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Sample records for molecular aspects integrative

  1. The molecular aspects of chordoma.

    PubMed

    Gulluoglu, Sukru; Turksoy, Ozlem; Kuskucu, Aysegul; Ture, Ugur; Bayrak, Omer Faruk

    2016-04-01

    Chordomas are one of the rarest bone tumors, and they originate from remnants of embryonic notochord along the spine, more frequently at the skull base and sacrum. Although they are relatively slow growing and low grade, chordomas are highly recurrent, aggressive, locally invasive, and prone to metastasize to the lungs, bone, and the liver. Chordomas highly and generally show a dual epithelial-mesenchymal differentiation. These tumors resist chemotherapy and radiotherapy; therefore, radical surgery and high-dose radiation are the most used treatments, although there is no standard way to treat the disease. The molecular biology process behind the initiation and progression of a chordoma needs to be revealed for a better understanding of the disease and to develop more effective therapies. Efforts to discover the mysteries of these molecular aspects have delineated several molecular and genetic alterations in this tumor. Here, we review and describe the emerging insights into the molecular landscape of chordomas.

  2. Educational aspects of molecular simulation

    NASA Astrophysics Data System (ADS)

    Allen, Michael P.

    This article addresses some aspects of teaching simulation methods to undergraduates and graduate students. Simulation is increasingly a cross-disciplinary activity, which means that the students who need to learn about simulation methods may have widely differing backgrounds. Also, they may have a wide range of views on what constitutes an interesting application of simulation methods. Almost always, a successful simulation course includes an element of practical, hands-on activity: a balance always needs to be struck between treating the simulation software as a 'black box', and becoming bogged down in programming issues. With notebook computers becoming widely available, students often wish to take away the programs to run themselves, and access to raw computer power is not the limiting factor that it once was; on the other hand, the software should be portable and, if possible, free. Examples will be drawn from the author's experience in three different contexts. (1) An annual simulation summer school for graduate students, run by the UK CCP5 organization, in which practical sessions are combined with an intensive programme of lectures describing the methodology. (2) A molecular modelling module, given as part of a doctoral training centre in the Life Sciences at Warwick, for students who might not have a first degree in the physical sciences. (3) An undergraduate module in Physics at Warwick, also taken by students from other disciplines, teaching high performance computing, visualization, and scripting in the context of a physical application such as Monte Carlo simulation.

  3. Papillomaviruses: Molecular and clinical aspects

    SciTech Connect

    Howley, P.M.; Broker, T.R.

    1985-01-01

    This book contains nine sections, each consisting of several papers. The section headings are : Papillomaviruses and Human Genital Tract Diseases;Papillomaviruses and Human Cutaneous Diseases, Papillomaviruses and Human Oral and Laryngeal Diseases;Therapeutic Approaches to Papillomavirus Infections;Animal Papillomaviruses;Molecular Biology;Transcription, Replication, and Genome Organization;Epithelial Cell Culture;Papillomavirus Transformation;and Viral Vectors.

  4. Molecular aspects of charm physics

    SciTech Connect

    Fernandez, F.; Ortega, P. G.; Entem, D. R.

    2013-03-25

    We study the influence of possible molecular structures in the charmonium spectrum. We focus on the 0{sup ++}, 1{sup ++} and 1{sup --} sectors. In the first one we coupled the 2{sup 3}P{sub 0}cc pair with DD, J/{psi}{omega}, D{sub s}D{sub s} and J/{psi}{phi} channels and we obtain two states compatibles with the X(3945) and the Y(3940). In the second one we couple the 2{sup 3}P{sub 1}cc state with the DD{sup *} channel and we obtain a dressed state compatible with the X(3940) and a new state that we assign to the X(3872). In the third one we include the 3{sup 3}S{sub 1} and 2{sup 3}D{sub 1} charmonium states coupled to DD, DD{sup *}, D{sup *}D{sup *}, D{sub s}D{sub s}, D{sub s}D{sup *}s and D{sup *}{sub s}D{sup *}{sub s}. In this calculation we obtain a new molecular state that could be the G(3900) or the controversial Y(4008) and two cc states dressed by the molecular components assigned to the {psi}(4040) and the {psi}(4160). Finally we perform a calculation in the five quark sector where we can describe the {Lambda}{sub c}(2940){sup +} as a ND{sup *} molecular state and predict a {Lambda}{sub b}(6248){sup +} state.

  5. Molecular aspects of multiple myeloma.

    PubMed

    Kastrinakis, N G; Gorgoulis, V G; Foukas, P G; Dimopoulos, M A; Kittas, C

    2000-10-01

    Multiple myeloma (MM) is a B-cell neoplasm characterized by bone marrow infiltration with malignant plasma cells, which synthesize and secrete monoclonal immunoglobulin (Ig) fragments. Despite the considerable progress in the understanding of MM biology, the molecular basis of the disease remains elusive. The initial transformation is thought to occur in a postgerminal center B-lineage cell, carrying a somatically hypermutated Ig heavy chain (IGH) gene. This plasmablastic precursor cell colonizes the bone marrow, propagates clonally and differentiates into a slowly proliferating myeloma cell population, all under the influence of specific cell adhesion molecules and cytokines. Production of interleukin-6 by stromal cells, osteoblasts and, in some cases, neoplastic cells is an essential element of myeloma cell growth, with the cytokine stimulus being delivered intracellularly via the Jack-STAT and ras signaling pathways. While karyotypic changes have been identified in up to 50% of MM patients, recent molecular cytogenetic techniques have revealed chromosomal abnormalities in the vast majority of examined cases. Translocations mostly involve illegal switch rearrangements of the IGH locus with various partner genes (CCND1, FGFR3, c-maf). Such events have been assigned a critical role in MM development. Mutations in coding and regulatory regions, as well as aberrant expression patterns of several oncogenes (c-myc, ras) and tumor suppressor genes (p16, p15) have been reported. Key regulators of programmed cell death (BCL-2, Fas), tumor expansion (metalloproteinases) and drug responsiveness (topoisomerase II alpha) have also been implicated in the pathogenesis of this hematologic malignancy. A tumorigenic role for human herpesvirus 8 (HHV8) was postulated recently, following the detection of viral sequences in bone marrow dendritic cells of MM patients. However, since several research groups were unable to confirm this observation, the role of HHV8 remains unclear

  6. [Molecular aspects of renal desease].

    PubMed

    Nichik, T E; Lin'kova, N S; Kraskovskaia, N A; Dudkov, A V; Khavinson, V Kh

    2014-01-01

    The review considers molecular mechanisms of chronic renal failure and cancer kidney disease. The most important molecules inducing inflammation are cytokines (MCP-1, TNFalpha, IFN-gamma, IL-1,6,8,18), matrix metalloproteinases MMP-2,3,9,14, tissue inhibitors of metalloproteinases (TIMPs) and grow factors (VEGF PDGE FGF). This signal molecules regulate the activity of immune cells and remodeling extracellular matrix (ECM) components taken place in inflammatory reactions, proliferation, apoptosis and also in the differentiation of kidney cells. On the basis of these data nowadays developed new highly selective approaches to diagnosis, prediction, estimation of efficiency of treatment of renal disease and creating of target drugs. PMID:25707263

  7. Progressive multifocal leukoencephalopathy: Clinical and molecular aspects

    PubMed Central

    Tavazzi, Eleonora; White, Martyn K.; Khalili, Kamel

    2011-01-01

    The fatal CNS demyelinating disease, progressive multifocal leukoencephalopathy (PML), is rare and appears to occur almost always as a consequence of immune dysfunction. Thus it is associated with HIV/AIDS and also as a side-effect of certain immunomodulatory monoclonal antibody therapies. In contrast to the rarity of PML, the etiological agent of the disease, the polyomavirus JC (JCV) is widespread in populations worldwide. In the forty years since JCV was first isolated, much has been learned about the virus and the disease from laboratory and clinical observations. However, there are many aspects of the viral life cycle and the pathogenesis of the disease that still remain unclear and our understanding is constantly evolving. In this review, we will discuss our current understanding of the clinical features of PML and molecular characteristics of JCV and how they relate to each other. Clinical observations can inform molecular studies of the virus and likewise molecular findings concerning the life cycle of the virus can guide the development of novel therapeutic strategies. PMID:21936015

  8. [Migrant workers. The critical aspects of integration].

    PubMed

    Berra, Alessandro

    2011-01-01

    The integration of migrant poplulations with the indigeneous population is regulated by the Italian Decree, D.Lgs 9/7/2003 n. 215 in enforcement of the directive 2000/43/EC implementing the principle of equal treatment between persons irrespective of racial or ethnic origin. The Italian decree, D.Lgs 215/2003, at present in force, according to regulation stipulated as to the equal treatment of diverse cohabiting populations, explicitly forbids any form of discrimination whatsoever, be it direct or indirect. A first description of today's migrant panorama is offered by the Caritas Migrantes and the CNEL (Italian National Council of the Economy of Labour). The most critical aspects on the integration of migrants are described and discussed in the text.

  9. Ricin Toxicity: Clinical and Molecular Aspects

    PubMed Central

    Moshiri, Mohammad; Hamid, Fatemeh; Etemad, Leila

    2016-01-01

    Seeds of the castor bean plant Ricinuscommunis L (CB) contain ricin toxin (RT), one of the most poisonous naturally-occurring substances known. Ricin toxin, a water-soluble glycoprotein that does not partition into the oil extract, is a ribosome-inactivating toxin composed of two chains, labeled A and B. Severity of the toxicity varies depending on the route of exposure to the toxin. Inhalational is the most toxic route, followed by oral ingestion. Orally-ingested RT accumulates in the liver and spleen but other cells are also affected. The main clinical manifestations are also related to the administration route. Oral ingestion of CB or RT results in abdominal pain, vomiting, diarrhea, and various types of gastrointestinal bleeding that leading to volume depletion, hypovolemic shock, and renal failure. Inhalation of the toxin presents with non-cardiogenic pulmonary edema, diffuse necrotizing pneumonia, interstitial and alveolar inflammation, and edema. Local injection of RT induces indurations at the injection site, swelling of regional lymph nodes, hypotension, and death. An enzyme-linked immunosorbent assay (ELISA) has been developed to detect RT in animal tissues and fluids. Ricinine, an alkaloid of CB, can be detected in rat urine within 48 h of RT exposure. Supportive care is the basic treatment and standard biowarfare decontamination protocols are used for RT intoxication. Dexamethasone and difluoromethylornithine might be effective treatments. This review examines the clinical and molecular aspects of ricin toxicity. PMID:27536698

  10. Ricin Toxicity: Clinical and Molecular Aspects.

    PubMed

    Moshiri, Mohammad; Hamid, Fatemeh; Etemad, Leila

    2016-04-01

    Seeds of the castor bean plant Ricinuscommunis L (CB) contain ricin toxin (RT), one of the most poisonous naturally-occurring substances known. Ricin toxin, a water-soluble glycoprotein that does not partition into the oil extract, is a ribosome-inactivating toxin composed of two chains, labeled A and B. Severity of the toxicity varies depending on the route of exposure to the toxin. Inhalational is the most toxic route, followed by oral ingestion. Orally-ingested RT accumulates in the liver and spleen but other cells are also affected. The main clinical manifestations are also related to the administration route. Oral ingestion of CB or RT results in abdominal pain, vomiting, diarrhea, and various types of gastrointestinal bleeding that leading to volume depletion, hypovolemic shock, and renal failure. Inhalation of the toxin presents with non-cardiogenic pulmonary edema, diffuse necrotizing pneumonia, interstitial and alveolar inflammation, and edema. Local injection of RT induces indurations at the injection site, swelling of regional lymph nodes, hypotension, and death. An enzyme-linked immunosorbent assay (ELISA) has been developed to detect RT in animal tissues and fluids. Ricinine, an alkaloid of CB, can be detected in rat urine within 48 h of RT exposure. Supportive care is the basic treatment and standard biowarfare decontamination protocols are used for RT intoxication. Dexamethasone and difluoromethylornithine might be effective treatments. This review examines the clinical and molecular aspects of ricin toxicity. PMID:27536698

  11. Molecular and cellular aspects of rhabdovirus entry.

    PubMed

    Albertini, Aurélie A V; Baquero, Eduard; Ferlin, Anna; Gaudin, Yves

    2012-01-01

    Rhabdoviruses enter the cell via the endocytic pathway and subsequently fuse with a cellular membrane within the acidic environment of the endosome. Both receptor recognition and membrane fusion are mediated by a single transmembrane viral glycoprotein (G). Fusion is triggered via a low-pH induced structural rearrangement. G is an atypical fusion protein as there is a pH-dependent equilibrium between its pre- and post-fusion conformations. The elucidation of the atomic structures of these two conformations for the vesicular stomatitis virus (VSV) G has revealed that it is different from the previously characterized class I and class II fusion proteins. In this review, the pre- and post-fusion VSV G structures are presented in detail demonstrating that G combines the features of the class I and class II fusion proteins. In addition to these similarities, these G structures also reveal some particularities that expand our understanding of the working of fusion machineries. Combined with data from recent studies that revealed the cellular aspects of the initial stages of rhabdovirus infection, all these data give an integrated view of the entry pathway of rhabdoviruses into their host cell.

  12. Molecular and Cellular Aspects of Rhabdovirus Entry

    PubMed Central

    Albertini, Aurélie A. V.; Baquero, Eduard; Ferlin, Anna; Gaudin, Yves

    2012-01-01

    Rhabdoviruses enter the cell via the endocytic pathway and subsequently fuse with a cellular membrane within the acidic environment of the endosome. Both receptor recognition and membrane fusion are mediated by a single transmembrane viral glycoprotein (G). Fusion is triggered via a low-pH induced structural rearrangement. G is an atypical fusion protein as there is a pH-dependent equilibrium between its pre- and post-fusion conformations. The elucidation of the atomic structures of these two conformations for the vesicular stomatitis virus (VSV) G has revealed that it is different from the previously characterized class I and class II fusion proteins. In this review, the pre- and post-fusion VSV G structures are presented in detail demonstrating that G combines the features of the class I and class II fusion proteins. In addition to these similarities, these G structures also reveal some particularities that expand our understanding of the working of fusion machineries. Combined with data from recent studies that revealed the cellular aspects of the initial stages of rhabdovirus infection, all these data give an integrated view of the entry pathway of rhabdoviruses into their host cell. PMID:22355455

  13. Thermal aspects of grinding for surface integrity

    NASA Astrophysics Data System (ADS)

    Ju, Yongqing

    Thermal aspects of grinding are analyzed in detail since it is argued that temperature controls the effect of grinding on workpiece surface integrity. Transient and steady state heat partition in sliding contact is discussed in detail. This leads to a complete thermal model for heat partition and temperatures in surface grinding. Numerical predictions of the model are shown to agree with experimental results available in the literature. Effects of grinding conditions including real contact area ratio, thermal properties, feeds and speeds, and type of cut (down or up grinding) on heat partition and workpiece temperature are studied systematically. It is shown that the presence of the fluid inside the grinding zone can reduce the heat flux into the workpiece and workpiece temperature significantly. It is also found that some ratios of workpiece velocity to wheel velocity result in high temperatures and therefore should be avoided. This result provides a basis for the difference between conventional and creep-feed grinding regions. After obtaining temperature, an efficient and robust FFT approach is developed to obtain the thermal stress field induced by moving heat sources. Study of the 'hot spot' problem shows that the effect of hot spots on surface displacement and stress is small suggesting that grinding thermal stress is induced by the global temperature while local temperature controls metallurgical phase transformations. It is also shown that thermal stress is dominant on the global scale while the global scale mechanical stress is insignificant. Thus, the superior thermal properties of CBN compared to Alsb2Osb3 leads to low temperature and less deleterious residual stresses. Finally, spectral analysis is performed to evaluate contact behavior of the finished surface. This analysis shows that a good grinding process improves not only the magnitude of the surface roughness but the frequency content as well.

  14. Genetic and molecular aspects of spinocerebellar ataxias

    PubMed Central

    Honti, Viktor; Vécsei, László

    2005-01-01

    The group of spinocerebellar ataxias (SCAs) includes more than 20 subgroups based only on genetic research. The “ataxia genes” are autosomal; the “disease-alleles” are dominant, and many of them, but not all, encode a protein with an abnormally long polyglutamine domain. In DNA, this domain can be detected as an elongated CAG repeat region, which is the basis of genetic diagnostics. The polyglutamine tails often tend to aggregate and form inclusions. In some cases, protein–protein interactions are the key to understanding the disease. Protein partners of ataxia proteins include phosphatases and components of chromatin and the transcriptional machinery. To date, investigation of spinocerebellar ataxias involves population genetics, molecular methods, and studying model organisms. However, there is still no efficient therapy for patients. Here, we review the genetic and molecular data gained on spinocerebellar ataxias. PMID:18568057

  15. Molecular and clinical aspects of apoptosis.

    PubMed

    Uren, A G; Vaux, D L

    1996-01-01

    Unwanted cells are removed by physiological cell death processes that are highly conserved throughout the animal kingdom. Physiological cell death plays an important role in development, tissue homeostasis and defence against viral infection and mutation. This review describes the molecular components that implement this process, the relevance of these to a variety of human diseases, and discusses the potential for novel therapies based on our understanding of them. PMID:8981570

  16. Molecular aspects of DNA splicing system

    NASA Astrophysics Data System (ADS)

    Yusof, Yuhani; Lim, Wen Li; Goode, T. Elizabeth; Sarmin, Nor Haniza; Heng, Fong Wan; Wahab, Mohd Firdaus Abd

    2015-05-01

    The pioneer model of deoxyribonucleic acid (DNA) splicing system in a framework of Formal Language Theory was introduced by Head that led to the existence of other models of splicing system, namely Paun, Pixton and Yusof-Goode. These entire models are inspired by the molecular biological process of DNA splicing. Hence, this paper focuses on the translucent DNA splicing process, particularly on the generated language. Starting with some preliminaries in a limit graph, this paper also provides the experimental design with the predicted and actual result.

  17. Molecular and Functional Aspects of Bacterial Chemotaxis

    NASA Astrophysics Data System (ADS)

    Celani, A.; Shimizu, T. S.; Vergassola, M.

    2011-07-01

    We consider the dynamics of chemotaxis in the model bacterium Escherichia coli. We analyze both its molecular mechanisms and the functional causes governing the evolution of the observed behaviors. We review molecular models of the transduction network controlling the bacterial chemotaxis in response to chemoattractant binding to the receptors. In particular, recent progress stimulated by FRET experiments is presented for statistical physics allosteric models. The response function to a pulse of chemoattractant is expressed in terms of microscopic parameters of the allosteric models. The functional causes for the shape of the response function, as measured in experimental tethering assay, are then investigated. A hydrodynamic equation, valid for space-time scales larger than the microscopic running length and time, is derived for the position of a swimming bacterium. It is then shown how optimization over the microscopic parameters of the response function yields the curve observed experimentally. In particular, the observed property of adaptation to the background level of aspartate emerges as being produced by fluctuations in the space-time chemoattractant profiles sensed by bacteria along their trajectories. This functional cause is distinct from arguments based on the extension of the dynamical range. Future directions and experiments to probe the adaptation of E. coli chemotaxis to the environmental conditions and its response to realistic space-time chemoattractant stimuli are finally discussed.

  18. Genetic and molecular aspects of hypertension.

    PubMed

    Padmanabhan, Sandosh; Caulfield, Mark; Dominiczak, Anna F

    2015-03-13

    Until recently, significant advances in our understanding of the mechanisms of blood pressure regulation arose from studies of monogenic forms of hypertension and hypotension, which identified rare variants that primarily alter renal salt handling. Genome-wide association and exome sequencing studies over the past 6 years have resulted in an unparalleled burst of discovery in the genetics of blood pressure regulation and hypertension. More importantly, genome-wide association studies, while expanding the list of common genetic variants associated with blood pressure and hypertension, are also uncovering novel pathways of blood pressure regulation that augur a new era of novel drug development, repurposing, and stratification in the management of hypertension. In this review, we describe the current state of the art of the genetic and molecular basis of blood pressure and hypertension.

  19. [Glucotransporters: clinical, molecular and genetic aspects].

    PubMed

    Sandoval-Muñiz, Roberto de Jesús; Vargas-Guerrero, Belinda; Flores-Alvarado, Luis Javier; Gurrola-Díaz, Carmen Magdalena

    2016-01-01

    Oxidation of glucose is the major source of obtaining cell energy, this process requires glucose transport into the cell. However, cell membranes are not permeable to polar molecules such as glucose; therefore its internalization is accomplished by transporter proteins coupled to the cell membrane. In eukaryotic cells, there are two types of carriers coupled to the membrane: 1) cotransporter Na+-glucose (SGLT) where Na+ ion provides motive power for the glucose´s internalization, and 2) the glucotransporters (GLUT) act by facilitated diffusion. This review will focus on the 14 GLUT so far described. Despite the structural homology of GLUT, different genetic alterations of each GLUT cause specific clinical entities. Therefore, the aim of this review is to gather the molecular and biochemical available information of each GLUT as well as the particular syndromes and pathologies related with GLUT´s alterations and their clinical approaches. PMID:27595260

  20. Molecular aspects of the endocytic pathway.

    PubMed Central

    Clague, M J

    1998-01-01

    Observation of the flow of material along the endocytic pathway has lead to the description of the basic architecture of the pathway and provided insight into the relationship between compartments. Significant advances have been made in the study of endocytic transport steps at the molecular level, of which studies of cargo selection, vesicle budding and membrane fusion events comprise the major part. Progress in this area has been driven by two approaches, yeast genetics and in vitro or cell-free assays, which reconstitute particular transport steps and allow biochemical manipulation. The complex protein machineries that control vesicle budding and fusion are significantly conserved between the secretory and endocytic pathways such that proteins that regulate particular steps are often part of a larger family of proteins which exercise a conserved function at other locations within the cell. Well characterized examples include vesicle coat proteins, rabs (small GTPases) and soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein (SNAP) receptors (SNAREs). Intracompartmental pH, lipid composition and cytoskeletal organization have also been identified as important determinants of the orderly flow of material within the endocytic pathway. PMID:9820800

  1. Molecular and Clinical Aspects of Angelman Syndrome

    PubMed Central

    Dagli, A.; Buiting, K.; Williams, C.A.

    2012-01-01

    The Angelman syndrome is caused by disruption of the UBE3A gene and is clinically delineated by the combination of severe mental disability, seizures, absent speech, hypermotoric and ataxic movements, and certain remarkable behaviors. Those with the syndrome have a predisposition toward apparent happiness and paroxysms of laughter, and this finding helps distinguish Angelman syndrome from other conditions involving severe developmental handicap. Accurate diagnosis rests on a combination of clinical criteria and molecular and/or cytogenetic testing. Analysis of parent-specific DNA methylation imprints in the critical 15q11.2–q13 genomic region identifies 75–80% of all individuals with the syndrome, including those with cytogenetic deletions, imprinting center defects and paternal uniparental disomy. In the remaining group, UBE3A sequence analysis identifies an additional percentage of patients, but 5–10% will remain who appear to have the major clinical phenotypic features but do not have any identifiable genetic abnormalities. Genetic counseling for recurrence risk is complicated because multiple genetic mechanisms can disrupt the UBE3A gene, and there is also a unique inheritance pattern associated with UBE3A imprinting. Angelman syndrome is a prototypical developmental syndrome due to its remarkable behavioral phenotype and because UBE3A is so crucial to normal synaptic function and neural plasticity. PMID:22670133

  2. Atomic and Molecular Aspects of Astronomical Spectra

    NASA Astrophysics Data System (ADS)

    Sochi, Taha

    2012-11-01

    In the first section we present the atomic part where a C2+ atomic target was prepared and used to generate theoretical data to investigate recombination lines arising from electron-ion collisions in thin plasma. R-matrix method was used to describe the C2+ plus electron system. Theoretical data concerning bound and autoionizing states were generated in the intermediate-coupling approximation. The data were used to generate dielectronic recombination data for C+ which include transition lines, oscillator strengths, radiative transition probabilities, emissivities and dielectronic recombination coefficients. The data were cast in a line list containing 6187 optically-allowed transitions which include many C II lines observed in astronomical spectra. This line list was used to analyze the spectra from a number of astronomical objects, mainly planetary nebulae, and identify their electron temperature. The electron temperature investigation was also extended to include free electron energy analysis to investigate the long-standing problem of discrepancy between the results of recombination and forbidden lines analysis and its possible connection to the electron distribution. In the second section we present the results of our molecular investigation; the generation of a comprehensive, calculated line list of frequencies and transition probabilities for H2D+. The line list contains over 22 million rotational-vibrational transitions occurring between more than 33 thousand energy levels and covers frequencies up to 18500 cm-1. About 15% of these levels are fully assigned with approximate rotational and vibrational quantum numbers. A temperature-dependent partition function and cooling function are presented. Temperature-dependent synthetic spectra for the temperatures T=100, 500, 1000 and 2000 K in the frequency range 0-10000 cm-1 were also generated and presented graphically.

  3. Molecular and Biotechnological Aspects of Microbial Proteases†

    PubMed Central

    Rao, Mala B.; Tanksale, Aparna M.; Ghatge, Mohini S.; Deshpande, Vasanti V.

    1998-01-01

    diverse origins have been analyzed with the aim of studying their evolutionary relationships. Despite the extensive research on several aspects of proteases, there is a paucity of knowledge about the roles that govern the diverse specificity of these enzymes. Deciphering these secrets would enable us to exploit proteases for their applications in biotechnology. PMID:9729602

  4. Molecular aspects of intestinal calcium absorption.

    PubMed

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-06-21

    Intestinal Ca(2+) absorption is a crucial physiological process for maintaining bone mineralization and Ca(2+) homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca(2+) across the brush border membranes (BBM) of enterocytes through epithelial Ca(2+) channels TRPV6, TRPV5, and Cav1.3; Ca(2+) movement from the BBM to the basolateral membranes by binding proteins with high Ca(2+) affinity (such as CB9k); and Ca(2+) extrusion into the blood. Plasma membrane Ca(2+) ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca(2+) from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca(2+) transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca(2+) transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca(2+) absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca(2+) transport to control values. Calcitriol [1,25(OH)₂D₃] is the major controlling hormone of intestinal Ca(2+) transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca(2+) transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)₂D₃ production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca(2+) absorption according to Ca(2+) demands. Better knowledge of the molecular details of intestinal Ca(2

  5. Molecular aspects of intestinal calcium absorption

    PubMed Central

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-01-01

    Intestinal Ca2+ absorption is a crucial physiological process for maintaining bone mineralization and Ca2+ homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca2+ across the brush border membranes (BBM) of enterocytes through epithelial Ca2+ channels TRPV6, TRPV5, and Cav1.3; Ca2+ movement from the BBM to the basolateral membranes by binding proteins with high Ca2+ affinity (such as CB9k); and Ca2+ extrusion into the blood. Plasma membrane Ca2+ ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca2+ from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca2+ transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca2+ transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca2+ absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca2+ transport to control values. Calcitriol [1,25(OH)2D3] is the major controlling hormone of intestinal Ca2+ transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca2+ transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)2D3 production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca2+ absorption according to Ca2+ demands. Better knowledge of the molecular details of intestinal Ca2+ absorption could lead to the development of

  6. Molecular aspects of intestinal calcium absorption.

    PubMed

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-06-21

    Intestinal Ca(2+) absorption is a crucial physiological process for maintaining bone mineralization and Ca(2+) homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca(2+) across the brush border membranes (BBM) of enterocytes through epithelial Ca(2+) channels TRPV6, TRPV5, and Cav1.3; Ca(2+) movement from the BBM to the basolateral membranes by binding proteins with high Ca(2+) affinity (such as CB9k); and Ca(2+) extrusion into the blood. Plasma membrane Ca(2+) ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca(2+) from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca(2+) transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca(2+) transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca(2+) absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca(2+) transport to control values. Calcitriol [1,25(OH)₂D₃] is the major controlling hormone of intestinal Ca(2+) transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca(2+) transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)₂D₃ production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca(2+) absorption according to Ca(2+) demands. Better knowledge of the molecular details of intestinal Ca(2

  7. Making mathematics and science integration happen: key aspects of practice

    NASA Astrophysics Data System (ADS)

    Ríordáin, Máire Ní; Johnston, Jennifer; Walshe, Gráinne

    2016-02-01

    The integration of mathematics and science teaching and learning facilitates student learning, engagement, motivation, problem-solving, criticality and real-life application. However, the actual implementation of an integrative approach to the teaching and learning of both subjects at classroom level, with in-service teachers working collaboratively, at second-level education, is under-researched due to the complexities of school-based research. This study reports on a year-long case study on the implementation of an integrated unit of learning on distance, speed and time, within three second-level schools in Ireland. This study employed a qualitative approach and examined the key aspects of practice that impact on the integration of mathematics and science teaching and learning. We argue that teacher perspective, teacher knowledge of the 'other subject' and of technological pedagogical content knowledge (TPACK), and teacher collaboration and support all impact on the implementation of an integrative approach to mathematics and science education.

  8. Cellular and molecular aspects of plant adaptation to microgravity

    NASA Astrophysics Data System (ADS)

    Kordyum, Elizabeth; Kozeko, Liudmyla

    2016-07-01

    Elucidation of the range and mechanisms of the biological effects of microgravity is one of the urgent fundamental tasks of space and gravitational biology. The absence of forbidding on plant growth and development in orbital flight allows studying different aspects of plant adaptation to this factor that is directly connected with development of the technologies of bioregenerative life-support systems. Microgravity belongs to the environmental factors which cause adaptive reactions at the cellular and molecular levels in the range of physiological responses in the framework of genetically determined program of ontogenesis. It is known that cells of a multicellular organism not only take part in reactions of the organism but also carry out processes that maintain their integrity. In light of these principles, the problem of identification of biochemical, physiological and structural patterns that can have adaptive significance at the cellular and molecular levels in real and simulated microgravity is considered. It is pointed that plant cell responses in microgravity and under clinorotation vary according to growth phase, physiological state, and taxonomic position of the object. At the same time, the responses have, to some degree, a similar character reflecting the changes in the cell organelle functional load. The maintenance of the plasmalemma fluidity at the certain level, an activation of both the antioxidant system and expression of HSP genes, especially HSP70, under increasing reactive oxygen species, lipid peroxidation intensity and alteration in protein homeostasis, are a strategic paradigm of rapid (primary) cell adaptation to microgravity. In this sense, biological membranes, especially plasmalemma, and their properties and functions may be considered as the most sensitive indicators of the influence of gravity or altered gravity on a cell. The plasmalemma lipid bilayer is a border between the cell internal content and environment, so it is a mediator

  9. Cellular and molecular aspects of plant adaptation to microgravity

    NASA Astrophysics Data System (ADS)

    Kordyum, Elizabeth; Kozeko, Liudmyla

    2016-07-01

    Elucidation of the range and mechanisms of the biological effects of microgravity is one of the urgent fundamental tasks of space and gravitational biology. The absence of forbidding on plant growth and development in orbital flight allows studying different aspects of plant adaptation to this factor that is directly connected with development of the technologies of bioregenerative life-support systems. Microgravity belongs to the environmental factors which cause adaptive reactions at the cellular and molecular levels in the range of physiological responses in the framework of genetically determined program of ontogenesis. It is known that cells of a multicellular organism not only take part in reactions of the organism but also carry out processes that maintain their integrity. In light of these principles, the problem of identification of biochemical, physiological and structural patterns that can have adaptive significance at the cellular and molecular levels in real and simulated microgravity is considered. It is pointed that plant cell responses in microgravity and under clinorotation vary according to growth phase, physiological state, and taxonomic position of the object. At the same time, the responses have, to some degree, a similar character reflecting the changes in the cell organelle functional load. The maintenance of the plasmalemma fluidity at the certain level, an activation of both the antioxidant system and expression of HSP genes, especially HSP70, under increasing reactive oxygen species, lipid peroxidation intensity and alteration in protein homeostasis, are a strategic paradigm of rapid (primary) cell adaptation to microgravity. In this sense, biological membranes, especially plasmalemma, and their properties and functions may be considered as the most sensitive indicators of the influence of gravity or altered gravity on a cell. The plasmalemma lipid bilayer is a border between the cell internal content and environment, so it is a mediator

  10. Molecular and Clinical Aspects of Drug-induced Gingival Overgrowth

    PubMed Central

    Kantarci, A.

    2015-01-01

    Drug-induced gingival overgrowth is a tissue-specific condition and is estimated to affect approximately one million North Americans. Lesions occur principally as side-effects from phenytoin, nifedipine, or ciclosporin therapy in approximately half of the people who take these agents. Due to new indications for these drugs, their use continues to grow. Here, we review the molecular and cellular characteristics of human gingival overgrowth lesions and highlight how they differ considerably as a function of the causative drug. Analyses of molecular signaling pathways in cultured human gingival fibroblasts have provided evidence for their unique aspects compared with fibroblasts from the lung and kidney. These findings provide insights into both the basis for tissue specificity and into possible therapeutic opportunities which are reviewed here. Although ciclosporin-induced gingival overgrowth lesions exhibit principally the presence of inflammation and little fibrosis, nifedipine- and especially phenytoin-induced lesions are highly fibrotic. The increased expression of markers of gingival fibrosis, particularly CCN2 [also known as connective tissue growth factor (CTGF)], markers of epithelial to mesenchymal transition, and more recently periostin and members of the lysyl oxidase family of enzymes have been documented in phenytoin or nifedipine lesions. Some oral fibrotic conditions such as leukoplakia and oral submucous fibrosis, after subsequent additional genetic damage, can develop into oral cancer. Since many pathways are shared, the study of gingival fibrosis and comparisons with characteristics and molecular drivers of oral cancer would likely enhance understandings and functional roles of molecular drivers of these oral pathologies. PMID:25680368

  11. Molecular and biological aspects of the bovine immunodeficiency virus.

    PubMed

    Corredor, Andrea G; St-Louis, Marie-Claude; Archambault, Denis

    2010-01-01

    The bovine immunodeficiency virus (BIV) was isolated in 1969 from a cow, R-29, with a wasting syndrome suggesting bovine leucosis. The virus, first designated bovine visna-like virus, remained unstudied until HIV was discovered in 1983. Then, it was demonstrated in 1987 that the bovine R-29 isolate was a lentivirus with striking similarity to the human immunodeficiency virus (HIV). Moreover, BIV has the most complex genomic structure among all identified lentiviruses shown by several regulatory/accessory genes encoding proteins, some of which are involved in the regulation of virus gene expression. This manuscript aims to review biological and molecular aspects of BIV, with emphasis on regulatory/accessory viral genes/proteins which are involved in virus expression. PMID:20210777

  12. Molecular Aspects of Bone Resorption in β-Thalassemia Major

    PubMed Central

    Saki, Najmaldin; Abroun, Saeid; Salari, Fatemeh; Rahim, Fakher; Shahjahani, Mohammad; Javad, Mohammadi-Asl

    2015-01-01

    β-thalassemia is the most common single gene disorder worldwide, in which hemoglobin β-chain production is decreased. Today, the life expectancy of thalassemic patients is increased because of a variety of treatment methods; however treatment related complications have also increased. The most common side effect is osteoporosis, which usually occurs in early adulthood as a consequence of increased bone resorption. Increased bone resorption mainly results from factors such as delayed puberty, diabetes mellitus, hypothyroidism, ineffective hematopoiesis as well as hyperplasia of the bone marrow, parathyroid gland dysfunction, toxic effect of iron on osteoblasts, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) deficiency. These factors disrupt the balance between osteoblasts and osteoclasts by interfering with various molecular mechanisms and result in decreased bone density. Given the high prevalence of osteopenia and osteoporosis in thalassemic patients and complexity of their development process, the goal of this review is to evaluate the molecular aspects involved in osteopenia and osteoporosis in thalassemic patients, which may be useful for therapeutic purposes. PMID:26199898

  13. Molecular biological aspects on canine and human mammary tumors.

    PubMed

    Rivera, P; von Euler, H

    2011-01-01

    The high incidence of mammary tumor disease reported in certain canine breeds suggests a significant genetic component, as has already been described in human familial breast cancer-in BRCA1- and BRCA2-associated breast cancer in particular. The identification of genetic risk factors is critical to improvements in the prevention, diagnosis, and treatment of these tumors. In recent years, there has been significant progress in developing the tools and reagents necessary to analyze the canine genome. This work has culminated in a high-quality draft genome sequence, as well as a single-nucleotide polymorphism map and single-nucleotide polymorphism arrays for genomewide association analysis. These tools provide an unprecedented opportunity to characterize the genetic influences in canine diseases such as cancer, eventually allowing for exploration of more effective therapies. Given the high homology between the canine genome sequence and its human counterpart--as well as the many similarities regarding the morphology, biological behavior, and clinical course of mammary tumors in both species--the dog has proven to be an excellent comparative model. This review highlights the comparative aspects regarding certain areas within molecular biology, and it discusses future perspectives. The findings in larger genomewide association analyses and cDNA expression arrays are described, and the BRCA1/BRCA2 complex is compared in detail between the 2 species. PMID:21147766

  14. Some aspects of powerplant airframe integration affecting fuel conservation

    NASA Technical Reports Server (NTRS)

    Farbridge, J. E.

