a mode that is distinct from that of fractalkine. Collectively, these results build on recent studies demonstrating the importance of RSV G in antibody-mediated protection from severe RSV disease, and the structural information presented here should guide the development of new vaccines and antibody-based therapies for RSV. PMID:29509814

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

Benioff, Paul

This paper describes the effects of a complex scalar scaling field on quantum mechanics. The field origin is an extension of the gauge freedom for basis choice in gauge theories to the underlying scalar field. The extension is based on the idea that the value of a number at one space time point does not determine the value at another point. This, combined with the description of mathematical systems as structures of different types, results in the presence of separate number fields and vector spaces as structures, at different space time locations. Complex number structures and vector spaces at eachmore » location are scaled by a complex space time dependent scaling factor. The effect of this scaling factor on several physical and geometric quantities has been described in other work. Here the emphasis is on quantum mechanics of one and two particles, their states and properties. Multiparticle states are also briefly described. The effect shows as a complex, nonunitary, scalar field connection on a fiber bundle description of nonrelativistic quantum mechanics. Here, the lack of physical evidence for the presence of this field so far means that the coupling constant of this field to fermions is very small. It also means that the gradient of the field must be very small in a local region of cosmological space and time. Outside this region, there are no restrictions on the field gradient.« less

Effects of a scalar scaling field on quantum mechanics

DOE PAGES

Benioff, Paul

2016-04-18

This paper describes the effects of a complex scalar scaling field on quantum mechanics. The field origin is an extension of the gauge freedom for basis choice in gauge theories to the underlying scalar field. The extension is based on the idea that the value of a number at one space time point does not determine the value at another point. This, combined with the description of mathematical systems as structures of different types, results in the presence of separate number fields and vector spaces as structures, at different space time locations. Complex number structures and vector spaces at eachmore » location are scaled by a complex space time dependent scaling factor. The effect of this scaling factor on several physical and geometric quantities has been described in other work. Here the emphasis is on quantum mechanics of one and two particles, their states and properties. Multiparticle states are also briefly described. The effect shows as a complex, nonunitary, scalar field connection on a fiber bundle description of nonrelativistic quantum mechanics. Here, the lack of physical evidence for the presence of this field so far means that the coupling constant of this field to fermions is very small. It also means that the gradient of the field must be very small in a local region of cosmological space and time. Outside this region, there are no restrictions on the field gradient.« less

Structural brain aging and speech production: a surface-based brain morphometry study.

PubMed

Tremblay, Pascale; Deschamps, Isabelle

2016-07-01

While there has been a growing number of studies examining the neurofunctional correlates of speech production over the past decade, the neurostructural correlates of this immensely important human behaviour remain less well understood, despite the fact that previous studies have established links between brain structure and behaviour, including speech and language. In the present study, we thus examined, for the first time, the relationship between surface-based cortical thickness (CT) and three different behavioural indexes of sublexical speech production: response duration, reaction times and articulatory accuracy, in healthy young and older adults during the production of simple and complex meaningless sequences of syllables (e.g., /pa-pa-pa/ vs. /pa-ta-ka/). The results show that each behavioural speech measure was sensitive to the complexity of the sequences, as indicated by slower reaction times, longer response durations and decreased articulatory accuracy in both groups for the complex sequences. Older adults produced longer speech responses, particularly during the production of complex sequence. Unique age-independent and age-dependent relationships between brain structure and each of these behavioural measures were found in several cortical and subcortical regions known for their involvement in speech production, including the bilateral anterior insula, the left primary motor area, the rostral supramarginal gyrus, the right inferior frontal sulcus, the bilateral putamen and caudate, and in some region less typically associated with speech production, such as the posterior cingulate cortex.

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

Chrencik, Jill E.; Orans, Jillian; Moore, Linda B.

The human nuclear xenobiotic receptor, pregnane X receptor (PXR), detects a variety of structurally distinct endogenous and xenobiotic compounds and controls expression of genes central to drug and cholesterol metabolism. The macrolide antibiotic rifampicin, a front-line treatment for tuberculosis, is an established PXR agonist and, at 823 Da, is one of the largest known ligands for the receptor. We present the 2.8 {angstrom} crystal structure of the ligand-binding domain of human PXR in complex with rifampicin. We also use structural and mutagenesis data to examine the origins of the directed promiscuity exhibited by the PXRs across species. Three structurally flexiblemore » loops adjacent to the ligand-binding pocket of PXR are disordered in this crystal structure, including the 200-210 region that is part of a sequence insert novel to the promiscuous PXRs relative to other members of the nuclear receptor superfamily. The 4-methyl-1-piperazinyl ring of rifampicin, which would lie adjacent to the disordered protein regions, is also disordered and not observed in the structure. Taken together, our results indicate that one wall of the PXR ligand-binding cavity can remain flexible even when the receptor is in complex with an activating ligand. These observations highlight the key role that structural flexibility plays in PXR's promiscuous response to xenobiotics.« less

A Quantitative Measure of Conformational Changes in Apo, Holo and Ligand-Bound Forms of Enzymes.

PubMed

Singh, Satendra; Singh, Atul Kumar; Wadhwa, Gulshan; Singh, Dev Bukhsh; Dwivedi, Seema; Gautam, Budhayash; Ramteke, Pramod W

2016-06-01

Determination of the native geometry of the enzymes and ligand complexes is a key step in the process of structure-based drug designing. Enzymes and ligands show flexibility in structural behavior as they come in contact with each other. When ligand binds with active site of the enzyme, in the presence of cofactor some structural changes are expected to occur in the active site. Motivation behind this study is to determine the nature of conformational changes as well as regions where such changes are more pronounced. To measure the structural changes due to cofactor and ligand complex, enzyme in apo, holo and ligand-bound forms is selected. Enzyme data set was retrieved from protein data bank. Fifteen triplet groups were selected for the analysis of structural changes based on selection criteria. Structural features for selected enzymes were compared at the global as well as local region. Accessible surface area for the enzymes in entire triplet set was calculated, which describes the change in accessible surface area upon binding of cofactor and ligand with the enzyme. It was observed that some structural changes take place during binding of ligand in the presence of cofactor. This study will helps in understanding the level of flexibility in protein-ligand interaction for computer-aided drug designing.

Analysis of magnetotelluric profile data from the Ruby Mountains metamorphic core complex and southern Carlin Trend region, Nevada

USGS Publications Warehouse

Wannamaker, Philip E.; Doerner, William M.; Stodt, John A.; Sodergen, Timothy L.; Rodriguez, Brian D.

2002-01-01

We have collected about 150 magnetotelluric (MT) soundings in northeastern Nevada in the region of the Ruby Mountains metamorphic core complex uplift and southern Carlin mineral trend, in an effort to illuminate controls on core complex evolution and deposition of world-class gold deposits. The region has experienced a broad range of tectonic events including several periods of compressional and extensional deformation, which have contributed to the total expression of electrical resistivity. Most of the soundings are in three east-west profiles across increasing degrees of core uplift to the north (Bald Mountain, Harrison Pass and Secret Pass latitudes). Two shorter lines cross a prominent east-west structure to the north of the northern profile. MT impedance tensor and vertical magnetic field rotations imply a N-NNE average regional geoelectric strike, similar to surface geologic trends. Model resistivity cross sections were derived using a 2-D inversion algorithm, which damps departures of model parameters from an a priori structure, emphasizing the transverse magnetic (TM) mode and vertical magnetic field data. Geological interpretation of the resistivity combines previous seismic, potential field and isotope models, structural and petrological models for regional compression and extension, and detailed structural/stratigraphic interpretations incorporating drilling for petroleum and mineral exploration. To first order, the resistivity structure is one of a moderately conductive, Phanerozoic sedimentary section fundamentally disrupted by intrusion and uplift of resistive crystalline rocks. Late Devonian and early Mississippian shales of the Pilot and Chainman Formations together form an important conductive marker sequence in the stratigraphy and show pronounced increases in conductance (conductivity-thickness product) from east to west. These increases in conductance are attributed to graphitization caused by Elko-Sevier era compressional shear deformation and possibly by intrusive heating. The resistive crystalline central massifs adjoin the host stratigraphy across crustal-scale, subvertical fault zones. These zones provide electric current pathways to the lower crust for heterogeneous, upper crustal induced current flow. Resistive core complex crust may be steeply bounded under the middle of the neighboring grabens and not deepen at a shallow angle to arbitrary distances to the west. The numerous crustal breaks imaged with MT may contribute to the low effective elastic thickness estimated regionally for the Great Basin and exemplify the mid-crustal, steeply dipping slip zones in which major earthquakes nucleate. An east-west oriented conductor in the crystalline upper crust spans the East Humboldt Range and northern Ruby Mountains. The conductor may be related to an inferred ArcheanProterozoic suture or nearby graphitic metasediments, with possible alteration by middle Tertiary magmatic activity. Lower crustal resistivity everywhere under the profiles is low and appears quasi one-dimensional. It is consistent with a low rock porosity (

Studies of the nucleon structure in back-to-back SIDIS

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

Avakian, Harut

2016-03-01

The Deep Inelastic Scattering (DIS) proved to be a great tool in testing of the theory of strong interactions, which was a major focus in last decades. Semi-Inclusive DIS (SIDIS), with detection of an additional hadron allowed first studies of 3D structure of the nucleon, moving the main focus from testing the QCD to understanding of strong interactions and quark gluon dynamics to address a number of puzzles accumulated in recent years. Detection of two hadrons in SIDIS, which is even more complicated, provides access to details of quark gluon interactions inaccessible in single-hadron SIDIS, providing a new avenue tomore » study the complex nucleon structure. Large acceptance of the Electron Ion Collider, allowing detection of two hadrons, produced back-to-back in the current and target fragmentation regions, combined with clear separation of two regions, would provide a unique possibility to study the nucleon structure in target fragmentation region, and correlations of target and current fragmentation regions.« less

Seafloor morphology in the different domains of the Calabrian Arc subduction complex - Ionian Sea

NASA Astrophysics Data System (ADS)

Riminucci, F.; Polonia, A.; Torelli, L.; Mussoni, P.

2010-05-01

The Calabrian Arc (CA) is a subduction system that develops along the African-Eurasian plate boundary in the Ionian Sea and connects the E-W trending Sicilian Maghrebian belt with the NW-SE trending Southern Apennines. The first systematic geophysical investigation in the offshore region of the CA was conducted during the 70's by the Institute of Marine Geology (now ISMAR) with the R/V 'Bannock' [1]. In the last 30 years, further geophysical data (high penetration multichannel seismics, CHIRP and multibeam data) has been acquired in the offshore of the CA, down to the Ionian Abyssal Plain. The integrated interpretation of the existing geophysical data [2] has outlined the regional architecture of the subduction complex, the main tectonic features absorbing plate motion and variation of seafloor morphology in the different structural domains. Pre-stack depth migrated seismic profiles has revealed that the accretionary complex is constituted by two distinct wedges whose geometry, structural style and seafloor morphology widely vary. The outermost accretionary wedge has been emplaced in post-messinian times. It is a salt-bearing complex as pointed out by the internal structure of the wedge (acoustically transparent assemblage), very low taper angle and high seismic velocities. The seafloor shows a rough morphology, short wavelength folds and depressions superimposed on a rather constant gentle regional slope. Landward of the outer wedge, the evaporites are no longer present and the transition to the clastic rock assemblage is reflected in a different structural architecture, which shows steeper slopes and a succession of topographic scarps separated by sedimentary basins and mid slope terraces. The topographic scarps are controlled in depth by a series of high angle landward dipping reflectors, that we interpreted as out of sequence thrust faults absorbing shortening at the rear of the wedge. Landward of the inner wedge a mid slope terrace develops (inner plateau) between 1300 and 1600 m water depth. It is a relatively flat area of variable width ranging from 10 to 50 Km, represented by the forearc basin and the innermost accretionary wedge. Seafloor morphology is related to small undulation of the seafloor. A thick section of Plio-Quaternary and Messinian sediments is present below the flat terrace. Sediments appear to be folded and, in some regions highly disrupted along local sub-circular structures that affect the seafloor morphology as well. Geometry and seismic facies of these sub-circular swells rising from the surrounding suggest they are diapiric structures. Variation of seafloor morphology is strictly related to the progression of structural domains within the Calabrian Arc subduction complex. The integrated analysis of seafloor morphology and structural style through an integrated approach involving the interpretation of seismic data at different scales has been carried out in order to outline relationships between shallow tectonic processes and deep structures. Moreover, the analysis of morphobathymetric and seismic data, combined with well targeted sediment samples has the potential to reveal relationships between tectonics, sedimentation and fluid flow in the different portions of the accretionary wedge. References: 1 - Rossi S., Sartori R. 1981. A seismic reflection study of the External Calabrian Arc in the Northern Ionian Sea (Eastern Mediterranean). Marine Geoph. Res., 4, 403-426. 2 - Polonia A. et al., The Calabrian Arc subduction complex: plate convergence, active faults, and mud diapirism. New results from the CALAMARE-2008 cruise (N/R CNR Urania). Submitted to G3.

Kinematic structure of the 30 Doradus giant H II region

NASA Technical Reports Server (NTRS)

Chu, You-Hua; Kennicutt, Robert C., Jr.

1994-01-01

We have used the echelle CCD spectrograph on the Cerro Tololo Inter-American Observatory (CTIO) 4 m telescope to map the nebular velocity field in the 30 Doradus giant H II region. The kinematics of 30 Dor are very complex. The outer regions are charaterized by a smooth velocity field, but its turbulent velocity, 30-40 km/s Full Width Half Maximum (FWHM), is considerably higher than those in most smaller H II regions. In the central 9 min core, multiple velocity components are observed at most positions. The velocity field is dominated by a large number of expanding structures, ranging in size from 1 to 100 pc and expansion velocities of 20-200 km/s, and often organized into large hierarchical networks. The integral of these complex expanding structures in 30 Dor produces a surprisingly simple profile with a broad Gaussian core and faint extended wings. Several fast-expanding shells, with diameters of 2-20 pc, expansion velocities of 100-300 km/s, and kinetic energies of 0.5-10 x 10(exp 50) ergs have been identified. The large fast-expanding shells and networks are coincident with extended X-ray sources and are probably associated with supernova remnants embedded in supershells produced by the combined effects of stellar winds and supernovae from OB associations. We have used the intensity-calibrated echelle spectra to determine the basic physical and dynamical properties of the kinematic features in 30 Dor. The expanding shells contain roughly half of the kinetic energy in the 30 Dor complex, and this energy is several times higher than the gravitational binding energy of the region. The energetic requirements of the gas are consistent with the observed stellar content of 30 Dor, if the gas is accelerated by a combination of stellar winds and supernovae. Extrapolating the current energy injection rate in the nebula over the lifetime of the OB complex suggest that 30 Dor and its vicinity will evolve into a supergiant shell as seen in the LMC and other nearby galaxies.

Bow shock formation in a complex plasma.

PubMed

Saitou, Y; Nakamura, Y; Kamimura, T; Ishihara, O

2012-02-10

A bow shock is observed in a two-dimensional supersonic flow of charged microparticles in a complex plasma. A thin conducting needle is used to make a potential barrier as an obstacle for the particle flow in the complex plasma. The flow is generated and the flow velocity is controlled by changing a tilt angle of the device under the gravitational force. A void, microparticle-free region, is formed around the potential barrier surrounding the obstacle. The flow is bent around the leading edge of the void and forms an arcuate structure when the flow is supersonic. The structure is characterized by the bow shock as confirmed by a polytropic hydrodynamic theory as well as numerical simulation.

Sea-town interactions over Marseille: 3D urban boundary layer and thermodynamic fields near the surface

NASA Astrophysics Data System (ADS)

Lemonsu, A.; Pigeon, G.; Masson, V.; Moppert, C.

2006-02-01

3D numerical simulations with the Meso-NH atmospheric model including the Town Energy Balance urban parameterization, are conducted over the south-east of France and the one million inhabitants city of Marseille in the frameworks of the ESCOMPTE-UBL program. The geographic situation of the area is relatively complex, because of the proximity of the Mediterranean Sea and the presence of numerous massifs, inducing complex meteorological flows. The present work is focused on six days of the campaign, characterized by the development of strong summer sea-breeze circulations. A complete evaluation of the model is initially realized at both regional- and city-scales, by using the large available database. The regional evaluation shows a good behavior of the model, during the six days of simulation, either for the parameters near the surface or for the vertical profiles describing the structure of the atmosphere. The urban-scale evaluation indicates that the fine structure of the horizontal fields of air temperature above the city is correctly simulated by the model. A specific attention is then pointed to the 250-m horizontal resolution outputs, focused on the Marseille area, for two days of the campaign. From the study of the vertical structure of the Urban Boundary Layer and the thermodynamic fields near the surface, one underscores the important differences due to the regional and local flows, and the complex interactions that occur between the urban effects and the effects of sea breezes.

Cardiac myocyte diversity and a fibroblast network in the junctional region of the zebrafish heart revealed by transmission and serial block-face scanning electron microscopy.

PubMed

Lafontant, Pascal J; Behzad, Ali R; Brown, Evelyn; Landry, Paul; Hu, Norman; Burns, Alan R

2013-01-01

The zebrafish has emerged as an important model of heart development and regeneration. While the structural characteristics of the developing and adult zebrafish ventricle have been previously studied, little attention has been paid to the nature of the interface between the compact and spongy myocardium. Here we describe how these two distinct layers are structurally and functionally integrated. We demonstrate by transmission electron microscopy that this interface is complex and composed primarily of a junctional region occupied by collagen, as well as a population of fibroblasts that form a highly complex network. We also describe a continuum of uniquely flattened transitional cardiac myocytes that form a circumferential plate upon which the radially-oriented luminal trabeculae are anchored. In addition, we have uncovered within the transitional ring a subpopulation of markedly electron dense cardiac myocytes. At discrete intervals the transitional cardiac myocytes form contact bridges across the junctional space that are stabilized through localized desmosomes and fascia adherentes junctions with adjacent compact cardiac myocytes. Finally using serial block-face scanning electron microscopy, segmentation and volume reconstruction, we confirm the three-dimensional nature of the junctional region as well as the presence of the sheet-like fibroblast network. These ultrastructural studies demonstrate the previously unrecognized complexity with which the compact and spongy layers are structurally integrated, and provide a new basis for understanding development and regeneration in the zebrafish heart.

Exploring the Active Center of the LSD1/CoREST Complex by Molecular Dynamics Simulation Utilizing Its Co-crystallized Co-factor Tetrahydrofolate as a Probe.

PubMed

Zalloum, Waleed A; Zalloum, Hiba M

2017-12-26

Epigenetic targeting of cancer is a recent effort to manipulate the gene without destroying the genetic material. Lysine-specific demethylase 1 (LSD1) is one of the enzymes associated with the chromatin for post-translational modifications, where it demethylates lysine amino acid in the chromatin H3 tail. Many studies showed that inhibiting LSD1 could potentially be used to treat cancer epigenetically. LSD1 is associated with its corepressor protein CoREST, and it uses tetrahydrofolate as a co-factor to accept CH 2 from the demethylation process. In this study, the co-crystallized co-factor tetrahydrofolate was utilized to determine possible binding regions in the active center of the LSD1/CoREST complex. Also, the flexibility of the complex has been investigated by molecular dynamics simulation and subsequent analysis by clustering and principal component analysis. This research supported other studies and showed that LSD1/CoREST complex exists in two main conformational structures: open and closed. Furthermore, this study showed that tetrahydrofolate stably binds to the LSD1/CoREST complex, in its open conformation, at its entrance. It then binds to the core of the complex, inducing the closed conformation. Furthermore, the interactions of tetrahydrofolate to these two binding regions and the corresponding binding mode of tetrahydrofolate were investigated to be used in structure-based drug design.

Spatial Distributions of Guest Molecule and Hydration Level in Dendrimer-Based Guest–Host Complex

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

Liu, Chih-Ying; Chen, Hsin-Lung; Do, Changwoo

2016-08-09

Using the electrostatic complex of G4 poly(amidoamine) (PAMAM) dendrimer with an amphiphilic surfactant as a model system, contrast variation small angle neutron scattering (SANS) is implemented to resolve the key structural characteristics of dendrimer-based guest–host system. Quantifications of the radial distributions of the scattering length density and the hydration level within the complex molecule reveal that the surfactant is embedded in the peripheral region of dendrimer and the steric crowding in this region increases the backfolding of the dendritic segments, thereby reducing the hydration level throughout the complex molecule. Here, the insights into the spatial location of the guest moleculesmore » as well as the perturbations of dendrimer conformation and hydration level deduced here are crucial for the delicate design of dendrimer-based guest–host system for biomedical applications.« less

Patterns of precipitation and soil moisture extremes in Texas, US: A complex network analysis

NASA Astrophysics Data System (ADS)

Sun, Alexander Y.; Xia, Youlong; Caldwell, Todd G.; Hao, Zengchao

2018-02-01

Understanding of the spatial and temporal dynamics of extreme precipitation not only improves prediction skills, but also helps to prioritize hazard mitigation efforts. This study seeks to enhance the understanding of spatiotemporal covariation patterns embedded in precipitation (P) and soil moisture (SM) by using an event-based, complex-network-theoretic approach. Events concurrences are quantified using a nonparametric event synchronization measure, and spatial patterns of hydroclimate variables are analyzed by using several network measures and a community detection algorithm. SM-P coupling is examined using a directional event coincidence analysis measure that takes the order of event occurrences into account. The complex network approach is demonstrated for Texas, US, a region possessing a rich set of hydroclimate features and is frequented by catastrophic flooding. Gridded daily observed P data and simulated SM data are used to create complex networks of P and SM extremes. The uncovered high degree centrality regions and community structures are qualitatively in agreement with the overall existing knowledge of hydroclimate extremes in the study region. Our analyses provide new visual insights on the propagation, connectivity, and synchronicity of P extremes, as well as the SM-P coupling, in this flood-prone region, and can be readily used as a basis for event-driven predictive analytics for other regions.

Significant Centers of Tectonic Activity as Identified by Wrinkle Ridges for the Western Hemisphere of Mars

NASA Technical Reports Server (NTRS)

Anderson, R.C.; Haldemann, A. F. C.; Golombek, M. P.; Franklin, B. J.; Dohm, J. M.; Lias, J.

2000-01-01

The western hemisphere region of Mars has been the site of numerous scientific investigations regarding its tectonic evolution. For this region of Mars, the dominant tectonic region is the Tharsis province. Tharsis is characterized by an enormous system of radiating grabens and a circumferential system of wrinkle ridges. Past investigations of grabens associated with Tharsis have identified specific centers of tectonic activity. A recent structural analysis of the western hemisphere region of Mars which includes the Tharsis region, utilized 25,000 structures to determine the history of local and regional centers of tectonic activity based primarily on the spatial and temporal relationships of extensional features. This investigation revealed that Tharsis is more structurally complex (heterogeneous) than has been previously identified: it consists of numerous regional and local centers of tectonic activity (some are more dominant and/or more long lived than others). Here we use the same approach as Anderson et al. to determine whether the centers of tectonic activity that formed the extensional features also contributed to wrinkle ridge (compressional) formation.

Carbon cycling at the tipping point: Does ecosystem structure predict resistance to disturbance?

NASA Astrophysics Data System (ADS)

Gough, C. M.; Bond-Lamberty, B. P.; Stuart-Haentjens, E.; Atkins, J.; Haber, L.; Fahey, R. T.

2017-12-01

Ecosystems worldwide are subjected to disturbances that reshape their physical and biological structure and modify biogeochemical processes, including carbon storage and cycling rates. Disturbances, including those from insect pests, pathogens, and extreme weather, span a continuum of severity and, accordingly, may have different effects on carbon cycling processes. Some ecosystems resist biogeochemical changes following disturbance, until a critical threshold of severity is exceeded. The ecosystem properties underlying such functional resistance, and signifying when a tipping point will occur, however, are almost entirely unknown. Here, we present observational and experimental results from forests in the Great Lakes region, showing ecosystem structure is closely coupled with carbon cycling responses to disturbance, with shifts in structure predicting thresholds of and, in some cases, increases in carbon storage. We find, among forests in the region, that carbon storage regularly exhibits a non-linear threshold response to increasing disturbance levels, but the severity at which a threshold is reached varies among disturbed forests. More biologically and structurally complex forest ecosystems sometimes exhibit greater functional resistance than simpler forests, and consequently may have a higher disturbance severity threshold. Counter to model predictions but consistent with some theoretical frameworks, empirical data show moderate levels of disturbance may increase ecosystem complexity to a point, thereby increasing rates of carbon storage. Disturbances that increase complexity therefore may stimulate carbon storage, while severe disturbances at or beyond thresholds may simplify structure, leading to carbon storage declines. We conclude that ecosystem structural attributes are closely coupled with biogeochemical thresholds across disturbance severity gradients, suggesting that improved predictions of disturbance-related changes in the carbon cycle require better representation of ecosystem structure in models.

Corolla Is a Novel Protein That Contributes to the Architecture of the Synaptonemal Complex of Drosophila

PubMed Central

Collins, Kimberly A.; Unruh, Jay R.; Slaughter, Brian D.; Yu, Zulin; Lake, Cathleen M.; Nielsen, Rachel J.; Box, Kimberly S.; Miller, Danny E.; Blumenstiel, Justin P.; Perera, Anoja G.; Malanowski, Kathryn E.; Hawley, R. Scott

2014-01-01

In most organisms the synaptonemal complex (SC) connects paired homologs along their entire length during much of meiotic prophase. To better understand the structure of the SC, we aim to identify its components and to determine how each of these components contributes to SC function. Here, we report the identification of a novel SC component in Drosophila melanogaster female oocytes, which we have named Corolla. Using structured illumination microscopy, we demonstrate that Corolla is a component of the central region of the SC. Consistent with its localization, we show by yeast two-hybrid analysis that Corolla strongly interacts with Cona, a central element protein, demonstrating the first direct interaction between two inner-synaptonemal complex proteins in Drosophila. These observations help provide a more complete model of SC structure and function in Drosophila females. PMID:24913682

Signalling networks and dynamics of allosteric transitions in bacterial chaperonin GroEL: implications for iterative annealing of misfolded proteins.

PubMed

Thirumalai, D; Hyeon, Changbong

2018-06-19

Signal transmission at the molecular level in many biological complexes occurs through allosteric transitions. Allostery describes the responses of a complex to binding of ligands at sites that are spatially well separated from the binding region. We describe the structural perturbation method, based on phonon propagation in solids, which can be used to determine the signal-transmitting allostery wiring diagram (AWD) in large but finite-sized biological complexes. Application to the bacterial chaperonin GroEL-GroES complex shows that the AWD determined from structures also drives the allosteric transitions dynamically. From both a structural and dynamical perspective these transitions are largely determined by formation and rupture of salt-bridges. The molecular description of allostery in GroEL provides insights into its function, which is quantitatively described by the iterative annealing mechanism. Remarkably, in this complex molecular machine, a deep connection is established between the structures, reaction cycle during which GroEL undergoes a sequence of allosteric transitions, and function, in a self-consistent manner.This article is part of a discussion meeting issue 'Allostery and molecular machines'. © 2018 The Author(s).

The structure of the NO(X (2)Pi)-N(2) complex: A joint experimental-theoretical study.

PubMed

Wen, B; Meyer, H; Kłos, J

2010-04-21

We report the first measurement of the spectrum of the NO-N(2) complex in the region of the first vibrational NO overtone transition. The origin band of the complex is blueshifted by 0.30 cm(-1) from the corresponding NO monomer frequency. The observed spectrum consists of three bands assigned to the origin band, the excitation of one quantum of z-axis rotation and one associated hot band. The spacing of the bands and the rotational structure indicate a T-shaped vibrationally averaged structure with the NO molecule forming the top of the T. These findings are confirmed by high level ab initio calculations of the potential energy surfaces in planar symmetry. The deepest minimum is found for a T-shaped geometry on the A(")-surface. As a result the sum potential also has the global minimum for this structure. The different potential surfaces show several additional local minima at slightly higher energies indicating that the complex most likely will perform large amplitude motion even in its ground vibrational state. Nevertheless, as suggested by the measured spectra, the complex must, on average, spend a substantial amount of time near the T-shaped configuration.

Amyloidogenic Regions and Interaction Surfaces Overlap in Globular Proteins Related to Conformational Diseases

PubMed Central

Castillo, Virginia; Ventura, Salvador

2009-01-01

Protein aggregation underlies a wide range of human disorders. The polypeptides involved in these pathologies might be intrinsically unstructured or display a defined 3D-structure. Little is known about how globular proteins aggregate into toxic assemblies under physiological conditions, where they display an initially folded conformation. Protein aggregation is, however, always initiated by the establishment of anomalous protein-protein interactions. Therefore, in the present work, we have explored the extent to which protein interaction surfaces and aggregation-prone regions overlap in globular proteins associated with conformational diseases. Computational analysis of the native complexes formed by these proteins shows that aggregation-prone regions do frequently overlap with protein interfaces. The spatial coincidence of interaction sites and aggregating regions suggests that the formation of functional complexes and the aggregation of their individual subunits might compete in the cell. Accordingly, single mutations affecting complex interface or stability usually result in the formation of toxic aggregates. It is suggested that the stabilization of existing interfaces in multimeric proteins or the formation of new complexes in monomeric polypeptides might become effective strategies to prevent disease-linked aggregation of globular proteins. PMID:19696882

Structural Characterization of Amyloid β17-42 Dimer by Potential of Mean Force Analysis: Insights from Molecular Dynamics Simulations.

PubMed

Dutta, Mary; Chutia, Rajkalyan; Mattaparthi, Venkata Satish Kumar

2017-01-01

Recent experiments with Amyloid β1-42 peptide have indicated that the initial dimerization of Aβ1-42 monomers to form amyloid dimers stand out as a key event in the generation of toxic oligomers. However, the structural characterization of Aβ1-42 dimer at the atomistic level and the dimerization mechanism by which Aβ1-42 peptides co-aggregate still remains not clear. In the present study, the process of Aβ17-42 peptide dimerization which is known to play an important role in the plaque formation in Alzheimer's disease was evaluated in terms of potential of mean force. The Aβ17-42 dimer was constructed using PatchDock server. We have used molecular dynamics (MD) simulation with the umbrella sampling methodology to compute the Potential of Mean Force for the dimerization of Aβ17-42. The global minima structure at the minimum distance of separation was isolated from the calculated free energy profile and the interactions involved in the formation of the dimer structure were examined. Protein-protein interfaces and the residueresidue interactions vital for generation of the dimer complexes were also evaluated. The simulation results elucidated the interaction between the monomeric units to be governed primarily by the hydrophobic and hydrogen bonds. The resultant Aβ17-42 dimer was found to have an increased β-strands propensity at the hydrophobic regions encompassing the CHC region. Furthermore, specific hydrophobic residues were found to play a vital role in the formation of the dimer complex. From the results we may therefore conclude hydrophobic region encompassing the CHC region to be crucial in dimerization process. The findings from this study provide detailed information for the complex process of early events of Aβ aggregation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Crustal structure of norther Oaxaca terrane; The Oaxaca and caltepec faults, and the Tehuacan Valley. A gravity study.

NASA Astrophysics Data System (ADS)

Campos-Enriquez, J. O.; Alatorre-Zamora, M. A.; Ramón, V. M.; Belmonte, S.

2014-12-01

Northern Oaxaca terrane, southern Mexico, is bound by the Caltepec and Oaxaca faults to the west and east, respectively. These faults juxtapose the Oaxaca terrane against the Mixteca and Juarez terranes, respectively. The Oaxaca Fault also forms the eastern boundary of the Cenozoic Tehuacan depression. Several gravity profiles across these faults and the Oaxaca terrane (including the Tehuacan Valley) enables us to establish the upper crustal structure of this region. Accordingly, the Oaxaca terrane is downward displaced to the east in two steps. First the Santa Lucia Fault puts into contact the granulitic basamental rocks with Phanerozoic volcanic and sedimentary rocks. Finally, the Gavilan Fault puts into contact the Oaxaca terrane basement (Oaxaca Complex) into contact with the volcano-sedimentary infill of the valley. This gravity study reveals that the Oaxaca Fault system gives rise to a series of east tilted basamental blocks (Oaxaca Complex?). A structural high at the western Tehuacan depression accomadates the east dipping faults (Santa Lucia and Gavilan faults) and the west dipping faults of the Oaxaca Fault System. To the west of this high structural we have the depper depocenters. The Oaxaca Complex, the Caltepec and Santa Lucia faults continue northwestwards beneath Phanerozoic rocks. The faults are regional tectonic structures. They seem to continue northwards below the Trans-Mexican Volcanic Belt. A major E-W to NE-SW discontinuity on the Oaxaca terrane is inferred to exist between profiles 1 and 2. The Tehuacan Valley posses a large groundwater potential.

Crystal structure of an FIV/HIV chimeric protease complexed with the broad-based inhibitor, TL-3

PubMed Central

Heaslet, Holly; Lin, Ying-Chuan; Tam, Karen; Torbett, Bruce E; Elder, John H; Stout, C David

2007-01-01

We have obtained the 1.7 Å crystal structure of FIV protease (PR) in which 12 critical residues around the active site have been substituted with the structurally equivalent residues of HIV PR (12X FIV PR). The chimeric PR was crystallized in complex with the broad-based inhibitor TL-3, which inhibits wild type FIV and HIV PRs, as well as 12X FIV PR and several drug-resistant HIV mutants [1-4]. Biochemical analyses have demonstrated that TL-3 inhibits these PRs in the order HIV PR > 12X FIV PR > FIV PR, with Ki values of 1.5 nM, 10 nM, and 41 nM, respectively [2-4]. Comparison of the crystal structures of the TL-3 complexes of 12X FIV and wild-typeFIV PR revealed theformation of additinal van der Waals interactions between the enzyme inhibitor in the mutant PR. The 12X FIV PR retained the hydrogen bonding interactions between residues in the flap regions and active site involving the enzyme and the TL-3 inhibitor in comparison to both FIV PR and HIV PR. However, the flap regions of the 12X FIV PR more closely resemble those of HIV PR, having gained several stabilizing intra-flap interactions not present in wild type FIV PR. These findings offer a structural explanation for the observed inhibitor/substrate binding properties of the chimeric PR. PMID:17212810

Conserved Structural Elements in the V3 Crown of HIV-1 gp120

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

Jiang, X.; Burke, V; Totrov, M

2010-01-01

Binding of the third variable region (V3) of the HIV-1 envelope glycoprotein gp120 to the cell-surface coreceptors CCR5 or CXCR4 during viral entry suggests that there are conserved structural elements in this sequence-variable region. These conserved elements could serve as epitopes to be targeted by a vaccine against HIV-1. Here we perform a systematic structural analysis of representative human anti-V3 monoclonal antibodies in complex with V3 peptides, revealing that the crown of V3 has four conserved structural elements: an arch, a band, a hydrophobic core and the peptide backbone. These are either unaffected by or are subject to minimal sequencemore » variation. As these regions are targeted by cross-clade neutralizing human antibodies, they provide a blueprint for the design of vaccine immunogens that could elicit broadly cross-reactive protective antibodies.« less

Structural complexity and land-surface energy exchange along a gradient from arctic tundra to boreal forest

USGS Publications Warehouse

Thompson, C.; Beringer, J.; Chapin, F. S.; McGuire, A.D.

2004-01-01

Question: Current climate changes in the Alaskan Arctic, which are characterized by increases in temperature and length of growing season, could alter vegetation structure, especially through increases in shrub cover or the movement of treeline. These changes in vegetation structure have consequences for the climate system. What is the relationship between structural complexity and partitioning of surface energy along a gradient from tundra through shrub tundra to closed canopy forest? Location: Arctic tundra-boreal forest transition in the Alaskan Arctic. Methods: Along this gradient of increasing canopy complexity, we measured key vegetation characteristics, including community composition, biomass, cover, height, leaf area index and stem area index. We relate these vegetation characteristics to albedo and the partitioning of net radiation into ground, latent, and sensible heating fluxes. Results: Canopy complexity increased along the sequence from tundra to forest due to the addition of new plant functional types. This led to non-linear changes in biomass, cover, and height in the understory. The increased canopy complexity resulted in reduced ground heat fluxes, relatively conserved latent heat fluxes and increased sensible heat fluxes. The localized warming associated with increased sensible heating over more complex canopies may amplify regional warming, causing further vegetation change in the Alaskan Arctic.

THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity.

PubMed

Kolb, Bryan; Li, Yilin; Robinson, Terry; Parker, Linda A

2018-03-01

Psychoactive drugs have the ability to alter the morphology of neuronal dendrites and spines and to influence later experience-dependent structural plasticity. If rats are given repeated injections of psychomotor stimulants (amphetamine, cocaine, nicotine) prior to being placed in complex environments, the drug experience interferes with the ability of the environment to increase dendritic arborization and spine density. Repeated exposure to Delta 9-Tetrahydrocannabinol (THC) changes the morphology of dendrites in medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc). To determine if drugs other than psychomotor stimulants will also interfere with later experience-dependent structural plasticity we gave Long-Evans rats THC (0.5 mg/kg) or saline for 11 days before placing them in complex environments or standard laboratory caging for 90 days. Brains were subsequently processed for Golgi-Cox staining and analysis of dendritic morphology and spine density mPFC, orbital frontal cortex (OFC), and NAcc. THC altered both dendritic arborization and spine density in all three regions, and, like psychomotor stimulants, THC influenced the effect of later experience in complex environments to shape the structure of neurons in these three regions. We conclude that THC may therefore contribute to persistent behavioral and cognitive deficits associated with prolonged use of the drug. © 2017 Wiley Periodicals, Inc.

An efficient synthetic method for organometallic radicals: structures and properties of gold(i)-(nitronyl nitroxide)-2-ide complexes.

PubMed

Suzuki, Shuichi; Kira, Sayaka; Kozaki, Masatoshi; Yamamura, Masaki; Hasegawa, Toru; Nabeshima, Tatsuya; Okada, Keiji

2017-02-21

One-pot synthesis of (nitronyl nitroxide)-gold(i)-phosphine (NN-Au-P) complexes has been developed using chloro(tetrahydrothiophene)gold(i), phosphine ligands, nitronyl nitroxide radicals, and sodium hydroxide. The NN-Au-P complexes can be easily handled because they were quite stable under aerated conditions in both solution and crystalline states. They showed weak absorption bands with vibrational structures in the 450-650 nm region. The oxidation potentials assigned to the NN moieties of NN-Au-P complexes with aromatic phosphines were observed around -0.1 V vs. Fc/Fc + (-0.11 V for NN-Au-1, -0.08 V for NN-Au-2, -0.13 V for NN-Au-5, and -0.07 V for NN-Au-6), somewhat lower than that of NN-Au-P complexes with aliphatic phosphines (-0.25 V for NN-Au-3 and -0.17 V for NN-Au-4).

Oxidized derivatives of Octopus vulgaris and Carcinus aestuarii hemocyanins at pH 7.5 and related models by x-ray absorption spectroscopy.

PubMed Central

Borghi, Elena; Solari, Pier Lorenzo; Beltramini, Mariano; Bubacco, Luigi; Di Muro, Paolo; Salvato, Benedetto

2002-01-01

The binuclear copper sites of the met and met-azido derivatives of Octopus vulgaris and Carcinus aestuarii hemocyanins at pH 7.5 were characterized by high-resolution x-ray absorption spectroscopy in the low energy region (XANES) and in the higher region (EXAFS). The accuracy of the analysis of the data was tested with two mononuclear and six binuclear copper(II) complexes of the poly(benzimidazole) ligand systems 2-BB, L-5,5 and L-6,6 (Casella et al., 1993, Inorg. Chem. 32:2056-2067; 1996, Inorg. Chem. 35:1101-1113). Their structural and reactivity properties are related to those of the protein's derivatives. The results obtained for those models with resolved x-ray structure (the 2-BB-aquo and azido mononuclear complexes, and the binuclear L-5,5 Cu(II)-bis(hydroxo) (Casella et al., unpublished)), extends the validity of our approach to the other poly(benzimidazole)-containing complexes and to the hemocyanin derivatives. Comparison between the protein's and the complexes' data, support a description of the met-derivatives as a five-coordinated O-bridged binuclear copper(II) center and favors, for both species, a bis(hydroxo) structure with a 3-A Cu-Cu distance. For O. vulgaris met-azido derivative a mu-1,3 bridging mode for the ligand appears the most likely. The structural situation of C. aestuarii met-azido-derivative is less clear: a mu-1,1 mode is favored, but a terminal mode cannot be excluded. PMID:12023249

Neuroarchitecture and neuroanatomy of the Drosophila central complex: A GAL4-based dissection of protocerebral bridge neurons and circuits.

PubMed

Wolff, Tanya; Iyer, Nirmala A; Rubin, Gerald M

2015-05-01

Insects exhibit an elaborate repertoire of behaviors in response to environmental stimuli. The central complex plays a key role in combining various modalities of sensory information with an insect's internal state and past experience to select appropriate responses. Progress has been made in understanding the broad spectrum of outputs from the central complex neuropils and circuits involved in numerous behaviors. Many resident neurons have also been identified. However, the specific roles of these intricate structures and the functional connections between them remain largely obscure. Significant gains rely on obtaining a comprehensive catalog of the neurons and associated GAL4 lines that arborize within these brain regions, and on mapping neuronal pathways connecting these structures. To this end, small populations of neurons in the Drosophila melanogaster central complex were stochastically labeled using the multicolor flip-out technique and a catalog was created of the neurons, their morphologies, trajectories, relative arrangements, and corresponding GAL4 lines. This report focuses on one structure of the central complex, the protocerebral bridge, and identifies just 17 morphologically distinct cell types that arborize in this structure. This work also provides new insights into the anatomical structure of the four components of the central complex and its accessory neuropils. Most strikingly, we found that the protocerebral bridge contains 18 glomeruli, not 16, as previously believed. Revised wiring diagrams that take into account this updated architectural design are presented. This updated map of the Drosophila central complex will facilitate a deeper behavioral and physiological dissection of this sophisticated set of structures. © 2014 Wiley Periodicals, Inc.

K-band observations of boxy bulges - I. Morphology and surface brightness profiles

NASA Astrophysics Data System (ADS)

Bureau, M.; Aronica, G.; Athanassoula, E.; Dettmar, R.-J.; Bosma, A.; Freeman, K. C.

2006-08-01

In this first paper of a series on the structure of boxy and peanut-shaped (B/PS) bulges, Kn-band observations of a sample of 30 edge-on spiral galaxies are described and discussed. Kn-band observations best trace the dominant luminous galactic mass and are minimally affected by dust. Images, unsharp-masked images, as well as major-axis and vertically summed surface brightness profiles are presented and discussed. Galaxies with a B/PS bulge tend to have a more complex morphology than galaxies with other bulge types, more often showing centred or off-centred X structures, secondary maxima along the major-axis and spiral-like structures. While probably not uniquely related to bars, those features are observed in three-dimensional N-body simulations of barred discs and may trace the main bar orbit families. The surface brightness profiles of galaxies with a B/PS bulge are also more complex, typically containing three or more clearly separated regions, including a shallow or flat intermediate region (Freeman Type II profiles). The breaks in the profiles offer evidence for bar-driven transfer of angular momentum and radial redistribution of material. The profiles further suggest a rapid variation of the scaleheight of the disc material, contrary to conventional wisdom but again as expected from the vertical resonances and instabilities present in barred discs. Interestingly, the steep inner region of the surface brightness profiles is often shorter than the isophotally thick part of the galaxies, itself always shorter than the flat intermediate region of the profiles. The steep inner region is also much more prominent along the major-axis than in the vertically summed profiles. Similarly to other recent work but contrary to the standard `bulge + disc' model (where the bulge is both thick and steep), we thus propose that galaxies with a B/PS bulge are composed of a thin concentrated disc (a disc-like bulge) contained within a partially thick bar (the B/PS bulge), itself contained within a thin outer disc. The inner disc likely formed secularly through bar-driven processes and is responsible for the steep inner region of the surface brightness profiles, traditionally associated with a classic bulge, while the bar is responsible for the flat intermediate region of the surface brightness profiles and the thick complex morphological structures observed. Those components are strongly coupled dynamically and are formed mostly of the same (disc) material, shaped by the weak but relentless action of the bar resonances. Any competing formation scenario for galaxies with a B/PS bulge, which represent at least 45 per cent of the local disc galaxy population, must explain equally well and self-consistently the above morphological and photometric properties, the complex gas and stellar kinematics observed, and the correlations between them.

Geological History of the Tyre Region of Europa: A Regional Perspective on Europan Surface Features and Ice Thickness

NASA Technical Reports Server (NTRS)

Kadel, Steven D.; Chuang, Frank C.; Greeley, Ronald; Moore, Jeffrey M.

2000-01-01

Galileo images of the Tyre Macula region of Europa at regional (170 m/pixel) and local (approx. 40 m/pixel) scales allow mapping and understanding of surface processes and landforms. Ridged plains, doublet and complex ridges, shallow pits, domes, "chaos" areas. impact structures, tilted blocks and massifs, and young fracture systems indicate a complex history of surface deformation on Europa. Regional and local morphologies of the Tyre region of Europa suggest that an impactor penetrated through several kilometers of water ice tc a mobile layer below. The surface morphology was initially dominated by formation of ridged plains, followed by development of ridge bands and doublet ridges, with chaos and fracture formation dominating the latter part of the geologic history of the Tyre region. Two distinct types of chaos have been identified which, along with upwarped dome materials, appear to represent a continuum of features (domes-play chaos-knobby chaos) resulting from increasing degree of surface disruption associated with local lithospheric heating and thinning. Local and regional stratigraphic relationships, block heights, and the morphology of the Tyre impact structure suggest the presence of low-viscosity ice or liquid water beneath a thin (severa1 kilometers) surface ice shell at the time of the impact. The very low impact crater density on the surface of Europa suggests that this thin shell has either formed or been thoroughly resurfaced in the very recent past.

Research on spatial economic structure for different economic sectors from a perspective of a complex network

NASA Astrophysics Data System (ADS)

Hu, Sen; Yang, Hualei; Cai, Boliang; Yang, Chunxia

2013-09-01

The economy system is a complex system, and the complex network is a powerful tool to study its complexity. Here we calculate the economic distance matrices based on annual GDP of nine economic sectors from 1995-2010 in 31 Chinese provinces and autonomous regions,1 then build several spatial economic networks through the threshold method and the Minimal Spanning Tree method. After the analysis on the structure of the networks and the influence of geographic distance, some conclusions are drawn. First, connectivity distribution of a spatial economic network does not follow the power law. Second, according to the network structure, nine economic sectors could be divided into two groups, and there is significant discrepancy of network structure between these two groups. Moreover, the influence of the geographic distance plays an important role on the structure of a spatial economic network, network parameters are changed with the influence of the geographic distance. At last, 2000 km is the critical value for geographic distance: for real estate and finance, the spearman’s rho with l<2000 is bigger than that with l>2000, and the case is opposite for other economic sectors.

Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity

PubMed Central

Yourik, Paul; Aitken, Colin Echeverría; Zhou, Fujun; Gupta, Neha

2017-01-01

eIF4A is a DEAD-box RNA-dependent ATPase thought to unwind RNA secondary structure in the 5'-untranslated regions (UTRs) of mRNAs to promote their recruitment to the eukaryotic translation pre-initiation complex (PIC). We show that eIF4A's ATPase activity is markedly stimulated in the presence of the PIC, independently of eIF4E•eIF4G, but dependent on subunits i and g of the heteromeric eIF3 complex. Surprisingly, eIF4A accelerated the rate of recruitment of all mRNAs tested, regardless of their degree of structural complexity. Structures in the 5'-UTR and 3' of the start codon synergistically inhibit mRNA recruitment in a manner relieved by eIF4A, indicating that the factor does not act solely to melt hairpins in 5'-UTRs. Our findings that eIF4A functionally interacts with the PIC and plays important roles beyond unwinding 5'-UTR structure is consistent with a recent proposal that eIF4A modulates the conformation of the 40S ribosomal subunit to promote mRNA recruitment. PMID:29192585

Training verb argument structure production in agrammatic aphasia: Behavioral and neural recovery patterns

PubMed Central

Thompson, Cynthia K.; Riley, Ellyn A.; den Ouden, Dirk-Bart; Meltzer-Asscher, Aya; Lukic, Sladjana

2013-01-01

Introduction Neuroimaging and lesion studies indicate a left hemisphere network for verb and verb argument structure processing, involving both frontal and temporoparietal brain regions. Although their verb comprehension is generally unimpaired, it is well known that individuals with agrammatic aphasia often present with verb production deficits, characterized by an argument structure complexity hierarchy, indicating faulty access to argument structure representations for production and integration into syntactic contexts. Recovery of verb processing in agrammatism, however, has received little attention and no studies have examined the neural mechanisms associated with improved verb and argument structure processing. In the present study we trained agrammatic individuals on verbs with complex argument structure in sentence contexts and examined generalization to verbs with less complex argument structure. The neural substrates of improved verb production were examined using functional magnetic resonance imaging (fMRI). Methods Eight individuals with chronic agrammatic aphasia participated in the study (four experimental and four control participants). Production of three-argument verbs in active sentences was trained using a sentence generation task emphasizing the verb’s argument structure and the thematic roles of sentential noun phrases. Before and after training, production of trained and untrained verbs was tested in naming and sentence production and fMRI scans were obtained, using an action naming task. Results Significant pre- to post-training improvement in trained and untrained (one- and two-argument) verbs was found for treated, but not control, participants, with between-group differences found for verb naming, production of verbs in sentences, and production of argument structure. fMRI activation derived from post-treatment compared to pre-treatment scans revealed upregulation in cortical regions implicated for verb and argument structure processing in healthy controls. Conclusions Training verb deficits emphasizing argument structure and thematic role mapping is effective for improving verb and sentence production and results in recruitment of neural networks engaged for verb and argument structure processing in healthy individuals. PMID:23514929

The neural correlates of morphological complexity processing: Detecting structure in pseudowords.

