cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Para-(benzoyl)-phenylalanine as a potential inhibitor against LpxC of Leptospira spp.: homology modeling, docking, and molecular dynamics study
Creators: name: Dibyabhaba Pradhan
name: Vani Priyadarshini
name: Munikumar, Manne
name: Swargam, Sandeep
name: Amineni Umamaheswari
name: Bitla, Aparna
Publisher: name: Taylor & Francis
Year: 2013
Subjects: Molecular Biology

description: Leptospira interrogans, a Gram-negative bacterial pathogen is the main cause of human leptospirosis. Lipid A is a highly immunoreactive endotoxic center of lipopolysaccharide (LPS) that anchors LPS into the outer membrane of Leptospira. Discovery of compounds inhibiting lipid-A biosynthetic pathway would be promising for dissolving the structural integrity of membrane leading to cell lysis and death of Leptospira. LpxC, a unique enzyme of lipid-A biosynthetic pathway was identified as common drug target of Leptospira. Herein, homology modeling, docking, and molecular dynamics (MD) simulations were employed to discover potential inhibitors of LpxC. A reliable tertiary structure of LpxC in complex with inhibitor BB-78485 was constructed in Modeller 9v8. A data-set of BB-78485 structural analogs were docked with LpxC in Maestro v9.2 virtual screening workflow, which implements three stage Glide docking protocol. Twelve lead molecules with better XP Gscore compared to BB-78485 were proposed as potential inhibitors of LpxC. Para-(benzoyl)-phenylalanine – that showed lowest XP Gscore (−10.35 kcal/mol) – was predicted to have best binding affinity towards LpxC. MD simulations were performed for LpxC and para-(benzoyl)-phenylalanine docking complex in Desmond v3.0. Trajectory analysis showed the docking complex and inter-molecular interactions was stable throughout the entire production part of MD simulations. The results indicate para-(benzoyl)-phenylalanine as a potent drug molecule against leptospirosis. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:10
Fibrillation of human serum albumin shows nonspecific coordination on stoichiometric increment of Copper(II)
Creators: name: Nitin Kumar Pandey
name: Ghosh, Sudeshna
name: Nagy, Nóra Veronika
name: Swagata Dasgupta
Publisher: name: Taylor & Francis
Year: 2014
Subjects: Molecular Biology

description: Protein aggregation is related to a series of pathological disorders the main cause of which are the fibrillar species generated during the process. Human serum albumin (HSA) undergoes rapid fibrillation in the presence of Cu(II) at pH 7.4 in 60% ethanol after 6-h incubation (∼65 °C) followed by room temperature incubation. Here, we have investigated the effect of a stoichiometric variation of Cu(II) on the self-assembly of HSA using Congo red and thioflavin T dye-binding studies, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, electron paramagnetic resonance spectroscopy, fluorescence microscopy and transmission electron microscopy. The simulation of EPR spectra suggests that with the increment in Cu(II) ion concentration, there is a change in ligand field coordination. Kinetic parameters indicate reduced cooperativity that may be related to the nonspecific coordination on increment of Cu(II) concentration. Cu(II) is also able to direct the accumulation of a large number of fibers along with a formation of dense fibrillar network which is evident from microscopic images.
Interactions of selected indole derivatives with COX-2 and their in silico structure modifications towards the development of novel NSAIDs
Creators: name: K.V. Dileep
name: C. Remya
name: I. Tintu
name: C. Sadasivan
Publisher: name: Taylor & Francis
Year: 2014
Subjects: Molecular Biology

description: Cyclooxygenase-2 (COX-2) is an important enzyme responsible for the formation of potent inflammatory mediators like prostaglandins, prostacyclin and thromboxane. Hence, inhibition of COX-2 is one of the best ways to control the inflammation. Non-steroidal anti-inflammatory drugs can control inflammation by inhibiting Cyclooxygenase. Selective inhibition of COX-2 is preferable over the inhibition of COX-1 because of the fewer adverse effects produced. Molecular modeling and docking of 134 selected indole compounds were done against COX-2. The pharmacophore-based in silico structural modifications of the best scored compounds were carried out in order to enhance the binding affinity and selectivity. The modification resulted in derivatives with better binding energies than that of known COX-2 inhibitors. The four best derivatives in terms of the binding energies were selected and their binding stabilities were studied by molecular dynamics simulation methods.
title: Angeblichen und echten Krisen zum Trotz: Die Europäische Union ist das bisher beste politische Projekt der Europäerinnen und Europäer
Creators: name: Giegerich, Thomas
Publisher: name: Fachinformationsdienst für internationale und interdisziplinäre Rechtsforschung
Year: 2019
Subjects: subject: 340

description: Saar Briefs
title: Noch ist der Rechtsstaat nicht verloren: Der EuGH stellt eine Verletzung der richterlichen Unabhängigkeit durch den polnischen Gesetzgeber fest
Creators: name: Giegerich, Thomas
Publisher: name: Fachinformationsdienst für internationale und interdisziplinäre Rechtsforschung
Year: 2019
Subjects: subject: 340

description: Saar Briefs
Topographical and microstructural property relationships of plasma sprayed yttria stabilised zirconia coatings on complex surfaces
Creators: name: Sesso, Mitchell Lawrence
Publisher: name: Swinburne
Year: 2024