    1978-01-01

    The performance criteria for STOL transport aircraft place many constraints on engineering design, which, in turn, may have a direct bearing on fuel efficiency: these constraints become even more severe with the introduction of powered-lift for turbofan aircraft. Consideration is given to some aspects of performance and design which arise as a result of powerplant/airframe integration and an attempt is made to assess these factors in terms of transport fuel efficiency. The drag polars of various powered lift concepts are analyzed to determine the installed thrust/weight required and a simple method of relating this to fuel efficiency is suggested. Some other factors have been identified as being important to this aspect of design and these are discussed in more general terms. Finally, special consideration is given to recent Canadian research in the realm of supercritical airfoil technology as applied to an multi-foil section which could be utilized both for the STOL regime of flight and for cruise at transonic speeds.

  15. Quantitative Molecular Thermochemistry Based on Path Integrals

    SciTech Connect

    Glaesemann, K R; Fried, L E

    2005-03-14

    The calculation of thermochemical data requires accurate molecular energies and heat capacities. Traditional methods rely upon the standard harmonic normal mode analysis to calculate the vibrational and rotational contributions. We utilize path integral Monte Carlo (PIMC) for going beyond the harmonic analysis, to calculate the vibrational and rotational contributions to ab initio energies. This is an application and extension of a method previously developed in our group.

  16. Molecular Aspects of Transport in Thin Films of Controlled Architecture

    SciTech Connect

    Paul W. Bohn

    2009-04-16

    coupled to analyte sampling both by LIF and mass spectrometry. Detection of electrophoresis separation products by electrospray mass spectrometry was achieved through direct interfacing to an electrospray mass spectrometer. Pb(II) interactions with the DNAzyme have been realized in an NCAM-coupled integrated microfluidic structure allowing cation separations to be coupled to molecular beacon detection motifs for the determination of Pb(II) in an electroplating sludge reference material. By changing the DNAzyme to select for other compounds of interest, it is possible to incorporate multiple sensing systems within a single device, thereby achieving great flexibility.

  17. The roles of integration in molecular systems biology.

    PubMed

    O'Malley, Maureen A; Soyer, Orkun S

    2012-03-01

    A common way to think about scientific practice involves classifying it as hypothesis- or data-driven. We argue that although such distinctions might illuminate scientific practice very generally, they are not sufficient to understand the day-to-day dynamics of scientific activity and the development of programmes of research. One aspect of everyday scientific practice that is beginning to gain more attention is integration. This paper outlines what is meant by this term and how it has been discussed from scientific and philosophical points of view. We focus on methodological, data and explanatory integration, and show how they are connected. Then, using some examples from molecular systems biology, we will show how integration works in a range of inquiries to generate surprising insights and even new fields of research. From these examples we try to gain a broader perspective on integration in relation to the contexts of inquiry in which it is implemented. In today's environment of data-intensive large-scale science, integration has become both a practical and normative requirement with corresponding implications for meta-methodological accounts of scientific practice. We conclude with a discussion of why an understanding of integration and its dynamics is useful for philosophy of science and scientific practice in general.

  18. Microelectromechanical systems integrating molecular spin crossover actuators

    NASA Astrophysics Data System (ADS)

    Manrique-Juarez, Maria D.; Rat, Sylvain; Mathieu, Fabrice; Saya, Daisuke; Séguy, Isabelle; Leïchlé, Thierry; Nicu, Liviu; Salmon, Lionel; Molnár, Gábor; Bousseksou, Azzedine

    2016-08-01

    Silicon MEMS cantilevers coated with a 200 nm thin layer of the molecular spin crossover complex [Fe(H2B(pz)2)2(phen)] (H2B(pz)2 = dihydrobis(pyrazolyl)borate and phen = 1,10-phenantroline) were actuated using an external magnetic field and their resonance frequency was tracked by means of integrated piezoresistive detection. The light-induced spin-state switching of the molecules from the ground low spin to the metastable high spin state at 10 K led to a well-reproducible shift of the cantilever's resonance frequency (Δfr = -0.52 Hz). Control experiments at different temperatures using coated as well as uncoated devices along with simple calculations support the assignment of this effect to the spin transition. This latter translates into changes in mechanical behavior of the cantilever due to the strong spin-state/lattice coupling. A guideline for the optimization of device parameters is proposed so as to efficiently harness molecular scale movements for large-scale mechanical work, thus paving the road for nanoelectromechanical systems (NEMS) actuators based on molecular materials.

  19. Molecular aspects of flow-induced crystallization of polypropylene

    NASA Astrophysics Data System (ADS)

    Thurman, Derek W.

    Using a novel shearing device, we investigate-flow-induced crystallization of bimodal blends of polypropylenes (PP) in which we vary the molecular character (concentration, molecular weight, regularity) of the high molecular weight mode. We apply a number of in situ characterization tools (rheo-optics, rheo-WAXD) to the development of transient structure and interpret our findings in light of ex situ microscopic examination of the final morphology. Blending a well-characterized high molecular weight isotactic polypropylene into a "base iPP" at various concentrations (c), we determined that less than 1% of long chains with Mw five times larger than the Mw of the base resin profoundly affected the flow-induced crystallization kinetics and morphology. Varying the concentration from below to above c* indicated that the effect of the long chains involves cooperative interactions enhanced by long chain-long chain overlap. The long chains particularly influence the formation of anisotropic nuclei. Studying a series of bimodal blends in which the long chain molecular weight (ML) was varied, we found that increasing ML increased the tendency to form threadlike precursors to oriented crystallization. This was highlighted by a marked decrease in the threshold stress (sigma*) necessary to induce oriented crystallization. A minimum separation in relaxation time scales (˜100 times slower) between the long chains and the average was necessary to form long lived oriented precursor structures. A novel "depth sectioning" analysis technique allowed us to gain depth dependent information from real-time rheo-optical and rheo-WAXD experiments. We identify a promising set of conditions that may be used to measure the thread propagation velocity for this material if the appropriate length scale can be assigned by microscopy. Threads first form near the channel wall and grow in length with prolonged flow until thread length per unit volume saturates. Prior to saturation, the thread

  20. Molecular aspects of prostate cancer with neuroendocrine differentiation

    PubMed Central

    Li, Qi; Zhang, Connie S.

    2016-01-01

    Neuroendocrine differentiation (NED), which is not uncommon in prostate cancer, is increases in prostate cancer after androgen-deprivation therapy (ADT) and generally appears in castration-resistant prostate cancer (CRPC). Neuroendocrine cells, which are found in normal prostate tissue, are a small subset of cells and have unique function in regulating the growth of prostate cells. Prostate cancer with NED includes different types of tumor, including focal NED, pure neuroendocrine tumor or mixed neuroendocrine-adenocarcinoma. Although more and more studies are carried out on NED in prostate cancer, the molecular components that are involved in NED are still poorly elucidated. We review neuroendocrine cells in normal prostate tissue, NED in prostate cancer, terminology of NED and biomarkers used for detecting NED in routine pathological practice. Some recently reported molecular components which drive NED in prostate cancer are listed in the review. PMID:27041934

  1. Molecular and genetic aspects of odontogenic tumors: a review

    PubMed Central

    Garg, Kavita; Chandra, Shaleen; Raj, Vineet; Fareed, Wamiq; Zafar, Muhammad

    2015-01-01

    Odontogenic tumors contain a heterogeneous collection of lesions that are categorized from hamartomas to benign and malignant neoplasms of inconstant aggressiveness. Odontogenic tumors are usually extraordinary with assessed frequency of short of 0.5 cases/100,000 population for every year. The lesions such as odontogenic tumors are inferred from the components of the tooth-structuring contraption. They are discovered solely inside the maxillary and mandibular bones. This audit speaks to experiences and cooperation of the molecular and genetic variations connected to the development and movement of odontogenic tumors which incorporate oncogenes, tumor-silencer genes, APC gene, retinoblastoma genes, DNA repair genes, onco-viruses, development components, telomerase, cell cycle controllers, apoptosis-related elements, and regulators/conttrollers of tooth development. The reasonable and better understanding of the molecular components may prompt new ideas for their detection and administrating a better prognosis of odontogenic tumors. PMID:26221475

  2. Theoretical aspects of gas-phase molecular dynamics

    SciTech Connect

    Muckerman, J.T.

    1993-12-01

    Research in this program is focused on the development and application of time-dependent quantum mechanical and semiclassical methods for treating inelastic and reactive molecular collisions, and the photochemistry and photophysics of atoms and molecules in laser fields. Particular emphasis is placed on the development and application of grid methods based on discrete variable representations, on time-propagation methods, and, in systems with more that a few degrees of freedom, on the combined use of quantal wavepackets and classical trajectories.

  3. Molecular diagnosis of sepsis: New aspects and recent developments

    PubMed Central

    Lehman, L.; Hunfeld, K.-P.; Kost, G.

    2014-01-01

    By shortening the time to pathogen identification and allowing for detection of organisms missed by blood culture, new molecular methods may provide clinical benefits for the management of patients with sepsis. While a number of reviews on the diagnosis of sepsis have recently been published we here present up-to-date new developments including multiplex PCR, mass spectrometry and array techniques. We focus on those techniques that are commercially available and for which clinical studies have been performed and published. PMID:24678402

  4. Collective aspects of singlet fission in molecular crystals

    SciTech Connect

    Teichen, Paul E.; Eaves, Joel D.

    2015-07-28

    We present a model to describe collective features of singlet fission in molecular crystals and analyze it using many-body theory. The model we develop allows excitonic states to delocalize over several chromophores which is consistent with the character of the excited states in many molecular crystals, such as the acenes, where singlet fission occurs. As singlet states become more delocalized and triplet states more localized, the rate of singlet fission increases. We also determine the conditions under which the two triplets resulting from fission are correlated. Using the Bethe Ansatz and an entanglement measure for indistinguishable bipartite systems, we calculate the triplet-triplet entanglement as a function of the biexciton interaction strength. The biexciton interaction can produce bound biexciton states and provides a source of entanglement between the two triplets even when the triplets are spatially well separated. Significant entanglement between the triplet pair occurs well below the threshold for bound pair formation. Our results paint a dynamical picture that helps to explain why fission has been observed to be more efficient in molecular crystals than in their covalent dimer analogues and have consequences for photovoltaic efficiency models that assume that the two triplets can be extracted independently.

  5. Integrating pathways of Parkinson's disease in a molecular interaction map.

    PubMed

    Fujita, Kazuhiro A; Ostaszewski, Marek; Matsuoka, Yukiko; Ghosh, Samik; Glaab, Enrico; Trefois, Christophe; Crespo, Isaac; Perumal, Thanneer M; Jurkowski, Wiktor; Antony, Paul M A; Diederich, Nico; Buttini, Manuel; Kodama, Akihiko; Satagopam, Venkata P; Eifes, Serge; Del Sol, Antonio; Schneider, Reinhard; Kitano, Hiroaki; Balling, Rudi

    2014-02-01

    Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is rapidly increasing and needs to be efficiently organized, so that the resulting data is available for exploration and analysis. Here we introduce a computationally tractable, comprehensive molecular interaction map of PD. This map integrates pathways implicated in PD pathogenesis such as synaptic and mitochondrial dysfunction, impaired protein degradation, alpha-synuclein pathobiology and neuroinflammation. We also present bioinformatics tools for the analysis, enrichment and annotation of the map, allowing the research community to open new avenues in PD research. The PD map is accessible at http://minerva.uni.lu/pd_map .

  6. Monogenec Arrhythmic Syndromes: From Molecular and Genetic Aspects to Bedside.

    PubMed

    E Z, Golukhova; O I, Gromova; R A, Shomahov; N I, Bulaeva; L A, Bockeria

    2016-01-01

    The abrupt cessation of effective cardiac function that is generally due to heart rhythm disorders can cause sudden and unexpected death at any age and is referred to as a syndrome called "sudden cardiac death" (SCD). Annually, about 400,000 cases of SCD occur in the United States alone. Less than 5% of the resuscitation techniques are effective. The prevalence of SCD in a population rises with age according to the prevalence of coronary artery disease, which is the most common cause of sudden cardiac arrest. However, there is a peak in SCD incidence for the age below 5 years, which is equal to 17 cases per 100,000 of the population. This peak is due to congenital monogenic arrhythmic canalopathies. Despite their relative rarity, these cases are obviously the most tragic. The immediate causes, or mechanisms, of SCD are comprehensive. Generally, it is arrhythmic death due to ventricular tachyarrythmias - sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Bradyarrhythmias and pulseless electrical activity account for no more than 40% of all registered cardiac arrests, and they are more often the outcome of the abovementioned arrhythmias. Our current understanding of the mechanisms responsible for SCD has emerged from decades of basic science investigation into the normal electrophysiology of the heart, the molecular physiology of cardiac ion channels, the fundamental cellular and tissue events associated with cardiac arrhythmias, and the molecular genetics of monogenic disorders of the heart rhythm (for example, the long QT syndrome). This review presents an overview of the molecular and genetic basis of SCD in the long QT syndrome, Brugada syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia and idiopathic ventricular fibrillation, and arrhythmogenic right ventricular dysplasia, and sudden cardiac death prevention strategies by modern techniques (including implantable cardioverter-defibrillator). PMID:27437140

  7. Monogenec Arrhythmic Syndromes: From Molecular and Genetic Aspects to Bedside

    PubMed Central

    E.Z., Golukhova; O.I., Gromova; R.A., Shomahov; N.I., Bulaeva; L.A., Bockeria

    2016-01-01

    The abrupt cessation of effective cardiac function that is generally due to heart rhythm disorders can cause sudden and unexpected death at any age and is referred to as a syndrome called “sudden cardiac death” (SCD). Annually, about 400,000 cases of SCD occur in the United States alone. Less than 5% of the resuscitation techniques are effective. The prevalence of SCD in a population rises with age according to the prevalence of coronary artery disease, which is the most common cause of sudden cardiac arrest. However, there is a peak in SCD incidence for the age below 5 years, which is equal to 17 cases per 100,000 of the population. This peak is due to congenital monogenic arrhythmic canalopathies. Despite their relative rarity, these cases are obviously the most tragic. The immediate causes, or mechanisms, of SCD are comprehensive. Generally, it is arrhythmic death due to ventricular tachyarrythmias – sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Bradyarrhythmias and pulseless electrical activity account for no more than 40% of all registered cardiac arrests, and they are more often the outcome of the abovementioned arrhythmias. Our current understanding of the mechanisms responsible for SCD has emerged from decades of basic science investigation into the normal electrophysiology of the heart, the molecular physiology of cardiac ion channels, the fundamental cellular and tissue events associated with cardiac arrhythmias, and the molecular genetics of monogenic disorders of the heart rhythm (for example, the long QT syndrome). This review presents an overview of the molecular and genetic basis of SCD in the long QT syndrome, Brugada syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia and idiopathic ventricular fibrillation, and arrhythmogenic right ventricular dysplasia, and sudden cardiac death prevention strategies by modern techniques (including implantable cardioverter-defibrillator) PMID:27437140

  8. Mathematical aspects of molecular replacement. II. Geometry of motion spaces.

    PubMed

    Chirikjian, Gregory S; Yan, Yan

    2012-03-01

    Molecular replacement (MR) is a well established computational method for phasing in macromolecular crystallography. In MR searches, spaces of motions are explored for determining the appropriate placement of rigid models of macromolecules in crystallographic asymmetric units. In the first paper of this series, it was shown that this space of motions, when endowed with an appropriate composition operator, forms an algebraic structure called a quasigroup. In this second paper, the geometric properties of these MR search spaces are explored and analyzed. This analysis includes the local differential geometry, global geometry and symmetry properties of these spaces.

  9. The Warburg effect: molecular aspects and therapeutic possibilities.

    PubMed

    Ngo, Hanh; Tortorella, Stephanie M; Ververis, Katherine; Karagiannis, Tom C

    2015-04-01

    It has been about nine decades since the proposal of Otto Warburg on the metabolism of cancer cells. Unlike normal cells which undergo glycolysis and oxidative phosphorylation in the presence of oxygen, proliferating and cancer cells exhibit an increased uptake of glucose and increased rate of glycolysis and predominantly undergo lactic acid fermentation. Whether this phenomenon is the consequence of genetic dysregulation in cancer or is the cause of cancer still remains unknown. However, there is certainly a strong link between the genetic factors, epigenetic modulation, cancer immunosurveillance and the Warburg effect, which will be discussed in this review. Dichloroacetate and 3-bromopyruvate are among the substances that have been studied as potential cancer therapies. With our expanding knowledge of cellular metabolism, therapies targeting the Warburg effect appear very promising. This review discusses different aspects of these emerging therapies. PMID:25253100

  10. Making Mathematics and Science Integration Happen: Key Aspects of Practice

    ERIC Educational Resources Information Center

    Ríordáin, Máire Ní; Johnston, Jennifer; Walshe, Gráinne

    2016-01-01

    The integration of mathematics and science teaching and learning facilitates student learning, engagement, motivation, problem-solving, criticality and real-life application. However, the actual implementation of an integrative approach to the teaching and learning of both subjects at classroom level, with in-service teachers working…

  11. Responses of plant seedlings to hypergravity: cellular and molecular aspects

    NASA Astrophysics Data System (ADS)

    Hoson, T.; Yoshioka, R.; Soga, K.; Wakabayashi, K.; Takeba, G.

    Hypergravity produced by centrifugation has been used to analyze the responses of plant seedlings to gravity stimulus. Elongation growth of stem organs is suppressed by hypergravity, which can be recognized as a way for plants to resist gravitational force. The mechanisms inducing growth suppression under hypergravity conditions were analyzed at cellular and molecular levels. When growth was suppressed by hypergravity, a decrease in the cell wall extensibility was brought about in various plants. Hypergravity also induced a cell wall thickening and an increase in the molecular mass of the certain hemicellulosic polysaccharides. Both a decrease in the activities hydrolyzing such polysaccharides and an increase in the apoplast pH were involved in such changes in the cell wall constituents. Thus, the cell wall metabolism is greatly modified under hypergravity conditions, which causes a decrease in the cell wall extensibility, thereby inhibiting elongation growth in stem organs. On the other hand, to identify genes involved in hypergravity-induced growth suppression, changes in gene expression by hypergravity treatment were analyzed in Arabidopsis hypocotyls by differential display method. Sixty-two genes were expressed differentially: expression levels of 39 genes increased, whereas those of 23 genes decreased under hypergravity conditions. The expression of these genes was further analyzed using RT-PCR. One of genes upregulated by hypergravity encoded hydroxymethylglutaryl-CoA reductase (HMGR), which catalyzes a reaction producing mevalonic acid, a key precursor of hormones such as gibberellic acid and abscisic acid. The expression of HMGR gene increased within several hours after hypergravity treatment. Also, compactin, an inhibitor of HMGR activity, prevented hypergravity-induced growth suppression, suggesting that HMGR is involved in suppression of Arabidopsis hypocotyl growth by hypergravity. In addition, hypergravity increased the expression levels of CCR1 and

  12. Autoimmune regulator and self-tolerance - molecular and clinical aspects.

    PubMed

    Abramson, Jakub; Husebye, Eystein S

    2016-05-01

    The establishment of central tolerance in the thymus is critical for avoiding deleterious autoimmune diseases. Autoimmune regulator (AIRE), the causative gene in autoimmune polyendocrine syndrome type-1 (APS-1), is crucial for the establishment of self-tolerance in the thymus by promoting promiscuous expression of a wide array of tissue-restricted self-antigens. This step is critical for elimination of high-affinity self-reactive T cells from the immunological repertoire, and for the induction of a specific subset of Foxp3(+) T-regulatory (Treg ) cells. In this review, we discuss the most recent advances in our understanding of how AIRE operates on molecular and cellular levels, as well as of how its loss of function results in breakdown of self-tolerance mechanisms characterized by a broad and heterogeneous repertoire of autoimmune phenotypes. PMID:27088911

  13. Molecular aspects of stress-gene regulation during spaceflight

    NASA Technical Reports Server (NTRS)

    Paul, Anna-Lisa; Ferl, Robert J.

    2002-01-01

    Spaceflight-associated stress has been the topic of investigation since the first terrestrial organisms were exposed to this unique environment. Organisms that evolved under the selection pressures of earth-normal environments can perceive spaceflight as a stress, either directly because gravity influences an intrinsic biological process, or indirectly because of secondary effects imparted by spaceflight upon environmental conditions. Different organisms and even different organs within an organism adapt to a spaceflight environment with a diversity of tactics. Plants are keenly sensitive to gravity for directed development, and are also sensitive to other stresses associated with closed-system spaceflight environments. Within the past decade, the tools of molecular biology have begun to provide a sophisticated evaluation of spaceflight-associated stress and the genetic responses that accompany metabolic adaptation to spaceflight.

  14. [Asbestos and malignant pleural mesothelioma: molecular, cellular and physiopathological aspects].

    PubMed

    Mohr, Steve; Keith, Gérard; Rihn, Bertrand

    2005-11-01

    Asbestos is known as mutagenic and carcinogenic for human and is responsible for many pulmonary diseases including asbestosis, bronchogenic carcinoma and malignant pleural mesothelioma. Occupational exposure to asbestos is involved in 70-80% of all malignant pleural mesothelioma. The later presents a growing challenge for both researcher and clinician. The diagnosis of malignant pleural mesothelioma is difficult and the current treatments did not show significant improvement of the survival. The increasing incidence of malignant pleural mesothelioma, its gravity and its human, social and financial consequences are of high concern in public health. In this paper we summarize the so far knowledge on cellular, molecular and pathophysiological events involved in genesis and development of malignant pleural mesothelioma. Finally, the paper also report recent data sourced from the study of malignant pleural mesothelioma transcriptome using high-throughput technologies such as gene expression array. These data should improve the accuracy of mesothelioma diagnosis and therapy.

  15. Angelman syndrome: review of clinical and molecular aspects.

    PubMed

    Bird, Lynne M

    2014-01-01

    "Angelman syndrome" (AS) is a neurodevelopmental disorder whose main features are intellectual disability, lack of speech, seizures, and a characteristic behavioral profile. The behavioral features of AS include a happy demeanor, easily provoked laughter, short attention span, hypermotoric behavior, mouthing of objects, sleep disturbance, and an affinity for water. Microcephaly and subtle dysmorphic features, as well as ataxia and other movement disturbances, are additional features seen in most affected individuals. AS is due to deficient expression of the ubiquitin protein ligase E3A (UBE3A) gene, which displays paternal imprinting. There are four molecular classes of AS, and some genotype-phenotype correlations have emerged. Much remains to be understood regarding how insufficiency of E6-AP, the protein product of UBE3A, results in the observed neurodevelopmental deficits. Studies of mouse models of AS have implicated UBE3A in experience-dependent synaptic remodeling. PMID:24876791

  16. Molecular Aspects of Flow-Induced Crystallization of Polymers

    NASA Astrophysics Data System (ADS)

    Kornfield, J.

    Like teeth, bone and sea shells, semicrystalline polymers combine strength with toughness by forming a nano-scale composite with platelet-like crystals stacked with noncrystalline material between them. The morphology and orientation distribution of the nanostructure dictate the material properties. Dynamics of polymer chains in the melt play an important role in controlling the morphology, especially under the influence of flow. Using bimodal isotactic polypropylenes to reveal the effects of small concentrations of very long chains, in collaboration with Mitsubishi Chemical, we show that long chains have a profound effect when they are so long that they can undergo chain stretching, particularly when the long chain concentration is at or above their overlap concentration. When subjected to identical stress at identical subcooling, the blends containing long chains undergo dramatically faster crystallization with very strong orientation. The ``long chains" enhance formatio n of highly oriented crystallization precursors (``shish") on which oriented lamellae (``kebabs") subsequently grow. In collaboration with Sumitomo Chemical and The University of Tokyo, we test the hypothesis that the kebabs are actually composed of long chains using isotopic labelling of selected fractions and small angle neutron scattering (SANS). The results show that long chains in the shish are at the same concentration as they are everywhere else: there is no neutron scattering contrast when the long chains are the deuterium labelled ones! The long chains are essential for the formation of shish and they play their role by ``recruiting" adjacent chains into formation of the shish. Placing molecular defects on the longest chains inhibits their ability to serve this role, providing a molecular tool to independently control the melt elasticity (by choice of the length and concentration of the long chains) and the flow-induced crystallization behavior (by selecting the com onomer content, for

  17. Some aspects of integral transport method for deep penetration problem

    SciTech Connect

    Takahashi, H.

    1982-01-01

    An analytical expression of the integral transport method for an experimental hole in fission reactors has been developed. This analytical method might still be useful for designing a fusion reactor without using large computer machine time.

  18. Molecular Aspect of Good Eating Quality Formation in Japonica Rice

    PubMed Central

    Sun, Ming-Mao; Abdula, Sailila E.; Lee, Hye-Jung; Cho, Young-Chan; Han, Long-Zhi; Koh, Hee-Jong; Cho, Yong-Gu

    2011-01-01

    The composition of amylopectin is the determinant of rice eating quality under certain threshold of protein content and the ratio of amylose and amylopectin. In molecular biology level, the fine structure of amylopectin is determined by relative activities of starch branching enzyme (SBE), granule-bound starch synthase (GBSS), and soluble starch synthase (SSS) in rice grain under the same ADP-Glucose level. But the underlying mechanism of eating quality in molecular biology level remains unclear. This paper reports the differences on major parameters such as SNP and insertion-deletion sites, RNA expressions, and enzyme activities associated with eating quality of japonica varieties. Eight japonica rice varieties with significant differences in various eating quality parameters such as palatability and protein content were used in this experiment. Association analysis between nucleotide polymorphism and eating quality showed that S12 and S13 loci in SBE1, S55 in SSS1, S58 in SSS2A were significantly associated with apparent amylose content, alkali digestion value, setback viscosity, consistency viscosity, pasting temperature, which explained most of the variation in apparent amylose content, setback viscosity, and consistency viscosity; and explained almost all variations in alkali digestion value and pasting temperature. Thirty-five SNPs and insertion-deletions from SBE1, SBE3, GBSS1, SSS1, and SSS2A differentiated high or intermediate palatability rice varieties from low palatability rice varieties. Correlation analysis between enzyme activities and eating quality properties revealed that SBE25 and SSS15/W15 were positively correlated with palatability, whereas GBSS10 and GBSS15 were negatively correlated. Gene expressions showed that SBE1 and SBE3 expressions in high palatability varieties tended to be higher than middle and low palatability varieties. Collectively, SBE1, SBE3, SSS1, and SSS2A, especially SBE1 and SBE3 could improve eating quality, but GBSS1

  19. [Dicentric Y chromosomes. First part: cytogenetic and molecular aspects].

    PubMed

    Bouayed Abdelmoula, N; Amouri, A

    2005-01-01

    Dicentric Y chromosomes have been reviewed twice in 1994 by Hsu et al. and in 1995 by Tuck-Muller et al. who showed that dic(Y) are the most common Y structural abnormalities and that their influence on gonadal and somatic development is extremely variable. The prediction of their phenotypic consequences is often difficult because of the variety of genomic sequences concerned by duplications and deletions, because of the variable degrees of mosaicism (cell line 45,X in particular) and at the end, because of identification and analysis technical difficulties of the structure of the rearranged Y chromosome. The clinical specter of this cytogenetic abnormality is rather wide going from almost-normal or infertile males, to females with or without stigmas of Turner syndrome. Middle phenotypes consist of various degrees of genital ambiguities. However, clinical expression seems to be related to the genomic capital of the Y chromosome, mainly the Y genes involved in the control of the process of the determination of gonads (Yp) and spermatogenesis (Yq) as well as control of the growth and the skeletal development (Yp). Here, we report a third comprehensive review of the literature concerning dicentric Y chromosomes reported since 1994. In the light of previous reviews as well as the recent data of the genetic cartography of the Y chromosome, we try, in this first part, to determine characteristics of reported dicentric Y chromosomes as well as their chromosomal mechanics, their mitotic stability and finally their cytogenetic and molecular investigations.

  20. Molecular layer interneurons of the cerebellum: developmental and morphological aspects.

    PubMed

    Sotelo, Constantino

    2015-10-01

    During the past 25 years, our knowledge on the development of basket and stellate cells (molecular layer interneurons [MLIs]) has completely changed, not only regarding their origin from the ventricular zone, corresponding to the primitive cerebellar neuroepithelium, instead of the external granular layer, but above all by providing an almost complete account of the genetic regulations (transcription factors and other genes) involved in their differentiation and synaptogenesis. Moreover, it has been shown that MLIs' precursors (dividing neuroblasts) and not young postmitotic neurons, as in other germinal neuroepithelia, leave the germinative zone and migrate all along a complex and lengthy path throughout the presumptive cerebellar white matter, which provides suitable niches exerting epigenetic influences on their ultimate neuronal identities. Recent studies carried out on the anatomical-functional properties of adult MLIs emphasize the importance of these interneurons in regulating PC inhibition, and point out the crucial role played by electrical synaptic transmission between MLIs as well as ephaptic interactions between them and Purkinje cells at the pinceaux level, in the regulation of this inhibition.

  1. Resistance to Tospoviruses in Vegetable Crops: Epidemiological and Molecular Aspects.

    PubMed

    Turina, Massimo; Kormelink, Richard; Resende, Renato O

    2016-08-01

    During the past three decades, the economic impact of tospoviruses has increased, causing high yield losses in a variety of crops and ornamentals. Owing to the difficulty in combating thrips vectors with insecticides, the best way to limit/prevent tospovirus-induced diseases involves a management strategy that includes virus resistance. This review briefly presents current tospovirus taxonomy, diversity, molecular biology, and cytopathology as an introduction to a more extensive description of the two main resistance genes employed against tospoviruses: the Sw5 gene in tomato and the Tsw in pepper. Natural and experimental resistance-breaking (RB) isolates allowed the identification of the viral avirulence protein triggering each of the two resistance gene products; epidemiology of RB isolates is discussed to reinforce the need for allelic variants and the need to search for new/alternative resistance genes. Ongoing efforts for alternative resistance strategies are described not only for Tomato spotted wilt virus (TSWV) in pepper and tomato but also for other vegetable crops heavily impacted by tospoviruses. PMID:27296139

  2. Molecular and Pathogenetic Aspects of Tumor Budding in Colorectal Cancer

    PubMed Central

    Dawson, Heather; Lugli, Alessandro

    2015-01-01

    In recent years, tumor budding in colorectal cancer has gained much attention as an indicator of lymph node metastasis, distant metastatic disease, local recurrence, worse overall and disease-free survival, and as an independent prognostic factor. Tumor buds, defined as the presence of single tumor cells or small clusters of up to five tumor cells at the peritumoral invasive front (peritumoral buds) or within the main tumor body (intratumoral buds), are thought to represent the morphological correlate of cancer cells having undergone epithelial–mesenchymal transition (EMT), an important mechanism for the progression of epithelial cancers. In contrast to their undisputed prognostic power and potential to influence clinical management, our current understanding of the biological background of tumor buds is less established. Most studies examining tumor buds have attempted to recapitulate findings of mechanistic EMT studies using immunohistochemical markers. The aim of this review is to provide a comprehensive summary of studies examining protein expression profiles of tumor buds and to illustrate the molecular pathways and crosstalk involved in their formation and maintenance. PMID:25806371

  3. Ferric Enterochelin Transport in Yersinia enterocolitica: Molecular and Evolutionary Aspects

    PubMed Central

    Schubert, S.; Fischer, D.; Heesemann, J.

    1999-01-01

    Yersinia enterocolitica is well equipped for siderophore piracy, encompassing the utilization of siderophores such as ferrioxamine, ferrichrome, and ferrienterochelin. In this study, we report on the molecular and functional characterization of the Yersinia fep-fes gene cluster orthologous to the Escherichia coli ferrienterochelin transport genes (fepA, fepDGC, and fepB) and the esterase gene fes. In vitro transcription-translation analysis identified polypeptides of 30 and 35 kDa encoded by fepC and fes, respectively. A frameshift mutation within the fepA gene led to expression of a truncated polypeptide of 40 kDa. The fepD, fepG, and fes genes of Y. enterocolitica were shown to complement corresponding E. coli mutants. Insertional mutagenesis of fepD or fes genes abrogates enterochelin-supported growth of Y. enterocolitica on iron-chelated media. In contrast to E. coli, the fep-fes gene cluster in Y. enterocolitica consists solely of genes required for uptake and utilization of enterochelin (fep) and not of enterochelin synthesis genes such as entF. By Southern hybridization, fepDGC and fes sequences could be detected in Y. enterocolitica biotypes IB, IA, and II but not in biotype IV strains, Yersinia pestis, and Yersinia pseudotuberculosis strains. According to sequence alignment data and the coherent structure of the Yersinia fep-fes gene cluster, we suggest early genetic divergence of ferrienterochelin uptake determinants among species of the family Enterobacteriaceae. PMID:10515929

  4. Molecular aspects of bovine cystic ovarian disease pathogenesis.

    PubMed

    Ortega, Hugo H; Marelli, Belkis E; Rey, Florencia; Amweg, Ayelen N; Díaz, Pablo U; Stangaferro, Matías L; Salvetti, Natalia R

    2015-06-01

    Cystic ovarian disease (COD) is one of the main causes of reproductive failure in cattle and causes severe economic loss to the dairy farm industry because it increases both days open in the post partum period and replacement rates due to infertility. This disease is the consequence of the failure of a mature follicle to ovulate at the time of ovulation in the estrous cycle. This review examines the evidence for the role of altered steroid and gonadotropin signaling systems and the proliferation/apoptosis balance in the ovary with cystic structures. This evidence suggests that changes in the expression of ovarian molecular components associated with these cellular mechanisms could play a fundamental role in the pathogenesis of COD. The evidence also shows that gonadotropin receptor expression in bovine cystic follicles is altered, which suggests that changes in the signaling system of gonadotropins could play a fundamental role in the pathogenesis of conditions characterized by altered ovulation, such as COD. Ovaries from animals with COD exhibit a disrupted steroid receptor pattern with modifications in the expression of coregulatory proteins. These changes in the pathways of endocrine action would trigger the changes in proliferation and apoptosis underlying the aberrant persistence of follicular cysts. Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/149/6/R251/suppl/DC1.