PubMed

Schuster, Swetlana; Scharinger, Mathias; Brooks, Colin; Lahiri, Aditi; Hartwigsen, Gesa

2018-06-01

Morphological complexity is a highly debated issue in visual word recognition. Previous neuroimaging studies have shown that speakers are sensitive to degrees of morphological complexity. Two-step derived complex words (bridging through bridge N  > bridge V  > bridging) led to more enhanced activation in the left inferior frontal gyrus than their 1-step derived counterparts (running through run V  > running). However, it remains unclear whether sensitivity to degrees of morphological complexity extends to pseudowords. If this were the case, it would indicate that abstract knowledge of morphological structure is independent of lexicality. We addressed this question by investigating the processing of two sets of pseudowords in German. Both sets contained morphologically viable two-step derived pseudowords differing in the number of derivational steps required to access an existing lexical representation and therefore the degree of structural analysis expected during processing. Using a 2 × 2 factorial design, we found lexicality effects to be distinct from processing signatures relating to structural analysis in pseudowords. Semantically-driven processes such as lexical search showed a more frontal distribution while combinatorial processes related to structural analysis engaged more parietal parts of the network. Specifically, more complex pseudowords showed increased activation in parietal regions (right superior parietal lobe and left precuneus) relative to pseudowords that required less structural analysis to arrive at an existing lexical representation. As the two sets were matched on cohort size and surface form, these results highlight the role of internal levels of morphological structure even in forms that do not possess a lexical representation. © 2018 Wiley Periodicals, Inc.

The neural correlates of obsessive-compulsive disorder: a multimodal perspective.

PubMed

Moreira, P S; Marques, P; Soriano-Mas, C; Magalhães, R; Sousa, N; Soares, J M; Morgado, P

2017-08-29

Obsessive-compulsive disorder (OCD) is one of the most debilitating psychiatric conditions. An extensive body of the literature has described some of the neurobiological mechanisms underlying the core manifestations of the disorder. Nevertheless, most reports have focused on individual modalities of structural/functional brain alterations, mainly through targeted approaches, thus possibly precluding the power of unbiased exploratory approaches. Eighty subjects (40 OCD and 40 healthy controls) participated in a multimodal magnetic resonance imaging (MRI) investigation, integrating structural and functional data. Voxel-based morphometry analysis was conducted to compare between-group volumetric differences. The whole-brain functional connectome, derived from resting-state functional connectivity (FC), was analyzed with the network-based statistic methodology. Results from structural and functional analysis were integrated in mediation models. OCD patients revealed volumetric reductions in the right superior temporal sulcus. Patients had significantly decreased FC in two distinct subnetworks: the first, involving the orbitofrontal cortex, temporal poles and the subgenual anterior cingulate cortex; the second, comprising the lingual and postcentral gyri. On the opposite, a network formed by connections between thalamic and occipital regions had significantly increased FC in patients. Integrative models revealed direct and indirect associations between volumetric alterations and FC networks. This study suggests that OCD patients display alterations in brain structure and FC, involving complex networks of brain regions. Furthermore, we provided evidence for direct and indirect associations between structural and functional alterations representing complex patterns of interactions between separate brain regions, which may be of upmost relevance for explaining the pathophysiology of the disorder.

Build-a-Brain Project: Students Design and Model the Brain of an Imaginary Animal

ERIC Educational Resources Information Center

Demetrikopoulos, Melissa K.; Pecore, John; Rose, Jordan D.; Fobbs, Archibald J., Jr.; Johnson, John I.; Carruth, Laura L.

2006-01-01

The brain is a truly fascinating structure! It controls the body and allows everyone to think, learn, speak, move, feel, remember, and experience emotions. Although the brain is a single organ, it is very complex and has several regions, each having a specific function. These functionally diverse regions work together to allow for coordination of…

Stabilization of non-productive conformations underpins rapid electron transfer to electron-transferring flavoprotein.

PubMed

Toogood, Helen S; van Thiel, Adam; Scrutton, Nigel S; Leys, David

2005-08-26

Crystal structures of protein complexes with electron-transferring flavoprotein (ETF) have revealed a dual protein-protein interface with one region serving as anchor while the ETF FAD domain samples available space within the complex. We show that mutation of the conserved Glu-165beta in human ETF leads to drastically modulated rates of interprotein electron transfer with both medium chain acyl-CoA dehydrogenase and dimethylglycine dehydrogenase. The crystal structure of free E165betaA ETF is essentially identical to that of wild-type ETF, but the crystal structure of the E165betaA ETF.medium chain acyl-CoA dehydrogenase complex reveals clear electron density for the FAD domain in a position optimal for fast interprotein electron transfer. Based on our observations, we present a dynamic multistate model for conformational sampling that for the wild-type ETF. medium chain acyl-CoA dehydrogenase complex involves random motion between three distinct positions for the ETF FAD domain. ETF Glu-165beta plays a key role in stabilizing positions incompatible with fast interprotein electron transfer, thus ensuring high rates of complex dissociation.

On the robustness of complex heterogeneous gene expression networks.

PubMed

Gómez-Gardeñes, Jesús; Moreno, Yamir; Floría, Luis M

2005-04-01

We analyze a continuous gene expression model on the underlying topology of a complex heterogeneous network. Numerical simulations aimed at studying the chaotic and periodic dynamics of the model are performed. The results clearly indicate that there is a region in which the dynamical and structural complexity of the system avoid chaotic attractors. However, contrary to what has been reported for Random Boolean Networks, the chaotic phase cannot be completely suppressed, which has important bearings on network robustness and gene expression modeling.

Malleable machines in transcription regulation: the mediator complex.

PubMed

Tóth-Petróczy, Agnes; Oldfield, Christopher J; Simon, István; Takagi, Yuichiro; Dunker, A Keith; Uversky, Vladimir N; Fuxreiter, Monika

2008-12-01

The Mediator complex provides an interface between gene-specific regulatory proteins and the general transcription machinery including RNA polymerase II (RNAP II). The complex has a modular architecture (Head, Middle, and Tail) and cryoelectron microscopy analysis suggested that it undergoes dramatic conformational changes upon interactions with activators and RNAP II. These rearrangements have been proposed to play a role in the assembly of the preinitiation complex and also to contribute to the regulatory mechanism of Mediator. In analogy to many regulatory and transcriptional proteins, we reasoned that Mediator might also utilize intrinsically disordered regions (IDRs) to facilitate structural transitions and transmit transcriptional signals. Indeed, a high prevalence of IDRs was found in various subunits of Mediator from both Saccharomyces cerevisiae and Homo sapiens, especially in the Tail and the Middle modules. The level of disorder increases from yeast to man, although in both organisms it significantly exceeds that of multiprotein complexes of a similar size. IDRs can contribute to Mediator's function in three different ways: they can individually serve as target sites for multiple partners having distinctive structures; they can act as malleable linkers connecting globular domains that impart modular functionality on the complex; and they can also facilitate assembly and disassembly of complexes in response to regulatory signals. Short segments of IDRs, termed molecular recognition features (MoRFs) distinguished by a high protein-protein interaction propensity, were identified in 16 and 19 subunits of the yeast and human Mediator, respectively. In Saccharomyces cerevisiae, the functional roles of 11 MoRFs have been experimentally verified, and those in the Med8/Med18/Med20 and Med7/Med21 complexes were structurally confirmed. Although the Saccharomyces cerevisiae and Homo sapiens Mediator sequences are only weakly conserved, the arrangements of the disordered regions and their embedded interaction sites are quite similar in the two organisms. All of these data suggest an integral role for intrinsic disorder in Mediator's function.

Taking advantage of local structure descriptors to analyze interresidue contacts in protein structures and protein complexes.

PubMed

Martin, Juliette; Regad, Leslie; Etchebest, Catherine; Camproux, Anne-Claude

2008-11-15

Interresidue protein contacts in proteins structures and at protein-protein interface are classically described by the amino acid types of interacting residues and the local structural context of the contact, if any, is described using secondary structures. In this study, we present an alternate analysis of interresidue contact using local structures defined by the structural alphabet introduced by Camproux et al. This structural alphabet allows to describe a 3D structure as a sequence of prototype fragments called structural letters, of 27 different types. Each residue can then be assigned to a particular local structure, even in loop regions. The analysis of interresidue contacts within protein structures defined using Voronoï tessellations reveals that pairwise contact specificity is greater in terms of structural letters than amino acids. Using a simple heuristic based on specificity score comparison, we find that 74% of the long-range contacts within protein structures are better described using structural letters than amino acid types. The investigation is extended to a set of protein-protein complexes, showing that the similar global rules apply as for intraprotein contacts, with 64% of the interprotein contacts best described by local structures. We then present an evaluation of pairing functions integrating structural letters to decoy scoring and show that some complexes could benefit from the use of structural letter-based pairing functions.

Comparative Genomic Analyses of the Human NPHP1 Locus Reveal Complex Genomic Architecture and Its Regional Evolution in Primates

PubMed Central

Yuan, Bo; Liu, Pengfei; Gupta, Aditya; Beck, Christine R.; Tejomurtula, Anusha; Campbell, Ian M.; Gambin, Tomasz; Simmons, Alexandra D.; Withers, Marjorie A.; Harris, R. Alan; Rogers, Jeffrey; Schwartz, David C.; Lupski, James R.

2015-01-01

Many loci in the human genome harbor complex genomic structures that can result in susceptibility to genomic rearrangements leading to various genomic disorders. Nephronophthisis 1 (NPHP1, MIM# 256100) is an autosomal recessive disorder that can be caused by defects of NPHP1; the gene maps within the human 2q13 region where low copy repeats (LCRs) are abundant. Loss of function of NPHP1 is responsible for approximately 85% of the NPHP1 cases—about 80% of such individuals carry a large recurrent homozygous NPHP1 deletion that occurs via nonallelic homologous recombination (NAHR) between two flanking directly oriented ~45 kb LCRs. Published data revealed a non-pathogenic inversion polymorphism involving the NPHP1 gene flanked by two inverted ~358 kb LCRs. Using optical mapping and array-comparative genomic hybridization, we identified three potential novel structural variant (SV) haplotypes at the NPHP1 locus that may protect a haploid genome from the NPHP1 deletion. Inter-species comparative genomic analyses among primate genomes revealed massive genomic changes during evolution. The aggregated data suggest that dynamic genomic rearrangements occurred historically within the NPHP1 locus and generated SV haplotypes observed in the human population today, which may confer differential susceptibility to genomic instability and the NPHP1 deletion within a personal genome. Our study documents diverse SV haplotypes at a complex LCR-laden human genomic region. Comparative analyses provide a model for how this complex region arose during primate evolution, and studies among humans suggest that intra-species polymorphism may potentially modulate an individual’s susceptibility to acquiring disease-associated alleles. PMID:26641089

Recognition and stabilization of geranylgeranylated human Rab5 by the GDP Dissociation Inhibitor (GDI).

PubMed

Edler, Eileen; Stein, Matthias

2017-10-25

The small GTPase Rab5 is the key regulator of early endosomal fusion. It is post-translationally modified by covalent attachment of two geranylgeranyl (GG) chains to adjacent cysteine residues of the C-terminal hypervariable region (HVR). The GDP dissociation inhibitor (GDI) recognizes membrane-associated Rab5(GDP) and serves to release it into the cytoplasm where it is kept in a soluble state. A detailed new structural and dynamic model for human Rab5(GDP) recognition and binding with human GDI at the early endosome membrane and in its dissociated state is presented. In the cytoplasm, the GDI protein accommodates the GG chains in a transient hydrophobic binding pocket. In solution, two different binding modes of the isoprenoid chains inserted into the hydrophobic pocket of the Rab5(GDP):GDI complex can be identified. This equilibrium between the two states helps to stabilize the protein-protein complex in solution. Interprotein contacts between the Rab5 switch regions and characteristic patches of GDI residues from the Rab binding platform (RBP) and the C-terminus coordinating region (CCR) reveal insight on the formation of such a stable complex. GDI binding to membrane-anchored Rab5(GDP) is initially mediated by the solvent accessible switch regions of the Rab-specific RBP. Formation of the membrane-associated Rab5(GDP):GDI complex induces a GDI reorientation to establish additional interactions with the Rab5 HVR. These results allow to devise a detailed structural model for the process of extraction of GG-Rab5(GDP) by GDI from the membrane and the dissociation from targeting factors and effector proteins prior to GDI binding.

Dyke-sill relationships in Karoo dolerites as indicators of propagation and emplacement processes of mafic magmas in the shallow crust

NASA Astrophysics Data System (ADS)

Coetzee, A.; Kisters, A. F. M.

2017-04-01

This paper describes the spatial and temporal relationships between Karoo-age (ca. 180 Ma) dolerite dykes and a regional-scale saucer-sill complex from the Secunda (coal mine) Complex in the northeastern parts of the Karoo Basin of South Africa. Unlike parallel dyke swarms of regional extensional settings, mafic dykes commonly show curved geometries and highly variable orientations, short strike extents and complex cross-cutting and intersecting relationships. Importantly, the dyke networks originate from the upper contacts of the first-order dolerite sill-saucer structure and are not the feeders of the saucer complex. Cross-cutting relationships indicate the largely contemporaneous formation of dykes and the inner sill and inclined sheets of the underlying saucer. Systematic dykes form a distinct boxwork-type pattern of two high-angle, interconnected dyke sets. The formation and orientation of this dyke set is interpreted to be related to the stretching of roof strata above elongated magma lobes that facilitated the propagation of the inner sill, similar to the "cracked lid" model described for large saucer complexes in Antarctica. Dyke patterns generally reflect the saucer emplacement process and the associated deformation of wall rocks rather than far-field regional stresses.

Identification of vacancy-oxygen complexes in oxygen-implanted silicon probed with slow positrons

NASA Astrophysics Data System (ADS)

Fujinami, M.; Miyagoe, T.; Sawada, T.; Suzuki, R.; Ohdaira, T.; Akahane, T.

2004-04-01

Defects and their annealing behavior for low (2×1015/cm2) and high (1.7×1018/cm2) doses of 180 keV oxygen-implanted silicon have been investigated by the coincidence Doppler broadening (CDB) and lifetime measurements in variable-energy positron annihilation spectroscopy. In the low-dose sample, divacancies are induced throughout the entire implantation region. In the vacancy-oxygen coexisting region (300-500 nm depths), by raising the annealing temperature to 600 °C, vacancy-oxygen VxOy complexes with one vacant site are formed and, simultaneously, the migration of oxygen begins to takes place. In the vacancy-rich region (-200 nm depths), the evolution of simple vacancy clusters to V4 is mainly observed below 600 °C. From CDB and lifetime measurements, it has been proven that after annealing at 800 °C, the VxOy complexes are formed throughout the implanted region and they contain four vacant sites and a high ratio of y to x. On the other hand, high-dose implantation at 550 °C produces the VxOy complexes with a lifetime of a 430 ps in the near-surface region (less than 200 nm deep) and annealing at 1100 °C leads to the highest ratio of y to x. These complexes cannot be annealed out even by annealing at 1350 °C, and their structure is found to be very similar to that for the electron-irradiated amorphous SiO2.

The intrinsic flexibility of the aptamer targeting the ribosomal protein S8 is a key factor for the molecular recognition.

PubMed

Autiero, Ida; Ruvo, Menotti; Improta, Roberto; Vitagliano, Luigi

2018-04-01

Aptamers are RNA/DNA biomolecules representing an emerging class of protein interactors and regulators. Despite the growing interest in these molecules, current understanding of chemical-physical basis of their target recognition is limited. Recently, the characterization of the aptamer targeting the protein-S8 has suggested that flexibility plays important functional roles. We investigated the structural versatility of the S8-aptamer by molecular dynamics simulations. Five different simulations have been conducted by varying starting structures and temperatures. The simulation of S8-aptamer complex provides a dynamic view of the contacts occurring at the complex interface. The simulation of the aptamer in ligand-free state indicates that its central region is intrinsically endowed with a remarkable flexibility. Nevertheless, none of the trajectory structures adopts the structure observed in the S8-aptamer complex. The aptamer ligand-bound is very rigid in the simulation carried out at 300 K. A structural transition of this state, providing insights into the aptamer-protein recognition process, is observed in a simulation carried out at 400 K. These data indicate that a key event in the binding is linked to the widening of the central region of the aptamer. Particularly relevant is switch of the A26 base from its ligand-free state to a location that allows the G13-C28 base-pairing. Intrinsic flexibility of the aptamer is essential for partner recognition. Present data indicate that S8 recognizes the aptamer through an induced-fit rather than a population-shift mechanism. The present study provides deeper understanding of the structural basis of the structural versatility of aptamers. Copyright © 2018 Elsevier B.V. All rights reserved.

Anatomy of the human hypothalamus (chiasmatic and tuberal region).

PubMed

Braak, H; Braak, E

1992-01-01

The hypothalamus sensu stricto consists of the chiasmatic, the tuberal and the mamillary region. The present study is confined to the poorly myelinated chiasmatic and tuberal region. Both regions harbor many nuclear grays with relatively clear-cut boundaries embedded in an ill-defined nerve cell assembly referred to as the hypothalamic gray. Prominent components of the chiasmatic region are the magnocellular neurosecretory complex (supraoptic nucleus, paraventricular nucleus, accessory neurosecretory nucleus), the sexually dimorphic intermediate nucleus, the suprachiasmatic and retrochiasmatic nuclei. The dominating structure of the tuberal region is the complex of the ventromedial, posteromedial and dorsomedial nuclei supplemented by the periventricular and infundibular nuclei. Lateral portions of the tuber cinereum harbor the lateral tuberal nucleus and the tuberomamillary nucleus. The lateral tuberal nucleus exhibits pronounced cell loss in Huntington's chorea and is also severely involved in cases of dementia with argyrophilic grains. The large nerve cells of the tuberomamillary nucleus show particularly severe affection in both Alzheimer's (intraneuronal neurofibrillary changes) and Parkinson's disease (Lewy bodies).

Tertiary model of a plant cellulose synthase

PubMed Central

Sethaphong, Latsavongsakda; Haigler, Candace H.; Kubicki, James D.; Zimmer, Jochen; Bonetta, Dario; DeBolt, Seth; Yingling, Yaroslava G.

2013-01-01

A 3D atomistic model of a plant cellulose synthase (CESA) has remained elusive despite over forty years of experimental effort. Here, we report a computationally predicted 3D structure of 506 amino acids of cotton CESA within the cytosolic region. Comparison of the predicted plant CESA structure with the solved structure of a bacterial cellulose-synthesizing protein validates the overall fold of the modeled glycosyltransferase (GT) domain. The coaligned plant and bacterial GT domains share a six-stranded β-sheet, five α-helices, and conserved motifs similar to those required for catalysis in other GT-2 glycosyltransferases. Extending beyond the cross-kingdom similarities related to cellulose polymerization, the predicted structure of cotton CESA reveals that plant-specific modules (plant-conserved region and class-specific region) fold into distinct subdomains on the periphery of the catalytic region. Computational results support the importance of the plant-conserved region and/or class-specific region in CESA oligomerization to form the multimeric cellulose–synthesis complexes that are characteristic of plants. Relatively high sequence conservation between plant CESAs allowed mapping of known mutations and two previously undescribed mutations that perturb cellulose synthesis in Arabidopsis thaliana to their analogous positions in the modeled structure. Most of these mutation sites are near the predicted catalytic region, and the confluence of other mutation sites supports the existence of previously undefined functional nodes within the catalytic core of CESA. Overall, the predicted tertiary structure provides a platform for the biochemical engineering of plant CESAs. PMID:23592721

The ambient stress field in the continental margin around the Korean Peninsula and Japanese islands

NASA Astrophysics Data System (ADS)

Lee, J.; Hong, T. K.; Chang, C.

2016-12-01

The ambient stress field is mainly influenced by regional tectonics. The stress field composition is crucial information for seismic hazard assessment. The Korean Peninsula, Japanese Islands and East Sea comprise the eastern margin of the Eurasian plate. The regions are surrounded by the Okhotsk, Pacific, and Philippine Sea plates. We investigate the regional stress field around the Korean Peninsula and Japanese islands using the focal mechanism solutions of regional earthquakes. Complex lateral and vertical variations of regional crustal stress fields are observed around a continental margin. The dominant compression directions are ENE-WSW around the Korean Peninsula and eastern China, E-W in the central East Sea and northern and southern Japan, NW-SE in the central Japan, and N-S around the northern Nankai trough. The horizontal compression directions are observed to be different by fault type, suggesting structure-dependent stress field distortion. The regional stress field change by depth and location, suggesting that the compression and tension stress may alternate in local region. The stress field and structures affect mutually, causing stress field distortion and reactivation of paleo-structures. These observation may be useful for understanding of local stress-field perturbation for seismic hazard mitigation of the region.

Structural insight into the rearrangement of the switch I region in GTP-bound G12A K-Ras.

PubMed

Xu, Shenyuan; Long, Brian N; Boris, Gabriel H; Chen, Anqi; Ni, Shuisong; Kennedy, Michael A

2017-12-01

K-Ras, a molecular switch that regulates cell growth, apoptosis and metabolism, is activated when it undergoes a conformation change upon binding GTP and is deactivated following the hydrolysis of GTP to GDP. Hydrolysis of GTP in water is accelerated by coordination to K-Ras, where GTP adopts a high-energy conformation approaching the transition state. The G12A mutation reduces intrinsic K-Ras GTP hydrolysis by an unexplained mechanism. Here, crystal structures of G12A K-Ras in complex with GDP, GTP, GTPγS and GppNHp, and of Q61A K-Ras in complex with GDP, are reported. In the G12A K-Ras-GTP complex, the switch I region undergoes a significant reorganization such that the Tyr32 side chain points towards the GTP-binding pocket and forms a hydrogen bond to the GTP γ-phosphate, effectively stabilizing GTP in its precatalytic state, increasing the activation energy required to reach the transition state and contributing to the reduced intrinsic GTPase activity of G12A K-Ras mutants.

Structural insight into the rearrangement of the switch I region in GTP-bound G12A K-Ras

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

Xu, Shenyuan; Long, Brian N.; Boris, Gabriel H.

K-Ras, a molecular switch that regulates cell growth, apoptosis and metabolism, is activated when it undergoes a conformation change upon binding GTP and is deactivated following the hydrolysis of GTP to GDP. Hydrolysis of GTP in water is accelerated by coordination to K-Ras, where GTP adopts a high-energy conformation approaching the transition state. The G12A mutation reduces intrinsic K-Ras GTP hydrolysis by an unexplained mechanism. Here, crystal structures of G12A K-Ras in complex with GDP, GTP, GTPγS and GppNHp, and of Q61A K-Ras in complex with GDP, are reported. In the G12A K-Ras–GTP complex, the switch I region undergoes amore » significant reorganization such that the Tyr32 side chain points towards the GTP-binding pocket and forms a hydrogen bond to the GTP γ-phosphate, effectively stabilizing GTP in its precatalytic state, increasing the activation energy required to reach the transition state and contributing to the reduced intrinsic GTPase activity of G12A K-Ras mutants.« less

Integrative Approach for Computationally Inferring Interactions between the Alpha and Beta Subunits of the Calcium-Activated Potassium Channel (BK): a Docking Study

PubMed Central

González, Janneth; Gálvez, Angela; Morales, Ludis; Barreto, George E.; Capani, Francisco; Sierra, Omar; Torres, Yolima

2013-01-01

Three-dimensional models of the alpha- and beta-1 subunits of the calcium-activated potassium channel (BK) were predicted by threading modeling. A recursive approach comprising of sequence alignment and model building based on three templates was used to build these models, with the refinement of non-conserved regions carried out using threading techniques. The complex formed by the subunits was studied by means of docking techniques, using 3D models of the two subunits, and an approach based on rigid-body structures. Structural effects of the complex were analyzed with respect to hydrogen-bond interactions and binding-energy calculations. Potential interaction sites of the complex were determined by referencing a study of the difference accessible surface area (DASA) of the protein subunits in the complex. PMID:23492851

Structural and functional properties of the HIV-1 RNA-tRNA(Lys)3 primer complex annealed by the nucleocapsid protein: comparison with the heat-annealed complex.

PubMed Central

Brulé, Fabienne; Marquet, Roland; Rong, Liwei; Wainberg, Mark A; Roques, Bernard P; Le Grice, Stuart F J; Ehresmann, Bernard; Ehresmann, Chantal

2002-01-01

The conversion of the single-stranded RNA genome into double-stranded DNA by virus-coded reverse transcriptase (RT) is an essential step of the retrovirus life cycle. In human immunodeficiency virus type 1 (HIV-1), RT uses the cellular tRNA(Lys)3 to initiate the (-) strand DNA synthesis. Placement of the primer tRNA(Lys)3 involves binding of its 3'-terminal 18 nt to a complementary region of genomic RNA termed PBS. However, the PBS sequence is not the unique determinant of primer usage and additional contacts are important. This placement is believed to be achieved in vivo by the nucleocapsid domain of Gag or by the mature protein NCp. Up to now, structural information essentially arose from heat-annealed primer-template complexes (Isel et al., J Mol Biol, 1995, 247:236-250; Isel et al., EMBO J, 1999, 18:1038-1048). Here, we investigated the formation of the primer-template complex mediated by NCp and compared structural and functional properties of heat- and NCp-annealed complexes. We showed that both heat- and NCp-mediated procedures allow comparable high yields of annealing. Then, we investigated structural features of both kinds of complexes by enzymatic probing, and we compared their relative efficiency in (-) strong stop DNA synthesis. We did not find any significant differences between these complexes, suggesting that information derived from the heat-annealed complex can be transposed to the NCp-mediated complex and most likely to complexes formed in vivo. PMID:11873759

Neural substrates of decision-making.

PubMed

Broche-Pérez, Y; Herrera Jiménez, L F; Omar-Martínez, E

2016-06-01

Decision-making is the process of selecting a course of action from among 2 or more alternatives by considering the potential outcomes of selecting each option and estimating its consequences in the short, medium and long term. The prefrontal cortex (PFC) has traditionally been considered the key neural structure in decision-making process. However, new studies support the hypothesis that describes a complex neural network including both cortical and subcortical structures. The aim of this review is to summarise evidence on the anatomical structures underlying the decision-making process, considering new findings that support the existence of a complex neural network that gives rise to this complex neuropsychological process. Current evidence shows that the cortical structures involved in decision-making include the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). This process is assisted by subcortical structures including the amygdala, thalamus, and cerebellum. Findings to date show that both cortical and subcortical brain regions contribute to the decision-making process. The neural basis of decision-making is a complex neural network of cortico-cortical and cortico-subcortical connections which includes subareas of the PFC, limbic structures, and the cerebellum. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

A Novel Mammalian Complex Containing Sin3B Mitigates Histone Acetylation and RNA Polymerase II Progression within Transcribed Loci▿

PubMed Central

Jelinic, Petar; Pellegrino, Jessica; David, Gregory

2011-01-01

Transcription requires the progression of RNA polymerase II (RNAP II) through a permissive chromatin structure. Recent studies of Saccharomyces cerevisiae have demonstrated that the yeast Sin3 protein contributes to the restoration of the repressed chromatin structure at actively transcribed loci. Yet, the mechanisms underlying the restoration of the repressive chromatin structure at transcribed loci and its significance in gene expression have not been investigated in mammals. We report here the identification of a mammalian complex containing the corepressor Sin3B, the histone deacetylase HDAC1, Mrg15, and the PHD finger-containing Pf1 and show that this complex plays important roles in regulation of transcription. We demonstrate that this complex localizes at discrete loci approximately 1 kb downstream of the transcription start site of transcribed genes, and this localization requires both Pf1's and Mrg15's interaction with chromatin. Inactivation of this mammalian complex promotes increased RNAP II progression within transcribed regions and subsequent increased transcription. Our results define a novel mammalian complex that contributes to the regulation of transcription and point to divergent uses of the Sin3 protein homologues throughout evolution in the modulation of transcription. PMID:21041482

Mycobacterium tuberculosis acyl carrier protein synthase adopts two different pH-dependent structural conformations

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

Gokulan, Kuppan; Aggarwal, Anup; Shipman, Lance

2011-09-20

The crystal structures of acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis (Mtb) and Corynebacterium ammoniagenes determined at pH 5.3 and pH 6.5, respectively, are reported. Comparison of the Mtb apo-AcpS structure with the recently reported structure of the Mtb AcpS-ADP complex revealed that AcpS adopts two different conformations: the orthorhombic and trigonal space-group structures show structural differences in the {alpha}2 helix and in the conformation of the {alpha}3-{alpha}4 connecting loop, which is in a closed conformation. The apo-AcpS structure shows electron density for the entire model and was obtained at lower pH values (4.4-6.0). In contrast, at a highermore » pH value (6.5) AcpS undergoes significant conformational changes, resulting in disordered regions that show no electron density in the AcpS model. The solved structures also reveal that C. ammoniagenes AcpS undergoes structural rearrangement in two regions, similar to the recently reported Mtb AcpS-ADP complex structure. In vitro reconstitution experiments show that AcpS has a higher post-translational modification activity between pH 4.4 and 6.0 than at pH values above 6.5, where the activity drops owing to the change in conformation. The results show that apo-AcpS and AcpS-ADP adopt different conformations depending upon the pH conditions of the crystallization solution.« less

Predicting protein complexes using a supervised learning method combined with local structural information.

PubMed

Dong, Yadong; Sun, Yongqi; Qin, Chao

2018-01-01

The existing protein complex detection methods can be broadly divided into two categories: unsupervised and supervised learning methods. Most of the unsupervised learning methods assume that protein complexes are in dense regions of protein-protein interaction (PPI) networks even though many true complexes are not dense subgraphs. Supervised learning methods utilize the informative properties of known complexes; they often extract features from existing complexes and then use the features to train a classification model. The trained model is used to guide the search process for new complexes. However, insufficient extracted features, noise in the PPI data and the incompleteness of complex data make the classification model imprecise. Consequently, the classification model is not sufficient for guiding the detection of complexes. Therefore, we propose a new robust score function that combines the classification model with local structural information. Based on the score function, we provide a search method that works both forwards and backwards. The results from experiments on six benchmark PPI datasets and three protein complex datasets show that our approach can achieve better performance compared with the state-of-the-art supervised, semi-supervised and unsupervised methods for protein complex detection, occasionally significantly outperforming such methods.

The relation between the column density structures and the magnetic field orientation in the Vela C molecular complex

NASA Astrophysics Data System (ADS)

Soler, J. D.; Ade, P. A. R.; Angilè, F. E.; Ashton, P.; Benton, S. J.; Devlin, M. J.; Dober, B.; Fissel, L. M.; Fukui, Y.; Galitzki, N.; Gandilo, N. N.; Hennebelle, P.; Klein, J.; Li, Z.-Y.; Korotkov, A. L.; Martin, P. G.; Matthews, T. G.; Moncelsi, L.; Netterfield, C. B.; Novak, G.; Pascale, E.; Poidevin, F.; Santos, F. P.; Savini, G.; Scott, D.; Shariff, J. A.; Thomas, N. E.; Tucker, C. E.; Tucker, G. S.; Ward-Thompson, D.

2017-07-01

We statistically evaluated the relative orientation between gas column density structures, inferred from Herschel submillimetre observations, and the magnetic field projected on the plane of sky, inferred from polarized thermal emission of Galactic dust observed by the Balloon-borne Large-Aperture Submillimetre Telescope for Polarimetry (BLASTPol) at 250, 350, and 500 μm, towards the Vela C molecular complex. First, we find very good agreement between the polarization orientations in the three wavelength-bands, suggesting that, at the considered common angular resolution of 3.´0 that corresponds to a physical scale of approximately 0.61 pc, the inferred magnetic field orientation is not significantly affected by temperature or dust grain alignment effects. Second, we find that the relative orientation between gas column density structures and the magnetic field changes progressively with increasing gas column density, from mostly parallel or having no preferred orientation at low column densities to mostly perpendicular at the highest column densities. This observation is in agreement with previous studies by the Planck collaboration towards more nearby molecular clouds. Finally, we find a correspondencebetween (a) the trends in relative orientation between the column density structures and the projected magnetic field; and (b) the shape of the column density probability distribution functions (PDFs). In the sub-regions of Vela C dominated by one clear filamentary structure, or "ridges", where the high-column density tails of the PDFs are flatter, we find a sharp transition from preferentially parallel or having no preferred relative orientation at low column densities to preferentially perpendicular at highest column densities. In the sub-regions of Vela C dominated by several filamentary structures with multiple orientations, or "nests", where the maximum values of the column density are smaller than in the ridge-like sub-regions and the high-column density tails of the PDFs are steeper, such a transition is also present, but it is clearly less sharp than in the ridge-like sub-regions. Both of these results suggest that the magnetic field is dynamically important for the formation of density structures in this region.

Automatic high-throughput screening of colloidal crystals using machine learning

NASA Astrophysics Data System (ADS)

Spellings, Matthew; Glotzer, Sharon C.

Recent improvements in hardware and software have united to pose an interesting problem for computational scientists studying self-assembly of particles into crystal structures: while studies covering large swathes of parameter space can be dispatched at once using modern supercomputers and parallel architectures, identifying the different regions of a phase diagram is often a serial task completed by hand. While analytic methods exist to distinguish some simple structures, they can be difficult to apply, and automatic identification of more complex structures is still lacking. In this talk we describe one method to create numerical ``fingerprints'' of local order and use them to analyze a study of complex ordered structures. We can use these methods as first steps toward automatic exploration of parameter space and, more broadly, the strategic design of new materials.

Self-rolling up micro 3D structures using temperature-responsive hydrogel sheet

NASA Astrophysics Data System (ADS)

Iwata, Y.; Miyashita, S.; Iwase, E.

2017-12-01

This paper proposes a micro self-folding using a self-rolling up deformation. In the fabrication method at micro scale, self-folding is an especially useful method of easily fabricating complex three-dimensional (3D) structures from engineered two-dimensional (2D) sheets. However, most self-folded structures are limited to 3D structures with a hollow region. Therefore, we made 3D structures with a small hollow region by self-rolling up a 2D sheet consisting of SU-8 and a temperature-responsive hybrid hydrogel of poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM-AAc). The temperature-responsive hydrogel can provide repetitive deformation, which is a good feature for micro soft robots or actuators, using hydrogel shrinking and swelling. Our micro self-rolling up method is a self-folding method for a 3D structure performed by rolling up a 2D flat sheet, like making a croissant, through continuous self-folding. We used our method to fabricate 3D structures with a small hollow region, such as cylindrical, conical, and croissant-like ellipsoidal structures, and 3D structures with a hollow region, such as spiral shapes. All the structures showed repetitive deformation, forward rolling up in 20 °C cold water and backward rolling up in 40 °C hot water. The results demonstrate that self-rolling up deformation can be useful in the field of micro soft devices.

A long-lived mesoscale convective complex. II - Evolution and structure of the mature complex

NASA Technical Reports Server (NTRS)

Wetzel, P. J.; Cotton, W. R.; Mcanelly, R. L.

1983-01-01

The present investigation is concerned with an eight-day episode, during which a series of mesoscale convective complexes (MCC) developed and moved across the country, producing heavy rain and some flooding over an extensive region. An overview of the considered period from August 3 to August 10, 1977 is presented, and the evolution of the August 4 storm is examined. The structure of the mature MCC is discussed, taking into account the August 4-5 storm, a comparative case involving the August 3-4 storm, and an evaluation of the observed phenomena. It is concluded that MCCs are basically tropical in nature and that their dynamics are dominated by buoyant accelerations. It was found that the MCCs developed a warm-core, divergent anticyclonic flow pattern in the upper troposphere which was not present prior to the development of convection. A similar structure is observed in tropical cloud clusters.

Middle region of FancM interacts with Mhf and Rmi1 in silkworms, a species lacking the Fanconi anaemia (FA) core complex.

PubMed

Sugahara, R; Mon, H; Lee, J M; Kusakabe, T

2014-04-01

The Fanconi anaemia (FA) pathway is responsible for interstrand crosslink (ICL) repair. Among the FA core complex components, FANCM is believed to act as a damage sensor for the ICL-blocked replication fork and also as a molecular platform for FA core complex assembly and interaction with Bloom's syndrome (BS) complex that is thought to play an important role in the processing of DNA structures such as stalled replication forks. In the present study, we found that in silkworms, Bombyx mori, a species lacking the major FA core complex components (FANCA, B, C, E, F, and G), FancM is required for FancD2 monoubiquitination and cell proliferation in the presence of mitomycin C (MMC). Silkworm FancM (BmFancM) was phosphorylated in the middle regions, and the modification was associated with its subcellular localization. In addition, BmFancM interacted with Mhf1, a histone-fold protein, and Rmi1, a subunit of the BS complex, in the different regions. The interaction region containing at least these two protein-binding domains played an essential role in FancM-dependent resistance to MMC. Our results suggest that BmFancM also acts as a platform for recruitment of both the FA protein and the BS protein, although the silkworm genome seems to lose FAAP24, a FancM-binding partner protein in mammals. © 2013 The Royal Entomological Society.

Fiber Diffraction of the Prion-Forming Domain HET-s(218-289) Shows Dehydration-Induced Deformation of a Complex Amyloid Structure

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

Wan, William; Stubbs, Gerald

2014-05-01

Amyloids are filamentous protein aggregates that can be formed by many different proteins and are associated with both disease and biological functions. The pathogenicities or biological functions of amyloids are determined by their particular molecular structures, making accurate structural models a requirement for understanding their biological effects. One potential factor that can affect amyloid structures is hydration. Previous studies of simple stacked β-sheet amyloids have suggested that dehydration does not impact structure, but other studies indicated dehydration-related structural changes of a putative water-filled nanotube. Our results show that dehydration significantly affects the molecular structure of the fungal prion-forming domain HET-s(218–289),more » which forms a β-solenoid with no internal solvent-accessible regions. The dehydration-related structural deformation of HET-s(218–289) indicates that water can play a significant role in complex amyloid structures, even when no obvious water-accessible cavities are present.« less

Disruption of Higher Order DNA Structures in Friedreich’s Ataxia (GAA)n Repeats by PNA or LNA Targeting

PubMed Central

Bergquist, Helen; Rocha, Cristina S. J.; Álvarez-Asencio, Rubén; Nguyen, Chi-Hung; Rutland, Mark. W.; Smith, C. I. Edvard; Good, Liam; Nielsen, Peter E.; Zain, Rula

2016-01-01

Expansion of (GAA)n repeats in the first intron of the Frataxin gene is associated with reduced mRNA and protein levels and the development of Friedreich’s ataxia. (GAA)n expansions form non-canonical structures, including intramolecular triplex (H-DNA), and R-loops and are associated with epigenetic modifications. With the aim of interfering with higher order H-DNA (like) DNA structures within pathological (GAA)n expansions, we examined sequence-specific interaction of peptide nucleic acid (PNA) with (GAA)n repeats of different lengths (short: n=9, medium: n=75 or long: n=115) by chemical probing of triple helical and single stranded regions. We found that a triplex structure (H-DNA) forms at GAA repeats of different lengths; however, single stranded regions were not detected within the medium size pathological repeat, suggesting the presence of a more complex structure. Furthermore, (GAA)4-PNA binding of the repeat abolished all detectable triplex DNA structures, whereas (CTT)5-PNA did not. We present evidence that (GAA)4-PNA can invade the DNA at the repeat region by binding the DNA CTT strand, thereby preventing non-canonical-DNA formation, and that triplex invasion complexes by (CTT)5-PNA form at the GAA repeats. Locked nucleic acid (LNA) oligonucleotides also inhibited triplex formation at GAA repeat expansions, and atomic force microscopy analysis showed significant relaxation of plasmid morphology in the presence of GAA-LNA. Thus, by inhibiting disease related higher order DNA structures in the Frataxin gene, such PNA and LNA oligomers may have potential for discovery of drugs aiming at recovering Frataxin expression. PMID:27846236

Crystal structure of the DNA-binding domain of the LysR-type transcriptional regulator CbnR in complex with a DNA fragment of the recognition-binding site in the promoter region.

PubMed

Koentjoro, Maharani Pertiwi; Adachi, Naruhiko; Senda, Miki; Ogawa, Naoto; Senda, Toshiya

2018-03-01

LysR-type transcriptional regulators (LTTRs) are among the most abundant transcriptional regulators in bacteria. CbnR is an LTTR derived from Cupriavidus necator (formerly Alcaligenes eutrophus or Ralstonia eutropha) NH9 and is involved in transcriptional activation of the cbnABCD genes encoding chlorocatechol degradative enzymes. CbnR interacts with a cbnA promoter region of approximately 60 bp in length that contains the recognition-binding site (RBS) and activation-binding site (ABS). Upon inducer binding, CbnR seems to undergo conformational changes, leading to the activation of the transcription. Since the interaction of an LTTR with RBS is considered to be the first step of the transcriptional activation, the CbnR-RBS interaction is responsible for the selectivity of the promoter to be activated. To understand the sequence selectivity of CbnR, we determined the crystal structure of the DNA-binding domain of CbnR in complex with RBS of the cbnA promoter at 2.55 Å resolution. The crystal structure revealed details of the interactions between the DNA-binding domain and the promoter DNA. A comparison with the previously reported crystal structure of the DNA-binding domain of BenM in complex with its cognate RBS showed several differences in the DNA interactions, despite the structural similarity between CbnR and BenM. These differences explain the observed promoter sequence selectivity between CbnR and BenM. Particularly, the difference between Thr33 in CbnR and Ser33 in BenM appears to affect the conformations of neighboring residues, leading to the selective interactions with DNA. Atomic coordinates and structure factors for the DNA-binding domain of Cupriavidus necatorNH9 CbnR in complex with RBS are available in the Protein Data Bank under the accession code 5XXP. © 2018 Federation of European Biochemical Societies.

Influence of Anthropogenic Disturbances on Stand Structural Complexity in Andean Temperate Forests: Implications for Managing Key Habitat for Biodiversity.

PubMed

Caviedes, Julián; Ibarra, José Tomás

2017-01-01

Forest attributes and their abundances define the stand structural complexity available as habitat for faunal biodiversity; however, intensive anthropogenic disturbances have the potential to degrade and simplify forest stands. In this paper we develop an index of stand structural complexity and show how anthropogenic disturbances, namely fire, logging, livestock, and their combined presence, affect stand structural complexity in a southern Global Biodiversity Hotspot. From 2011 to 2013, we measured forest structural attributes as well as the presence of anthropogenic disturbances in 505 plots in the Andean zone of the La Araucanía Region, Chile. In each plot, understory density, coarse woody debris, number of snags, tree diameter at breast height, and litter depth were measured, along with signs of the presence of anthropogenic disturbances. Ninety-five percent of the plots showed signs of anthropogenic disturbance (N = 475), with the combined presence of fire, logging, and livestock being the most common disturbance (N = 222; 44% of plots). The lowest values for the index were measured in plots combining fire, logging, and livestock. Undisturbed plots and plots with the presence of relatively old fires (> 70 years) showed the highest values for the index of stand structural complexity. Our results suggest that secondary forests < 70-year post-fire event, with the presence of habitat legacies (e.g. snags and CWD), can reach a structural complexity as high as undisturbed plots. Temperate forests should be managed to retain structural attributes, including understory density (7.2 ± 2.5 # contacts), volume of CWD (22.4 ± 25.8 m3/ha), snag density (94.4 ± 71.0 stems/ha), stand basal area (61.2 ± 31.4 m2/ha), and litter depth (7.5 ± 2.7 cm). Achieving these values will increase forest structural complexity, likely benefiting a range of faunal species in South American temperate forests.

Influence of Anthropogenic Disturbances on Stand Structural Complexity in Andean Temperate Forests: Implications for Managing Key Habitat for Biodiversity

PubMed Central

2017-01-01

Forest attributes and their abundances define the stand structural complexity available as habitat for faunal biodiversity; however, intensive anthropogenic disturbances have the potential to degrade and simplify forest stands. In this paper we develop an index of stand structural complexity and show how anthropogenic disturbances, namely fire, logging, livestock, and their combined presence, affect stand structural complexity in a southern Global Biodiversity Hotspot. From 2011 to 2013, we measured forest structural attributes as well as the presence of anthropogenic disturbances in 505 plots in the Andean zone of the La Araucanía Region, Chile. In each plot, understory density, coarse woody debris, number of snags, tree diameter at breast height, and litter depth were measured, along with signs of the presence of anthropogenic disturbances. Ninety-five percent of the plots showed signs of anthropogenic disturbance (N = 475), with the combined presence of fire, logging, and livestock being the most common disturbance (N = 222; 44% of plots). The lowest values for the index were measured in plots combining fire, logging, and livestock. Undisturbed plots and plots with the presence of relatively old fires (> 70 years) showed the highest values for the index of stand structural complexity. Our results suggest that secondary forests < 70-year post-fire event, with the presence of habitat legacies (e.g. snags and CWD), can reach a structural complexity as high as undisturbed plots. Temperate forests should be managed to retain structural attributes, including understory density (7.2 ± 2.5 # contacts), volume of CWD (22.4 ± 25.8 m3/ha), snag density (94.4 ± 71.0 stems/ha), stand basal area (61.2 ± 31.4 m2/ha), and litter depth (7.5 ± 2.7 cm). Achieving these values will increase forest structural complexity, likely benefiting a range of faunal species in South American temperate forests. PMID:28068349

[Conceptual approach to formation of a modern system of medical provision].

PubMed

Belevitin, A B; Miroshnichenko, Iu V; Bunin, S A; Goriachev, A B; Krasavin, K D

2009-09-01

Within the frame of forming of a new face of medical service of the Armed Forces, were determined the principle approaches to optimization of the process of development of the system of medical supply. It was proposed to use the following principles: principle of hierarchic structuring, principle of purposeful orientation, principle of vertical task sharing, principle of horizontal task sharing, principle of complex simulation, principle of permanent perfection. The main direction of optimization of structure and composition of system of medical supply of the Armed Forces are: forming of modern institutes of medical supply--centers of support by technique and facilities on the base of central, regional storehouses, and attachment of several functions of organs of military government to them; creation of medical supply office on the base military hospitals, being basing treatment-prophylaxis institutes, in adjusted territorial zones of responsibility for the purpose of realization of complex of tasks of supplying the units and institutes, attached to them on medical support, by medical equipment. Building of medical support system is realized on three levels: Center - Military region (NAVY region) - territorial zone of responsibility.

Architecture and Flexibility of the Yeast Ndc80 Kinetochore Complex

PubMed Central

Wang, Hong-Wei; Long, Sydney; Ciferri, Claudio; Westermann, Stefan; Drubin, David; Barnes, Georjana; Nogales, Eva

2008-01-01

Kinetochores mediate microtubule–chromosome attachment and ensure accurate segregation of sister chromatids. The highly conserved Ndc80 kinetochore complex makes direct contacts with the microtubule and is essential for spindle checkpoint signaling. It contains a long coiled-coil region with globular domains at each end involved in kinetochore localization and microtubule binding, respectively. We have directly visualized the architecture of the yeast Ndc80 complex and found a dramatic kink within the 560-Å coiled-coil rod located about 160 Å from the larger globular head. Comparison of our electron microscopy images to the structure of the human Ndc80 complex allowed us to position the kink proximal to the microtubule-binding end and to define the conformational range of the complex. The position of the kink coincides with a coiled-coil breaking region conserved across eukaryotes. We hypothesize that the kink in Ndc80 is essential for correct kinetochore geometry and could be part of a tension-sensing mechanism at the kinetochore. PMID:18793650

On the Importance of Polar Interactions for Complexes Containing Intrinsically Disordered Proteins

PubMed Central

Wong, Eric T. C.; Na, Dokyun; Gsponer, Jörg

2013-01-01

There is a growing recognition for the importance of proteins with large intrinsically disordered (ID) segments in cell signaling and regulation. ID segments in these proteins often harbor regions that mediate molecular recognition. Coupled folding and binding of the recognition regions has been proposed to confer high specificity to interactions involving ID segments. However, researchers recently questioned the origin of the interaction specificity of ID proteins because of the overrepresentation of hydrophobic residues in their interaction interfaces. Here, we focused on the role of polar and charged residues in interactions mediated by ID segments. Making use of the extended nature of most ID segments when in complex with globular proteins, we first identified large numbers of complexes between globular proteins and ID segments by using radius-of-gyration-based selection criteria. Consistent with previous studies, we found the interfaces of these complexes to be enriched in hydrophobic residues, and that these residues contribute significantly to the stability of the interaction interface. However, our analyses also show that polar interactions play a larger role in these complexes than in structured protein complexes. Computational alanine scanning and salt-bridge analysis indicate that interfaces in ID complexes are highly complementary with respect to electrostatics, more so than interfaces of globular proteins. Follow-up calculations of the electrostatic contributions to the free energy of binding uncovered significantly stronger Coulombic interactions in complexes harbouring ID segments than in structured protein complexes. However, they are counter-balanced by even higher polar-desolvation penalties. We propose that polar interactions are a key contributing factor to the observed high specificity of ID segment-mediated interactions. PMID:23990768

Receiver Functions From Regional and Near-Teleseismic P Waves

NASA Astrophysics Data System (ADS)

Park, J.; Levin, V.