description: Understanding the process-property relationships of plasma sprayed ceramic coatings is key to expanding their use into current and future applications, allowing for greater operational and environmental efficiencies. This work developed methods to quantify the intricate surface topography of plasma sprayed yttria stabilised zirconia coatings deposited onto complex shaped geometries. New useful relationships were uncovered, including a correlation among surface topography, thickness and microstructure that will assist in the quality assessment of coatings applied to complex shapes. The overall understanding of these relationships will aid in the optimisation and enhanced efficiency for the predictable design of future coatings on complex surfaces.
Phosphorylation of Ser-180 of rat aquaporin-4 shows marginal affect on regulation of water permeability: molecular dynamics study
Creators: name: Sachdeva, Ruchi
name: Singh, Balvinder
Publisher: name: Taylor & Francis
Year: 2014
Subjects: Molecular Biology

description: Water permeation through rat aquaporin-4 (rAQP4), predominantly found in mammalian brain is regulated by phosphorylation of Ser-180. The present study has been carried out to understand the structural mechanism of regulation of water permeability across the channel. Molecular dynamics (MD) simulations have been carried out to investigate the structural changes caused due to phosphorylation of Ser-180 in the tetrameric assembly of rAQP4 along with predicted C-terminal region (255–323). The interactions involving opposite charges are observed between cytoplasmic loops and the C-terminal region during MD simulations. This results in movement of C-terminal region of rAQP4 towards the cytoplasmic mouth of water channel. Despite this movement, there was a gap between C-terminal region and cytoplasmic mouth of the channel through which water molecules were able to gain entry into the channel. The interactions between C-terminus and loop D of neighboring monomers in a tetrameric assembly appear to prevent the complete closure of cytoplasmic mouth of the water channel. Further, the rates of water permeation through phosphorylated and unphosphorylated rAQP4 have also been compared. The simulation studies showed a continuous movement of water in a single file across pore of unphosphorylated as well as phosphorylated rAQP4.
Phosphorylation of Ser-180 of rat aquaporin-4 shows marginal affect on regulation of water permeability: molecular dynamics study
Creators: name: Sachdeva, Ruchi
name: Singh, Balvinder
Publisher: name: Taylor & Francis
Year: 2013
Subjects: Molecular Biology

description: Water permeation through rat aquaporin-4 (rAQP4), predominantly found in mammalian brain is regulated by phosphorylation of Ser-180. The present study has been carried out to understand the structural mechanism of regulation of water permeability across the channel. Molecular dynamics (MD) simulations have been carried out to investigate the structural changes caused due to phosphorylation of Ser-180 in the tetrameric assembly of rAQP4 along with predicted C-terminal region (255–323). The interactions involving opposite charges are observed between cytoplasmic loops and the C-terminal region during MD simulations. This results in movement of C-terminal region of rAQP4 towards the cytoplasmic mouth of water channel. Despite this movement, there was a gap between C-terminal region and cytoplasmic mouth of the channel through which water molecules were able to gain entry into the channel. The interactions between C-terminus and loop D of neighboring monomers in a tetrameric assembly appear to prevent the complete closure of cytoplasmic mouth of the water channel. Further, the rates of water permeation through phosphorylated and unphosphorylated rAQP4 have also been compared. The simulation studies showed a continuous movement of water in a single file across pore of unphosphorylated as well as phosphorylated rAQP4.
Validation of potential inhibitors for SrtA against Bacillus anthracis by combined approach of ligand-based and molecular dynamics simulation
Creators: name: Chandrabose Selvaraj
name: Singh, Sanjeev Kumar
Publisher: name: Taylor & Francis
Year: 2014
Subjects: Molecular Biology

description: The development of SrtA inhibitors targeting the biothreat organism namely Bacillus anthracis was achieved by the combined approach of pharmacophore modeling, binding interactions, electron transferring capacity, ADME, and Molecular dynamics studies. In this study, experimentally reported Ba-SrtA inhibitors (pyridazinone and pyrazolethione derivatives) were considered for the development of enhanced pharmacophoric model. The obtained AAAHR hypothesis was a pure theoretical concept that accounts for common molecular interaction network present in experimentally active pyridazinone and pyrazolethione derivatives. Pharmacophore-based screening of AAAHR hypothesis provides several new compounds, and those compounds were treated with four phases of docking protocols with combined Glide-QPLD docking approach. In this approach, scoring and charge accuracy variations were seen to be dominated by QM/MM approach through the allocation of partial charges. Finally, we reported the best compounds from binding db, Chembridge db, and Toslab based on scoring values, energy parameters, electron transfer reaction, ADME, and cell adhesion inhibition activity. The dynamic state of interaction and binding energy assess that new compounds are more active inside the binding pocket and these compounds on experimental validations will survive as better inhibitors for targeting the cell adhesion mechanism of Ba-SrtA.
A communication network within the cytoplasmic domain of toll-like receptors has remained conserved during evolution
Creators: name: Singh, Shikha
name: Pandey, Kalpana
name: Rathore, Yogendra S.
name: Sagar, Amin
name: U. Bharat K. Pattnaik
name: , Ashish
Publisher: name: Taylor & Francis
Year: 2014
Subjects: Molecular Biology