  5. Serrated polyposis syndrome: molecular, pathological and clinical aspects.

    PubMed

    Guarinos, Carla; Sánchez-Fortún, Cristina; Rodríguez-Soler, María; Alenda, Cristina; Payá, Artemio; Jover, Rodrigo

    2012-05-28

    Hyperplastic polyps have traditionally been considered not to have malignant potential. New pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolutionized the concepts and revitalized the research in this area. Until recently, it has been thought that most colorectal cancers arise from conventional adenomas via the traditional tumor suppressor pathway initiated by a mutation of the APC gene, but it has been found that this pathway accounts for only approximately 70%-80% of colorectal cancer (CRC) cases. The majority of the remaining colorectal cancer cases follow an alternative pathway leading to CpG island methylator phenotype carcinoma with BRAF mutation and with or without microsatellite instability. The mechanism of carcinomas arising from this alternative pathway seems to begin with an activating mutation of the BRAF oncogene. Serrated polyposis syndrome is a relatively rare condition characterized by multiple and/or large serrated polyps of the colon. Clinical characteristics, etiology and relationship of serrated polyposis syndrome to CRC have not been clarified yet. Patients with this syndrome show a high risk of CRC and both sporadic and hereditary cases have been described. Clinical criteria have been used for diagnosis and frequent colonoscopy surveillance should be performed in order to prevent colorectal cancer. In this review, we try to gather new insights into the molecular pathogenesis of serrated polyps in order to understand their possible clinical implications and to make an approach to the management of this syndrome.

  6. Molecular Aspects of Plasmodium falciparum Infection during Pregnancy

    PubMed Central

    Ndam, Nicaise Tuikue; Deloron, Philippe

    2007-01-01

    Cytoadherence of Plasmodium-falciparum-parasitized red blood cells (PRBCs) to host receptors is the key phenomenon in the pathological process of the malaria disease. Some of these interactions can originate poor outcomes responsible for 1 to 3 million annual deaths mostly occurring among children in sub-Saharan Africa. Pregnancy-associated malaria (PAM) represents an important exception of the disease occurring at adulthood in malaria endemic settings. Consequences of this are shared between the mother (maternal anemia) and the baby (low birth weight and infant mortality). Demonstrating that parasites causing PAM express specific variant surface antigens (VSAPAM), including the P. falciparum erythrocyte membrane protein 1 (P f EMP1) variant VAR2CSA, that are targets for protective immunity has strengthened the possibility for the development of PAM-specific vaccine. In this paper, we review the molecular basis of malaria pathogenesis attributable to the erythrocyte stages of the parasites, and findings supporting potential anti-PAM vaccine components evidenced in PAM. PMID:17641725

  7. Molecular aspects of restitution: functions of trefoil peptides.

    PubMed Central

    Poulsom, R.; Begos, D. E.; Modlin, I. M.

    1996-01-01

    Healing of mucosal damage takes place in two phases: restitution of mucosal integrity and remodeling towards recreating the original glandular arrangements. These processes can be observed in several experimental rodent models: e.g., cryoprobe or NSAID-generated ulcers in the gastric or duodenal mucosa and following surgical resection of the small or large bowel. In some studies, it has been possible to detect changes in the expression of peptides, either in the reparative epithelium or adjacent to the damage, that may contribute to the healing processes. Trefoil peptides are expressed constitutively by epithelial cells in specific regions of the gastrointestinal tract, in association with mucins. Several studies have shown that trefoil peptide expression is enhanced at sites of damage in man and rat, and experimental evidence supports their active participation in the healing process. Recombinant trefoil peptides are able to enhance the rate of epithelial cell migration in vitro and are able to protect against indomethacin-induced damage in vivo, yet they do not depend upon TGF-beta for enhancing cell migration and do not appear to affect acid secretion. The mode of action of trefoil peptides appears to be receptor-mediated but is not simple. There is good evidence that there are interactions between members of the trefoil family and the EGF family that are beneficial for mucosal defense and repair. This raises the possibility that combining trefoil peptides with other growth factors or small molecules may be advantageous for treatment of ulceration. Images Figure 1 Figure 2 PMID:9112745

  8. Biomining Microorganisms: Molecular Aspects and Applications in Biotechnology and Bioremediation

    NASA Astrophysics Data System (ADS)

    Jerez, Carlos A.

    The microbial solubilization of metals using chemolithoautotrophic microorganisms has successfully been used in industrial processes called biomining to extract metals such as copper, gold, uranium and others. The most studied leaching bacteria are from the genus Acidithiobacillus belonging to the Gram-negative γ-proteobacteria. Acidithiobacillus spp. obtain their energy from the oxidation of ferrous iron, elemental sulfur, or partially oxidized sulfur compounds. Other thermophilic archaeons capable of oxidizing sulfur and iron (II) have also been known for many years, and they are mainly from the genera Sulfolobus, Acidianus, Metallosphaera and Sulfurisphaera. Recently, some mesophilic iron (II)-oxidizing archaeons such as Ferroplasma acidiphilium and F. acidarmanus belonging to the Thermoplasmales have also been isolated and characterized. Recent studies of microorganisms consider them in their consortia, integrating fundamental biological knowledge with metagenomics, metaproteomics, and other data to obtain a global picture of how a microbial community functions. The understanding of microbial growth and activities in oxidizing metal ions will be useful for improving applied microbial biotechnologies such as biomining, bioshrouding, biomonitoring and bioremediation of metals in acidic environments.

  9. Health-related aspects of integrated pest management.

    PubMed Central

    Smith, R F; Calvert, D J

    1976-01-01

    Basic concepts and philosophy of integrated pest management are presented in order to dispel several misconceptions and to provide the necessary background information for discussion of its relationship to the health-related effects of pesticide use. Implications for human health of current pesticide practices in Central America are examined to illustrate major problems associated with the injudicious use of insecticides, i.e., human pesticide poisonings, development of insect resistance, and persistence in the environment. Mitigation of these problems would ideally be achieved through the efforts and cooperation of a multidisciplinary team of scientists and technical people in the medical and agricultural sciences. The dilemma associated with the development of integrated pest control systems in developing countries is discussed. The FAO/UNEP Global Programme was reviewed. PMID:976225

  10. Translational neurocardiology: preclinical models and cardioneural integrative aspects.

    PubMed

    Ardell, J L; Andresen, M C; Armour, J A; Billman, G E; Chen, P-S; Foreman, R D; Herring, N; O'Leary, D S; Sabbah, H N; Schultz, H D; Sunagawa, K; Zucker, I H

    2016-07-15

    Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics. PMID:27098459

  11. Symbolic programming language in molecular multicenter integral problem

    NASA Astrophysics Data System (ADS)

    Safouhi, Hassan; Bouferguene, Ahmed

    It is well known that in any ab initio molecular orbital (MO) calculation, the major task involves the computation of molecular integrals, among which the computation of three-center nuclear attraction and Coulomb integrals is the most frequently encountered. As the molecular system becomes larger, computation of these integrals becomes one of the most laborious and time-consuming steps in molecular systems calculation. Improvement of the computational methods of molecular integrals would be indispensable to further development in computational studies of large molecular systems. To develop fast and accurate algorithms for the numerical evaluation of these integrals over B functions, we used nonlinear transformations for improving convergence of highly oscillatory integrals. These methods form the basis of new methods for solving various problems that were unsolvable otherwise and have many applications as well. To apply these nonlinear transformations, the integrands should satisfy linear differential equations with coefficients having asymptotic power series in the sense of Poincaré, which in their turn should satisfy some limit conditions. These differential equations are very difficult to obtain explicitly. In the case of molecular integrals, we used a symbolic programming language (MAPLE) to demonstrate that all the conditions required to apply these nonlinear transformation methods are satisfied. Differential equations are obtained explicitly, allowing us to demonstrate that the limit conditions are also satisfied.

  12. Internal radiation therapy: a neglected aspect of nuclear medicine in the molecular era

    PubMed Central

    Lin, Yansong

    2015-01-01

    Abstract With increasing evidence, internal radiation therapy, also known as brachytherapy, has become a neglected aspect of nuclear medicine in the molecular era. In this paper, recent developments regarding internal radiation therapy, including developments in radioiodine-131 (131I) and thyroid, radioimmunotherapy (RIT) for non-Hodgkin lymphoma (NHL), and radiopharmaceuticals for bone metastases. Relevant differences and status of their applications in China were mentioned as well. These molecular mediated internal radiation therapies are gaining increasing importance by providing palliative and curative treatments for an increasing number of diseases and becoming one of the important parts of molecular nuclear medicine. PMID:26445567

  13. Glycoprotein Biochemistry (Biosynthesis)--A Vehicle for Teaching Many Aspects of Biochemistry and Molecular Biology.

    ERIC Educational Resources Information Center

    Cole, Clair R.; Smith, Christopher A.

    1990-01-01

    Information about the biosynthesis of the carbohydrate portions or glycans of glycoproteins is presented. The teaching of glycosylation can be used to develop and emphasize many general aspects of biosynthesis, in addition to explaining specific biochemical and molecular biological features associated with producing the oligosaccharide portions of…

  14. Some aspects of integrated water resources management in central Asia

    NASA Astrophysics Data System (ADS)

    Khaydarova, V.; Penkova, N.; Pak, E.; Poberejsky, L.; Beltrao, J.

    2003-04-01

    Two main tasks are to be implemented for elaboration of the governmental water distribution criteria in Central Asia: 1 -development of the common methodological basis for the intergovernmental water distribution; and 2 - to reopen and continue both theoretical and experimental researches of various aspects of the wastewater reuse. The prospects of socio economic development of all Central Asian countries are substantially defined by the water resources availability. The water resources of Central Asia belong, mainly, watersheds of the Syr-Darya and Amu Darya rivers. The basic flow of Amu Darya is formed in territory of Tajikistan. Then the Amu Darya river proceeds along border of Afghanistan with Uzbekistan, crosses Turkmenistan and again comes back to Uzbekistan and then runs into the Aral Sea. The Syr-Darya is second river on the water discharge and is first river on length in Central Asia. The basic flow of Syr Darya is formed in territory of Kyrgyzstan. Then the Syr-Darya river crosses of Uzbekistan and Tajikistan and runs into the Aral Sea in territory of Kazakhstan. During the Soviet Union the water resources of two river watersheds were divided among the Central Asian republics on the basis of the general plans developed by the center in Moscow. In the beginning of 90s years, after taking of sovereignty by the former Soviet republics, the unified control system of water resources management was abolished and the various approaches to its transformation caused by features of the national economy developing, elected models of transition from command to market mechanisms of economic activity, and also specificity of political and social processes in each of the states of region were planned. The distinctions of modern priorities of economic development of the states of region have generated the contradiction of interests in the intergovernmental water distribution that can in the long term become complicated even more in connection with the increasing of water

  15. Some aspects of integrated water resources management in central Asia

    NASA Astrophysics Data System (ADS)

    Khaydarova, V.; Penkova, N.; Pak, E.; Poberejsky, L.; Beltrao, J.

    2003-04-01

    Two main tasks are to be implemented for elaboration of the governmental water distribution criteria in Central Asia: 1 -development of the common methodological basis for the intergovernmental water distribution; and 2 - to reopen and continue both theoretical and experimental researches of various aspects of the wastewater reuse. The prospects of socio economic development of all Central Asian countries are substantially defined by the water resources availability. The water resources of Central Asia belong, mainly, watersheds of the Syr-Darya and Amu Darya rivers. The basic flow of Amu Darya is formed in territory of Tajikistan. Then the Amu Darya river proceeds along border of Afghanistan with Uzbekistan, crosses Turkmenistan and again comes back to Uzbekistan and then runs into the Aral Sea. The Syr-Darya is second river on the water discharge and is first river on length in Central Asia. The basic flow of Syr Darya is formed in territory of Kyrgyzstan. Then the Syr-Darya river crosses of Uzbekistan and Tajikistan and runs into the Aral Sea in territory of Kazakhstan. During the Soviet Union the water resources of two river watersheds were divided among the Central Asian republics on the basis of the general plans developed by the center in Moscow. In the beginning of 90s years, after taking of sovereignty by the former Soviet republics, the unified control system of water resources management was abolished and the various approaches to its transformation caused by features of the national economy developing, elected models of transition from command to market mechanisms of economic activity, and also specificity of political and social processes in each of the states of region were planned. The distinctions of modern priorities of economic development of the states of region have generated the contradiction of interests in the intergovernmental water distribution that can in the long term become complicated even more in connection with the increasing of water

  16. Non-equilibrium Aspects of Quantum Integrable Systems

    NASA Astrophysics Data System (ADS)

    Andrei, Natan

    The study of non-equilibrium dynamics of interacting many body systems is currently one of the main challenges of modern condensed matter physics, driven by the spectacular progress in the ability to create experimental systems - trapped cold atomic gases are a prime example - that can be isolated from their environment and be highly controlled. Many old and new questions can be addressed: thermalization of isolated systems, nonequilibrium steady states, the interplay between non equilibrium currents and strong correlations, quantum phase transitions in time, universality among others. In this talk I will describe nonequilibrium quench dynamics in integrable quantum systems. I'll discuss the time evolution of the Lieb-Liniger system, a gas of interacting bosons moving on the continuous infinite line and interacting via a short range potential. Considering a finite number of bosons on the line we find that for any value of repulsive coupling the system asymptotes towards a strongly repulsive gas for any initial state, while for an attractive coupling, the system forms a maximal bound state that dominates at longer times. In the thermodynamic limit -with the number of bosons and the system size sent to infinity at a constant density and the long time limit taken subsequently- I'll show that the density and density-density correlation functions for strong but finite positive coupling are described by GGE for translationally invariant initial states with short range correlations. As examples I'll discuss quenches from a Mott insulator initial state or a Newton's Cradle. Then I will show that if the initial state is strongly non translational invariant, e.g. a domain wall configuration, the system does not equilibrate but evolves into a nonequilibrium steady state (NESS). A related NESS arises when the quench consists of coupling a quantum dot to two leads held at different chemical potential, leading in the long time limit to a steady state current. Time permitting I

  17. Coupling, Q-Factor, and Integration Aspects of Microsphere Applications

    NASA Technical Reports Server (NTRS)

    Ilchenko, V. S.; Yao, X. S.; Maleki, L.

    2000-01-01

    With suggested applications varying from microlaser and cavity QED through optical locking of diode lasers to modulators and sensors, high-Q silica microspheres with whispering-gallery (WG) modes so far remain the subject of tabletop feasibility demonstrations. Despite the uniquely high quality-factor and submillimeter dimensions suitable for tight packaging, this novel type of high-finesse cavity still has to be adapted to fiber- and integrated-optic hardware. In the visible and near infrared-band experiments (633-850nm) measuring the ringdown time tau of free oscillations, Q = (0.6 to 0.8 ) x 10(exp 10) has been obtained in silica spheres of diameter -800 microns (corresponding tau = 3 to 4 microseconds). It was proved that under normal laboratory conditions, quality-factor is subject to deterioration within several-minute scale down to (2 ... 3 ) x 10(exp 9). The responsible mechanism was identified as adsorption of a monolayer of atmospheric water, so that preservation of the ultimate Q requires manipulation in dry environment, or fast packaging into sealed devices. Larger Q can be expected closer to minimum of attenuation in fused silica alpha = 0.2 dB/km; Q greater than or equal to 1 x 10(exp 11) at lambda=1.55 microns, with corresponding energy storage time tau approx. 0.1ms. Experiments are currently underway to determine whether this high Q can be realized experimentally. The evident difficulty is that OH-related optical absorption has its peaks located near the reported minimum of attenuation in silica. We can also mention here that some of proposed fiber materials, yet not ready for fiber drawing, have been predicted to have smaller attenuation than fused silica and may be suitable for microsphere fabrication (sodium-magnesium silicate glass, alpha = 0.06dB/km). WG modes possess very small radiative loss (it does not prevent Q-10(exp 20) and more) and therefore are electromagnetically isolated and cannot be excited by free-space beams. If no modification

  18. Molecular basis of cell integrity and morphogenesis in Saccharomyces cerevisiae.

    PubMed Central

    Cid, V J; Durán, A; del Rey, F; Snyder, M P; Nombela, C; Sánchez, M

    1995-01-01

    In fungi and many other organisms, a thick outer cell wall is responsible for determining the shape of the cell and for maintaining its integrity. The budding yeast Saccharomyces cerevisiae has been a useful model organism for the study of cell wall synthesis, and over the past few decades, many aspects of the composition, structure, and enzymology of the cell wall have been elucidated. The cell wall of budding yeasts is a complex and dynamic structure; its arrangement alters as the cell grows, and its composition changes in response to different environmental conditions and at different times during the yeast life cycle. In the past few years, we have witnessed a profilic genetic and molecular characterization of some key aspects of cell wall polymer synthesis and hydrolysis in the budding yeast. Furthermore, this organism has been the target of numerous recent studies on the topic of morphogenesis, which have had an enormous impact on our understanding of the intracellular events that participate in directed cell wall synthesis. A number of components that direct polarized secretion, including those involved in assembly and organization of the actin cytoskeleton, secretory pathways, and a series of novel signal transduction systems and regulatory components have been identified. Analysis of these different components has suggested pathways by which polarized secretion is directed and controlled. Our aim is to offer an overall view of the current understanding of cell wall dynamics and of the complex network that controls polarized growth at particular stages of the budding yeast cell cycle and life cycle. PMID:7565410

  19. Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Jerzy Bernholc

    2011-02-03

    will some day reach a miniaturization limit, forcing designers of Si-based electronics to pursue increased performance by other means. Any other alternative approach would have the unenviable task of matching the ability of Si technology to pack more than a billion interconnected and addressable devices on a chip the size of a thumbnail. Nevertheless, the prospects of developing alternative approaches to fabricate electronic devices have spurred an ever-increasing pace of fundamental research. One of the promising possibilities is molecular electronics (ME), self-assembled molecular-based electronic systems composed of single-molecule devices in ultra dense, ultra fast molecular-sized components. This project focused on developing accurate, reliable theoretical modeling capabilities for describing molecular electronics devices. The participants in the project are given in Table 1. The primary outcomes of this fundamental computational science grant are publications in the open scientific literature. As listed below, 62 papers have been published from this project. In addition, the research has also been the subject of more than 100 invited talks at conferences, including several plenary or keynote lectures. Many of the goals of the original proposal were completed. Specifically, the multi-disciplinary group developed a unique set of capabilities and tools for investigating electron transport in fabricated and self-assembled nanostructures at multiple length and time scales.

  20. Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Weinan E

    2012-03-29

    The main bottleneck in modeling transport in molecular devices is to develop the correct formulation of the problem and efficient algorithms for analyzing the electronic structure and dynamics using, for example, the time-dependent density functional theory. We have divided this task into several steps. The first step is to developing the right mathematical formulation and numerical algorithms for analyzing the electronic structure using density functional theory. The second step is to study time-dependent density functional theory, particularly the far-field boundary conditions. The third step is to study electronic transport in molecular devices. We are now at the end of the first step. Under DOE support, we have made subtantial progress in developing linear scaling and sub-linear scaling algorithms for electronic structure analysis. Although there has been a huge amount of effort in the past on developing linear scaling algorithms, most of the algorithms developed suffer from the lack of robustness and controllable accuracy. We have made the following progress: (1) We have analyzed thoroughly the localization properties of the wave-functions. We have developed a clear understanding of the physical as well as mathematical origin of the decay properties. One important conclusion is that even for metals, one can choose wavefunctions that decay faster than any algebraic power. (2) We have developed algorithms that make use of these localization properties. Our algorithms are based on non-orthogonal formulations of the density functional theory. Our key contribution is to add a localization step into the algorithm. The addition of this localization step makes the algorithm quite robust and much more accurate. Moreover, we can control the accuracy of these algorithms by changing the numerical parameters. (3) We have considerably improved the Fermi operator expansion (FOE) approach. Through pole expansion, we have developed the optimal scaling FOE algorithm.

  1. Choosing the right molecular genetic markers for studying biodiversity: from molecular evolution to practical aspects.

    PubMed

    Chenuil, Anne; Anne, Chenuil

    2006-05-01

    The use of molecular genetic markers (MGMs) has become widespread among evolutionary biologists, and the methods of analysis of genetic data improve rapidly, yet an organized framework in which scientists can work is lacking. Elements of molecular evolution are summarized to explain the origin of variation at the DNA level, its measures, and the relationships linking genetic variability to the biological parameters of the studied organisms. MGM are defined by two components: the DNA region(s) screened, and the technique used to reveal its variation. Criteria of choice belong to three categories: (1) the level of variability, (2) the nature of the information (e.g. dominance vs. codominance, ploidy, ... ) which must be determined according to the biological question and (3) some practical criteria which mainly depend on the equipment of the laboratory and experience of the scientist. A three-step procedure is proposed for drawing up MGMs suitable to answer given biological questions, and compiled data are organized to guide the choice at each step: (1) choice, determined by the biological question, of the level of variability and of the criteria of the nature of information, (2) choice of the DNA region and (3) choice of the technique.

  2. Organisational Learning and the Organisational Life Cycle: The Differential Aspects of an Integrated Relationship in SMEs

    ERIC Educational Resources Information Center

    Tam, Steven; Gray, David E.

    2016-01-01

    Purpose: The purpose of this study is to relate the practice of organisational learning in small- and medium-sized enterprises (SMEs) to the organisational life cycle (OLC), contextualising the differential aspects of an integrated relationship between them. Design/methodology/approach: It is a mixed-method study with two consecutive phases. In…

  3. Integrating influenza antigenic dynamics with molecular evolution

    PubMed Central

    Bedford, Trevor; Suchard, Marc A; Lemey, Philippe; Dudas, Gytis; Gregory, Victoria; Hay, Alan J; McCauley, John W; Russell, Colin A; Smith, Derek J; Rambaut, Andrew

    2014-01-01

    Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution. DOI: http://dx.doi.org/10.7554/eLife.01914.001 PMID:24497547

  4. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    NASA Astrophysics Data System (ADS)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    ) experience with methods of protein purification; (iii) incorporation of appropriate controls into experiments; (iv) use of basic statistics in data analysis; (v) writing papers and grant proposals in accepted scientific style; (vi) peer review; (vii) oral presentation of results and proposals; and (viii) introduction to molecular modeling. Figure 1 illustrates the modular nature of the lab curriculum. Elements from each of the exercises can be separated and treated as stand-alone exercises, or combined into short or long projects. We have been able to offer the opportunity to use sophisticated molecular modeling in the final module through funding from an NSF-ILI grant. However, many of the benefits of the research proposal can be achieved with other computer programs, or even by literature survey alone. Figure 1.Design of project-based biochemistry laboratory. Modules (projects, or portions of projects) are indicated as boxes. Each of these can be treated independently, or used as part of a larger project. Solid lines indicate some suggested paths from one module to the next. The skills and knowledge required for protein purification and design are developed in three units: (i) an introduction to critical assays needed to monitor degree of purification, including an evaluation of assay parameters; (ii) partial purification by ion-exchange techniques; and (iii) preparation of a grant proposal on protein design by mutagenesis. Brief descriptions of each of these units follow, with experimental details of each project at the end of this paper. Assays for Lysozyme Activity and Protein Concentration (4 weeks) The assays mastered during the first unit are a necessary tool for determining the purity of the enzyme during the second unit on purification by ion exchange. These assays allow an introduction to the concept of specific activity (units of enzyme activity per milligram of total protein) as a measure of purity. In this first sequence, students learn a turbidimetric assay

  5. Quantum tunneling splittings from path-integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Mátyus, Edit; Wales, David J.; Althorpe, Stuart C.

    2016-03-01

    We illustrate how path-integral molecular dynamics can be used to calculate ground-state tunnelling splittings in molecules or clusters. The method obtains the splittings from ratios of density matrix elements between the degenerate wells connected by the tunnelling. We propose a simple thermodynamic integration scheme for evaluating these elements. Numerical tests on fully dimensional malonaldehyde yield tunnelling splittings in good overall agreement with the results of diffusion Monte Carlo calculations.

  6. US-Latin American Workshop on Molecular and Materials Sciences: Theoretical and Computational Aspects

    NASA Astrophysics Data System (ADS)

    Micha, David A.

    1994-08-01

    Partial contents include: time-dependent theory of photoabsorption processes; molecular simulation of a chemical reaction in supercritical water; many-body methods for electron correlation; conformational studies of PAF and PAF-antagonists; electric properties of atomic anions; theoretical interpretation of the Li4(-) spectrum using path integrals and ab initio methods; energy levels and structure of tetra-atomic van der Vaals clusters; technology for modern computational science: the John Slater Computing Facility; carbohydrates on the stabilization of biological structures: molecular dynamics simulation; the role of quantum chemistry in heterogeneous catalysis; and corrections to the Born-Oppenheimer approximation by means of perturbation theory.

  7. Confirming an integrated pathology of diabetes and its complications by molecular biomarker-target network analysis.

    PubMed

    Zhao, Zide; Zhang, Yingying; Gai, Fengchun; Wang, Ying

    2016-09-01

    Despite ongoing research into diabetes and its complications, the underlying molecular associations remain to be elucidated. The systematic identification of molecular interactions in associated diseases may be approached using a network analysis strategy. The biomarker-target interrelated molecules associated with diabetes and its complications were identified via the Comparative Toxicogenomics Database (CTD); the Search Tool for Recurring Instances of Neighboring Genes was utilized for network construction. Functional enrichment analysis was performed with Database for Annotation, Visualization and Integrated Discovery software to investigate connections between diabetes and its complications. A total of 142 (including 122 biomarkers, 10 therapeutic targets and 10 overlapping molecules) biomarker-target interrelated molecules associated with diabetes and its complications were identified via the CTD database, and analysis of the network yielded 1,087 biological processes and fifteen Kyoto Encyclopedia of Genes and Genomes pathways with significant P‑values. Various critical aspects of the networks were examined in the present study: a) Intermolecular horizontal and vertical combinations in biomarkers and therapeutic targets associated with diabetes and its complicationb) network topology properties associated with molecular pathological responsec) contribution of key molecules to integrated regulation; and d) crosstalk between multiple pathways. Based on a multi-dimensional analysis, it was concluded that the integrated molecular pathological development of diabetes and its complications does not proceed randomly, which suggests a requirement for integrated, multi-target intervention. PMID:27430657

  8. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    NASA Astrophysics Data System (ADS)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    ) experience with methods of protein purification; (iii) incorporation of appropriate controls into experiments; (iv) use of basic statistics in data analysis; (v) writing papers and grant proposals in accepted scientific style; (vi) peer review; (vii) oral presentation of results and proposals; and (viii) introduction to molecular modeling. Figure 1 illustrates the modular nature of the lab curriculum. Elements from each of the exercises can be separated and treated as stand-alone exercises, or combined into short or long projects. We have been able to offer the opportunity to use sophisticated molecular modeling in the final module through funding from an NSF-ILI grant. However, many of the benefits of the research proposal can be achieved with other computer programs, or even by literature survey alone. Figure 1.Design of project-based biochemistry laboratory. Modules (projects, or portions of projects) are indicated as boxes. Each of these can be treated independently, or used as part of a larger project. Solid lines indicate some suggested paths from one module to the next. The skills and knowledge required for protein purification and design are developed in three units: (i) an introduction to critical assays needed to monitor degree of purification, including an evaluation of assay parameters; (ii) partial purification by ion-exchange techniques; and (iii) preparation of a grant proposal on protein design by mutagenesis. Brief descriptions of each of these units follow, with experimental details of each project at the end of this paper. Assays for Lysozyme Activity and Protein Concentration (4 weeks) The assays mastered during the first unit are a necessary tool for determining the purity of the enzyme during the second unit on purification by ion exchange. These assays allow an introduction to the concept of specific activity (units of enzyme activity per milligram of total protein) as a measure of purity. In this first sequence, students learn a turbidimetric assay

  9. Integrating molecular diagnostics into histopathology training: the Belfast model.

    PubMed

    Flynn, C; James, J; Maxwell, P; McQuaid, S; Ervine, A; Catherwood, M; Loughrey, M B; McGibben, D; Somerville, J; McManus, D T; Gray, M; Herron, B; Salto-Tellez, M

    2014-07-01

    Molecular medicine is transforming modern clinical practice, from diagnostics to therapeutics. Discoveries in research are being incorporated into the clinical setting with increasing rapidity. This transformation is also deeply changing the way we practise pathology. The great advances in cell and molecular biology which have accelerated our understanding of the pathogenesis of solid tumours have been embraced with variable degrees of enthusiasm by diverse medical professional specialties. While histopathologists have not been prompt to adopt molecular diagnostics to date, the need to incorporate molecular pathology into the training of future histopathologists is imperative. Our goal is to create, within an existing 5-year histopathology training curriculum, the structure for formal substantial teaching of molecular diagnostics. This specialist training has two main goals: (1) to equip future practising histopathologists with basic knowledge of molecular diagnostics and (2) to create the option for those interested in a subspecialty experience in tissue molecular diagnostics to pursue this training. It is our belief that this training will help to maintain in future the role of the pathologist at the centre of patient care as the integrator of clinical, morphological and molecular information.

  10. Hereditary nonpolyposis colorectal cancer: Review of clinical, molecular genetics, and counseling aspects

    SciTech Connect

    Bellacosa, A.; Genuardi, M.; Anti, M.; Viel, A.; Ponz de Leon, M.

    1996-04-24

    Lynch syndrome, or hereditary nonpolyposis colon cancer (HNPCC), is an autosomal dominant disease accounting for approximately 1-5% of all colorectal cancer cases. Due to the lack of pathognomonic morphological or biomolecular markers, HNPCC has traditionally posed unique problems to clinicians and geneticists alike, both in terms of diagnosis and clinical management. Recently, novel insight into the pathogenesis of this syndrome has been provided by the identification of its molecular basis. In HNPCC families, germline mutations in any of four genes encoding proteins of a specialized DNA repair system, the mismatch repair, predispose to cancer development. Mutations in mismatch repair genes lead to an overall increase of the mutation rate and are associated with a phenotype of length instability of microsatellite loci. The present report summarizes the clinicopathological aspects of HNPCC and reviews the most recent molecular and biochemical findings. 115 refs., 2 figs., 3 tabs.

  11. A review of feline infectious peritonitis virus: molecular biology, immunopathogenesis, clinical aspects, and vaccination.

    PubMed

    Olsen, C W

    1993-07-01

    Feline infectious peritonitis (FIP) has been an elusive and frustrating problem for veterinary practitioners and cat breeders for many years. Over the last several years, reports have begun to elucidate aspects of the molecular biology of the causal virus (FIPV). These papers complement a rapidly growing base of knowledge concerning the molecular organization and replication of coronaviruses in general. The fascinating immunopathogenesis of FIPV infection and the virus' interaction with macrophages has also been the subject of several recent papers. It is now clear that FIPV may be of interest to scientists other than veterinary virologists since its pathogenesis may provide a useful model system for other viruses whose infectivity is enhanced in the presence of virus-specific antibody. With these advances and the recent release of the first commercially-available FIPV vaccine, it is appropriate to review what is known about the organization and replication of coronaviruses and the pathogenesis of FIPV infection.

  12. Particular aspects in the cytogenetics and molecular biology of salivary gland tumours - current review of reports.

    PubMed

    Ochal-Choińska, Aleksandra J; Osuch-Wójcikiewicz, Ewa

    2016-01-01

    Salivary gland tumours are a group of lesions whose heterogeneity of biological and pathological features is widely reflected in the molecular aspect. This is demonstrated by an increasing number of studies in the field of genetics of these tumours. The aim of this study was to collect the most significant scientific reports on the cytogenetic and molecular data concerning these tumours, which might facilitate the identification of potential biomarkers and therapeutic targets. The analysis covered 71 papers included in the PubMed database. We focused on the most common tumours, such as pleomorphic adenoma, Warthin tumour, mucoepidermoid carcinoma, and others. The aim of this study is to present current knowledge about widely explored genotypic alterations (such as PLAG1 gene in pleomorphic adenoma or MECT1 gene in mucoepidermoid carcinoma), and also about rare markers, like Mena or SOX10 protein, which might also be associated with tumourigenesis and carcinogenesis of these tumours. PMID:27688723

  13. Integrative clustering methods for high-dimensional molecular data

    PubMed Central

    Chalise, Prabhakar; Koestler, Devin C.; Bimali, Milan; Yu, Qing; Fridley, Brooke L.

    2014-01-01

    High-throughput ‘omic’ data, such as gene expression, DNA methylation, DNA copy number, has played an instrumental role in furthering our understanding of the molecular basis in states of human health and disease. As cells with similar morphological characteristics can exhibit entirely different molecular profiles and because of the potential that these discrepancies might further our understanding of patient-level variability in clinical outcomes, there is significant interest in the use of high-throughput ‘omic’ data for the identification of novel molecular subtypes of a disease. While numerous clustering methods have been proposed for identifying of molecular subtypes, most were developed for single “omic’ data types and may not be appropriate when more than one ‘omic’ data type are collected on study subjects. Given that complex diseases, such as cancer, arise as a result of genomic, epigenomic, transcriptomic, and proteomic alterations, integrative clustering methods for the simultaneous clustering of multiple ‘omic’ data types have great potential to aid in molecular subtype discovery. Traditionally, ad hoc manual data integration has been performed using the results obtained from the clustering of individual ‘omic’ data types on the same set of patient samples. However, such methods often result in inconsistent assignment of subjects to the molecular cancer subtypes. Recently, several methods have been proposed in the literature that offers a rigorous framework for the simultaneous integration of multiple ‘omic’ data types in a single comprehensive analysis. In this paper, we present a systematic review of existing integrative clustering methods. PMID:25243110

  14. Inferring Diversity and Evolution in Fish by Means of Integrative Molecular Cytogenetics

    PubMed Central

    Artoni, Roberto Ferreira; Castro, Jonathan Pena; Jacobina, Uedson Pereira; Lima-Filho, Paulo Augusto; Félix da Costa, Gideão Wagner Werneck; Molina, Wagner Franco

    2015-01-01

    Fish constitute a paraphyletic and profusely diversified group that has historically puzzled ichthyologists. Hard efforts are necessary to better understand this group, due to its extensive diversity. New species are often identified and it leads to questions about their phylogenetic aspects. Cytogenetics is becoming an important biodiversity-detection tool also used to measure biodiversity evolutionary aspects. Molecular cytogenetics by fluorescence in situ hybridization (FISH) allowed integrating quantitative and qualitative data from DNA sequences and their physical location in chromosomes and genomes. Although there is no intention on presenting a broader review, the current study presents some evidences on the need of integrating molecular cytogenetic data to other evolutionary biology tools to more precisely infer cryptic species detection, population structuring in marine environments, intra- and interspecific karyoevolutionary aspects of freshwater groups, evolutionary dynamics of marine fish chromosomes, and the origin and differentiation of sexual and B chromosomes. The new cytogenetic field, called cytogenomics, is spreading due to its capacity to give resolute answers to countless questions that cannot be answered by traditional methodologies. Indeed, the association between chromosomal markers and DNA sequencing as well as between biological diversity analysis methodologies and phylogenetics triggers the will to search for answers about fish evolutionary, taxonomic, and structural features. PMID:26345638

  15. Inferring Diversity and Evolution in Fish by Means of Integrative Molecular Cytogenetics.

    PubMed

    Artoni, Roberto Ferreira; Castro, Jonathan Pena; Jacobina, Uedson Pereira; Lima-Filho, Paulo Augusto; da Costa, Gideão Wagner Werneck Félix; Molina, Wagner Franco

    2015-01-01

    Fish constitute a paraphyletic and profusely diversified group that has historically puzzled ichthyologists. Hard efforts are necessary to better understand this group, due to its extensive diversity. New species are often identified and it leads to questions about their phylogenetic aspects. Cytogenetics is becoming an important biodiversity-detection tool also used to measure biodiversity evolutionary aspects. Molecular cytogenetics by fluorescence in situ hybridization (FISH) allowed integrating quantitative and qualitative data from DNA sequences and their physical location in chromosomes and genomes. Although there is no intention on presenting a broader review, the current study presents some evidences on the need of integrating molecular cytogenetic data to other evolutionary biology tools to more precisely infer cryptic species detection, population structuring in marine environments, intra- and interspecific karyoevolutionary aspects of freshwater groups, evolutionary dynamics of marine fish chromosomes, and the origin and differentiation of sexual and B chromosomes. The new cytogenetic field, called cytogenomics, is spreading due to its capacity to give resolute answers to countless questions that cannot be answered by traditional methodologies. Indeed, the association between chromosomal markers and DNA sequencing as well as between biological diversity analysis methodologies and phylogenetics triggers the will to search for answers about fish evolutionary, taxonomic, and structural features.