2001-05-01

P waves from regional-distance earthquakes are complex and reverberatory, as would be expected from a combination of head waves, post-critical crustal reflections and shallow-incident P from the upper mantle. Although developed to analyze steeply-incident teleseismic P waves, receiver function analysis can also retrieve information about crustal structure from regional and near-teleseismic P. Using a new method to estimate receiver functions, based on multiple-taper spectral analysis, regional-distance RFs for GSN stations RAYN and ANTO show broad agreement with teleseismic RFs. At RAYN the moveout of the Moho-converted Ps phase, relative to direct P, follows well the predictions of the IASP91 earth model. The Moho-converted Ps phase shows complexity associated with the transition-zone triplication near Δ =20o and constant delay (zero moveout) as Δ -> 0, consistent with conversion from Pn. Similar behavior is seen for ANTO for events that arrive from the west. For eastern backazimuths the ANTO RFs show features whose moveout is negative as Δ -> 0. This moveout is poorly fit by reverberations in flat layers or by direct scattering from a dipping interface, but is consistent with a topographic scatterer 20--30 km eastward of the ANTO site. Regional receiver functions may therefore be useful in judging whether teleseismic RFs at a particular station are suitable candidates for a 1-D velocity structure inversion. Synthetic seismograms of regional P phases, computed with a locked-mode reflectivity approach, confirm broad features of the RAYN and ANTO regional receiver functions.

Complex folding and misfolding effects of deer-specific amino acid substitutions in the β2-α2 loop of murine prion protein

NASA Astrophysics Data System (ADS)

Agarwal, Sonya; Döring, Kristina; Gierusz, Leszek A.; Iyer, Pooja; Lane, Fiona M.; Graham, James F.; Goldmann, Wilfred; Pinheiro, Teresa J. T.; Gill, Andrew C.

2015-10-01

The β2-α2 loop of PrPC is a key modulator of disease-associated prion protein misfolding. Amino acids that differentiate mouse (Ser169, Asn173) and deer (Asn169, Thr173) PrPC appear to confer dramatically different structural properties in this region and it has been suggested that amino acid sequences associated with structural rigidity of the loop also confer susceptibility to prion disease. Using mouse recombinant PrP, we show that mutating residue 173 from Asn to Thr alters protein stability and misfolding only subtly, whilst changing Ser to Asn at codon 169 causes instability in the protein, promotes oligomer formation and dramatically potentiates fibril formation. The doubly mutated protein exhibits more complex folding and misfolding behaviour than either single mutant, suggestive of differential effects of the β2-α2 loop sequence on both protein stability and on specific misfolding pathways. Molecular dynamics simulation of protein structure suggests a key role for the solvent accessibility of Tyr168 in promoting molecular interactions that may lead to prion protein misfolding. Thus, we conclude that ‘rigidity’ in the β2-α2 loop region of the normal conformer of PrP has less effect on misfolding than other sequence-related effects in this region.

Crustal structure associated with Gondwana graben across the Narmada-Son lineament in India: An inference from aeromagnetics

NASA Astrophysics Data System (ADS)

Rao, D. Atchuta; Babu, H. V. Ram; Sinha, G. D. J. Sivakumar

1992-10-01

Aeromagnetic data over an 80-km-wide belt along the ENE-trending Narmada-Son lineament (NSL), starting from Baroda in the west and continuing to the south of Jabalpur in the east, has been studied to understand the structural and tectonic framework of the region. The area is covered by generally E-W-trending steeply dipping and folded Archean phyllites and quartzites as basement, with Bijawars (Upper Precambrian), upper Vindhyans (Upper Proterozoic), and Gondwanas (Upper Carboniferous) overlying them. Overlapping them all are the Deccan trap (Cretaceous-Eocene) flows. Aeromagnetic linements and their disposition and pattern in this region suggest major dislocations in the crust. The region around Hoshangabad, which is the intersection point of the NSL and the northwestern extension of the Godavari lineament, appears to have been intensely disturbed. Spectral analysis of aeromagnetic profiles across the NSL belt brought out a deep magnetic interface within crust at depths varying from 4 km to about 20 km below the surface, perhaps corresponding to the discontinuity characterized by the interface of granitic and basaltic rocks. There is a significant downwarping of this interface under the Hoshangabad region, suggesting that this is perhaps related to the evolution of the Gondwana basin structure in this area. This warping of the magnetic interface may be a reflection of the crustal flexuring and rift faulting. Elsewhere in the world, concentrations of carbonatite complexes and dike swarms are known to occur in areas of crustal flexuring and rift faulting. The occurrence of carbonatite complexes in this region (e.g. at Amba Dongar and Barwaha, and dike swarms in the Dadiapada region) gives credence to the present inferences from the aeromagnetic study.

Deciphering the Dynamic Interaction Profile of an Intrinsically Disordered Protein by NMR Exchange Spectroscopy.

PubMed

Delaforge, Elise; Kragelj, Jaka; Tengo, Laura; Palencia, Andrés; Milles, Sigrid; Bouvignies, Guillaume; Salvi, Nicola; Blackledge, Martin; Jensen, Malene Ringkjøbing

2018-01-24

Intrinsically disordered proteins (IDPs) display a large number of interaction modes including folding-upon-binding, binding without major structural transitions, or binding through highly dynamic, so-called fuzzy, complexes. The vast majority of experimental information about IDP binding modes have been inferred from crystal structures of proteins in complex with short peptides of IDPs. However, crystal structures provide a mainly static view of the complexes and do not give information about the conformational dynamics experienced by the IDP in the bound state. Knowledge of the dynamics of IDP complexes is of fundamental importance to understand how IDPs engage in highly specific interactions without concomitantly high binding affinity. Here, we combine rotating-frame R 1ρ , Carr-Purcell-Meiboom Gill relaxation dispersion as well as chemical exchange saturation transfer to decipher the dynamic interaction profile of an IDP in complex with its partner. We apply the approach to the dynamic signaling complex formed between the mitogen-activated protein kinase (MAPK) p38α and the intrinsically disordered regulatory domain of the MAPK kinase MKK4. Our study demonstrates that MKK4 employs a subtle combination of interaction modes in order to bind to p38α, leading to a complex displaying significantly different dynamics across the bound regions.

Natural and land-use history of the Northwest mountain ecoregions (USA) in relation to patterns of plant invasions.

Treesearch

Catherine G. Parks; Steven R. Radosevich; Bryan A. Endress; Bridgett J. Naylor; Dawn Anzinger; Lisa J. Rew; Bruce D. Maxwell; Kathleen A. Dwire

2005-01-01

Although the Northwest currently has the least proportion of non-native invasive plant species relative to other regions or North America, invasions continue to increase into the mountainous areas of the region. Landscape structure, such as the variation found along the complex gradients of the Northwest mountain ecoregions, affects the expansion of invasive plant...

Current forest conditions of older stands of the mixed mesophytic forest region on the Appalachian Plateaus Province of eastern Kentucky

Treesearch

James F. Jr. Rosson

2008-01-01

E. Lucy Braun coined the term "mixed mesophytic forest" in 1916. These forests are structurally complex and occur extensively across the Appalachian Plateaus Province. This region is considered the epicenter of highest development of the eastern deciduous forest. I used U.S. Forest Service, Forest Inventory and Analysis (FIA) data to study current forest...

Atomic force microscopy studies of native photosynthetic membranes.

PubMed

Sturgis, James N; Tucker, Jaimey D; Olsen, John D; Hunter, C Neil; Niederman, Robert A

2009-05-05

In addition to providing the earliest surface images of a native photosynthetic membrane at submolecular resolution, examination of the intracytoplasmic membrane (ICM) of purple bacteria by atomic force microscopy (AFM) has revealed a wide diversity of species-dependent arrangements of closely packed light-harvesting (LH) antennae, capable of fulfilling the basic requirements for efficient collection, transmission, and trapping of radiant energy. A highly organized architecture was observed with fused preparations of the pseudocrystalline ICM of Blastochloris viridis, consiting of hexagonally packed monomeric reaction center light-harvesting 1 (RC-LH1) core complexes. Among strains which also form a peripheral LH2 antenna, images of ICM patches from Rhodobacter sphaeroides exhibited well-ordered, interconnected networks of dimeric RC-LH1 core complexes intercalated by rows of LH2, coexisting with LH2-only domains. Other peripheral antenna-containing species, notably Rhodospirillum photometricum and Rhodopseudomonas palustris, showed a less regular organization, with mixed regions of LH2 and RC-LH1 cores, intermingled with large, paracrystalline domains. The ATP synthase and cytochrome bc(1) complex were not observed in any of these topographs and are thought to be localized in the adjacent cytoplasmic membrane or in inaccessible ICM regions separated from the flat regions imaged by AFM. The AFM images have served as a basis for atomic-resolution modeling of the ICM vesicle surface, as well as forces driving segregation of photosynthetic complexes into distinct domains. Docking of atomic-resolution molecular structures into AFM topographs of Rsp. photometricum membranes generated precise in situ structural models of the core complex surrounded by LH2 rings and a region of tightly packed LH2 complexes. A similar approach has generated a model of the highly curved LH2-only membranes of Rba. sphaeroides which predicts that sufficient space exists between LH2 complexes for quinones to diffuse freely. Measurement of the intercomplex distances between adjacent LH2 rings of Phaeospirillum molischianum has permitted the first calculation of the separation of bacteriochlorophyll a molecules in the native ICM. A recent AFM analysis of the organization of green plant photosystem II (PSII) in grana thylakoids revealed the protruding oxygen-evolving complex, crowded together in parallel alignment at three distinct levels of stacked membranes over the lumenal surface. The results also confirmed that PSII-LHCII supercomplexes are displaced relative to one another in opposing grana membranes.

Neuroarchitecture and neuroanatomy of the Drosophila central complex: A GAL4-based dissection of protocerebral bridge neurons and circuits

PubMed Central

Wolff, Tanya; Iyer, Nirmala A; Rubin, Gerald M

2015-01-01

Insects exhibit an elaborate repertoire of behaviors in response to environmental stimuli. The central complex plays a key role in combining various modalities of sensory information with an insect's internal state and past experience to select appropriate responses. Progress has been made in understanding the broad spectrum of outputs from the central complex neuropils and circuits involved in numerous behaviors. Many resident neurons have also been identified. However, the specific roles of these intricate structures and the functional connections between them remain largely obscure. Significant gains rely on obtaining a comprehensive catalog of the neurons and associated GAL4 lines that arborize within these brain regions, and on mapping neuronal pathways connecting these structures. To this end, small populations of neurons in the Drosophila melanogaster central complex were stochastically labeled using the multicolor flip-out technique and a catalog was created of the neurons, their morphologies, trajectories, relative arrangements, and corresponding GAL4 lines. This report focuses on one structure of the central complex, the protocerebral bridge, and identifies just 17 morphologically distinct cell types that arborize in this structure. This work also provides new insights into the anatomical structure of the four components of the central complex and its accessory neuropils. Most strikingly, we found that the protocerebral bridge contains 18 glomeruli, not 16, as previously believed. Revised wiring diagrams that take into account this updated architectural design are presented. This updated map of the Drosophila central complex will facilitate a deeper behavioral and physiological dissection of this sophisticated set of structures. J. Comp. Neurol. 523:997–1037, 2015. © 2014 Wiley Periodicals, Inc. PMID:25380328

Structural Confirmation of a Bent and Open Model for the Initiation Complex of T7 RNA Polymerase

PubMed Central

Turingan, Rosemary S.; Liu, Cuihua; Hawkins, Mary E.; Martin, Craig T.

2008-01-01

T7 RNA polymerase is known to induce bending of its promoter DNA upon binding, as evidenced by gel-shift assays and by recent end-to-end fluorescence energy transfer distance measurements. Crystal structures of promoter-bound and initially transcribing complexes, however, lack downstream DNA, providing no information on the overall path of the DNA through the protein. Crystal structures of the elongation complex do include downstream DNA and provide valuable guidance in the design of models for the complete melted bubble structure at initiation. In the current study, we test a specific structural model for the initiation complex, obtained by alignment of the C-terminal regions of the protein structures from both initiation and elongation and then simple transferal of the downstream DNA from the elongation complex onto the initiation complex. FRET measurement of distances from a point upstream on the promoter DNA to various points along the downstream helix reproduce the expected helical periodicity in the distances and support the model’s orientation and phasing of the downstream DNA. The model also makes predictions about the extent of melting downstream of the active site. By monitoring fluorescent base analogs incorporated at various positions in the DNA we have mapped the downstream edge of the bubble, confirming the model. The initially melted bubble, in the absence of substrate, encompasses 7–8 bases and is sufficient to allow synthesis of a 3 base transcript before further melting is required. The results demonstrate that despite massive changes in the N-terminal portion of the protein and in the DNA upstream of the active site, the DNA downstream of the active site is virtually identical in both initiation and elongation complexes. PMID:17253774

A compilation of mineral occurrences and the relationship of occurrences to structural elements of the Kentucky and Tennessee region

NASA Technical Reports Server (NTRS)

Mayhew, M. A.; Myers, D. M.

1984-01-01

A very prominent magnetic anomaly measured by MAGSAT over the eastern mid-continent of the United States was inferred to have a source region beneath Kentucky and Tennessee. Prominent aeromagnetic and gravity anomalies are also associated with the inferred source region. A crustal model constructed to fit these anomalies interpreted the complex as a large mafic plutonic intrusion of Precambrian age. The complex was named the Kentucky body. It was noticed that the Jessamine Dome, which is a locus of intense faulting and mineralization, occurs near the northern end of the Kentucky body, and that more generally there seemed to be a spatial relationship between mineral occurrence and the body. The relationship between mineral deposits in Kentucky and Tennessee and the Kentucky body was investigated. A compilation of mineral occurrences in the region, classified according to type and age, is presented.

Organization and hierarchy of the human functional brain network lead to a chain-like core.

PubMed

Mastrandrea, Rossana; Gabrielli, Andrea; Piras, Fabrizio; Spalletta, Gianfranco; Caldarelli, Guido; Gili, Tommaso

2017-07-07

The brain is a paradigmatic example of a complex system: its functionality emerges as a global property of local mesoscopic and microscopic interactions. Complex network theory allows to elicit the functional architecture of the brain in terms of links (correlations) between nodes (grey matter regions) and to extract information out of the noise. Here we present the analysis of functional magnetic resonance imaging data from forty healthy humans at rest for the investigation of the basal scaffold of the functional brain network organization. We show how brain regions tend to coordinate by forming a highly hierarchical chain-like structure of homogeneously clustered anatomical areas. A maximum spanning tree approach revealed the centrality of the occipital cortex and the peculiar aggregation of cerebellar regions to form a closed core. We also report the hierarchy of network segregation and the level of clusters integration as a function of the connectivity strength between brain regions.

Harmonic template neurons in primate auditory cortex underlying complex sound processing

PubMed Central

Feng, Lei

2017-01-01

Harmonicity is a fundamental element of music, speech, and animal vocalizations. How the auditory system extracts harmonic structures embedded in complex sounds and uses them to form a coherent unitary entity is not fully understood. Despite the prevalence of sounds rich in harmonic structures in our everyday hearing environment, it has remained largely unknown what neural mechanisms are used by the primate auditory cortex to extract these biologically important acoustic structures. In this study, we discovered a unique class of harmonic template neurons in the core region of auditory cortex of a highly vocal New World primate, the common marmoset (Callithrix jacchus), across the entire hearing frequency range. Marmosets have a rich vocal repertoire and a similar hearing range to that of humans. Responses of these neurons show nonlinear facilitation to harmonic complex sounds over inharmonic sounds, selectivity for particular harmonic structures beyond two-tone combinations, and sensitivity to harmonic number and spectral regularity. Our findings suggest that the harmonic template neurons in auditory cortex may play an important role in processing sounds with harmonic structures, such as animal vocalizations, human speech, and music. PMID:28096341

Morphological relationships in the chromospheric H-alpha fine structure

NASA Technical Reports Server (NTRS)

Foukal, P.

1971-01-01

A continuous relationship is proposed between the basic elements of the dark fine structure of the quiet and active chromosphere. A progression from chromospheric bushes to fibrils, then to chromospheric threads and active region filaments, and finally to diffuse quiescent filaments, is described. It is shown that the horizontal component of the field on opposite sides of an active region quiescent filament can be in the same direction and closely parallel to the filament axis. Consequently, it is unnecessary to postulate twisted or otherwise complex field configurations to reconcile the support mechanism of filaments with the observed motion along their axis.

Interactions of Twisted Ω-loops in a Model Solar Convection Zone

NASA Astrophysics Data System (ADS)

Jouve, L.; Brun, A. S.; Aulanier, G.

2018-04-01

This study aims at investigating the ability of strong interactions between magnetic field concentrations during their rise through the convection zone to produce complex active regions at the solar surface. To do so, we perform numerical simulations of buoyant magnetic structures evolving and interacting in a model solar convection zone. We first produce a 3D model of rotating convection and then introduce idealized magnetic structures close to the bottom of the computational domain. These structures possess a certain degree of field line twist and they are made buoyant on a particular extension in longitude. The resulting twisted Ω-loops will thus evolve inside a spherical convective shell possessing large-scale mean flows. We present results on the interaction between two such loops with various initial parameters (mainly buoyancy and twist) and on the complexity of the emerging magnetic field. In agreement with analytical predictions, we find that if the loops are introduced with opposite handedness and same axial field direction or the same handedness but opposite axial field, they bounce against each other. The emerging region is then constituted of two separated bipolar structures. On the contrary, if the loops are introduced with the same direction of axial and peripheral magnetic fields and are sufficiently close, they merge while rising. This more interesting case produces complex magnetic structures with a high degree of non-neutralized currents, especially when the convective motions act significantly on the magnetic field. This indicates that those interactions could be good candidates to produce eruptive events like flares or CMEs.

Seismicity in Azerbaijan and Adjacent Caspian Sea

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

Panahi, Behrouz M.

2006-03-23

So far no general view on the geodynamic evolution of the Black Sea to the Caspian Sea region is elaborated. This is associated with the geological and structural complexities of the region revealed by geophysical, geochemical, petrologic, structural, and other studies. A clash of opinions on geodynamic conditions of the Caucasus region, sometimes mutually exclusive, can be explained by a simplified interpretation of the seismic data. In this paper I analyze available data on earthquake occurrences in Azerbaijan and the adjacent Caspian Sea region. The results of the analysis of macroseismic and instrumental data, seismic regime, and earthquake reoccurrence indicatemore » that a level of seismicity in the region is moderate, and seismic event are concentrated in the shallow part of the lithosphere. Seismicity is mostly intra-plate, and spatial distribution of earthquake epicenters does not correlate with the plate boundaries.« less

Structural mimicry of O-antigen by a peptide revealed in a complex with an antibody raised against Shigella flexneri serotype 2a.

PubMed

Theillet, François-Xavier; Saul, Frederick A; Vulliez-Le Normand, Brigitte; Hoos, Sylviane; Felici, Franco; Weintraub, Andrej; Mulard, Laurence A; Phalipon, Armelle; Delepierre, Muriel; Bentley, Graham A

2009-05-15

The use of carbohydrate-mimicking peptides to induce immune responses against surface polysaccharides of pathogenic bacteria offers a novel approach to vaccine development. Factors governing antigenic and immunogenic mimicry, however, are complex and poorly understood. We have addressed this question using the anti-lipopolysaccharide monoclonal antibody F22-4, which was raised against Shigella flexneri serotype 2a and shown to protect against homologous infection in a mouse model. In a previous crystallographic study, we described F22-4 in complex with two synthetic fragments of the O-antigen, the serotype-specific saccharide moiety of lipopolysaccharide. Here, we present a crystallographic and NMR study of the interaction of F22-4 with a dodecapeptide selected by phage display using the monoclonal antibody. Like the synthetic decasaccharide, the peptide binds to F22-4 with micromolar affinity. Although the peptide and decasaccharide use very similar regions of the antigen-binding site, indicating good antigenic mimicry, immunogenic mimicry by the peptide was not observed. The F22-4-antigen interaction is significantly more hydrophobic with the peptide than with oligosaccharides; nonetheless, all hydrogen bonds formed between the peptide and F22-4 have equivalents in the oligosaccharide complex. Two bridging water molecules are also in common, adding to partial structural mimicry. Whereas the bound peptide is entirely helical, its structure in solution, as shown by NMR, is helical in the central region only. Moreover, docking the NMR structure into the antigen-binding site shows that steric hindrance would occur, revealing poor complementarity between the major solution conformation and the antibody that could contribute to the absence of immunogenic mimicry.

Combined MCD/DFT/TDDFT Study of the Electronic Structure of Axially Pyridine Coordinated Metallocorroles.

PubMed

Rhoda, Hannah M; Crandall, Laura A; Geier, G Richard; Ziegler, Christopher J; Nemykin, Victor N

2015-05-18

A series of metallocorroles were investigated by UV-vis and magnetic circular dichroism spectroscopies. The diamagnetic distorted square-pyramidal main-group corrole Ga(tpfc)py (2), the diamagnetic distorted octahedral transition-metal adduct Co(tpfc)(py)2 (3), and paramagnetic distorted octahedral transition-metal complex Fe(tpfc)(py)2 (4) [H3tpfc = tris(perfluorophenyl)corrole] were studied to investigate similarities and differences in the electronic structure and spectroscopy of the closed- and open-shell metallocorroles. Similar to the free-base H3tpfc (1), inspection of the MCD Faraday B-terms for all of the macrocycles presented in this report revealed that a ΔHOMO < ΔLUMO [ΔHOMO is the energy difference between two highest energy corrole-centered π-orbitals and ΔLUMO is the energy difference between two lowest energy corrole-centered π*-orbitals originating from ML ± 4 and ML ± 5 pairs of perimeter] condition is present for each complex, which results in an unusual sign-reversed sequence for π-π* transitions in their MCD spectra. In addition, the MCD spectra of the cobalt and the iron complexes were also complicated by a number of charge-transfer states in the visible region. Iron complex 4 also exhibits a low-energy absorption in the NIR region (1023 nm). DFT and TDDFT calculations were used to elaborate the electronic structures and provide band assignments in UV-vis and MCD spectra of the metallocorroles. DFT and TDDFT calculations predict that the orientation of the axial pyridine ligand(s) has a very minor influence on the calculated electronic structures and absorption spectra in the target systems.

Structural determinants of ligand binding in the ternary complex of human ileal bile acid binding protein with glycocholate and glycochenodeoxycholate obtained from solution NMR.

PubMed

Horváth, Gergő; Bencsura, Ákos; Simon, Ágnes; Tochtrop, Gregory P; DeKoster, Gregory T; Covey, Douglas F; Cistola, David P; Toke, Orsolya

2016-02-01

Besides aiding digestion, bile salts are important signal molecules exhibiting a regulatory role in metabolic processes. Human ileal bile acid binding protein (I-BABP) is an intracellular carrier of bile salts in the epithelial cells of the distal small intestine and has a key role in the enterohepatic circulation of bile salts. Positive binding cooperativity combined with site selectivity of glycocholate and glycochenodeoxycholate, the two most abundant bile salts in the human body, make human I-BABP a unique member of the family of intracellular lipid binding proteins. Solution NMR structure of the ternary complex of human I-BABP with glycocholate and glycochenodeoxycholate reveals an extensive network of hydrogen bonds and hydrophobic interactions stabilizing the bound bile salts. Conformational changes accompanying bile salt binding affects four major regions in the protein including the C/D, E/F and G/H loops as well as the helical segment. Most of these protein regions coincide with a previously described network of millisecond time scale fluctuations in the apo protein, a motion absent in the bound state. Comparison of the heterotypic doubly ligated complex with the unligated form provides further evidence of a conformation selection mechanism of ligand entry. Structural and dynamic aspects of human I-BABP-bile salt interaction are discussed and compared with characteristics of ligand binding in other members of the intracellular lipid binding protein family. The coordinates of the 10 lowest energy structures of the human I-BABP : GCDA : GCA complex as well as the distance restraints used to calculate the final ensemble have been deposited in the Brookhaven Protein Data Bank with accession number 2MM3. © 2015 FEBS.

Structural influence in the interaction of cysteine with five coordinated copper complexes: Theoretical and experimental studies

NASA Astrophysics Data System (ADS)

Huerta-Aguilar, Carlos Alberto; Thangarasu, Pandiyan; Mora, Jesús Gracia

2018-04-01

Copper complexes of N,N,N‧,N‧-tetrakis(pyridyl-2-ylmethyl)-1,2-diaminoethane (L1) and N,N,N‧,N‧-tetrakis(pyridyl-2-ylmethyl)-1,3-diaminopropane (L2) prepared were characterized completely by different analytical methods. The X-structure of the complexes shows that Cu(II) presents in trigonal bi-pyramidal (TBP) geometry, consisting with the electronic spectra where two visible bands corresponding to five coordinated structure were observed. Thus TD-DFT was used to analyze the orbital contribution to the electronic transitions for the visible bands. Furthermore, the interaction of cysteine with the complexes was spectrally studied, and the results were explained through DFT analysis, observing that the geometrical parameters and oxidation state of metal ions play a vital role in the binding of cysteine with copper ion. It appears that the TBP structure is being changed into octahedral geometry during the addition of cysteine to the complexes as two bands (from complex) is turned to a broad band in visible region, signifying the occupation of cysteine molecule at sixth position of octahedral geometry. In the molecular orbital analysis, the existence of a strong overlapping of HOMOs (from cysteine) with LUMOs of Cu ion was observed. The total energy of the systems calculated by DFT shows that cysteine binds favorably with copper (I) than that with Cu(II).

Dynamics of water around the complex structures formed between the KH domains of far upstream element binding protein and single-stranded DNA molecules

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

Chakraborty, Kaushik; Bandyopadhyay, Sanjoy, E-mail: sanjoy@chem.iitkgp.ernet.in

2015-07-28

Single-stranded DNA (ss-DNA) binding proteins specifically bind to the single-stranded regions of the DNA and protect it from premature annealing, thereby stabilizing the DNA structure. We have carried out atomistic molecular dynamics simulations of the aqueous solutions of two DNA binding K homology (KH) domains (KH3 and KH4) of the far upstream element binding protein complexed with two short ss-DNA segments. Attempts have been made to explore the influence of the formation of such complex structures on the microscopic dynamics and hydrogen bond properties of the interfacial water molecules. It is found that the water molecules involved in bridging themore » ss-DNA segments and the protein domains form a highly constrained thin layer with extremely retarded mobility. These water molecules play important roles in freezing the conformational oscillations of the ss-DNA oligomers and thereby forming rigid complex structures. Further, it is demonstrated that the effect of complexation on the slow long-time relaxations of hydrogen bonds at the interface is correlated with hindered motions of the surrounding water molecules. Importantly, it is observed that the highly restricted motions of the water molecules bridging the protein and the DNA components in the complexed forms originate from more frequent hydrogen bond reformations.« less

Helium defectoscopy of cerium gadolinium ceramics Ce0.8Gd0.2O1.9 with a submicrocrystalline structure in the impurity disorder region

NASA Astrophysics Data System (ADS)

Koromyslov, A. V.; Zhiganov, A. N.; Kovalenko, M. A.; Kupryazhkin, A. Ya.

2013-12-01

The concentration of impurity anion vacancies formed upon the dissociation of gadolinium-vacancy complexes has been determined using helium defectoscopy of the cerium gadolinium ceramics Ce0.8Gd0.2O1.9 with a submicrocrystalline structure in the temperature range T = 740-1123 K and at saturation pressures ranging from 0.05 to 15 MPa. It has been found that the energy of dissociation of gadoliniumvacancy complexes is E {eff/ D }= 0.26 ± 0.06 eV, and the energy of dissolution of helium in anion vacancies in the impurity disorder region is E P = -0.31 ± 0.09 eV. The proposed mechanism of dissolution has been confirmed by the investigation of the electrical conductivity of the cerium gadolinium ceramics, as well as by the high-speed molecular dynamics simulation of the dissociation of gadolinium-vacancy complexes. It has been assumed that a decrease in the effective dissolution energy in comparison with the results of the previously performed low-temperature investigations is caused by the mutual repulsion of vacancies formed upon the dissociation of gadolinium-vacancy complexes in highly concentrated solutions of gadolinium in CeO2 with increasing temperature.

Dynamics of the Stratiform Sector of a Tropical Cyclone Rainband

NASA Astrophysics Data System (ADS)

Didlake, A. C.; Houze, R.

2013-12-01

Airborne Doppler radar collected observations of the stationary rainband complex of Hurricane Rita (2005) in exceptional detail. Dynamics of the stationary rainband complex play a large role in the evolution of the tropical cyclone's internal structure. The stratiform sector of the stationary rainband complex occurs on the downwind end of the complex. This stratiform rainband is a mesoscale feature consisting of nearly uniform precipitation and weak vertical velocities from collapsing convective cells. Upward transport and associated latent heating occur within the stratiform cloud layer in the form of rising radial outflow. Below the cloud layer, descending radial inflow was driven by horizontal buoyancy gradients, and thus horizontal vorticity generation, introduced by regions of sublimational and melting cooling. The organization of this transport initially is robust but fades downwind as the convection dissipates. This descending inflow advected higher angular momentum inward, which resulted in the development of a midlevel tangential jet and broadening of the tangential wind field. This circulation may have also contributed to ventilation of the eyewall as inflow of low-entropy air continued past the rainband in both the boundary layer and midlevels. Given the expanse of the stratiform rainband region, its thermodynamic and kinematic impacts likely help to modify the structure and intensity of the overall storm.

Identifying DNA-binding proteins using structural motifs and the electrostatic potential

PubMed Central

Shanahan, Hugh P.; Garcia, Mario A.; Jones, Susan; Thornton, Janet M.

2004-01-01

Robust methods to detect DNA-binding proteins from structures of unknown function are important for structural biology. This paper describes a method for identifying such proteins that (i) have a solvent accessible structural motif necessary for DNA-binding and (ii) a positive electrostatic potential in the region of the binding region. We focus on three structural motifs: helix–turn-helix (HTH), helix–hairpin–helix (HhH) and helix–loop–helix (HLH). We find that the combination of these variables detect 78% of proteins with an HTH motif, which is a substantial improvement over previous work based purely on structural templates and is comparable to more complex methods of identifying DNA-binding proteins. Similar true positive fractions are achieved for the HhH and HLH motifs. We see evidence of wide evolutionary diversity for DNA-binding proteins with an HTH motif, and much smaller diversity for those with an HhH or HLH motif. PMID:15356290

Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains

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

Moldoveanu, Tudor; Gehring, Kalle; Green, Douglas R.

2009-01-15

Ca{sup 2+}-dependent cysteine proteases, calpains, regulate cell migration, cell death, insulin secretion, synaptic function and muscle homeostasis. Their endogenous inhibitor, calpastatin, consists of four inhibitory repeats, each of which neutralizes an activated calpain with exquisite specificity and potency. Despite the physiological importance of this interaction, the structural basis of calpain inhibition by calpastatin is unknown. Here we report the 3.0 A structure of Ca{sup 2+}-bound m-calpain in complex with the first calpastatin repeat, both from rat, revealing the mechanism of exclusive specificity. The structure highlights the complexity of calpain activation by Ca{sup 2+}, illustrating key residues in a peripheral domainmore » that serve to stabilize the protease core on Ca{sup 2+} binding. Fully activated calpain binds ten Ca{sup 2+} atoms, resulting in several conformational changes allowing recognition by calpastatin. Calpain inhibition is mediated by the intimate contact with three critical regions of calpastatin. Two regions target the penta-EF-hand domains of calpain and the third occupies the substrate-binding cleft, projecting a loop around the active site thiol to evade proteolysis.« less

A Conformational Investigation of Propeptide Binding to the Integral Membrane Protein γ-Glutamyl Carboxylase Using Nanodisc Hydrogen Exchange Mass Spectrometry

PubMed Central

2015-01-01

Gamma (γ)-glutamyl carboxylase (GGCX) is an integral membrane protein responsible for the post-translational catalytic conversion of select glutamic acid (Glu) residues to γ-carboxy glutamic acid (Gla) in vitamin K-dependent (VKD) proteins. Understanding the mechanism of carboxylation and the role of GGCX in the vitamin K cycle is of biological interest in the development of therapeutics for blood coagulation disorders. Historically, biophysical investigations and structural characterizations of GGCX have been limited due to complexities involving the availability of an appropriate model membrane system. In previous work, a hydrogen exchange mass spectrometry (HX MS) platform was developed to study the structural configuration of GGCX in a near-native nanodisc phospholipid environment. Here we have applied the nanodisc–HX MS approach to characterize specific domains of GGCX that exhibit structural rearrangements upon binding the high-affinity consensus propeptide (pCon; AVFLSREQANQVLQRRRR). pCon binding was shown to be specific for monomeric GGCX-nanodiscs and promoted enhanced structural stability to the nanodisc-integrated complex while maintaining catalytic activity in the presence of carboxylation co-substrates. Noteworthy modifications in HX of GGCX were prominently observed in GGCX peptides 491–507 and 395–401 upon pCon association, consistent with regions previously identified as sites for propeptide and glutamate binding. Several additional protein regions exhibited minor gains in solvent protection upon propeptide incorporation, providing evidence for a structural reorientation of the GGCX complex in association with VKD carboxylation. The results herein demonstrate that nanodisc–HX MS can be utilized to study molecular interactions of membrane-bound enzymes in the absence of a complete three-dimensional structure and to map dynamic rearrangements induced upon ligand binding. PMID:24512177

Geophysical studies of the Syncline Ridge area, Nevada Test Site, Nye County, Nevada

USGS Publications Warehouse

Hoover, D.B.; Hanna, W.F.; Anderson, L.A.; Flanigan, V.J.; Pankratz, L.W.

1982-01-01

A wide variety of geophysical methods were employed to study a proposed nuclear waste site at Syncline Ridge on the Nevada Test Site, Nev. The proposed site was believed to be a relatively undisturbed synclinal structure containing a thick argillite unit of Misslsslppian age, the Eleana Formation unit J, which would be the emplacement medium. Data acquisition for the geophysical studies was constrained because of rugged topography in a block of Tipplpah Limestone overlying the central part of the proposed site. This study employed gravity, magnetic, seismic refraction and reflection, and four distinct electrical methods to try and define the structural integrity and shape of the proposed repository medium. Detailed and regional gravity work revealed complex structure at the site. Magnetics helped only in identifying small areas of Tertiary volcanic rocks because of low magnetization of the rocks. Seismic refraction assisted in identifying near surface faulting and bedrock structure. Difficulty was experienced in obtaining good quality reflection data. This implied significant structural complexity but also revealed the principal features that were supported by other data. Electrical methods were used for fault identification and for mapping of a thick argillaceous unit of the Eleana Formation in which nuclear waste was to be emplaced. The geophysical studies indicate that major faults along the axis of Syncline Ridge and on both margins have large vertical offsets displacing units so as not only to make mining difficult, but also providing potential paths for waste migration to underlying carbonate aquifers. The Eleana Formation appeared heterogeneous, which was inferred to be due to structural complexity. Only a small region in the northwest part of the study area was found to contain a thick and relatively undisturbed volume of host rock.

Geodynamic models of the deep structure of the natural disaster regions of the Earth

NASA Astrophysics Data System (ADS)

Rodnikov, A. G.; Sergeyeva, N. A.; Zabarinskaya, L. P.

2012-04-01

Investigation of the deep structure and creation of geodynamic models of natural disaster regions are important for understanding of the nature of such phenomena as earthquakes, eruptions of volcanoes, tsunami and others. Carrying out of such researches is necessary for definition of areas of potential risk, forecasting and the prevention of negative consequences of acts of nature. Research region is active continental margins of the Sea of Okhotsk, and especially the area of Neftegorsk earthquake which has occurred on May, 28th 1995 in the North Sakhalin and caused many victims and destructions. The geodynamic model of the lithosphere in the region of Neftegorsk earthquake has been constructed along the profile crossing the North Sakhalin Basin, Deryugin Basin and ophiolite complex between them. The Deryugin Basin was formed at the site of an ancient deep trench after the subduction of the Okhotsk Sea Plate under Sakhalin. The basin is located above a hot plume in the mantle at a depth of 25 km. The ophiolite belt of ultramafic magmatic rocks is an ancient (K2-Pg) paleosubduction zone separating the Deryugin basin from the North Sakhalin Basin. The thickness of the ancient seismic focal zone is 80 km. It is probably that the structures of the North Sakhalin have been formed in the following way. In the Late Cretaceous the oceanic Okhotsk Sea Plate subducted under Sakhalin, the eastern part of which was an andesite island arc. Approximately in Miocene the subduction of the plate apparently ceased. In that time the Tatar Rift Strait was formed. Ophiolite rocks of the subduction zones as a result of compression have been squeezed out on a surface. The ophiolite complex combined by the ultrabasic rocks, fixes position of ancient subduction zone. It is probable that the manifestation of the Neftegorsk earthquake was a result of activization of this ancient subduction zone. On a surface the subduction zone manifests itself as deep faults running along Sakhalin. The center of the Neftegorsk earthquake was directly formed by burst of activity of this ancient subduction zone. From a position of the ancient subduction zone under Sakhalin, which is a cause of strong earthquakes here, it follows that the region is one of seismic dangerous in Russia. Constructed on the basis of complex interpretation of the geologic-geophysical data the geodynamic models of natural disaster regions give the chance: to study a deep structure under seismic dangerous zones; to investigate a role of deep processes in the upper mantle in formation of structures of earth crust; to relate the geological features, tectonomagmatic, hydrothermal activity with the processes in the upper mantle; to plot maps in detail with zones of increasing risks to prevent active building or other economic activities in such dangerous regions.

Insensitive dependence of delay-induced oscillation death on complex networks

NASA Astrophysics Data System (ADS)

Zou, Wei; Zheng, Xing; Zhan, Meng

2011-06-01

Oscillation death (also called amplitude death), a phenomenon of coupling induced stabilization of an unstable equilibrium, is studied for an arbitrary symmetric complex network with delay-coupled oscillators, and the critical conditions for its linear stability are explicitly obtained. All cases including one oscillator, a pair of oscillators, regular oscillator networks, and complex oscillator networks with delay feedback coupling, can be treated in a unified form. For an arbitrary symmetric network, we find that the corresponding smallest eigenvalue of the Laplacian λN (0 >λN ≥ -1) completely determines the death island, and as λN is located within the insensitive parameter region for nearly all complex networks, the death island keeps nearly the largest and does not sensitively depend on the complex network structures. This insensitivity effect has been tested for many typical complex networks including Watts-Strogatz (WS) and Newman-Watts (NW) small world networks, general scale-free (SF) networks, Erdos-Renyi (ER) random networks, geographical networks, and networks with community structures and is expected to be helpful for our understanding of dynamics on complex networks.

Prediction of binding hot spot residues by using structural and evolutionary parameters.

PubMed

Higa, Roberto Hiroshi; Tozzi, Clésio Luis

2009-07-01

In this work, we present a method for predicting hot spot residues by using a set of structural and evolutionary parameters. Unlike previous studies, we use a set of parameters which do not depend on the structure of the protein in complex, so that the predictor can also be used when the interface region is unknown. Despite the fact that no information concerning proteins in complex is used for prediction, the application of the method to a compiled dataset described in the literature achieved a performance of 60.4%, as measured by F-Measure, corresponding to a recall of 78.1% and a precision of 49.5%. This result is higher than those reported by previous studies using the same data set.

Central Arctic Crustal Modeling Constrained by Potential Field data and recent ECS Seismic Data

NASA Astrophysics Data System (ADS)

Evangelatos, John; Oakey, Gordon; Saltus, Rick

2017-04-01

2-D gravity and magnetic models have been generated for several transects across the Alpha-Mendeleev ridge complex to study the regional variability of the crustal structure and identify large scale lateral changes. The geometry and density parameters for the models have been constrained using recently acquired seismic reflection and refraction data collected jointly by Canada and the United States as part of their collaborative Arctic ECS programs. A total of fifteen models have been generated perpendicular to the ridge complex, typically 50 to 150 km apart. A minimalist approach to modeling involved maintaining a simple, laterally continuous density structure for the crust while varying the model geometry to fit the observed gravity field. This approach is justified because low amplitude residual Bouguer anomalies suggest a relatively homogenous density structure within the ridge complex. These models have provided a new measure of the regional variability in crustal thickness. Typically, models with thinner crust correspond with deeper bathymetric depths of the ridge which is consistent with regional isostatic equilibrium. Complex "chaotic" magnetic anomalies are associated with the Alpha-Mendeleev ridge complex, which extends beneath the surrounding sedimentary basins. Pseudogravity inversion (magnetic potential) of the magnetic field provides a quantifiable areal extent of ˜1.3 x106 km2. Forward modeling confirms that the magnetic anomalies are not solely the result of magnetized bathymetric highs, but are caused to a great extent by mid- and lower crustal sources. The magnetization of the crust inferred from modeling is significantly higher than available lab measurements of onshore volcanic rocks. Although the 2-D models cannot uniquely identify whether the crustal protolith was continental or oceanic, there is a necessity for a significant content of high density and highly magnetic (ultramafic) material. Based on the crustal thickness estimates from our regional 2-D gravity models and the two possible protoliths, we determine volumetric estimates of the volcanic composition to ˜ 6 × 106 km3 for the mid- and upper-crust and between 10 × 106 and 14 × 106 km3 within the lower crust — for a total of at least ˜16 × 106 km3. This exceeds any estimates for the onshore circum-Arctic HALIP by more than an order of magnitude.

Modeling the blockage of Lg waves from 3-D variations in crustal structure

NASA Astrophysics Data System (ADS)

Sanborn, Christopher J.; Cormier, Vernon F.

2018-05-01

Comprised of S waves trapped in Earth's crust, the high frequency (2-10 Hz) Lg wave is important to discriminating earthquakes from explosions by comparing its amplitude and waveform to those of Pg and Pn waves. Lateral variations in crustal structure, including variations in crustal thickness, intrinsic attenuation, and scattering, affect the efficiency of Lg propagation and its consistency as a source discriminant at regional (200-1500 km) distances. To investigate the effects of laterally varying Earth structure on the efficiency of propagation of Lg and Pg, we apply a radiative transport algorithm to model complete, high-frequency (2-4 Hz), regional coda envelopes. The algorithm propagates packets of energy with ray theory through large-scale 3-D structure, and includes stochastic effects of multiple-scattering by small-scale heterogeneities within the large-scale structure. Source-radiation patterns are described by moment tensors. Seismograms of explosion and earthquake sources are synthesized in canonical models to predict effects on waveforms of paths crossing regions of crustal thinning (pull-apart basins and ocean/continent transitions) and thickening (collisional mountain belts), For paths crossing crustal thinning regions, Lg is amplified at receivers within the thinned region but strongly disrupted and attenuated at receivers beyond the thinned region. For paths crossing regions of crustal thickening, Lg amplitude is attenuated at receivers within the thickened region, but experiences little or no reduction in amplitude at receivers beyond the thickened region. The length of the Lg propagation within a thickened region and the complexity of over- and under-thrust crustal layers, can produce localized zones of Lg amplification or attenuation. Regions of intense scattering within laterally homogeneous models of the crust increase Lg attenuation but do not disrupt its coda shape.

Structural characterization of the Yersinia pestis type III secretion system needle protein YscF in complex with its heterodimeric chaperone YscE/YscG

PubMed Central

Sun, Ping; Tropea, Joseph E.; Austin, Brian P.; Cherry, Scott; Waugh, David S.

2008-01-01

Summary The plague-causing bacterium Yersinia pestis utilizes a Type III Secretion System (T3SS) to deliver effector proteins into mammalian cells where they interfere with signal transduction pathways that mediate phagocytosis and the inflammatory response. Effector proteins are injected through a hollow needle structure composed of the protein YscF. YscG and YscE act as "chaperones" to prevent premature polymerization of YscF in the cytosol of the bacterium prior to assembly of the needle. Here, we report the crystal structure of the YscEFG protein complex at 1.8 Å resolution. Overall, the structure is similar to that of the analogous PscEFG complex from the Pseudomonas aeruginosa T3SS, but there are noteworthy differences. The structure confirms that, like PscG, YscG is a member of the tetratricopeptide repeat (TPR) family of proteins. YscG binds tightly to the C-terminal half of YscF, implying that it is this region of YscF that controls its polymerization into the needle structure. YscE interacts with the N-terminal TPR motif of YscG but makes very little direct contact with YscF. Its function may be to stabilize the structure of YscG and/or to participate in recruiting the complex to the secretion apparatus. No electron density could be observed for the N-terminal 49 residues of YscF. This and additional evidence suggest that the N-terminus of YscF is disordered in the complex with YscE and YscG. As expected, conserved residues in the C-terminal half of YscF mediate important intra- and intermolecular interactions in the complex. Moreover, the phenotypes of some previously characterized mutations in the C-terminal half of YscF can be rationalized in terms of the structure of the heterotrimeric YscEFG complex. PMID:18281060

Structural Characterization of the Yersinia pestis Type III Secretion System Needle Protein YscF in Complex with Its Heterodimeric Chaperone YscE/YscG

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

Sun, Ping; Tropea, Joseph E.; Austin, Brian P.

2008-05-03

The plague-causing bacterium Yersinia pestis utilizes a type III secretion system to deliver effector proteins into mammalian cells where they interfere with signal transduction pathways that mediate phagocytosis and the inflammatory response. Effector proteins are injected through a hollow needle structure composed of the protein YscF. YscG and YscE act as 'chaperones' to prevent premature polymerization of YscF in the cytosol of the bacterium prior to assembly of the needle. Here, we report the crystal structure of the YscEFG protein complex at 1.8 {angstrom} resolution. Overall, the structure is similar to that of the analogous PscEFG complex from the Pseudomonasmore » aeruginosa type III secretion system, but there are noteworthy differences. The structure confirms that, like PscG, YscG is a member of the tetratricopeptide repeat family of proteins. YscG binds tightly to the C-terminal half of YscF, implying that it is this region of YscF that controls its polymerization into the needle structure. YscE interacts with the N-terminal tetratricopeptide repeat motif of YscG but makes very little direct contact with YscF. Its function may be to stabilize the structure of YscG and/or to participate in recruiting the complex to the secretion apparatus. No electron density could be observed for the 49 N-terminal residues of YscF. This and additional evidence suggest that the N-terminus of YscF is disordered in the complex with YscE and YscG. As expected, conserved residues in the C-terminal half of YscF mediate important intra- and intermolecular interactions in the complex. Moreover, the phenotypes of some previously characterized mutations in the C-terminal half of YscF can be rationalized in terms of the structure of the heterotrimeric YscEFG complex.« less

Staging in polyacetylene-iodine conductors

NASA Astrophysics Data System (ADS)

Baughman, R. H.; Murthy, N. S.; Miller, G. G.; Shacklette, L. W.

1983-07-01

Evidence is presented for the existence of highly conducting polyacetylene complexes with structures related to high-stage graphite, as well as structures related to first-stage graphite. X-ray diffraction measurements on polyacetylene-iodine complexes indicate equatorial lines at 7.7-8.0 and 13.8-14.3 Å. The shorter spacing arises in part from a structure in which iodine-rich planes alternate with planes of polyacetylene chains. The longer spacing, which disappears upon atmospheric exposure, is consistent with a structure analogous to third-stage graphite in which dopant-rich planes are separated by three close-packed planes of polyacetylene chains. The third-stage complex can be viewed as a perturbation of the structure of undoped polyacetylene, with the region between dopant layers consisting essentially of a one unit cell thickness of the parent polymer structure. Packing calculations for this model, in which a linear column of anions (I3- and/or I5-) displaces either every chain or every other chain in the dopant-rich layer, provide an interlayer spacing which is equal to that observed. Evidence consistent with third-stage structures (with both fractional occupation and complete occupation of the dopant plane) is also found by reexamination of published sorption data, which provides slope changes at close to the calculated limiting compositions for these structures [(CHI0.056)x and (CHI0.13)x]. However, a first-stage structure with alternating dopant arrays and polymer chains in the dopant plane [for which (CHI0.13)x is calculated] provides a better explanation for the second slope change, as well as for the composition obtained under dynamic vacuum, (CHI0.14)x. These results for iodine complexes are compared with those derived for the group VA halide complexes of polyacetylene.

Beyond the G-spot: clitourethrovaginal complex anatomy in female orgasm.