description: Toll/IL-1R (TIR) domain, that is, the cytoplasmic domain, in toll-like receptors (TLRs) from different species showed high sequence conservation in stretches spread across the surface as well as the core of the domain. To probe the structure–function significance of these residues, especially those coming from the core of TIR domains, we analyzed molecular dynamics trajectories of sequence similarity based models of human TIR domains. This study brought forth that N-terminal of the TIR domain simultaneously interacts with the flanking residues of the BB loop and central β-sheets. At the same time, residues of the central β-strands form favorable contacts with the DD loop and C-terminal, thus forming a two-way circuit between the N- and C-termini. In this work, the array of intradomain interactions is termed as communication network. Importantly, the “hubs” of this communication network were found to be conserved in all human TLRs. Earlier mutagenesis–function correlation work brought forth that certain mutations in the “core” of the TIR domain of TLR4 (e.g. in IFI767–769AAA and L815A) led to almost complete abrogation of signaling and reasoning for this dramatic loss-of-function has remained unclear, since these sites are not surface exposed. Using MD studies, we show here that this communication network gets disrupted in mutants of human TLR4 which were earlier reported to be functionally compromised. Extension of MD studies to heterodimer of TLR1/2 suggested that this evolutionarily conserved communication network senses the interactions formed upon dimerization and relays it to surfaces which are not involved in direct interdomain contacts.
Ultrafast folding and molecular dynamics of a linear hydrophobic β-hairpin
Creators: name: Upadhyayula Surya Raghavender
Publisher: name: Taylor & Francis
Year: 2013
Subjects: Molecular Biology

description: The first computational study of the folding and dynamics of a hydrophobic β-hairpin containing a central heterochiral diproline segment is reported. Linear hydrophobic sequences containing centrally positioned diproline motifs, heterochiral (DL/LD) and homochiral (LL/DD)), are investigated for their ability to form β-hairpins. Heterochiral diproline motifs (LD/DL) reveal the formation of stable β-hairpins with the backbone adopting β-turn conformation and the formation of backbone hydrogen bonds with antiparallel cross-strand registry, whereas the homochiral diproline (LL/DD) containing sequences tend to adopt PPII helix conformation. The competition between the β-turn formation and the backbone H-bond ladder of the antiparallel β-strands in heterochiral diproline containing sequences is employed to validate the hypothesis that β-turn formation precedes inter-strand registry in the folding of a β-hairpin (“zipper” mechanism). The observation of noncanonical hydrogen bonds leads to a folded β-hairpin-like conformation and points to the existence of relatively stable transition state intermediates, between the unfolded (extended) and folded (β-hairpin) states. The MD simulations are in excellent agreement with the experimental studies on the model system and constitute the very first computational investigation of the folding and dynamics of a completely hydrophobic synthetic β-hairpin containing heterogeneous residues of mixed chirality.
Effects of glycosylation and pH conditions in the dynamics of human arylsulfatase A
Creators: name: Madza Yasodara Farias Virgens
name: Laercio Pol-Fachin
name: Verli, Hugo
name: Saraiva-Pereira, Maria Luiza
Publisher: name: Taylor & Francis
Year: 2014
Subjects: Molecular Biology

description: Arylsulfatase A (ARSA) is a lysosomal sulfatase that catalyzes the hydrolysis of cerebroside sulfate. Its deficiency results in Metachromatic Leukodystrophy, whereas a minor condition called ARSA pseudodeficiency occurs in healthy individuals, which has been associated with the substitution of the glycosylated Asn350 by a Ser and with the loss of the polyadenylation signal. In this work, we have investigated ARSA dynamics employing molecular dynamics simulations in response to (1) different pH’s, as, beyond its natural lysossomal environment, it has been recently identified in cytoplasmatic medium and (2) glycan occupancies, including its normal glycosylation state, presenting three high mannose-type oligosaccharides. Accordingly, four systems were studied considering ARSA under different conditions: (1) nonglycosylated at pH ∼ 7 (ARSApH7); (2) non-glycosylated at pH ∼ 5 (ARSApH5); (3) triple glycosylated at pH ∼ 5 (ARSAglyc,pH5); and (4) ARSA-N350S mutant at pH ∼ 5 (ARSAN350S,pH5). Lowering pH and increasing glycosylation was found to reduce the flexibility of the enzyme. In addition, at acidic pH, the glycosylated enzyme presented a higher secondary conformational stability when compared to its nonglycosylated counterpart, supporting experimental findings on triple glycosylation as the essential state of ARSA. The N350S mutant exhibited a consistent degree of unfolding, which may be related to its in vitro reduced stability. Finally, the obtained data are discussed in the search for structural evidences able to contribute to the understanding of biological activity of ARSA and molecular etiology of ARSA pseudodeficiency, as determined by ARSA-N350S in the absence of polyadenylation defect.
Probing the structure of Mycobacterium tuberculosis MbtA: model validation using molecular dynamics simulations and docking studies
Creators: name: Maganti, Lakshmi
name: Open Source Drug Discovery Consortium
name: Ghoshal, Nanda
Publisher: name: Taylor & Francis
Year: 2013
Subjects: Molecular Biology