  16. Monitoring molecular, functional and morphologic aspects of bone metastases using non-invasive imaging.

    PubMed

    Bauerle, Tobias; Komljenovic, Dorde; Semmler, Wolfhard

    2012-03-01

    Bone is among the most common locations of metastasis and therefore represents an important clinical target for diagnostic follow-up in cancer patients. In the pathogenesis of bone metastases, disseminated tumor cells proliferating in bone interact with the local microenvironment stimulating or inhibiting osteoclast and osteoblast activity. Non-invasive imaging methods monitor molecular, functional and morphologic changes in both compartments of these skeletal lesions - the bone and the soft tissue tumor compartment. In the bone compartment, morphologic information on skeletal destruction is assessed by computed tomography (CT) and radiography. Pathogenic processes of osteoclast and osteoblast activity, however, can be imaged using optical imaging, positron emission tomography (PET), single photon emission CT (SPECT) and skeletal scintigraphy. Accordingly, conventional magnetic resonance imaging (MRI) and CT as well as diffusion- weighted MRI and optical imaging are used to assess morphologic aspects on the macroscopic and cellular level of the soft tissue tumor compartment. Imaging methods such as PET, MR spectroscopy, dynamic contrast-enhanced techniques and vessel size imaging further elucidate on pathogenic processes in this compartment including information on metabolism and vascularization. By monitoring these aspects in bone lesions, new insights in the pathogenesis of skeletal metastases can be gained. In translation to the clinical situation, these novel methods for the monitoring of bone metastases might be applied in patients to improve follow-up of these lesions, in particular after therapeutic intervention. This review summarizes established and experimental imaging techniques for the monitoring of tumor and bone cell activity including molecular, functional and morphological aspects in bone metastases. PMID:22214500

  17. Integration of molecular network data reconstructs Gene Ontology

    PubMed Central

    Gligorijević, Vladimir; Janjić, Vuk; Pržulj, Nataša

    2014-01-01

    Motivation: Recently, a shift was made from using Gene Ontology (GO) to evaluate molecular network data to using these data to construct and evaluate GO. Dutkowski et al. provide the first evidence that a large part of GO can be reconstructed solely from topologies of molecular networks. Motivated by this work, we develop a novel data integration framework that integrates multiple types of molecular network data to reconstruct and update GO. We ask how much of GO can be recovered by integrating various molecular interaction data. Results: We introduce a computational framework for integration of various biological networks using penalized non-negative matrix tri-factorization (PNMTF). It takes all network data in a matrix form and performs simultaneous clustering of genes and GO terms, inducing new relations between genes and GO terms (annotations) and between GO terms themselves. To improve the accuracy of our predicted relations, we extend the integration methodology to include additional topological information represented as the similarity in wiring around non-interacting genes. Surprisingly, by integrating topologies of bakers’ yeasts protein–protein interaction, genetic interaction (GI) and co-expression networks, our method reports as related 96% of GO terms that are directly related in GO. The inclusion of the wiring similarity of non-interacting genes contributes 6% to this large GO term association capture. Furthermore, we use our method to infer new relationships between GO terms solely from the topologies of these networks and validate 44% of our predictions in the literature. In addition, our integration method reproduces 48% of cellular component, 41% of molecular function and 41% of biological process GO terms, outperforming the previous method in the former two domains of GO. Finally, we predict new GO annotations of yeast genes and validate our predictions through GIs profiling. Availability and implementation: Supplementary Tables of new GO

  18. Chemical and molecular aspects on interactions of galanthamine and its derivatives with cholinesterases.

    PubMed

    Gulcan, Hayrettin O; Orhan, Ilkay E; Sener, Bilge

    2015-01-01

    Dual action of galanthamine as potent cholinesterase inhibitor and nicotinic modulator has attracted a great attention to be used in the treatment of AD. Consequently, galanthamine, a natural alkaloid isolated from a Galanthus species (snowdrop, Amaryllidaceae), has become an attractive model compound for synthesis of its novel derivatives to discover new drug candidates. Numerous studies have been done to elucidate interactions between galanthamine and its different derivatives and the enzymes; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using in vitro and in silico experimental models. The in vitro studies revealed that galanthamine inhibits AChE in strong, competitive, long-acting, and reversible manner as well as BChE, although its selectivity towards AChE is much higher than BChE. The in silico studies carried out by employing molecular docking experiments as well as molecular dynamics simulations pointed out to existence of strong interactions of galanthamine with the active gorge of AChE, mostly of Torpedo californica (the Pasific electric ray) origin. In this review, we evaluate the mainstays of cholinesterase inhibitory action of galanthamine and its various derivatives from the point of view of chemical and molecular aspects. PMID:25483718

  19. Chemical and molecular aspects on interactions of galanthamine and its derivatives with cholinesterases.

    PubMed

    Gulcan, Hayrettin O; Orhan, Ilkay E; Sener, Bilge

    2015-01-01

    Dual action of galanthamine as potent cholinesterase inhibitor and nicotinic modulator has attracted a great attention to be used in the treatment of AD. Consequently, galanthamine, a natural alkaloid isolated from a Galanthus species (snowdrop, Amaryllidaceae), has become an attractive model compound for synthesis of its novel derivatives to discover new drug candidates. Numerous studies have been done to elucidate interactions between galanthamine and its different derivatives and the enzymes; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using in vitro and in silico experimental models. The in vitro studies revealed that galanthamine inhibits AChE in strong, competitive, long-acting, and reversible manner as well as BChE, although its selectivity towards AChE is much higher than BChE. The in silico studies carried out by employing molecular docking experiments as well as molecular dynamics simulations pointed out to existence of strong interactions of galanthamine with the active gorge of AChE, mostly of Torpedo californica (the Pasific electric ray) origin. In this review, we evaluate the mainstays of cholinesterase inhibitory action of galanthamine and its various derivatives from the point of view of chemical and molecular aspects.

  20. Integration of gender-specific aspects into medical curricula--status quo and future perspectives.

    PubMed

    Pfleiderer, Bettina; Burghaus, Désirée; Bayer, Gudrun; Kindler-Röhrborn, Andrea; Heue, Matthias; Becker, Jan Carl

    2012-01-01

    The consideration of gender aspects in clinical routine is of high importance towards an individualized patient care and a starting point of diversity medicine. Gender-specific awareness is an indispensable basis for an optimized medical treatment. A current study at the medical faculties of Muenster and Duisburg-Essen University (Germany) revealed an insufficient knowledge among students and lecturers in this area. An interdisciplinary, international workshop took place in Muenster (Germany) in May 2012 on the topic how to integrate gender aspects into medical curricula in the future aiming at a better health care for both sexes in long term. This position paper summarizes the conclusions. It was suggested to teach gender-specific contents from the first semester comprehensively - using standardized definitions and a gender-neutral language, since it is crucial not to increase the students' workload any further. The key to success is to implement gender aspects by using meaningful examples on a regular basis - ideally in a longitudinal manner. The content of teaching should be selected by the lecturers and full professors and be considered within students´ exams. To reach these goals, an absolute support of the respective medical faculties as well as the integration of these gender-specific learning objectives into the national competence-based learning catalogue for medical education (NKLM) is obligatory. PMID:23255960

  1. Molecularly imprinted Ru complex catalysts integrated on oxide surfaces.

    PubMed

    Muratsugu, Satoshi; Tada, Mizuki

    2013-02-19

    Selective catalysis is critical for the development of green chemical processes, and natural enzymes that possess specialized three-dimensional reaction pockets with catalytically active sites represent the most sophisticated systems for selective catalysis. A reaction space in an enzyme consists of an active metal center, functional groups for molecular recognition (such as amino acids), and a surrounding protein matrix to prepare the reaction pocket. The artificial design of such an integrated catalytic unit in a non-enzymatic system remains challenging. Molecular imprinting of a supported metal complex provides a promising approach for shape-selective catalysis. In this process, an imprinted cavity with a shape matched to a template molecule is created in a polymer matrix with a catalytically active metal site. In this Account, we review our studies on molecularly imprinted metal complex catalysts, focusing on Ru complexes, on oxide surfaces for shape-selective catalysis. Oxide surface-attached transition metal complex catalysts not only improve thermal stability and catalyst dispersion but also provide unique catalytic performance not observed in homogeneous precursors. We designed molecularly imprinted Ru complexes by using surface-attached Ru complexes with template ligands and inorganic/organic surface matrix overlayers to control the chemical environment around the active metal complex catalysts on oxide surfaces. We prepared the designed, molecularly imprinted Ru complexes on SiO(2) surfaces in a step-by-step manner and characterized them with solid-state (SS) NMR, diffuse-reflectance (DR) UV-vis, X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller isotherm (BET), X-ray fluorescence (XRF), and Ru K-edge extended X-ray absorption fine structure (EXAFS). The catalytic performances of these Ru complexes suggest that this process of molecular imprinting facilitates the artificial integration of catalytic functions at surfaces. Further advances such

  2. Fabrication of high-aspect-ratio nanotips integrated with single-crystal silicon cantilevers

    NASA Astrophysics Data System (ADS)

    Chen, Henry J. H.; Hung, C. S.

    2007-09-01

    This work presents a novel fabrication technique for an atomic force microscope (AFM) nanotip. The high-aspect-ratio silicon nanotip on a single-crystal silicon cantilever was manufactured using inductive coupling plasma (ICP) anisotropic etching and XeF2 isotropic silicon etching processes. The cantilever shape was defined and the high-aspect-ratio silicon nanotip structure was fabricated by ICP anisotropic deep silicon etching (~50-80 µm deep). Nanotip sharpening and single-crystal Si cantilever undercutting were achieved simultaneously via two-step XeF2 isotropic silicon etching. The final structures were observed by a scanning electron microscope (SEM) and the diameter of the nanotip was about ~30 nm. This process is simple, easy to use, CMOS post-process-compatible and suitable for the future IC integrated AFM nanotip applications.

  3. Modulation of HIV transmission by Neisseria gonorrhoeae: molecular and immunological aspects.

    PubMed

    Jarvis, Gary A; Chang, Theresa L

    2012-04-01

    Neisseria gonorrhoeae (GC), a major cause of pelvic inflammatory disease, can facilitate HIV transmission. In response to GC infection, genital epithelial cells can produce cytokines, chemokines and defensins to modulate HIV infection and infectivity. GC can also induce the production of cytokines and chemokines in monocytes and modulate T cell activation. In vivo, an increase in the number of endocervical CD4+ T cells has been found in GC-infected women. Additionally, GC appears to modulate HIV-specific immune responses in HIV-exposed sex workers. Interestingly, in vitro, GC exhibits HIV enhancing or inhibitory effects depending on the HIV target cells. This review summarizes molecular and immunological aspects of the modulation of HIV infection and transmission by GC. Future studies using a multi-cellular system or in animal models will offer insight into the mechanisms by which GC increases HIV transmission.

  4. Novel aspects of the Jahn-Teller effect in molecular and solid-state systems

    NASA Astrophysics Data System (ADS)

    Ernst, Wolfgang E.; Köppel, Horst

    2015-10-01

    The Jahn-Teller effect continues to be a source of insight and inspiration for the interpretation of structural instabilities and dynamic phenomena in molecules and solids. About two decades passed between the publication of the proof of the Jahn-Teller theorem in 1937 and broad scientific activity in the field (although clear experimental evidence of the effect in the ESR spectra of bivalent copper compounds became available in 1950). Then a rapid development set in, and suitable model treatments were set up in the literature and applied to various kinds of problems in molecular and solid-state spectroscopy. Different possibilities for structural distortions, and the associated dynamical (tunneling) processes, were explored, and consequences for magnetic resonance and optical spectra revealed. Key extensions followed, regarding the structural and also dynamic aspects of the Jahn-Teller effect (JTE): similar distortions may also occur in near-degeneracy situations, termed pseudo JTE, which enhances the importance of the effects.

  5. Engineering aspects of design and integration of ECE diagnostic in ITER

    DOE PAGES

    Udintsev, V. S.; Taylor, G.; Pandya, H. K.B.; Austin, M. E.; Casal, N.; Catalin, R.; Clough, M.; Cuquel, B.; Dapena, M.; Drevon, J. -M.; et al

    2015-03-12

    ITER ECE diagnostic [1] needs not only to meet measurement requirements, but also to withstand various loads, such as electromagnetic, mechanical, neutronic and thermal, and to be protected from stray ECH radiation at 170 GHz and other millimeter wave emission, like Collective Thomson scattering which is planned to operate at 60 GHz. Same or similar loads will be applied to other millimetre-wave diagnostics [2], located both in-vessel and in-port plugs. These loads must be taken into account throughout the design phases of the ECE and other microwave diagnostics to ensure their structural integrity and maintainability. The integration of microwave diagnosticsmore » with other ITER systems is another challenging activity which is currently ongoing through port integration and in-vessel integration work. Port Integration has to address the maintenance and the safety aspects of diagnostics, too. Engineering solutions which are being developed to support and to operate ITER ECE diagnostic, whilst complying with safety and maintenance requirements, are discussed in this paper.« less

  6. Engineering aspects of design and integration of ECE diagnostic in ITER

    SciTech Connect

    Udintsev, V. S.; Taylor, G.; Pandya, H. K.B.; Austin, M. E.; Casal, N.; Catalin, R.; Clough, M.; Cuquel, B.; Dapena, M.; Drevon, J. -M.; Feder, R.; Friconneau, J. P.; Giacomin, T.; Guirao, J.; Henderson, M. A.; Hughes, S.; Iglesias, S.; Johnson, D.; Kumar, Siddhart; Kumar, Vina; Levesy, B.; Loesser, D.; Messineo, M.; Penot, C.; Portalès, M.; Oosterbeek, J. W.; Sirinelli, A; Vacas, C.; Vayakis, G.; Walsh, M. J.; Kubo, S.

    2015-03-12

    ITER ECE diagnostic [1] needs not only to meet measurement requirements, but also to withstand various loads, such as electromagnetic, mechanical, neutronic and thermal, and to be protected from stray ECH radiation at 170 GHz and other millimeter wave emission, like Collective Thomson scattering which is planned to operate at 60 GHz. Same or similar loads will be applied to other millimetre-wave diagnostics [2], located both in-vessel and in-port plugs. These loads must be taken into account throughout the design phases of the ECE and other microwave diagnostics to ensure their structural integrity and maintainability. The integration of microwave diagnostics with other ITER systems is another challenging activity which is currently ongoing through port integration and in-vessel integration work. Port Integration has to address the maintenance and the safety aspects of diagnostics, too. Engineering solutions which are being developed to support and to operate ITER ECE diagnostic, whilst complying with safety and maintenance requirements, are discussed in this paper.

  7. Modeling Molecular and Cellular Aspects of Human Disease using the Nematode Caenorhabditis elegans

    PubMed Central

    Silverman, Gary A.; Luke, Cliff J.; Bhatia, Sangeeta R.; Long, Olivia S.; Vetica, Anne C.; Perlmutter, David H.; Pak, Stephen C.

    2009-01-01

    As an experimental system, Caenorhabditis elegans, offers a unique opportunity to interrogate in vivo the genetic and molecular functions of human disease-related genes. For example, C. elegans has provided crucial insights into fundamental biological processes such as cell death and cell fate determinations, as well as pathological processes such as neurodegeneration and microbial susceptibility. The C. elegans model has several distinct advantages including a completely sequenced genome that shares extensive homology with that of mammals, ease of cultivation and storage, a relatively short lifespan and techniques for generating null and transgenic animals. However, the ability to conduct unbiased forward and reverse genetic screens in C. elegans remains one of the most powerful experimental paradigms for discovering the biochemical pathways underlying human disease phenotypes. The identification of these pathways leads to a better understanding of the molecular interactions that perturb cellular physiology, and forms the foundation for designing mechanism-based therapies. To this end, the ability to process large numbers of isogenic animals through automated work stations suggests that C. elegans, manifesting different aspects of human disease phenotypes, will become the platform of choice for in vivo drug discovery and target validation using high-throughput/content screening technologies. PMID:18852689

  8. Apert and Crouzon syndromes-Cognitive development, brain abnormalities, and molecular aspects.

    PubMed

    Fernandes, Marilyse B L; Maximino, Luciana P; Perosa, Gimol B; Abramides, Dagma V M; Passos-Bueno, Maria Rita; Yacubian-Fernandes, Adriano

    2016-06-01

    Apert and Crouzon are the most common craniosynostosis syndromes associated with mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. We conducted a study to examine the molecular biology, brain abnormalities, and cognitive development of individuals with these syndromes. A retrospective longitudinal review of 14 patients with Apert and Crouzon syndromes seen at the outpatient Craniofacial Surgery Hospital for Rehabilitation of Craniofacial Anomalies in Brazil from January 1999 through August 2010 was performed. Patients between 11 and 36 years of age (mean 18.29 ± 5.80), received cognitive evaluations, cerebral magnetic resonance imaging, and molecular DNA analyses. Eight patients with Apert syndrome (AS) had full scale intelligence quotients (FSIQs) that ranged from 47 to 108 (mean 76.9 ± 20.2), and structural brain abnormalities were identified in five of eight patients. Six patients presented with a gain-of-function mutation (p.Ser252Trp) in FGFR2 and FSIQs in those patients ranged from 47 to78 (mean 67.2 ± 10.7). One patient with a gain-of-function mutation (p.Pro253Arg) had a FSIQ of 108 and another patient with an atypical splice mutation (940-2A →G) had a FSIQ of 104. Six patients with Crouzon syndrome had with mutations in exons IIIa and IIIc of FGFR2 and their FSIQs ranged from 82 to 102 (mean 93.5 ± 6.7). These reveal that molecular aspects are another factor that can be considered in studies of global and cognitive development of patients with Apert and Crouzon syndrome (CS). © 2016 Wiley Periodicals, Inc. PMID:27028366

  9. Numerical solution of boundary-integral equations for molecular electrostatics.

    SciTech Connect

    Bardhan, J.; Mathematics and Computer Science; Rush Univ.

    2009-03-07

    Numerous molecular processes, such as ion permeation through channel proteins, are governed by relatively small changes in energetics. As a result, theoretical investigations of these processes require accurate numerical methods. In the present paper, we evaluate the accuracy of two approaches to simulating boundary-integral equations for continuum models of the electrostatics of solvation. The analysis emphasizes boundary-element method simulations of the integral-equation formulation known as the apparent-surface-charge (ASC) method or polarizable-continuum model (PCM). In many numerical implementations of the ASC/PCM model, one forces the integral equation to be satisfied exactly at a set of discrete points on the boundary. We demonstrate in this paper that this approach to discretization, known as point collocation, is significantly less accurate than an alternative approach known as qualocation. Furthermore, the qualocation method offers this improvement in accuracy without increasing simulation time. Numerical examples demonstrate that electrostatic part of the solvation free energy, when calculated using the collocation and qualocation methods, can differ significantly; for a polypeptide, the answers can differ by as much as 10 kcal/mol (approximately 4% of the total electrostatic contribution to solvation). The applicability of the qualocation discretization to other integral-equation formulations is also discussed, and two equivalences between integral-equation methods are derived.

  10. Integrative network analysis reveals molecular mechanisms of blood pressure regulation.

    PubMed

    Huan, Tianxiao; Meng, Qingying; Saleh, Mohamed A; Norlander, Allison E; Joehanes, Roby; Zhu, Jun; Chen, Brian H; Zhang, Bin; Johnson, Andrew D; Ying, Saixia; Courchesne, Paul; Raghavachari, Nalini; Wang, Richard; Liu, Poching; O'Donnell, Christopher J; Vasan, Ramachandran; Munson, Peter J; Madhur, Meena S; Harrison, David G; Yang, Xia; Levy, Daniel

    2015-01-01

    Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expression-related SNPs for their corresponding genes demonstrated enrichment for BP GWAS signals. Genes from the four modules were further projected onto predefined molecular interaction networks, revealing key drivers. Gene subnetworks entailing molecular interactions between key drivers and BP-related genes were uncovered. As proof-of-concept, we validated SH2B3, one of the top key drivers, using Sh2b3(-/-) mice. We found that a significant number of genes predicted to be regulated by SH2B3 in gene networks are perturbed in Sh2b3(-/-) mice, which demonstrate an exaggerated pressor response to angiotensin II infusion. Our findings may help to identify novel targets for the prevention or treatment of hypertension.

  11. Integrative network analysis reveals molecular mechanisms of blood pressure regulation.

    PubMed

    Huan, Tianxiao; Meng, Qingying; Saleh, Mohamed A; Norlander, Allison E; Joehanes, Roby; Zhu, Jun; Chen, Brian H; Zhang, Bin; Johnson, Andrew D; Ying, Saixia; Courchesne, Paul; Raghavachari, Nalini; Wang, Richard; Liu, Poching; O'Donnell, Christopher J; Vasan, Ramachandran; Munson, Peter J; Madhur, Meena S; Harrison, David G; Yang, Xia; Levy, Daniel

    2015-04-01

    Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expression-related SNPs for their corresponding genes demonstrated enrichment for BP GWAS signals. Genes from the four modules were further projected onto predefined molecular interaction networks, revealing key drivers. Gene subnetworks entailing molecular interactions between key drivers and BP-related genes were uncovered. As proof-of-concept, we validated SH2B3, one of the top key drivers, using Sh2b3−/− mice. We found that a significant number of genes predicted to be regulated by SH2B3 in gene networks are perturbed in Sh2b3−/− mice, which demonstrate an exaggerated pressor response to angiotensin II infusion. Our findings may help to identify novel targets for the prevention or treatment of hypertension.

  12. Prediction of Drug Combinations by Integrating Molecular and Pharmacological Data

    PubMed Central

    Zhao, Xing-Ming; Iskar, Murat; Zeller, Georg; Kuhn, Michael; van Noort, Vera; Bork, Peer

    2011-01-01

    Combinatorial therapy is a promising strategy for combating complex disorders due to improved efficacy and reduced side effects. However, screening new drug combinations exhaustively is impractical considering all possible combinations between drugs. Here, we present a novel computational approach to predict drug combinations by integrating molecular and pharmacological data. Specifically, drugs are represented by a set of their properties, such as their targets or indications. By integrating several of these features, we show that feature patterns enriched in approved drug combinations are not only predictive for new drug combinations but also provide insights into mechanisms underlying combinatorial therapy. Further analysis confirmed that among our top ranked predictions of effective combinations, 69% are supported by literature, while the others represent novel potential drug combinations. We believe that our proposed approach can help to limit the search space of drug combinations and provide a new way to effectively utilize existing drugs for new purposes. PMID:22219721

  13. Clinical and molecular aspects of the live attenuated Oka varicella vaccine.

    PubMed

    Quinlivan, Mark; Breuer, Judy

    2014-07-01

    VZV is a ubiquitous member of the Herpesviridae family that causes varicella (chicken pox) and herpes zoster (shingles). Both manifestations can cause great morbidity and mortality and are therefore of significant economic burden. The introduction of varicella vaccination as part of childhood immunization programs has resulted in a remarkable decline in varicella incidence, and associated hospitalizations and deaths, particularly in the USA. The vaccine preparation, vOka, is a live attenuated virus produced by serial passage of a wild-type clinical isolate termed pOka in human and guinea pig cell lines. Although vOka is clinically attenuated, it can cause mild varicella, establish latency, and reactivate to cause herpes zoster. Sequence analysis has shown that vOka differs from pOka by at least 42 loci; however, not all genomes possess the novel vOka change at all positions, creating a heterogeneous population of genetically distinct haplotypes. This, together with the extreme cell-associated nature of VZV replication in cell culture and the lack of an animal model, in which the complete VZV life cycle can be replicated, has limited studies into the molecular basis for vOka attenuation. Comparative studies of vOka with pOka replication in T cells, dorsal root ganglia, and skin indicate that attenuation likely involves multiple mutations within ORF 62 and several other genes. This article presents an overview of the clinical aspects of the vaccine and current progress on understanding the molecular mechanisms that account for the clinical phenotype of reduced virulence.

  14. Integration of Ligand Field Molecular Mechanics in Tinker.

    PubMed

    Foscato, Marco; Deeth, Robert J; Jensen, Vidar R

    2015-06-22

    The ligand field molecular mechanics (LFMM) method for transition-metal complexes has been integrated in Tinker, an easily available and popular molecular modeling software package. The capability to calculate LFMM potentials has been provided by extending the functional forms of the Tinker package as well as by integrating routines for calculating the ligand field stabilization energy (LFSE), which is central to LFMM. The capabilities of the implementation are illustrated by both static calculations on the two spin states of [Fe(NH3)6](2+) and on [Cu(NH3)m](2+) (m = 4, 5, 6) and dynamic (LFMD) simulations of an FeN6-type spin-crossover compound. In addition to showing that results obtained with the Tinker-LFMM implementation are consistent with those of experiment and other computational methods and programs, we note that whereas LFMM is able to handle the conventional tetragonal Jahn-Teller distortion of the bond distances in [Cu(NH3)6](2+), the LFSE term is also necessary in order to obtain even qualitatively correct coordination geometries for the two lower-coordinate copper complexes. PMID:25970002

  15. Molecular aspects on the interaction of phenosafranine to deoxyribonucleic acid: Model for intercalative drug DNA binding

    NASA Astrophysics Data System (ADS)

    Das, Suman; Kumar, Gopinatha Suresh

    2008-01-01

    The mode, mechanism and energetics of interaction of phenosafranine, the planar, cationic and rigid phenazium dye to calf thymus DNA was investigated from absorption, fluorescence, circular dichroism, isothermal titration calorimetry, thermal melting, and viscosity. The study revealed non-cooperative binding of the dye to DNA with an affinity in the range (3.81-4.22) × 10 5 M -1 as observed from diverse techniques and obeying neighbor exclusion principle. The stoichiometry of binding was characterized to be one phenosafranine molecule per two base pairs. The binding was characterized by strong stabilization of DNA against thermal strand separation, large intrinsic circular dichroic changes of DNA by itself and the generation of induced circular dichroism for the optically inactive phenosafranine molecules. Hydrodynamic and fluorescence quenching studies revealed strong evidence that the phenosafranine molecules are intercalated between every alternate base pairs of calf thymus DNA. Isothermal titration calorimetry studies suggested that the binding was exothermic and favoured by both negative enthalpy and positive entropy changes. This study for the first time presents the complete molecular aspects and energetics of phenosafranine complexation to DNA as model for intercalative drug-DNA interaction.

  16. Cellular and molecular aspects of rhabdovirus interactions with insect and plant hosts.

    PubMed

    Ammar, El-Desouky; Tsai, Chi-Wei; Whitfield, Anna E; Redinbaugh, Margaret G; Hogenhout, Saskia A

    2009-01-01

    The rhabdoviruses form a large family (Rhabdoviridae) whose host ranges include humans, other vertebrates, invertebrates, and plants. There are at least 90 plant-infecting rhabdoviruses, several of which are economically important pathogens of various crops. All definitive plant-infecting and many vertebrate-infecting rhabdoviruses are persistently transmitted by insect vectors, and a few putative plant rhabdoviruses are transmitted by mites. Plant rhabdoviruses replicate in their plant and arthropod hosts, and transmission by vectors is highly specific, with each virus species transmitted by one or a few related insect species, mainly aphids, leafhoppers, or planthoppers. Here, we provide an overview of plant rhabdovirus interactions with their insect hosts and of how these interactions compare with those of vertebrate-infecting viruses and with the Sigma rhabdovirus that infects Drosophila flies. We focus on cellular and molecular aspects of vector/host specificity, transmission barriers, and virus receptors in the vectors. In addition, we briefly discuss recent advances in understanding rhabdovirus-plant interactions.

  17. Angular momentum in molecular quantum mechanical integral evaluation

    NASA Astrophysics Data System (ADS)

    Dunlap, Brett I.

    2005-01-01

    Solid-harmonic derivatives of quantum-mechanical integrals over Gaussian transforms of scalar, or radial, atomic basis functions create angular momentum about each center. Generalized Gaunt coefficients limit the amount of cross differentiation for multi-center integrals to ensure that cross differentiation does not affect the total angular momentum. The generalized Gaunt coefficients satisfy a number of other selection rules, which are exploited in a new computer code for computing forces in analytic density-functional theory based on robust and variational fitting of the Kohn-Sham potential. Two-center exponents are defined for four or more solid-harmonic differentiations of matrix elements. Those differentiations can either build up angular momentum about the centers or give forces on molecular potential-energy surfaces, thus generalized Gaunt coefficients of order greater than the number of centers are considered. These 4- j generalized Gaunt coefficients and two-center exponents are used to compute the first derivatives of all integrals involving all the Gaussian exponents on a triplet of centers at once. First all angular factors are contracted with the corresponding part of the linear-combination-of-atomic-orbitals density matrix. This intermediate quantity is then reused for the nuclear attraction integral and the integrals corresponding to each basis function in the analytic fit of the Kohn-Sham potential in the muffin-tin-like, but analytic, Slater-Roothaan method that allows molecules to dissociate into atoms having any desired energy, including the experimental electronic energy. The energy is stationary in all respects and all forces precisely agree with a previous code in tests on small molecules. During geometry optimization of an icosahedral C 720 fullerene computing these angular factors and transforming them via the 4- j generalized Gaunt coefficient takes more than sixty percent of the total computer time. These same angular factors could be used

  18. Integrated molecular portrait of non-small cell lung cancers

    PubMed Central

    2013-01-01

    Background Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC. Methods Comparative genomic hybridization followed by mutational analysis, gene expression and miRNA microarray profiling were performed on 123 paired tumor and non-tumor tissue samples from patients with NSCLC. Results At DNA, mRNA and miRNA levels we could identify molecular markers that discriminated significantly between the various histopathological entities of NSCLC. We identified 34 genomic clusters using aCGH data; several genes exhibited a different profile of aberrations between AC and SCC, including PIK3CA, SOX2, THPO, TP63, PDGFB genes. Gene expression profiling analysis identified SPP1, CTHRC1and GREM1 as potential biomarkers for early diagnosis of the cancer, and SPINK1 and BMP7 to distinguish between AC and SCC in small biopsies or in blood samples. Using integrated genomics approach we found in recurrently altered regions a list of three potential driver genes, MRPS22, NDRG1 and RNF7, which were consistently over-expressed in amplified regions, had wide-spread correlation with an average of ~800 genes throughout the genome and highly associated with histological types. Using a network enrichment analysis, the targets of these potential drivers were seen to be involved in DNA replication, cell cycle, mismatch repair, p53 signalling pathway and other lung cancer related signalling pathways, and many immunological pathways. Furthermore, we also identified one potential driver miRNA hsa-miR-944. Conclusions Integrated molecular characterization of AC and SCC helped identify clinically relevant markers

  19. Growth, modification and integration of carbon nanotubes into molecular electronics

    NASA Astrophysics Data System (ADS)

    Moscatello, Jason P.

    Molecules are the smallest possible elements for electronic devices, with active elements for such devices typically a few Angstroms in footprint area. Owing to the possibility of producing ultra-high density devices, tremendous effort has been invested in producing electronic junctions by using various types of molecules. The major issues for molecular electronics include (1) developing an effective scheme to connect molecules with the present micro- and nano-technology, (2) increasing the lifetime and stabilities of the devices, and (3) increasing their performance in comparison to the state-of-the-art devices. In this work, we attempt to use carbon nanotubes (CNTs) as the interconnecting nanoelectrodes between molecules and microelectrodes. The ultimate goal is to use two individual CNTs to sandwich molecules in a cross-bar configuration while having these CNTs connected with microelectrodes such that the junction displays the electronic character of the molecule chosen. We have successfully developed an effective scheme to connect molecules with CNTs, which is scalable to arrays of molecular electronic devices. To realize this far reaching goal, the following technical topics have been investigated. (1) Synthesis of multi-walled carbon nanotubes (MWCNTs) by thermal chemical vapor deposition (T-CVD) and plasma-enhanced chemical vapor deposition (PECVD) techniques (Chapter 3). We have evaluated the potential use of tubular and bamboo-like MWCNTs grown by T-CVD and PE-CVD in terms of their structural properties. (2) Horizontal dispersion of MWCNTs with and without surfactants, and the integration of MWCNTs to microelectrodes using deposition by dielectrophoresis (DEP) (Chapter 4). We have systematically studied the use of surfactant molecules to disperse and horizontally align MWCNTs on substrates. In addition, DEP is shown to produce impurityfree placement of MWCNTs, forming connections between microelectrodes. We demonstrate the deposition density is tunable by

  20. Aspects of Piaget's cognitive developmental psychology and neurobiology of psychotic disorders - an integrative model.

    PubMed

    Gebhardt, Stefan; Grant, Phillip; von Georgi, Richard; Huber, Martin T

    2008-09-01

    Psychological, neurobiological and neurodevelopmental approaches have frequently been used to provide pathogenic concepts on psychotic disorders. However, aspects of cognitive developmental psychology have hardly been considered in current models. Using a hypothesis-generating approach an integration of these concepts was conducted. According to Piaget (1896-1980), assimilation and accommodation as forms of maintenance and modification of cognitive schemata represent fundamental processes of the brain. In general, based on the perceived input stimuli, cognitive schemata are developed resulting in a conception of the world, the realistic validity and the actuality of which is still being controlled and modified by cognitive adjustment processes. In psychotic disorders, however, a disproportion of environmental demands and the ability to activate required neuronal adaptation processes occurs. We therefore hypothesize a failure of the adjustment of real and requested output patterns. As a consequence autonomous cognitive schemata are generated, which fail to adjust with reality resulting in psychotic symptomatology. Neurobiological, especially neuromodulatory and neuroplastic processes play a central role in these perceptive and cognitive processes. In conclusion, integration of cognitive developmental psychology into the existing pathogenic concepts of psychotic disorders leads to interesting insights into basic disease mechanisms and also guides future research in the cognitive neuroscience of such disorders.