PubMed

Jannini, Emmanuele A; Buisson, Odile; Rubio-Casillas, Alberto

2014-09-01

The search for the legendary, highly erogenous vaginal region, the Gräfenberg spot (G-spot), has produced important data, substantially improving understanding of the complex anatomy and physiology of sexual responses in women. Modern imaging techniques have enabled visualization of dynamic interactions of female genitals during self-sexual stimulation or coitus. Although no single structure consistent with a distinct G-spot has been identified, the vagina is not a passive organ but a highly dynamic structure with an active role in sexual arousal and intercourse. The anatomical relationships and dynamic interactions between the clitoris, urethra, and anterior vaginal wall have led to the concept of a clitourethrovaginal (CUV) complex, defining a variable, multifaceted morphofunctional area that, when properly stimulated during penetration, could induce orgasmic responses. Knowledge of the anatomy and physiology of the CUV complex might help to avoid damage to its neural, muscular, and vascular components during urological and gynaecological surgical procedures.

Influence of Forest-Canopy Morphology and Relief on Spectral Characteristics of Taiga Forests

NASA Astrophysics Data System (ADS)

Zhirin, V. M.; Knyazeva, S. V.; Eydlina, S. P.

2017-12-01

The article deals with the results of a statistical analysis reflecting tendencies (trends) of the relationship between spectral characteristics of taiga forests, indicators of the morphological structure of forest canopy and illumination of the territory. The study was carried out on the example of the model forest territory of the Priangarskiy taiga region of Eastern Siberia (Krasnoyarsk krai) using historical data (forest inventory 1992, Landsat 5 TM 16.06.1989) and the digital elevation model. This article describes a method for determining the quantitative indicator of morphological structure of forest canopy based on taxation data, and the authors propose to subdivide the morphological structure into high complexity, medium complexity, and relatively simple. As a result of the research, dependences of average values of spectral brightness in near and short-wave infrared channels of a Landsat 5 TM image for dark-coniferous, light-coniferous and deciduous forests from the degree of complexity of the forest-canopy structure are received. A high level of variance and maximum brightness average values are marked in green moss (hilocominosa) dark-coniferous and various-grass (larioherbosa) dark-coniferous forests and light-coniferous forests with a complex structure of canopy. The parvifoliate forests are characterized by high values of brightness in stands with a relatively simple structure of the canopy and by a small variance in brightness of any degree of the structure of the canopy complexity. The increase in brightness for the lit slopes in comparison with shaded ones in all stands with a difficult morphological canopy structure is revealed. However, the brightness values of the lit and shaded slopes do not differ for stands with a medium complexity of the structure. It is noted that, in addition to the indicator of the forest-canopy structure, the possible impact on increasing the variance of spectral brightness for the taxation plot has a variability of the slope ratio of "microslopes" inside the forest plot if it exceeds 60%.

Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformation.

PubMed

Yin, Hsien-Sheng; Wen, Xiaolin; Paterson, Reay G; Lamb, Robert A; Jardetzky, Theodore S

2006-01-05

Enveloped viruses have evolved complex glycoprotein machinery that drives the fusion of viral and cellular membranes, permitting entry of the viral genome into the cell. For the paramyxoviruses, the fusion (F) protein catalyses this membrane merger and entry step, and it has been postulated that the F protein undergoes complex refolding during this process. Here we report the crystal structure of the parainfluenza virus 5 F protein in its prefusion conformation, stabilized by the addition of a carboxy-terminal trimerization domain. The structure of the F protein shows that there are profound conformational differences between the pre- and postfusion states, involving transformations in secondary and tertiary structure. The positions and structural transitions of key parts of the fusion machinery, including the hydrophobic fusion peptide and two helical heptad repeat regions, clarify the mechanism of membrane fusion mediated by the F protein.

Structure of Arabidopsis HYPONASTIC LEAVES1 and Its Molecular Implications for miRNA Processing

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

Yang, S.; Chen, H; Yang, J

2010-01-01

The Arabidopsis HYPONASTIC LEAVES1 (HYL1) is a double-stranded RNA-binding protein that forms a complex with DICER-LIKE1 (DCL1) and SERRATE to facilitate processing of primary miRNAs into microRNAs (miRNAs). However, the structural mechanisms of miRNA maturation by this complex are poorly understood. Here, we present the crystal structures of double-stranded RNA binding domains (dsRBD1 and dsRBD2) of HYL1 and HYL1 dsRBD1 (HR1)/dsRNA complex as well as human TRBP2 dsRBD2 (TR2)/dsRNA complex for comparison analysis. Structural and functional study demonstrates that both HR1 and TR2 are canonical dsRBDs for dsRNA binding, whereas HR2 of HYL1 is a non-canonical dsRBD harboring a putativemore » dimerization interface. Domain swapping within the context of HYL1 demonstrates that TR2 can supplant the function of HR1 in vitro and in vivo. Further biochemical analyses suggest that HYL1 probably binds to the miRNA/miRNA* region of precursors as a dimer mediated by HR2.« less

The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a ligand conformation that modulates protein dynamics.

PubMed

Liu, Xu; Shepherd, Tyson R; Murray, Ann M; Xu, Zhen; Fuentes, Ernesto J

2013-03-05

PDZ (PSD-95/Dlg/ZO-1) domains are protein-protein interaction modules often regulated by ligand phosphorylation. Here, we investigated the specificity, structure, and dynamics of Tiam1 PDZ domain/ligand interactions. We show that the PDZ domain specifically binds syndecan1 (SDC1), phosphorylated SDC1 (pSDC1), and SDC3 but not other syndecan isoforms. The crystal structure of the PDZ/SDC1 complex indicates that syndecan affinity is derived from amino acids beyond the four C-terminal residues. Remarkably, the crystal structure of the PDZ/pSDC1 complex reveals a binding pocket that accommodates the phosphoryl group. Methyl relaxation experiments of PDZ/SCD1 and PDZ/pSDC1 complexes reveal that PDZ-phosphoryl interactions dampen dynamic motions in a distal region of the PDZ domain by decoupling them from the ligand-binding site. Our data are consistent with a selection model by which specificity and phosphorylation regulate PDZ/syndecan interactions and signaling events. Importantly, our relaxation data demonstrate that PDZ/phospho-ligand interactions regulate protein dynamics and their coupling to distal sites. Copyright © 2013 Elsevier Ltd. All rights reserved.

Functional Architecture of T7 RNA Polymerase Transcription Complexes

PubMed Central

Nayak, Dhananjaya; Guo, Qing; Sousa, Rui

2007-01-01

Summary T7 RNA polymerase is the best-characterized member of a widespread family of single-subunit RNA polymerases. Crystal structures of T7 RNA polymerase initiation and elongation complexes have provided a wealth of detailed information on RNA polymerase interactions with the promoter and transcription bubble, but the absence of DNA downstream of the melted region of the template in the initiation complex structure, and the absence of DNA upstream of the transcription bubble in the elongation complex structure means that our picture of the functional architecture of T7 RNA polymerase transcription complexes remains incomplete. Here we use the site-specifically tethered chemical nucleases and functional characterization of directed T7 RNAP mutants to both reveal the architecture of the duplex DNA that flanks the transcription bubble in the T7 RNAP initiation and elongation complexes, and to define the function of the interactions made by these duplex elements. We find that downstream duplex interactions made with a cluster of lysines (K711/K713/K714) are present during both elongation and initiation where they contribute to stabilizing a bend in the downstream DNA that is important for promoter opening. The upstream DNA in the elongation complex is also found to be sharply bent at the upstream edge of the transcription bubble, thereby allowing formation of upstream duplex:polymerase interactions that contribute to elongation complex stability. PMID:17580086

Numerical simulation of the structure of the high-latitude ionospheric F region during meridional HF propagation

NASA Astrophysics Data System (ADS)

Andreev, M. Yu.; Mingaleva, G. I.; Mingalev, V. S.

2007-08-01

A previously developed model of the high-latitude ionosphere is used to calculate the distribution of the ionospheric parameters in the polar region. A specific method for specifying input parameters of the mathematical model, using the experimental data obtained by the method of satellite radio tomography, is used in this case. The spatial distributions of the ionospheric parameters characterized by a complex inhomogeneous structure in the high-latitude region, calculated with the help of the mathematical model, are used to simulate the HF propagation along the meridionally oriented radio paths extending from middle to high latitudes. The method for improving the HF communication between a midlatitude transmitter and a polar-cap receiver is proposed.

Phylogeographic Insights into a Peripheral Refugium: The Importance of Cumulative Effect of Glaciation on the Genetic Structure of Two Endemic Plants

PubMed Central

Zecca, Giovanni; Minuto, Luigi

2016-01-01

Quaternary glaciations and mostly last glacial maximum have shaped the contemporary distribution of many species in the Alps. However, in the Maritime and Ligurian Alps a more complex picture is suggested by the presence of many Tertiary paleoendemisms and by the divergence time between lineages in one endemic species predating the Late Pleistocene glaciation. The low number of endemic species studied limits the understanding of the processes that took place within this region. We used species distribution models and phylogeographical methods to infer glacial refugia and to reconstruct the phylogeographical pattern of Silene cordifolia All. and Viola argenteria Moraldo & Forneris. The predicted suitable area for last glacial maximum roughly fitted current known distribution. Our results suggest that separation of the major clades predates the last glacial maximum and the following repeated glacial and interglacial periods probably drove differentiations. The complex phylogeographical pattern observed in the study species suggests that both populations and genotypes extinction was minimal during the last glacial maximum, probably due to the low impact of glaciations and to topographic complexity in this area. This study underlines the importance of cumulative effect of previous glacial cycles in shaping the genetic structure of plant species in Maritime and Ligurian Alps, as expected for a Mediterranean mountain region more than for an Alpine region. PMID:27870888

Structural complexity of Dengue virus untranslated regions: cis-acting RNA motifs and pseudoknot interactions modulating functionality of the viral genome

PubMed Central

Sztuba-Solinska, Joanna; Teramoto, Tadahisa; Rausch, Jason W.; Shapiro, Bruce A.; Padmanabhan, Radhakrishnan; Le Grice, Stuart F. J.

2013-01-01

The Dengue virus (DENV) genome contains multiple cis-acting elements required for translation and replication. Previous studies indicated that a 719-nt subgenomic minigenome (DENV-MINI) is an efficient template for translation and (−) strand RNA synthesis in vitro. We performed a detailed structural analysis of DENV-MINI RNA, combining chemical acylation techniques, Pb2+ ion-induced hydrolysis and site-directed mutagenesis. Our results highlight protein-independent 5′–3′ terminal interactions involving hybridization between recognized cis-acting motifs. Probing analyses identified tandem dumbbell structures (DBs) within the 3′ terminus spaced by single-stranded regions, internal loops and hairpins with embedded GNRA-like motifs. Analysis of conserved motifs and top loops (TLs) of these dumbbells, and their proposed interactions with downstream pseudoknot (PK) regions, predicted an H-type pseudoknot involving TL1 of the 5′ DB and the complementary region, PK2. As disrupting the TL1/PK2 interaction, via ‘flipping’ mutations of PK2, previously attenuated DENV replication, this pseudoknot may participate in regulation of RNA synthesis. Computer modeling implied that this motif might function as autonomous structural/regulatory element. In addition, our studies targeting elements of the 3′ DB and its complementary region PK1 indicated that communication between 5′–3′ terminal regions strongly depends on structure and sequence composition of the 5′ cyclization region. PMID:23531545

Probing the hammerhead ribozyme structure with ribonucleases.

PubMed Central

Hodgson, R A; Shirley, N J; Symons, R H

1994-01-01

Susceptibility to RNase digestion has been used to probe the conformation of the hammerhead ribozyme structure prepared from chemically synthesised RNAs. Less than about 1.5% of the total sample was digested to obtain a profile of RNase digestion sites. The observed digestion profiles confirmed the predicted base-paired secondary structure for the hammerhead. Digestion profiles of both cis and trans hammerhead structures were nearly identical which indicated that the structural interactions leading to self-cleavage were similar for both systems. Furthermore, the presence or absence of Mg2+ did not affect the RNase digestion profiles, thus indicating that Mg2+ did not modify the hammerhead structure significantly to induce self-cleavage. The base-paired stems I and II in the hammerhead structure were stable whereas stem III, which was susceptible to digestion, appeared to be an unstable region. The single strand domains separating the stems were susceptible to digestion with the exception of sites adjacent to guanosines; GL2.1 in the stem II loop and G12 in the conserved GAAAC sequence, which separates stems II and III. The absence of digestion at GL2.1 in the stem II hairpin loop of the hammerhead complex was maintained in uncomplexed ribozyme and in short oligonucleotides containing only the stem II hairpin region. In contrast, the G12 site became susceptible when the ribozyme was not complexed with its substrate. Overall the results are consistent with the role of Mg2+ in the hammerhead self-cleavage reaction being catalytic and not structural. Images PMID:8202361

Sounds of silence: synonymous nucleotides as a key to biological regulation and complexity

PubMed Central

Shabalina, Svetlana A.; Spiridonov, Nikolay A.; Kashina, Anna

2013-01-01

Messenger RNA is a key component of an intricate regulatory network of its own. It accommodates numerous nucleotide signals that overlap protein coding sequences and are responsible for multiple levels of regulation and generation of biological complexity. A wealth of structural and regulatory information, which mRNA carries in addition to the encoded amino acid sequence, raises the question of how these signals and overlapping codes are delineated along non-synonymous and synonymous positions in protein coding regions, especially in eukaryotes. Silent or synonymous codon positions, which do not determine amino acid sequences of the encoded proteins, define mRNA secondary structure and stability and affect the rate of translation, folding and post-translational modifications of nascent polypeptides. The RNA level selection is acting on synonymous sites in both prokaryotes and eukaryotes and is more common than previously thought. Selection pressure on the coding gene regions follows three-nucleotide periodic pattern of nucleotide base-pairing in mRNA, which is imposed by the genetic code. Synonymous positions of the coding regions have a higher level of hybridization potential relative to non-synonymous positions, and are multifunctional in their regulatory and structural roles. Recent experimental evidence and analysis of mRNA structure and interspecies conservation suggest that there is an evolutionary tradeoff between selective pressure acting at the RNA and protein levels. Here we provide a comprehensive overview of the studies that define the role of silent positions in regulating RNA structure and processing that exert downstream effects on proteins and their functions. PMID:23293005

Solution structure of the chick TGFbeta type II receptor ligand-binding domain.

PubMed

Marlow, Michael S; Brown, Christopher B; Barnett, Joey V; Krezel, Andrzej M

2003-02-28

The transforming growth factor beta (TGFbeta) signaling pathway influences cell proliferation, immune responses, and extracellular matrix reorganization throughout the vertebrate life cycle. The signaling cascade is initiated by ligand-binding to its cognate type II receptor. Here, we present the structure of the chick type II TGFbeta receptor determined by solution NMR methods. Distance and angular constraints were derived from 15N and 13C edited NMR experiments. Torsion angle dynamics was used throughout the structure calculations and refinement. The 20 final structures were energy minimized using the generalized Born solvent model. For these 20 structures, the average backbone root-mean-square distance from the average structure is below 0.6A. The overall fold of this 109-residue domain is conserved within the superfamily of these receptors. Chick receptors fully recognize and respond to human TGFbeta ligands despite only 60% identity at the sequence level. Comparison with the human TGFbeta receptor determined by X-ray crystallography reveals different conformations in several regions. Sequence divergence and crystal packing interactions under low pH conditions are likely causes. This solution structure identifies regions were structural changes, however subtle, may occur upon ligand-binding. We also identified two very well conserved molecular surfaces. One was found to bind ligand in the crystallized human TGFbeta3:TGFbeta type II receptor complex. The other, newly identified area can be the interaction site with type I and/or type III receptors of the TGFbeta signaling complex.

Experimental studies on flow visualization and velocity field of compression ramp with different incoming boundary layers

NASA Astrophysics Data System (ADS)

Wu, Yu; Yi, Shi-He; He, Lin; Chen, Zhi; Zhu, Yang-Zhu

2014-11-01

Experimental studies which focus on flow visualization and the velocity field of a supersonic laminar/turbulent flow over a compression ramp were carried out in a Mach 3.0 wind tunnel. Fine flow structures and velocity field structures were obtained via NPLS (nanoparticle-tracer planar laser scattering) and PIV (particle image velocimetry) techniques, time-averaged flow structures were researched, and spatiotemporal evolutions of transient flow structures were analyzed. The flow visualization results indicated that when the ramp angles were 25°, a typical separation occurred in the laminar flow, some typical flow structures such as shock induced by the boundary layer, separation shock, reversed flow and reattachment shock were visible clearly. While a certain extent separation occurred in turbulent flow, the separation region was much smaller. When the ramp angles were 28°, laminar flow separated further, and the separation region expanded evidently, flow structures in the separation region were complex. While a typical separation occurred in turbulent flow, reversed flow structures were significant, flow structures in the separation region were relatively simple. The experimental results of velocity field were corresponding to flow visualization, and the velocity field structures of both compression ramp flows agreed with the flow structures well. There were three layered structures in the U component velocity, and the V component velocity appeared like an oblique “v”. Some differences between these two compression ramp flows can be observed in the velocity profiles of the shear layer and the shearing intensity.

Molecular interactions between photosystem I and ferredoxin: an integrated energy frustration and experimental model

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

Cashman, Derek J.; Zhu, Tuo; Simmerman, Richard F.

2014-08-01

The stromal domain (PsaC, PsaD, and PsaE) of photosystem I (PSI) reduces transiently bound ferredoxin (Fd) or flavodoxin. Experimental structures exist for all of these protein partners individually, but no experimental structure of the PSI/Fd or PSI/flavodoxin complexes is presently available. Molecular models of Fd docked onto the stromal domain of the cyanobacterial PSI site are constructed here utilizing X-ray and NMR structures of PSI and Fd, respectively. Moreover, predictions of potential protein-protein interaction regions are based on experimental site-directed mutagenesis and cross-linking studies to guide rigid body docking calculations of Fd into PSI, complemented by energy landscape theory tomore » bring together regions of high energetic frustration on each of the interacting proteins. Results identify two regions of high localized frustration on the surface of Fd that contain negatively charged Asp and Glu residues. Our study predicts that these regions interact predominantly with regions of high localized frustration on the PsaC, PsaD, and PsaE chains of PSI, which include several residues predicted by previous experimental studies.« less

Large-scale model of flow in heterogeneous and hierarchical porous media

NASA Astrophysics Data System (ADS)

Chabanon, Morgan; Valdés-Parada, Francisco J.; Ochoa-Tapia, J. Alberto; Goyeau, Benoît

2017-11-01

Heterogeneous porous structures are very often encountered in natural environments, bioremediation processes among many others. Reliable models for momentum transport are crucial whenever mass transport or convective heat occurs in these systems. In this work, we derive a large-scale average model for incompressible single-phase flow in heterogeneous and hierarchical soil porous media composed of two distinct porous regions embedding a solid impermeable structure. The model, based on the local mechanical equilibrium assumption between the porous regions, results in a unique momentum transport equation where the global effective permeability naturally depends on the permeabilities at the intermediate mesoscopic scales and therefore includes the complex hierarchical structure of the soil. The associated closure problem is numerically solved for various configurations and properties of the heterogeneous medium. The results clearly show that the effective permeability increases with the volume fraction of the most permeable porous region. It is also shown that the effective permeability is sensitive to the dimensionality spatial arrangement of the porous regions and in particular depends on the contact between the impermeable solid and the two porous regions.

Genetic environment of metallo-β-lactamase genes in Pseudomonas aeruginosa isolates from the UK.

PubMed

Wright, Laura L; Turton, Jane F; Hopkins, Katie L; Livermore, David M; Woodford, Neil

2015-12-01

We sought to characterize the genetic environment of blaVIM and blaIMP genes in Pseudomonas aeruginosa isolates from the UK; these included members of six previously described prevalent complexes, A-F, which correspond to international 'high-risk clones', along with diverse strains. Metallo-β-lactamase (MBL)-encoding class 1 integrons were amplified by PCR from 218 P. aeruginosa isolates producing VIM-type (n = 196) or IMP-type (n = 22) enzymes, referred from UK hospital laboratories between 2003 and 2012. The variable regions of selected integrons were sequenced using a primer walking method. One-hundred-and-nineteen isolates had an MBL-encoding integron with the 3' conserved sequence (3'CS), 65 had Tn5090-like 3' regions and 17 had the sul1 gene, but lacked the qacEΔ1 gene; the 3' region could not be amplified using any primer combinations for the remaining 17 isolates. Six integron profiles were each seen in more than five isolates. Predominant integron types were seen amongst isolates belonging to STs 111, 233, 654/964 and 773 (complexes A, C, D and F, respectively), whereas diverse integron profiles were seen in isolates belonging to ST235 (complex B) and ST357 (complex E). In UK P. aeruginosa isolates, MBL genes occur in diverse class 1 integron structures, though commonly with 3' regions containing the classical 3'CS or Tn5090-like regions. Four of the six main clonal complexes, referred from multiple laboratories, carried a predominant integron type, whereas the remaining two had more diverse types. © Crown copyright 2015.

The Aegean/Cycladic and the Basin and Range Extensional Provinces - A Tectonic and Geochronologic Perspective

NASA Astrophysics Data System (ADS)

Stockli, D. F.

2017-12-01

The Aegean/Cycladic region (AC) and the Basin and Range Province (B&R) are two of the most famous Cenozoic extensional provinces and have greatly influenced our thinking about syn-convergent back-arc extension, core complex formation, syn-extensional magmatism, and kinematic transitions. They share numerous tectonic and structural similarities, such as a syn-convergent setting, previous contractional deformation, and core complex formation, but fundamental geological ambiguities remain, mainly centering around timing. The B&R affected a previously contractional belt (Sevier) and voluminous continental magmatic arc that created a pre-extensional orogenic highland. Extension was long-lived and complex, driven by both gravitational collapse and temporally distinct kinematic boundary condition changes. The B&R was also affected by massive, largely pre-extensional regional magmatic flare-ups that modified both the thermal and crustal composition. As the B&R occupies an elevated interior plateau, syn-extensional basin deposits are exclusively continental in character. In contrast, the AC is a classic marine back-arc extensional province that affected an active subduction margin with numerous accreted oceanic and continental ribbons, exhuming an early Cenozoic HP-LT subduction complex. Exhumation of the HP-LT complex, however, was accommodated both by vertical extrusion and crustal extension. Late Cenozoic extensional faulting was contemporaneous with S-ward sweeping arc magmatism and affected by little to no kinematic changes. As both the AC and B&R experienced contractional deformation during K-Cz subduction and J-K shortening, respectively, it is critical to differentiate between contractional and extensional structures and fabrics. The lack of temporal constraints hampers the reconstructions of pre-extensional structural anatomies and extensional strain magnitudes or even the attribution of structures to specific geodynamic settings. Novel methodologies in petrochronology, detrital geochronology, and high- and low-T thermochronometry allow us to elucidate pre-extensional crustal geometries, differentiate contractional from extensional fabrics, and understand the thermal and rheological evolution of these extensional provinces in a more holistic fashion.

Optimization of protein-protein docking for predicting Fc-protein interactions.

PubMed

Agostino, Mark; Mancera, Ricardo L; Ramsland, Paul A; Fernández-Recio, Juan

2016-11-01

The antibody crystallizable fragment (Fc) is recognized by effector proteins as part of the immune system. Pathogens produce proteins that bind Fc in order to subvert or evade the immune response. The structural characterization of the determinants of Fc-protein association is essential to improve our understanding of the immune system at the molecular level and to develop new therapeutic agents. Furthermore, Fc-binding peptides and proteins are frequently used to purify therapeutic antibodies. Although several structures of Fc-protein complexes are available, numerous others have not yet been determined. Protein-protein docking could be used to investigate Fc-protein complexes; however, improved approaches are necessary to efficiently model such cases. In this study, a docking-based structural bioinformatics approach is developed for predicting the structures of Fc-protein complexes. Based on the available set of X-ray structures of Fc-protein complexes, three regions of the Fc, loosely corresponding to three turns within the structure, were defined as containing the essential features for protein recognition and used as restraints to filter the initial docking search. Rescoring the filtered poses with an optimal scoring strategy provided a success rate of approximately 80% of the test cases examined within the top ranked 20 poses, compared to approximately 20% by the initial unrestrained docking. The developed docking protocol provides a significant improvement over the initial unrestrained docking and will be valuable for predicting the structures of currently undetermined Fc-protein complexes, as well as in the design of peptides and proteins that target Fc. Copyright © 2016 John Wiley & Sons, Ltd.

Tiopronin Gold Nanoparticle Precursor Forms Aurophilic Ring Tetramer

PubMed Central

Simpson, Carrie A.; Farrow, Christopher L.; Tian, Peng; Billinge, Simon J.L.; Huffman, Brian J.; Harkness, Kellen M.; Cliffel, David E.

2010-01-01

In the two step synthesis of thiolate-monolayer protected clusters (MPCs), the first step of the reaction is a mild reduction of gold(III) by thiols that generates gold(I) thiolate complexes as intermediates. Using tiopronin (Tio) as the thiol reductant, the characterization of the intermediate Au4Tio4 complex was accomplished with various analytical and structural techniques. Nuclear magnetic resonance (NMR), elemental analysis, thermogravimetric analysis (TGA), and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) were all consistent with a cyclic gold(I)-thiol tetramer structure, and final structural analysis was gathered through the use of powder diffraction and pair distribution functions (PDF). Crystallographic data has proved challenging for almost all previous gold(I)-thiolate complexes. Herein, a novel characterization technique when combined with standard analytical assessment to elucidate structure without crystallographic data proved invaluable to the study of these complexes. This in conjunction with other analytical techniques, in particular mass spectrometry, can elucidate a structure when crystallographic data is unavailable. In addition, luminescent properties provided evidence of aurophilicity within the molecule. The concept of aurophilicity has been introduced to describe a select group of gold-thiolate structures, which possess unique characteristics, mainly red photoluminescence and a distinct Au-Au intramolecular distance indicating a weak metal-metal bond as also evidenced by the structural model of the tetramer. Significant features of both the tetrameric and aurophilic properties of the intermediate gold(I) tiopronin complex are retained after borohydride reduction to form the MPC, including gold(I) tiopronin partial rings as capping motifs, or “staples”, and weak red photoluminescence that extends into the Near Infrared region. PMID:21067183

Drone based structural mapping at Holuhraun indicates fault reactivation and complexity

NASA Astrophysics Data System (ADS)

Mueller, Daniel; Walter, Thomas R.; Steinke, Bastian; Witt, Tanja; Schoepa, Anne; Duerig, Tobi; Gudmundsson, Magnus T.

2016-04-01

Accompanied by an intense seismic swarm in August 2014, a dike laterally formed, starting under Icelands Vatnajökull glacier, propagating over a distance of more than 45 km within only two weeks, leading to the largest eruption by volume since the 1783-84 Laki eruption. Along its propagation path, the dike caused intense surface displacements up to meters. Based on seismicity, GPS and InSAR, the propagation has already been analysed and described as segmented lateral dike growth. We now focus on few smaller regions of the dike. We consider the Terrasar-X tandem digital elevation map and aerial photos and find localized zones where structural fissures formed and curved. At these localized, regions we performed a field campaign in summer 2015, applying the close range remote sensing techniques Structure from Motion (SfM) and Terrestrial Laser Scanning (TLS). Over 4 TLS scan were collected, along with over 5,000 aerial images. Point clouds from SfM and TLS are merged and compared, and local structural lineaments analysed. As a result, we obtained an unprecedentedly high-resolution digital elevation map. With this map, we analyse the structural expression of the fissure eruption at the surface and improve understanding on the conditions that influenced the magma propagation path. We elaborate scenarios that lead to complexities of the surface structures and the link to the underlying dike intrusion.

Crystal structure of the Mus81-Eme1 complex.

PubMed

Chang, Jeong Ho; Kim, Jeong Joo; Choi, Jung Min; Lee, Jung Hoon; Cho, Yunje

2008-04-15

The Mus81-Eme1 complex is a structure-specific endonuclease that plays an important role in rescuing stalled replication forks and resolving the meiotic recombination intermediates in eukaryotes. We have determined the crystal structure of the Mus81-Eme1 complex. Both Mus81 and Eme1 consist of a central nuclease domain, two repeats of the helix-hairpin-helix (HhH) motif at their C-terminal region, and a linker helix. While each domain structure resembles archaeal XPF homologs, the overall structure is significantly different from those due to the structure of a linker helix. We show that a flexible intradomain linker that formed with 36 residues in the nuclease domain of Eme1 is essential for the recognition of DNA. We identified several basic residues lining the outer surface of the active site cleft of Mus81 that are involved in the interaction with a flexible arm of a nicked Holliday junction (HJ). These interactions might contribute to the optimal positioning of the opposite junction across the nick into the catalytic site, which provided the basis for the "nick and counternick" mechanism of Mus81-Eme1 and for the nicked HJ to be the favored in vitro substrate of this enzyme.

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

Avakian, Harut; Pisano, Silvia

The Deep Inelastic Scattering (DIS) proved to be a great tool in testing of the theory of strong in- teractions. Semi-Inclusive DIS (SIDIS), with detection of an additional hadron allowed first stud- ies of 3D structure of the nucleon, moving the main focus from testing the QCD to understanding of strong interactions and quark gluon dynamics to address a number of puzzles accumulated in recent years. Detection of two hadrons in SIDIS, which is even more complicated, provides ac- cess to details of quark gluon interactions inaccessible in single-hadron SIDIS, providing a new avenue to study the complex nucleon structure.more » Large acceptance of the CLAS detector at Jef- ferson Lab, allowing detection of two hadrons, produced back-to-back (b2b) in the current and target fragmentation regions, provides a unique possibility to study the nucleon structure in target fragmentation region, and correlations of target and current fragmentation regions« less

Complex Regional Pain Syndrome Type I Affects Brain Structure in Prefrontal and Motor Cortex

PubMed Central

Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

2014-01-01

The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the “non-flipped” data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the “flipped” data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control. PMID:24416397

A new insight into the three-dimensional architecture of the Golgi complex: Characterization of unusual structures in epididymal principal cells

PubMed Central

Martínez-Martínez, Narcisa; Martínez-Alonso, Emma; Tomás, Mónica; Neumüller, Josef; Pavelka, Margit

2017-01-01

Principal epididymal cells have one of the largest and more developed Golgi complex of mammalian cells. In the present study, we have used this cell as model for the study of the three-dimensional architecture of the Golgi complex of highly secretory and endocytic cells. Electron tomography demonstrated the presence in this cell type of some unknown or very unusual Golgi structures such as branched cisternae, pocket-like cisternal invaginations or tubular connections. In addition, we have used this methodology and immunoelectron microscopy to analyze the close relationship between this organelle and both the endoplasmic reticulum and microtubules, and to describe in detail how these elements interact with compact and non-compact regions of the ribbon. PMID:28957389

New mixed valence defect dicubane cobalt(II)/cobalt(III) complex: Synthesis, crystal structure, photoluminescence and magnetic properties

NASA Astrophysics Data System (ADS)

Coban, Mustafa Burak; Gungor, Elif; Kara, Hulya; Baisch, Ulrich; Acar, Yasemin

2018-02-01

A new defect dicubane cobalt(II)/cobalt(III), [(CoII2CoIII2L42(H2O)(CH3COO)(CH3COOH]. 4H2O complex (1) where H2L = [1-(3-hydroxypropyliminomethyl)naphthalene-2-ol], has been synthesized and characterized by element analysis, FT-IR, solid UV-Vis spectroscopy and single crystal X-ray diffraction. The crystal structure determination shows a cationic tetrameric arrangement consisting of a defect dicubane core with two missing vertexes. Each cobalt ion has a distorted octahedral geometry with six coordinate ordered CoII and CoIII ions. The solid state photoluminescence properties of complex (1) and its ligand H2L have been investigated under UV light at 349 nm in the visible region. H2L exhibits blue emission while complex (1) shows red emission at room temperature. Variable-temperature magnetic susceptibility measurements on the complex (1) in the range 2-300 K indicate an antiferromagnetic interaction.

Combing Chromosomal DNA Mediated by the SMC Complex: Structure and Mechanisms.

PubMed

Kamada, Katsuhiko; Barillà, Daniela

2018-02-01

Genome maintenance requires various nucleoid-associated factors in prokaryotes. Among them, the SMC (Structural Maintenance of Chromosomes) protein has been thought to play a static role in the organization and segregation of the chromosome during cell division. However, recent studies have shown that the bacterial SMC is required to align left and right arms of the emerging chromosome and that the protein dynamically travels from origin to Ter region. A rod form of the SMC complex mediates DNA bridging and has been recognized as a machinery responsible for DNA loop extrusion, like eukaryotic condensin or cohesin complexes, which act as chromosome organizers. Attention is now turning to how the prototype of the complex is loaded on the entry site and translocated on chromosomal DNA, explaining its overall conformational changes at atomic levels. Here, we review and highlight recent findings concerning the prokaryotic SMC complex and discuss possible mechanisms from the viewpoint of protein architecture. © 2017 The Authors. BioEssays Published by WILEY Periodicals, Inc.

Lithospheric Structure of Central Asia

NASA Astrophysics Data System (ADS)

Martin, R. J.; Gulen, L.; Sun, Y.; Toksoz, M. N.

2009-12-01

The active tectonics of Central Asia is the result of ongoing, active continental collision between the Indian and the Eurasian plates. This geologically and tectonically complex area is also one of the most seismically active regions in the world. Previous studies in this region mostly depended on teleseismic data and the local and regional data from the stations located in China. In this study we used the local travel time data from Kazakhstan, Kyrgyzstan, Tajikistan, and Uzbekistan to study the lithospheric structure in this region. We selected the events and stations between 32°N-65°E and 45°N-85°E and focused on the areas of Pamir and Tien Shan. In this data set, there are more than 3000 P and S arrivals received at 68 stations from about 220 events. The double difference tomography is applied to relocate events and to invert for seismic structure simultaneously. Our results provide accurate locations of earthquakes and high resolution lithospheric structure in this region. We use both; the local travel times, and also the regional travel times to invert the 3D lithospheric velocity structure in this region. More than 2200 P wave phase picks were used in the inversion. The average grid spacing is 100km and the inverted grids lay on six layers. Then we use the Double Difference Tomography method developed by Zhang and Thurber (2003, 2006) to invert the 3-D P-wave velocity structure. Our tomographic results show highly heterogeneous crust and upper mantle structure for Central Asia. Some crustal low velocity zones are found beneath Tien Shan, the northern Pamir, and the Tajik depression, while high velocity anomalies are found beneath the Kazakh shield, the southern Pamir, and the Tarim basin.

Thermostability of photosystem I trimers and monomers from the cyanobacterium Thermosynechococcus elongatus

NASA Astrophysics Data System (ADS)

Shubin, Vladimir V.; Terekhova, Irina V.; Bolychevtseva, Yulia V.; El-Mohsnawy, Eithar; Rögner, Matthias; Mäntele, Werner; Kopczak, Marta J.; Džafić, Enela

2017-05-01

The performance of solar energy conversion into alternative energy sources in artificial systems highly depends on the thermostability of photosystem I (PSI) complexes Terasaki et al. (2007), Iwuchukwu et al. (2010), Kothe et al. (2013) . To assess the thermostability of PSI complexes from the thermophilic cyanobacterium Thermosynechococcus elongatus heating induced perturbations on the level of secondary structure of the proteins were studied. Changes were monitored by Fourier transform infrared (FT-IR) spectra in the mid-IR region upon slow heating (1 °C per minute) of samples in D2O phosphate buffer (pD 7.4) from 20 °C to 100 °C. These spectra showed distinct changes in the Amide I region of PSI complexes as a function of the rising temperature. Absorbance at the Amide I maximum of PSI monomers (centered around 1653 cm- 1), gradually dropped in two temperature intervals, i.e. 60-75 and 80-90 °C. In contrast, absorbance at the Amide I maximum of PSI trimers (around 1656 cm- 1) dropped only in one temperature interval 80-95 °C. The thermal profile of the spectral shift of α-helices bands in the region 1656-1642 cm- 1 confirms the same two temperature intervals for PSI monomers and only one interval for trimers. Apparently, the observed absorbance changes at the Amide I maximum during heating of PSI monomers and trimers are caused by deformation and unfolding of α-helices. The absence of absorbance changes in the interval of 20-65 °C in PSI trimers is probably caused by a greater stability of protein secondary structure as compared to that in monomers. Upon heating above 80 °C a large part of α-helices both in trimers and monomers converts to unordered and aggregated structures. Spectral changes of PSI trimers and monomers heated up to 100 °C are irreversible due to protein denaturation and non-specific aggregation of complexes leading to new absorption bands at 1618-1620 cm- 1. We propose that monomers shield the denaturation sensitive sides at the monomer/monomer interface within a trimer, making the oligomeric structure more stable against thermal stress.

Landscape genetics of Schistocephalus solidus parasites in threespine stickleback (Gasterosteus aculeatus) from Alaska.

PubMed

Sprehn, C Grace; Blum, Michael J; Quinn, Thomas P; Heins, David C

2015-01-01

The nature of gene flow in parasites with complex life cycles is poorly understood, particularly when intermediate and definitive hosts have contrasting movement potential. We examined whether the fine-scale population genetic structure of the diphyllobothriidean cestode Schistocephalus solidus reflects the habits of intermediate threespine stickleback hosts or those of its definitive hosts, semi-aquatic piscivorous birds, to better understand complex host-parasite interactions. Seventeen lakes in the Cook Inlet region of south-central Alaska were sampled, including ten in the Matanuska-Susitna Valley, five on the Kenai Peninsula, and two in the Bristol Bay drainage. We analyzed sequence variation across a 759 bp region of the mitochondrial DNA (mtDNA) cytochrome oxidase I region for 1,026 S. solidus individuals sampled from 2009-2012. We also analyzed allelic variation at 8 microsatellite loci for 1,243 individuals. Analysis of mtDNA haplotype and microsatellite genotype variation recovered evidence of significant population genetic structure within S. solidus. Host, location, and year were factors in structuring observed genetic variation. Pairwise measures revealed significant differentiation among lakes, including a pattern of isolation-by-distance. Bayesian analysis identified three distinct genotypic clusters in the study region, little admixture within hosts and lakes, and a shift in genotype frequencies over time. Evidence of fine-scale population structure in S. solidus indicates that movement of its vagile, definitive avian hosts has less influence on gene flow than expected based solely on movement potential. Observed patterns of genetic variation may reflect genetic drift, behaviors of definitive hosts that constrain dispersal, life history of intermediate hosts, and adaptive specificity of S. solidus to intermediate host genotype.

Arp2/3 complex inhibition radically alters lamellipodial actin architecture, suspended cell shape, and the cell spreading process

PubMed Central

Henson, John H.; Yeterian, Mesrob; Weeks, Richard M.; Medrano, Angela E.; Brown, Briana L.; Geist, Heather L.; Pais, Mollyann D.; Oldenbourg, Rudolf; Shuster, Charles B.

2015-01-01

Recent studies have investigated the dendritic actin cytoskeleton of the cell edge's lamellipodial (LP) region by experimentally decreasing the activity of the actin filament nucleator and branch former, the Arp2/3 complex. Here we extend these studies via pharmacological inhibition of the Arp2/3 complex in sea urchin coelomocytes, cells that possess an unusually broad LP region and display correspondingly exaggerated centripetal flow. Using light and electron microscopy, we demonstrate that Arp2/3 complex inhibition via the drug CK666 dramatically altered LP actin architecture, slowed centripetal flow, drove a lamellipodial-to-filopodial shape change in suspended cells, and induced a novel actin structural organization during cell spreading. A general feature of the CK666 phenotype in coelomocytes was transverse actin arcs, and arc generation was arrested by a formin inhibitor. We also demonstrate that CK666 treatment produces actin arcs in other cells with broad LP regions, namely fish keratocytes and Drosophila S2 cells. We hypothesize that the actin arcs made visible by Arp2/3 complex inhibition in coelomocytes may represent an exaggerated manifestation of the elongate mother filaments that could possibly serve as the scaffold for the production of the dendritic actin network. PMID:25568343

Design of complex bone internal structure using topology optimization with perimeter control.

PubMed

Park, Jaejong; Sutradhar, Alok; Shah, Jami J; Paulino, Glaucio H

2018-03-01

Large facial bone loss usually requires patient-specific bone implants to restore the structural integrity and functionality that also affects the appearance of each patient. Titanium alloys (e.g., Ti-6Al-4V) are typically used in the interfacial porous coatings between the implant and the surrounding bone to promote stability. There exists a property mismatch between the two that in general leads to complications such as stress-shielding. This biomechanical discrepancy is a hurdle in the design of bone replacements. To alleviate the mismatch, the internal structure of the bone replacements should match that of the bone. Topology optimization has proven to be a good technique for designing bone replacements. However, the complex internal structure of the bone is difficult to mimic using conventional topology optimization methods without additional restrictions. In this work, the complex bone internal structure is recovered using a perimeter control based topology optimization approach. By restricting the solution space by means of the perimeter, the intricate design complexity of bones can be achieved. Three different bone regions with well-known physiological loadings are selected to illustrate the method. Additionally, we found that the target perimeter value and the pattern of the initial distribution play a vital role in obtaining the natural curvatures in the bone internal structures as well as avoiding excessive island patterns. Copyright © 2018 Elsevier Ltd. All rights reserved.

Air-flow distortion and turbulence statistics near an animal facility

NASA Astrophysics Data System (ADS)

Prueger, J. H.; Eichinger, W. E.; Hipps, L. E.; Hatfield, J. L.; Cooper, D. I.

The emission and dispersion of particulates and gases from concentrated animal feeding operations (CAFO) at local to regional scales is a current issue in science and society. The transport of particulates, odors and toxic chemical species from the source into the local and eventually regional atmosphere is largely determined by turbulence. Any models that attempt to simulate the dispersion of particles must either specify or assume various statistical properties of the turbulence field. Statistical properties of turbulence are well documented for idealized boundary layers above uniform surfaces. However, an animal production facility is a complex surface with structures that act as bluff bodies that distort the turbulence intensity near the buildings. As a result, the initial release and subsequent dispersion of effluents in the region near a facility will be affected by the complex nature of the surface. Previous Lidar studies of plume dispersion over the facility used in this study indicated that plumes move in complex yet organized patterns that would not be explained by the properties of turbulence generally assumed in models. The objective of this study was to characterize the near-surface turbulence statistics in the flow field around an array of animal confinement buildings. Eddy covariance towers were erected in the upwind, within the building array and downwind regions of the flow field. Substantial changes in turbulence intensity statistics and turbulence-kinetic energy (TKE) were observed as the mean wind flow encountered the building structures. Spectra analysis demonstrated unique distribution of the spectral energy in the vertical profile above the buildings.

Comparison of Observed Spatio-temporal Aftershock Patterns with Earthquake Simulator Results

NASA Astrophysics Data System (ADS)

Kroll, K.; Richards-Dinger, K. B.; Dieterich, J. H.

2013-12-01

Due to the complex nature of faulting in southern California, knowledge of rupture behavior near fault step-overs is of critical importance to properly quantify and mitigate seismic hazards. Estimates of earthquake probability are complicated by the uncertainty that a rupture will stop at or jump a fault step-over, which affects both the magnitude and frequency of occurrence of earthquakes. In recent years, earthquake simulators and dynamic rupture models have begun to address the effects of complex fault geometries on earthquake ground motions and rupture propagation. Early models incorporated vertical faults with highly simplified geometries. Many current studies examine the effects of varied fault geometry, fault step-overs, and fault bends on rupture patterns; however, these works are limited by the small numbers of integrated fault segments and simplified orientations. The previous work of Kroll et al., 2013 on the northern extent of the 2010 El Mayor-Cucapah rupture in the Yuha Desert region uses precise aftershock relocations to show an area of complex conjugate faulting within the step-over region between the Elsinore and Laguna Salada faults. Here, we employ an innovative approach of incorporating this fine-scale fault structure defined through seismological, geologic and geodetic means in the physics-based earthquake simulator, RSQSim, to explore the effects of fine-scale structures on stress transfer and rupture propagation and examine the mechanisms that control aftershock activity and local triggering of other large events. We run simulations with primary fault structures in state of California and northern Baja California and incorporate complex secondary faults in the Yuha Desert region. These models produce aftershock activity that enables comparison between the observed and predicted distribution and allow for examination of the mechanisms that control them. We investigate how the spatial and temporal distribution of aftershocks are affected by changes to model parameters such as shear and normal stress, rate-and-state frictional properties, fault geometry, and slip rate.

No Evidence for Connectivity between the Bushveld Igneous Complex and the Molopo Farms Complex from Forward Modeling of Receiver Functions

NASA Astrophysics Data System (ADS)

Skryzalin, P. A.; Ramirez, C.; Durrheim, R. J.; Raveloson, A.; Nyblade, A.; Feineman, M. D.

2016-12-01

The Bushveld Igneous Complex contains one of the most studied and economically important layered mafic intrusions in the world. The Rustenburg Layered Suite outcrops in northern South Africa over an area of 65,000 km2, and has a volume of up to 1,000,000 km3. Both the Bushveld Igneous Complex and the Molopo Farms Complex in Botswana intruded the crust at 2.05 Ga. Despite being extensively exploited by the mining industry, many questions still exist regarding the structure of the Bushveld Igneous Complex, specifically the total size and connectivity of the different outcrops. In this study, we used receiver function analysis, a technique for determining the seismic velocity structure of the crust and upper mantle, to search for evidence of the Bushveld at station LBTB, which lies in Botswana, between the Far Western Limb of the Bushveld and the Molopo Farms Complex. The goal of our study was to determine whether a fast, high-density mafic body can be seen in the crust beneath this region using receiver functions. Observation of a high density layer would argue in favor of connectivity of the Bushveld between The Far Western Limb and the Molopo Farms Complex. We forward modeled stacks of receiver functions as well as sub-stacks that were split into azimuthal groups which share similar characteristics. We found that there was no evidence for a high velocity zone in the crust, and that the Moho in this region is located at a depth of 38 ± 3 km, about 8-9 km shallower than Moho depths determined beneath the Bushveld Complex. These two lines of evidence give no reason to assume connectivity between the Bushveld Igneous Complex and the Molopo Farms Complex, and rather suggest two separate intrusive suites.

Structure of homeodomain-leucine zipper/DNA complexes studied using hydroxyl radical cleavage of DNA and methylation interference.

PubMed

Tron, Adriana E; Comelli, Raúl N; Gonzalez, Daniel H

2005-12-27

Homeodomain-leucine zipper (HD-Zip) proteins, unlike most homeodomain proteins, bind a pseudopalindromic DNA sequence as dimers. We have investigated the structure of the DNA complexes formed by two HD-Zip proteins with different nucleotide preferences at the central position of the binding site using footprinting and interference methods. The results indicate that the respective complexes are not symmetric, with the strand bearing a central purine (top strand) showing higher protection around the central region and the bottom strand protected toward the 3' end. Binding to a sequence with a nonpreferred central base pair produces a decrease in protection in either the top or the bottom strand, depending upon the protein. Modeling studies derived from the complex formed by the monomeric Antennapedia homeodomain with DNA indicate that in the HD-Zip/DNA complex the recognition helix of one of the monomers is displaced within the major groove respective to the other one. This monomer seems to lose contacts with a part of the recognition sequence upon binding to the nonpreferred site. The results show that the structure of the complex formed by HD-Zip proteins with DNA is dependent upon both protein intrinsic characteristics and the nucleotides present at the central position of the recognition sequence.

Maturation of Shark Single-Domain (IgNAR) Antibodies: Evidence for Induced-Fit Binding

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

Stanfield, R.L.; Dooley, H.; Verdino, P.

2007-07-13

Sharks express an unusual heavy-chain isotype called IgNAR, whose variable regions bind antigen as independent soluble domains. To further probe affinity maturation of the IgNAR response, we structurally characterized the germline and somatically matured versions of a type II variable (V) region, both in the presence and absence of its antigen, hen egg-white lysozyme. Despite a disulfide bond linking complementarity determining regions (CDRs) 1 and 3, both germline and somatically matured V regions displayed significant structural changes in these CDRs upon complex formation with antigen. Somatic mutations in the IgNAR V region serve to increase the number of contacts withmore » antigen, as reflected by a tenfold increase in affinity, and one of these mutations appears to stabilize the CDR3 region. In addition, a residue in the HV4 loop plays an important role in antibody-antigen interaction, consistent with the high rate of somatic mutations in this non-CDR loop.« less

Seismic detection of the summit magma complex of kilauea volcano, hawaii.

PubMed

Thurber, C H

1984-01-13

Application of simultaneous inversion of seismic P-wave arrival time data to the investigation of the crust beneath Kilauea Volcano yields a detailed picture of the volcano's heterogeneous structure. Zones of anomalously high seismic velocity are found associated with the volcano's rift zones. A low-velocity zone at shallow depth directly beneath the caldera coincides with an aseismic region interpreted as being the locus of Kilauea's summit magma complex.

Crystal structures of η''-Cu3+xSi and η'''-Cu3+xSi.