description: Multidrug resistance capacity of Mycobacterium tuberculosis demands urgent need for developing new antitubercular drugs. The present work is on M. tuberculosis-MbtA, an enzyme involved in the biosynthesis of siderophores, having a critical role in bacterial growth and virulence. The molecular models of both holo and apo forms of M. tuberculosis-MbtA have been constructed and validated. A docking study with a series of 42 5′-O-[N-(salicyl) sulfamoyl] adenosine derivatives, using GOLD software, revealed significant correlation (R2 = 0.8611) between Goldscore and the reported binding affinity data. Further, binding energies of the docked poses were calculated and compared with the observed binding affinities (R2 = 0.901). All-atom molecular dynamics simulation was performed for apo form, holo form without ligand and holo form with ligands. The holo form without ligand on molecular dynamics simulation for 20 ns converged to the apo form and the apo form upon induced fit docking of the natural substrate, 2,3-dihydroxybenzoic acid-adenylate, yielded the holo structure. The molecular dynamics simulation of the holo form with ligands across the time period of 20 ns provided with the insights into ligand–receptor interactions for inhibition of the enzyme. A thorough study involving interaction energy calculation between the ligands and the active site residues of MbtA model identified the key residues implicated in ligand binding. The holo model was capable to differentiate active compounds from decoys. In the absence of experimental structure of MbtA, the homology models together with the insights gained from this study will promote the rational design of potent and selective MbtA inhibitors as antitubercular therapeutics.An animated interactive 3D complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:33
A new Eocaiman (Alligatoridae, Crocodylia) from the Itaboraí Basin, Paleogene of Rio de Janeiro, Brazil
Creators: name: Pol, Diego
name: Pinheiro, André E.P.
name: Fortier, Daniel C.
name: Diógenes A. Campos
name: Lílian P. Bergqvist
Publisher: name: Taylor & Francis
Year: 2013
Subjects: History

description: A new small species of Eocaiman is described on the basis of three anterior left mandibular rami and one isolated tooth. The specimens came from the middle-upper Paleocene Itaboraí Basin (Rio de Janeiro State, Brazil; Itaboraian South American Land Mammal Age). The new taxon differs from the other two Eocaiman species, such as its small size, likely participation of the splenial in the mandibular symphysis, a reduced angle between the longitudinal axis of the symphysis and the mandibular ramus, and enlarged ninth and tenth dentary teeth (in addition to the large first and fourth dentary teeth). The participation of the splenial in the mandibular symphysis is a unique character among caimanines (with the only possible exception being Tsoabichi greenriverensis). The new taxon provides new information on the taxonomic and anatomical diversity of the genus Eocaiman, a taxon of prime importance to understand the evolutionary origins of caimans given its position as the basalmost member of Caimaninae. Furthermore, the new taxon has a relatively small body size in comparison with other species of Eocaiman, a case paralleled by other Itaboraian reptilian groups (e.g. snakes), suggesting that this ecosystem provides critical data to test the relationship between reptilian body size and climate. http://zoobank.org/83636F22-D121-4A77-9141-BE68987B6CBF
Effects of glycosylation and pH conditions in the dynamics of human arylsulfatase A
Creators: name: Madza Yasodara Farias Virgens
name: Laercio Pol-Fachin
name: Verli, Hugo
name: Saraiva-Pereira, Maria Luiza
Publisher: name: Taylor & Francis
Year: 2013
Subjects: Molecular Biology

description: Arylsulfatase A (ARSA) is a lysosomal sulfatase that catalyzes the hydrolysis of cerebroside sulfate. Its deficiency results in Metachromatic Leukodystrophy, whereas a minor condition called ARSA pseudodeficiency occurs in healthy individuals, which has been associated with the substitution of the glycosylated Asn350 by a Ser and with the loss of the polyadenylation signal. In this work, we have investigated ARSA dynamics employing molecular dynamics simulations in response to (1) different pH’s, as, beyond its natural lysossomal environment, it has been recently identified in cytoplasmatic medium and (2) glycan occupancies, including its normal glycosylation state, presenting three high mannose-type oligosaccharides. Accordingly, four systems were studied considering ARSA under different conditions: (1) nonglycosylated at pH ∼ 7 (ARSApH7); (2) non-glycosylated at pH ∼ 5 (ARSApH5); (3) triple glycosylated at pH ∼ 5 (ARSAglyc,pH5); and (4) ARSA-N350S mutant at pH ∼ 5 (ARSAN350S,pH5). Lowering pH and increasing glycosylation was found to reduce the flexibility of the enzyme. In addition, at acidic pH, the glycosylated enzyme presented a higher secondary conformational stability when compared to its nonglycosylated counterpart, supporting experimental findings on triple glycosylation as the essential state of ARSA. The N350S mutant exhibited a consistent degree of unfolding, which may be related to its in vitro reduced stability. Finally, the obtained data are discussed in the search for structural evidences able to contribute to the understanding of biological activity of ARSA and molecular etiology of ARSA pseudodeficiency, as determined by ARSA-N350S in the absence of polyadenylation defect.
Butterflies (Lepidoptera: Papilionoidea) of Mount Kilimanjaro: introduction and family Papilionidae
Creators: name: Liseki, Steven D.
name: Vane-Wright, Richard I.
Publisher: name: Taylor & Francis
Year: 2011
Subjects: History

description: This article marks the beginning of a short series on the butterfly fauna of Mount Kilimanjaro. It commences with a brief overview of the topography, tectonic history, climate, ecological zonation and conservation significance of Africa's highest mountain. Following an introductory account to the butterfly fauna, the rest of this paper presents an annotated checklist of the swallowtails (Papilionidae). Eight papilionid species are currently believed to occur within the main forest zone, from 1800 to 2800 m (in places this zone extends down to c.1600 m). Another 10 have been recorded from the lower slopes, which include some disturbed forest and forest relicts, from 700–1800 m. The need for better data is discussed in light of the suggestion that the butterflies of Mount Kilimanjaro could become a focal group for monitoring effects of climate change. An identification key to families, together with a key to the swallowtail species and colour illustrations of adults, are included as online Supplementary Information.
Faunal nestedness and species–area relationship for small non-volant mammals in “sky islands” of northern Venezuela
Creators: name: Anderson, Robert P.
name: Eliécer E. Gutiérrez
name: Ochoa-G., José
name: Franger J. García
name: Aguilera, Marisol
Publisher: name: Taylor & Francis
Year: 2012
Subjects: Environmental Science