  1. Structural and dynamical aspects of Streptococcus gordonii FabH through molecular docking and MD simulations.

    PubMed

    Shamim, Amen; Abbasi, Sumra Wajid; Azam, Syed Sikander

    2015-07-01

    β-Ketoacyl-ACP-synthase III (FabH or KAS III) has become an attractive target for the development of new antibacterial agents which can overcome the multidrug resistance. Unraveling the fatty acid biosynthesis (FAB) metabolic pathway and understanding structural coordinates of FabH will provide valuable insights to target Streptococcus gordonii for curing oral infection. In this study, we designed inhibitors against therapeutic target FabH, in order to block the FAB pathway. As compared to other targets, FabH has more interactions with other proteins, located on the leading strand with higher codon adaptation index value and associated with lipid metabolism category of COG. Current study aims to gain in silico insights into the structural and dynamical aspect of S. gordonii FabH via molecular docking and molecular dynamics (MD) simulations. The FabH protein is catalytically active in dimerization while it can lock in monomeric state. Current study highlights two residues Pro88 and Leu315 that are close to each other by dimerization. The active site of FabH is composed of the catalytic triad formed by residues Cys112, His249, and Asn279 in which Cys112 is involved in acetyl transfer, while His249 and Asn279 play an active role in decarboxylation. Docking analysis revealed that among the studied compounds, methyl-CoA disulfide has highest GOLD score (82.75), binding affinity (-11 kcal/mol) and exhibited consistently better interactions. During MD simulations, the FabH structure remained stable with the average RMSD value of 1.7 Å and 1.6 Å for undocked protein and docked complex, respectively. Further, crucial hydrogen bonding of the conserved catalytic triad for exhibiting high affinity between the FabH protein and ligand is observed by RDF analysis. The MD simulation results clearly demonstrated that binding of the inhibitor with S. gordonii FabH enhanced the structure and stabilized the dimeric FabH protein. Therefore, the inhibitor has the potential to become

  2. Integrative transcriptome, proteome, phosphoproteome and genetic mapping reveals new aspects in a fiberless mutant of cotton.

    PubMed

    Ma, Qi-Feng; Wu, Chun-Hui; Wu, Man; Pei, Wen-Feng; Li, Xing-Li; Wang, Wen-Kui; Zhang, Jinfa; Yu, Ji-Wen; Yu, Shu-Xun

    2016-01-01

    To investigate the molecular mechanisms of fiber initiation in cotton (Gossypium spp.), an integrated approach combining transcriptome, iTRAQ-based proteome and genetic mapping was taken to compare the ovules of the Xuzhou 142 wild type (WT) with its fuzzless-lintless (fl) mutant at -3 and 0 day post-anthesis. A total of 1,953 mRNAs, 187 proteins, and 131 phosphoproteins were differentially expressed (DE) between WT and fl, and the levels of transcripts and their encoded proteins and phosphoproteins were highly congruent. A functional analysis suggested that the abundance of proteins were mainly involved in amino sugar, nucleotide sugar and fatty acid metabolism, one carbon pool for folate metabolism and flavonoid biosynthesis. qRT-PCR, Western blotting, and enzymatic assays were performed to confirm the regulation of these transcripts and proteins. A molecular mapping located the lintless gene li3 in the fl mutant on chromosome 26 for the first time. A further in-silico physical mapping of DE genes with sequence variations between fl and WT identified one and four candidate genes in the li3 and n2 regions, respectively. Taken together, the transcript abundance, phosphorylation status of proteins at the fiber initiation stage and candidate genes have provided insights into regulatory processes underlying cotton fiber initiation.

  3. Integrative transcriptome, proteome, phosphoproteome and genetic mapping reveals new aspects in a fiberless mutant of cotton

    PubMed Central

    Ma, Qi-Feng; Wu, Chun-Hui; Wu, Man; Pei, Wen-Feng; Li, Xing-Li; Wang, Wen-Kui; Zhang, Jinfa; Yu, Ji-Wen; Yu, Shu-Xun

    2016-01-01

    To investigate the molecular mechanisms of fiber initiation in cotton (Gossypium spp.), an integrated approach combining transcriptome, iTRAQ-based proteome and genetic mapping was taken to compare the ovules of the Xuzhou 142 wild type (WT) with its fuzzless-lintless (fl) mutant at −3 and 0 day post-anthesis. A total of 1,953 mRNAs, 187 proteins, and 131 phosphoproteins were differentially expressed (DE) between WT and fl, and the levels of transcripts and their encoded proteins and phosphoproteins were highly congruent. A functional analysis suggested that the abundance of proteins were mainly involved in amino sugar, nucleotide sugar and fatty acid metabolism, one carbon pool for folate metabolism and flavonoid biosynthesis. qRT-PCR, Western blotting, and enzymatic assays were performed to confirm the regulation of these transcripts and proteins. A molecular mapping located the lintless gene li3 in the fl mutant on chromosome 26 for the first time. A further in-silico physical mapping of DE genes with sequence variations between fl and WT identified one and four candidate genes in the li3 and n2 regions, respectively. Taken together, the transcript abundance, phosphorylation status of proteins at the fiber initiation stage and candidate genes have provided insights into regulatory processes underlying cotton fiber initiation. PMID:27075604

  4. Quantum Thermal Bath for Path Integral Molecular Dynamics Simulation.

    PubMed

    Brieuc, Fabien; Dammak, Hichem; Hayoun, Marc

    2016-03-01

    The quantum thermal bath (QTB) method has been recently developed to account for the quantum nature of the nuclei by using standard molecular dynamics (MD) simulation. QTB-MD is an efficient but approximate method when dealing with strongly anharmonic systems, while path integral molecular dynamics (PIMD) gives exact results but in a huge amount of computation time. The QTB and PIMD methods have been combined in order to improve the PIMD convergence or correct the failures of the QTB-MD technique. Therefore, a new power spectral density of the random force within the QTB has been developed. A modified centroid-virial estimator of the kinetic energy, especially adapted to QTB-PIMD, has also been proposed. The method is applied to selected systems: a one-dimensional double-well system, a ferroelectric phase transition, and the position distribution of an hydrogen atom in a fuel cell material. The advantage of the QTB-PIMD method is its ability to give exact results with a more reasonable computation time for strongly anharmonic systems.

  5. Drug repositioning by kernel-based integration of molecular structure, molecular activity, and phenotype data.

    PubMed

    Wang, Yongcui; Chen, Shilong; Deng, Naiyang; Wang, Yong

    2013-01-01

    Computational inference of novel therapeutic values for existing drugs, i.e., drug repositioning, offers the great prospect for faster and low-risk drug development. Previous researches have indicated that chemical structures, target proteins, and side-effects could provide rich information in drug similarity assessment and further disease similarity. However, each single data source is important in its own way and data integration holds the great promise to reposition drug more accurately. Here, we propose a new method for drug repositioning, PreDR (Predict Drug Repositioning), to integrate molecular structure, molecular activity, and phenotype data. Specifically, we characterize drug by profiling in chemical structure, target protein, and side-effects space, and define a kernel function to correlate drugs with diseases. Then we train a support vector machine (SVM) to computationally predict novel drug-disease interactions. PreDR is validated on a well-established drug-disease network with 1,933 interactions among 593 drugs and 313 diseases. By cross-validation, we find that chemical structure, drug target, and side-effects information are all predictive for drug-disease relationships. More experimentally observed drug-disease interactions can be revealed by integrating these three data sources. Comparison with existing methods demonstrates that PreDR is competitive both in accuracy and coverage. Follow-up database search and pathway analysis indicate that our new predictions are worthy of further experimental validation. Particularly several novel predictions are supported by clinical trials databases and this shows the significant prospects of PreDR in future drug treatment. In conclusion, our new method, PreDR, can serve as a useful tool in drug discovery to efficiently identify novel drug-disease interactions. In addition, our heterogeneous data integration framework can be applied to other problems.

  6. Integrating fossils with molecular phylogenies improves inference of trait evolution.

    PubMed

    Slater, Graham J; Harmon, Luke J; Alfaro, Michael E

    2012-12-01

    Comparative biologists often attempt to draw inferences about tempo and mode in evolution by comparing the fit of evolutionary models to phylogenetic comparative data consisting of a molecular phylogeny with branch lengths and trait measurements from extant taxa. These kinds of approaches ignore historical evidence for evolutionary pattern and process contained in the fossil record. In this article, we show through simulation that incorporation of fossil information dramatically improves our ability to distinguish among models of quantitative trait evolution using comparative data. We further suggest a novel Bayesian approach that allows fossil information to be integrated even when explicit phylogenetic hypotheses are lacking for extinct representatives of extant clades. By applying this approach to a comparative dataset comprising body sizes for caniform carnivorans, we show that incorporation of fossil information not only improves ancestral state estimates relative to those derived from extant taxa alone, but also results in preference of a model of evolution with trend toward large body size over alternative models such as Brownian motion or Ornstein-Uhlenbeck processes. Our approach highlights the importance of considering fossil information when making macroevolutionary inference, and provides a way to integrate the kind of sparse fossil information that is available to most evolutionary biologists.

  7. Some Aspects of the Implementation of Double Group Symmetry and Electron Correlation in Molecular 4-Component Calculations

    NASA Technical Reports Server (NTRS)

    Dyall, Kenneth G.; Arnold, James O. (Technical Monitor)

    1994-01-01

    The efficient implementation of method for electron correlation in molecular 4-component calculations demands that symmetry be exploited where possible. Algorithms for the construction of matrices and the transformation of integrals over symmetry-adapted basis functions, where the point group is restricted to D(sub 2h) and subgroups, will be presented. The merits of keeping the primitive integrals in the scalar basis will be compared with those of transforming them to the 2-spinor basis.

  8. Integration of the stratigraphic aspects of very large sea-floor databases using information processing

    USGS Publications Warehouse

    Jenkins, Clinton N.; Flocks, J.; Kulp, M.; ,

    2006-01-01

    Information-processing methods are described that integrate the stratigraphic aspects of large and diverse collections of sea-floor sample data. They efficiently convert common types of sea-floor data into database and GIS (geographical information system) tables, visual core logs, stratigraphic fence diagrams and sophisticated stratigraphic statistics. The input data are held in structured documents, essentially written core logs that are particularly efficient to create from raw input datasets. Techniques are described that permit efficient construction of regional databases consisting of hundreds of cores. The sedimentological observations in each core are located by their downhole depths (metres below sea floor - mbsf) and also by a verbal term that describes the sample 'situation' - a special fraction of the sediment or position in the core. The main processing creates a separate output event for each instance of top, bottom and situation, assigning top-base mbsf values from numeric or, where possible, from word-based relative locational information such as 'core catcher' in reference to sampler device, and recovery or penetration length. The processing outputs represent the sub-bottom as a sparse matrix of over 20 sediment properties of interest, such as grain size, porosity and colour. They can be plotted in a range of core-log programs including an in-built facility that better suits the requirements of sea-floor data. Finally, a suite of stratigraphic statistics are computed, including volumetric grades, overburdens, thicknesses and degrees of layering. ?? The Geological Society of London 2006.

  9. Integrating the Ontological, Epistemological, and Sociocultural Aspects: A Holistic View of Teacher Education

    ERIC Educational Resources Information Center

    Huang, Teng

    2016-01-01

    The three aspects of teacher change--ontological, epistemological, and sociocultural--are traditionally regarded as independent. Usually only the epistemological aspect is highlighted in formal teacher education. In this paper, I argue that a holistic and interdependent view of these aspects is needed. Thus, this paper aims to explore the process…

  10. Environmental Epigenetics and a Unified Theory of the Molecular Aspects of Evolution: A Neo-Lamarckian Concept that Facilitates Neo-Darwinian Evolution

    PubMed Central

    Skinner, Michael K.

    2015-01-01

    Environment has a critical role in the natural selection process for Darwinian evolution. The primary molecular component currently considered for neo-Darwinian evolution involves genetic alterations and random mutations that generate the phenotypic variation required for natural selection to act. The vast majority of environmental factors cannot directly alter DNA sequence. Epigenetic mechanisms directly regulate genetic processes and can be dramatically altered by environmental factors. Therefore, environmental epigenetics provides a molecular mechanism to directly alter phenotypic variation generationally. Lamarck proposed in 1802 the concept that environment can directly alter phenotype in a heritable manner. Environmental epigenetics and epigenetic transgenerational inheritance provide molecular mechanisms for this process. Therefore, environment can on a molecular level influence the phenotypic variation directly. The ability of environmental epigenetics to alter phenotypic and genotypic variation directly can significantly impact natural selection. Neo-Lamarckian concept can facilitate neo-Darwinian evolution. A unified theory of evolution is presented to describe the integration of environmental epigenetic and genetic aspects of evolution. PMID:25917417

  11. Environmental Epigenetics and a Unified Theory of the Molecular Aspects of Evolution: A Neo-Lamarckian Concept that Facilitates Neo-Darwinian Evolution.

    PubMed

    Skinner, Michael K

    2015-04-26

    Environment has a critical role in the natural selection process for Darwinian evolution. The primary molecular component currently considered for neo-Darwinian evolution involves genetic alterations and random mutations that generate the phenotypic variation required for natural selection to act. The vast majority of environmental factors cannot directly alter DNA sequence. Epigenetic mechanisms directly regulate genetic processes and can be dramatically altered by environmental factors. Therefore, environmental epigenetics provides a molecular mechanism to directly alter phenotypic variation generationally. Lamarck proposed in 1802 the concept that environment can directly alter phenotype in a heritable manner. Environmental epigenetics and epigenetic transgenerational inheritance provide molecular mechanisms for this process. Therefore, environment can on a molecular level influence the phenotypic variation directly. The ability of environmental epigenetics to alter phenotypic and genotypic variation directly can significantly impact natural selection. Neo-Lamarckian concept can facilitate neo-Darwinian evolution. A unified theory of evolution is presented to describe the integration of environmental epigenetic and genetic aspects of evolution.

  12. A portable, integrated analyzer for microfluidic - based molecular analysis.

    PubMed

    Qiu, Xianbo; Chen, Dafeng; Liu, Changchun; Mauk, Michael G; Kientz, Terry; Bau, Haim H

    2011-10-01

    A portable, fully automated analyzer that provides actuation and flow control to a disposable, self-contained, microfluidic cassette ("chip") for point-of-care, molecular testing is described. The analyzer provides mechanical actuation to compress pouches that pump liquids in the cassette, to open and close diaphragm valves for flow control, and to induce vibrations that enhance stirring. The analyzer also provides thermal actuation for the temperature cycling needed for polymerase chain reaction (PCR) amplification of nucleic acids and for various drying processes. To improve the temperature uniformity of the PCR chamber, the system utilizes a double-sided heating/cooling scheme with a custom feedforward, variable, structural proportional-integral-derivative (FVSPID) controller. The analyzer includes a programmable central processing unit that directs the sequence and timing of the various operations and that is interfaced with a computer. The disposable cassette receives a sample, and it carries out cell lysis, nucleic acid isolation, concentration, and purification, thermal cycling, and either real time or lateral flow (LF) based detection. The system's operation was demonstrated by processing saliva samples spiked with B. cereus cells. The amplicons were detected with a lateral flow assay using upconverting phosphor reporter particles. This system is particularly suited for use in regions lacking centralized laboratory facilities and skilled personnel.

  13. Integrated molecular analysis of adult T cell leukemia/lymphoma.

    PubMed

    Kataoka, Keisuke; Nagata, Yasunobu; Kitanaka, Akira; Shiraishi, Yuichi; Shimamura, Teppei; Yasunaga, Jun-Ichirou; Totoki, Yasushi; Chiba, Kenichi; Sato-Otsubo, Aiko; Nagae, Genta; Ishii, Ryohei; Muto, Satsuki; Kotani, Shinichi; Watatani, Yosaku; Takeda, June; Sanada, Masashi; Tanaka, Hiroko; Suzuki, Hiromichi; Sato, Yusuke; Shiozawa, Yusuke; Yoshizato, Tetsuichi; Yoshida, Kenichi; Makishima, Hideki; Iwanaga, Masako; Ma, Guangyong; Nosaka, Kisato; Hishizawa, Masakatsu; Itonaga, Hidehiro; Imaizumi, Yoshitaka; Munakata, Wataru; Ogasawara, Hideaki; Sato, Toshitaka; Sasai, Ken; Muramoto, Kenzo; Penova, Marina; Kawaguchi, Takahisa; Nakamura, Hiromi; Hama, Natsuko; Shide, Kotaro; Kubuki, Yoko; Hidaka, Tomonori; Kameda, Takuro; Nakamaki, Tsuyoshi; Ishiyama, Ken; Miyawaki, Shuichi; Yoon, Sung-Soo; Tobinai, Kensei; Miyazaki, Yasushi; Takaori-Kondo, Akifumi; Matsuda, Fumihiko; Takeuchi, Kengo; Nureki, Osamu; Aburatani, Hiroyuki; Watanabe, Toshiki; Shibata, Tatsuhiro; Matsuoka, Masao; Miyano, Satoru; Shimoda, Kazuya; Ogawa, Seishi

    2015-11-01

    Adult T cell leukemia/lymphoma (ATL) is a peripheral T cell neoplasm of largely unknown genetic basis, associated with human T cell leukemia virus type-1 (HTLV-1) infection. Here we describe an integrated molecular study in which we performed whole-genome, exome, transcriptome and targeted resequencing, as well as array-based copy number and methylation analyses, in a total of 426 ATL cases. The identified alterations overlap significantly with the HTLV-1 Tax interactome and are highly enriched for T cell receptor-NF-κB signaling, T cell trafficking and other T cell-related pathways as well as immunosurveillance. Other notable features include a predominance of activating mutations (in PLCG1, PRKCB, CARD11, VAV1, IRF4, FYN, CCR4 and CCR7) and gene fusions (CTLA4-CD28 and ICOS-CD28). We also discovered frequent intragenic deletions involving IKZF2, CARD11 and TP73 and mutations in GATA3, HNRNPA2B1, GPR183, CSNK2A1, CSNK2B and CSNK1A1. Our findings not only provide unique insights into key molecules in T cell signaling but will also guide the development of new diagnostics and therapeutics in this intractable tumor. PMID:26437031

  14. Key aspects of the molecular and cellular basis of inhalational anthrax.

    PubMed

    Cote, Christopher K; Welkos, Susan L; Bozue, Joel

    2011-12-01

    Bacillus anthracis is the etiologic agent of the disease inhalational anthrax, an acute systemic infection initiated by inhaling spores, which if not rapidly detected and treated, results in death. Decades of research have elucidated novel aspects of anthrax pathogenesis but there are many issues left unresolved.

  15. The Glutamatergic Aspects of Schizophrenia Molecular Pathophysiology: Role of the Postsynaptic Density, and Implications for Treatment

    PubMed Central

    Iasevoli, Felice; Tomasetti, Carmine; Buonaguro, Elisabetta F.; de Bartolomeis, Andrea

    2014-01-01

    Schizophrenia is one of the most debilitating psychiatric diseases with a lifetime prevalence of approximately 1%. Although the specific molecular underpinnings of schizophrenia are still unknown, evidence has long linked its pathophysiology to postsynaptic abnormalities. The postsynaptic density (PSD) is among the molecular structures suggested to be potentially involved in schizophrenia. More specifically, the PSD is an electron-dense thickening of glutamatergic synapses, including ionotropic and metabotropic glutamate receptors, cytoskeletal and scaffolding proteins, and adhesion and signaling molecules. Being implicated in the postsynaptic signaling of multiple neurotransmitter systems, mostly dopamine and glutamate, the PSD constitutes an ideal candidate for studying dopamine-glutamate disturbances in schizophrenia. Recent evidence suggests that some PSD proteins, such as PSD-95, Shank, and Homer are implicated in severe behavioral disorders, including schizophrenia. These findings, further corroborated by genetic and animal studies of schizophrenia, offer new insights for the development of pharmacological strategies able to overcome the limitations in terms of efficacy and side effects of current schizophrenia treatment. Indeed, PSD proteins are now being considered as potential molecular targets against this devastating illness. The current paper reviews the most recent hypotheses on the molecular mechanisms underlying schizophrenia pathophysiology. First, we review glutamatergic dysfunctions in schizophrenia and we provide an update on postsynaptic molecules involvement in schizophrenia pathophysiology by addressing both human and animal studies. Finally, the possibility that PSD proteins may represent potential targets for new molecular interventions in psychosis will be discussed. PMID:24851087

  16. Final Report for Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Glotzer, Sharon C.

    2013-08-28

    In collaboration with researchers at Vanderbilt University, North Carolina State University, Princeton and Oakridge National Laboratory we developed multiscale modeling and simulation methods capable of modeling the synthesis, assembly, and operation of molecular electronics devices. Our role in this project included the development of coarse-grained molecular and mesoscale models and simulation methods capable of simulating the assembly of millions of organic conducting molecules and other molecular components into nanowires, crossbars, and other organized patterns.

  17. Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research.

    PubMed

    Akhmanova, Maria; Osidak, Egor; Domogatsky, Sergey; Rodin, Sergey; Domogatskaya, Anna

    2015-01-01

    Extracellular matrix can influence stem cell choices, such as self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation, or apoptosis. Three aspects of extracellular matrix were extensively studied during the last decade: physical properties, spatial presentation of adhesive epitopes, and molecular complexity. Over 15 different parameters have been shown to influence stem cell choices. Physical aspects include stiffness (or elasticity), viscoelasticity, pore size, porosity, amplitude and frequency of static and dynamic deformations applied to the matrix. Spatial aspects include scaffold dimensionality (2D or 3D) and thickness; cell polarity; area, shape, and microscale topography of cell adhesion surface; epitope concentration, epitope clustering characteristics (number of epitopes per cluster, spacing between epitopes within cluster, spacing between separate clusters, cluster patterns, and level of disorder in epitope arrangement), and nanotopography. Biochemical characteristics of natural extracellular matrix molecules regard diversity and structural complexity of matrix molecules, affinity and specificity of epitope interaction with cell receptors, role of non-affinity domains, complexity of supramolecular organization, and co-signaling by growth factors or matrix epitopes. Synergy between several matrix aspects enables stem cells to retain their function in vivo and may be a key to generation of long-term, robust, and effective in vitro stem cell culture systems. PMID:26351461

  18. Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research

    PubMed Central

    Akhmanova, Maria; Osidak, Egor; Domogatsky, Sergey; Rodin, Sergey; Domogatskaya, Anna

    2015-01-01

    Extracellular matrix can influence stem cell choices, such as self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation, or apoptosis. Three aspects of extracellular matrix were extensively studied during the last decade: physical properties, spatial presentation of adhesive epitopes, and molecular complexity. Over 15 different parameters have been shown to influence stem cell choices. Physical aspects include stiffness (or elasticity), viscoelasticity, pore size, porosity, amplitude and frequency of static and dynamic deformations applied to the matrix. Spatial aspects include scaffold dimensionality (2D or 3D) and thickness; cell polarity; area, shape, and microscale topography of cell adhesion surface; epitope concentration, epitope clustering characteristics (number of epitopes per cluster, spacing between epitopes within cluster, spacing between separate clusters, cluster patterns, and level of disorder in epitope arrangement), and nanotopography. Biochemical characteristics of natural extracellular matrix molecules regard diversity and structural complexity of matrix molecules, affinity and specificity of epitope interaction with cell receptors, role of non-affinity domains, complexity of supramolecular organization, and co-signaling by growth factors or matrix epitopes. Synergy between several matrix aspects enables stem cells to retain their function in vivo and may be a key to generation of long-term, robust, and effective in vitro stem cell culture systems. PMID:26351461

  19. Humic substances biological activity at the plant-soil interface: from environmental aspects to molecular factors.

    PubMed

    Trevisan, Sara; Francioso, Ornella; Quaggiotti, Silvia; Nardi, Serenella

    2010-06-01

    Humic substances (HS) represent the organic material mainly widespread in nature. HS have positive effects on plant physiology by improving soil structure and fertility and by influencing nutrient uptake and root architecture. The biochemical and molecular mechanisms underlying these events are only partially known. HS have been shown to contain auxin and an "auxin-like" activity of humic substances has been proposed, but support to this hypothesis is fragmentary. In this review article, we are giving an overview of available data concerning molecular structures and biological activities of humic substances, with special emphasis on their hormone-like activities. PMID:20495384

  20. Molecular Assemblies, Genes and Genomics Integrated Efficiently (MAGGIE)

    SciTech Connect

    Baliga, Nitin S

    2011-05-26

    Final report on MAGGIE. We set ambitious goals to model the functions of individual organisms and their community from molecular to systems scale. These scientific goals are driving the development of sophisticated algorithms to analyze large amounts of experimental measurements made using high throughput technologies to explain and predict how the environment influences biological function at multiple scales and how the microbial systems in turn modify the environment. By experimentally evaluating predictions made using these models we will test the degree to which our quantitative multiscale understanding wilt help to rationally steer individual microbes and their communities towards specific tasks. Towards this end we have made substantial progress towards understanding evolution of gene families, transcriptional structures, detailed structures of keystone molecular assemblies (proteins and complexes), protein interactions, biological networks, microbial interactions, and community structure. Using comparative analysis we have tracked the evolutionary history of gene functions to understand how novel functions evolve. One level up, we have used proteomics data, high-resolution genome tiling microarrays, and 5' RNA sequencing to revise genome annotations, discover new genes including ncRNAs, and map dynamically changing operon structures of five model organisms: For Desulfovibrio vulgaris Hildenborough, Pyrococcus furiosis, Sulfolobus solfataricus, Methanococcus maripaludis and Haiobacterium salinarum NROL We have developed machine learning algorithms to accurately identify protein interactions at a near-zero false positive rate from noisy data generated using tagfess complex purification, TAP purification, and analysis of membrane complexes. Combining other genome-scale datasets produced by ENIGMA (in particular, microarray data) and available from literature we have been able to achieve a true positive rate as high as 65% at almost zero false positives when

  1. Integrating multiple disturbance aspects: management of an invasive thistle, Carduus nutans

    PubMed Central

    Zhang, Rui; Shea, Katriona

    2012-01-01

    Background and Aims Disturbances occur in most ecological systems, and play an important role in biological invasions. We delimit five key disturbance aspects: intensity, frequency, timing, duration and extent. Few studies address more than one of these aspects, yet interactions and interdependence between aspects may lead to complex outcomes. Methods In a two-cohort experimental study, we examined how multiple aspects (intensity, frequency and timing) of a mowing disturbance regime affect the survival, phenology, growth and reproduction of an invasive thistle Carduus nutans (musk thistle). Key Results Our results show that high intensity and late timing strongly delay flowering phenology and reduce plant survival, capitulum production and plant height. A significant interaction between intensity and timing further magnifies the main effects. Unexpectedly, high frequency alone did not effectively reduce reproduction. However, a study examining only frequency and intensity, and not timing, would have erroneously attributed the importance of timing to frequency. Conclusions We used management of an invasive species as an example to demonstrate the importance of a multiple-aspect disturbance framework. Failure to consider possible interactions, and the inherent interdependence of certain aspects, could result in misinterpretation and inappropriate management efforts. This framework can be broadly applied to improve our understanding of disturbance effects on individual responses, population dynamics and community composition. PMID:22199031

  2. Molecular aspects of glucose homeostasis in skeletal muscle--A focus on the molecular mechanisms of insulin resistance.

    PubMed

    Carnagarin, Revathy; Dharmarajan, Arun M; Dass, Crispin R

    2015-12-01

    Among all the varied actions of insulin, regulation of glucose homeostasis is the most critical and intensively studied. With the availability of glucose from nutrient metabolism, insulin action in muscle results in increased glucose disposal via uptake from the circulation and storage of excess, thereby maintaining euglycemia. This major action of insulin is executed by redistribution of the glucose transporter protein, GLUT4 from intracellular storage sites to the plasma membrane and storage of glucose in the form of glycogen which also involves modulation of actin dynamics that govern trafficking of all the signal proteins of insulin signal transduction. The cellular mechanisms responsible for these trafficking events and the defects associated with insulin resistance are largely enigmatic, and this review provides a consolidated overview of the various molecular mechanisms involved in insulin-dependent glucose homeostasis in skeletal muscle, as insulin resistance at this major peripheral site impacts whole body glucose homeostasis.

  3. Particular aspects in the cytogenetics and molecular biology of salivary gland tumours – current review of reports

    PubMed Central

    Osuch-Wójcikiewicz, Ewa

    2016-01-01

    Salivary gland tumours are a group of lesions whose heterogeneity of biological and pathological features is widely reflected in the molecular aspect. This is demonstrated by an increasing number of studies in the field of genetics of these tumours. The aim of this study was to collect the most significant scientific reports on the cytogenetic and molecular data concerning these tumours, which might facilitate the identification of potential biomarkers and therapeutic targets. The analysis covered 71 papers included in the PubMed database. We focused on the most common tumours, such as pleomorphic adenoma, Warthin tumour, mucoepidermoid carcinoma, and others. The aim of this study is to present current knowledge about widely explored genotypic alterations (such as PLAG1 gene in pleomorphic adenoma or MECT1 gene in mucoepidermoid carcinoma), and also about rare markers, like Mena or SOX10 protein, which might also be associated with tumourigenesis and carcinogenesis of these tumours. PMID:27688723

  4. Particular aspects in the cytogenetics and molecular biology of salivary gland tumours – current review of reports

    PubMed Central

    Osuch-Wójcikiewicz, Ewa

    2016-01-01

    Salivary gland tumours are a group of lesions whose heterogeneity of biological and pathological features is widely reflected in the molecular aspect. This is demonstrated by an increasing number of studies in the field of genetics of these tumours. The aim of this study was to collect the most significant scientific reports on the cytogenetic and molecular data concerning these tumours, which might facilitate the identification of potential biomarkers and therapeutic targets. The analysis covered 71 papers included in the PubMed database. We focused on the most common tumours, such as pleomorphic adenoma, Warthin tumour, mucoepidermoid carcinoma, and others. The aim of this study is to present current knowledge about widely explored genotypic alterations (such as PLAG1 gene in pleomorphic adenoma or MECT1 gene in mucoepidermoid carcinoma), and also about rare markers, like Mena or SOX10 protein, which might also be associated with tumourigenesis and carcinogenesis of these tumours.

  5. Integrable perturbed magnetic fields in toroidal geometry: An exact analytical flux surface label for large aspect ratio

    SciTech Connect

    Kallinikos, N.; Isliker, H.; Vlahos, L.; Meletlidou, E.

    2014-06-15

    An analytical description of magnetic islands is presented for the typical case of a single perturbation mode introduced to tokamak plasma equilibrium in the large aspect ratio approximation. Following the Hamiltonian structure directly in terms of toroidal coordinates, the well known integrability of this system is exploited, laying out a precise and practical way for determining the island topology features, as required in various applications, through an analytical and exact flux surface label.

  6. Physical aspects of the structure and function of helicases as rotary molecular motors

    SciTech Connect

    Pikin, S. A.

    2009-11-15

    Helicases were shown to have common physical properties with rotary molecular motors, such as F{sub 0}F{sub 1}-ATP synthase and type I restriction-modification (RM) enzymes. The necessary conditions for action of molecular motors are chirality, the presence of the C{sub 2} (or lower) symmetry axis within rather large atomic groups, and polarization properties. The estimates were made for the material parameters of helicases, which translocate DNA due to moving chiral kinks without DNA cleavage and are characterized by higher viscosity, low mobility, and smaller chiral kinetic coefficients than type II RM enzymes. This paper discusses the efficiency of helicases with opposite polarities that drive DNA translocation in opposite directions.

  7. Molecular Aspects of Mucoadhesive Carrier Development for Drug Delivery and Improved Absorption

    PubMed Central

    Peppas, Nicholas A; Thomas, J. Brock; McGinity, James

    2011-01-01

    Although the oral route remains the most favored route of drug administration, major scientific obstacles prevent the effective and efficient delivery of low-molecular-mass drugs, peptides and proteins that exhibit poor solubility and permeability. Mucoadhesive dosage forms and the associated drug carriers have the ability to interact at a molecular level with the mucus gel layer that lines the epithelial surfaces of the major absorptive regions of the body. This interaction provides an increased residence time of the therapeutic formulation while localizing the drug at the site of administration. Such local, non-specific targeting leads to an increase in both oral absorption and bioavailability. Fundamental understanding of the biological processes encountered along the gastrointestinal tract can provide a sufficient engineer of carriers that are capable to provide this increase in residence time. Here we discuss the theoretical framework for achieving mucoadhesive systems as related to biomaterials science and the structure of the biomaterials used. PMID:19105897

  8. Biological and molecular aspects of lymph node metastasis in gastro-intestinal cancer.

    PubMed

    Mimori, Koshi; Shinden, Yoshiharu; Eguchi, Hidetoshi; Sudo, Tomoya; Sugimachi, Keishi

    2013-10-01

    Recently, the existence of lymph node micrometastasis, including isolated tumor cells, has been the focus of the development of molecular diagnostic tools for lymph node metastasis in various malignant neoplasms, including those of the GI tract. In this review, we summarize recent molecular biological studies that might provide two reasons to explain the survival of single isolated cancer cells in lymph nodes. One is the specific characteristics of cancer cells, which can exist under severe circumstances, along with recent technological innovations to obtain expression profiles and sequencing from a single cell. The other is microenvironmental factors that support the formation of micrometastasis even in small numbers of cancer cells. The expression profile of whole transcriptome sequencing, genomic sequencing and epigenetic sequencing of a single cancer cell with tumorigenic properties in lymph node metastases should be disclosed in the near future.

  9. Clinical and Molecular Aspects of MBD5-Associated Neurodevelopmental Disorder (MAND).

    PubMed

    Mullegama, Sureni V; Elsea, Sarah H

    2016-08-01

    MBD5-associated neurodevelopmental disorder (MAND) is an umbrella term that describes a group of disorders, 2q23.1 deletion syndrome, 2q23.1 duplication syndrome, and MBD5 variants, that affect the function of methyl-binding domain 5 (MBD5) and share a common set of neurodevelopmental, cognitive, and behavioral impairments. This review provides a comprehensive clinical and molecular synopsis of 2q23.1 deletion syndrome. Approaches to diagnosis, genetic counseling, and up-to-date management are summarized, followed by a discussion of the molecular and functional role of MBD5. Finally, we also include a brief summary of MBD5 variants that affect function of MBD5 and 2q23.1 duplication syndrome.

  10. Solution of multi-center molecular integrals of Slater-type orbitals

    NASA Technical Reports Server (NTRS)

    Tai, H.

    1989-01-01

    The troublesome multi-center molecular integrals of Slater-type orbitals (STO) in molecular physics calculations can be evaluated by using the Fourier transform and proper coupling of the two center exchange integrals. A numerical integration procedure is then readily rendered to the final expression in which the integrand consists of well known special functions of arguments containing the geometrical arrangement of the nuclear centers and the exponents of the atomic orbitals. A practical procedure was devised for the calculation of a general multi-center molecular integrals coupling arbitrary Slater-type orbitals. Symmetry relations and asymptotic conditions are discussed. Explicit expressions of three-center one-electron nuclear-attraction integrals and four-center two-electron repulsion integrals for STO of principal quantum number n=2 are listed. A few numerical results are given for the purpose of comparison.

  11. Physiological and Molecular Aspects of the Inorganic Carbon-Concentrating Mechanism in Cyanobacteria 1

    PubMed Central

    Kaplan, Aaron; Schwarz, Rakefet; Lieman-Hurwitz, Judy; Reinhold, Leonora

    1991-01-01

    This paper reviews progress made in elucidating the inorganic carbon concentrating mechanism in cyanobacteria at the physiological and molecular levels. Emphasis is placed on the mechanism of inorganic carbon transport, physiological and genetical analysis of high-CO2-requiring mutants, the polypeptides induced during adaptation to low CO2, the functional significance of carboxysomes, and the role of carbonic anhydrase. We also make occasional reference to the green algal inorganic carbon-concentrating mechanism. PMID:16668522

  12. Methodological and Clinical Aspects of the Molecular Epidemiology of Mycobacterium tuberculosis and Other Mycobacteria.