PubMed

Corrêa, Cinthia Antunes; Perez, Olivier; Kopeček, Jaromír; Brázda, Petr; Klementová, Mariana; Palatinus, Lukáš

2017-08-01

The binary phase diagram of Cu-Si is unexpectedly complex in the vicinity of Cu 3+x Si. The low-temperature region contains three closely related incommensurately modulated phases denoted, in order of increasing temperature of stability, η''', η'' and η'. The structure analysis of η' has been reported previously [Palatinus et al. (2011). Inorg. Chem. 50, 3743]. Here the structure model for the phases η'' and η''' is reported. The structures could be solved in superspace, but no superspace structure model could be constructed due to the complexity of the modulation functions. Therefore, the structures were described in a supercell approximation, which involved a 4 × 4 × 3 supercell for the η'' phase and a 14 × 14 × 3 supercell for the η''' phase. Both structures are very similar and differ only by a subtle symmetry lowering from η'' to η'''. A comparison of the structure models of η'' and η''' with the reported structure of η' suggests that the reported structure model of η' contains an incorrect assignment of atomic types.

Identification and characterization of ten new water gaps in seeds and fruits with physical dormancy and classification of water-gap complexes.

PubMed

Gama-Arachchige, N S; Baskin, J M; Geneve, R L; Baskin, C C

2013-07-01

Physical dormancy (PY) occurs in seeds or fruits of 18 angiosperm families and is caused by a water-impermeable palisade cell layer(s) in seed or fruit coats. Prior to germination, the seed or fruit coat of species with PY must become permeable in order to imbibe water. Breaking of PY involves formation of a small opening(s) (water gap) in a morpho-anatomically specialized area in seeds or fruits known as the water-gap complex. Twelve different water-gap regions in seven families have previously been characterized. However, the water-gap regions had not been characterized in Cucurbitaceae; clade Cladrastis of Fabaceae; subfamilies Bombacoideae, Brownlowioideae and Bythnerioideae of Malvaceae; Nelumbonaceae; subfamily Sapindoideae of Sapindaceae; Rhamnaceae; or Surianaceae. The primary aims of this study were to identify and describe the water gaps of these taxa and to classify all the known water-gap regions based on their morpho-anatomical features. Physical dormancy in 15 species was broken by exposing seeds or fruits to wet or dry heat under laboratory conditions. Water-gap regions of fruits and seeds were identified and characterized by use of microtome sectioning, light microscopy, scanning electron microscopy, dye tracking and blocking experiments. Ten new water-gap regions were identified in seven different families, and two previously hypothesized regions were confirmed. Water-gap complexes consist of (1) an opening that forms after PY is broken; (2) a specialized structure that occludes the gap; and (3) associated specialized tissues. In some species, more than one opening is involved in the initial imbibition of water. Based on morpho-anatomical features, three basic water-gap complexes (Types-I, -II and -III) were identified in species with PY in 16 families. Depending on the number of openings involved in initial imbibition, the water-gap complexes were sub-divided into simple and compound. The proposed classification system enables understanding of the relationships between the water-gap complexes of taxonomically unrelated species with PY.

Biochemical and structural characterization of a novel cooperative binding mode by Pit-1 with CATT repeats in the macrophage migration inhibitory factor promoter

PubMed Central

Agarwal, Sorabh

2018-01-01

Abstract Overexpression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) is linked to a number of autoimmune diseases and cancer. MIF production has been correlated to the number of CATT repeats in a microsatellite region upstream of the MIF gene. We have characterized the interaction of pituitary-specific positive transcription factor 1 (Pit-1) with a portion of the MIF promoter region flanking a microsatellite polymorphism (−794 CATT5–8). Using fluorescence anisotropy, we quantified tight complex formation between Pit-1 and an oligonucleotide consisting of eight consecutive CATT repeats (8xCATT) with an apparent Kd of 35 nM. Using competition experiments we found a 23 base pair oligonucleotide with 4xCATT repeats to be the minimum DNA sequence necessary for high affinity interaction with Pit-1. The stoichiometry of the Pit-1 DNA interaction was determined to be 2:1 and binding is cooperative in nature. We subsequently structurally characterized the complex and discovered a completely novel binding mode for Pit-1 in contrast to previously described Pit-1 complex structures. The affinity of Pit-1 for the CATT target sequence was found to be highly dependent on cooperativity. This work lays the groundwork for understanding transcriptional regulation of MIF and pursuing Pit-1 as a therapeutic target to treat MIF-mediated inflammatory disorders. PMID:29186613

Collision-induced dissociative chemical cross-linking reagents and methodology: Applications to protein structural characterization using tandem mass spectrometry analysis.

PubMed

Soderblom, Erik J; Goshe, Michael B

2006-12-01

Chemical cross-linking combined with mass spectrometry is a viable approach to study the low-resolution structure of protein and protein complexes. However, unambiguous identification of the residues involved in a cross-link remains analytically challenging. To enable a more effective analysis across various MS platforms, we have developed a novel set of collision-induced dissociative cross-linking reagents and methodology for chemical cross-linking experiments using tandem mass spectrometry (CID-CXL-MS/MS). These reagents incorporate a single gas-phase cleavable bond within their linker region that can be selectively fragmented within the in-source region of the mass spectrometer, enabling independent MS/MS analysis for each peptide. Initial design concepts were characterized using a synthesized cross-linked peptide complex. Following verification and subsequent optimization of cross-linked peptide complex dissociation, our reagents were applied to homodimeric glutathione S-transferase and monomeric bovine serum albumin. Cross-linked residues identified by our CID-CXL-MS/MS method were in agreement with published crystal structures and previous cross-linking studies using conventional approaches. Common LC/MS/MS acquisition approaches such as data-dependent acquisition experiments using ion trap mass spectrometers and product ion spectral analysis using SEQUEST were shown to be compatible with our CID-CXL-MS/MS reagents, obviating the requirement for high resolution and high mass accuracy measurements to identify both intra- and interpeptide cross-links.

Structural and Biochemical Studies of Actin in Complex with Synthetic Macrolide Tail Analogues

DOE PAGES

Pereira, Jose H.; Petchprayoon, Chutima; Hoepker, Alexander C.; ...

2014-07-22

The actin filament-binding and filament-severing activities of the aplyronine, kabiramide, and reidispongiolide families of marine macrolides are located within the hydrophobic tail region of the molecule. Two synthetic tail analogues of aplyronine C (SF-01 and GC-04) are shown to bind to G-actin with dissociation constants of (285±33) and (132±13) nM, respectively. The crystal structures of actin complexes with GC-04, SF-01, and kabiramide C reveal a conserved mode of tail binding within the cleft that forms between subdomains (SD) 1 and 3. Our studies support the view that filament severing is brought about by specific binding of the tail region tomore » the SD1/SD3 cleft on the upper protomer, which displaces loop-D from the lower protomer on the same half-filament. With previous studies showing that the GC-04 analogue can sever actin filaments, it is argued that the shorter complex lifetime of tail analogues with F-actin would make them more effective at severing filaments compared with plasma gelsolin. In conclusion, structure-based analyses are used to suggest more reactive or targetable forms of GC-04 and SF-01, which may serve to boost the capacity of the serum actin scavenging system, to generate antibody conjugates against tumor cell antigens, and to decrease sputum viscosity in children with cystic fibrosis.« less

Unbound Young Stellar Systems: Star Formation on the Loose

NASA Astrophysics Data System (ADS)

Gouliermis, Dimitrios A.

2018-07-01

Unbound young stellar systems, the loose ensembles of physically related young bright stars, trace the typical regions of recent star formation in galaxies. Their morphologies vary from small few pc-size associations of newly formed stars to enormous few kpc-size complexes composed of stars few 100 Myr old. These stellar conglomerations are located within the disks and along the spiral arms and rings of star-forming disk galaxies, and they are the active star-forming centers of dwarf and starburst galaxies. Being associated with star-forming regions of various sizes, these stellar structures trace the regions where stars form at various length- and timescales, from compact clusters to whole galactic disks. Stellar associations, the prototypical unbound young systems, and their larger counterparts, stellar aggregates, and stellar complexes, have been the focus of several studies for quite a few decades, with special interest on their demographics, classification, and structural morphology. The compiled surveys of these loose young stellar systems demonstrate that the clear distinction of these systems into well-defined classes is not as straightforward as for stellar clusters, due to their low densities, asymmetric shapes and variety in structural parameters. These surveys also illustrate that unbound stellar structures follow a clear hierarchical pattern in the clustering of their stars across various scales. Stellar associations are characterized by significant sub-structure with bound stellar clusters being their most compact parts, while associations themselves are the brighter denser parts of larger stellar aggregates and stellar complexes, which are members of larger super-structures up to the scale of a whole star-forming galaxy. This structural pattern, which is usually characterized as self-similar or fractal, appears to be identical to that of star-forming giant molecular clouds and interstellar gas, driven mainly by turbulence cascade. In this short review, I make a concise compilation of our understanding of unbound young stellar systems across various environments in the local universe, as it is developed during the last 60 years. I present a factual assessment of the clustering behavior of star formation, as revealed from the assembling pattern of stars across loose stellar structures and its relation to the interstellar medium and the environmental conditions. I also provide a consistent account of the processes that possibly play important role in the formation of unbound stellar systems, compiled from both theoretical and observational investigations on the field.

Structured grid technology to enable flow simulation in an integrated system environment

NASA Astrophysics Data System (ADS)

Remotigue, Michael Gerard

An application-driven Computational Fluid Dynamics (CFD) environment needs flexible and general tools to effectively solve complex problems in a timely manner. In addition, reusable, portable, and maintainable specialized libraries will aid in rapidly developing integrated systems or procedures. The presented structured grid technology enables the flow simulation for complex geometries by addressing grid generation, grid decomposition/solver setup, solution, and interpretation. Grid generation is accomplished with the graphical, arbitrarily-connected, multi-block structured grid generation software system (GUM-B) developed and presented here. GUM-B is an integrated system comprised of specialized libraries for the graphical user interface and graphical display coupled with a solid-modeling data structure that utilizes a structured grid generation library and a geometric library based on Non-Uniform Rational B-Splines (NURBS). A presented modification of the solid-modeling data structure provides the capability for arbitrarily-connected regions between the grid blocks. The presented grid generation library provides algorithms that are reliable and accurate. GUM-B has been utilized to generate numerous structured grids for complex geometries in hydrodynamics, propulsors, and aerodynamics. The versatility of the libraries that compose GUM-B is also displayed in a prototype to automatically regenerate a grid for a free-surface solution. Grid decomposition and solver setup is accomplished with the graphical grid manipulation and repartition software system (GUMBO) developed and presented here. GUMBO is an integrated system comprised of specialized libraries for the graphical user interface and graphical display coupled with a structured grid-tools library. The described functions within the grid-tools library reduce the possibility of human error during decomposition and setup for the numerical solver by accounting for boundary conditions and connectivity. GUMBO is linked with a flow solver interface, to the parallel UNCLE code, to provide load balancing tools and solver setup. Weeks of boundary condition and connectivity specification and validation has been reduced to hours. The UNCLE flow solver is utilized for the solution of the flow field. To accelerate convergence toward a quick engineering answer, a full multigrid (FMG) approach coupled with UNCLE, which is a full approximation scheme (FAS), is presented. The prolongation operators used in the FMG-FAS method are compared. The procedure is demonstrated on a marine propeller in incompressible flow. Interpretation of the solution is accomplished by vortex feature detection. Regions of "Intrinsic Swirl" are located by interrogating the velocity gradient tensor for complex eigenvalues. The "Intrinsic Swirl" parameter is visualized on a solution of a marine propeller to determine if any vortical features are captured. The libraries and the structured grid technology presented herein are flexible and general enough to tackle a variety of complex applications. This technology has significantly enabled the capability of the ERC personnel to effectively calculate solutions for complex geometries.

Delineation of the calcineurin-interacting region of cyclophilin B.

PubMed

Carpentier, M; Allain, F; Haendler, B; Slomianny, M C; Spik, G

2000-12-01

The immunosuppressant drug cyclosporin A (CsA) inhibits T-cell function by blocking the phosphatase activity of calcineurin. This effect is mediated by formation of a complex between the drug and cyclophilin (CyP), which creates a composite surface able to make high-affinity contacts with calcineurin. In vitro, the CyPB/CsA complex is more effective in inhibiting calcineurin than the CyPA/CsA and CyPC/CsA complexes, pointing to fine structural differences in the calcineurin-binding region. To delineate the calcineurin-binding region of CyPB, we mutated several amino acids, located in two loops corresponding to CyPA regions known to be involved, as follows: R76A, G77H, D155R, and D158R. Compared to wild-type CyPB, the G77H, D155R, and D158R mutants had intact isomerase and CsA-binding activities, indicating that no major conformational changes had taken place. When complexed to CsA, they all displayed only reduced affinity for calcineurin and much decreased inhibition of calcineurin phosphatase activity. These results strongly suggest that the three amino acids G77, D155, and D158 are directly involved in the interaction of CyPB/CsA with calcineurin, in agreement with their exposed position. The G77, D155, and D158 residues are not maintained in CyPA and might therefore account for the higher affinity of the CyPB/CsA complex for calcineurin.

The measles virus N(TAIL)-XD complex: an illustrative example of fuzziness.

PubMed

Longhi, Sonia

2012-01-01

In this chapter, I focus on the biochemical and structural characterization of the complex between the intrinsically disordered C-terminal domain of the measles virus nucleoprotein (N(TAIL)) and the C-terminal X domain (XD) of the viral phosphoprotein (P). I summarize the main experimental data available so far pointing out the prevalently disordered nature of N(TAIL) even after complex formation and the role of the flexible C-terminal appendage in the binding reaction. I finally discuss the possible functional role of these residual disordered regions within the complex in terms of their ability to capture other regulatory, binding partners.

Phylogeography and biogeography of the lower Central American Neotropics: diversification between two continents and between two seas.

PubMed

Bagley, Justin C; Johnson, Jerald B

2014-11-01

Lower Central America (LCA) provides a geologically complex and dynamic, richly biodiverse model for studying the recent assembly and diversification of a Neotropical biota. Here, we review the growing literature of LCA phylogeography studies and their contribution to understanding the origins, assembly, and diversification of the LCA biota against the backdrop of regional geologic and climatic history, and previous biogeographical inquiry. Studies to date reveal that phylogeographical signal within taxa of differing distributions reflects a diversity of patterns and processes rivalling the complexities of LCA landscapes themselves. Even so, phylogeography is providing novel insights into regional diversification (e.g. cryptic lineage divergences), and general evolutionary patterns are emerging. Congruent multi-taxon phylogeographic breaks are found across the Nicaraguan depression, Chorotega volcanic front, western and central Panama, and the Darién isthmus, indicating that a potentially shared history of responses to regional-scale (e.g. geological) processes has shaped the genetic diversity of LCA communities. By contrast, other species show unique demographic histories in response to overriding historical events, including no phylogeographic structure at all. These low-structure or incongruent patterns provide some evidence for a role of local, ecological factors (e.g. long-distance dispersal and gene flow in plants and bats) in shaping LCA communities. Temporally, comparative phylogeographical structuring reflects Pliocene-Pleistocene dispersal and vicariance events consistent with the timeline of emergence of the LCA isthmus and its major physiographic features, e.g. cordilleras. We emphasise the need to improve biogeographic inferences in LCA through in-depth comparative phylogeography projects capitalising on the latest statistical phylogeographical methods. While meeting the challenges of reconstructing the biogeographical history of this complex region, phylogeographers should also take up the critical service to society of applying their work to the conservation of its fascinating biodiversity. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

Results and Lessons Learned from a Coupled Social and Physical Hydrology Model: Testing Alternative Water Management Policies and Institutional Structures Using Agent-Based Modeling and Regional Hydrology

NASA Astrophysics Data System (ADS)

Murphy, J.; Lammers, R. B.; Prousevitch, A.; Ozik, J.; Altaweel, M.; Collier, N. T.; Kliskey, A. D.; Alessa, L.

2015-12-01

Water Management in the U.S. Southwest is under increasing scrutiny as many areas endure persistent drought. The impact of these prolonged dry conditions is a product of regional climate and hydrological conditions, but also of a highly engineered water management infrastructure and a complex web of social arrangements whereby water is allocated, shared, exchanged, used, re-used, and finally consumed. We coupled an agent-based model with a regional hydrological model to understand the dynamics in one richly studied and highly populous area: southern Arizona, U.S.A., including metropolitan Phoenix and Tucson. There, multiple management entities representing an array of municipalities and other water providers and customers, including private companies and Native American tribes are enmeshed in a complex legal and economic context in which water is bought, leased, banked, and exchanged in a variety of ways and on multiple temporal and physical scales. A recurrent question in the literature of adaptive management is the impact of management structure on overall system performance. To explore this, we constructed an agent-based model to capture this social complexity, and coupled this with a physical hydrological model that we used to drive the system under a variety of water stress scenarios and to assess the regional impact of the social system's performance. We report the outcomes of ensembles of runs in which varieties of alternative policy constraints and management strategies are considered. We hope to contribute to policy discussions in this area and connected and legislatively similar areas (such as California) as current conditions change and existing legal and policy structures are revised. Additionally, we comment on the challenges of integrating models that ostensibly are in different domains (physical and social) but that independently represent a system in which physical processes and human actions are closely intertwined and difficult to disentangle.

Circular Dichroism reveals evidence of coupling between immunoglobulin constant and variable region secondary structure.

PubMed

Janda, Alena; Casadevall, Arturo

2010-04-01

Antibodies (Ab) are bifunctional molecules with two domains, a constant region (C) that confers effector properties and a variable (V) region responsible of antigen (Ag) binding. Historically the C and V regions were considered to be functionally independent, with Ag specificity being solely determined by the V region. However, recent studies suggest that the C region can affect Ab fine specificity. This has led to the proposal that the C(H) domain influences the structure of the V region, thus affecting Ab affinity and fine specificity. An inference from this proposal is that V region identical monoclonal Abs (mAbs) differing in C region (eg isotype) would manifest different secondary structures arising from isotype-induced variation in the V-C regions after Ag binding. We hypothesized that such effects could translate into differences in Circular Dichroism (CD) upon Ag-Ab complexes formation. Consequently we studied the interaction of a set of V region identical IgG(1), IgG(2a), IgG(2b) and IgG(3) mAbs with glucuronoxylomannan (GXM). The native CD spectra of the pairs IgG(1)/IgG(2a) and IgG(3)/IgG(2b) were strikingly similar, implying similar secondary structure content. GXM binding by IgG(1), IgG(2a), IgG(2b) and IgG(3) produced different CD changes, with the pairs IgG(1)/IgG(2a) and IgG(3)/IgG(2b) again manifesting qualitatively similar trends in secondary structure changes. The magnitude of the changes differed among the isotypes with IgG(2a)>IgG(3)>IgG(2b)>IgG(1). These differences in CD changes were interpreted to reflect differences in V-C secondary structures. Copyright 2010 Elsevier Ltd. All rights reserved.

Using Brain Imaging to Extract the Structure of Complex Events at the Rational Time Band

PubMed Central

Anderson, John R.; Qin, Yulin

2017-01-01

A functional magnetic resonance imaging (fMRI) study was performed in which participants performed a complex series of mental calculations that spanned about 2 min. An Adaptive Control of Thought—Rational (ACT-R) model [Anderson, J. R. How can the human mind occur in the physical universe? New York: Oxford University Press, 2007] was developed that successfully fit the distribution of latencies. This model generated predictions for the fMRI signal in six brain regions that have been associated with modules in the ACT-R theory. The model’s predictions were confirmed for a fusiform region that reflects the visual module, for a prefrontal region that reflects the retrieval module, and for an anterior cingulate region that reflects the goal module. In addition, the only significant deviations to the motor region that reflects the manual module were anticipatory hand movements. In contrast, the predictions were relatively poor for a parietal region that reflects an imaginal module and for a caudate region that reflects the procedural module. Possible explanations of these poor fits are discussed. In addition, exploratory analyses were performed to find regions that might correspond to the predictions of the modules. PMID:18345979

Using brain imaging to extract the structure of complex events at the rational time band.

PubMed

Anderson, John R; Qin, Yulin

2008-09-01

A functional magnetic resonance imaging (fMRI) study was performed in which participants performed a complex series of mental calculations that spanned about 2 min. An Adaptive Control of Thought--Rational (ACT-R) model [Anderson, J. R. How can the human mind occur in the physical universe? New York: Oxford University Press, 2007] was developed that successfully fit the distribution of latencies. This model generated predictions for the fMRI signal in six brain regions that have been associated with modules in the ACT-R theory. The model's predictions were confirmed for a fusiform region that reflects the visual module, for a prefrontal region that reflects the retrieval module, and for an anterior cingulate region that reflects the goal module. In addition, the only significant deviations to the motor region that reflects the manual module were anticipatory hand movements. In contrast, the predictions were relatively poor for a parietal region that reflects an imaginal module and for a caudate region that reflects the procedural module. Possible explanations of these poor fits are discussed. In addition, exploratory analyses were performed to find regions that might correspond to the predictions of the modules.

Structural basis for the inhibition of insulin-like growth factors by insulin-like growth factor-binding proteins

PubMed Central

Sitar, Tomasz; Popowicz, Grzegorz M.; Siwanowicz, Igor; Huber, Robert; Holak, Tad A.

2006-01-01

Insulin-like growth factor-binding proteins (IGFBPs) control bioavailability, activity, and distribution of insulin-like growth factor (IGF)1 and -2 through high-affinity IGFBP/IGF complexes. IGF-binding sites are found on N- and C-terminal fragments of IGFBPs, the two conserved domains of IGFBPs. The relative contributions of these domains to IGFBP/IGF complexation has been difficult to analyze, in part, because of the lack of appropriate three-dimensional structures. To analyze the effects of N- and C-terminal domain interactions, we determined several x-ray structures: first, of a ternary complex of N- and C-terminal domain fragments of IGFBP4 and IGF1 and second, of a “hybrid” ternary complex using the C-terminal domain fragment of IGFBP1 instead of IGFBP4. We also solved the binary complex of the N-terminal domains of IGFBP4 and IGF1, again to analyze C- and N-terminal domain interactions by comparison with the ternary complexes. The structures reveal the mechanisms of IGF signaling regulation via IGFBP binding. This finding supports research into the design of IGFBP variants as therapeutic IGF inhibitors for diseases of IGF disregulation. In IGFBP4, residues 1–38 form a rigid disulphide bond ladder-like structure, and the first five N-terminal residues bind to IGF and partially mask IGF residues responsible for the type 1 IGF receptor binding. A high-affinity IGF1-binding site is located in a globular structure between residues 39 and 82. Although the C-terminal domains do not form stable binary complexes with either IGF1 or the N-terminal domain of IGFBP4, in the ternary complex, the C-terminal domain contacts both and contributes to blocking of the IGF1 receptor-binding region of IGF1. PMID:16924115

Water-refined solution structure of the human Grb7-SH2 domain in complex with the erbB2 receptor peptide pY1139.

PubMed

Pias, Sally C; Johnson, Dennis L; Smith, David E; Lyons, Barbara A

2012-08-01

We report a refinement in implicit water of the previously published solution structure of the Grb7-SH2 domain bound to the erbB2 receptor peptide pY1139. Structure quality measures indicate substantial improvement, with residues in the most favored regions of the Ramachandran plot increasing by 14 % and with WHAT IF statistics (Vriend, G. J. Mol. Graph., 1990, 8(1), 52-56) falling closer to expected values for well-refined structures.

Building bridges between cellular and molecular structural biology.

PubMed

Patwardhan, Ardan; Brandt, Robert; Butcher, Sarah J; Collinson, Lucy; Gault, David; Grünewald, Kay; Hecksel, Corey; Huiskonen, Juha T; Iudin, Andrii; Jones, Martin L; Korir, Paul K; Koster, Abraham J; Lagerstedt, Ingvar; Lawson, Catherine L; Mastronarde, David; McCormick, Matthew; Parkinson, Helen; Rosenthal, Peter B; Saalfeld, Stephan; Saibil, Helen R; Sarntivijai, Sirarat; Solanes Valero, Irene; Subramaniam, Sriram; Swedlow, Jason R; Tudose, Ilinca; Winn, Martyn; Kleywegt, Gerard J

2017-07-06

The integration of cellular and molecular structural data is key to understanding the function of macromolecular assemblies and complexes in their in vivo context. Here we report on the outcomes of a workshop that discussed how to integrate structural data from a range of public archives. The workshop identified two main priorities: the development of tools and file formats to support segmentation (that is, the decomposition of a three-dimensional volume into regions that can be associated with defined objects), and the development of tools to support the annotation of biological structures.

FTIR Study of Comustion Species in Several Regions of a Candle Flame

NASA Astrophysics Data System (ADS)

White, Allen R.

2013-06-01

The complex chemical structure of the fuel in a candle flame, parafin, is broken down into smaller hydrocarbons in the dark region just above the candle wick during combustion. This creates fuel-rich, fuel-lean, hydrocarbon reaction, and combustion product regions in the flame during combustion that are spectroscopically rich, particularly in the infrared. IR emissions were measured for each reaction region via collection optics focused into an FTIR and used to identify IR active species present in that region and, when possible, temperature of the sampling region. The results of the measurements are useful for combustion reaction modeling as well as for future validation of mass spectroscopy sampling systems.

ExpandplusCrystal Structures of Poly(ADP-ribose) Polymerase-1 (PARP-1) Zinc Fingers Bound to DNA

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

M Langelier; J Planck; S Roy

2011-12-31

Poly(ADP-ribose) polymerase-1 (PARP-1) has two homologous zinc finger domains, Zn1 and Zn2, that bind to a variety of DNA structures to stimulate poly(ADP-ribose) synthesis activity and to mediate PARP-1 interaction with chromatin. The structural basis for interaction with DNA is unknown, which limits our understanding of PARP-1 regulation and involvement in DNA repair and transcription. Here, we have determined crystal structures for the individual Zn1 and Zn2 domains in complex with a DNA double strand break, providing the first views of PARP-1 zinc fingers bound to DNA. The Zn1-DNA and Zn2-DNA structures establish a novel, bipartite mode of sequence-independent DNAmore » interaction that engages a continuous region of the phosphodiester backbone and the hydrophobic faces of exposed nucleotide bases. Biochemical and cell biological analysis indicate that the Zn1 and Zn2 domains perform distinct functions. The Zn2 domain exhibits high binding affinity to DNA compared with the Zn1 domain. However, the Zn1 domain is essential for DNA-dependent PARP-1 activity in vitro and in vivo, whereas the Zn2 domain is not strictly required. Structural differences between the Zn1-DNA and Zn2-DNA complexes, combined with mutational and structural analysis, indicate that a specialized region of the Zn1 domain is re-configured through the hydrophobic interaction with exposed nucleotide bases to initiate PARP-1 activation.« less

Me-3,2-HOPO Complexes of Near Infra-Red (NIR) Emitting Lanthanides: Efficient Sensitization of Yb(III) and Nd(III) in Aqueous Solution

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

Moore, Evan G.; Xu, Jide; Dodani, Sheel

2009-11-10

The synthesis, X-ray structure, solution stability, and photophysical properties of several trivalent lanthanide complexes of Yb(III) and Nd(III) using both tetradentate and octadentate ligand design strategies and incorporating the 1-methyl-3-hydroxy-pyridin-2-one (Me-3,2-HOPO) chelate group are reported. Both the Yb(III) and Nd(III) complexes have emission bands in the Near Infra-Red (NIR) region, and this luminescence is retained in aqueous solution ({Phi}{sub tot}{sup Yb} {approx} 0.09-0.22%). Furthermore, the complexes demonstrate very high stability (pYb {approx} 18.8-21.9) in aqueous solution, making them good candidates for further development as probes for NIR imaging. Analysis of the low temperature (77 K) photophysical measurements for a modelmore » Gd(III) complex were used to gain an insight into the electronic structure, and were found to agree well with corresponding TD-DFT calculations at the B3LYP/6-311G{sup ++}(d,p) level of theory for a simplified model monovalent sodium complex.« less

Crystal structure of a complex between the phosphorelay protein YPD1 and the response regulator domain of SLN1 bound to a phosphoryl analog

PubMed Central

Zhao, Xiaodong; Copeland, Daniel M.; Soares, Alexei S.; West, Ann H.

2008-01-01

Summary The crystal structure of the yeast SLN1 response regulator domain bound to both a phosphoryl analog (BeF3−) and Mg2+ ion in complex with its downstream phosphorelay signaling partner YPD1 has been determined at a resolution of 1.70 Å. Comparisons between the beryllium fluoride-activated complex and the unliganded (or apo) complex determined previously reveal modest but important differences. The SLN1-R1•Mg2+•BeF3− structure from the complex provides evidence for the first time that the mechanism of phosphorylation-induced activation is highly conserved between bacterial response regulator domains and this example from a eukaryotic organism. Residues in and around the active site undergo slight rearrangements in order to form bonds to the essential divalent cation and fluorine atoms of BeF3−. Two conserved switch-like residues (Thr 1173 and Phe 1192) occupy distinctly different positions in the apo- versus BeF3−-bound structures consistent with the “Y-T” coupling mechanism proposed for activation of CheY and other bacterial response regulators. Several loop regions and the α4-β5-α5 surface of the SLN1-R1 domain undergo subtle conformational changes (∼1-3 Å displacements relative to the apo-structure) that lead to significant changes in terms of contacts that are formed with YPD1. Detailed structural comparisons of protein-protein interactions in the apo- and BeF3−-bound complexes suggest at least a two-state equilibrium model for formation of a transient encounter complex, in which phosphorylation of the response regulator promotes the formation of a phosphotransfer-competent complex. In the BeF3−-activated complex, the position of His 64 from YPD1 is within ideal distance and near linear geometry with Asp 1144 from the SLN1-R1 domain for phosphotransfer to occur. The ground state structure presented here suggests that phosphoryl transfer will likely proceed through an associative mechanism involving formation of a pentacoordinate phosphorus intermediate. PMID:18076904

Non-interacting surface solvation and dynamics in protein-protein interactions.

PubMed

Visscher, Koen M; Kastritis, Panagiotis L; Bonvin, Alexandre M J J

2015-03-01

Protein-protein interactions control a plethora of cellular processes, including cell proliferation, differentiation, apoptosis, and signal transduction. Understanding how and why proteins interact will inevitably lead to novel structure-based drug design methods, as well as design of de novo binders with preferred interaction properties. At a structural and molecular level, interface and rim regions are not enough to fully account for the energetics of protein-protein binding, even for simple lock-and-key rigid binders. As we have recently shown, properties of the global surface might also play a role in protein-protein interactions. Here, we report on molecular dynamics simulations performed to understand solvent effects on protein-protein surfaces. We compare properties of the interface, rim, and non-interacting surface regions for five different complexes and their free components. Interface and rim residues become, as expected, less mobile upon complexation. However, non-interacting surface appears more flexible in the complex. Fluctuations of polar residues are always lower compared with charged ones, independent of the protein state. Further, stable water molecules are often observed around polar residues, in contrast to charged ones. Our analysis reveals that (a) upon complexation, the non-interacting surface can have a direct entropic compensation for the lower interface and rim entropy and (b) the mobility of the first hydration layer, which is linked to the stability of the protein-protein complex, is influenced by the local chemical properties of the surface. These findings corroborate previous hypotheses on the role of the hydration layer in shielding protein-protein complexes from unintended protein-protein interactions. © 2014 Wiley Periodicals, Inc.

Using a composite grid approach in a complex coastal domain to estimate estuarine residence time

USGS Publications Warehouse

Warner, John C.; Geyer, W. Rockwell; Arango, Herman G.

2010-01-01

We investigate the processes that influence residence time in a partially mixed estuary using a three-dimensional circulation model. The complex geometry of the study region is not optimal for a structured grid model and so we developed a new method of grid connectivity. This involves a novel approach that allows an unlimited number of individual grids to be combined in an efficient manner to produce a composite grid. We then implemented this new method into the numerical Regional Ocean Modeling System (ROMS) and developed a composite grid of the Hudson River estuary region to investigate the residence time of a passive tracer. Results show that the residence time is a strong function of the time of release (spring vs. neap tide), the along-channel location, and the initial vertical placement. During neap tides there is a maximum in residence time near the bottom of the estuary at the mid-salt intrusion length. During spring tides the residence time is primarily a function of along-channel location and does not exhibit a strong vertical variability. This model study of residence time illustrates the utility of the grid connectivity method for circulation and dispersion studies in regions of complex geometry.

Effect of substrate RNA sequence on the cleavage reaction by a short ribozyme.

PubMed Central

Ohmichi, T; Okumoto, Y; Sugimoto, N

1998-01-01

Leadzyme is a ribozyme that requires Pb2+. The catalytic sequence, CUGGGAGUCC, binds to an RNA substrate, GGACC downward arrowGAGCCAG, cleaving the RNA substrate at one site. We have investigated the effect of the substrate sequence on the cleavage activity of leadzyme using mutant substrates in order to structurally understand the RNA catalysis. The results showed that leadzyme acted as a catalyst for single site cleavage of a C5 deletion mutant substrate, GGAC downward arrowGAGCCAG, as well as the wild-type substrate. However, a mutant substrate GGACCGACCAG, which had G8 deleted from the wild-type substrate, was not cleaved. Kinetic studies by surface plasmon resonance indicated that the difference between active and inactive structures reflected the slow association and dissociation rate constants of complex formation induced by Pb2+rather than differences in complex stability. CD spectra showed that the active form of the substrate-leadzyme complex was rearranged by Pb2+binding. The G8 of the wild-type substrate, which was absent in the inactive complex, is not near the cleavage site. Thus, these results show that the active substrate-leadzyme complex has a Pb2+binding site at the junction between the unpaired region (asymmetric internal loop) and the stem region, which is distal to the cleavage site. Pb2+may play a role in rearranging the bases in the asymmetric internal loop to the correct position for catalysis. PMID:9837996

Geologic structures related to New Madrid earthquakes near Memphis, Tennessee, based on gravity and magnetic interpretations

USGS Publications Warehouse

Hildenbrand, T.G.; Stuart, W.D.; Talwani, P.

2001-01-01

New inversions of gravity and magnetic data in the region north of memphis. Tennessee, and south of latitude 36?? define boundaries of regional structures and igneous complexes in the upper crust. Microseismicity patterns near interpreted boundaries suggest that igneous complexes influence the locations of microseismicity. A weak seismicity cluster occurs near one intrusion (Covington pluton), at the intersection of the southwest margin of the Missouri batholith and the southeast margin of the Reelfoot rift. A narrow seismicity trend along the Reelfoot rift axis becomes diffuse near a second intrusion (Osceola intrusive complex) and changes direction to an area along the northwest flank of the intrusion. The axial seismicity trend also contains a tight cluster of earthquakes located just outside the Osceola intrusive complex. The mechanical explanation of the two seismicity patterns is uncertain, but the first cluster may be caused by stress concentration due to the high elastic stiffness and strength of the Covington intrusion. The spatially changing seismicity pattern near the Osceola complex may be caused by the preceding factors plus interaction with faulting along the rift axis. The axial seismicity strand itself is one of several connected and interacting active strands that may produce stress concentrations at strand ends and junctions. The microseismicity clusters at the peripheries of the two intrusions lead us to conclude that these stress concentrations or stressed volumes may be locations of future moderate to large earthquakes near Memphis. Published by Elsevier Science B.V.

The effects of lithium and anticonvulsants on brain structure in bipolar disorder.

PubMed

Germaná, C; Kempton, M J; Sarnicola, A; Christodoulou, T; Haldane, M; Hadjulis, M; Girardi, P; Tatarelli, R; Frangou, S

2010-12-01

To investigate the effect of lithium, anticonvulsants and antipsychotics on brain structure in bipolar disorder (BD). A cross-sectional structural brain magnetic resonance imaging study of 74 remitted patients with BD, aged 18-65, who were receiving long-term prophylactic treatment with lithium or anticonvulsants or antipsychotics. Global and regional grey matter, white matter, and cerebrospinal fluid volumes were compared between treatment groups. Grey matter in the subgenual anterior cingulate gyrus on the right (extending into the hypothalamus) and in the postcentral gyrus, the hippocampus/amygdale complex and the insula on the left was greater in BD patients on lithium treatment compared to all other treatment groups. Lithium treatment in BD has a significant effect on brain structure particularly in limbic/paralimbic regions associated with emotional processing. © 2010 John Wiley & Sons A/S.

Multi-wavelength Observations and Modeling of Solar Flares: Magnetic Structures

NASA Astrophysics Data System (ADS)

Su, Y.

2017-12-01

We present a review of our recent investigations on multi-wavelength observations and magnetic field modeling of solar flares. High-resolution observations taken by NVST and BBSO/NST reveal unprecedented fine structures of the flaring regions. Observations by SDO, IRIS, and GOES provide the complementary information. The magnetic field models are constructed using either non-linear force free field extrapolations or flux rope insertion method. Our studies have shown that the flaring regions often consist of double or multiple flux ropes, which often exist at different heights. The fine flare ribbon structures may be due to the magnetic reconnection in the complex quasi separatrix layers. The magnetic field modeling of several large flares suggests that the so called hot-channel structure is corresponding to the erupting flux rope above the X-point in a magnetic configuration with Hyperbolic Flux Tube.

Protein-Protein Docking in Drug Design and Discovery.

PubMed

Kaczor, Agnieszka A; Bartuzi, Damian; Stępniewski, Tomasz Maciej; Matosiuk, Dariusz; Selent, Jana

2018-01-01

Protein-protein interactions (PPIs) are responsible for a number of key physiological processes in the living cells and underlie the pathomechanism of many diseases. Nowadays, along with the concept of so-called "hot spots" in protein-protein interactions, which are well-defined interface regions responsible for most of the binding energy, these interfaces can be targeted with modulators. In order to apply structure-based design techniques to design PPIs modulators, a three-dimensional structure of protein complex has to be available. In this context in silico approaches, in particular protein-protein docking, are a valuable complement to experimental methods for elucidating 3D structure of protein complexes. Protein-protein docking is easy to use and does not require significant computer resources and time (in contrast to molecular dynamics) and it results in 3D structure of a protein complex (in contrast to sequence-based methods of predicting binding interfaces). However, protein-protein docking cannot address all the aspects of protein dynamics, in particular the global conformational changes during protein complex formation. In spite of this fact, protein-protein docking is widely used to model complexes of water-soluble proteins and less commonly to predict structures of transmembrane protein assemblies, including dimers and oligomers of G protein-coupled receptors (GPCRs). In this chapter we review the principles of protein-protein docking, available algorithms and software and discuss the recent examples, benefits, and drawbacks of protein-protein docking application to water-soluble proteins, membrane anchoring and transmembrane proteins, including GPCRs.

Site-Selective Benzannulation of N-Heterocycles in Bidentate Ligands Leads to Blue-Shifted Emission from [( P^N)Cu]2(μ-X)2 Dimers.

PubMed

Mondal, Rajarshi; Lozada, Issiah B; Davis, Rebecca L; Williams, J A Gareth; Herbert, David E

2018-05-07

Benzannulated bidentate pyridine/phosphine ( P^N) ligands bearing quinoline or phenanthridine (3,4-benzoquinoline) units have been prepared, along with their halide-bridged, dimeric Cu(I) complexes of the form [( P^N)Cu] 2 (μ-X) 2 . The copper complexes are phosphorescent in the orange-red region of the spectrum in the solid-state under ambient conditions. Structural characterization in solution and the solid-state reveals a flexible conformational landscape, with both diamond-like and butterfly motifs available to the Cu 2 X 2 cores. Comparing the photophysical properties of complexes of (quinolinyl)phosphine ligands with those of π-extended (phenanthridinyl)phosphines has revealed a counterintuitive impact of site-selective benzannulation. Contrary to conventional assumptions regarding π-extension and a bathochromic shift in the lowest energy absorption maxima, a blue shift of nearly 40 nm in the emission wavelength is observed for the complexes with larger ligand π-systems, which is assigned as phosphorescence on the basis of emission energies and lifetimes. Comparison of the ground-state and triplet excited state structures optimized from DFT and TD-DFT calculations allows attribution of this effect to a greater rigidity for the benzannulated complexes resulting in a higher energy emissive triplet state, rather than significant perturbation of orbital energies. This study reveals that ligand structure can impact photophysical properties for emissive molecules by influencing their structural rigidity, in addition to their electronic structure.

The role of the Ord Arid Intrusion in the historical and contemporary genetic division of long-tailed finch subspecies in northern Australia

PubMed Central

Rollins, Lee Ann; Svedin, Nina; Pryke, Sarah R; Griffith, Simon C

2012-01-01

The effect of separation by biogeographic features followed by secondary contact can blur taxonomic boundaries and produce complex genetic signatures. We analyzed population structure and gene flow across the range of the long-tailed finch (Poephila acuticauda) in northern Australia (1) to test the hypothesis that Ord Arid Intrusion acted as the causative barrier that led to divergence of P. acuticauda subspecies, (2) to determine whether genetic data support the presence of a gradual cline across the range or a sudden shift, both of which have been suggested based on morphological data, and (3) to estimate levels of contemporary gene flow within this species complex. We collected samples from 302 individuals from 10 localities. Analyses of 12 microsatellite loci and sequence data from 333 base pairs of the mitochondrial control region were used to estimate population structure and gene flow, using analysis of molecular variance (AMOVA), haplotype network analysis, frequency statistics, and clustering methods. Mitochondrial sequence data indicated the presence of three genetic groups (regions) across the range of P. acuticauda. Genetic diversity was highest in the east and lowest in the west. The Ord Arid Intrusion appears to have functioned as a biogeographic barrier in the past, according to mtDNA evidence presented here and evidence from previous studies. The absence of isolation by distance between adjacent regions and the lack of population genetic structure of mtDNA within regions indicates that genetic changes across the range of P. acuticauda subspecies are characterized by discrete breaks between regions. While microsatellite data indicate a complete absence of genetic structure across this species’ range, it appears unlikely that this results from high levels of gene flow. Mitochondrial data do not support the presence of contemporary gene flow across the range of this species. PMID:22833795

Structural insight into the role of VAL1 B3 domain for targeting to FLC locus in Arabidopsis thaliana.

PubMed

Wu, Baixing; Zhang, Mengmeng; Su, Shichen; Liu, Hehua; Gan, Jianhua; Ma, Jinbiao

2018-06-22

Vernalization is a pivotal stage for some plants involving many epigenetic changes during cold exposure. In Arabidopsis, an essential step in vernalization for further flowering is successful silence the potent floral repressor Flowering Locus C (FLC) by repressing histone mark. AtVal1 is a multi-function protein containing five domains that participate into many recognition processes and is validated to recruit the repress histone modifier PHD-PRC2 complex and interact with components of the ASAP complex target to the FLC nucleation region through recognizing a cis element known as CME (cold memory element) by its plant-specific B3 domain. Here, we determine the crystal structure of the B3 domain in complex with Sph/RY motif in CME. Our structural analysis reveals the specific DNA recognition by B3 domain, combined with our in vitro experiments, we provide the structural insight into the important implication of AtVAL1-B3 domain in flowering process. Copyright © 2018 Elsevier Inc. All rights reserved.

Complex damage distribution behaviour in cobalt implanted rutile TiO2 (1 1 0) lattice

NASA Astrophysics Data System (ADS)

Joshi, Shalik Ram; Padmanabhan, B.; Chanda, Anupama; Ojha, Sunil; Kanjilal, D.; Varma, Shikha

2017-11-01

The present work investigates the radiation damage, amorphization and structural modifications that are produced by ion-solid interactions in TiO2 crystals during 200 keV Cobalt ion implantation. RBS/C and GIXRD have been utilized to evaluate the damage in the host lattice as a function of ion fluence. Multiple scattering formalism has been applied to extract the depth dependent damage distributions in TiO2(1 1 0). The results have been compared with the MC simulations performed using SRIM-2013. RBS/C results delineate a buried amorphous layer at a low fluence. Surprisingly, ion induced dynamic activation produces a recovery in this damage at higher fluences. This improvement interestingly occurs only in deep regions (60-300 nm) where a systematic lowering in damage with fluence is observed. Formation of Co-Ti-O phases and generation of stress in TiO2 lattice can also be responsible for this improvement in deep regions. In contrast, surface region (0-60 nm) indicates a gradual increase in damage with fluence. Such a switch in the damage behavior creates a cross point in damage profiles at 60 nm. Surface region is a sink of vacancies whereas deep layers are interstitial rich. However, these regions are far separated from each other resulting in an intermediate (100-150 nm) region with a significant dip (valley) in damage which can be characterized by enhanced recombination of point defects. The damage profiles thus indicate a very complex behavior. MC simulations, however, present very different results. They depict a damage profile that extends to a depth of only 150 nm, which is only about half of the damage- width observed here via RBS/C. Moreover, MC simulations do not indicate presence of any valley like structure in the damage profile. The complex nature of damage distribution observed here via RBS/C may be related to the high ionic nature of the chemical bonds in the TiO2 lattice.

Structure of PINK1 in complex with its substrate ubiquitin

PubMed Central

Schubert, Alexander F.; Gladkova, Christina; Pardon, Els; Wagstaff, Jane L.; Freund, Stefan M.V.; Steyaert, Jan; Maslen, Sarah L.; Komander, David

2018-01-01

Autosomal recessive juvenile Parkinsonism (AR-JP) is caused by mutations in a number of PARK genes, in particular in the E3 ubiquitin ligase Parkin (PARK2), and in its upstream protein kinase PINK1 (PARK6). PINK1 phosphorylates ubiquitin and the Parkin ubiquitin-like domain on structurally protected Ser65 to trigger mitophagy. We here report a crystal structure of a nanobody stabilised complex between Pediculus humanus corporis (Ph)PINK1 bound to ubiquitin in the ‘C-terminally retracted’ (Ub-CR) conformation. The structure reveals many peculiarities of PINK1, including the architecture of the C-terminal region, and reveals how the PINK1 N-lobe binds ubiquitin via a unique insertion. The flexible Ser65-loop in the Ub-CR conformation reaches the activation segment, facilitating placement of Ser65 in a phosphate accepting position. The structure also explains how autophosphorylation in the N-lobe stabilises structurally and functionally important insertions, and reveals the molecular basis for AR-JP causing mutations, some of which disrupt ubiquitin binding. PMID:29160309

Prediction of binding hot spot residues by using structural and evolutionary parameters

PubMed Central

2009-01-01

In this work, we present a method for predicting hot spot residues by using a set of structural and evolutionary parameters. Unlike previous studies, we use a set of parameters which do not depend on the structure of the protein in complex, so that the predictor can also be used when the interface region is unknown. Despite the fact that no information concerning proteins in complex is used for prediction, the application of the method to a compiled dataset described in the literature achieved a performance of 60.4%, as measured by F-Measure, corresponding to a recall of 78.1% and a precision of 49.5%. This result is higher than those reported by previous studies using the same data set. PMID:21637529

Cone beam tomographic imaging anatomy of the maxillofacial region.

PubMed

Angelopoulos, Christos

2008-10-01

Multiplanar imaging is a fairly new concept in diagnostic imaging available with a number of contemporary imaging modalities such as CT, MR imaging, diagnostic ultrasound, and others. This modality allows reconstruction of images in different planes (flat or curved) from a volume of data that was acquired previously. This concept makes the diagnostic process more interactive, and proper use may increase diagnostic potential. At the same time, the complexity of the anatomical structures on the maxillofacial region may make it harder for these images to be interpreted. This article reviews the anatomy of maxillofacial structures in planar imaging, and more specifically cone-beam CT images.

The intrinsically disordered C-terminal domain of the measles virus nucleoprotein interacts with the C-terminal domain of the phosphoprotein via two distinct sites and remains predominantly unfolded

PubMed Central

Bourhis, Jean-Marie; Receveur-Bréchot, Véronique; Oglesbee, Michael; Zhang, Xinsheng; Buccellato, Matthew; Darbon, Hervé; Canard, Bruno; Finet, Stéphanie; Longhi, Sonia

2005-01-01

Measles virus is a negative-sense, single-stranded RNA virus within theMononegavirales order,which includes several human pathogens, including rabies, Ebola, Nipah, and Hendra viruses. Themeasles virus nucleoprotein consists of a structured N-terminal domain, and of an intrinsically disordered C-terminal domain, NTAIL (aa 401–525), which undergoes induced folding in the presence of the C-terminal domain (XD, aa 459–507) of the viral phosphoprotein. With in NTAIL, an α-helical molecular recognition element (α-MoRE, aa 488–499) involved in binding to P and in induced folding was identified and then observed in the crystal structure of XD. Using small-angle X-ray scattering, we have derived a low-resolution structural model of the complex between XD and NTAIL, which shows that most of NTAIL remains disordered in the complex despite P-induced folding within the α-MoRE. The model consists of an extended shape accommodating the multiple conformations adopted by the disordered N-terminal region of NTAIL, and of a bulky globular region, corresponding to XD and to the C terminus of NTAIL (aa 486–525). Using surface plasmon resonance, circular dichroism, fluorescence spectroscopy, and heteronuclear magnetic resonance, we show that NTAIL has an additional site (aa 517–525) involved in binding to XD but not in the unstructured-to-structured transition. This work provides evidence that intrinsically disordered domains can establish complex interactions with their partners, and can contact them through multiple sites that do not all necessarily gain regular secondary structure. PMID:16046624

Robust estimation of fractal measures for characterizing the structural complexity of the human brain: optimization and reproducibility

PubMed Central

Goñi, Joaquín; Sporns, Olaf; Cheng, Hu; Aznárez-Sanado, Maite; Wang, Yang; Josa, Santiago; Arrondo, Gonzalo; Mathews, Vincent P; Hummer, Tom A; Kronenberger, William G; Avena-Koenigsberger, Andrea; Saykin, Andrew J.; Pastor, María A.