description: We study the biogeography of small non-volant mammals in mesic montane sky islands of northern Venezuela. Fieldwork, examination of museum specimens, and critical use of literature yielded species lists for the Cordillera de Mérida, Cordillera de la Costa, Serranía de San Luis, and Cerro Santa Ana. Fieldwork confirmed the species known from Cerro Santa Ana and added 12 species for the Serranía de San Luis. Richness decreases with smaller area. Furthermore, the faunas are highly nested, with taxa dropping out at successive depressions. Species deviating from nestedness provide a signal indicative of in situ speciation in rodents but not in marsupials.
Patterns of species richness and biogeographic regionalization of the avifaunas of the seasonally dry tropical forest in Mesoamerica
Creators: name: Ríos-Muñoz, César A.
name: Navarro-Sigüenza, Adolfo G.
Publisher: name: Taylor & Francis
Year: 2012
Subjects: Environmental Science

description: Biogeographic patterns of avifaunas associated with seasonally dry tropical forests in Mesoamerica are poorly understood despite their high levels of species richness and endemism. Through the parsimony analysis of endemicity, we analyzed biogeographic relationships of 650 resident species of birds associated with seasonally dry tropical forests from Mexico to Panama, based on potential distributions obtained through ecological niche modeling. Results show two general avifaunal groups, east and west of the Isthmus of Tehuantepec. Patterns of biogeographic distribution and species richness also helped illuminate the importance of key areas for birds associated to this habitat in the region. Los patrones biogeográficos de las avifaunas asociadas a los bosques tropicales estacionalmente secos en Mesoamérica están pobremente entendidos, a pesar de que estas áreas poseen una gran riqueza de especies y endemismo. Analizamos las relaciones biogeográficas con base en distribuciones potenciales, hechas a partir de modelos del nicho ecológico usando el análisis de parsimonia de endemismos, de 650 especies de aves residentes asociadas a los bosques tropicales estacionalmente secos desde México hasta Panamá. Los resultados muestran dos grupos generales de la avifauna, al este y oeste del Istmo de Tehuantepec. El contexto biogeográfico y la riqueza de especies resalta también la importancia de áreas clave para las aves asociadas a este tipo de hábitat en la región.
Probing the structure of Mycobacterium tuberculosis MbtA: model validation using molecular dynamics simulations and docking studies
Creators: name: Maganti, Lakshmi
name: Open Source Drug Discovery Consortium
name: Ghoshal, Nanda
Publisher: name: Taylor & Francis
Year: 2013
Subjects: Molecular Biology

description: Multidrug resistance capacity of Mycobacterium tuberculosis demands urgent need for developing new antitubercular drugs. The present work is on M. tuberculosis-MbtA, an enzyme involved in the biosynthesis of siderophores, having a critical role in bacterial growth and virulence. The molecular models of both holo and apo forms of M. tuberculosis-MbtA have been constructed and validated. A docking study with a series of 42 5′-O-[N-(salicyl) sulfamoyl] adenosine derivatives, using GOLD software, revealed significant correlation (R2 = 0.8611) between Goldscore and the reported binding affinity data. Further, binding energies of the docked poses were calculated and compared with the observed binding affinities (R2 = 0.901). All-atom molecular dynamics simulation was performed for apo form, holo form without ligand and holo form with ligands. The holo form without ligand on molecular dynamics simulation for 20 ns converged to the apo form and the apo form upon induced fit docking of the natural substrate, 2,3-dihydroxybenzoic acid-adenylate, yielded the holo structure. The molecular dynamics simulation of the holo form with ligands across the time period of 20 ns provided with the insights into ligand–receptor interactions for inhibition of the enzyme. A thorough study involving interaction energy calculation between the ligands and the active site residues of MbtA model identified the key residues implicated in ligand binding. The holo model was capable to differentiate active compounds from decoys. In the absence of experimental structure of MbtA, the homology models together with the insights gained from this study will promote the rational design of potent and selective MbtA inhibitors as antitubercular therapeutics. An animated interactive 3D complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:33
Occurrence of selected perfluorinated alkyl acids in lunch meals served at school canteens in Italy and their relevance for children’s intake
Creators: name: Dellatte, Elena
name: Brambilla, Gianfranco
name: Filippis, Stefania Paola De
name: Domenico, Alessandro Di
name: Pulkrabova, Jana
name: Eschauzier, Christian
name: Klenow, Stefanie
name: Heinemeyer, Gerhard
name: Voogt, Pim De
Publisher: name: Taylor & Francis
Year: 2013
Subjects: subject: Microbiology
subject: FOS: Biological sciences