    PubMed

    Jagielski, Tomasz; Minias, Alina; van Ingen, Jakko; Rastogi, Nalin; Brzostek, Anna; Żaczek, Anna; Dziadek, Jarosław

    2016-04-01

    Molecular typing has revolutionized epidemiological studies of infectious diseases, including those of a mycobacterial etiology. With the advent of fingerprinting techniques, many traditional concepts regarding transmission, infectivity, or pathogenicity of mycobacterial bacilli have been revisited, and their conventional interpretations have been challenged. Since the mid-1990s, when the first typing methods were introduced, a plethora of other modalities have been proposed. So-called molecular epidemiology has become an essential subdiscipline of modern mycobacteriology. It serves as a resource for understanding the key issues in the epidemiology of tuberculosis and other mycobacterial diseases. Among these issues are disclosing sources of infection, quantifying recent transmission, identifying transmission links, discerning reinfection from relapse, tracking the geographic distribution and clonal expansion of specific strains, and exploring the genetic mechanisms underlying specific phenotypic traits, including virulence, organ tropism, transmissibility, or drug resistance. Since genotyping continues to unravel the biology of mycobacteria, it offers enormous promise in the fight against and prevention of the diseases caused by these pathogens. In this review, molecular typing methods for Mycobacterium tuberculosis and nontuberculous mycobacteria elaborated over the last 2 decades are summarized. The relevance of these methods to the epidemiological investigation, diagnosis, evolution, and control of mycobacterial diseases is discussed.

  13. Evolutionary and molecular aspects of Indian tomato leaf curl virus coat protein.

    PubMed

    Kumar, Sivakumar Prasanth; Patel, Saumya K; Kapopara, Ravi G; Jasrai, Yogesh T; Pandya, Himanshu A

    2012-01-01

    Tomato leaf curl disease (ToLCD) is manifested by yellowing of leaf lamina with upward leaf curl, leaf distortion, shrinking of the leaf surface, and stunted plant growth caused by tomato leaf curl virus (ToLCV). In the present study, using computational methods we explored the evolutionary and molecular prospects of viral coat protein derived from an isolate of Vadodara district, Gujarat (ToLCGV-[Vad]), India. We found that the amino acids in coat protein required for systemic infection, viral particle formation, and insect transmission to host cells were conserved amongst Indian strains. Phylogenetic studies on Indian ToLCV coat proteins showed evolutionary compatibility with other viral taxa. Modeling of coat protein revealed a topology similar to characteristic Geminate viral particle consisting of antiparallel β-barrel motif with N-terminus α-helix. The molecular interaction of coat protein with the viral DNA required for encapsidation and nuclear shuttling was investigated through sequence- and structure-based approaches. We further emphasized the role of loops in coat protein structure as molecular recognition interface.

  14. Effects of molecular symmetry on quantum reaction dynamics: novel aspects of photoinduced nonadiabatic dynamics.

    PubMed

    Al-Jabour, Salih; Leibscher, Monika

    2015-01-15

    Nonadiabatic coupling terms (NACTs) between different electronic states lead to fast radiationless decay in photoexcited molecules. Using molecular symmetry, i.e., symmetry with respect to permutation of identical nuclei and inversion of the molecule in space, the irreducible representations of the NACTs can be determined with a combination of molecular symmetry arguments and quantization rules. Here, we extend these symmetry rules for electronic states and coupling elements and demonstrate the importance of molecular symmetry for nonadiabatic nuclear dynamics. As an example, we consider the NACTs related to the torsion around the CN bond in C5H4NH. We present the results of quantum dynamical simulations of the photoinduced large amplitude torsion on three coupled electronic states and show how the interference between wavepackets leads to radiationless decay, which depends on the symmetry of the NACTs. Moreover, we show that the nuclear spin of the system determines the symmetry of the initial nuclear wave function and thus influences the torsional dynamics. This may open new possibilities for nuclear spin selective laser control of nuclear dynamics.

  15. AlphaSpectrum ASPECT analysis code for background correction & peak integration

    2005-04-13

    The ASPECT code provides a means for rapid analysis of energy-resolved spectra obtained by multi-channel pulse-height analysis (MCA) during (or after) counting of alpha-emissions from a filter air sample (or other suitably prepared sample) utilizing a solid-state detector, or other detector having sufficient energy resolution indiviual radioisotope peaks indentified in a spectrum are fitted using a peak shape algorithm by non-linear least-square fitting procedures that minimize Chi-square differences between the data and a fitted peakmore » function. The code accomplishes the identification of all significant peaks present in the spectrum with automatic recalibration to the 7.68 Po-214 alpha peak from the Radon-222 decay chain, the subtraction of all radon progeny interference overlaps with lower energy peaks in the energy range of Pu-238, Am-241, Pu-239, and U-234/Th-232, and the integration of the counts in any peak identified for these transuranic radionuclides. The output is therefore in the form of isotope specific net transuranic CPM, DPM or concentration, available in near real-time during air sampling. In this "copyright" version, the assumption is made that the alpha spectra to be analyzed have been stored by unique name in sequential form: "FileName(i)", where "FileName" can be any name and i is the index number of the file saved (e.g., i = 1,2, ..., n). this format is one automatically generated by the alpha Environmental Continuous Air Monitor (ECAM), developed by Los Alamos National Laboratory, and manufactured by Canberra Industries, a Laboratory Industrial Partner for this technology. It is assumed in this version of the code that the alpha spectrum data are stored in a 256 channel spectrum, although a larger num ber of channels could be easily accommodated by small code changes. The ECAM data output format is RADNET compliant (an inidustry standard developed at Los Alamos), and include, in addition to a 256-channel alpha spectrum, data on the

  16. Pathophysiology and molecular aspects of diffuse large B-cell lymphoma

    PubMed Central

    Gouveia, Gisele Rodrigues; Siqueira, Sheila Aparecida Coelho; Pereira, Juliana

    2012-01-01

    Diffuse large B-Cell lymphoma is the most common subtype of non-Hodgkin lymphoma in the West. In Brazil, it is the fifth cause of cancer, with more than 55,000 cases and 26,000 deaths per year. At Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, diffuse large B-Cell lymphoma represents 49.7% of all non-Hodgkin lymphoma cases. Initially, the classification of non-Hodgkin lymphoma was based on morphology, but advances in immunology and molecular medicine allowed the introduction of a biological classification for these diseases. As for other cancers, non-Hodgkin lymphoma involves patterns of multifactorial pathogenesis with environmental factors, as well as genetic, occupational and dietary factors, contributing to its development. Multiple lesions involving molecular pathways of B-cell proliferation and differentiation may result in the activation of oncogenes such as the BCL2, BCL6, and MYC genes and the inactivation of tumor suppressor genes such as p53 and INK4, as well as other important transcription factors such as OCT-1 and OCT-2. A dramatic improvement in survival was seen after the recent introduction of the anti-CD20 monoclonal antibody. The association of this antibody to the cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone (CHOP) regimen has increased overall survival of diffuse large B-Cell lymphoma and follicular lymphoma patients by 20%. However, 50% of all diffuse large B-Cell lymphoma patients remain incurable, creating a demand for more research with new advances in treatment. Thus, it is important to know and understand the key factors and molecular pathways involved in the pathogenesis of diffuse large B-Cell lymphoma. PMID:23323070

  17. Food allergens: molecular and immunological aspects, allergen databases and cross-reactivity.

    PubMed

    Lorenz, Anne-Regine; Scheurer, Stephan; Vieths, Stefan

    2015-01-01

    The currently known food allergens are assigned to a relatively small number of protein families. Food allergens grouped into protein families share common functional and structural features that can be attributed to the allergenic potency and potential cross-reactivity of certain proteins. Molecular data, in terms of structural information, biochemical characteristics and clinical relevance for each known allergen, including isoforms and variants, are mainly compiled into four open-access databases. Allergens are designated according to defined criteria by the World Health Organization and the International Union of Immunological Societies Allergen Nomenclature Sub-committee. Food allergies are caused by primary sensitisation to the disease-eliciting food allergens (class I food allergen), or they can be elicited as a consequence of a primary sensitisation to inhalant allergens and subsequent IgE cross-reaction to homologous proteins in food (class II food allergens). Class I and class II allergens display different clinical significance in children and adults and are characterised by different molecular features. In line with this, high stability when exposed to gastrointestinal digestion and heat treatment is attributed to many class I food allergens that frequently induce severe reactions. The stability of a food allergen is determined by its molecular characteristics and can be influenced by structural (chemical) modifications due to thermal processing. Moreover, the immunogenicity and allergenicity of food allergens further depends on specific T cell and B cell epitopes. Although the T cell epitope pattern can be highly diverse for individual patients, several immuno-prominent T cell epitopes have been identified. Such conserved T cell epitopes and IgE cross-reactive B cell epitopes contribute to cross-reactivity between food allergens of the same family and to clinical cross-reactivity, similar to the birch pollen-food syndrome. PMID:26022861

  18. Molecular genetics and clinical aspects of inherited disorders of nerve and muscle.

    PubMed

    Harding, A E

    1992-10-01

    Rapid progress has been made in elucidating the molecular genetic basis of several neuromuscular disorders in the past year. Candidate genes have been identified or analysed in hereditary motor and sensory neuropathy (HMSN) type I, X-linked bulbospinal neuronopathy and non-dystrophic myotonic disorders, and further mutations causing amyloidosis have been identified. A familial amyotrophic lateral sclerosis (ALS) locus maps to chromosome 21 in some families, and the chronic childhood spinal muscular atrophy (SMA), facioscapulohumeral muscular dystrophy (FSHD) and malignant hyperthermia loci have been localized more precisely. PMID:1392132

  19. The Hibernation Continuum: Physiological and Molecular Aspects of Metabolic Plasticity in Mammals.

    PubMed

    van Breukelen, Frank; Martin, Sandra L

    2015-07-01

    Mammals are often considered to be masters of homeostasis, with the ability to maintain a constant internal milieu, despite marked changes in the environment; however, many species exhibit striking physiological and biochemical plasticity in the face of environmental fluctuations. Here, we review metabolic depression and body temperature fluctuation in mammals, with a focus on the extreme example of hibernation in small-bodied eutherian species. Careful exploitation of the phenotypic plasticity of mammals with metabolic flexibility may provide the key to unlocking the molecular secrets of orchestrating and surviving reversible metabolic depression in less plastic species, including humans.

  20. Molecular and genetic aspects in the etiopathogenesis of ameloblastoma: An update

    PubMed Central

    Nagi, Ravleen; Sahu, Shashikant; Rakesh, N

    2016-01-01

    Ameloblastoma is the second most common benign epithelial odontogenic tumor and though it is of a benign nature, it is locally invasive, has a high recurrence rate and could potentially become malignant. Many theories have been proposed to explain the pathogenesis of ameloblastoma. Proper understanding of the pathogenic mechanism involved in ameloblastoma and its proliferation aids in constituting proper treatment of choice at an early stage, preventing morbidity associated with extensive therapy. An attempt has been made to discuss the current concepts related to molecular and genetic changes that occur in ameloblastoma as these could affect treatment plan and prognosis. PMID:27721617

  1. Adolescent Risk-Taking: Integrating Personal, Cognitive, and Social Aspects of Judgment

    ERIC Educational Resources Information Center

    Boyer, Ty W.; Byrnes, James P.

    2009-01-01

    Developmental research has examined individual differences, cognitive developmental bases, and psychosocial factors of adolescent risk-taking. The current paper presents a general adolescent risk-taking model that adopts aspects of each of these primarily independent areas. This model is based on the premise that adolescents take risks when (a)…

  2. Exploring Social Equity Aspects in Integrating Technology in Primary Mathematics Education

    ERIC Educational Resources Information Center

    Stoilescu, Dorian

    2014-01-01

    This research focus on aspects of equity related to the introduction of using technology in classrooms. Technology has the potential to support mathematics pedagogy with visual representations and offer modelling and simulation facilities, increasing the creativity of the learning and teaching processes (Kaput, Ness, & Hoyles, 2008; Stoilescu…

  3. Molecular aspects of gene transfer and foreign DNA acquisition in prokaryotes with regard to safety issues.

    PubMed

    Brigulla, Matthias; Wackernagel, Wilfried

    2010-04-01

    Horizontal gene transfer (HGT) is part of prokaryotic life style and a major factor in evolution. In principle, any combinations of genetic information can be explored via HGT for effects on prokaryotic fitness. HGT mechanisms including transformation, conjugation, transduction, and variations of these plus the role of mobile genetic elements are summarized with emphasis on their potential to translocate foreign DNA. Complementarily, we discuss how foreign DNA can be integrated in recipient cells through homologous recombination (HR), illegitimate recombination (IR), and combinations of both, site-specific recombination, and the reconstitution of plasmids. Integration of foreign DNA by IR is very low, and combinations of IR with HR provide intermediate levels compared to the high frequency of homologous integration. A survey of studies on potential HGT from various transgenic plants indicates very rare transfer of foreign DNA. At the same time, in prokaryotic habitats, genes introduced into transgenic plants are abundant, and natural HGT frequencies are relatively high providing a greater chance for direct transfer instead of via transgenic plants. It is concluded that potential HGT from transgenic plants to prokaryotes is not expected to influence prokaryotic evolution and to have negative effects on human or animal health and the environment.

  4. Final technical report for DOE Computational Nanoscience Project: Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Cummings, P. T.

    2010-02-08

    This document reports the outcomes of the Computational Nanoscience Project, "Integrated Multiscale Modeling of Molecular Computing Devices". It includes a list of participants and publications arising from the research supported.

  5. Mathematical aspects of molecular replacement. I. Algebraic properties of motion spaces

    PubMed Central

    Chirikjian, Gregory S.

    2011-01-01

    Molecular replacement (MR) is a well established method for phasing of X-ray diffraction patterns for crystals composed of biological macromolecules of known chemical structure but unknown conformation. In MR, the starting point is known structural domains that are presumed to be similar in shape to those in the macromolecular structure which is to be determined. A search is then performed over positions and orientations of the known domains within a model of the crystallographic asymmetric unit so as to best match a computed diffraction pattern with experimental data. Unlike continuous rigid-body motions in Euclidean space and the discrete crystallographic space groups, the set of motions over which molecular replacement searches are performed does not form a group under the operation of composition, which is shown here to lack the associative property. However, the set of rigid-body motions in the asymmetric unit forms another mathematical structure called a quasigroup, which can be identified with right-coset spaces of the full group of rigid-body motions with respect to the chiral space group of the macromolecular crystal. The algebraic properties of this space of motions are articulated here. PMID:21844648

  6. Membrane curvature in cell biology: An integration of molecular mechanisms.

    PubMed

    Jarsch, Iris K; Daste, Frederic; Gallop, Jennifer L

    2016-08-15

    Curving biological membranes establishes the complex architecture of the cell and mediates membrane traffic to control flux through subcellular compartments. Common molecular mechanisms for bending membranes are evident in different cell biological contexts across eukaryotic phyla. These mechanisms can be intrinsic to the membrane bilayer (either the lipid or protein components) or can be brought about by extrinsic factors, including the cytoskeleton. Here, we review examples of membrane curvature generation in animals, fungi, and plants. We showcase the molecular mechanisms involved and how they collaborate and go on to highlight contexts of curvature that are exciting areas of future research. Lessons from how membranes are bent in yeast and mammals give hints as to the molecular mechanisms we expect to see used by plants and protists.

  7. Membrane curvature in cell biology: An integration of molecular mechanisms.

    PubMed

    Jarsch, Iris K; Daste, Frederic; Gallop, Jennifer L

    2016-08-15

    Curving biological membranes establishes the complex architecture of the cell and mediates membrane traffic to control flux through subcellular compartments. Common molecular mechanisms for bending membranes are evident in different cell biological contexts across eukaryotic phyla. These mechanisms can be intrinsic to the membrane bilayer (either the lipid or protein components) or can be brought about by extrinsic factors, including the cytoskeleton. Here, we review examples of membrane curvature generation in animals, fungi, and plants. We showcase the molecular mechanisms involved and how they collaborate and go on to highlight contexts of curvature that are exciting areas of future research. Lessons from how membranes are bent in yeast and mammals give hints as to the molecular mechanisms we expect to see used by plants and protists. PMID:27528656

  8. Diversification of Neoaves: integration of molecular sequence data and fossils

    PubMed Central

    Ericson, Per G.P; Anderson, Cajsa L; Britton, Tom; Elzanowski, Andrzej; Johansson, Ulf S; Källersjö, Mari; Ohlson, Jan I; Parsons, Thomas J; Zuccon, Dario; Mayr, Gerald

    2006-01-01

    Patterns of diversification and timing of evolution within Neoaves, which includes almost 95% of all bird species, are virtually unknown. On the other hand, molecular data consistently indicate a Cretaceous origin of many neoavian lineages and the fossil record seems to support an Early Tertiary diversification. Here, we present the first well-resolved molecular phylogeny for Neoaves, together with divergence time estimates calibrated with a large number of stratigraphically and phylogenetically well-documented fossils. Our study defines several well-supported clades within Neoaves. The calibration results suggest that Neoaves, after an initial split from Galloanseres in Mid-Cretaceous, diversified around or soon after the K/T boundary. Our results thus do not contradict palaeontological data and show that there is no solid molecular evidence for an extensive pre-Tertiary radiation of Neoaves. PMID:17148284

  9. [Molecular aspects of the antiviral response against hepatitis C virus implicated in vaccines development].

    PubMed

    Llanes, María Soledad; Palacios, Natalia Soledad; Piccione, Magalí; Ruiz, María Guillermina; Layana, Carla

    2015-04-01

    Hepatitis C is a contagious liver disease caused by hepacivirus of the Flaviviridae family. It has a RNA genome, a unique highly variable molecule. It encodes ten proteins which are necessary to infect cells and multiply. Replication occurs only in hepatocytes. Because of its wide genomic variability and the absence of symptoms, it is difficult to make an early diagnosis and successful treatment. In this review we analyze the molecular mechanism by which the virus infects the hepatocytes and causes the disease. We focused the analysis on different therapies, with the possibility of improving treatment with the use of new specific vaccines. We highlight the use of new therapies based on nucleic acids, mainly DNA vectors. In the near future, once this treatment is adequately evaluated in clinical trials, and the costs are calculated, it could be a very beneficial alternative to conventional methods.

  10. Mitochondrial Disease: Clinical Aspects, Molecular Mechanisms, Translational Science, and Clinical Frontiers

    PubMed Central

    Thornton, Ben; Cohen, Bruce; Copeland, William; Maria, Bernard L.

    2015-01-01

    Mitochondrial medicine provides a metabolic perspective on the pathology of conditions linked with inadequate oxidative phosphorylation. Dysfunction in the mitochondrial machinery can result in improper energy production, leading to cellular injury or even apoptosis. Clinical presentations are often subtle, so clinicians must have a high index of suspicion to make early diagnoses. Symptoms could include muscle weakness and pain, seizures, loss of motor control, decreased visual and auditory functions, metabolic acidosis, acute developmental regression, and immune system dysfunction. The 2013 Neurobiology of Disease in Children Symposium, held in conjunction with the 42nd Annual Meeting of the Child Neurology Society, aimed to (1) describe accepted clinical phenotypes of mitochondrial disease produced from various mitochondrial mutations, (2) discuss contemporary understanding of molecular mechanisms that contribute to disease pathology, (3) highlight the systemic effects produced by dysfunction within the mitochondrial machinery, and (4) introduce current strategies that are being translated from bench to bedside as potential therapeutics. PMID:24916430

  11. Batten Disease: Clinical Aspects, Molecular Mechanisms, Translational Science, and Future Directions

    PubMed Central

    Dolisca, Sarah-Bianca; Mehta, Mitali; Pearce, David A.; Mink, Jonathan W.; Maria, Bernard L.

    2014-01-01

    The neuronal ceroid lipofuscinoses, collectively the most common neurodegenerative disorders of childhood, are primarily caused by an autosomal recessive genetic mutation leading to a lysosomal storage disease. Clinically these diseases manifest at varying ages of onset, and associated symptoms include cognitive decline, movement disorders, seizures, and retinopathy. The underlying cell biology and biochemistry that cause the clinical phenotypes of neuronal ceroid lipofuscinoses are still being elaborated. The 2012 Neurobiology of Disease in Children Symposium, held in conjunction with the 41st Annual Meeting of the Child Neurology Society, aimed to (1) provide a survey of the currently accepted forms of neuronal ceroid lipofuscinoses and their associated genetic mutations and clinical phenotypes; (2) highlight the specific pathology of Batten disease; (3) discuss the contemporary understanding of the molecular mechanisms that lead to pathology; and (4) introduce strategies that are being translated from bench to bedside as potential therapeutics. PMID:23838031

  12. Molecular and cellular aspects of iron-induced hepatic cirrhosis in rodents.

    PubMed Central

    Pietrangelo, A; Gualdi, R; Casalgrandi, G; Montosi, G; Ventura, E

    1995-01-01

    Hepatic fibrosis and cirrhosis are common findings in humans with hemochromatosis. In this study we investigated the molecular pathways of iron-induced hepatic fibrosis and evaluated the anti-fibrogenic effect of vitamin E. Male gerbils were treated with iron-dextran and fed a standard diet or a alpha-tocopherol enriched diet (250 mg/Kg diet). In gerbils on the standard diet at 6 wk after dosing with iron, in situ hybridization analysis documented a dramatic increase of signal for collagen mRNA around iron foci onto liver fat storing cells (FSC), as identified by immunocytochemistry with desmin antibody. After 4 mo, micronodular cirrhosis developed in these animals, with nonparenchymal cells surrounding hepatocyte nodules and expressing high level of TGF beta mRNA. In this group, in vivo labeling with [3H]-thymidine showed a marked proliferation of nonparenchymal cells, including FSC. In iron-dosed gerbils on the vitamin E-enriched diet for 4 mo, in spite of a severe liver iron burden, a normal lobular architecture was found, with a dramatic decrease of collagen mRNA accumulation and collagen deposition. At the molecular level, a total suppression of nonparenchymal cell proliferation was appreciable, although expression of collagen and TGF beta mRNAs was still present into microscopic iron-filled nonparenchymal cell aggregates scattered throughout the hepatic lobule. In conclusion, our study shows that anti-oxidant treatment during experimental hepatic fibrosis arrests fibrogenesis and completely prevents iron induced hepatic cirrhosis mainly through inhibition of nonparenchymal cell proliferation induced by iron. Images PMID:7706489

  13. Multiple time step integrators in ab initio molecular dynamics

    SciTech Connect

    Luehr, Nathan; Martínez, Todd J.; Markland, Thomas E.

    2014-02-28

    Multiple time-scale algorithms exploit the natural separation of time-scales in chemical systems to greatly accelerate the efficiency of molecular dynamics simulations. Although the utility of these methods in systems where the interactions are described by empirical potentials is now well established, their application to ab initio molecular dynamics calculations has been limited by difficulties associated with splitting the ab initio potential into fast and slowly varying components. Here we present two schemes that enable efficient time-scale separation in ab initio calculations: one based on fragment decomposition and the other on range separation of the Coulomb operator in the electronic Hamiltonian. We demonstrate for both water clusters and a solvated hydroxide ion that multiple time-scale molecular dynamics allows for outer time steps of 2.5 fs, which are as large as those obtained when such schemes are applied to empirical potentials, while still allowing for bonds to be broken and reformed throughout the dynamics. This permits computational speedups of up to 4.4x, compared to standard Born-Oppenheimer ab initio molecular dynamics with a 0.5 fs time step, while maintaining the same energy conservation and accuracy.

  14. Integrated Multiscale Modeling of Molecular Computing Devices. Final Report

    SciTech Connect

    Tim Schulze

    2012-11-01

    The general theme of this research has been to expand the capabilities of a simulation technique, Kinetic Monte Carlo (KMC) and apply it to study self-assembled nano-structures on epitaxial thin films. KMC simulates thin film growth and evolution by replacing the detailed dynamics of the system's evolution, which might otherwise be studied using molecular dynamics, with an appropriate stochastic process.

  15. Single nucleotide polymorphism screening, molecular characterization, and evolutionary aspects of chicken Piwi genes.

    PubMed

    Wang, H Z; Ma, T; Chang, G B; Wan, F; Liu, X P; Lu, L; Xu, L; Chen, J; Chen, G H

    2015-01-01

    The P-element-induced wimpy testis (Piwi) gene is involved in germline stem cell self-renewal, meiosis, RNA silencing, and transcriptional regulation. Piwi genes are relatively well conserved in many species, but their function in poultry species is unclear. In this study, Piwi genes were sequenced using a target-sequence capture assay in quail and 28 breeds of chicken. Single nucleotide polymorphisms (SNPs) and evolutionary aspects of these chicken breeds were then analyzed. We found that SNP sites existed mainly in the introns of a few chicken breeds, and we selected an SNP on intron 4 for further verification by Sanger sequencing, the results of which were similar to those obtained by the target-capture sequencing assay. The evolutionary analysis revealed that there were more mutations in the Chahua and Leghorn breeds than in the other breeds, and that the phylogenetic tree was divided into four main categories that suggested that Piwi is evolutionarily conserved, and mutations in the introns might be associated with gametogenesis. The screened SNPs can be used as candidate markers for Piwi, and our results provide basic information for the further study of Piwi function in poultry.

  16. Molecular and cellular aspects and regulation of intestinal lactase-phlorizin hydrolase.

    PubMed

    Naim, H Y

    2001-04-01

    Carbohydrates are hydrolyzed in the intestinal lumen by specific enzymes to monosaccharides before transport across the brush border membrane of epithelial cells into the cell interior. The enzymes implicated in the digestion of carbohydrates in the intestinal lumen are membrane-bound glycoproteins that are expressed at the apical domain of the enterocytes. Absent or reduced activity of one of these enzymes is the cause of disaccharide intolerance and malabsorption, the symptoms of which are abdominal pain, cramps or distention, flatulence, nausea and osmotic diarrhea. Lactose intolerance is the most common intestinal disorder that is associated with an absence or drastically reduced levels of an intestinal enzyme, in this case lactase-phlorizin hydrolase (LPH). The pattern of reduction of activity has been termed late onset of lactase deficiency or adult type hypolactasia. It was thought that the regulation of LPH was post-translational and was associated with altered structural features of the enzyme. Recent studies, however, suggest that the major mechanism of regulation of LPH is transcriptional. Other forms of lactose intolerance include the rare congenital lactase deficiency and secondary forms, such as those caused by mucosal injury, due to infectious gastroenteritis, celiac disease, parasitic infection, drug-induced enteritis and Crohn's disease. This review will shed light on important strucural and biosynthetic aspects of LPH, the role played by particular regions of the LPH protein in its transport, polarized sorting, and function, as well as on the gene expession and regulation of the activity of the enzyme.

  17. Molecular and behavioral aspects of the actions of alcohol on the adult and developing brain.

    PubMed

    Alfonso-Loeches, Silvia; Guerri, Consuelo

    2011-01-01

    The brain is one of the major target organs of alcohol actions. Alcohol abuse can lead to alterations in brain structure and functions and, in some cases, to neurodegeneration. Cognitive deficits and alcohol dependence are highly damaging consequences of alcohol abuse. Clinical and experimental studies have demonstrated that the developing brain is particularly vulnerable to alcohol, and that drinking during gestation can lead to a range of physical, learning and behavioral defects (fetal alcohol spectrum disorders), with the most dramatic presentation corresponding to fetal alcohol syndrome. Recent findings also indicate that adolescence is a stage of brain maturation and that heavy drinking at this stage can have a negative impact on brain structure and functions causing important short- and long-term cognitive and behavioral consequences. The effects of alcohol on the brain are not uniform; some brain areas or cell populations are more vulnerable than others. The prefrontal cortex, the hippocampus, the cerebellum, the white matter and glial cells are particularly susceptible to the effects of ethanol. The molecular actions of alcohol on the brain are complex and involve numerous mechanisms and signaling pathways. Some of the mechanisms involved are common for the adult brain and for the developing brain, while others depend on the developmental stage. During brain ontogeny, alcohol causes irreversible alterations to the brain structure. It also impairs several molecular, neurochemical and cellular events taking place during normal brain development, including alterations in both gene expression regulation and the molecules involved in cell-cell interactions, interference with the mitogenic and growth factor response, enhancement of free radical formation and derangements of glial cell functions. However, in both adult and adolescent brains, alcohol damages specific brain areas through mechanisms involving excitotoxicity, free radical formation and

  18. Concepts and Molecular Aspects in the Polypharmacology of PARP-1 Inhibitors.

    PubMed

    Passeri, Daniela; Camaioni, Emidio; Liscio, Paride; Sabbatini, Paola; Ferri, Martina; Carotti, Andrea; Giacchè, Nicola; Pellicciari, Roberto; Gioiello, Antimo; Macchiarulo, Antonio

    2016-06-20

    Recent years have witnessed a renewed interest in PARP-1 inhibitors as promising anticancer agents with multifaceted functions. Particularly exciting developments include the approval of olaparib (Lynparza) for the treatment of refractory ovarian cancer in patients with BRCA1/2 mutations, and the increasing understanding of the polypharmacology of PARP-1 inhibitors. The aim of this review article is to provide the reader with a comprehensive overview of the distinct levels of the polypharmacology of PARP-1 inhibitors, including 1) inter-family polypharmacology, 2) intra-family polypharmacology, and 3) multi-signaling polypharmacology. Progress made in gaining insight into the molecular basis of these multiple target-independent and target-dependent activities of PARP-1 inhibitors are discussed, with an outlook on the potential impact that a better understanding of polypharmacology may have in aiding the explanation as to why some drug candidates work better than others in clinical settings, albeit acting on the same target with similar inhibitory potency.

  19. Milk proteins-derived bioactive peptides in dairy products: molecular, biological and methodological aspects.

    PubMed

    Dziuba, Bartłomiej; Dziuba, Marta

    2014-01-01

    Proteins are one of the primary components of the food, both in terms of nutrition and function. They are main source of amino acids, essential for synthesis of proteins, and also source of energy. Additionally, many proteins exhibit specific biological activities, which may have effect on functional or pro-health properties of food products. These proteins and their hydrolysis products, peptides, may influence the properties of food and human organism. The number of commercially available food products containing bioactive peptides is very low, apart from that milk proteins are their rich source. It could be supposed that number of available products with declared activity will rise in near future because of observed strong uptrend on interest in such products. Molecular and biological properties of milk proteins, as precursors of bioactive peptides was characterised in the work. Therefore, the strategy of research and obtaining of such peptides both in laboratory and industrial scale, as well as the range of their commercial application, was presented. Several examples of research efforts presenting high potential to develop new products containing bioactive peptides from milk proteins and predetermined as nutraceuticals was described.

  20. Comparative Proteomic Study Reveals the Molecular Aspects of Delayed Ocular Symptoms Induced by Sulfur Mustard

    PubMed Central

    Pashandi, Zaiddodine; Saraygord-Afshari, Neda; Naderi-Manesh, Hossein; Naderi, Mostafa

    2015-01-01

    Objective. Sulfur mustard (SM) is a highly reactive alkylating agent which produces ocular, respiratory, and skin damages. Eyes are the most sensitive organ to SM due to high intrinsic metabolic and rapid turnover rate of corneal epithelium and aqueous-mucous interfaces of the cornea and conjunctiva. Here we investigate underlying molecular mechanism of SM exposure delayed effects which is still a controversial issue after about 30 years. Materials and Methods. Following ethical approval, we have analyzed serum proteome of ten severe SM exposed male patients with delayed eye symptoms with two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry. The western blotting was used to confirm the proteins that have been identified. Results. We have identified thirteen proteins including albumin, haptoglobin, and keratin isoforms as well as immunoglobulin kappa chain which showed upregulation while transferrin and alpha 1 antitrypsin revealed downregulation in these patients in comparison with healthy control group. Conclusions. Our results elevated participation of free iron circulatory imbalance and local matrix-metalloproteinase activity in development of delayed ocular symptoms induced by SM. It demonstrates that SM induced systemic toxicity leads to some serum protein changes that continually and gradually exacerbate the ocular surface injuries. PMID:25685557

  1. Biochemical and molecular aspects of mammalian susceptibility to aflatoxin B{sub 1} carcinogenicity

    SciTech Connect

    Massey, T.E.; Stewart, R.K.; Daniels, J.M.

    1995-03-01

    Aflatoxin B{sub 1} (AFB{sub 1}) is a fungal toxin that has been implicated as a causative agent in human hepatic and extrahepatic carcinogenesis. In this review, the mechanisms involved in AFB{sub 1} toxicity are delineated, in order to describe the features that make a specific cell, tissue, or species susceptible to the mycotoxin. Important considerations include: (i) different mechanisms for bioactivation of AFB{sub 1} to its ultimate carcinogenic epoxide metabolite; (ii) the balance between bioactivation to and detoxification of the epoxide; (iii) the interaction of AFB{sub 1} epoxide with DNA and the mutational events leading to neoplastic transformation; (iv) the role of cytotoxicity in AFB{sub 1} carcinogenesis; (v) the significance of nonepoxide metabolites in toxicity; and (vi) the contribution of mycotoxin-unrelated disease processes. Although considerable controversy remains about the importance of specific events, a great deal has been learned about biochemical and molecular actions of AFB{sub 1}. 157 refs., 4 figs., 1 tab.

  2. Molecular aspects of the ontogeny of the pituitary-gonadal axis.

    PubMed

    Huhtaniemi, I

    1995-01-01

    The endocrine function of the mammalian pituitary-gonadal axis begins in utero. This is important particularly for the ontogeny and function of the male reproductive organs, the induction of which is critically dependent on the two fetal testicular hormones, testosterone and anti-müllerian hormone. In contrast, ovarian endocrine activity begins only after birth. The earliest phases of testicular hormone production are probably under autocrine or paracrine regulation, but the dependence on gonadotrophins starts in fetal life. During maturation of the hypothalamic-pituitary-testicular axis, the target organs acquire their responsiveness (viz receptors) before the onset of secretion of the tropic hormonal stimulus. The last link to develop is the feedback regulation, and the whole axis is functional in the developing male rat during the last days of gestation. Although gonadotrophin secretion starts in both sexes simultaneously, the fetal ovary is endocrinologically quiescent--its gonadotrophin responsiveness and endocrine activity begin only after birth. The fetal and postnatal periods of testicular activity have crucial effects on male sexual differentiation, whereas in the female, early sexual development occurs autonomously without influence of ovarian function. The purpose of this review is to elucidate some of the recent findings on the molecular mechanisms involved in the perinatal maturation of the rat hypothalamic-pituitary-gonadal axis.