2013-01-01

High-resolution isotropic three-dimensional reconstructions of human brain gray and white matter structures can be characterized to quantify aspects of their shape, volume and topological complexity. In particular, methods based on fractal analysis have been applied in neuroimaging studies to quantify the structural complexity of the brain in both healthy and impaired conditions. The usefulness of such measures for characterizing individual differences in brain structure critically depends on their within-subject reproducibility in order to allow the robust detection of between-subject differences. This study analyzes key analytic parameters of three fractal-based methods that rely on the box-counting algorithm with the aim to maximize within-subject reproducibility of the fractal characterizations of different brain objects, including the pial surface, the cortical ribbon volume, the white matter volume and the grey matter/white matter boundary. Two separate datasets originating from different imaging centers were analyzed, comprising, 50 subjects with three and 24 subjects with four successive scanning sessions per subject, respectively. The reproducibility of fractal measures was statistically assessed by computing their intra-class correlations. Results reveal differences between different fractal estimators and allow the identification of several parameters that are critical for high reproducibility. Highest reproducibility with intra-class correlations in the range of 0.9–0.95 is achieved with the correlation dimension. Further analyses of the fractal dimensions of parcellated cortical and subcortical gray matter regions suggest robustly estimated and region-specific patterns of individual variability. These results are valuable for defining appropriate parameter configurations when studying changes in fractal descriptors of human brain structure, for instance in studies of neurological diseases that do not allow repeated measurements or for disease-course longitudinal studies. PMID:23831414

Structural Characterization of Myotoxic Ecarpholin S From Echis carinatus Venom

PubMed Central

Zhou, Xingding; Tan, Tien-Chye; Valiyaveettil, S.; Go, Mei Lin; Kini, R. Manjunatha; Velazquez-Campoy, Adrian; Sivaraman, J.

2008-01-01

Phospholipase A2 (PLA2), a common toxic component of snake venom, has been implicated in various pharmacological effects. Ecarpholin S, isolated from the venom of the snake Echis carinatus sochureki, is a phospholipase A2 (PLA2) belonging to the Ser49-PLA2 subgroup. It has been characterized as having low enzymatic but potent myotoxic activities. The crystal structures of native ecarpholin S and its complexes with lauric acid, and its inhibitor suramin, were elucidated. This is the first report of the structure of a member of the Ser49-PLA2 subgroup. We also examined interactions of ecarpholin S with phosphatidylglycerol and lauric acid, using surface plasmon resonance, and of suramin with isothermal titration calorimetry. Most Ca2+-dependent PLA2 enzymes have Asp in position 49, which plays a crucial role in Ca2+ binding. The three-dimensional structure of ecarpholin S reveals a unique conformation of the Ca2+-binding loop that is not favorable for Ca2+ coordination. Furthermore, the endogenously bound fatty acid (lauric acid) in the hydrophobic channel may also interrupt the catalytic cycle. These two observations may account for the low enzymatic activity of ecarpholin S, despite full retention of the catalytic machinery. These observations may also be applicable to other non-Asp49-PLA2 enzymes. The interaction of suramin in its complex with ecarpholin S is quite different from that reported for the Lys49-PLA2/suramin complex, where the interfacial recognition face (i-face), C-terminal region, and N-terminal region of ecarpholin S play important roles. This study provides significant structural and functional insights into the myotoxic activity of ecarpholin S and, in general, of non-Asp49-PLA2 enzymes. PMID:18586854

Structural Characterization of Myotoxic Ecarpholin S From Echis carinatus Venom

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

Zhou, X.; Tan, T; Valiyaveettil, S

2008-01-01

Phospholipase A2 (PLA2), a common toxic component of snake venom, has been implicated in various pharmacological effects. Ecarpholin S, isolated from the venom of the snake Echis carinatus sochureki, is a phospholipase A2 (PLA2) belonging to the Ser49-PLA2 subgroup. It has been characterized as having low enzymatic but potent myotoxic activities. The crystal structures of native ecarpholin S and its complexes with lauric acid, and its inhibitor suramin, were elucidated. This is the first report of the structure of a member of the Ser49-PLA2 subgroup. We also examined interactions of ecarpholin S with phosphatidylglycerol and lauric acid, using surface plasmonmore » resonance, and of suramin with isothermal titration calorimetry. Most Ca2+-dependent PLA2 enzymes have Asp in position 49, which plays a crucial role in Ca2+ binding. The three-dimensional structure of ecarpholin S reveals a unique conformation of the Ca2+-binding loop that is not favorable for Ca2+ coordination. Furthermore, the endogenously bound fatty acid (lauric acid) in the hydrophobic channel may also interrupt the catalytic cycle. These two observations may account for the low enzymatic activity of ecarpholin S, despite full retention of the catalytic machinery. These observations may also be applicable to other non-Asp49-PLA2 enzymes. The interaction of suramin in its complex with ecarpholin S is quite different from that reported for the Lys49-PLA2/suramin complex, where the interfacial recognition face (i-face), C-terminal region, and N-terminal region of ecarpholin S play important roles. This study provides significant structural and functional insights into the myotoxic activity of ecarpholin S and, in general, of non-Asp49-PLA2 enzymes.« less

Serotype-Specific Structural Differences in the Protease-Cofactor Complexes of the Dengue Virus Family

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

Chandramouli, Sumana; Joseph, Jeremiah S.; Daudenarde, Sophie

With an estimated 40% of the world population at risk, dengue poses a significant threat to human health, especially in tropical and subtropical regions. Preventative and curative efforts, such as vaccine development and drug discovery, face additional challenges due to the occurrence of four antigenically distinct serotypes of the causative dengue virus (DEN1 to -4). Complex immune responses resulting from repeat assaults by the different serotypes necessitate simultaneous targeting of all forms of the virus. One of the promising targets for drug development is the highly conserved two-component viral protease NS2B-NS3, which plays an essential role in viral replication bymore » processing the viral precursor polyprotein into functional proteins. In this paper, we report the 2.1-{angstrom} crystal structure of the DEN1 NS2B hydrophilic core (residues 49 to 95) in complex with the NS3 protease domain (residues 1 to 186) carrying an internal deletion in the N terminus (residues 11 to 20). While the overall folds within the protease core are similar to those of DEN2 and DEN4 proteases, the conformation of the cofactor NS2B is dramatically different from those of other flaviviral apoprotease structures. The differences are especially apparent within its C-terminal region, implicated in substrate binding. The structure reveals for the first time serotype-specific structural elements in the dengue virus family, with the reported alternate conformation resulting from a unique metal-binding site within the DEN1 sequence. We also report the identification of a 10-residue stretch within NS3pro that separates the substrate-binding function from the catalytic turnover rate of the enzyme. Implications for broad-spectrum drug discovery are discussed.« less

Modeling of the structure and interactions of the B. anthracis antitoxin, MoxX: deletion mutant studies highlight its modular structure and repressor function

NASA Astrophysics Data System (ADS)

Chopra, Nikita; Agarwal, Shivangi; Verma, Shashikala; Bhatnagar, Sonika; Bhatnagar, Rakesh

2011-03-01

Our previous report on Bacillus anthracis toxin-antitoxin module (MoxXT) identified it to be a two component system wherein, PemK-like toxin (MoxT) functions as a ribonuclease (Agarwal S et al. JBC 285:7254-7270, 2010). The labile antitoxin (MoxX) can bind to/neutralize the action of the toxin and is also a DNA-binding protein mediating autoregulation. In this study, molecular modeling of MoxX in its biologically active dimeric form was done. It was found that it contains a conserved Ribbon-Helix-Helix (RHH) motif, consistent with its DNA-binding function. The modeled MoxX monomers dimerize to form a two-stranded antiparallel ribbon, while the C-terminal region adopts an extended conformation. Knowledge guided protein-protein docking, molecular dynamics simulation, and energy minimization was performed to obtain the structure of the MoxXT complex, which was exploited for the de novo design of a peptide capable of binding to MoxT. It was found that the designed peptide caused a decrease in MoxX binding to MoxT by 42% at a concentration of 2 μM in vitro. We also show that MoxX mediates negative transcriptional autoregulation by binding to its own upstream DNA. The interacting regions of both MoxX and DNA were identified in order to model their complex. The repressor activity of MoxX was found to be mediated by the 16 N-terminal residues that contains the ribbon of the RHH motif. Based on homology with other RHH proteins and deletion mutant studies, we propose a model of the MoxX-DNA interaction, with the antiparallel β-sheet of the MoxX dimer inserted into the major groove of its cognate DNA. The structure of the complex of MoxX with MoxT and its own upstream regulatory region will facilitate design of molecules that can disrupt these interactions, a strategy for development of novel antibacterials.

Electroencephalogram complexity analysis in children with attention-deficit/hyperactivity disorder during a visual cognitive task.

PubMed

Zarafshan, Hadi; Khaleghi, Ali; Mohammadi, Mohammad Reza; Moeini, Mahdi; Malmir, Nastaran

2016-01-01

The aim of this study was to investigate electroencephalogram (EEG) dynamics using complexity analysis in children with attention-deficit/hyperactivity disorder (ADHD) compared with healthy control children when performing a cognitive task. Thirty 7-12-year-old children meeting Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) criteria for ADHD and 30 healthy control children underwent an EEG evaluation during a cognitive task, and Lempel-Ziv complexity (LZC) values were computed. There were no significant differences between ADHD and control groups on age and gender. The mean LZC of the ADHD children was significantly larger than healthy children over the right anterior and right posterior regions during the cognitive performance. In the ADHD group, complexity of the right hemisphere was higher than that of the left hemisphere, but the complexity of the left hemisphere was higher than that of the right hemisphere in the normal group. Although fronto-striatal dysfunction is considered conclusive evidence for the pathophysiology of ADHD, our arithmetic mental task has provided evidence of structural and functional changes in the posterior regions and probably cerebellum in ADHD.

Functional interplay among the flavivirus NS3 protease, helicase, and cofactors.

PubMed

Li, Kuohan; Phoo, Wint Wint; Luo, Dahai

2014-04-01

Flaviviruses are positive-sense RNA viruses, and many are important human pathogens. Nonstructural protein 2B and 3 of the flaviviruses (NS2BNS3) form an endoplasmic reticulum (ER) membrane-associated hetero-dimeric complex through the NS2B transmembrane region. The NS2BNS3 complex is multifunctional. The N-terminal region of NS3, and its cofactor NS2B fold into a protease that is responsible for viral polyprotein processing, and the C-terminal domain of NS3 possesses NTPase/RNA helicase activities and is involved in viral RNA replication and virus particle formation. In addition, NS2BNS3 complex has also been shown to modulate viral pathogenesis and the host immune response. Because of the essential functions that the NS2BNS3 complex plays in the flavivirus life cycle, it is an attractive target for antiviral development. This review focuses on the recent biochemical and structural advances of NS2BNS3 and provides a brief update on the current status of drug development targeting this viral protein complex.

Electromagnetic optimisation of a 2.45 GHz microwave plasma source operated at atmospheric pressure and designed for hydrogen production

NASA Astrophysics Data System (ADS)

Miotk, R.; Jasiński, M.; Mizeraczyk, J.

2018-03-01

This paper presents the partial electromagnetic optimisation of a 2.45 GHz cylindrical-type microwave plasma source (MPS) operated at atmospheric pressure. The presented device is designed for hydrogen production from liquid fuels, e.g. hydrocarbons and alcohols. Due to industrial requirements regarding low costs for hydrogen produced in this way, previous testing indicated that improvements were required to the electromagnetic performance of the MPS. The MPS has a duct discontinuity region, which is a result of the cylindrical structure located within the device. The microwave plasma is generated in this discontinuity region. Rigorous analysis of the region requires solving a set of Maxwell equations, which is burdensome for complicated structures. Furthermore, the presence of the microwave plasma increases the complexity of this task. To avoid calculating the complex Maxwell equations, we suggest the use of the equivalent circuit method. This work is based upon the idea of using a Weissfloch circuit to characterize the area of the duct discontinuity and the plasma. The resulting MPS equivalent circuit allowed the calculation of a capacitive metallic diaphragm, through which an improvement in the electromagnetic performance of the plasma source was obtained.

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

Ortiz, Rosario, E-mail: r_oh@ciencias.unam.mx; Kouznetsova, Anna, E-mail: Anna.Kouznetsova@ki.se; Echeverría-Martínez, Olga M., E-mail: omem@ciencias.unam.mx

The synaptonemal complex (SC) is a proteinaceous structure that holds the homologous chromosomes in close proximity while they exchange genetic material in a process known as meiotic recombination. This meiotic recombination leads to genetic variability in sexually reproducing organisms. The ultrastructure of the SC is studied by electron microscopy and it is observed as a tripartite structure. Two lateral elements (LE) separated by a central region (CR) confer its classical tripartite organization. The LEs are the anchoring platform for the replicated homologous chromosomes to properly exchange genetic material with one another. An accurate assembly of the LE is indispensable formore » the proper completion of meiosis. Ultrastructural studies suggested that the LE is organized as a multilayered unit. However, no validation of this model has been previously provided. In this ultrastructural study, by using mice with different genetic backgrounds that affect the LE width, we provide further evidence that support a multilayered organization of the LE. Additionally, we provide data suggesting additional roles of the different cohesin complex components in the structure of the LEs of the SC. - Highlights: • The lateral element of the synaptonemal complex is a multilayered structure. • The width of the lateral element in synaptonemal complex-null mice is different. • Two cohesin complex cores plus one axial element form a wild-type lateral element. • The layers of the lateral element can be analyzed in different null mice models.« less

Effect of salt and surfactant concentration on the structure of polyacrylate gel/surfactant complexes.

PubMed

Nilsson, Peter; Unga, Johan; Hansson, Per

2007-09-20

Small-angle X-ray scattering was used to elucidate the structure of crosslinked polyacrylate gel/dodecyltrimethylammonium bromide complexes equilibrated in solutions of varying concentrations of surfactant and sodium bromide (NaBr). Samples were swollen with no ordering (micelle free), or they were collapsed with either several distinct peaks (cubic Pm3n) or one broad correlation peak (disordered micellar). The main factor determining the structure of the collapsed complexes was found to be the NaBr concentration, with the cubic structure existing up to approximately 150 mM NaBr and above which only the disordered micellar structure was found. Increasing the salt concentration decreases the polyion mediated attractive forces holding the micelles together causing swelling of the gel. At sufficiently high salt concentration the micelle-micelle distance in the gel becomes too large for the cubic structure to be retained, and it melts into a disordered micellar structure. As most samples were above the critical micelle concentration, the bulk of the surfactant was in the form of micelles in the solution and the surfactant concentration thereby had only a minor influence on the structure. However, in the region around 150 mM NaBr, increasing the surfactant concentration, at constant NaBr concentration, was found to change the structure from disordered micellar to ordered cubic and back to disordered again.

Utility of a thermal-based two-source energy balance model for estimating surface fluxes over complex landscapes

USDA-ARS?s Scientific Manuscript database

Many landscapes are comprised of a variety of vegetation types with different canopy structure, rooting depth, physiological characteristics, including response to environmental stressors, etc. Even in agricultural regions, different management practices, including crop rotations, irrigation schedu...

Genetic diversity based on 28S rDNA sequences among populations of Culex quinquefasciatus collected at different locations in Tamil Nadu, India.

PubMed

Sakthivelkumar, S; Ramaraj, P; Veeramani, V; Janarthanan, S

2015-09-01

The basis of the present study was to distinguish the existence of any genetic variability among populations of Culex quinquefasciatus which would be a valuable tool in the management of mosquito control programmes. In the present study, population of Cx. quinquefasciatus collected at different locations in Tamil Nadu were analyzed for their genetic variation based on 28S rDNA D2 region nucleotide sequences. A high degree of genetic polymorphism was detected in the sequences of D2 region of 28S rDNA on the predicted secondary structures in spite of high nucleotide sequence similarity. The findings based on secondary structure using rDNA sequences suggested the existence of a complex genotypic diversity of Cx. quinquefasciatus population collected at different locations of Tamil Nadu, India. This complexity in genetic diversity in a single mosquito population collected at different locations is considered an important issue towards their influence and nature of vector potential of these mosquitoes.

Cis- and trans-regulation of luteovirus gene expression by the 3’ end of the viral genome

PubMed Central

Miller, W. Allen; Jackson, Jacquelyn; Feng, Ying

2016-01-01

Translation of the 5.7 kb luteovirus genome is controlled by the 3’ untranslated region (UTR). Base pairing between regions of the 3’ UTR and sequences kilobases upstream is required for cap-independent translation and ribosomal frameshifting needed to synthesize the viral replicase. Luteoviruses produce subgenomic RNAs, which can serve as mRNA, but one sgRNA also regulates translation initiation in trans. As on all viruses, the 3’ and 5’ ends contain structures that are presumed to facilitate RNA synthesis. This review describes the structures and interactions of Barley yellow dwarf virus RNA that facilitate the complex interplay between the above events and result in a successful virus infection. We also present surprising results on the apparent lack of need for some subgenomic RNAs for the virus to infect cells or whole plants. In summary, the UTRs of luteoviruses are highly complex entities that control and fine-tune many key events of the virus replication cycle. PMID:25858272

Investigating Flow-Structure Interactions in Cerebral Aneurysms

ScienceCinema

None

2018-06-05

Visualization of blood flow in a cerebral aneurysm. Streamlines (colored by fluid velocity magnitude) reveal the complexity of the flow, isocontours of vorticity show blood vortex structures (colored by pressure), and the flexible arterial wall is colored by the stress magnitude, where regions in red indicate areas of high stress. Credits: Science: Paris Perdikaris, Yue Yu, George Em. Karniadakis and Leopold Grinberg Visualization: Joseph A. Insley and Michael E. Papka

Coronal loops and active region structure

NASA Technical Reports Server (NTRS)

Webb, D. F.; Zirin, H.

1981-01-01

Synoptic H-alpha Ca K, magnetograph and Skylab soft X-ray and EUV data were compared for the purpose of identifying the basic coronal magnetic structure of loops in a 'typical' active region and studying its evolution. A complex of activity in July 1973, especially McMath 12417, was emphasized. The principal results are: (1) most of the brightest loops connected the bright f plage to either the sunspot penumbra or to p satellite spots; no non-flaring X-ray loops end in umbrae; (2) short, bright loops had one or both ends in regions of emergent flux, strong field or high field gradients; (3) stable, strongly sheared loop arcades formed over filaments; (4) EFRs were always associated with compact X-ray arcades; and (5) loops connecting to other active regions had their bases in outlying plage of weak field strength in McM 417 where H-alpha fibrils marked the direction of the loops

Multimeric complexes among ankyrin-repeat and SOCS-box protein 9 (ASB9), ElonginBC, and Cullin 5: insights into the structure and assembly of ECS-type Cullin-RING E3 ubiquitin ligases.

PubMed

Thomas, Jemima C; Matak-Vinkovic, Dijana; Van Molle, Inge; Ciulli, Alessio

2013-08-06

Proteins of the ankyrin-repeat and SOCS-box (ASB) family act as the substrate-recognition subunits of ECS-type (ElonginBC-Cullin-SOCS-box) Cullin RING E3 ubiquitin ligase (CRL) complexes that catalyze the specific polyubiquitination of cellular proteins to target them for degradation by the proteasome. Therefore, ASB multimeric complexes are involved in numerous cell processes and pathways; however, their interactions, assembly, and biological roles remain poorly understood. To enhance our understanding of ASB CRL systems, we investigated the structure, affinity, and assembly of the quaternary multisubunit complex formed by ASB9, Elongin B, Elongin C (EloBC), and Cullin 5. Here, we describe the application of several biophysical techniques including differential scanning fluorimetry, isothermal titration calorimetry (ITC), nanoelectrospray ionization, and ion-mobility mass spectrometry (IM-MS) to provide structural and thermodynamic information for a quaternary ASB CRL complex. We find that ASB9 is unstable alone but forms a stable ternary complex with EloBC that binds with high affinity to the Cullin 5 N-terminal domain (Cul5NTD) but not to Cul2NTD. The structure of the monomeric ASB9-EloBC-Cul5NTD quaternary complex is revealed by molecular modeling and is consistent with IM-MS and temperature-dependent ITC data. This is the first experimental study to validate structural information for the assembly of the quaternary N-terminal region of an ASB CRL complex. The results suggest that ASB E3 ligase complexes function and assemble in an analogous manner to that of other CRL systems and provide a platform for further molecular investigation of this important protein family. The data reported here will also be of use for the future development of chemical probes to examine the biological function and modulation of other ECS-type CRL systems.

Multimeric Complexes among Ankyrin-Repeat and SOCS-box Protein 9 (ASB9), ElonginBC, and Cullin 5: Insights into the Structure and Assembly of ECS-type Cullin-RING E3 Ubiquitin Ligases

PubMed Central

2013-01-01

Proteins of the ankyrin-repeat and SOCS-box (ASB) family act as the substrate-recognition subunits of ECS-type (ElonginBC–Cullin–SOCS-box) Cullin RING E3 ubiquitin ligase (CRL) complexes that catalyze the specific polyubiquitination of cellular proteins to target them for degradation by the proteasome. Therefore, ASB multimeric complexes are involved in numerous cell processes and pathways; however, their interactions, assembly, and biological roles remain poorly understood. To enhance our understanding of ASB CRL systems, we investigated the structure, affinity, and assembly of the quaternary multisubunit complex formed by ASB9, Elongin B, Elongin C (EloBC), and Cullin 5. Here, we describe the application of several biophysical techniques including differential scanning fluorimetry, isothermal titration calorimetry (ITC), nanoelectrospray ionization, and ion-mobility mass spectrometry (IM–MS) to provide structural and thermodynamic information for a quaternary ASB CRL complex. We find that ASB9 is unstable alone but forms a stable ternary complex with EloBC that binds with high affinity to the Cullin 5 N-terminal domain (Cul5NTD) but not to Cul2NTD. The structure of the monomeric ASB9–EloBC–Cul5NTD quaternary complex is revealed by molecular modeling and is consistent with IM–MS and temperature-dependent ITC data. This is the first experimental study to validate structural information for the assembly of the quaternary N-terminal region of an ASB CRL complex. The results suggest that ASB E3 ligase complexes function and assemble in an analogous manner to that of other CRL systems and provide a platform for further molecular investigation of this important protein family. The data reported here will also be of use for the future development of chemical probes to examine the biological function and modulation of other ECS-type CRL systems. PMID:23837592

Interpreting the structural and electrochemical complexity of 0.5Li{sub 2}MnO{sub 3}{lg_bullet}.0.5LiMO{sub 2} electrodes for lithium batteries (M=Mn{sub 0.5-x}Ni{sub 0.5-x}Co{sub 2x}, 0{le}x{le}0.5).

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

Kang, S. H.; Kempgens, P.; Greenbaum, S.

2007-01-01

The structural and electrochemical features of layered 0.5Li{sub 2}MnO{sub 3} {center_dot} 0.5LiMO{sub 2} electrodes, in which M = Mn{sub 0.5-x}Ni{sub 0.5-x}Co{sub 2x} (0{le} x {le} 0.5), have been studied by powder X-ray diffraction, electrochemical differential-capacity measurements, {sup 7}Li magic-angle-spinning nuclear magnetic resonance, and X-ray absorption near-edge spectroscopy. Li{sub 2}MnO{sub 3}-like regions in the as-prepared samples were observed for all values of x, with transition-metal cation disorder between the LiMO{sub 2} and Li{sub 2}MnO{sub 3} components increasing with cobalt content (i.e., the value of x). The structural disorder and complexity of the electrochemical redox reactions increase when the Li{sub 2}MnO{sub 3}-likemore » regions within the electrode are activated to 4.6 V in lithium cells; interpretations of structural and electrochemical phenomena are provided.« less

Identification of both copy number variation-type and constant-type core elements in a large segmental duplication region of the mouse genome

PubMed Central

2013-01-01

Background Copy number variation (CNV), an important source of diversity in genomic structure, is frequently found in clusters called CNV regions (CNVRs). CNVRs are strongly associated with segmental duplications (SDs), but the composition of these complex repetitive structures remains unclear. Results We conducted self-comparative-plot analysis of all mouse chromosomes using the high-speed and large-scale-homology search algorithm SHEAP. For eight chromosomes, we identified various types of large SD as tartan-checked patterns within the self-comparative plots. A complex arrangement of diagonal split lines in the self-comparative-plots indicated the presence of large homologous repetitive sequences. We focused on one SD on chromosome 13 (SD13M), and developed SHEPHERD, a stepwise ab initio method, to extract longer repetitive elements and to characterize repetitive structures in this region. Analysis using SHEPHERD showed the existence of 60 core elements, which were expected to be the basic units that form SDs within the repetitive structure of SD13M. The demonstration that sequences homologous to the core elements (>70% homology) covered approximately 90% of the SD13M region indicated that our method can characterize the repetitive structure of SD13M effectively. Core elements were composed largely of fragmented repeats of a previously identified type, such as long interspersed nuclear elements (LINEs), together with partial genic regions. Comparative genome hybridization array analysis showed that whereas 42 core elements were components of CNVR that varied among mouse strains, 8 did not vary among strains (constant type), and the status of the others could not be determined. The CNV-type core elements contained significantly larger proportions of long terminal repeat (LTR) types of retrotransposon than the constant-type core elements, which had no CNV. The higher divergence rates observed in the CNV-type core elements than in the constant type indicate that the CNV-type core elements have a longer evolutionary history than constant-type core elements in SD13M. Conclusions Our methodology for the identification of repetitive core sequences simplifies characterization of the structures of large SDs and detailed analysis of CNV. The results of detailed structural and quantitative analyses in this study might help to elucidate the biological role of one of the SDs on chromosome 13. PMID:23834397

Mycobacterium tuberculosis acyl carrier protein synthase adopts two different pH-dependent structural conformations

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

Gokulan, Kuppan; Aggarwal, Anup; Shipman, Lance

2011-07-01

Bacterial acyl carrier protein synthase plays an essential role in the synthesis of fatty acids, nonribosomal peptides and polyketides. In Mycobacterium tuberculosis, AcpS or group I phosphopentatheine transferase exhibits two different structural conformations depending upon the pH. The crystal structures of acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis (Mtb) and Corynebacterium ammoniagenes determined at pH 5.3 and pH 6.5, respectively, are reported. Comparison of the Mtb apo-AcpS structure with the recently reported structure of the Mtb AcpS–ADP complex revealed that AcpS adopts two different conformations: the orthorhombic and trigonal space-group structures show structural differences in the α2 helix andmore » in the conformation of the α3–α4 connecting loop, which is in a closed conformation. The apo-AcpS structure shows electron density for the entire model and was obtained at lower pH values (4.4–6.0). In contrast, at a higher pH value (6.5) AcpS undergoes significant conformational changes, resulting in disordered regions that show no electron density in the AcpS model. The solved structures also reveal that C. ammoniagenes AcpS undergoes structural rearrangement in two regions, similar to the recently reported Mtb AcpS–ADP complex structure. In vitro reconstitution experiments show that AcpS has a higher post-translational modification activity between pH 4.4 and 6.0 than at pH values above 6.5, where the activity drops owing to the change in conformation. The results show that apo-AcpS and AcpS–ADP adopt different conformations depending upon the pH conditions of the crystallization solution.« less

The Ordered Network Structure and Prediction Summary for M≥7 Earthquakes in Xinjiang Region of China

NASA Astrophysics Data System (ADS)

Men, Ke-Pei; Zhao, Kai

2014-12-01

M ≥7 earthquakes have showed an obvious commensurability and orderliness in Xinjiang of China and its adjacent region since 1800. The main orderly values are 30 a × k (k = 1,2,3), 11 12 a, 41 43 a, 18 19 a, and 5 6 a. In the guidance of the information forecasting theory of Wen-Bo Weng, based on previous research results, combining ordered network structure analysis with complex network technology, we focus on the prediction summary of M ≥ 7 earthquakes by using the ordered network structure, and add new information to further optimize network, hence construct the 2D- and 3D-ordered network structure of M ≥ 7 earthquakes. In this paper, the network structure revealed fully the regularity of seismic activity of M ≥ 7 earthquakes in the study region during the past 210 years. Based on this, the Karakorum M7.1 earthquake in 1996, the M7.9 earthquake on the frontier of Russia, Mongol, and China in 2003, and two Yutian M7.3 earthquakes in 2008 and 2014 were predicted successfully. At the same time, a new prediction opinion is presented that the future two M ≥ 7 earthquakes will probably occur around 2019 - 2020 and 2025 - 2026 in this region. The results show that large earthquake occurred in defined region can be predicted. The method of ordered network structure analysis produces satisfactory results for the mid-and-long term prediction of M ≥ 7 earthquakes.

The influence of a reverse-reactivated normal fault on natural fracture geometries and relative chronologies at Castle Cove, Otway Basin

NASA Astrophysics Data System (ADS)

Debenham, Natalie; King, Rosalind C.; Holford, Simon P.

2018-07-01

Despite the ubiquity of normal faults that have undergone compressional inversion, documentation of the structural history of natural fractures around these structures is limited. In this paper, we investigate the geometries and relative chronologies of natural fractures adjacent to a reverse-reactivated normal fault, the Castle Cove Fault in the Otway Basin, southeast Australia. Local variations in strain resulted in greater deformation within the fault damage zone closer to the fault. Structural mapping within the damage zone reveals a complex tectonic history recording both regional and local perturbations in stress and a total of 11 fracture sets were identified, with three sets geometrically related to the Castle Cove Fault. The remaining fracture sets formed in response to local stresses at Castle Cove. Rifting in the late Cretaceous resulted in normal movement of the Castle Cove Fault and associated rollover folding, and the formation of the largest fracture set. Reverse-reactivation of the fault and associated anticlinal folding occurred during late Miocene to Pliocene compression. Rollover folding may have provided structural traps if seals were not breached by fractures, however anticlinal folding likely post-dated the main episodes of hydrocarbon generation and migration in the region. This study highlights the need to conduct careful reconstruction of the structural histories of fault zones that experienced complex reactivation histories when attempting to define off-fault fluid flow properties.

Trans-Dimensional Bayesian Imaging of 3-D Crustal and Upper Mantle Structure in Northeast Asia

NASA Astrophysics Data System (ADS)

Kim, S.; Tkalcic, H.; Rhie, J.; Chen, Y.

2016-12-01

Imaging 3-D structures using stepwise inversions of ambient noise and receiver function data is now a routine work. Here, we carry out the inversion in the trans-dimensional and hierarchical extension of the Bayesian framework to obtain rigorous estimates of uncertainty and high-resolution images of crustal and upper mantle structures beneath Northeast (NE) Asia. The methods inherently account for data sensitivities by means of using adaptive parameterizations and treating data noise as free parameters. Therefore, parsimonious results from the methods are balanced out between model complexity and data fitting. This allows fully exploiting data information, preventing from over- or under-estimation of the data fit, and increases model resolution. In addition, the reliability of results is more rigorously checked through the use of Bayesian uncertainties. It is shown by various synthetic recovery tests that complex and spatially variable features are well resolved in our resulting images of NE Asia. Rayleigh wave phase and group velocity tomograms (8-70 s), a 3-D shear-wave velocity model from depth inversions of the estimated dispersion maps, and regional 3-D models (NE China, the Korean Peninsula, and the Japanese islands) from joint inversions with receiver function data of dense networks are presented. High-resolution models are characterized by a number of tectonically meaningful features. We focus our interpretation on complex patterns of sub-lithospheric low velocity structures that extend from back-arc regions to continental margins. We interpret the anomalies in conjunction with distal and distributed intraplate volcanoes in NE Asia. Further discussion on other imaged features will be presented.

Influence of poly(L-lysine) on the structure of dipalmitoylphosphatidylglycerol/water dispersions studied by X-ray scattering.

PubMed

Förster, G; Schwieger, C; Faber, F; Weber, T; Blume, A

2007-04-01

The interaction between the negatively charged phospholipid DPPG and positively charged poly(L: -lysine) (PLL) of different lengths was studied by X-ray scattering in the SAXS and WAXS region. As a reference pure DPPG (Na salt) was investigated over a wide temperature range (-30 to 70 degrees C). The phase behavior of DPPG in aqueous and in buffer/salt dispersions showed a metastable subgel phase at low temperatures and a recrystallization upon heating before reaching the liquid-crystalline phase. The presence of additional salt stabilizes the bilayer structure and decreases the recrystallization temperature. Large changes in the SAXS region are not connected with changes in chain packing. In DPPG/PLL samples, the PLL is inserted between adjacent headgroup layers and liberates counterions which give rise to a freezing point depression. In the complex with DPPG PLL form an alpha-helical secondary structure at pH 7 and temperatures below the gel to liquid-crystalline phase transition. This prevents DPPG from recrystallization and strongly increases the stacking order. The lamellar repeat distance is decreased and fixed by the helix conformation of PLL in the gel phase. PLL with n = 14 is too short to form helices and is squeezed out reversibly from the interbilayer space upon cooling by freezing of trapped water. In dispersions with longer PLLs (n > 400) at -20 degrees C a 1D crystallization of PLL alpha-helices in the aqueous layer between the headgroups takes place. A structural model is presented for the lateral periodic complex, which is similar to the known cationic lipid/DNA complex.

Fine-scale human genetic structure in Western France.

PubMed

Karakachoff, Matilde; Duforet-Frebourg, Nicolas; Simonet, Floriane; Le Scouarnec, Solena; Pellen, Nadine; Lecointe, Simon; Charpentier, Eric; Gros, Françoise; Cauchi, Stéphane; Froguel, Philippe; Copin, Nane; Le Tourneau, Thierry; Probst, Vincent; Le Marec, Hervé; Molinaro, Sabrina; Balkau, Beverley; Redon, Richard; Schott, Jean-Jacques; Blum, Michael Gb; Dina, Christian

2015-06-01

The difficulties arising from association analysis with rare variants underline the importance of suitable reference population cohorts, which integrate detailed spatial information. We analyzed a sample of 1684 individuals from Western France, who were genotyped at genome-wide level, from two cohorts D.E.S.I.R and CavsGen. We found that fine-scale population structure occurs at the scale of Western France, with distinct admixture proportions for individuals originating from the Brittany Region and the Vendée Department. Genetic differentiation increases with distance at a high rate in these two parts of Northwestern France and linkage disequilibrium is higher in Brittany suggesting a lower effective population size. When looking for genomic regions informative about Breton origin, we found two prominent associated regions that include the lactase region and the HLA complex. For both the lactase and the HLA regions, there is a low differentiation between Bretons and Irish, and this is also found at the genome-wide level. At a more refined scale, and within the Pays de la Loire Region, we also found evidence of fine-scale population structure, although principal component analysis showed that individuals from different departments cannot be confidently discriminated. Because of the evidence for fine-scale genetic structure in Western France, we anticipate that rare and geographically localized variants will be identified in future full-sequence analyses.

Crystal structures of the apo and ATP bound Mycobacterium tuberculosis nitrogen regulatory PII protein

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

Shetty, Nishant D.; Reddy, Manchi C.M.; Palaninathan, Satheesh K.

2010-10-11

PII constitutes a family of signal transduction proteins that act as nitrogen sensors in microorganisms and plants. Mycobacterium tuberculosis (Mtb) has a single homologue of PII whose precise role has as yet not been explored. We have solved the crystal structures of the Mtb PII protein in its apo and ATP bound forms to 1.4 and 2.4 {angstrom} resolutions, respectively. The protein forms a trimeric assembly in the crystal lattice and folds similarly to the other PII family proteins. The Mtb PII:ATP binary complex structure reveals three ATP molecules per trimer, each bound between the base of the T-loop ofmore » one subunit and the C-loop of the neighboring subunit. In contrast to the apo structure, at least one subunit of the binary complex structure contains a completely ordered T-loop indicating that ATP binding plays a role in orienting this loop region towards target proteins like the ammonium transporter, AmtB. Arg38 of the T-loop makes direct contact with the {gamma}-phosphate of the ATP molecule replacing the Mg{sup 2+} position seen in the Methanococcus jannaschii GlnK1 structure. The C-loop of a neighboring subunit encloses the other side of the ATP molecule, placing the GlnK specific C-terminal 3{sub 10} helix in the vicinity. Homology modeling studies with the E. coli GlnK:AmtB complex reveal that Mtb PII could form a complex similar to the complex in E. coli. The structural conservation and operon organization suggests that the Mtb PII gene encodes for a GlnK protein and might play a key role in the nitrogen regulatory pathway.« less

The VMC Survey. XXVII. Young Stellar Structures in the LMC’s Bar Star-forming Complex

NASA Astrophysics Data System (ADS)

Sun, Ning-Chen; de Grijs, Richard; Subramanian, Smitha; Bekki, Kenji; Bell, Cameron P. M.; Cioni, Maria-Rosa L.; Ivanov, Valentin D.; Marconi, Marcella; Oliveira, Joana M.; Piatti, Andrés E.; Ripepi, Vincenzo; Rubele, Stefano; Tatton, Ben L.; van Loon, Jacco Th.

2017-11-01

Star formation is a hierarchical process, forming young stellar structures of star clusters, associations, and complexes over a wide range of scales. The star-forming complex in the bar region of the Large Magellanic Cloud is investigated with upper main-sequence stars observed by the VISTA Survey of the Magellanic Clouds. The upper main-sequence stars exhibit highly nonuniform distributions. Young stellar structures inside the complex are identified from the stellar density map as density enhancements of different significance levels. We find that these structures are hierarchically organized such that larger, lower-density structures contain one or several smaller, higher-density ones. They follow power-law size and mass distributions, as well as a lognormal surface density distribution. All these results support a scenario of hierarchical star formation regulated by turbulence. The temporal evolution of young stellar structures is explored by using subsamples of upper main-sequence stars with different magnitude and age ranges. While the youngest subsample, with a median age of log(τ/yr) = 7.2, contains the most substructure, progressively older ones are less and less substructured. The oldest subsample, with a median age of log(τ/yr) = 8.0, is almost indistinguishable from a uniform distribution on spatial scales of 30-300 pc, suggesting that the young stellar structures are completely dispersed on a timescale of ˜100 Myr. These results are consistent with the characteristics of the 30 Doradus complex and the entire Large Magellanic Cloud, suggesting no significant environmental effects. We further point out that the fractal dimension may be method dependent for stellar samples with significant age spreads.

Structural bioinformatics of the human spliceosomal proteome

PubMed Central

Korneta, Iga; Magnus, Marcin; Bujnicki, Janusz M.

2012-01-01

In this work, we describe the results of a comprehensive structural bioinformatics analysis of the spliceosomal proteome. We used fold recognition analysis to complement prior data on the ordered domains of 252 human splicing proteins. Examples of newly identified domains include a PWI domain in the U5 snRNP protein 200K (hBrr2, residues 258–338), while examples of previously known domains with a newly determined fold include the DUF1115 domain of the U4/U6 di-snRNP protein 90K (hPrp3, residues 540–683). We also established a non-redundant set of experimental models of spliceosomal proteins, as well as constructed in silico models for regions without an experimental structure. The combined set of structural models is available for download. Altogether, over 90% of the ordered regions of the spliceosomal proteome can be represented structurally with a high degree of confidence. We analyzed the reduced spliceosomal proteome of the intron-poor organism Giardia lamblia, and as a result, we proposed a candidate set of ordered structural regions necessary for a functional spliceosome. The results of this work will aid experimental and structural analyses of the spliceosomal proteins and complexes, and can serve as a starting point for multiscale modeling of the structure of the entire spliceosome. PMID:22573172

Application of remote sensing to the geological study of the alkaline complex region of Itatiaia. [Brazil

NASA Technical Reports Server (NTRS)

Dejesusparada, N. (Principal Investigator); Rodrigues, J. E.

1980-01-01

The methodology of remote sensing applied to geological study in a complex area was evaluated. Itatiaia was selected as a test area, which covers the alkaline massives and its precambrian basement. LANDSAT-MSS and radar mosaic of the RADAMBRASIL Project were used for photointerpretation. Previous geological works were consulted and many discrepancies in the distribution of stratigraphic units were found. Moreover, structural lineaments and talus deposits were clearly delineated.

Automated identification of complementarity determining regions (CDRs) reveals peculiar characteristics of CDRs and B cell epitopes.

PubMed

Ofran, Yanay; Schlessinger, Avner; Rost, Burkhard

2008-11-01

Exact identification of complementarity determining regions (CDRs) is crucial for understanding and manipulating antigenic interactions. One way to do this is by marking residues on the antibody that interact with B cell epitopes on the antigen. This, of course, requires identification of B cell epitopes, which could be done by marking residues on the antigen that bind to CDRs, thus requiring identification of CDRs. To circumvent this vicious circle, existing tools for identifying CDRs are based on sequence analysis or general biophysical principles. Often, these tools, which are based on partial data, fail to agree on the boundaries of the CDRs. Herein we present an automated procedure for identifying CDRs and B cell epitopes using consensus structural regions that interact with the antigens in all known antibody-protein complexes. Consequently, we provide the first comprehensive analysis of all CDR-epitope complexes of known three-dimensional structure. The CDRs we identify only partially overlap with the regions suggested by existing methods. We found that the general physicochemical properties of both CDRs and B cell epitopes are rather peculiar. In particular, only four amino acids account for most of the sequence of CDRs, and several types of amino acids almost never appear in them. The secondary structure content and the conservation of B cell epitopes are found to be different than previously thought. These characteristics of CDRs and epitopes may be instrumental in choosing which residues to mutate in experimental search for epitopes. They may also assist in computational design of antibodies and in predicting B cell epitopes.

The role of different network modifying cations on the speciation of the Co2 + complex in silicates and implication in the investigation of historical glasses

NASA Astrophysics Data System (ADS)

Fornacelli, Cristina; Ceglia, Andrea; Bracci, Susanna; Vilarigues, Marcia

2018-01-01

In the last decades the speciation of the cobalt complex in a glass matrix has been extensively studied. Bivalent cobalt ions in glasses of different composition commonly adopt a tetrahedral coordination, though hexa- or penta-coordinated species are also possible. Changes in the absorbance spectrum of Co-doped glasses were attested in previous studies according to the introduction of different modifying cations. A shifting of the first sub-band characterizing the typical triplets of tetrahedral Co2 + ions in both the visible and near infrared regions was observed, but discrepancies in literature suggested a relevant role of glass composition on the definition of the optical signature of cobalt. Co-doped glasses with different composition (soda-lime, potash-lime, mixed alkali and ZnO-Na2O-CaO-SiO2) were studied via Fiber Optic Reflectance Spectroscopy (FORS). Pseudo-Voigt functions were used for the deconvolution of the absorbance spectra and the features of the bands characteristic of each cobalt complex were investigated. The structural role played by each modifying cation and the fundamental implications of glass basicity on the speciation of different Co-complexes were stressed. Changes in glass structure resulted in different equilibria between the three absorbing species whose specific optical signatures in the 480-530 nm region interact to determine the resulting absorbance spectrum.

Functional Coupling between HIV-1 Integrase and the SWI/SNF Chromatin Remodeling Complex for Efficient in vitro Integration into Stable Nucleosomes

PubMed Central

Lesbats, Paul; Botbol, Yair; Chevereau, Guillaume; Vaillant, Cédric; Calmels, Christina; Arneodo, Alain; Andreola, Marie-Line; Lavigne, Marc; Parissi, Vincent

2011-01-01

Establishment of stable HIV-1 infection requires the efficient integration of the retroviral genome into the host DNA. The molecular mechanism underlying the control of this process by the chromatin structure has not yet been elucidated. We show here that stably associated nucleosomes strongly inhibit in vitro two viral-end integration by decreasing the accessibility of DNA to integrase. Remodeling of the chromatinized template by the SWI/SNF complex, whose INI1 major component interacts with IN, restores and redirects the full-site integration into the stable nucleosome region. These effects are not observed after remodeling by other human remodeling factors such as SNF2H or BRG1 lacking the integrase binding protein INI1. This suggests that the restoration process depends on the direct interaction between IN and the whole SWI/SNF complex, supporting a functional coupling between the remodeling and integration complexes. Furthermore, in silico comparison between more than 40,000 non-redundant cellular integration sites selected from literature and nucleosome occupancy predictions also supports that HIV-1 integration is promoted in the genomic region of weaker intrinsic nucleosome density in the infected cell. Our data indicate that some chromatin structures can be refractory for integration and that coupling between nucleosome remodeling and HIV-1 integration is required to overcome this natural barrier. PMID:21347347

Identification of amino acid residues in protein SRP72 required for binding to a kinked 5e motif of the human signal recognition particle RNA.

PubMed

Iakhiaeva, Elena; Iakhiaev, Alexei; Zwieb, Christian

2010-11-13

Human cells depend critically on the signal recognition particle (SRP) for the sorting and delivery of their proteins. The SRP is a ribonucleoprotein complex which binds to signal sequences of secretory polypeptides as they emerge from the ribosome. Among the six proteins of the eukaryotic SRP, the largest protein, SRP72, is essential for protein targeting and possesses a poorly characterized RNA binding domain. We delineated the minimal region of SRP72 capable of forming a stable complex with an SRP RNA fragment. The region encompassed residues 545 to 585 of the full-length human SRP72 and contained a lysine-rich cluster (KKKKKKKKGK) at postions 552 to 561 as well as a conserved Pfam motif with the sequence PDPXRWLPXXER at positions 572 to 583. We demonstrated by site-directed mutagenesis that both regions participated in the formation of a complex with the RNA. In agreement with biochemical data and results from chymotryptic digestion experiments, molecular modeling of SRP72 implied that the invariant W577 was located inside the predicted structure of an RNA binding domain. The 11-nucleotide 5e motif contained within the SRP RNA fragment was shown by comparative electrophoresis on native polyacrylamide gels to conform to an RNA kink-turn. The model of the complex suggested that the conserved A240 of the K-turn, previously identified as being essential for the binding to SRP72, could protrude into a groove of the SRP72 RNA binding domain, similar but not identical to how other K-turn recognizing proteins interact with RNA. The results from the presented experiments provided insights into the molecular details of a functionally important and structurally interesting RNA-protein interaction. A model for how a ligand binding pocket of SRP72 can accommodate a new RNA K-turn in the 5e region of the eukaryotic SRP RNA is proposed.

Identification of amino acid residues in protein SRP72 required for binding to a kinked 5e motif of the human signal recognition particle RNA

PubMed Central

2010-01-01

Background Human cells depend critically on the signal recognition particle (SRP) for the sorting and delivery of their proteins. The SRP is a ribonucleoprotein complex which binds to signal sequences of secretory polypeptides as they emerge from the ribosome. Among the six proteins of the eukaryotic SRP, the largest protein, SRP72, is essential for protein targeting and possesses a poorly characterized RNA binding domain. Results We delineated the minimal region of SRP72 capable of forming a stable complex with an SRP RNA fragment. The region encompassed residues 545 to 585 of the full-length human SRP72 and contained a lysine-rich cluster (KKKKKKKKGK) at postions 552 to 561 as well as a conserved Pfam motif with the sequence PDPXRWLPXXER at positions 572 to 583. We demonstrated by site-directed mutagenesis that both regions participated in the formation of a complex with the RNA. In agreement with biochemical data and results from chymotryptic digestion experiments, molecular modeling of SRP72 implied that the invariant W577 was located inside the predicted structure of an RNA binding domain. The 11-nucleotide 5e motif contained within the SRP RNA fragment was shown by comparative electrophoresis on native polyacrylamide gels to conform to an RNA kink-turn. The model of the complex suggested that the conserved A240 of the K-turn, previously identified as being essential for the binding to SRP72, could protrude into a groove of the SRP72 RNA binding domain, similar but not identical to how other K-turn recognizing proteins interact with RNA. Conclusions The results from the presented experiments provided insights into the molecular details of a functionally important and structurally interesting RNA-protein interaction. A model for how a ligand binding pocket of SRP72 can accommodate a new RNA K-turn in the 5e region of the eukaryotic SRP RNA is proposed. PMID:21073748

Northeastern Brazilian margin: Regional tectonic evolution based on integrated analysis of seismic reflection and potential field data and modelling

NASA Astrophysics Data System (ADS)

Blaich, Olav A.; Tsikalas, Filippos; Faleide, Jan Inge

2008-10-01

Integration of regional seismic reflection and potential field data along the northeastern Brazilian margin, complemented by crustal-scale gravity modelling, is used to reveal and illustrate onshore-offshore crustal structure correlation, the character of the continent-ocean boundary, and the relationship of crustal structure to regional variation of potential field anomalies. The study reveals distinct along-margin structural and magmatic changes that are spatially related to a number of conjugate Brazil-West Africa transfer systems, governing the margin segmentation and evolution. Several conceptual tectonic models are invoked to explain the structural evolution of the different margin segments in a conjugate margin context. Furthermore, the constructed transects, the observed and modelled Moho relief, and the potential field anomalies indicate that the Recôncavo, Tucano and Jatobá rift system may reflect a polyphase deformation rifting-mode associated with a complex time-dependent thermal structure of the lithosphere. The constructed transects and available seismic reflection profiles, indicate that the northern part of the study area lacks major breakup-related magmatic activity, suggesting a rifted non-volcanic margin affinity. In contrast, the southern part of the study area is characterized by abrupt crustal thinning and evidence for breakup magmatic activity, suggesting that this region evolved, partially, with a rifted volcanic margin affinity and character.