description: Ready-to-eat servings may be more contaminated with perfluorinated alkyl acids (PFAAs) than the corresponding unprocessed foods due to the presence of PFAAs in and transfer from food contact materials (FCM) and cookware. Therefore, the presence of selected PFAAs in meals served weekly at lunch time in six Italian school canteens was assessed. Five towns were selected representing different areas with local water and food supply. Daily lunch menus were sampled and pooled to form a composite. Analyses were carried out on the weekly composite from each canteen. UPLC-MS/MS quantification limits were in the 6.0–12 pg g–1 range for the selected PFAAs (PFHxA, PFOA, PFNA, PFDA, PFUnDA, PFHxS, branched and non-branched PFOS). Non-branched PFOS was quantified in four out of six composites, with levels ranging from 14 to 25 pg g–1, while PFOA and PFDA were determined in two out of six in the range 6.5–8.2 pg g–1. Theoretical estimates and analytical results in the same order of magnitude indicate a negligible contribution from food processing and serving to meal contamination. When composite analytical data are transposed into dietary estimates, it is shown that Italian school-age children have intakes in the range of 0.3–1.1 and 0.5–1.4 ng kg–1 bw day–1 for PFOA and PFOS respectively, well below the corresponding tolerable daily intakes (TDIs).
Acrylamide concentrations in potato crisps in Europe from 2002 to 2011
Creators: name: Powers, Stephen J.
name: Mottram, Donald S.
name: Curtis, Andrew
name: Halford, Nigel G.
Publisher: name: Taylor & Francis
Year: 2013
Subjects: subject: Microbiology
subject: FOS: Biological sciences

description: A dataset of manufacturers’ measurements of acrylamide levels in 40,455 samples of fresh sliced potato crisps from 20 European countries for years 2002 to 2011 was compiled. This dataset is by far the largest ever compiled relating to acrylamide levels in potato crisps. Analysis of variance was applied to the data and showed a clear, significant downward trend for mean levels of acrylamide, from 763 ± 91.1 ng g−1 (parts per billion) in 2002 to 358 ± 2.5 ng g−1 in 2011; this was a decrease of 53% ± 13.5%. The yearly 95th quantile values were also subject to a clear downward trend. The effect of seasonality arising from the influence of potato storage on acrylamide levels was evident, with acrylamide in the first 6 months of the year being significantly higher than in the second 6 months. The proportion of samples containing acrylamide at a level above the indicative value of 1000 ng g−1 for potato crisps introduced by the European Commission in 2011 fell from 23.8% in 2002 to 3.2% in 2011. Nevertheless, even in 2011, a small proportion of samples still contained high levels of acrylamide, with 0.2% exceeding 2000 ng g−1.
Mycotoxins in corn and wheat silage in Israel
Creators: name: J.A. Shimshoni
name: O. Cuneah
name: M. Sulyok
name: R. Krska
name: N. Galon
name: B. Sharir
name: A. Shlosberg
Publisher: name: Taylor & Francis
Year: 2013
Subjects: subject: Microbiology
subject: FOS: Biological sciences

description: Silage is an important feed source for intensive dairy herds worldwide. Fungal growth and mycotoxin production before and during silage storage is a well-known phenomenon, resulting in reduced nutritional value and a possible risk factor for animal health. With this in mind, a survey was conducted to determine for the first time the occurrence of mycotoxins in corn and wheat silage in Israel. A total of 30 corn and wheat silage samples were collected from many sources and analysed using a multi-mycotoxin method based on LC-MS/MS. Most mycotoxins recorded in the present study have not been reported before in Israel. Overall, 23 mycotoxins were found in corn silage; while wheat silage showed a similar pattern of mycotoxin occurrence comprising 20 mycotoxins. The most common post-harvest mycotoxins produced by the Penicillium roqueforti complex were not found in any tested samples, indicative of high-quality preparation and use of silage. Moreover, none of the European Union-regulated mycotoxins – aflatoxin B1, ochratoxin, T-2 toxin, diacetoxyscirpenol and deoxynivalenol – were found above their limits of detection (LODs). The Alternaria mycotoxins – macrosporin, tentoxin and alternariol methyl ether – were highly prevalent in both corn and wheat silage (>80%), but at low concentrations. The most prominent (>80%) Fusarium mycotoxins in corn silage were fusaric acid, fumonisins, beauvericin, monilifomin, equisetin, zearalenone and enniatins, whereas in wheat silage only beauvericin, zearalenone and enniatins occurred in more than 80% of the samples. The high prevalence and concentration of fusaric acid (mean = 765 µg kg–1) in Israeli corn silage indicates that this may be the toxin of highest potential concern to dairy cow performance. However, more data from different harvest years and seasons are needed in order to establish a more precise evaluation of the mycotoxin burden in Israeli silage.
The intrinsic stability of the human prion β-sheet region investigated by molecular dynamics
Creators: name: Simone, Alfonso De
name: Stanzione, Francesca
name: Marasco, Daniela
name: Vitagliano, Luigi
name: Esposito, Luciana
Publisher: name: Taylor & Francis
Year: 2013
Subjects: Molecular Biology

description: Human prion diseases are neurodegenerative disorders associated to the misfolding of the prion protein (PrP). Common features of prion disorders are the fibrillar amyloid deposits and the formation of prefibrillar oligomeric species also suggested as the origin of cytotoxicity associated with diseases. Although the process of PrP misfolding has been extensively investigated, many crucial aspects of this process remain unclear. We have here carried out a molecular dynamics study to evaluate the intrinsic dynamics of PrP β-sheet, a region that is believed to play a crucial role in prion aggregation. Moreover, as this region mediates protein association in dimeric assemblies frequently observed in prion crystallographic investigations, we also analyzed the dynamics of these intermolecular interactions. The extensive sampling of replica exchange shows that the native antiparallel β-structure of the prion is endowed with a remarkable stability. Therefore, upon unfolding, the persistence of a structured β-region may seed molecular association and influence the subsequent phases of the aggregation process. The analysis of the four-stranded β-sheet detected in the dimeric assemblies of PrP shows a tendency of this region to form dynamical structured states. The impact on the β-sheet structure and dynamics of disease associated point mutations has also been evaluated.
Structural dynamics of V3 loop with different electrostatics: implications on co-receptor recognition: a molecular dynamics study of HIV gp120
Creators: name: Balasubramanian Chandramouli
name: Chillemi, Giovanni
name: Giombini, Emanuela
name: Capobianchi, Maria R.
name: Rozera, Gabriella
name: Desideri, Alessandro
Publisher: name: Taylor & Francis
Year: 2013
Subjects: Molecular Biology