  3. Hemoglobin Lepore EF Bart's disease: a molecular, hematological, and diagnostic aspects.

    PubMed

    Chaibunruang, Attawut; Fucharoen, Goonnapa; Jetsrisuparb, Arunee; Fucharoen, Supan

    2011-11-01

    We report the molecular basis and hematological phenotype associated with a hitherto undescribed interaction of hemoglobin (Hb) Lepore-Hollandia, Hb E and a deletion of three α-globin genes found in a 3-year-old Thai girl. She had mild anemia with Hb 10.9 g/dl and Hct 35.9% and had never received blood transfusion. Hb analysis revealed Hb E (22.1%) with a normal level of Hb A(2) (1.9%), unusually elevated Hb F (65.9%), Hb Lepore (4.0%), and 5.4% Hb Bart's. Globin gene analyses demonstrated that she carried the Hb Lepore-Hollandia mutation in trans to the Hb E and a compound heterozygosity for α(0)-thalassemia (SEA deletion) and α(+)-thalassemia (3.7 kb deletion), leading to the Hb Lepore EF Bart's disease. Hematological data and diagnostics using combined Hb-HPLC, capillary electrophoresis, and PCR analysis of this condition were presented and compared with those of the patients with other forms of EF Bart's disease and EE Bart's disease in our series. PMID:21302111

  4. Molecular and genetic aspects of controlling the soilborne necrotrophic pathogens Rhizoctonia and Pythium.

    PubMed

    Okubara, Patricia A; Dickman, Martin B; Blechl, Ann E

    2014-11-01

    The soilborne necrotrophic pathogens Rhizoctonia and Pythium infect a wide range of crops in the US and worldwide. These pathogens pose challenges to growers because the diseases they cause are not adequately controlled by fungicides, rotation or, for many hosts, natural genetic resistance. Although a combination of management practices are likely to be required for control of Rhizoctonia and Pythium, genetic resistance remains a key missing component. This review discusses the recent deployment of introduced genes and genome-based information for control of Rhizoctonia, with emphasis on three pathosystems: Rhizoctonia solani AG8 and wheat, R. solani AG1-IA and rice, and R. solani AG3 or AG4 and potato. Molecular mechanisms underlying disease suppression will be addressed, if appropriate. Although less is known about genes and factors suppressive to Pythium, pathogen genomics and biological control studies are providing useful leads to effectors and antifungal factors. Prospects for resistance to Rhizoctonia and Pythium spp. will continue to improve with growing knowledge of pathogenicity strategies, host defense gene action relative to the pathogen infection process, and the role of environmental factors on pathogen-host interactions.

  5. Molecular aspects and chemoprevention of dimethylaminoazobenzene-induced hepatocarcinogenesis: A review.

    PubMed

    Thomas, Nisha Susan; George, Kiran; Namasivayam, Nalini

    2016-01-01

    The lipophilic azo dye dimethylaminoazobenzene (DAB) is a potent hepatocarcinogen accounted as a group-2B carcinogen causing risk to humans. DAB is commonly used as a coloring agent in food, pharmaceuticals, beverages, soap and polishes. The exploration of DAB-induced hepatocarcinogenesis in animal models helped to an extent to perceive the histological, biochemical and molecular mechanisms of DAB carcinogenesis and also the severity of DAB exposure to humans. In experimental animal models, it is well-proved that the procarcinogen DAB is predominantly metabolized by cytochrome P450 enzymes giving rise to the formation of toxic electrophiles and reactive oxygen species (ROS), which further forms DNA adducts leading to the development of hepatic tumors. Recently, research evidence suggests that dietary phytochemicals and plant polyphenols are promising agents to control the incidence of DAB-induced hepatocarcinogenesis by preventing the generation of toxic electrophiles and ROS thereby inhibiting the formation of DNA adducts. This review highlights the role of specific dietary factors, biotransformation of DAB, phenotypic and genotypic alterations, and significance of certain chemopreventive agents against DAB-induced hepatocarcinogenesis. PMID:26272071

  6. Molecular and genetic aspects of controlling the soilborne necrotrophic pathogens Rhizoctonia and Pythium.

    PubMed

    Okubara, Patricia A; Dickman, Martin B; Blechl, Ann E

    2014-11-01

    The soilborne necrotrophic pathogens Rhizoctonia and Pythium infect a wide range of crops in the US and worldwide. These pathogens pose challenges to growers because the diseases they cause are not adequately controlled by fungicides, rotation or, for many hosts, natural genetic resistance. Although a combination of management practices are likely to be required for control of Rhizoctonia and Pythium, genetic resistance remains a key missing component. This review discusses the recent deployment of introduced genes and genome-based information for control of Rhizoctonia, with emphasis on three pathosystems: Rhizoctonia solani AG8 and wheat, R. solani AG1-IA and rice, and R. solani AG3 or AG4 and potato. Molecular mechanisms underlying disease suppression will be addressed, if appropriate. Although less is known about genes and factors suppressive to Pythium, pathogen genomics and biological control studies are providing useful leads to effectors and antifungal factors. Prospects for resistance to Rhizoctonia and Pythium spp. will continue to improve with growing knowledge of pathogenicity strategies, host defense gene action relative to the pathogen infection process, and the role of environmental factors on pathogen-host interactions. PMID:25438786

  7. The Effect of Diabetes Mellitus on Apoptosis in Hippocampus: Cellular and Molecular Aspects

    PubMed Central

    Sadeghi, Akram; Hami, Javad; Razavi, Shahnaz; Esfandiary, Ebrahim; Hejazi, Zahra

    2016-01-01

    Background: Diabetes mellitus is associated with cognitive deficits in humans and animals. These deficits are paralleled by neurophysiological and structural changes in brain. In diabetic animals, impairments of spatial learning, memory, and cognition occur in association with distinct changes in hippocampus, a key brain area for many forms of learning and memory and are particularly sensitive to changes in glucose homeostasis. However, the multifactorial pathogenesis of diabetic encephalopathy is not yet completely understood. Apoptosis plays a crucial role in diabetes-induce neuronal loss in hippocampus. Methods: The effects of diabetes on hippocampus and cognitive/behavioral dysfunctions in experimental models of diabetes are reviewed, with a focus on the negative impact on increased neuronal apoptosis and related cellular and molecular mechanisms. Results: Of all articles that were assessed, most of the experimental studies clearly showed that diabetes causes neuronal apoptosis in hippocampus through multiple mechanisms, including oxidative stress, inhibition of caspases, disturbance in expression of apoptosis regulator genes, as well as deficits in mitochondrial function. The balance between pro-apoptotic and anti-apoptotic signaling may determine the neuronal apoptotic outcome in vitro and in vivo models of experimental diabetes. Conclusions: Dissecting out the mechanisms responsible for diabetes-related changes in the hippocampal cell apoptosis helps improve treatment of impaired cognitive and memory functions in diabetic individuals. PMID:27076895

  8. Molecular aspects and chemoprevention of dimethylaminoazobenzene-induced hepatocarcinogenesis: A review.

    PubMed

    Thomas, Nisha Susan; George, Kiran; Namasivayam, Nalini

    2016-01-01

    The lipophilic azo dye dimethylaminoazobenzene (DAB) is a potent hepatocarcinogen accounted as a group-2B carcinogen causing risk to humans. DAB is commonly used as a coloring agent in food, pharmaceuticals, beverages, soap and polishes. The exploration of DAB-induced hepatocarcinogenesis in animal models helped to an extent to perceive the histological, biochemical and molecular mechanisms of DAB carcinogenesis and also the severity of DAB exposure to humans. In experimental animal models, it is well-proved that the procarcinogen DAB is predominantly metabolized by cytochrome P450 enzymes giving rise to the formation of toxic electrophiles and reactive oxygen species (ROS), which further forms DNA adducts leading to the development of hepatic tumors. Recently, research evidence suggests that dietary phytochemicals and plant polyphenols are promising agents to control the incidence of DAB-induced hepatocarcinogenesis by preventing the generation of toxic electrophiles and ROS thereby inhibiting the formation of DNA adducts. This review highlights the role of specific dietary factors, biotransformation of DAB, phenotypic and genotypic alterations, and significance of certain chemopreventive agents against DAB-induced hepatocarcinogenesis.

  9. Molecular aspects of plant adaptation to life in the Chernobyl zone.

    PubMed

    Kovalchuk, Igor; Abramov, Vladimir; Pogribny, Igor; Kovalchuk, Olga

    2004-05-01

    With each passing year since the Chernobyl accident of 1986, more questions arise about the potential for organisms to adapt to radiation exposure. Often this is thought to be attributed to somatic and germline mutation rates in various organisms. We analyzed the adaptability of native Arabidopsis plants collected from areas with different levels of contamination around the Chernobyl nuclear power plant from 1986 to 1992. Notably, progeny of Chernobyl plants resisted higher concentrations of the mutagens Rose Bengal and methyl methane sulfonate. We analyzed the possible molecular mechanisms of their resistance to mutagens and found a more than 10-fold lower frequency of extrachromosomal homologous recombination, significant differences in the expression of radical scavenging (CAT1 and FSD3) and DNA-repair (RAD1 and RAD51-like) genes upon exposure to mutagens (Rose Bengal and x-rays), and a higher level of global genome methylation. This data suggests that adaptation to ionizing radiation is a complex process involving epigenetic regulation of gene expression and genome stabilization that improves plants' resistance to environmental mutagens.

  10. Physiological and Molecular Aspects of Tolerance to Environmental Constraints in Grain and Forage Legumes

    PubMed Central

    Bargaz, Adnane; Zaman-Allah, Mainassara; Farissi, Mohamed; Lazali, Mohamed; Drevon, Jean-Jacques; Maougal, Rim T.; Carlsson, Georg

    2015-01-01

    Despite the agronomical and environmental advantages of the cultivation of legumes, their production is limited by various environmental constraints such as water or nutrient limitation, frost or heat stress and soil salinity, which may be the result of pedoclimatic conditions, intensive use of agricultural lands, decline in soil fertility and environmental degradation. The development of more sustainable agroecosystems that are resilient to environmental constraints will therefore require better understanding of the key mechanisms underlying plant tolerance to abiotic constraints. This review provides highlights of legume tolerance to abiotic constraints with a focus on soil nutrient deficiencies, drought, and salinity. More specifically, recent advances in the physiological and molecular levels of the adaptation of grain and forage legumes to abiotic constraints are discussed. Such adaptation involves complex multigene controlled-traits which also involve multiple sub-traits that are likely regulated under the control of a number of candidate genes. This multi-genetic control of tolerance traits might also be multifunctional, with extended action in response to a number of abiotic constraints. Thus, concrete efforts are required to breed for multifunctional candidate genes in order to boost plant stability under various abiotic constraints. PMID:26287163

  11. Cellular and molecular aspects of diabetic nephropathy; the role of VEGF-A.

    PubMed

    Carranza, Katherine; Veron, Dolores; Cercado, Alicia; Bautista, Noemi; Pozo, Wilson; Tufro, Alda; Veron, Delma

    2015-01-01

    The prevalence of diabetes mellitus increased during the last century and it is estimated that 45% of the patients are not diagnosed. In South America the prevalence of diabetes and chronic kidney disease (CKD) increased, with a great disparity among the countries with respect to access to dialysis. In Ecuador it is one of the main causes of mortality, principally in the provinces located on the coast of the Pacific Ocean. The greatest single cause of beginning dialysis is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the residual risk of proteinuria and of terminal CKD remains high. In this review we indicate the importance of the problem globally and in our region. We analyse relevant cellular and molecular studies that illustrate the crucial significance of glomerular events in DN development and evolution and in insulin resistance. We include basic anatomical, pathophysiological and clinical concepts, with special attention to the role of angiogenic factors such as the vascular endothelial growth factor (VEGF-A) and their relationship to the insulin receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins. We also propose various pathways that have therapeutic potential in our opinion. Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could provide solutions to the pressing world problem of DN and generate new treatment alternatives.

  12. DOE contractors' workshop: Cellular and molecular aspects of radiation induced DNA damage and repair

    SciTech Connect

    Not Available

    1987-01-01

    For four decades the US Department of Energy and its predecessors have been the lead federal agency in supporting radiation biology research. Over the years emphasis in this program has gradually shifted from dose-effect studies on animals to research on the effects of radiations of various qualities on cells and molecules. Mechanistic studies on the action of radiation at the subcellular level are few in number and there is a need for more research in this area if we are to gain a better understanding of how radiation affects living cells. The intent of this workshop was to bring together DOE contractors and grantees who are investigating the effects of radiation at the cellular and molecular levels. The aims were to foster the exchange of information on research projects and experimental results, promote collaborative research efforts, and obtain an overview of research currently supported by the Health Effects Research Division of the Office of Health and Environmental Research. The latter is needed by the Office for program planning purposes. This report on the workshop which took place in Albuquerque, New Mexico on March 10-11, 1987, includes an overview with future research recommendations, extended abstracts of the plenary presentations, shorter abstracts of each poster presentation, a workshop agenda and the names and addresses of the attendees.

  13. Cellular and molecular aspects of diabetic nephropathy; the role of VEGF-A.

    PubMed

    Carranza, Katherine; Veron, Dolores; Cercado, Alicia; Bautista, Noemi; Pozo, Wilson; Tufro, Alda; Veron, Delma

    2015-01-01

    The prevalence of diabetes mellitus increased during the last century and it is estimated that 45% of the patients are not diagnosed. In South America the prevalence of diabetes and chronic kidney disease (CKD) increased, with a great disparity among the countries with respect to access to dialysis. In Ecuador it is one of the main causes of mortality, principally in the provinces located on the coast of the Pacific Ocean. The greatest single cause of beginning dialysis is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the residual risk of proteinuria and of terminal CKD remains high. In this review we indicate the importance of the problem globally and in our region. We analyse relevant cellular and molecular studies that illustrate the crucial significance of glomerular events in DN development and evolution and in insulin resistance. We include basic anatomical, pathophysiological and clinical concepts, with special attention to the role of angiogenic factors such as the vascular endothelial growth factor (VEGF-A) and their relationship to the insulin receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins. We also propose various pathways that have therapeutic potential in our opinion. Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could provide solutions to the pressing world problem of DN and generate new treatment alternatives. PMID:26300505

  14. The why and how of enabling the integration of social and ethical aspects in research and development.

    PubMed

    Flipse, Steven M; van der Sanden, Maarten C A; Osseweijer, Patricia

    2013-09-01

    New and Emerging Science and Technology (NEST) based innovations, e.g. in the field of Life Sciences or Nanotechnology, frequently raise societal and political concerns. To address these concerns NEST researchers are expected to deploy socially responsible R&D practices. This requires researchers to integrate social and ethical aspects (SEAs) in their daily work. Many methods can facilitate such integration. Still, why and how researchers should and could use SEAs remains largely unclear. In this paper we aim to relate motivations for NEST researchers to include SEAs in their work, and the requirements to establish such integration from their perspectives, to existing approaches that can be used to establish integration of SEAs in the daily work of these NEST researchers. Based on our analyses, we argue that for the successful integration of SEAs in R&D practice, collaborative approaches between researchers and scholars from the social sciences and humanities seem the most successful. The only way to explore whether that is in fact the case, is by embarking on collaborative research endeavours.

  15. The Integration of Pedagogical Aspects in Environmental Management Systems in Selected South African Primary Schools

    ERIC Educational Resources Information Center

    Kanyimba, Alex; Richter, Barry; Raath, Schalk

    2015-01-01

    Environmental management systems implemented in schools are regarded by many as a mechanism for the integration of environmental matters in all the operational functions of the school. The links, however, between environmental management and curriculum practice have not been adequately addressed in the literature. This article reports on the…

  16. Clinical, morphological, and molecular aspects of sialic acid storage disease manifesting in utero

    PubMed Central

    Froissart, R; Cheillan, D; Bouvier, R; Tourret, S; Bonnet, V; Piraud, M; Maire, I

    2005-01-01

    Background: Sialic acid storage diseases (SASDs) are caused by the defective transport of free sialic acid outside the lysosome. Apart from the Salla presentation in Finland, SASD is a very rare form of lysosomal storage disease (LSD) with approximately 35 cases, all diagnosed after birth, having been reported worldwide. We report a series of 12 French patients with very early manifestations, including eight fetuses diagnosed in utero. Results: Ultrasound examination, fetal autopsy, or clinical examination showed prominent ascites, rarely progressing to complete hydrops, and highlighted the early severity of bone disease. Dramatic increase of free sialic acid in various biological samples confirmed the diagnosis in all cases. Storage staining affinities and storage distribution in placenta and fetal organs allowed differential diagnosis from other LSDs but cannot differentiate between SASD, sialidosis, and galactosialidosis. Fourteen different mutations were identified, showing the molecular heterogeneity of SASD in the French population. We found that the previously described p.Y306X mutation generated two different transcripts, and we identified seven novel mutations: three deletions (del exon 7, del exons10+11 and c.1296delT), one splice site mutation (c.1350+1G→T) one nonsense mutation (p.W339X), and two missense mutations (p.R57C and p.G127E). Conclusions: The severity of our patients' genotypes is in agreement with their phenotypes but not with the importance and early appearance of the very frequent in utero manifestations. Minimal fetal disease in some patients and a reported case of heterogeneity of fetal involvement within a family suggest that factors other than the genotype influence fetal manifestations. PMID:15805149

  17. Molecular aspect ratio and anchoring strength effects in a confined Gay-Berne liquid crystal

    NASA Astrophysics Data System (ADS)

    Cañeda-Guzmán, E.; Moreno-Razo, J. A.; Díaz-Herrera, E.; Sambriski, E. J.

    2014-04-01

    Phase diagrams for Gay-Berne (GB) fluids were obtained from molecular dynamics simulations for GB(2, 5, 1, 2) (i.e. short mesogens) and GB(3, 5, 1, 2) (i.e. long mesogens), which yield isotropic, nematic, and smectic-B phases. The long-mesogen fluid also yields the smectic-A phase. Ordered phases of the long-mesogen fluid form at higher temperatures and lower densities when compared to those of the short-mesogen fluid. The effect of confinement under weak and strong substrate couplings in slab geometry was investigated. Compared to the bulk, the isotropic-nematic transition does not shift in temprature significantly for the weakly coupled substrate in either mesogen fluid. However, the strongly coupled substrate shifts the transition to lower temperature. Confinement induces marked stratification in the short-mesogen fluid. This effect diminishes with distance from the substrate, yielding bulk-like behaviour in the slab central region. Fluid stratification is very weak for the long-mesogen fluid, but the strongly coupled substrate induces 'smectisation', an ordering effect that decays with distance. Orientation of the fluid on the substrate depends on the mesogen. There is no preferred orientation in a plane parallel to the substrate for the weakly coupled case. In the strongly coupled case, the mesogen orientation mimics that of adjacent fluid layers. Planar anchoring is observed with a broad distribution of orientations in the weakly coupled case. In the strongly coupled case, the distribution leans toward planar orientations for the short-mesogen fluid, while a marginal preference for tilting persists in the long-mesogen fluid.

  18. HAMLET kills tumor cells by an apoptosis-like mechanism--cellular, molecular, and therapeutic aspects.

    PubMed

    Svanborg, Catharina; Agerstam, Helena; Aronson, Annika; Bjerkvig, Rolf; Düringer, Caroline; Fischer, Walter; Gustafsson, Lotta; Hallgren, Oskar; Leijonhuvud, Irene; Linse, Sara; Mossberg, Ann-Kristin; Nilsson, Hanna; Pettersson, Jenny; Svensson, Malin

    2003-01-01

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex that induces apoptosis-like death in tumor cells, but leaves fully differentiated cells unaffected. This review summarizes the information on the in vivo effects of HAMLET in patients and tumor models on the tumor cell biology, and on the molecular characteristics of the complex. HAMLET limits the progression of human glioblastomas in a xenograft model and removes skin papillomas in patients. This broad anti-tumor activity includes >40 different lymphomas and carcinomas and apoptosis is independent of p53 or bcl-2. In tumor cells HAMLET enters the cytoplasm, translocates to the perinuclear area, and enters the nuclei where it accumulates. HAMLET binds strongly to histones and disrupts the chromatin organization. In the cytoplasm, HAMLET targets ribosomes and activates caspases. The formation of HAMLET relies on the propensity of alpha-lactalbumin to alter its conformation when the strongly bound Ca2+ ion is released and the protein adopts the apo-conformation that exposes a new fatty acid binding site. Oleic acid (C18:1,9 cis) fits this site with high specificity, and stabilizes the altered protein conformation. The results illustrate how protein folding variants may be beneficial, and how their formation in peripheral tissues may depend on the folding change and the availability of the lipid cofactor. One example is the acid pH in the stomach of the breast-fed child that promotes the formation of HAMLET. This mechanism may contribute to the protective effect of breastfeeding against childhood tumors. We propose that HAMLET should be explored as a novel approach to tumor therapy.

  19. Impulsivity and Concussion in Juvenile Rats: Examining Molecular and Structural Aspects of the Frontostriatal Pathway.

    PubMed

    Hehar, Harleen; Yeates, Keith; Kolb, Bryan; Esser, Michael J; Mychasiuk, Richelle

    2015-01-01

    the need to tailor treatment strategies for mTBI in light of an individual's premorbid characteristics, given significant differences in molecular profiles of the frontostriatal circuits that depend upon sex and the etiology of the behavioural phenotype. PMID:26448536

  20. Eco-innovative design approach: Integrating quality and environmental aspects in prioritizing and solving engineering problems

    NASA Astrophysics Data System (ADS)

    Chakroun, Mahmoud; Gogu, Grigore; Pacaud, Thomas; Thirion, François

    2014-09-01

    This study proposes an eco-innovative design process taking into consideration quality and environmental aspects in prioritizing and solving technical engineering problems. This approach provides a synergy between the Life Cycle Assessment (LCA), the nonquality matrix, the Theory of Inventive Problem Solving (TRIZ), morphological analysis and the Analytical Hierarchy Process (AHP). In the sequence of these tools, LCA assesses the environmental impacts generated by the system. Then, for a better consideration of environmental aspects, a new tool is developed, the non-quality matrix, which defines the problem to be solved first from an environmental point of view. The TRIZ method allows the generation of new concepts and contradiction resolution. Then, the morphological analysis offers the possibility of extending the search space of solutions in a design problem in a systematic way. Finally, the AHP identifies the promising solution(s) by providing a clear logic for the choice made. Their usefulness has been demonstrated through their application to a case study involving a centrifugal spreader with spinning discs.

  1. Quantifying biopsychosocial aspects in everyday contexts: an integrative methodological approach from the behavioral sciences.

    PubMed

    Portell, Mariona; Anguera, M Teresa; Hernández-Mendo, Antonio; Jonsson, Gudberg K

    2015-01-01

    Contextual factors are crucial for evaluative research in psychology, as they provide insights into what works, for whom, in what circumstances, in what respects, and why. Studying behavior in context, however, poses numerous methodological challenges. Although a comprehensive framework for classifying methods seeking to quantify biopsychosocial aspects in everyday contexts was recently proposed, this framework does not contemplate contributions from observational methodology. The aim of this paper is to justify and propose a more general framework that includes observational methodology approaches. Our analysis is rooted in two general concepts: ecological validity and methodological complementarity. We performed a narrative review of the literature on research methods and techniques for studying daily life and describe their shared properties and requirements (collection of data in real time, on repeated occasions, and in natural settings) and classification criteria (eg, variables of interest and level of participant involvement in the data collection process). We provide several examples that illustrate why, despite their higher costs, studies of behavior and experience in everyday contexts offer insights that complement findings provided by other methodological approaches. We urge that observational methodology be included in classifications of research methods and techniques for studying everyday behavior and advocate a renewed commitment to prioritizing ecological validity in behavioral research seeking to quantify biopsychosocial aspects.

  2. Quantifying biopsychosocial aspects in everyday contexts: an integrative methodological approach from the behavioral sciences

    PubMed Central

    Portell, Mariona; Anguera, M Teresa; Hernández-Mendo, Antonio; Jonsson, Gudberg K

    2015-01-01

    Contextual factors are crucial for evaluative research in psychology, as they provide insights into what works, for whom, in what circumstances, in what respects, and why. Studying behavior in context, however, poses numerous methodological challenges. Although a comprehensive framework for classifying methods seeking to quantify biopsychosocial aspects in everyday contexts was recently proposed, this framework does not contemplate contributions from observational methodology. The aim of this paper is to justify and propose a more general framework that includes observational methodology approaches. Our analysis is rooted in two general concepts: ecological validity and methodological complementarity. We performed a narrative review of the literature on research methods and techniques for studying daily life and describe their shared properties and requirements (collection of data in real time, on repeated occasions, and in natural settings) and classification criteria (eg, variables of interest and level of participant involvement in the data collection process). We provide several examples that illustrate why, despite their higher costs, studies of behavior and experience in everyday contexts offer insights that complement findings provided by other methodological approaches. We urge that observational methodology be included in classifications of research methods and techniques for studying everyday behavior and advocate a renewed commitment to prioritizing ecological validity in behavioral research seeking to quantify biopsychosocial aspects. PMID:26089708

  3. Impulsivity and Concussion in Juvenile Rats: Examining Molecular and Structural Aspects of the Frontostriatal Pathway

    PubMed Central

    Hehar, Harleen; Yeates, Keith; Kolb, Bryan; Esser, Michael J.; Mychasiuk, Richelle

    2015-01-01

    the need to tailor treatment strategies for mTBI in light of an individual’s premorbid characteristics, given significant differences in molecular profiles of the frontostriatal circuits that depend upon sex and the etiology of the behavioural phenotype. PMID:26448536

  4. Simple DFT-LSDA modeling of the molecular-like aspects of ultra-thin film properties

    SciTech Connect

    Trickey, S.B.; Mathar, R.J.; Boettger, J.C.

    1996-09-01

    Ordered ultra-thin films (UTF`s) are atomic n-layers (n = 1,2,3,...) with translational symmetry in-plane and molecular-like inter-planar spacings. Though commonly used (especially at relatively large n-values) as models of crystalline surfaces, they are intrinsically interesting and of growing technological significance as the basic building blocks of multi-layer electronic devices. Predicting the structure and properties of even a simple diatomic 1-layer means addressing aspects of molecular binding (and boundary conditions) in the context of an extended, periodically bounded system. At the level of refinement provided by the local spin density approximation to Density Functional Theory, the baseline standard of today`s predictive, chemically specific solid-state calculations, a number of technical and fundamental issues arise. The authors focus on treatment of the isolated atoms, on basis sets, and on numerical precision, as illustrated by the Fe atom and BN 1- and 2-layer calculations. Computational requirements are illustrated by a brief summary of recently completed calculations on crystalline sapphire, {alpha}-Al{sub 2}O{sub 3}, which used the same code.

  5. Mechanistic and clinical aspects of fatigue of ultrahigh molecular weight polyethylene

    NASA Astrophysics Data System (ADS)

    Furmanski, Jevan

    Ultrahigh molecular weight polyethylene (UHMWPE) is a tough semi-crystalline polymer employed widely as a bearing material in total joint replacements. While UHMWPE has been tremendously successful in this application, debris generated due to frictional contact may lead ultimately to an adverse biological reaction and failure of the implant. Radiation cross-linking of the polymer has been undertaken in order to improve its wear resistance, but this also reduces its strength, toughness, and ductility. The majority of implants using highly cross-linked UHMWPE seem to be functioning as designed, but a number of recent reports detail unexpected apparently brittle surface cracking and fracture of such devices. The work presented in this dissertation first documents and analyzes two series of clinical failures of total hip replacements employing highly cross-linked UHMWPE. In the first failure study, an implant was removed shortly after implantation due to infection, and the surface of the implant had sustained extensive surface cracking. An analysis showed that the femoral head contained an asphericity in the main weight bearing region, and a finite element analysis concluded that such a defect doubles the peak contact pressure in the bearing. The increased pressure and decreased toughness were then inferred to have cooperatively resulted in the observed surface cracking. A series of four catastrophically fractured UHMWPE total hip replacement bearings was also analyzed. In all cases, cracks initiated at a sharp notch in the periphery of the implant and propagated into the bulk. Finite element analysis predicted that these locations experienced maximal values of principal stress, and that the stress was of a magnitude and orientation appropriate to agree with the observed crack initiation. The brittle nature of fatigue crack propagation (FCP) in UHMWPE was then explored from a fundamental perspective, with special attention paid to the static mode nature of the process

  6. Integration of molecular pathology, epidemiology and social science for global precision medicine.

    PubMed

    Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L; Nishihara, Reiko; Tan, Andy S; Kawachi, Ichiro; Ogino, Shuji

    2016-01-01

    The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science.

  7. Benchmark values for molecular two-electron integrals arising from the Dirac equation

    NASA Astrophysics Data System (ADS)

    Baǧcı, A.; Hoggan, P. E.

    2015-02-01

    The two-center two-electron Coulomb and hybrid integrals arising in relativistic and nonrelativistic ab initio calculations on molecules are evaluated. Compact, arbitrarily accurate expressions are obtained. They are expressed through molecular auxiliary functions and evaluated with the numerical Global-adaptive method for arbitrary values of parameters in the noninteger Slater-type orbitals. Highly accurate benchmark values are presented for these integrals. The convergence properties of new molecular auxiliary functions are investigated. The comparison for two-center two-electron integrals is made with results obtained from single center expansions by translation of the wave function to a single center with integer principal quantum numbers and results obtained from the Cuba numerical integration algorithm, respectively. The procedures discussed in this work are capable of yielding highly accurate two-center two-electron integrals for all ranges of orbital parameters.

  8. Computational and numerical aspects of using the integral equation method for adhesive layer fracture mechanics analysis

    SciTech Connect

    Giurgiutiu, V.; Ionita, A.; Dillard, D.A.; Graffeo, J.K.

    1996-12-31

    Fracture mechanics analysis of adhesively bonded joints has attracted considerable attention in recent years. A possible approach to the analysis of adhesive layer cracks is to study a brittle adhesive between 2 elastic half-planes representing the substrates. A 2-material 3-region elasticity problem is set up and has to be solved. A modeling technique based on the work of Fleck, Hutchinson, and Suo is used. Two complex potential problems using Muskelishvili`s formulation are set up for the 3-region, 2-material model: (a) a distribution of edge dislocations is employed to simulate the crack and its near field; and (b) a crack-free problem is used to simulate the effect of the external loading applied in the far field. Superposition of the two problems is followed by matching tractions and displacements at the bimaterial boundaries. The Cauchy principal value integral is used to treat the singularities. Imposing the traction-free boundary conditions over the entire crack length yielded a linear system of two integral equations. The parameters of the problem are Dundurs` elastic mismatch coefficients, {alpha} and {beta}, and the ratio c/H representing the geometric position of the crack in the adhesive layer.

  9. Some Aspects of Satellite Imagery Integration from Eros B and Landsat 8

    NASA Astrophysics Data System (ADS)

    Fryskowska, A.; Wojtkowska, M.; Delis, P.; Grochala, A.

    2016-06-01

    The Landsat 8 satellite which was launched in 2013 is a next generation of the Landsat remote sensing satellites series. It is equipped with two new sensors: the Operational Land Imager (OLI) and the Thermal Infrared Sensor (TIRS). What distinguishes this satellite from the previous is four new bands (coastal aerosol, cirrus and two thermal infrared TIRS bands). Similar to its antecedent, Landsat 8 records electromagnetic radiation in a panchromatic band at a range of 0.5‐0.9 μm with a spatial resolution equal to 15 m. In the paper, multispectral imagery integration capabilities of Landsat 8 with data from the new high resolution panchromatic EROS B satellite are analyzed. The range of panchromatic band for EROS B is 0.4‐0.9 μm and spatial resolution is 0.7 m. Research relied on improving the spatial resolution of natural color band combinations (bands: 4,3,2) and of desired false color band composition of Landsat 8 satellite imagery. For this purpose, six algorithms have been tested: Brovey's, Mulitplicative, PCA, IHS, Ehler's, HPF. On the basis of the visual assessment, it was concluded that the best results of multispectral and panchromatic image integration, regardless land cover, are obtained for the multiplicative method. These conclusions were confirmed by statistical analysis using correlation coefficient, ERGAS and R-RMSE indicators.

  10. Updating the Mitochondrial Free Radical Theory of Aging: An Integrated View, Key Aspects, and Confounding Concepts

    PubMed Central

    2013-01-01

    Abstract An updated version of the mitochondrial free radical theory of aging (MFRTA) and longevity is reviewed. Key aspects of the theory are emphasized. Another main focus concerns common misconceptions that can mislead investigators from other specialties, even to wrongly discard the theory. Those different issues include (i) the main reactive oxygen species (ROS)-generating site in the respiratory chain in relation to aging and longevity: complex I; (ii) the close vicinity or even contact between that site and the mitochondrial DNA, in relation to the lack of local efficacy of antioxidants and to sub-cellular compartmentation; (iii) the relationship between mitochondrial ROS production and oxygen consumption; (iv) recent criticisms on the MFRTA; (v) the widespread assumption that ROS are simple “by-products” of the mitochondrial respiratory chain; (vi) the unnecessary postulation of “vicious cycle” hypotheses of mitochondrial ROS generation which are not central to the free radical theory of aging; and (vii) the role of DNA repair concerning endogenous versus exogenous damage. After considering the large body of data already available, two general characteristics responsible for the high maintenance degree of long-lived animals emerge: (i) a low generation rate of endogenous damage: and (ii) the possession of tissue macromolecules that are highly resistant to oxidative modification. Antioxid. Redox Signal. 19, 1420–1445. PMID:23642158

  11. Communication: Kirkwood-Buff integrals in the thermodynamic limit from small-sized molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Cortes-Huerto, R.; Kremer, K.; Potestio, R.

    2016-10-01

    We present an accurate and efficient method to obtain Kirkwood-Buff (KB) integrals in the thermodynamic limit from small-sized molecular dynamics simulations. By introducing finite size effects into integral equations of statistical mechanics, we derive an analytical expression connecting the KB integrals of the bulk system with the fluctuations of the number of molecules in the corresponding closed system. We validate the method by calculating the activity coefficients of aqueous urea mixtures and the KB integrals of Lennard-Jones fluids. Moreover, our results demonstrate how to identify simulation conditions under which computer simulations reach the thermodynamic limit.

  12. Biologic and clinical aspects of integration of different bone substitutes in oral surgery: a literature review.

    PubMed

    Zizzari, Vincenzo Luca; Zara, Susi; Tetè, Giulia; Vinci, Raffaele; Gherlone, Enrico; Cataldi, Amelia

    2016-10-01

    Many bone substitutes have been proposed for bone regeneration, and researchers have focused on the interactions occurring between grafts and host tissue, as the biologic response of host tissue is related to the origin of the biomaterial. Bone substitutes used in oral and maxillofacial surgery could be categorized according to their biologic origin and source as autologous bone graft when obtained from the same individual receiving the graft; homologous bone graft, or allograft, when harvested from an individual other than the one receiving the graft; animal-derived heterologous bone graft, or xenograft, when derived from a species other than human; and alloplastic graft, made of bone substitute of synthetic origin. The aim of this review is to describe the most commonly used bone substitutes, according to their origin, and to focus on the biologic events that ultimately lead to the integration of a biomaterial with the host tissue.

  13. Molecular clock integration of brown adipose tissue formation and function.

    PubMed

    Nam, Deokhwa; Yechoor, Vijay K; Ma, Ke

    2016-01-01

    The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbα, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation. PMID:27385482

  14. Molecular clock integration of brown adipose tissue formation and function

    PubMed Central

    Nam, Deokhwa; Yechoor, Vijay K.; Ma, Ke

    2016-01-01

    Abstract The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbα, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation. PMID:27385482

  15. Molecular clock integration of brown adipose tissue formation and function.

    PubMed

    Nam, Deokhwa; Yechoor, Vijay K; Ma, Ke

    2016-01-01

    The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbα, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation.

  16. An Integrated Approach to Economic and Environmental Aspects of Air Pollution and Climate Interactions

    NASA Astrophysics Data System (ADS)

    Sarofim, M. C.