Simulation of Different Truncated p16INK4a Forms and In Silico Study of Interaction with Cdk4

PubMed Central

Fahham, Najmeh; Ghahremani, Mohammad Hossein; Sardari, Soroush; Vaziri, Behrouz; Ostad, Seyed Nasser

2008-01-01

Protein-protein interactions studies can greatly increase the amount of structural and functional information pertaining to biologically active molecules and processes. The information obtained from such studies can lead to design and application of new modification in order to obtain a desired bioactivity. Many application packages and servers performing docking, such as HEX, DOT, AUTODOCK, and ZDOCK are now available for predicting the lowest free energy state of a protein complex. In this study, we have focused on cyclin-dependent kinase 4 (Cdk4), a key molecule in the regulation of cell cycle progression at the G1-S phase restriction point and p16INK4a, a tumor suppressor which inhibits Cdk4 activity. Truncated structures were created to find the more critical regions of p16 for interaction. The tertiary structures were determined by ProSAL, GENO3D Web Server. We evaluated their interactions with Cdk4 using two docking systems, HEX 4.5 and DOT 1. Calculations were performed on a high-speed computer. Minimizations and visualizations were carried out by PdbViewer 3.7. Considering shape and shape/electrostatic total energy, structures containing ANK II, III and IV motifs that lack the N-terminal region of the full length p16 molecule showed the best fit complexes among the p16 truncated forms. The free energies were compatible with that of p16 full length original form, the full length. It seems that the N-terminal of the molecule is not crucial for the interaction since the truncated structure containing only this region did not show a good total energy. PMID:19352455

Synthesis, spectroscopic characterization and structural studies of a new proton transfer (H-bonded) complex of o-phenylenediamine with L-tartaric acid

NASA Astrophysics Data System (ADS)

Khan, Ishaat M.; Ahmad, Afaq

2013-10-01

A proton transfer or H-bonded (CT) complex of o-phenylenediamine (OPD) as donor with L-tartaric acid (TART) as acceptor was synthesized and characterized by spectral techniques such as FTIR, 1H NMR, elemental analysis, TGA-TDA, X-ray crystallography and spectrophotometric studies. The structural investigations exhibit that the cation [OPD+] and anion [TART-] are linked together through strong N+-H⋯O- type hydrogen bonds due to transfer of proton from acceptor to donor. Formed H-bonded complex exhibits well resolved proton transfer bands in the regions where neither donor nor acceptor has any absorption. The stoichiometry of the H-bonded complex (HBC) was found to be 1:1, determined by straight line methods. Spectrophotometric studies have been performed at room temperature and Benesi-Hildebrand equation was used to determine formation constant (KCT), molar extinction coefficient (ɛCT) and also transition energy (ECT) of the H-bonded complex. Spectrophotomeric and crystallographic studies have ascertained the formation of 1:1 H-bonded complex. Thermal analysis (TGA-DTA) was also used to confirm the thermal fragmentation and the stability of the synthesized H-bonded complex.

A pulsed supersonic entrainment reactor for the rational preparation of cold ionic complexes

NASA Astrophysics Data System (ADS)

Robertson, W. H.; Kelley, J. A.; Johnson, M. A.

2000-12-01

We describe an ion source for the efficient preparation of cold ion-molecule complexes, X-ṡM. The method relies on condensation of solvent molecules, M, onto argon-solvated ions, X-ṡArm, where the X-ṡArm species are formed in a primary expansion and the molecular partner, M, is interfaced to this flow in the hydrodynamic region by supersonic entrainment. This hybrid "supersonic afterglow" reactor provides a clean synthetic approach for both bare and argon-solvated complexes, where the latter are particularly useful since their structures can be characterized by "nanomatrix" infrared predissociation spectroscopy.

The globular cluster system of NGC 1316. IV. Nature of the star cluster complex SH2

NASA Astrophysics Data System (ADS)

Richtler, T.; Husemann, B.; Hilker, M.; Puzia, T. H.; Bresolin, F.; Gómez, M.

2017-05-01

Context. The light of the merger remnant NGC 1316 (Fornax A) is dominated by old and intermediate-age stars. The only sign of current star formation in this big galaxy is the Hii region SH2, an isolated star cluster complex with a ring-like morphology and an estimated age of 0.1 Gyr at a galactocentric distance of about 35 kpc. A nearby intermediate-age globular cluster, surrounded by weak line emission and a few more young star clusters, is kinematically associated. The origin of this complex is enigmatic. Aims: We want to investigate the nature of this star cluster complex. The nebular emission lines permit a metallicity determination which can discriminate between a dwarf galaxy or other possible precursors. Methods: We used the Integral Field Unit (IFU) of the VIMOS instrument at the Very Large Telescope of the European Southern Observatory in high dispersion mode to study the morphology, kinematics, and metallicity employing line maps, velocity maps, and line diagnostics of a few characteristic spectra. Results: The line ratios of different spectra vary, indicating highly structured Hii regions, but define a locus of uniform metallicity. The strong-line diagnostic diagrams and empirical calibrations point to a nearly solar or even super-solar oxygen abundance. The velocity dispersion of the gas is highest in the region offset from the bright clusters. Star formation may be active on a low level. There is evidence for a large-scale disk-like structure in the region of SH2, which would make the similar radial velocity of the nearby globular cluster easier to understand. Conclusions: The high metallicity does not fit to a dwarf galaxy as progenitor. We favour the scenario of a free-floating gaseous complex having its origin in the merger 2 Gyr ago. Over a long period the densities increased secularly until finally the threshold for star formation was reached. SH2 illustrates how massive star clusters can form outside starbursts and without a considerable field population. Based on observations taken at the European Southern Observatory, Cerro Paranal, Chile, under the programme 082.B-0680, 076.B-0154, 065.N-0166, 065.N-0459.

Complex pegmatite - apelitic of Cabecinha - strategies appreciation of geological heritage and economic development of the region

NASA Astrophysics Data System (ADS)

Nobre, José; Cabral, Tiago; Cabral, João; Gomes, Ana

2014-05-01

The Complex pegmatite - apelitic of Cabecinha corresponds to an isolated ridge that reaches 933 meters, located in the middle zone of transition between the Hesperian massif and the Cova da Beira being located in the NE central part of Portugal, more specifically in the Mountainous region of the province of Beira Alta, council of Sabugal. This complex lies embedded in porphyritic granites with terms of switching to a medium-grained granite rich in sodium feldspars in which they are muscovite granite intrusions. The lodes have pegmatites with NE-SW orientation, presenting phases of predominantly quartz crystallization with multiple parageneses. The inclusions observed are veins filonianian secondary. Some veins have structural discontinuity due to further their training tectonics. The apelitico material is basic in nature engaging in descontinuiddes of pegmatite material, showing no preferred orientation. The petrological characteristics of the area in question provide the appearance of motivating exotic landforms of scientific interest. These landforms, over time, have motivated the popular level the emergence of various myths, thus contributing to the enrichment of the local cultural heritage. This study proceeded to the geological and geomorphological mapping an area of about 6945,350 m2 with a maximum length of 182 m. The huge patent mineralogical, petrological and geomorphological level geodiversity, allied to the structural complexity and associated cultural heritage, allow geoconservation strategies and recovery, using new multimedia technologies including use of QR codes and 3D. All this geological framework and environment becomes an asset for the scientific, educational and economic development of the region. On the other hand, it has the vital Importance in the context of the strategy of forming a geological park, in the point of view of tourism, research and interpretation.

Physical interpretation and development of ultrasonic nondestructive evaluation techniques applied to the quantitative characterization of textile composite materials

NASA Technical Reports Server (NTRS)

Miller, James G.

1994-01-01

In this Progress Report, we describe our continuing research activities concerning the development and implementation of advanced ultrasonic nondestructive evaluation methods applied to the inspection and characterization of complex composite structures. We explore the feasibility of implementing medical linear array imaging technology as a viable ultrasonic-based nondestructive evaluation method to inspect and characterize complex materials. As an initial step toward the application of linear array imaging technology to the interrogation of a wide range of complex composite structures, we present images obtained using an unmodified medical ultrasonic imaging system of two epoxy-bonded aluminum plate specimens, each with intentionally disbonded regions. These images are compared with corresponding conventional ultrasonic contact transducer measurements in order to assess whether these images can detect disbonded regions and provide information regarding the nature of the disbonded region. We present a description of a standoff/delay fixture which has been designed, constructed, and implemented on a Hewlett-Packard SONOS 1500 medical imaging system. This standoff/delay fixture, when attached to a 7.5 MHz linear array probe, greatly enhances our ability to interrogate flat plate specimens. The final section of this Progress Report describes a woven composite plate specimen that has been specially machined to include intentional flaws. This woven composite specimen will allow us to assess the feasibility of applying linear array imaging technology to the inspection and characterization of complex textile composite materials. We anticipate the results of this on-going investigation may provide a step toward the development of a rapid, real-time, and portable method of ultrasonic inspection and characterization based on linear array technology.

The crystal structure of the AgamOBP1•Icaridin complex reveals alternative binding modes and stereo-selective repellent recognition.

PubMed

Drakou, Christina E; Tsitsanou, Katerina E; Potamitis, Constantinos; Fessas, Dimitrios; Zervou, Maria; Zographos, Spyros E

2017-01-01

Anopheles gambiae Odorant Binding Protein 1 in complex with the most widely used insect repellent DEET, was the first reported crystal structure of an olfactory macromolecule with a repellent, and paved the way for OBP1-structure-based approaches for discovery of new host-seeking disruptors. In this work, we performed STD-NMR experiments to directly monitor and verify the formation of a complex between AgamOBP1 and Icaridin, an efficient DEET alternative. Furthermore, Isothermal Titration Calorimetry experiments provided evidence for two Icaridin-binding sites with different affinities (Kd = 0.034 and 0.714 mM) and thermodynamic profiles of ligand binding. To elucidate the binding mode of Icaridin, the crystal structure of AgamOBP1•Icaridin complex was determined at 1.75 Å resolution. We found that Icaridin binds to the DEET-binding site in two distinct orientations and also to a novel binding site located at the C-terminal region. Importantly, only the most active 1R,2S-isomer of Icaridin's equimolar diastereoisomeric mixture binds to the AgamOBP1 crystal, providing structural evidence for the possible contribution of OBP1 to the stereoselectivity of Icaridin perception in mosquitoes. Structural analysis revealed two ensembles of conformations differing mainly in spatial arrangement of their sec-butyl moieties. Moreover, structural comparison with DEET indicates a common recognition mechanism for these structurally related repellents. Ligand interactions with both sites and binding modes were further confirmed by 2D 1 H- 15 N HSQC NMR spectroscopy. The identification of a novel repellent-binding site in AgamOBP1 and the observed structural conservation and stereoselectivity of its DEET/Icaridin-binding sites open new perspectives for the OBP1-structure-based discovery of next-generation insect repellents.

Network representations of angular regions for electromagnetic scattering

PubMed Central

2017-01-01

Network modeling in electromagnetics is an effective technique in treating scattering problems by canonical and complex structures. Geometries constituted of angular regions (wedges) together with planar layers can now be approached with the Generalized Wiener-Hopf Technique supported by network representation in spectral domain. Even if the network representations in spectral planes are of great importance by themselves, the aim of this paper is to present a theoretical base and a general procedure for the formulation of complex scattering problems using network representation for the Generalized Wiener Hopf Technique starting basically from the wave equation. In particular while the spectral network representations are relatively well known for planar layers, the network modelling for an angular region requires a new theory that will be developed in this paper. With this theory we complete the formulation of a network methodology whose effectiveness is demonstrated by the application to a complex scattering problem with practical solutions given in terms of GTD/UTD diffraction coefficients and total far fields for engineering applications. The methodology can be applied to other physics fields. PMID:28817573

The structure of the Caenorhabditis elegans manganese superoxide dismutase MnSOD-3-azide complex

DOE PAGES

Hunter, Gary J.; Trinh, Chi H.; Bonetta, Rosalin; ...

2015-08-27

C. elegans MnSOD-3 has been implicated in the longevity pathway and its mechanism of catalysis is relevant to the aging process and carcinogenesis. The structures of MnSOD-3 provide unique crystallographic evidence of a dynamic region of the tetrameric interface (residues 41–54). We have determined the structure of the MnSOD-3-azide complex to 1.77-Å resolution. The analysis of this complex shows that the substrate analog, azide, binds end-on to the manganese center as a sixth ligand and that it ligates directly to a third and new solvent molecule also positioned within interacting distance to the His30 and Tyr34 residues of the substratemore » access funnel. This is the first structure of a eukaryotic MnSOD-azide complex that demonstrates the extended, uninterrupted hydrogen-bonded network that forms a proton relay incorporating three outer sphere solvent molecules, the substrate analog, the gateway residues, Gln142, and the solvent ligand. This configuration supports the formation and release of the hydrogen peroxide product in agreement with the 5-6-5 catalytic mechanism for MnSOD. The high product dissociation constant k₄ of MnSOD-3 reflects low product inhibition making this enzyme efficient even at high levels of superoxide.« less

Proteins evolve on the edge of supramolecular self-assembly.

PubMed

Garcia-Seisdedos, Hector; Empereur-Mot, Charly; Elad, Nadav; Levy, Emmanuel D

2017-08-10

The self-association of proteins into symmetric complexes is ubiquitous in all kingdoms of life. Symmetric complexes possess unique geometric and functional properties, but their internal symmetry can pose a risk. In sickle-cell disease, the symmetry of haemoglobin exacerbates the effect of a mutation, triggering assembly into harmful fibrils. Here we examine the universality of this mechanism and its relation to protein structure geometry. We introduced point mutations solely designed to increase surface hydrophobicity among 12 distinct symmetric complexes from Escherichia coli. Notably, all responded by forming supramolecular assemblies in vitro, as well as in vivo upon heterologous expression in Saccharomyces cerevisiae. Remarkably, in four cases, micrometre-long fibrils formed in vivo in response to a single point mutation. Biophysical measurements and electron microscopy revealed that mutants self-assembled in their folded states and so were not amyloid-like. Structural examination of 73 mutants identified supramolecular assembly hot spots predictable by geometry. A subsequent structural analysis of 7,471 symmetric complexes showed that geometric hot spots were buffered chemically by hydrophilic residues, suggesting a mechanism preventing mis-assembly of these regions. Thus, point mutations can frequently trigger folded proteins to self-assemble into higher-order structures. This potential is counterbalanced by negative selection and can be exploited to design nanomaterials in living cells.

Proteins evolve on the edge of supramolecular self-assembly

NASA Astrophysics Data System (ADS)

Garcia-Seisdedos, Hector; Empereur-Mot, Charly; Elad, Nadav; Levy, Emmanuel D.

2017-08-01

The self-association of proteins into symmetric complexes is ubiquitous in all kingdoms of life. Symmetric complexes possess unique geometric and functional properties, but their internal symmetry can pose a risk. In sickle-cell disease, the symmetry of haemoglobin exacerbates the effect of a mutation, triggering assembly into harmful fibrils. Here we examine the universality of this mechanism and its relation to protein structure geometry. We introduced point mutations solely designed to increase surface hydrophobicity among 12 distinct symmetric complexes from Escherichia coli. Notably, all responded by forming supramolecular assemblies in vitro, as well as in vivo upon heterologous expression in Saccharomyces cerevisiae. Remarkably, in four cases, micrometre-long fibrils formed in vivo in response to a single point mutation. Biophysical measurements and electron microscopy revealed that mutants self-assembled in their folded states and so were not amyloid-like. Structural examination of 73 mutants identified supramolecular assembly hot spots predictable by geometry. A subsequent structural analysis of 7,471 symmetric complexes showed that geometric hot spots were buffered chemically by hydrophilic residues, suggesting a mechanism preventing mis-assembly of these regions. Thus, point mutations can frequently trigger folded proteins to self-assemble into higher-order structures. This potential is counterbalanced by negative selection and can be exploited to design nanomaterials in living cells.

Evidence for the Location of the Allosteric Activation Switch in the Multisubunit Phosphorylase Kinase Complex from Mass Spectrometric Identification of Chemically Crosslinked Peptides*

PubMed Central

Nadeau, Owen W.; Anderson, David W.; Yang, Qing; Artigues, Antonio; Paschall, Justin E.; Wyckoff, Gerald J.; McClintock, Jennifer L.; Carlson, Gerald M.

2007-01-01

Phosphorylase kinase (PhK), an (αβγδ)4 complex, regulates glycogenolysis. Its activity, catalyzed by the γ subunit, is tightly controlled by phosphorylation and activators acting through allosteric sites on its regulatory α, β and δ subunits. Activation of the catalytic γ subunit in the PhK complex by phosphorylation is known to be predominantly mediated by the regulatory β subunit, which undergoes a conformational change that is structurally linked with the γ subunit and that is characterized by the ability to form β-β dimers using a short chemical crosslinker. To determine potential regions of interaction of the β and γ subunits, we have used chemical crosslinking and 2-hybrid screening. The β and γ subunits were chemically crosslinked to each other in phosphorylated PhK, and crosslinked peptides were identified in digests of the kinase by Fourier transform mass spectrometry in combination with a search engine developed ‘in house’ that generates a hypothetical list of crosslinked peptides. Such a conjugate between β and γ was identified, verified by MS/MS and shown to correspond to crosslinking between K303 in the C-terminal regulatory domain of γ (γCRD) and R18 in the N-terminal regulatory region of β (β1-31), which contains the phosphorylatable serines 11 and 26. A synthetic peptide corresponding to residues 1-22 of β inhibited the crosslinking between β and γ in the complex, and was itself crosslinked to K303 of γ. Through the use of 2-hybrid screening, the β1-31 region was also shown to control β subunit self-interactions, which were favored by truncation of this region or by mutation of the phosphorylatable serines 11 and 26, thus providing structural evidence for a phosphorylation-dependent subunit communication network in the PhK complex involving at least these two regulatory regions of the β and γ subunits. The sum of our results considered together with previous findings implicates the γCRD as being an allosteric activation switch in PhK that interacts with all three of the enzyme’s regulatory subunits and is proximal to the active site cleft. PMID:17123541

The statistical power to detect cross-scale interactions at macroscales

USGS Publications Warehouse

Wagner, Tyler; Fergus, C. Emi; Stow, Craig A.; Cheruvelil, Kendra S.; Soranno, Patricia A.

2016-01-01

Macroscale studies of ecological phenomena are increasingly common because stressors such as climate and land-use change operate at large spatial and temporal scales. Cross-scale interactions (CSIs), where ecological processes operating at one spatial or temporal scale interact with processes operating at another scale, have been documented in a variety of ecosystems and contribute to complex system dynamics. However, studies investigating CSIs are often dependent on compiling multiple data sets from different sources to create multithematic, multiscaled data sets, which results in structurally complex, and sometimes incomplete data sets. The statistical power to detect CSIs needs to be evaluated because of their importance and the challenge of quantifying CSIs using data sets with complex structures and missing observations. We studied this problem using a spatially hierarchical model that measures CSIs between regional agriculture and its effects on the relationship between lake nutrients and lake productivity. We used an existing large multithematic, multiscaled database, LAke multiscaled GeOSpatial, and temporal database (LAGOS), to parameterize the power analysis simulations. We found that the power to detect CSIs was more strongly related to the number of regions in the study rather than the number of lakes nested within each region. CSI power analyses will not only help ecologists design large-scale studies aimed at detecting CSIs, but will also focus attention on CSI effect sizes and the degree to which they are ecologically relevant and detectable with large data sets.

Concerted Multi-Pronged Attack by Calpastatin to Occlude the Catalytic Cleft of Heterodimeric Calpains

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

Moldoveanu, T.; Gehring, K; Green, D

2008-01-01

The Ca{sup 2+}-dependent cysteine proteases, calpains, regulate cell migration, cell death, insulin secretion, synaptic function and muscle homeostasis. Their endogenous inhibitor, calpastatin, consists of four inhibitory repeats, each of which neutralizes an activated calpain with exquisite specificity and potency. Despite the physiological importance of this interaction, the structural basis of calpain inhibition by calpastatin is unknown. Here we report the 3.0{angstrom} structure of Ca{sup 2+}-bound m-calpain in complex with the first calpastatin repeat, both from rat, revealing the mechanism of exclusive specificity. The structure highlights the complexity of calpain activation by Ca{sup 2+}, illustrating key residues in a peripheral domainmore » that serve to stabilize the protease core on Ca{sup 2+} binding. Fully activated calpain binds ten Ca{sup 2+} atoms, resulting in several conformational changes allowing recognition by calpastatin. Calpain inhibition is mediated by the intimate contact with three critical regions of calpastatin. Two regions target the penta-EF-hand domains of calpain and the third occupies the substrate-binding cleft, projecting a loop around the active site thiol to evade proteolysis.« less

Genome Re-Sequencing of Semi-Wild Soybean Reveals a Complex Soja Population Structure and Deep Introgression

PubMed Central

Wu, Sanling; Wang, Ying-Ying; Ye, Chu-Yu; Bai, Xuefei; Li, Zefeng; Yan, Chenghai; Wang, Weidi; Wang, Ziqiang; Shu, Qingyao; Xie, Jiahua; Lee, Suk-Ha; Fan, Longjiang

2014-01-01

Semi-wild soybean is a unique type of soybean that retains both wild and domesticated characteristics, which provides an important intermediate type for understanding the evolution of the subgenus Soja population in the Glycine genus. In this study, a semi-wild soybean line (Maliaodou) and a wild line (Lanxi 1) collected from the lower Yangtze regions were deeply sequenced while nine other semi-wild lines were sequenced to a 3-fold genome coverage. Sequence analysis revealed that (1) no independent phylogenetic branch covering all 10 semi-wild lines was observed in the Soja phylogenetic tree; (2) besides two distinct subpopulations of wild and cultivated soybean in the Soja population structure, all semi-wild lines were mixed with some wild lines into a subpopulation rather than an independent one or an intermediate transition type of soybean domestication; (3) high heterozygous rates (0.19–0.49) were observed in several semi-wild lines; and (4) over 100 putative selective regions were identified by selective sweep analysis, including those related to the development of seed size. Our results suggested a hybridization origin for the semi-wild soybean, which makes a complex Soja population structure. PMID:25265539

Calls reveal population structure of blue whales across the southeast Indian Ocean and the southwest Pacific Ocean.

PubMed

Balcazar, Naysa E; Tripovich, Joy S; Klinck, Holger; Nieukirk, Sharon L; Mellinger, David K; Dziak, Robert P; Rogers, Tracey L

2015-11-24

For effective species management, understanding population structure and distribution is critical. However, quantifying population structure is not always straightforward. Within the Southern Hemisphere, the blue whale ( Balaenoptera musculus ) complex is extremely diverse but difficult to study. Using automated detector methods, we identified "acoustic populations" of whales producing region-specific call types. We examined blue whale call types in passive acoustic data at sites spanning over 7,370 km across the southeast Indian Ocean and southwest Pacific Ocean (SWPO) from 2009 to 2012. In the absence of genetic resolution, these acoustic populations offer unique information about the blue whale population complex. We found that the Australian continent acts as a geographic boundary, separating Australia and New Zealand blue whale acoustic populations at the junction of the Indian and Pacific Ocean basins. We located blue whales in previously undocumented locations, including the far SWPO, in the Tasman Sea off the east coast of Australia, and along the Lau Basin near Tonga. Our understanding of population dynamics across this broad scale has significant implications to recovery and conservation management for this endangered species, at a regional and global scale.

In vitro fluorescence studies of transcription factor IIB-DNA interaction.

PubMed

Górecki, Andrzej; Figiel, Małgorzata; Dziedzicka-Wasylewska, Marta

2015-01-01

General transcription factor TFIIB is one of the basal constituents of the preinitiation complex of eukaryotic RNA polymerase II, acting as a bridge between the preinitiation complex and the polymerase, and binding promoter DNA in an asymmetric manner, thereby defining the direction of the transcription. Methods of fluorescence spectroscopy together with circular dichroism spectroscopy were used to observe conformational changes in the structure of recombinant human TFIIB after binding to specific DNA sequence. To facilitate the exploration of the structural changes, several site-directed mutations have been introduced altering the fluorescence properties of the protein. Our observations showed that binding of specific DNA sequences changed the protein structure and dynamics, and TFIIB may exist in two conformational states, which can be described by a different microenvironment of W52. Fluorescence studies using both intrinsic and exogenous fluorophores showed that these changes significantly depended on the recognition sequence and concerned various regions of the protein, including those interacting with other transcription factors and RNA polymerase II. DNA binding can cause rearrangements in regions of proteins interacting with the polymerase in a manner dependent on the recognized sequences, and therefore, influence the gene expression.

Structure and kinematics of a major tectonic contact, Michipicoten greenstone belt, Ontario

NASA Technical Reports Server (NTRS)

Mcgill, George E.

1992-01-01

The Michipicoten greenstone belt, Ontario, experienced a complex history of folding, faulting, and fabric development. Near Wawa, a major east-west contact, here named the Steep Hill Falls (SHF) contact, extends entirely across the belt. The SHF contact is both an angular unconformity and a fault and is interpreted to be a regionally significant tectonic contact separating distinct northern and southern terranes, both of which include volcanic rocks of probable island-arc origin. The amount of horizontal transport involved in bringing the two terranes together along the SHF contact is not known. Mapping and structural analysis suggest that regionally significant horizontal displacements took place, with movement vectors that changed with time. Early faults, folds, and fabrics imply north-south to northeast-southwest (with respect to present directions) convergence, with a vergence reversal occurring during this complex event. The most likely models infer early south vergence and later north vergence. Transecting the earliest structures are younger (but still Archean) northeast-striking steep cleavages with associated upright folds that may relate to northwest-southeast assembly of the Superior Province craton. The craton assembly event thus involved a transport direction at a high angle to that inferred for the earlier assembly of the Michipicoten greenstone belt.

[Continuity and discontinuity of the geomerida: the bionomic and biotic aspects].

PubMed

Kafanov, A I

2005-01-01

The view of the spatial structure of the geomerida (Earth's life cover) as a continuum that prevails in modern phytocoenology is mostly determined by a physiognomic (landscape-bionomic) discrimination of vegetation components. In this connection, geography of life forms appears as subject of the landscapebionomic biogeography. In zoocoenology there is a tendency of synthesis of alternative concepts based on the assumption that there are no absolute continuum and absolute discontinuum in the organic nature. The problem of continuum and discontinuum of living cover being problem of scale aries from fractal structure of geomerida. This problem arises from fractal nature of the spatial structure of geomerida. The continuum mainly belongs to regularities of topological order. At regional and subregional scale the continuum of biochores is rather rare. The objective evidences of relative discontinuity of the living cover are determined by significant alterations of species diversity at the regional, subregional and even topological scale Alternatively to conventionally discriminated units in physionomically continuous vegetation, the same biotic complexes, represented as operational units of biogeographical and biocenological zoning, are distinguished repeatedly and independently by different researchers. An area occupied by certain flora (fauna, biota) could be considered as elementary unit of biotic diversity (elementary biotic complex).

Direct evidence of an incommensurate phase in NaNbO{sub 3} and its implication in NaNbO{sub 3}-based lead-free antiferroelectrics

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

Guo, Hanzheng; Randall, Clive A., E-mail: car4@psu.edu; Shimizu, Hiroyuki

2015-09-14

Hot-stage in situ transmission electron microscopy was employed to investigate the temperature-induced complex sequence of phase transitions in NaNbO{sub 3} polycrystalline. In addition to the commonly recognized P (Pbma) → R (Pmnm) → S (Pnmm) phase transitions, incommensurate phases were observed to exist in P and R phase regions. The former (in the P → R transition region) is coincident with a diffused dielectric peak appearing at ∼170 °C, and the latter (in the R → S transition region) serves as an intermediate structure to bridge the two sub-phases in the R phase region. The incommensurate phase in the P phasemore » region can be inferred from the polarization current density and differential dielectric permittivity anomalies, and it provides the bridge structure during the electric field-induced polarization reversal and antiferroelectric-to-ferroelectric transition in NaNbO{sub 3} solid solutions.« less

Asynchronous oscillations of rigid rods drive viscous fluid to swirl

NASA Astrophysics Data System (ADS)

Hayashi, Rintaro; Takagi, Daisuke

2017-12-01

We present a minimal system for generating flow at low Reynolds number by oscillating a pair of rigid rods in silicone oil. Experiments show that oscillating them in phase produces no net flow, but a phase difference alone can generate rich flow fields. Tracer particles follow complex trajectory patterns consisting of small orbital movements every cycle and then drifting or swirling in larger regions after many cycles. Observations are consistent with simulations performed using the method of regularized Stokeslets, which reveal complex three-dimensional flow structures emerging from simple oscillatory actuation. Our findings reveal the basic underlying flow structure around oscillatory protrusions such as hairs and legs as commonly featured on living and nonliving bodies.

ANALYTICAL TOOL INTERFACE FOR LANDSCAPE ASSESSMENTS (ATIILA): AN ARCVIEW EXTENSION FOR THE ANALYSIS OF LANDSCAPE PATTERNS, COMPOSITION, AND STRUCTURE

EPA Science Inventory

Environmental management practices are trending away from simple, local- scale assessments toward complex, multiple-stressor regional assessments. Landscape ecology provides the theory behind these assessments while geographic information systems (GIS) supply the tools to impleme...

Deep drilling into the Chesapeake Bay impact structure

USGS Publications Warehouse

Gohn, G.S.; Koeberl, C.; Miller, K.G.; Reimold, W.U.; Browning, J.V.; Cockell, C.S.; Horton, J. Wright; Kenkmann, T.; Kulpecz, A.A.; Powars, D.S.; Sanford, W.E.; Voytek, M.A.

2008-01-01

Samples from a 1.76-kilometer-deep corehole drilled near the center of the late Eocene Chesapeake Bay impact structure (Virginia, USA) reveal its geologic, hydrologic, and biologic history. We conducted stratigraphic and petrologic analyses of the cores to elucidate the timing and results of impact-melt creation and distribution, transient-cavity collapse, and ocean-water resurge. Comparison of post-impact sedimentary sequences inside and outside the structure indicates that compaction of the crater fill influenced long-term sedimentation patterns in the mid-Atlantic region. Salty connate water of the target remains in the crater fill today, where it poses a potential threat to the regional groundwater resource. Observed depth variations in microbial abundance indicate a complex history of impact-related thermal sterilization and habitat modification, and subsequent post-impact repopulation.

Deep drilling into the Chesapeake Bay impact structure.

PubMed

Gohn, G S; Koeberl, C; Miller, K G; Reimold, W U; Browning, J V; Cockell, C S; Horton, J W; Kenkmann, T; Kulpecz, A A; Powars, D S; Sanford, W E; Voytek, M A

2008-06-27

Samples from a 1.76-kilometer-deep corehole drilled near the center of the late Eocene Chesapeake Bay impact structure (Virginia, USA) reveal its geologic, hydrologic, and biologic history. We conducted stratigraphic and petrologic analyses of the cores to elucidate the timing and results of impact-melt creation and distribution, transient-cavity collapse, and ocean-water resurge. Comparison of post-impact sedimentary sequences inside and outside the structure indicates that compaction of the crater fill influenced long-term sedimentation patterns in the mid-Atlantic region. Salty connate water of the target remains in the crater fill today, where it poses a potential threat to the regional groundwater resource. Observed depth variations in microbial abundance indicate a complex history of impact-related thermal sterilization and habitat modification, and subsequent post-impact repopulation.

Relative Travel Time Tomography for East Asia

NASA Astrophysics Data System (ADS)

Chang, S. J.; CHO, S.

2016-12-01

Japan island region is one of the most seismically active region in the world. As a large number of earthquakes have recently occurred along circum-Pacific belt called the ring of fire, concern over earthquakes is increasing in South Korea close to Japan. In this study, we perform seismic imaging based on relative S-wave travel-times to examine S-wave velocity upper mantle structure of East Asia. We used teleseismic events recorded at the Korea Institute of Geoscience and Mineral Resources (KIGAM) network and F-net network operated by the National Research Institute for Earth Science and Disaster Prevention (NIED). Relative travel-time residuals were obtained by a multi-channel cross-correlation method designed to automatically determine accurate relative phase arrival times. The resulting images show high-velocity anomalies along East and South side of Japan island region. These anomalies may indicate subducting Pacific and Philippine Sea plates, respectively. The velocity structure beneath southwest Japan is revealed very complex because the two slabs interact with each other there. Velocity structure of East Asia is useful to understand the tectonic evolution and the mechanism of earthquakes that occur in this region.

Three-Dimensional Passive-Source Reverse-Time Migration of Converted Waves: The Method

NASA Astrophysics Data System (ADS)

Li, Jiahang; Shen, Yang; Zhang, Wei

2018-02-01

At seismic discontinuities in the crust and mantle, part of the compressional wave energy converts to shear wave, and vice versa. These converted waves have been widely used in receiver function (RF) studies to image discontinuity structures in the Earth. While generally successful, the conventional RF method has its limitations and is suited mostly to flat or gently dipping structures. Among the efforts to overcome the limitations of the conventional RF method is the development of the wave-theory-based, passive-source reverse-time migration (PS-RTM) for imaging complex seismic discontinuities and scatters. To date, PS-RTM has been implemented only in 2D in the Cartesian coordinate for local problems and thus has limited applicability. In this paper, we introduce a 3D PS-RTM approach in the spherical coordinate, which is better suited for regional and global problems. New computational procedures are developed to reduce artifacts and enhance migrated images, including back-propagating the main arrival and the coda containing the converted waves separately, using a modified Helmholtz decomposition operator to separate the P and S modes in the back-propagated wavefields, and applying an imaging condition that maintains a consistent polarity for a given velocity contrast. Our new approach allows us to use migration velocity models with realistic velocity discontinuities, improving accuracy of the migrated images. We present several synthetic experiments to demonstrate the method, using regional and teleseismic sources. The results show that both regional and teleseismic sources can illuminate complex structures and this method is well suited for imaging dipping interfaces and sharp lateral changes in discontinuity structures.

A multidisciplinary study in the geodynamic active western Eger rift (Central Europe): The Quaternary volcanic complex Mytina and the recent CO2-degassing zone Hartousov

NASA Astrophysics Data System (ADS)

Flechsig, C.; Heinicke, J.; Kaempf, H. W.; Nickschick, T.; Mrlina, J.

2013-12-01

The Eger rift (Central Europe) belongs to the European Cenozoic rift system and represents an approximately 50 km wide and 300 km long ENE-WSW striking continental rift that formed during the Upper Cretaceous-Tertiary transition. This rift zone is one of the most active seismic regions in Central Europe. Especially, the western part of the Eger rift area is dominated by ongoing hidden magmatic processes in the intra-continental lithospheric mantle. Besides of known quaternary volcanoes, these processes take place in absence of any presently active volcanism at the surface. However, they are expressed by a series of phenomena distributed over a relatively large area, like occurrence of repeated earthquake swarms, surface exhalation of mantle-derived and CO2-enriched fluids at mofettes and mineral springs, and enhanced heat flow. At present this is the only known intra-continental region where such deep-seated, active lithospheric processes currently occur. The aim of the project is to investigate the tectonic/geologic near surface structure and the degassing processes of the mofette field of Hartousov, where soil gas measurements (concentration and flux rate) in an area of appr. 3x2 km traced a permeable NS extended segment of a fault zone and revealed highly permeable Diffuse Degassing Structures (DDS). The second target is volcanic environment of the Quaternary volcanic complex Mytina maar and the cinder cone Zelezna hurka/Eisenbühl. The investigations are intended to clarify: a) the spatio-temporal reconstruction of the maar complex, and the palaeo volcanic scenario (geological model, tectonic settings, distribution of pyroclastica, b) the geological structure and the tectonic control of the recent degassing zone, and c) the comperative interpretation of both regions in the consideration of potential future volcanic risk assessment in sub-regions of the western Eger Rift. To investigate both regions the following methods are used: geoelectrics, geomagnetics, shallow seismics, gravity and CO2-soil gas measurements, petrographic/petrophysical and remote sensing data. The results will be serve as for better understanding of geologic, volcanic and tectonic settings of the two regions as well as for the preparation of the ICDP drilling project 'Drilling the Eger rift' with a multidisciplinary approach consisting of geophysical, geochemical and other disciplines to understand the role of crustal fluid activity for swarm earthquake generation.

Progress in Grid Generation: From Chimera to DRAGON Grids

NASA Technical Reports Server (NTRS)

Liou, Meng-Sing; Kao, Kai-Hsiung

1994-01-01

Hybrid grids, composed of structured and unstructured grids, combines the best features of both. The chimera method is a major stepstone toward a hybrid grid from which the present approach is evolved. The chimera grid composes a set of overlapped structured grids which are independently generated and body-fitted, yielding a high quality grid readily accessible for efficient solution schemes. The chimera method has been shown to be efficient to generate a grid about complex geometries and has been demonstrated to deliver accurate aerodynamic prediction of complex flows. While its geometrical flexibility is attractive, interpolation of data in the overlapped regions - which in today's practice in 3D is done in a nonconservative fashion, is not. In the present paper we propose a hybrid grid scheme that maximizes the advantages of the chimera scheme and adapts the strengths of the unstructured grid while at the same time keeps its weaknesses minimal. Like the chimera method, we first divide up the physical domain by a set of structured body-fitted grids which are separately generated and overlaid throughout a complex configuration. To eliminate any pure data manipulation which does not necessarily follow governing equations, we use non-structured grids only to directly replace the region of the arbitrarily overlapped grids. This new adaptation to the chimera thinking is coined the DRAGON grid. The nonstructured grid region sandwiched between the structured grids is limited in size, resulting in only a small increase in memory and computational effort. The DRAGON method has three important advantages: (1) preserving strengths of the chimera grid; (2) eliminating difficulties sometimes encountered in the chimera scheme, such as the orphan points and bad quality of interpolation stencils; and (3) making grid communication in a fully conservative and consistent manner insofar as the governing equations are concerned. To demonstrate its use, the governing equations are discretized using the newly proposed flux scheme, AUSM+, which will be briefly described herein. Numerical tests on representative 2D inviscid flows are given for demonstration. Finally, extension to 3D is underway, only paced by the availability of the 3D unstructured grid generator.

The comparative osteology of the petrotympanic complex (ear region) of extant baleen whales (Cetacea: Mysticeti).

PubMed

Ekdale, Eric G; Berta, Annalisa; Deméré, Thomas A

2011-01-01

Anatomical comparisons of the ear region of baleen whales (Mysticeti) are provided through detailed osteological descriptions and high-resolution photographs of the petrotympanic complex (tympanic bulla and petrosal bone) of all extant species of mysticete cetaceans. Salient morphological features are illustrated and identified, including overall shape of the bulla, size of the conical process of the bulla, morphology of the promontorium, and the size and shape of the anterior process of the petrosal. We place our comparative osteological observations into a phylogenetic context in order to initiate an exploration into petrotympanic evolution within Mysticeti. The morphology of the petrotympanic complex is diagnostic for individual species of baleen whale (e.g., sigmoid and conical processes positioned at midline of bulla in Balaenoptera musculus; confluence of fenestra cochleae and perilymphatic foramen in Eschrichtius robustus), and several mysticete clades are united by derived characteristics. Balaenids and neobalaenids share derived features of the bulla, such as a rhomboid shape and a reduced anterior lobe (swelling) in ventral aspect, and eschrichtiids share derived morphologies of the petrosal with balaenopterids, including loss of a medial promontory groove and dorsomedial elongation of the promontorium. Monophyly of Balaenoidea (Balaenidae and Neobalaenidae) and Balaenopteroidea (Balaenopteridae and Eschrichtiidae) was recovered in phylogenetic analyses utilizing data exclusively from the petrotympanic complex. This study fills a major gap in our knowledge of the complex structures of the mysticete petrotympanic complex, which is an important anatomical region for the interpretation of the evolutionary history of mammals. In addition, we introduce a novel body of phylogenetically informative characters from the ear region of mysticetes. Our detailed anatomical descriptions, illustrations, and comparisons provide valuable data for current and future studies on the phylogenetic relationships, evolution, and auditory physiology of mysticetes and other cetaceans throughout Earth's history.

Structural Characterization of Sm(III)(EDTMP).

PubMed

Yang, Y; Pushie, M J; Cooper, D M L; Doschak, M R

2015-11-02

Samarium-153 ethylenediamine-N,N,N',N'-tetrakis(methylenephosphonic acid) ((153)Sm-EDTMP, or samarium lexidronam), also known by its registered trademark name Quadramet, is an approved therapeutic radiopharmaceutical used in the palliative treatment of painful bone metastases. Typically, patients with prostate, breast, or lung cancer are most likely to go on to require bone pain palliation treatment due to bone metastases. Sm(EDTMP) is a bone-seeking drug which accumulates on rapidly growing bone, thereby delivering a highly region-specific dose of radiation, chiefly through β particle emission. Even with its widespread clinical use, the structure of Sm(EDTMP) has not yet been characterized at atomic resolution, despite attempts to crystallize the complex. Herein, we prepared a 1:1 complex of the cold (stable isotope) of Sm(EDTMP) under alkaline conditions and then isolated and characterized the complex using conventional spectroscopic techniques, as well as with extended X-ray absorption fine structure (EXAFS) spectroscopy and density functional structure calculations, using natural abundance Sm. We present the atomic resolution structure of [Sm(III)(EDTMP)-8H](5-) for the first time, supported by the EXAFS data and complementary spectroscopic techniques, which demonstrate that the samarium coordination environment in solution is in agreement with the structure that has long been conjectured.

Crystal structure and functional interpretation of the erythrocyte spectrin tetramerization domain complex

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

Ipsaro, Jonathan J.; Harper, Sandra L.; Messick, Troy E.

2010-09-07

As the principal component of the membrane skeleton, spectrin confers integrity and flexibility to red cell membranes. Although this network involves many interactions, the most common hemolytic anemia mutations that disrupt erythrocyte morphology affect the spectrin tetramerization domains. Although much is known clinically about the resulting conditions (hereditary elliptocytosis and pyropoikilocytosis), the detailed structural basis for spectrin tetramerization and its disruption by hereditary anemia mutations remains elusive. Thus, to provide further insights into spectrin assembly and tetramer site mutations, a crystal structure of the spectrin tetramerization domain complex has been determined. Architecturally, this complex shows striking resemblance to multirepeat spectrinmore » fragments, with the interacting tetramer site region forming a central, composite repeat. This structure identifies conformational changes in {alpha}-spectrin that occur upon binding to {beta}-spectrin, and it reports the first structure of the {beta}-spectrin tetramerization domain. Analysis of the interaction surfaces indicates an extensive interface dominated by hydrophobic contacts and supplemented by electrostatic complementarity. Analysis of evolutionarily conserved residues suggests additional surfaces that may form important interactions. Finally, mapping of hereditary anemia-related mutations onto the structure demonstrate that most, but not all, local hereditary anemia mutations map to the interacting domains. The potential molecular effects of these mutations are described.« less

Crystal Structure and Functional Interpretation of the Erythrocyte spectrin Tetramerization Domain Complex

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

J Ipsaro; S Harper; T Messick

2011-12-31

As the principal component of the membrane skeleton, spectrin confers integrity and flexibility to red cell membranes. Although this network involves many interactions, the most common hemolytic anemia mutations that disrupt erythrocyte morphology affect the spectrin tetramerization domains. Although much is known clinically about the resulting conditions (hereditary elliptocytosis and pyropoikilocytosis), the detailed structural basis for spectrin tetramerization and its disruption by hereditary anemia mutations remains elusive. Thus, to provide further insights into spectrin assembly and tetramer site mutations, a crystal structure of the spectrin tetramerization domain complex has been determined. Architecturally, this complex shows striking resemblance to multirepeat spectrinmore » fragments, with the interacting tetramer site region forming a central, composite repeat. This structure identifies conformational changes in {alpha}-spectrin that occur upon binding to {beta}-spectrin, and it reports the first structure of the {beta}-spectrin tetramerization domain. Analysis of the interaction surfaces indicates an extensive interface dominated by hydrophobic contacts and supplemented by electrostatic complementarity. Analysis of evolutionarily conserved residues suggests additional surfaces that may form important interactions. Finally, mapping of hereditary anemia-related mutations onto the structure demonstrate that most, but not all, local hereditary anemia mutations map to the interacting domains. The potential molecular effects of these mutations are described.« less

Morphological study of the innervation pattern of the rabbit sinoatrial node

NASA Technical Reports Server (NTRS)

Roberts, L. A.; Slocum, G. R.; Riley, D. A.

1989-01-01

The pattern of sinoatrial (SA) node innervations in rabbit was elucidated using a newly developed highly reproducible cholinesterase/silver impregnation staining procedure which made it possible to delineate large nerves, fine processes, and ganglion cells. The SA node and dominant pacemaker sites were identified by microelectrode recording. A generalized pattern of innnervation was recognized, which includes a large ganglionic complex inferior to the SA node; two or more moderately large nerves traversing the SA node parallel to the crista terminalis; nerves entering the intercaval region from the septum, the superior vena cava, and the inferior vena cava to impinge on the SA node; and a fine network of nerve processes, which was particularly dense in the SA node. From the location and distribution of the nerves and ganglionic branches, it can be inferred that the neural network in the intercaval region is capable of performing complex modulatory and integrative functions among the structures within this region.

Mid-Infrared Observational and Theoretical Studies of Star Formation and Early Solar Systems

NASA Technical Reports Server (NTRS)

Jones, Barbara

1997-01-01

The first 2 years of this program were used to make mid-IR observations of regions of star formation in the Orion nebula with the UCSD mid-IR camera at the UCSD/University of Minnesota telescope at Mt. Lemmon. These observations attempted to make the first systematic study of an extended region, known to have newly forming stars, and expected to have complex mid-IR emission. We discovered, to our surprise, that most of the thermal emission originated from extended sources rather than from point sources. This interesting observation made the analysis of the data much more complex, since the chop/nod procedures used at these wavelengths produce a differential measurement of the emission in one region compared to that in the adjacent region. Disentangling complex extended emission in such a situation is very difficult. In parallel with this work we were also observing comets in the thermal infrared, the other component of the original proposal. Some spectacular data on the comet Swift-Tuttle was acquired and published. A changing jet structure observed over a 2 week period is described. The rotation period of the comet can be measured at 66 hours. The size of the nucleus can also be estimated (at 30 km) from the observed excess flux from the nucleus. These data have lead to the development of models describing the action of dust particles of differing sizes and composition leaving the nucleus. The spatial distribution of the predicted IR emission has been compared to the observed jet structures, leading to estimates of both particles sizes, relative amounts of silicate vs organic grains, and the amounts of dust emitted in the jets vs isotopic emission.

Role of DNA conformation & energetic insights in Msx-1-DNA recognition as revealed by molecular dynamics studies on specific and nonspecific complexes.

PubMed

Kachhap, Sangita; Singh, Balvinder

2015-01-01

In most of homeodomain-DNA complexes, glutamine or lysine is present at 50th position and interacts with 5th and 6th nucleotide of core recognition region. Molecular dynamics simulations of Msx-1-DNA complex (Q50-TG) and its variant complexes, that is specific (Q50K-CC), nonspecific (Q50-CC) having mutation in DNA and (Q50K-TG) in protein, have been carried out. Analysis of protein-DNA interactions and structure of DNA in specific and nonspecific complexes show that amino acid residues use sequence-dependent shape of DNA to interact. The binding free energies of all four complexes were analysed to define role of amino acid residue at 50th position in terms of binding strength considering the variation in DNA on stability of protein-DNA complexes. The order of stability of protein-DNA complexes shows that specific complexes are more stable than nonspecific ones. Decomposition analysis shows that N-terminal amino acid residues have been found to contribute maximally in binding free energy of protein-DNA complexes. Among specific protein-DNA complexes, K50 contributes more as compared to Q50 towards binding free energy in respective complexes. The sequence dependence of local conformation of DNA enables Q50/Q50K to make hydrogen bond with nucleotide(s) of DNA. The changes in amino acid sequence of protein are accommodated and stabilized around TAAT core region of DNA having variation in nucleotides.