description: The HIV’s envelope glycoprotein gp120 plays a major role in the entry of the virus into the host cell, through its successive interactions with the cell surface CD4 receptor and a co-receptor (CCR5 or CXCR4). The choice of a specific co-receptor by gp120 has an important consequence on HIV infection and pathogenesis. The third variable region within gp120, the V3 loop, is the principal determinant of the co-receptor usage by gp120. Here, we report the long time molecular dynamics simulations of four gp120 structures, having a V3 loop charge of +3 and +5, from both R5 and X4 specific strains of HIV. The results of the study highlight the properties of the V3 loop that can be critical for dictating the co-receptor recognition and selection in structural context. In detail, we observe that the structural orientation of the V3 loop in the 3D space is modulated by its net charge, whilst its co-receptor choice is likely dictated by a combined effect of both the electrostatics of the loop and its conformational variability at the level of its central crown region.
Assessment of new cationic porphyrin binding to plasma proteins by planar microarray and spectroscopic methods
Creators: name: Gyulkhandanyan, Aram
name: Gyulkhandanyan, Lusine
name: Ghazaryan, Robert
name: Fleury, Fabrice
name: Angelini, Marie
name: Gyulkhandanyan, Grigor
name: Vehary Sakanyan
Publisher: name: Taylor & Francis
Year: 2013
Subjects: Molecular Biology

description: Porphyrins have a unique aromatic structure determining particular photochemical properties that make them promising photosensitizers for anticancer therapy. Previously, we synthesized a set of artificial porphyrins by modifying side-chain functional groups and introducing different metals into the core structure. Here, we have performed a comparative study of the binding properties of 29 cationic porphyrins with plasma proteins by using microarray and spectroscopic approaches. The porphyrins were noncovalently immobilized onto hydrogel-covered glass slides and probed to bio-conjugated human and bovine serum albumins, as well as to human hemoglobin. The signal detection was carried out at the near-infrared fluorescence wavelength (800 nm) that enabled the effect of intrinsic visible wavelength fluorescence emitted by the porphyrins tested to be discarded. Competition assays on porphyrin microarrays indicated that long-chain fatty acids (FAs) (palmitic and stearic acids) decrease porphyrin binding to both serum albumin and hemoglobin. The binding affinity of different types of cationic porphyrins for plasma proteins was quantitatively assessed in the absence and presence of FAs by fluorescent and absorption spectroscopy. Molecular docking analysis confirmed results that new porphyrins and long-chain FAs compete for the common binding site FA1 in human serum albumin and meso-substituted functional groups in porphyrins play major role in the modulation of conformational rearrangements of the protein.
Efficient estimation of MMGBSA-based BEs for DNA and aromatic furan amidino derivatives
Creators: name: Srivastava, Hemant Kumar
name: G. Narahari Sastry
Publisher: name: Taylor & Francis
Year: 2013
Subjects: Molecular Biology

description: Molecular mechanics with Generalized Born surface area (MMGBSA) based binding energies (BEs) derived from the molecular dynamics (MD) trajectories are highly reliable and extensively used standards to estimate the strength of interactions between ligands and their receptor. MD simulations (5 ns) for 30 aromatic furan aminidino derivatives (anti-Pneumocystis carnii agents) have been carried out by using Amber program and BEs have been calculated by using Generalized Born (GB) method. Based on the generated data, we present a simple and effective method for the approximation of BEs without performing MD simulations and MMGBSA calculations. Quantum chemical (density functional theory based) and geometrical descriptors are used for the prediction of the BE values. All the developed models are statistically significant with high values of correlation and cross-validation coefficients. The prediction ability and effectiveness of the models are tested by the division of the data-set into four different training and test sets and the average error was only 4–7% (1.56–2.61 kcal/mol) of the actual BEs.
Disorderness in Escherichia coli proteome: perception of folding fidelity and protein–protein interactions
Creators: name: Bratati Kahali
name: Ghosh, Tapash Chandra
Publisher: name: Taylor & Francis
Year: 2013
Subjects: Molecular Biology

description: Traditionally biased usage of synonymous codons renders selective advantage to proteins expressed at high levels with a few exceptions like in Escherichia coli. Proteome-wide characteristics indicative of trends in highly expressed proteins of E. coli is analyzed in this communication. Implications for the nature of interactions performed by these two groups of highly expressed proteins are discussed here. The group of highly expressed proteins having optimized codon usage through employment of most abundant tRNAs is already shielded from misfolding by their improved error-prone translational machinery. Our data also provide evidence for mechanism by which a significant proportion of highly expressed proteins with high intrinsic disorder evade degradation and successfully carry out their function.
The role of salt concentration and magnesium binding in HIV-1 subtype-A and subtype-B kissing loop monomer structures
Creators: name: Taejin Kim
name: Shapiro, Bruce A.
Publisher: name: Taylor & Francis
Year: 2013
Subjects: Molecular Biology

description: The subtype-B monomers of the human immunodeficiency virus type-1 (HIV-1) have experimentally been shown to dimerize at high salt concentration or in the presence of magnesium, while the dimerization of the subtype-A monomers requires magnesium binding at the G273 or G274 phosphate groups regardless of salt concentration. We used explicit solvent molecular dynamics (MD) simulations to investigate the conformational changes in subtype-A and -B monomers in different salt concentrations, and we found that our MD simulation results are consistent with those of experiments. At low salt concentration, hairpin loop structures of both subtypes were deformed and bases in the hairpin loop were turned inside. At high salt concentrations, the subtype-B monomer maintained the hairpin loop shape and most bases in the hairpin loop pointed out, while the subtype-A monomer showed a severe deformation. We also found that the flanking bases in the subtype-B stabilize the hairpin loop, while the flanking base G273 in the subtype-A caused a significant deformation. However, a bound magnesium ion at the G273 or G274 phosphate groups controlled the behavior of the G273 base and prevented the subtype-A monomer from deformation. We also applied restraints to both subtypes to examine the role of high salt concentration or magnesium binding. While restraints were applied, both subtypes at 0 M salt concentration maintained their shapes. However, when restraints were removed, they deformed significantly. Therefore, we suggest that the dimerization of both subtypes requires the proper conformation of the monomers which is induced by the appropriate salt strength and magnesium ion binding.
The influence of biofilm structure and total interaction energy on Escherichia coli retention by Pseudomonas aeruginosa biofilm
Creators: name: Mau-Yi Wu
name: Varunraj Sendamangalam
name: Xue, Zheng
name: Youngwoo Seo
Publisher: name: Taylor & Francis
Year: 2012
Subjects: Marine Biology

description: The retention of a surrogate pathogenic bacterium, Escherichia coliT, in Pseudomonas aeruginosa biofilms (with various EPS excreting capacities) was investigated using a laboratory flow cell system. The structural characteristics of the biofilm, as well as the quantity of E. coliT retained in the biofilm, were assessed using confocal laser scanning microscopy coupled with image analysis. In addition, the total interaction energy between E. coliT and the P. aeruginosa biofilm was computed with the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, which provided an additional context to explain the pathogen interaction in aquatic biofilms. The correlations between the quantity of detained E. coliT cells and the structural characteristics of the biofilm were analysed and the results indicated that the heterogeneity of the biofilm could create a quiescent zone leading to temporary retention of E. coliT within the biofilm. Overall, this study provided insights toward understanding the retention of pathogenic bacteria in environmental biofilms.
Molecular and morphological evidence of the occurrence of the Norwegian skate Dipturus nidarosiensis (Storm, 1881) in the Mediterranean Sea
Creators: name: Cannas, Rita
name: Follesa, Maria Cristina
name: Cabiddu, Serenella
name: Porcu, Cristina
name: Salvadori, Susanna
name: Iglésias, Samuel Paco
name: Deiana, Anna Maria
name: Cau, Angelo
Publisher: name: Taylor & Francis
Year: 2010
Subjects: Marine Biology

description: Fourteen specimens of the Norwegian skate, Dipturus nidarosiensis (Rajiformes, Rajidae), were caught off the Sardinian coasts (Central Western Mediterranean Sea) in 2005–2008 between 600 and 1420 m of depth. Their identification has been confirmed by the sequencing of three regions of the mtDNA (16SrDNA, control region and cytochrome c oxidase subunit 1) and comparison of the obtained sequences with that of three species of Dipturus (D. batis, D. oxyrinchus and D. nidarosiensis) from the Mediterranean Sea and the adjacent North-eastern Atlantic Ocean. A simple PCR-RFLP assay has been developed for an easy, reliable and robust identification of these skate species. A morphological comparison of the Norwegian skate with congeneric species is given in order to help future identifications. This is the first record of D. nidarosiensis in the Mediterranean Sea; the possibility of recent or ancient but unnoticed occurrence of the Norwegian skate in the region is discussed.
Permian palynofloral changes in Uruguay and their relationships with lithostratigraphic units
Creators: name: Beri, Ángeles
name: Martínez-Blanco, Ximena
name: Tejera, Leticia
Publisher: name: Taylor & Francis
Year: 2013
Subjects: History

description: A total of 77 samples from Permian strata of Uruguay were extracted from eight boreholes drilled by Dirección Nacional de Minería y Geología of Uruguay, as well as from two outcrops located in El Barón Creek (1 sample) and on Route 26, east of Melo City (1 sample). These samples correspond to the San Gregorio-Cerro Pelado, Tres Islas, Fraile Muerto, Mangrullo and Paso Aguiar Formations from the early Cisuralian to approximately the early Guadalupian. To quantify change in palynological assemblages, 188 species of sporomorphs were identified and binned by geological formations. Extinction and originations were calculated between formations. There was no qualitative change in species composition in the San Gregorio-Cerro Pelado, Tres Islas and Fraile Muerto Formations. A turnover in sporomorph species assemblage was observed between the Fraile Muerto and the Mangrullo Formation, which coincides temporally with the onset of an arid climatic phase for the region. Plant assemblages were analysed taking into account that the botanical affinities of the sporomorphs show no significant change through the sampled time interval.