Two novel magnesium(II) meso-tetraphenylporphyrin-based coordination complexes: Syntheses, combined experimental and theoretical structures elucidation, spectroscopy, photophysical properties and antibacterial activity

NASA Astrophysics Data System (ADS)

Amiri, Nesrine; Hajji, Melek; Taheur, Fadia Ben; Chevreux, Sylviane; Roisnel, Thierry; Lemercier, Gilles; Nasri, Habib

2018-02-01

Two novel magnesium(II) tetraphenylporphyrin-based six-coordinate complexes; bis(hexamethylenetetramine)(5,10,15,2O tetrakis[4(benzoyloxy)phenyl]porphinato) magnesuim(II) (1) and bis(1,4-diazabicyclo(2.2.2)octane) (5,10,15,2O-tetrakis[4- (benzoyloxy)phenyl]porphinato)magnesium(II) (2) have been synthesised and confirmed by proton nuclear magnetic resonance, mass spectrometry, elemental analysis and IR spectroscopy. Both crystal structures were determined and described by single crystal X-ray diffraction analysis and Hirshfeld surfaces computational method. All Mg(II) atoms are surrounded by four porphyrin nitrogen atoms and two axial ligands coordinated to the metal ion through one nitrogen atom, forming a regular octahedron. In both complexes, molecular structures and three-dimensional framework are stabilised by inter-and intramolecular C-H ⋯O and C-H ⋯N hydrogen bonds, and by weak C-H ⋯Cg π interactions. UV-visible and Fluorescence investigations, respectively, show that studied complexes have a strong absorption in red part and exhibit an emission in the blue region. The HOMO-LUMO energy gap values, modelled using the DFT approach, indicates that both studied compounds can be classified as semiconductors. The role of these complexes as novel antibacterial agents was also performed.

Mapping the Sedna-Lavinia Region of Venus

NASA Technical Reports Server (NTRS)

Campbell, Bruce A.; Anderson, Ross F.

2008-01-01

Geologic mapping of Venus at 1:5 M scale has shown in great detail the flow complexes of volcanoes, coronae, and shield fields, and the varying structural patterns that differentiate tesserae from corona rims and isolated patches of densely lineated terrain. In most cases, however, the lower-elevation plains between the higher-standing landforms are discriminated only on the basis of potentially secondary features such as late-stage lava flooding or tectonic overprinting. This result, in which volcanoes and tesserae appear as "islands in the sea," places weak constraints on the relative age of large upland regions and the nature of the basement terrain. In this work, we focus on the spatial distribution and topography of densely lineated and tessera units over a large region of Venus, and their relationship to apparently later corona and shield flow complexes. The goal is to identify likely connections between patches of deformed terrain that suggest earlier features of regional extent, and to compare the topography of linked patches with other such clusters as a guide to whether they form larger tracts beneath the plains. Mapping Approach. We are mapping the region from 57S to 57N, 300E-60E. Since the 1:5 M quadrangles emphasize detail of tessera structure and corona/edifice flows, we simply adopt the outlines of these features as they relate to the outcrops of either "densely lineated terrain" or tessera (Fig. 1). The densely lineated material is mapped in many quadrangles based on pervasive structural deformation, typically with a single major axis (in contrast to the overlapping orthogonal patterns on tesserae). This unit definition is often extended to include material of corona rims. We do not at present differentiate between plains units, since earlier efforts show that their most defining attributes may be secondary to the original emplacement (e.g., lobate or sheet-like flooding by thin flow units, tectonic patterns related to regional and localized stress regimes) [1].

Structural controls on ground-water conditions and estimated aquifer properties near Bill Williams Mountain, Williams, Arizona

USGS Publications Warehouse

Pierce, Herbert A.

2001-01-01

As of 1999, surface water collected and stored in reservoirs is the sole source of municipal water for the city of Williams. During 1996 and 1999, reservoirs reached historically low levels. Understanding the ground-water flow system is critical to managing the ground-water resources in this part of the Coconino Plateau. The nearly 1,000-meter-deep regional aquifer in the Redwall and Muav Limestones, however, makes studying or utilizing the resource difficult. Near-vertical faults and complex geologic structures control the ground-water flow system on the southwest side of the Kaibab Uplift near Williams, Arizona. To address the hydrogeologic complexities in the study area, a suite of techniques, which included aeromagnetic, gravity, square-array resistivity, and audiomagnetotelluric surveys, were applied as part of a regional study near Bill Williams Mountain. Existing well data and interpreted geophysical data were compiled and used to estimate depths to the water table and to prepare a potentiometric map. Geologic characteristics, such as secondary porosity, coefficient of anisotropy, and fracture-strike direction, were calculated at several sites to examine how these characteristics change with depth. The 14-kilometer-wide, seismically active northwestward-trending Cataract Creek and the northeastward-trending Mesa Butte Fault systems intersect near Bill Williams Mountain. Several north-south-trending faults may provide additional block faulting north and west of Bill Williams Mountain. Because of the extensive block faulting and regional folding, the volcanic and sedimentary rocks are tilted toward one or more of these faults. These faults provide near-vertical flow paths to the regional water table. The nearly radial fractures allow water that reaches the regional aquifer to move away from the Bill Williams Mountain area. Depth to the regional aquifer is highly variable and depends on location and local structures. On the basis of interpreted audiomagnetotelluric and square-array resistivity sounding curves and limited well data, depths to water may range from 450 to 1,300 meters.

3D Modeling of Iran and Surrounding Areas from Simultaneous Inversion of Multiple Geophysical Datasets (Postprint). Annual Report 3

DTIC Science & Technology

2012-03-22

2003). This is particularly true at shallow depths where the shorter periods, which are primarily sensitive to upper crustal structures, are difficult...to measure, and especially true in tectonically and geologically complex areas. On the other hand, regional gravity inversions have the greatest...the slower deep crustal speeds into the Caspian region does not make sense geologically. These effects are driven by the simple Laplacian smoothness

Cryo-EM structure of Hepatitis C virus IRES bound to the human ribosome at 3.9-Å resolution

NASA Astrophysics Data System (ADS)

Quade, Nick; Boehringer, Daniel; Leibundgut, Marc; van den Heuvel, Joop; Ban, Nenad

2015-07-01

Hepatitis C virus (HCV), a widespread human pathogen, is dependent on a highly structured 5'-untranslated region of its mRNA, referred to as internal ribosome entry site (IRES), for the translation of all of its proteins. The HCV IRES initiates translation by directly binding to the small ribosomal subunit (40S), circumventing the need for many eukaryotic translation initiation factors required for mRNA scanning. Here we present the cryo-EM structure of the human 40S ribosomal subunit in complex with the HCV IRES at 3.9 Å resolution, determined by focused refinement of an 80S ribosome-HCV IRES complex. The structure reveals the molecular details of the interactions between the IRES and the 40S, showing that expansion segment 7 (ES7) of the 18S rRNA acts as a central anchor point for the HCV IRES. The structural data rationalizes previous biochemical and genetic evidence regarding the initiation mechanism of the HCV and other related IRESs.

Dynamic protein interaction networks and new structural paradigms in signaling

PubMed Central

Csizmok, Veronika; Follis, Ariele Viacava; Kriwacki, Richard W.; Forman-Kay, Julie D.

2017-01-01

Understanding signaling and other complex biological processes requires elucidating the critical roles of intrinsically disordered proteins and regions (IDPs/IDRs), which represent ~30% of the proteome and enable unique regulatory mechanisms. In this review we describe the structural heterogeneity of disordered proteins that underpins these mechanisms and the latest progress in obtaining structural descriptions of ensembles of disordered proteins that are needed for linking structure and dynamics to function. We describe the diverse interactions of IDPs that can have unusual characteristics such as “ultrasensitivity” and “regulated folding and unfolding”. We also summarize the mounting data showing that large-scale assembly and protein phase separation occurs within a variety of signaling complexes and cellular structures. In addition, we discuss efforts to therapeutically target disordered proteins with small molecules. Overall, we interpret the remodeling of disordered state ensembles due to binding and post-translational modifications within an expanded framework for allostery that provides significant insights into how disordered proteins transmit biological information. PMID:26922996

Cyg X-3: Not seen in high-energy gamma rays by COS-B

NASA Technical Reports Server (NTRS)

Hermsen, W.; Bennett, K.; Bignami, G. F.; Bloemen, J. B. G. M.; Buccheri, R.; Caraveo, P. A.; Mayer-Hasselwander, H. A.; Oezel, M. E.; Pollock, A. M. T.; Strong, A. W.

1985-01-01

COS-B had Cyg X-3 within its field of view during 7 observation periods between 1975 and 1982 for in total approximately 300 days. In the skymaps (70 meV E 5000 meV) of the Cyg-X region produced for each of these observations and in the summed map, a broad complex structure is visible in the region 72 deg approximately less than 1 approximately less than 85 deg, approximately less than 5 deg. No resolved source structure is visible at the position of Cyg X-3, but a weak signal from Cyg X-3 could be hidden in the structured gamma-ray background. Therefore, the data has been searched for a 4.8 h timing signature, as well as for a source signal in the sky map in addition to the diffuse background structure as estimated from tracers of atomic and molecular gas.

Microbial community structure in a shallow hydrocarbon-contaminated aquifer associated with high electrical conductivity

NASA Astrophysics Data System (ADS)

Duris, J. W.; Rossbach, S.; Atekwana, E. A.; Werkema, D., Jr.

2003-04-01

Little is known about the complex interactions between microbial communities and electrical properties in contaminated aquifers. In order to investigate possible connections between these parameters a study was undertaken to investigate the hypothesis that the degradation of hydrocarbons by resident microbial communities causes a local increase in organic acid concentrations, which in turn cause an increase in native mineral weathering and a concurrent increase in the bulk electrical conductivity of soil. Microbial community structure was analyzed using a 96-well most probable number (MPN) method and rDNA intergenic spacer region analysis (RISA). Microbial community structure was found to change in the presence of hydrocarbon contaminants and these changes were consistently observed in regions of high electrical conductivity. We infer from this relationship that geophysical methods for monitoring the subsurface are a promising new technology for monitoring changes in microbial community structure and simultaneous changes in geochemistry that are associated with hydrocarbon degradation.

A 1:2 crystalline complex of ApA:proflavine: a model for binding to single-stranded regions in RNA.

PubMed Central

Neidle, S; Taylor, G; Sanderson, M

1978-01-01

The structure of a 1"2 complex of adenylyl-(3',5')-adenosine phosphate and proflavine hemisulfate has been determined using the methods of x-ray crystallography. Since the ApA does not form a mini double helix, it may serve as a model for the interaction of planar molecules with single stranded nucleic acids. The dinucleotide adopts an extended conformation with the adenines in adjacent molecules forming base pairs. A most unusual feature of the molecule is that it does not obey the "rigid nucleotide" concept although none of the torsion angles occur in energetically unfavourable regions. This is most probably due to the strong interactions between the proflavine and the oligonucleotide. PMID:724521

Identification of three critical regions within mouse interleukin 2 by fine structural deletion analysis.

PubMed Central

Zurawski, S M; Zurawski, G

1988-01-01

We have analyzed structure--function relationships of the protein hormone murine interleukin 2 by fine structural deletion mapping. A total of 130 deletion mutant proteins, together with some substitution and insertion mutant proteins, was expressed in Escherichia coli and analyzed for their ability to sustain the proliferation of a cloned murine T cell line. This analysis has permitted a functional map of the protein to be drawn and classifies five segments of the protein, which together contain 48% of the sequence, as unessential to the biological activity of the protein. A further 26% of the protein is classified as important, but not crucial, for the activity. Three regions, consisting of amino acids 32-35, 66-77 and 119-141 contain the remaining 26% of the protein and are critical to the biological activity of the protein. The functional map is discussed in the context of the possible role of the identified critical regions in the structure of the hormone and its binding to the interleukin 2 receptor complex. Images PMID:3261239

The Employment of Structures and Work Patterns in Organizations Involved in Modern, Complex, Multi-National Operations

DTIC Science & Technology

2011-06-01

This has a particular impact on Command Management, through which the Commander establishes and maintains his headquarters structures, collaborations...tend to be organized in a ‘planning-centric’ fashion. Analysis tends to focus upon the interpretation of environmental phenomena (e.g. events...These will be used in the next stage to organize scenario development. for the future of the conflict region including the impact of the military

Tectonostratigraphy of the Passive Continental Margin Offshore Indus Pakistan

NASA Astrophysics Data System (ADS)

Aslam, K.; Khan, M.; Liu, Y.; Farid, A.

2017-12-01

The tectonic evolution and structural complexities are poorly understood in the passive continental margin of the Offshore Indus of Pakistan. In the present study, an attempt has been made to interpret the structural trends and seismic stratigraphic framework in relation to the tectonics of the region. Seismic reflection data revealed tectonically controlled, distinct episodes of normal faulting representing rifting at different ages and transpression in the Late Eocene time. This transpression has resulted in the reactivation of the Pre-Cambrian basement structures. The movement of these basement structures has considerably affected the younger sedimentary succession resulting in push up structures resembling anticlines. The structural growth of the push-up structures was computed. The most remarkable tectonic setting in the region is represented by the normal faulting and by the basement uplift which divides the rifting and transpression stages. Ten mappable seismic sequences have been identified on the seismic records. A Jurassic aged paleo-shelf has also been identified on all regional seismic profiles which is indicative of Indian-African Plates separation during the Jurassic time. Furthermore, the backstripping technique was applied which has been proved to be a powerful technique to quantify subsidence/uplift history of rift-type passive continental margins. The back strip curves suggest that transition from an extensional rifted margin to transpression occurred during Eocene time (50-30 Ma). The backstripping curves show uplift had happened in the area. We infer that the uplift has occurred due to the movement of basement structures by the transpression movements of Arabian and Indian Plates. The present study suggests that the structural styles and stratigraphy of the Offshore Indus Pakistan were significantly affected by the tectonic activities during the separation of Gondwanaland in the Mesozoic and northward movement of the Indian Plate, post-rifting, and sedimentations along its western margin during the Middle Cenozoic. The present comprehensive interpretation can help in understanding the structural complexities and stratigraphy associated with tectonics in other parts of the passive continental margins worldwide dominated by rifting and drifting tectonics.

Dissection of the complex genetic basis of craniofacial anomalies using haploid genetics and interspecies hybrids in Nasonia wasps

PubMed Central

Werren, John H.; Cohen, Lorna B.; Gadau, Juergen; Ponce, Rita; Baudry, Emmanuelle; Lynch, Jeremy A.

2016-01-01

The animal head is a complex structure where numerous sensory, structural and alimentary structures are concentrated and integrated, and its ontogeny requires precise and delicate interactions among genes, cells, and tissues. Thus, it is perhaps unsurprising that craniofacial abnormalities are among the most common birth defects in people, or that these defects have a complex genetic basis involving interactions among multiple loci. Developmental processes that depend on such epistatic interactions become exponentially more difficult to study in diploid organisms as the number of genes involved increases. Here, we present hybrid haploid males of the wasp species pair Nasonia vitripennis and Nasonia giraulti, which have distinct male head morphologies, as a genetic model of craniofacial development that possesses the genetic advantages of haploidy, along with many powerful genomic tools. Viable, fertile hybrids can be made between the species, and quantitative trail loci related to shape differences have been identified. In addition, a subset of hybrid males show head abnormalities, including clefting at the midline and asymmetries. Crucially, epistatic interactions among multiple loci underlie several developmental differences and defects observed in the F2 hybrid males. Furthermore, we demonstrate an introgression of a chromosomal region from N. giraulti into N. vitripennis that shows an abnormality in relative eye size, which maps to a region containing a major QTL for this trait. Therefore, the genetic sources of head morphology can, in principle, be identified by positional cloning. Thus, Nasonia is well positioned to be a uniquely powerful model invertebrate system with which to probe both development and complex genetics of craniofacial patterning and defects. PMID:26721604

The structure of unliganded reverse transcriptase from the human immunodeficiency virus type 1.

PubMed Central

Rodgers, D W; Gamblin, S J; Harris, B A; Ray, S; Culp, J S; Hellmig, B; Woolf, D J; Debouck, C; Harrison, S C

1995-01-01

The crystal structure of the reverse transcriptase (RT) from the type 1 human immunodeficiency virus has been determined at 3.2-A resolution. Comparison with complexes between RT and the polymerase inhibitor Nevirapine [Kohlstaedt, L.A., Wang, J., Friedman, J.M., Rice, P.A. & Steitz, T.A. (1992) Science 256, 1783-1790] and between RT and an oligonucleotide [Jacobo-Molina, A., Ding, J., Nanni, R., Clark, A. D., Lu, X., Tantillo, C., Williams, R. L., Kamer, G., Ferris, A. L., Clark, P., Hizi, A., Hughes, S. H. & Arnold, E. (1993) Proc. Natl. Acad. Sci. USA 90, 6320-6324] reveals changes associated with ligand binding. The enzyme is a heterodimer (p66/p51), with domains labeled "fingers," "thumb," "palm," and "connection" in both subunits, and a ribonuclease H domain in the larger subunit only. The most striking difference between RT and both complex structures is the change in orientation of the p66 thumb (approximately 33 degrees rotation). Smaller shifts relative to the core of the molecule were also found in other domains, including the p66 fingers and palm, which contain the polymerase active site. Within the polymerase catalytic region itself, there are no rearrangements between RT and the RT/DNA complex. In RT/Nevirapine, the drug binds in the p66 palm near the polymerase active site, a region that is well-packed hydrophobic core in the unliganded enzyme. Room for the drug is provided by movement of a small beta-sheet within the palm domain of the Nevirapine complex. The rearrangement within the palm and thumb, as well as domain shifts relative to the enzyme core, may prevent correct placement of the oligonucleotide substrate when the drug is bound. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7532306

Geologic Map of the Thaumasia Region, Mars

USGS Publications Warehouse

Dohm, Janes M.; Tanaka, Kenneth L.; Hare, Trent M.

2001-01-01

The geology of the Thaumasia region (fig. 1, sheet 3) includes a wide array of rock materials, depositional and erosional landforms, and tectonic structures. The region is dominated by the Thaumasia plateau, which includes central high lava plains ringed by highly deformed highlands; the plateau may comprise the ancestral center of Tharsis tectonism (Frey, 1979; Plescia and Saunders, 1982). The extensive structural deformation of the map region, which is without parallel on Mars in both complexity and diversity, occurred largely throughout the Noachian and Hesperian periods (Tanaka and Davis, 1988; Scott and Dohm, 1990a). The deformation produced small and large extensional and contractional structures (fig. 2, sheet 3) that resulted from stresses related to the formation of Tharsis (Frey, 1979; Wise and others, 1979; Plescia and Saunders, 1982; Banerdt and others, 1982, 1992; Watters and Maxwell, 1986; Tanaka and Davis, 1988; Francis, 1988; Watters, 1993; Schultz and Tanaka, 1994), from magmatic-driven uplifts, such as at Syria Planum (Tanaka and Davis, 1988; Dohm and others, 1998; Dohm and Tanaka, 1999) and central Valles Marineris (Dohm and others, 1998, Dohm and Tanaka, 1999), and from the Argyre impact (Wilhelms, 1973; Scott and Tanaka, 1986). In addition, volcanic, eolian, and fluvial processes have highly modified older surfaces in the map region. Local volcanic and tectonic activity often accompanied episodes of valley formation. Our mapping depicts and describes the diverse terrains and complex geologic history of this unique ancient tectonic region of Mars. The geologic (sheet 1), paleotectonic (sheet 2), and paleoerosional (sheet 3) maps of the Thaumasia region were compiled on a Viking 1:5,000,000-scale digital photomosaic base. The base is a combination of four quadrangles: the southeast part of Phoenicis Lacus (MC–17), most of the southern half of Coprates (MC–18), a large part of Thaumasia (MC–25), and the northwest margin of Argyre (MC–26). The medium-resolution Viking images used for mapping and base preparation also formed the basis of the 1:2,000,000 scale subquadrangle series. Earlier geologic maps of all or parts of the region include: (1) maps of the Phoenicis Lacus, Coprates, Thaumasia, and Argyre quadrangles at 1:5,000,000 scale based mainly on Mariner 9 images (respectively, Masursky and others, 1978; McCauley, 1978; McGill, 1978; and Hodges, 1980), (2) the global map of Mars at 1:25,000,000 (Scott and Carr, 1978) compiled largely from the 1:5,000,000 scale geologic maps, (3) maps showing lava flows in the Tharsis region at 1:2,000,000 scale compiled from Viking and Mariner 9 images (Scott, 1981; Scott and Tanaka, 1981a, b; Scott and others, 1981), (4) the map of the western equatorial region of Mars at 1:15,000,000 scale based on Viking images (Scott and Tanaka, 1986), and (5) the map of the Valles Marineris region at 1:2,000,000 scale compiled from Viking images (Witbeck and others, 1991). The previous maps have described the overall geology and geomorphology of the region but have not unraveled the detailed stratigraphy and complex evolution of this unique and geologically diverse martian province. The main purpose of this comprehensive mapping project is to reconstruct the stratigraphic, structural, and erosional histories of the Thaumasia region. The region is the last major province of the Tharsis region to undergo detailed structural mapping using Viking images; its history is essential to documenting the overall tectonic history of Tharsis. Other provinces of Tharsis that have been structurally mapped include Syria Planum (Tanaka and Davis, 1988), Tempe Terra and Ulysses Patera (Scott and Dohm, 1990b), and Alba Patera (Tanaka, 1990). Another primary mapping objective is to determine the region's volcanic history and assess the relations among fault systems and volcanoes (Wise and others, 1979; Scott and Tanaka, 1980; Whitford-Stark, 1982; Scott and Dohm, 1990a). A secondary mapping objective is to determine the distribution and ages of valleys. In our study, we incorporated detailed photogeologic mapping, comprehensive crater statistics (table 1), and geologic, paleotectonic, and paleoerosional Geographic Information System (GIS) databases. Sheets 1–3 show geologic units, faults and other significant structures, and valleys, respectively. To help unravel the complex geologic history of the Thaumasia region, we transferred the highly detailed geologic unit, paleotectonic, and paleoerosional information of sheets 1–3 into a multilayered GIS database for comparative analysis. The geologic information was transferred from hard copy into a digital format by scanning at 25 micron resolution on a drum scanner. The 2-bit scanned image was then converted to an x,y coordinate system using ARC/INFO's vectorization routine. The geologic unit, structural, and erosional data were transformed into the original map projection, Lambert Conformal. The average transformation root mean square error was 0.25 km (acceptable for the Thaumasia map base at 1:5,000,000 scale). After transformation, the features were properly attributed and tediously checked. Once digitized, the map data can be transformed into any map projection depending on the type of data analysis. For example, the equal-area sinusoidal projection was used for determining the precise area of geologic units (table 1). In addition to the geologic map and its attendant stratigraphic section, correlation chart, and description of map units, we include text sections that clarify the histories and temporal, spatial, and causal relations of the various geologic units and landforms of the Thaumasia region. The geologic summary section defines the sequence of major geologic events.

Structural Basis for Interactions Between Contactin Family Members and Protein-tyrosine Phosphatase Receptor Type G in Neural Tissues

DOE PAGES

Nikolaienko, Roman M.; Hammel, Michal; Dubreuil, Véronique; ...

2016-08-18

Protein-tyrosine phosphatase receptor type G (RPTPγ/PTPRG) interacts in vitro with contactin-3-6 (CNTN3-6), a group of glycophosphatidylinositol-anchored cell adhesion molecules involved in the wiring of the nervous system. In addition to PTPRG, CNTNs associate with multiple transmembrane proteins and signal inside the cell via cis-binding partners to alleviate the absence of an intracellular region. Here, we use comprehensive biochemical and structural analyses to demonstrate that PTPRG·CNTN3-6 complexes share similar binding affinities and a conserved arrangement. Furthermore, as a first step to identifying PTPRG·CNTN complexes in vivo, we found that PTPRG and CNTN3 associate in the outer segments of mouse rod photoreceptormore » cells. In particular, PTPRG and CNTN3 form cis-complexes at the surface of photoreceptors yet interact in trans when expressed on the surfaces of apposing cells. Further structural analyses suggest that all CNTN ectodomains adopt a bent conformation and might lie parallel to the cell surface to accommodate these cis and trans binding modes. Taken together, these studies identify a PTPRG·CNTN complex in vivo and provide novel insights into PTPRG- and CNTN-mediated signaling.« less

A study of the structure of the ν1(HF) absorption band of the СH3СN…HF complex

NASA Astrophysics Data System (ADS)

Gromova, E. I.; Glazachev, E. V.; Bulychev, V. P.; Koshevarnikov, A. M.; Tokhadze, K. G.

2015-09-01

The ν1(HF) absorption band shape of the CH3CN…HF complex is studied in the gas phase at a temperature of 293 K. The spectra of gas mixtures CH3CN/HF are recorded in the region of 4000-3400 cm-1 at a resolution from 0.1 to 0.005 cm-1 with a Bruker IFS-120 HR vacuum Fourier spectrometer in a cell 10 cm in length with wedge-shaped sapphire windows. The procedure used to separate the residual water absorption allows more than ten fine-structure bands to be recorded on the low-frequency wing of the ν1(HF) band. It is shown that the fine structure of the band is formed primarily due to hot transitions from excited states of the low-frequency ν7 librational vibration. Geometrical parameters of the equilibrium nuclear configuration, the binding energy, and the dipole moment of the complex are determined from a sufficiently accurate quantum-chemical calculation. The frequencies and intensities for a number of spectral transitions of this complex are obtained in the harmonic approximation and from variational solutions of anharmonic vibrational problems.

Microwave Spectra and AB Initio Studies of the Ne-Acetone Complex

NASA Astrophysics Data System (ADS)

Gao, Jiao; Thomas, Javix; Xu, Yunjie; Jäger, Wolfgang

2015-06-01

Microwave spectra of the neon-acetone van der Waals complex were measured using a cavity-based molecular beam Fourier-transform microwave spectrometer in the region from 5 to 18 GHz. Both 20Ne and 22Ne containing isotopologues were studied and both c- and weaker a-type rotational transitions were observed. The transitions are split into multiplets due to the internal rotation of two methyl groups in acetone. Electronic structure calculations were done at the MP2 level of theory with the 6-311++g (2d, p) basis set for all atoms and the internal rotation barrier height of the methyl groups was determined to be about 2.8 kJ/mol. The ab initio rotational constants were the basis for our spectroscopic searches, but the multiplet structures and floppiness of the complex made the quantum number assignment very difficult. The assignment was finally achieved with the aid of constructing closed frequency loops and predicting internal rotation splittings using the XIAM code. Analyses of the spectra yielded rotational and centrifugal distortion constants, as well as internal rotation parameters, which were interpreted in terms of structure and internal dynamics of the complex. H. Hartwig and H. Dreizler, Z. Naturforsch. A 51, 923 (1996).

Gemelli-obturator complex in the deep gluteal space: an anatomic and dynamic study.

PubMed

Balius, Ramon; Susín, Antonio; Morros, Carles; Pujol, Montse; Pérez-Cuenca, Dolores; Sala-Blanch, Xavier

2018-06-01

To investigate the behavior of the sciatic nerve during hip rotation at subgluteal space. Sonographic examination (high-resolution ultrasound machine at 5.0-14 MHZ) of the gemelli-obturator internus complex following two approaches: (1) a study on cadavers and (2) a study on healthy volunteers. The cadavers were examined in pronation, pelvis-fixed position by forcing internal and external rotations of the hip with the knee in 90° flexion. Healthy volunteers were examined during passive internal and external hip rotation (prone position; lumbar and pelvic regions fixed). Subjects with a history of major trauma, surgery or pathologies affecting the examined regions were excluded. The analysis included eight hemipelvis from six fresh cadavers and 31 healthy volunteers. The anatomical study revealed the presence of connective tissue attaching the sciatic nerve to the structures of the gemellus-obturator system at deep subgluteal space. The amplitude of the nerve curvature during rotating position was significantly greater than during resting position. During passive internal rotation, the sciatic nerve of both cadavers and healthy volunteers transformed from a straight structure to a curved structure tethered at two points as the tendon of the obturator internus contracted downwards. Conversely, external hip rotation caused the nerve to relax. Anatomically, the sciatic nerve is closely related to the gemelli-obturator internus complex. This relationship results in a reproducible dynamic behavior of the sciatic nerve during passive hip rotation, which may contribute to explain the pathological mechanisms of the obturator internal gemellus syndrome.

Complex Dynamic Development of Poliovirus Membranous Replication Complexes

PubMed Central

Nair, Vinod; Hansen, Bryan T.; Hoyt, Forrest H.; Fischer, Elizabeth R.; Ehrenfeld, Ellie

2012-01-01

Replication of all positive-strand RNA viruses is intimately associated with membranes. Here we utilize electron tomography and other methods to investigate the remodeling of membranes in poliovirus-infected cells. We found that the viral replication structures previously described as “vesicles” are in fact convoluted, branching chambers with complex and dynamic morphology. They are likely to originate from cis-Golgi membranes and are represented during the early stages of infection by single-walled connecting and branching tubular compartments. These early viral organelles gradually transform into double-membrane structures by extension of membranous walls and/or collapsing of the luminal cavity of the single-membrane structures. As the double-membrane regions develop, they enclose cytoplasmic material. At this stage, a continuous membranous structure may have double- and single-walled membrane morphology at adjacent cross-sections. In the late stages of the replication cycle, the structures are represented mostly by double-membrane vesicles. Viral replication proteins, double-stranded RNA species, and actively replicating RNA are associated with both double- and single-membrane structures. However, the exponential phase of viral RNA synthesis occurs when single-membrane formations are predominant in the cell. It has been shown previously that replication complexes of some other positive-strand RNA viruses form on membrane invaginations, which result from negative membrane curvature. Our data show that the remodeling of cellular membranes in poliovirus-infected cells produces structures with positive curvature of membranes. Thus, it is likely that there is a fundamental divergence in the requirements for the supporting cellular membrane-shaping machinery among different groups of positive-strand RNA viruses. PMID:22072780

Preliminary geologic map of the Thaniyat Turayf Quadrangle, sheet 29C, Kingdom of Saudi Arabia

USGS Publications Warehouse

Meissner, C.R.; Dini, S.M.; Farasani, A.M.; Riddler, G.P.; Smith, G.H.; Griffin, M.B.; Van Eck, Marcel

1990-01-01

A new structural concept introduced in this report extends the Wadi as Sirhan graben complex southeastward into the An Nafud. This concept increases the size of the potentially oil-and-gas-bearing Wadi as Sirhan region to include the An Nafud.

Single-molecule force-conductance spectroscopy of hydrogen-bonded complexes

NASA Astrophysics Data System (ADS)

Pirrotta, Alessandro; De Vico, Luca; Solomon, Gemma C.; Franco, Ignacio

2017-03-01

The emerging ability to study physical properties at the single-molecule limit highlights the disparity between what is observable in an ensemble of molecules and the heterogeneous contributions of its constituent parts. A particularly convenient platform for single-molecule studies are molecular junctions where forces and voltages can be applied to individual molecules, giving access to a series of electromechanical observables that can form the basis of highly discriminating multidimensional single-molecule spectroscopies. Here, we computationally examine the ability of force and conductance to inform about molecular recognition events at the single-molecule limit. For this, we consider the force-conductance characteristics of a prototypical class of hydrogen bonded bimolecular complexes sandwiched between gold electrodes. The complexes consist of derivatives of a barbituric acid and a Hamilton receptor that can form up to six simultaneous hydrogen bonds. The simulations combine classical molecular dynamics of the mechanical deformation of the junction with non-equilibrium Green's function computations of the electronic transport. As shown, in these complexes hydrogen bonds mediate transport either by directly participating as a possible transport pathway or by stabilizing molecular conformations with enhanced conductance properties. Further, we observe that force-conductance correlations can be very sensitive to small changes in the chemical structure of the complexes and provide detailed information about the behavior of single molecules that cannot be gleaned from either measurement alone. In fact, there are regions during the elongation that are only mechanically active, others that are only conductance active, and regions where both force and conductance changes as the complex is mechanically manipulated. The implication is that force and conductance provide complementary information about the evolution of molecules in junctions that can be used to interrogate basic structure-transport relations at the single-molecule limit.

Mononuclear zinc(II) complexes of 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols: Synthesis, structural characterization, DNA binding and cheminuclease activities

NASA Astrophysics Data System (ADS)

Ravichandran, J.; Gurumoorthy, P.; Karthick, C.; Kalilur Rahiman, A.

2014-03-01

Four new zinc(II) complexes [Zn(HL1-4)Cl2] (1-4), where HL1-4 = 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols, have been isolated and fully characterized using various spectro-analytical techniques. The X-ray crystal structure of complex 4 shows the distorted trigonal-bipyramidal coordination geometry around zinc(II) ion. The crystal packing is stabilized by intermolecular NH⋯O hydrogen bonding interaction. The complexes display no d-d electronic band in the visible region due to d10 electronic configuration of zinc(II) ion. The electrochemical properties of the synthesized ligands and their complexes exhibit similar voltammogram at reduction potential due to electrochemically innocent Zn(II) ion, which evidenced that the electron transfer is due to the nature of the ligand. Binding interaction of complexes with calf thymus DNA was studied by UV-Vis absorption titration, viscometric titration and cyclic voltammetry. All complexes bind with CT DNA by intercalation, giving the binding affinity in the order of 2 > 1 ≫ 3 > 4. The prominent cheminuclease activity of complexes on plasmid DNA (pBR322 DNA) was observed in the absence and presence of H2O2. Oxidative pathway reveals that the underlying mechanism involves hydroxyl radical.

Discrete Molecular Dynamics Can Predict Helical Prestructured Motifs in Disordered Proteins

PubMed Central

Han, Kyou-Hoon; Dokholyan, Nikolay V.; Tompa, Péter; Kalmár, Lajos; Hegedűs, Tamás

2014-01-01

Intrinsically disordered proteins (IDPs) lack a stable tertiary structure, but their short binding regions termed Pre-Structured Motifs (PreSMo) can form transient secondary structure elements in solution. Although disordered proteins are crucial in many biological processes and designing strategies to modulate their function is highly important, both experimental and computational tools to describe their conformational ensembles and the initial steps of folding are sparse. Here we report that discrete molecular dynamics (DMD) simulations combined with replica exchange (RX) method efficiently samples the conformational space and detects regions populating α-helical conformational states in disordered protein regions. While the available computational methods predict secondary structural propensities in IDPs based on the observation of protein-protein interactions, our ab initio method rests on physical principles of protein folding and dynamics. We show that RX-DMD predicts α-PreSMos with high confidence confirmed by comparison to experimental NMR data. Moreover, the method also can dissect α-PreSMos in close vicinity to each other and indicate helix stability. Importantly, simulations with disordered regions forming helices in X-ray structures of complexes indicate that a preformed helix is frequently the binding element itself, while in other cases it may have a role in initiating the binding process. Our results indicate that RX-DMD provides a breakthrough in the structural and dynamical characterization of disordered proteins by generating the structural ensembles of IDPs even when experimental data are not available. PMID:24763499

Solution and Crystallographic Structures of the Central Region of the Phosphoprotein from Human Metapneumovirus

PubMed Central

Leyrat, Cedric; Renner, Max; Harlos, Karl; Grimes, Jonathan M.

2013-01-01

Human metapneumovirus (HMPV) of the family Paramyxoviridae is a major cause of respiratory illness worldwide. Phosphoproteins (P) from Paramyxoviridae are essential co-factors of the viral RNA polymerase that form tetramers and possess long intrinsically disordered regions (IDRs). We located the central region of HMPV P (Pced) which is involved in tetramerization using disorder analysis and modeled its 3D structure ab initio using Rosetta fold-and-dock. We characterized the solution-structure of Pced using small angle X-ray scattering (SAXS) and carried out direct fitting to the scattering data to filter out incorrect models. Molecular dynamics simulations (MDS) and ensemble optimization were employed to select correct models and capture the dynamic character of Pced. Our analysis revealed that oligomerization involves a compact central core located between residues 169-194 (Pcore), that is surrounded by flexible regions with α-helical propensity. We crystallized this fragment and solved its structure at 3.1 Å resolution by molecular replacement, using the folded core from our SAXS-validated ab initio model. The RMSD between modeled and experimental tetramers is as low as 0.9 Å, demonstrating the accuracy of the approach. A comparison of the structure of HMPV P to existing mononegavirales Pced structures suggests that Pced evolved under weak selective pressure. Finally, we discuss the advantages of using SAXS in combination with ab initio modeling and MDS to solve the structure of small, homo-oligomeric protein complexes. PMID:24224051

Stark absorption spectroscopy on the carotenoids bound to B800-820 and B800-850 type LH2 complexes from a purple photosynthetic bacterium, Phaeospirillum molischianum strain DSM120.

PubMed

Horibe, Tomoko; Qian, Pu; Hunter, C Neil; Hashimoto, Hideki

2015-04-15

Stark absorption spectroscopy was applied to clarify the structural differences between carotenoids bound to the B800-820 and B800-850 LH2 complexes from a purple photosynthetic bacterium Phaeospirillum (Phs.) molischianum DSM120. The former complex is produced when the bacteria are grown under stressed conditions of low temperature and dim light. These two LH2 complexes bind carotenoids with similar composition, 10% lycopene and 80% rhodopin, each with the same number of conjugated CC double bonds (n=11). Quantitative classical and semi-quantum chemical analyses of Stark absorption spectra recorded in the carotenoid absorption region reveal that the absolute values of the difference dipole moments |Δμ| have substantial differences (2 [D/f]) for carotenoids bound to either B800-820 or B800-850 complexes. The origin of this striking difference in the |Δμ| values was analyzed using the X-ray crystal structure of the B800-850 LH2 complex from Phs. molischianum DSM119. Semi-empirical molecular orbital calculations predict structural deformations of the major carotenoid, rhodopin, bound within the B800-820 complex. We propose that simultaneous rotations around neighboring CC and CC bonds account for the differences in the 2 [D/f] of the |Δμ| value. The plausible position of the rotation is postulated to be located around C21-C24 bonds of rhodopin. Copyright © 2014 Elsevier Inc. All rights reserved.

Determinants for membrane association and permeabilization of the coxsackievirus 2B protein and the identification of the Golgi complex as the target organelle.

PubMed

de Jong, Arjan S; Wessels, Els; Dijkman, Henri B P M; Galama, Jochem M D; Melchers, Willem J G; Willems, Peter H G M; van Kuppeveld, Frank J M

2003-01-10

The 2B protein of enterovirus is responsible for the alterations in the permeability of secretory membranes and the plasma membrane in infected cells. The structural requirements for the membrane association and the subcellular localization of this essential virus protein, however, have not been defined. Here, we provide evidence that the 2B protein is an integral membrane protein in vivo that is predominantly localized at the Golgi complex upon individual expression. Addition of organelle-specific targeting signals to the 2B protein revealed that the Golgi localization is an absolute prerequisite for the ability of the protein to modify plasma membrane permeability. Expression of deletion mutants and heterologous proteins containing specific domains of the 2B protein demonstrated that each of the two hydrophobic regions could mediate membrane binding individually. However, the presence of both hydrophobic regions was required for the correct membrane association, efficient Golgi targeting, and the membrane-permeabilizing activity of the 2B protein, suggesting that the two hydrophobic regions are cooperatively involved in the formation of a membrane-integral complex. The formation of membrane-integral pores by the 2B protein in the Golgi complex and the possible mechanism by which a Golgi-localized virus protein modifies plasma membrane permeability are discussed.

Tectono-Magmatic Cycles and Geodynamic Settings of Ore-Bearing System Formation in the Southern Cis-Argun Region

NASA Astrophysics Data System (ADS)

Petrov, V. A.; Andreeva, O. V.; Poluektov, V. V.; Kovalenko, D. V.

2017-11-01

The ore-bearing geological structural units of the southern Cis-Argun region are considered in the context of varying geodynamic regimes related to the Proterozoic, Caledonian, and Hercynian tectono-magmatic cycles, as well as during the Late Mesozoic within-plate tectono-magmatic activity, which give rise to the formation of subalkaline igneous rocks of the Shakhtama Complex with Au, Cu-Mo, Pb-Zn-Ag metallogenic specialization; volcano-plutonic complexes of calderas with Mo-U, Pb-Zn, and fluorite ores; and rare-metal granite of the Kukulbei Complex with a Sn-W-Li-Ta spectrum of mineralization. The comparative geochemical characteristics inherent to Mesozoic ore-bearing felsic igneous rocks are considered, as well as geodynamic settings of ore-bearing fluido-magmatic systems, taking into consideration new data on geochemistry of bimodal trachybasalt-trachydacite series and rhyolite of the Turga Series, which fill the Strel'tsovka Caldera, whose trend of evolution is defined as a reference for geological history of the studied territory. The geodynamic conditions, phase composition, and geochemistry of rocks along with metallogenic specialization of Mesozoic volcano-plutonic complexes of southern Cis-Argun region are close to those of the Great Khingan Belt in northeastern China and eastern Mongolia.

Evaluating Changes in Tendon Crimp with Fatigue Loading as an ex vivo Structural Assessment of Tendon Damage

PubMed Central

Freedman, Benjamin R.; Zuskov, Andrey; Sarver, Joseph J.; Buckley, Mark R.; Soslowsky, Louis J.

2015-01-01

The complex structure of tendons relates to their mechanical properties. Previous research has associated the waviness of collagen fibers (crimp) during quasi-static tensile loading to tensile mechanics, but less is known about the role of fatigue loading on crimp properties. In this study (IACUC approved), mouse patellar tendons were fatigue loaded while an integrated plane polariscope simultaneously assessed crimp properties. We demonstrate a novel structural mechanism whereby tendon crimp amplitude and frequency are altered with fatigue loading. In particular, fatigue loading increased the crimp amplitude across the tendon width and length, and these structural alterations were shown to be both region and load dependent. The change in crimp amplitude was strongly correlated to mechanical tissue laxity (defined as the ratio of displacement and gauge length relative to the first cycle of fatigue loading assessed at constant load throughout testing), at all loads and regions evaluated. Together, this study highlights the role of fatigue loading on tendon crimp properties as a function of load applied and region evaluated, and offers an additional structural mechanism for mechanical alterations that may lead to ultimate tendon failure. PMID:25773654

State of the dam at the Zeya hydroelectric station with consideration of the geodynamic effect

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

Marchuk, A.N.; Dudchenko, L.N.; Bolgov, V.V.

1995-11-01

The buttress dam of the Zeya hydroelectric station has already been operating successfully for 20 years under complex climatic, geological, and seismological conditions. Additional difficulties are created by some uncertainty of the interaction of the structure with the geological environment subjected to tectonic movements. The seismotectonic conditions of the region of the Zeya reservoir are determined by proximity to the boundary of two large structural zones with a different character of tectonic movements: regions of the uplift of the Tukuringra-Soktokhan Range and the downwarping Amur-Zeya Plateau. This boundary is represented by the Pkan fault located about 1 km from themore » dam on the downstream side.« less

The balanced scorecard as a strategic management tool: its application in the regional public health system in Campania.

PubMed

Impagliazzo, Cira; Ippolito, Adelaide; Zoccoli, Paola

2009-01-01

Health, as a primary and advanced need, can only be guaranteed through the appropriate management of dedicated resources. As in any situation where funds are limited, it is vital to have logical frameworks and tools to set up structures capable of making a complex system like the health service work. Only through an appropriate and competent activity of governance can such structures be identified, organized, and rendered operational. This can be achieved by using ad hoc tools such as the Balanced Scorecard. Its application in the case of the Regional Government of Campania indicates that it is a valid tool in all circumstances except in situations of crisis.

Novel Na(+) doped Alq3 hybrid materials for organic light-emitting diode (OLED) devices and flat panel displays.

PubMed

Bhagat, S A; Borghate, S V; Kalyani, N Thejo; Dhoble, S J

2015-05-01

Pure and Na(+) -doped Alq3 complexes were synthesized by a simple precipitation method at room temperature, maintaining a stoichiometric ratio. These complexes were characterized by X-ray diffraction, Fourier transform infrared (FTIR), UV/Vis absorption and photoluminescence (PL) spectra. The X-ray diffractogram exhibits well-resolved peaks, revealing the crystalline nature of the synthesized complexes, FTIR confirms the molecular structure and the completion of quinoline ring formation in the metal complex. UV/Vis absorption and PL spectra of sodium-doped Alq3 complexes exhibit high emission intensity in comparison with Alq3 phosphor, proving that when doped in Alq3 , Na(+) enhances PL emission intensity. The excitation spectra of the synthesized complexes lie in the range 242-457 nm when weak shoulders are also considered. Because the sharp excitation peak falls in the blue region of visible radiation, the complexes can be employed for blue chip excitation. The emission wavelength of all the synthesized complexes lies in the bluish green/green region ranging between 485 and 531 nm. The intensity of the emission wavelength was found to be elevated when Na(+) is doped into Alq3 . Because both the excitation and emission wavelengths fall in the visible region of electromagnetic radiation, these phosphors can also be employed to improve the power conversion efficiency of photovoltaic cells by using the solar spectral conversion principle. Thus, the synthesized phosphors can be used as bluish green/green light-emitting phosphors for organic light-emitting diodes, flat panel displays, solid-state lighting technology - a step towards the desire to reduce energy consumption and generate pollution free light. Copyright © 2014 John Wiley & Sons, Ltd.

Seismic Observations of the Mid-Pacific Large Low Shear Velocity Province

NASA Astrophysics Data System (ADS)

Chan, A.; Helmberger, D. V.; Sun, D.; Li, D.; Jackson, J. M.

2015-12-01

Seismic data from earthquakes originating in the Fiji-Tonga region exhibits waveform complexity of a number of phases which may be attributed to various structures along ray paths to stations of USArray, including anomalous structures at the core-mantle boundary. The data shows variation in multipathing, that is, the presence of secondary arrivals following the S phase at diffracted distances (Sdiff) which suggests that the waveform complexity is due to structures at the eastern edge of the mid-Pacific Large Low Shear Velocity Province (LLSVP). This study examines data from earthquake events while the Transportable Array portion of USArray was situated in the midwest United States, reinforcing previous studies that indicate late arrivals occurring as long as 26 seconds after the primary arrivals (To et al., 2011). Using earth flattening transformations and finite difference methods, simulations of tapered wedge structures of low velocity material allow for wave energy trapping, producing the observed waveform complexity and delayed arrivals at large distances, with such structures having characteristic properties of, for example, a height of 70 km, in-plane extent more than 1000 km, and shear wave velocity drop of 3% at the top to 15% at the bottom relative to PREM. Differential arrival times for SH and SV components suggest anisotropy and possible wave propagation through downgoing slabs beneath the source region. The arrivals of the SPdKS phase further support the presence of an ultra-low velocity zone (ULVZ) within a two-humped LLSVP. Some systematic delays in arrival times of multiple phases for distances less than 102º are accounted for and attributed to the presence of a mantle slab underneath the continental United States. Comparisons to seismic data from earthquakes originating from other locations further constrain depths of the deep mantle structures. Possible explanations include iron-enrichment of deep mantle phases.

Structure of a short-chain dehydrogenase/reductase from Bacillus anthracis

PubMed Central

Hou, Jing; Wojciechowska, Kamila; Zheng, Heping; Chruszcz, Maksymilian; Cooper, David R.; Cymborowski, Marcin; Skarina, Tatiana; Gordon, Elena; Luo, Haibin; Savchenko, Alexei; Minor, Wladek

2012-01-01

The crystal structure of a short-chain dehydrogenase/reductase from Bacillus anthracis strain ‘Ames Ancestor’ complexed with NADP has been determined and refined to 1.87 Å resolution. The structure of the enzyme consists of a Rossmann fold composed of seven parallel β-strands sandwiched by three α-­helices on each side. An NADP molecule from an endogenous source is bound in the conserved binding pocket in the syn conformation. The loop region responsible for binding another substrate forms two perpendicular short helices connected by a sharp turn. PMID:22684058

Complex structural behavior of oligopurine-oligopyrimidine sequence cloned within the supercoiled plasmid.

PubMed Central

Parniewski, P; Galazka, G; Wilk, A; Klysik, J

1989-01-01

Synthetic sequence GATCC(AG)7ATCG(AT)4CG(AG)7 was cloned into plasmid and its structural behavior under the influence of supercoiling was analysed by chemical modification at variety of experimental conditions. It was found that this sequence adopts at least two different non-B conformations depending on -delta and pH values. Moreover, 12 nucleotide long non-pur.pyr spacer region separating two identical (AG)7 blocks does not provide a significant energy barrier protecting against unusual structures formation. Images PMID:2644622

RECURSIVE PROTEIN MODELING: A DIVIDE AND CONQUER STRATEGY FOR PROTEIN STRUCTURE PREDICTION AND ITS CASE STUDY IN CASP9

PubMed Central

CHENG, JIANLIN; EICKHOLT, JESSE; WANG, ZHENG; DENG, XIN

2013-01-01

After decades of research, protein structure prediction remains a very challenging problem. In order to address the different levels of complexity of structural modeling, two types of modeling techniques — template-based modeling and template-free modeling — have been developed. Template-based modeling can often generate a moderate- to high-resolution model when a similar, homologous template structure is found for a query protein but fails if no template or only incorrect templates are found. Template-free modeling, such as fragment-based assembly, may generate models of moderate resolution for small proteins of low topological complexity. Seldom have the two techniques been integrated together to improve protein modeling. Here we develop a recursive protein modeling approach to selectively and collaboratively apply template-based and template-free modeling methods to model template-covered (i.e. certain) and template-free (i.e. uncertain) regions of a protein. A preliminary implementation of the approach was tested on a number of hard modeling cases during the 9th Critical Assessment of Techniques for Protein Structure Prediction (CASP9) and successfully improved the quality of modeling in most of these cases. Recursive modeling can signicantly reduce the complexity of protein structure modeling and integrate template-based and template-free modeling to improve the quality and efficiency of protein structure prediction. PMID:22809379