    2007-12-01

    Emissions of greenhouses gases and conventional pollutants are closely linked through shared generation processes and thus policies directed toward long-lived greenhouse gases affect emissions of conventional pollutants and, similarly, policies directed toward conventional pollutants affect emissions of greenhouse gases. Some conventional pollutants such as aerosols also have direct radiative effects. NOx and VOCs are ozone precursors, another substance with both radiative and health impacts, and these ozone precursors also interact with the chemistry of the hydroxyl radical which is the major methane sink. Realistic scenarios of future emissions and concentrations must therefore account for both air pollution and greenhouse gas policies and how they interact economically as well as atmospherically, including the regional pattern of emissions and regulation. We have modified a 16 region computable general equilibrium economic model (the MIT Emissions Prediction and Policy Analysis model) by including elasticities of substitution for ozone precursors and aerosols in order to examine these interactions between climate policy and air pollution policy on a global scale. Urban emissions are distributed based on population density, and aged using a reduced form urban model before release into an atmospheric chemistry/climate model (the earth systems component of the MIT Integrated Global Systems Model). This integrated approach enables examination of the direct impacts of air pollution on climate, the ancillary and complementary interactions between air pollution and climate policies, and the impact of different population distribution algorithms or urban emission aging schemes on global scale properties. This modeling exercise shows that while ozone levels are reduced due to NOx and VOC reductions, these reductions lead to an increase in methane concentrations that eliminates the temperature effects of the ozone reductions. However, black carbon reductions do have

  17. Integrating molecular dynamics simulations with chemical probing experiments using SHAPE-FIT

    PubMed Central

    Kirmizialtin, Serdal; Hennelly, Scott P.; Schug, Alexander; Onuchic, Jose N.; Sanbonmatsu, Karissa Y.

    2016-01-01

    Integration and calibration of molecular dynamics simulations with experimental data remains a challenging endeavor. We have developed a novel method to integrate chemical probing experiments with molecular simulations of RNA molecules by using a native structure-based model. Selective 2’-hydroxyl acylation by primer extension (SHAPE) characterizes the mobility of each residue in the RNA. Our method, SHAPE-FIT, automatically optimizes the potential parameters of the forcefield according to measured reactivities from SHAPE. The optimized parameter set allows simulations of dynamics highly consistent with SHAPE probing experiments. Such atomistic simulations, thoroughly grounded in experiment, can open a new window on RNA structure-function relations. PMID:25726467

  18. Behavioral aspects of clinical trials. An integrated framework from behavior theory.

    PubMed

    Morrow, G R; Hickok, J T; Burish, T G

    1994-11-01

    A less-than-optimal proportion of patients with cancer are entered into National Cancer Institute-sponsored clinical trials. This article reviews the literature on accrual in oncology clinical trials to characterize the extent of the problem, identify reasons for low accrual, and suggest ways to promote accrual. Four well known theories of health behavior (the Health Belief Model, Subjective Expected Utility Theory, Protection Motivation Theory, and the Theory of Reasoned Action) point to central concepts involved in understanding patient health-related behavior: (1) the probability that an unwelcomed health event will happen to a patient, (2) the severity of that event if it does occur, (3) the effectiveness of a particular behavior (such as taking part in a clinical trial) to modify the severity, and (4) the cost of adopting that behavior. These concepts form a framework for integrating the available information about accrual to clinical oncology trials. Patient and physician factors previously related to clinical trials suggest specific recommendations for increasing accrual to clinical oncology trials. PMID:7954285

  19. Integrated molecular mechanism directing nucleosome reorganization by human FACT

    PubMed Central

    Tsunaka, Yasuo; Fujiwara, Yoshie; Oyama, Takuji; Hirose, Susumu; Morikawa, Kosuke

    2016-01-01

    Facilitates chromatin transcription (FACT) plays essential roles in chromatin remodeling during DNA transcription, replication, and repair. Our structural and biochemical studies of human FACT–histone interactions present precise views of nucleosome reorganization, conducted by the FACT-SPT16 (suppressor of Ty 16) Mid domain and its adjacent acidic AID segment. AID accesses the H2B N-terminal basic region exposed by partial unwrapping of the nucleosomal DNA, thereby triggering the invasion of FACT into the nucleosome. The crystal structure of the Mid domain complexed with an H3–H4 tetramer exhibits two separate contact sites; the Mid domain forms a novel intermolecular β structure with H4. At the other site, the Mid–H2A steric collision on the H2A-docking surface of the H3–H4 tetramer within the nucleosome induces H2A–H2B displacement. This integrated mechanism results in disrupting the H3 αN helix, which is essential for retaining the nucleosomal DNA ends, and hence facilitates DNA stripping from histone. PMID:26966247

  20. Source quality variations tied to sequence development: Integration of physical and chemical aspects, Lower to Middle Triassic, western Barents Sea

    SciTech Connect

    Bohacs, K.M.; Isaksen, G.H. )

    1991-03-01

    Triassic mudrocks from the Barents Sea area demonstrate to covariance of physical and chemical properties of mudrocks deposited in shelfal environments and the aspect of depositional sequences in distal settings. The tie of physical parameters to chemical character within a detailed sequence-stratigraphic framework enables the construction of depositional-facies models to predict organic-matter content and quality. This allows the explorer to more closely constrain and predict the nature of potential source rocks using seismic and well-log data. Changes in lithology, bedding geometry, sedimentary structures, body and trace-fossil assemblages, and inorganic, bulk-organic, and molecular geochemistry revealed the detailed depositional environments. The depositional environments stack predictably, according to their position in the depositional sequence: from aerobic lower-shoreface--offshore transition environments in lowstand systems tracts to dysaerobic-anaerobic distal open-marine-shelf environment in transgressive and early highstand systems tracts. Quantitative molecular geochemistry also revealed variations within this distal setting and strong covariance with sequence position. Input of organic matter from terrigenous higher plants dominates the lowstands whereas marine-algal organic matter is most prevalent within transgressive and highstand systems tracts. Specifically, the abundance of C{sub 30} steranes, total steranes, and moretane reflected development of the sequences.

  1. Cognitive and Neural Aspects of Information Processing in Major Depressive Disorder: An Integrative Perspective

    PubMed Central

    Foland-Ross, Lara C.; Gotlib, Ian H.

    2012-01-01

    Researchers using experimental paradigms to examine cognitive processes have demonstrated that Major Depressive Disorder (MDD) is associated not with a general deficit in cognitive functioning, but instead with more specific anomalies in the processing of negatively valenced material. Indeed, cognitive theories of depression posit that negative biases in the processing of information play a critical role in influencing the onset, maintenance, and recurrence of depressive episodes. In this paper we review findings from behavioral studies documenting that MDD is associated with specific difficulties in attentional disengagement from negatively valenced material, with tendencies to interpret information in a negative manner, with deficits in cognitive control in the processing of negative material, and with enhanced memory for negative material. To gain a better understanding of the neurobiological basis of these abnormalities, we also examine findings from functional neuroimaging studies of depression and show that dysfunction in neural systems that subserve emotion processing, inhibition, and attention may underlie and contribute to the deficits in cognition that have been documented in depressed individuals. Finally, we briefly review evidence from studies of children who are at high familial risk for depression that indicates that abnormalities in cognition and neural function are observable before the onset of MDD and, consequently, may represent a risk factor for the development of this disorder. By integrating research from cognitive and neural investigations of depression, we can gain a more comprehensive understanding not only of how cognitive and biological factors interact to affect the onset, maintenance, and course of MDD, but also of how such research can aid in the development of targeted strategies for the prevention and treatment of this debilitating disorder. PMID:23162521

  2. Conducting Polymer Nanostructures and Nanocomposites with Carbon Nanotubes: Hierarchical Assembly by Molecular Electrochemistry, Growth Aspects and Property Characterization.

    PubMed

    Gupta, Sanju; Price, Carson; Heintzman, Eli

    2016-01-01

    Conducting (or π-conjugated) polymers are promising materials for preparing supramolecular nano-structures and nanocomposites. We report controlled nanostructure syntheses of polypyrrole (PPy) and poylaniline (PANi) via electropolymerization (i.e., in-situ electrochemical anodic oxidation). The density, shape, caliber and thickness of self-assembled PPy micro-containers are regulated by electrochemical potential window for H2 bubbles and number of cyclic voltammetric (potentiodynamic) scans. Likewise, we employed amperometry, chronopotentiometry and potentiodynamic modes using hydrochloric acid as oxidizing agent to prepare PANi nanoparticles and nanotubules. We present our findings from the viewpoint of molecular electrochemistry with growth kinetic aspects yielding mechanistic details (initially forming dimers and oligomers as nucleating agents followed by polymer growth). Also targeted is forming nanocomposites with functionalized single- and multi-walled carbon nanotubes (FSWCNTs and FMWCNTs) as reinforced agent to optimize structural and functional properties. All of these novel nanomaterials are characterized using a range of complementary techniques to establish microscopic structure-property-function relationship. PMID:27398466

  3. Molecular and Clinical Aspects of the Target Therapy with the Calcimimetic Cinacalcet in the Treatment of Parathyroid Tumors.

    PubMed

    Mingione, Alessandra; Verdelli, Chiara; Terranegra, Annalisa; Soldati, Laura; Corbetta, Sabrina

    2015-01-01

    Parathyroid tumors are almost invariably associated with parathormone (PTH) hypersecretion resulting in primary (PHPT) or secondary (SHPT) hyperparathyroidism. PHPT is the third most common endocrine disorder with a prevalence of 1-2% in post-menopausal women; SHPT is a major complication of chronic kidney failure, the prevalence of which is increasing. The calciumsensing receptor (CASR) is the key molecule regulating PTH synthesis and release from the parathyroid cells in response to changes in extracellular calcium concentrations. A potent calcimimetic, cinacalcet, has been developed in the last ten years and made available for medical treatment of both PHPT and SHPT. Cinacalcet has been demonstrated to be effective in inhibiting PTH secretion, though the drug fails to normalize PTH release, both in PHPT and SHPT patients with different degrees of disease severity, including patients with parathyroid carcinomas and with MEN1-related parathyroid tumors. Here we reviewed the molecular aspects of CASR target therapy and the effect of the CASR gene single nucleotide polymorphisms. Clinical data concerning the efficacy and safety of cinacalcet in controlling hyperparathyroidism are reported, focusing on the treatment of the different types of parathyroid tumors. Finally, limits of this target therapy are analyzed, pointing out the lack of efficacy in improving kidney and bone morbidities in PHPT and cardiovascular diseases in SHPT. Though cinacalcet is a target therapeutic option for parathyroid tumors, further approaches are warranted to fully control these metabolic disorders and the underlying tumors. PMID:26033088

  4. Integration of Molecular, Cellular and Translational Researches in BioImpacts

    PubMed Central

    Omidi, Yadollah

    2011-01-01

    SUMMARY Integration of molecular cellular biology with advanced technologies (e.g., bioinformatics, omics,biophotonics and nanobiosensing) has significantly improved the translational medicine field. The integrative research in various biomedical sciences has also fastened the progression of drug discovery and development.Aiming to meet the highest standards of publication, the newly established multidisciplinary open access journal “BioImpacts”grants a free platform for all authors and readers to facilitate the integration of different scientific domains in biomedical sciences. PMID:23678402

  5. Improving the convergence of closed and open path integral molecular dynamics via higher order Trotter factorization schemes

    NASA Astrophysics Data System (ADS)

    Pérez, Alejandro; Tuckerman, Mark E.

    2011-08-01

    Higher order factorization schemes are developed for path integral molecular dynamics in order to improve the convergence of estimators for physical observables as a function of the Trotter number. The methods are based on the Takahashi-Imada and Susuki decompositions of the Boltzmann operator. The methods introduced improve the averages of the estimators by using the classical forces needed to carry out the dynamics to construct a posteriori weighting factors for standard path integral molecular dynamics. The new approaches are straightforward to implement in existing path integral codes and carry no significant overhead. The Suzuki higher order factorization was also used to improve the end-to-end distance estimator in open path integral molecular dynamics. The new schemes are tested in various model systems, including an ab initio path integral molecular dynamics calculation on the hydrogen molecule and a quantum water model. The proposed algorithms have potential utility for reducing the cost of path integral molecular dynamics calculations of bulk systems.

  6. XML-based approaches for the integration of heterogeneous bio-molecular data

    PubMed Central

    Mesiti, Marco; Jiménez-Ruiz, Ernesto; Sanz, Ismael; Berlanga-Llavori, Rafael; Perlasca, Paolo; Valentini, Giorgio; Manset, David

    2009-01-01

    Background The today's public database infrastructure spans a very large collection of heterogeneous biological data, opening new opportunities for molecular biology, bio-medical and bioinformatics research, but raising also new problems for their integration and computational processing. Results In this paper we survey the most interesting and novel approaches for the representation, integration and management of different kinds of biological data by exploiting XML and the related recommendations and approaches. Moreover, we present new and interesting cutting edge approaches for the appropriate management of heterogeneous biological data represented through XML. Conclusion XML has succeeded in the integration of heterogeneous biomolecular information, and has established itself as the syntactic glue for biological data sources. Nevertheless, a large variety of XML-based data formats have been proposed, thus resulting in a difficult effective integration of bioinformatics data schemes. The adoption of a few semantic-rich standard formats is urgent to achieve a seamless integration of the current biological resources. PMID:19828083

  7. Influence of platelet aspect ratio on the mechanical behaviour of bio-inspired nanocomposites using molecular dynamics.

    PubMed

    Mathiazhagan, S; Anup, S

    2016-06-01

    Superior mechanical properties of biocomposites such as nacre and bone are attributed to their basic building blocks. These basic building blocks have nanoscale features and play a major role in achieving combined stiffening, strengthening and toughening mechanisms. Bioinspired nanocomposites based on these basic building blocks, regularly and stairwise staggered arrangements of hard platelets in soft matrix, have huge potential for developing advanced materials. The study of applicability of mechanical principles of biological materials to engineered materials will guide designing advanced materials. To probe the generic mechanical characteristics of these bioinspired nanocomposites, the model material concept in molecular dynamics (MD) is used. In this paper, the effect of platelets aspect ratio (AR) on the mechanical behaviour of bioinspired nanocomposites is investigated. The obtained Young׳s moduli of both the models and the strengths of the regularly staggered models agree with the available theories. However, the strengths of the stairwise staggered models show significant difference. For the stairwise staggered model, we demonstrate the existence of two critical ARs, a smaller critical AR above which platelet fracture occurs and a higher critical AR above which composite strength remains constant. Our MD study also shows the existence of mechanisms of platelet pull-out and breakage for lower and higher ARs. Pullout mechanism acts as a major source of plasticity. Further, we find that the regularly staggered model can achieve an optimal combination of high Young׳s modulus, flow strength and toughness, and the stairwise staggered model is efficient in obtaining high Young׳s modulus and tensile strength. PMID:26741376

  8. Macroscopic contraction of a gel induced by the integrated motion of light-driven molecular motors

    NASA Astrophysics Data System (ADS)

    Li, Quan; Fuks, Gad; Moulin, Emilie; Maaloum, Mounir; Rawiso, Michel; Kulic, Igor; Foy, Justin T.; Giuseppone, Nicolas

    2015-02-01

    Making molecular machines that can be useful in the macroscopic world is a challenging long-term goal of nanoscience. Inspired by the protein machinery found in biological systems, and based on the theoretical understanding of the physics of motion at the nanoscale, organic chemists have developed a number of molecules that can produce work by contraction or rotation when triggered by various external chemical or physical stimuli. In particular, basic molecular switches that commute between at least two thermodynamic minima and more advanced molecular motors that behave as dissipative units working far from equilibrium when fuelled with external energy have been reported. However, despite recent progress, the ultimate challenge of coordinating individual molecular motors in a continuous mechanical process that can have a measurable effect at the macroscale has remained elusive. Here, we show that by integrating light-driven unidirectional molecular rotors as reticulating units in a polymer gel, it is possible to amplify their individual motions to achieve macroscopic contraction of the material. Our system uses the incoming light to operate under far-from-equilibrium conditions, and the work produced by the motor in the photostationary state is used to twist the entangled polymer chains up to the collapse of the gel. Our design could be a starting point to integrate nanomotors in metastable materials to store energy and eventually to convert it.

  9. The need for novel informatics tools for integrating and planning research in molecular and cellular cognition

    PubMed Central

    Müller, Klaus-Robert

    2015-01-01

    The sheer volume and complexity of publications in the biological sciences are straining traditional approaches to research planning. Nowhere is this problem more serious than in molecular and cellular cognition, since in this neuroscience field, researchers routinely use approaches and information from a variety of areas in neuroscience and other biology fields. Additionally, the multilevel integration process characteristic of this field involves the establishment of experimental connections between molecular, electrophysiological, behavioral, and even cognitive data. This multidisciplinary integration process requires strategies and approaches that originate in several different fields, which greatly increases the complexity and demands of this process. Although causal assertions, where phenomenon A is thought to contribute or relate to B, are at the center of this integration process and key to research in biology, there are currently no tools to help scientists keep track of the increasingly more complex network of causal connections they use when making research decisions. Here, we propose the development of semiautomated graphical and interactive tools to help neuroscientists and other biologists, including those working in molecular and cellular cognition, to track, map, and weight causal evidence in research papers. There is a great need for a concerted effort by biologists, computer scientists, and funding institutions to develop maps of causal information that would aid in integration of research findings and in experiment planning. PMID:26286658

  10. Integration and mining of malaria molecular, functional and pharmacological data: how far are we from a chemogenomic knowledge space?

    PubMed

    Birkholtz, Lyn-Marie; Bastien, Olivier; Wells, Gordon; Grando, Delphine; Joubert, Fourie; Kasam, Vinod; Zimmermann, Marc; Ortet, Philippe; Jacq, Nicolas; Saïdani, Nadia; Roy, Sylvaine; Hofmann-Apitius, Martin; Breton, Vincent; Louw, Abraham I; Maréchal, Eric

    2006-11-17

    The organization and mining of malaria genomic and post-genomic data is important to significantly increase the knowledge of the biology of its causative agents, and is motivated, on a longer term, by the necessity to predict and characterize new biological targets and new drugs. Biological targets are sought in a biological space designed from the genomic data from Plasmodium falciparum, but using also the millions of genomic data from other species. Drug candidates are sought in a chemical space containing the millions of small molecules stored in public and private chemolibraries. Data management should, therefore, be as reliable and versatile as possible. In this context, five aspects of the organization and mining of malaria genomic and post-genomic data were examined: 1) the comparison of protein sequences including compositionally atypical malaria sequences, 2) the high throughput reconstruction of molecular phylogenies, 3) the representation of biological processes, particularly metabolic pathways, 4) the versatile methods to integrate genomic data, biological representations and functional profiling obtained from X-omic experiments after drug treatments and 5) the determination and prediction of protein structures and their molecular docking with drug candidate structures. Recent progress towards a grid-enabled chemogenomic knowledge space is discussed.

  11. Mathematical analysis of the boundary-integral based electrostatics estimation approximation for molecular solvation: exact results for spherical inclusions.

    PubMed

    Bardhan, Jaydeep P; Knepley, Matthew G

    2011-09-28

    We analyze the mathematically rigorous BIBEE (boundary-integral based electrostatics estimation) approximation of the mixed-dielectric continuum model of molecular electrostatics, using the analytically solvable case of a spherical solute containing an arbitrary charge distribution. Our analysis, which builds on Kirkwood's solution using spherical harmonics, clarifies important aspects of the approximation and its relationship to generalized Born models. First, our results suggest a new perspective for analyzing fast electrostatic models: the separation of variables between material properties (the dielectric constants) and geometry (the solute dielectric boundary and charge distribution). Second, we find that the eigenfunctions of the reaction-potential operator are exactly preserved in the BIBEE model for the sphere, which supports the use of this approximation for analyzing charge-charge interactions in molecular binding. Third, a comparison of BIBEE to the recent GBε theory suggests a modified BIBEE model capable of predicting electrostatic solvation free energies to within 4% of a full numerical Poisson calculation. This modified model leads to a projection-framework understanding of BIBEE and suggests opportunities for future improvements.

  12. A comprehensive protein-centric ID mapping service for molecular data integration

    PubMed Central

    Huang, Hongzhan; Suzek, Baris E.; Mazumder, Raja; Zhang, Jian; Chen, Yongxing; Wu, Cathy H.

    2011-01-01

    Motivation: Identifier (ID) mapping establishes links between various biological databases and is an essential first step for molecular data integration and functional annotation. ID mapping allows diverse molecular data on genes and proteins to be combined and mapped to functional pathways and ontologies. We have developed comprehensive protein-centric ID mapping services providing mappings for 90 IDs derived from databases on genes, proteins, pathways, diseases, structures, protein families, protein interaction, literature, ontologies, etc. The services are widely used and have been regularly updated since 2006. Availability: www.uniprot.org/mappingandproteininformation-resource.org/pirwww/search/idmapping.shtml Contact: huang@dbi.udel.edu PMID:21478197

  13. A simple and accurate algorithm for path integral molecular dynamics with the Langevin thermostat.

    PubMed

    Liu, Jian; Li, Dezhang; Liu, Xinzijian

    2016-07-14

    We introduce a novel simple algorithm for thermostatting path integral molecular dynamics (PIMD) with the Langevin equation. The staging transformation of path integral beads is employed for demonstration. The optimum friction coefficients for the staging modes in the free particle limit are used for all systems. In comparison to the path integral Langevin equation thermostat, the new algorithm exploits a different order of splitting for the phase space propagator associated to the Langevin equation. While the error analysis is made for both algorithms, they are also employed in the PIMD simulations of three realistic systems (the H2O molecule, liquid para-hydrogen, and liquid water) for comparison. It is shown that the new thermostat increases the time interval of PIMD by a factor of 4-6 or more for achieving the same accuracy. In addition, the supplementary material shows the error analysis made for the algorithms when the normal-mode transformation of path integral beads is used.

  14. A simple and accurate algorithm for path integral molecular dynamics with the Langevin thermostat

    NASA Astrophysics Data System (ADS)

    Liu, Jian; Li, Dezhang; Liu, Xinzijian

    2016-07-01

    We introduce a novel simple algorithm for thermostatting path integral molecular dynamics (PIMD) with the Langevin equation. The staging transformation of path integral beads is employed for demonstration. The optimum friction coefficients for the staging modes in the free particle limit are used for all systems. In comparison to the path integral Langevin equation thermostat, the new algorithm exploits a different order of splitting for the phase space propagator associated to the Langevin equation. While the error analysis is made for both algorithms, they are also employed in the PIMD simulations of three realistic systems (the H2O molecule, liquid para-hydrogen, and liquid water) for comparison. It is shown that the new thermostat increases the time interval of PIMD by a factor of 4-6 or more for achieving the same accuracy. In addition, the supplementary material shows the error analysis made for the algorithms when the normal-mode transformation of path integral beads is used.

  15. The Adenovirus L4-22K Protein Is Multifunctional and Is an Integral Component of Crucial Aspects of Infection

    PubMed Central

    Wu, Kai; Orozco, Diana

    2012-01-01

    A variety of cellular and viral processes are coordinately regulated during adenovirus (Ad) infection to achieve optimal virus production. The Ad late gene product L4-22K has been associated with disparate activities during infection, including the regulation of late gene expression, viral DNA packaging, and infectious virus production. We generated and characterized two L4-22K mutant viruses to further explore L4-22K functions during viral infection. Our results show that L4-22K is indeed important for temporal control of viral gene expression not only because it activates late gene expression but also because it suppresses early gene expression. We also show that the L4-22K protein binds to viral packaging sequences in vivo and is essential to recruit two other packaging proteins, IVa2 and L1-52/55K, to this region. The elimination of L4-22K gave rise to the production of only empty virus capsids and not mature virions, which confirms that the L4-22K protein is required for Ad genome packaging. Finally, L4-22K contributes to adenovirus-induced cell death by regulating the expression of the adenovirus death protein. Thus, the adenovirus L4-22K protein is multifunctional and an integral component of crucial aspects of infection. PMID:22811519

  16. Antioxidant Capacity of Melatonin on Preimplantation Development of Fresh and Vitrified Rabbit Embryos: Morphological and Molecular Aspects

    PubMed Central

    Mehaisen, Gamal M. K.; Saeed, Ayman M.; Gad, Ahmed; Abass, Ahmed O.; Arafa, Mahmoud; El-Sayed, Ashraf

    2015-01-01

    Embryo cryopreservation remains an important technique to enhance the reconstitution and distribution of animal populations with high genetic merit. One of the major detrimental factors to this technique is the damage caused by oxidative stress. Melatonin is widely known as an antioxidant with multi-faceted ways to counteract the oxidative stress. In this paper, we investigated the role of melatonin in protecting rabbit embryos during preimplantation development from the potential harmful effects of oxidative stress induced by in vitro culture or vitrification. Rabbit embryos at morula stages were cultured for 2 hr with 0 or 10−3 M melatonin (C or M groups). Embryos of each group were either transferred to fresh culture media (CF and MF groups) or vitrified/devitrified (CV and MV groups), then cultured in vitro for 48 hr until the blastocyst stage. The culture media were used to measure the activity of antioxidant enzymes: glutathione-s-transferase (GST) and superoxide dismutase (SOD), as well as the levels of two oxidative substrates: lipid peroxidation (LPO) and nitric oxide (NO). The blastocysts from each group were used to measure the expression of developmental-related genes (GJA1, POU5F1 and Nanog) and oxidative-stress-response-related genes (NFE2L2, SOD1 and GPX1). The data showed that melatonin promoted significantly (P<0.05) the blastocyst rate by 17% and 12% in MF and MV groups compared to their controls (CF and CV groups). The GST and SOD activity significantly increased by the treatment of melatonin in fresh or vitrified embryos, while the levels of LPO and NO decreased (P<0.05). Additionally, melatonin considerably stimulated the relative expression of GJA1, NFE2L2 and SOD1 genes in MF and MV embryos compared to CF group. Furthermore, melatonin significantly ameliorated the reduction of POU5F1 and GPX1 expression induced by vitrification. The results obtained from the current investigation provide new and clear molecular aspects regarding the

  17. Model for integrated management of quality, labor risks prevention, environment and ethical aspects, applied to R&D&I and production processes in an organization

    NASA Astrophysics Data System (ADS)

    González, M. R.; Torres, F.; Yoldi, V.; Arcega, F.; Plaza, I.

    2012-04-01

    It is proposed an integrated management model for an organization. This model is based on the continuous improvement Plan-Do-Check-Act cycle and it intends to integrate the environmental, risk prevention and ethical aspects as well as research, development and innovation projects management in the general quality management structure proposed by ISO 9001:2008. It aims to fulfill the standards ISO 9001, ISO 14001, OSHAS 18001, SGE 21 y 166002.

  18. Dimensionality aspects of nano micro integrated metal oxide based early stage leak detection room temperature hydrogen sensor

    NASA Astrophysics Data System (ADS)

    Deshpande, Sameer Arun

    .). Highly porous SnO2 nanoparticles thin film (synthesized using template assisted) showed response time of about 25 seconds and sensitivity 4. The one dimensional tin oxide nanostructures (nanowires) based sensor showed a sensitivity of 4 and response time of 20 sec. Effect of aspect ratio of the nanowires on diffusion of hydrogen molecules in the tin oxide nanowires, effect of catalyst adsorption on nanowire surface and corresponding effect on sensor properties has been studied in detail. Nanotubes of TiO2 prepared using hydrothermal synthesis showed a sensitivity 30 with response time as low as 20 seconds where as, TiO 2 nanotubes synthesized using anodization showed poor sensitivity. The difference is mainly attributed to the issues related to integration of the anodized nanotubes with the MEMS devices. The effect of MEMS device architecture modulation, such as, finger spacing, number and length of fingers and electrode materials were studied. It has been found that faster sensor response (˜ 10 sec) was observed for smaller finger spacing. A diffusion model is proposed for elucidating the effect of inter-electrode distance variation on conductance change of a nano-micro integrated hydrogen sensor for room temperature operation. Both theoretical and experimental results showed a faster response upon exposure to hydrogen when sensor electrode gap was smaller. Also, a linear increase in the sensor sensitivity from 500 to 80000 was observed on increasing the electrode spacing from 2 to 20 mum. The improvement in sensitivity is attributed to the higher reactive sites available for the gaseous species to react on the sensor surface. This phenomenon also correlated to surface adsorbed oxygen vacancies (O-) and the rate of change of surface adsorbed oxygen vacancies. This dissertation studied in detail dimensionality aspects of materials as well as device in detecting hydrogen at room temperature.

  19. i-PI: A Python interface for ab initio path integral molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Ceriotti, Michele; More, Joshua; Manolopoulos, David E.

    2014-03-01

    Recent developments in path integral methodology have significantly reduced the computational expense of including quantum mechanical effects in the nuclear motion in ab initio molecular dynamics simulations. However, the implementation of these developments requires a considerable programming effort, which has hindered their adoption. Here we describe i-PI, an interface written in Python that has been designed to minimise the effort required to bring state-of-the-art path integral techniques to an electronic structure program. While it is best suited to first principles calculations and path integral molecular dynamics, i-PI can also be used to perform classical molecular dynamics simulations, and can just as easily be interfaced with an empirical forcefield code. To give just one example of the many potential applications of the interface, we use it in conjunction with the CP2K electronic structure package to showcase the importance of nuclear quantum effects in high-pressure water. Catalogue identifier: AERN_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AERN_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: GNU General Public License, version 3 No. of lines in distributed program, including test data, etc.: 138626 No. of bytes in distributed program, including test data, etc.: 3128618 Distribution format: tar.gz Programming language: Python. Computer: Multiple architectures. Operating system: Linux, Mac OSX, Windows. RAM: Less than 256 Mb Classification: 7.7. External routines: NumPy Nature of problem: Bringing the latest developments in the modelling of nuclear quantum effects with path integral molecular dynamics to ab initio electronic structure programs with minimal implementational effort. Solution method: State-of-the-art path integral molecular dynamics techniques are implemented in a Python interface. Any electronic structure code can be patched to receive the atomic

  20. Molecular evidence-based medicine: evolution and integration of information in the genomic era.

    PubMed

    Ioannidis, J P A

    2007-05-01

    Evidence-based medicine and molecular medicine have both been influential in biomedical research in the last 15 years. Despite following largely parallel routes to date, the goals and principles of evidence-based and molecular medicine are complementary and they should be converging. I define molecular evidence-based medicine as the study of medical information that makes sense of the advances of molecular biological disciplines and where errors and biases are properly appreciated and placed in context. Biomedical measurement capacity improves very rapidly. The exponentially growing mass of hypotheses being tested requires a new approach to both statistical and biological inference. Multidimensional biology requires careful exact replication of research findings, but indirect corroboration is often all that is achieved at best. Besides random error, bias remains a major threat. It is often difficult to separate bias from the spirit of scientific inquiry to force data into coherent and 'significant' biological stories. Transparency and public availability of protocols, data, analyses and results may be crucial to make sense of the complex biology of human disease and avoid being flooded by spurious research findings. Research efforts should be integrated across teams in an open, sharing environment. Most research in the future may be designed, performed, and integrated in the public cyberspace. PMID:17461979

  1. Integral Equation Theory of Molecular Solvation Coupled with Quantum Mechanical/Molecular Mechanics Method in NWChem Package

    SciTech Connect

    Chuev, Gennady N.; Valiev, Marat; Fedotova, Marina V.

    2012-04-10

    We have developed a hybrid approach based on a combination of integral equation theory of molecular liquids and QM/MM methodology in NorthWest computational Chemistry (NWChem) software package. We have split the evaluations into conse- quent QM/MM and statistical mechanics calculations based on the one-dimensional reference interaction site model, which allows us to reduce signicantly the time of computation. The method complements QM/MM capabilities existing in the NWChem package. The accuracy of the presented method was tested through com- putation of water structure around several organic solutes and their hydration free energies. We have also evaluated the solvent effect on the conformational equilibria. The applicability and limitations of the developed approach are discussed.

  2. New methods for accelerating the convergence of molecular electronic integrals over exponential type orbitals

    NASA Astrophysics Data System (ADS)

    Safouhi, Hassan; Hoggan, Philip

    2003-01-01

    This review on molecular integrals for large electronic systems (MILES) places the problem of analytical integration over exponential-type orbitals (ETOs) in a historical context. After reference to the pioneering work, particularly by Barnett, Shavitt and Yoshimine, it focuses on recent progress towards rapid and accurate analytic solutions of MILES over ETOs. Software such as the hydrogenlike wavefunction package Alchemy by Yoshimine and collaborators is described. The review focuses on convergence acceleration of these highly oscillatory integrals and in particular it highlights suitable nonlinear transformations. Work by Levin and Sidi is described and applied to MILES. A step by step description of progress in the use of nonlinear transformation methods to obtain efficient codes is provided. The recent approach developed by Safouhi is also presented. The current state of the art in this field is summarized to show that ab initio analytical work over ETOs is now a viable option.

  3. The semantic metadatabase (SEMEDA): ontology based integration of federated molecular biological data sources.

    PubMed

    Köhler, Jacob; Schulze-Kremer, Steffen

    2002-01-01

    A system for "intelligent" semantic integration and querying of federated databases is being implemented by using three main components: A component which enables SQL access to integrated databases by database federation (MARGBench), an ontology based semantic metadatabase (SEMEDA) and an ontology based query interface (SEMEDA-query). In this publication we explain and demonstrate the principles, architecture and the use of SEMEDA. Since SEMEDA is implemented as 3 tiered web application database providers can enter all relevant semantic and technical information about their databases by themselves via a web browser. SEMEDA' s collaborative ontology editing feature is not restricted to database integration, and might also be useful for ongoing ontology developments, such as the "Gene Ontology" [2]. SEMEDA can be found at http://www-bm.cs.uni-magdeburg.de/semeda/. We explain how this ontologically structured information can be used for semantic database integration. In addition, requirements to ontologies for molecular biological database integration are discussed and relevant existing ontologies are evaluated. We further discuss how ontologies and structured knowledge sources can be used in SEMEDA and whether they can be merged supplemented or updated to meet the requirements for semantic database integration.

  4. Integrated genomics and molecular breeding approaches for dissecting the complex quantitative traits in crop plants.

    PubMed

    Kujur, Alice; Saxena, Maneesha S; Bajaj, Deepak; Laxmi; Parida, Swarup K

    2013-12-01

    The enormous population growth, climate change and global warming are now considered major threats to agriculture and world's food security. To improve the productivity and sustainability of agriculture, the development of highyielding and durable abiotic and biotic stress-tolerant cultivars and/climate resilient crops is essential. Henceforth, understanding the molecular mechanism and dissection of complex quantitative yield and stress tolerance traits is the prime objective in current agricultural biotechnology research. In recent years, tremendous progress has been made in plant genomics and molecular breeding research pertaining to conventional and next-generation whole genome, transcriptome and epigenome sequencing efforts, generation of huge genomic, transcriptomic and epigenomic resources and development of modern genomics-assisted breeding approaches in diverse crop genotypes with contrasting yield and abiotic stress tolerance traits. Unfortunately, the detailed molecular mechanism and gene regulatory networks controlling such complex quantitative traits is not yet well understood in crop plants. Therefore, we propose an integrated strategies involving available enormous and diverse traditional and modern -omics (structural, functional, comparative and epigenomics) approaches/resources and genomics-assisted breeding methods which agricultural biotechnologist can adopt/utilize to dissect and decode the molecular and gene regulatory networks involved in the complex quantitative yield and stress tolerance traits in crop plants. This would provide clues and much needed inputs for rapid selection of novel functionally relevant molecular tags regulating such complex traits to expedite traditional and modern marker-assisted genetic enhancement studies in target crop species for developing high-yielding stress-tolerant varieties.

  5. Massively Parallel, Molecular Analysis Platform Developed Using a CMOS Integrated Circuit With Biological Nanopores

    PubMed Central

    Roever, Stefan

    2012-01-01

    A massively parallel, low cost molecular analysis platform will dramatically change the nature of protein, molecular and genomics research, DNA sequencing, and ultimately, molecular diagnostics. An integrated circuit (IC) with 264 sensors was fabricated using standard CMOS semiconductor processing technology. Each of these sensors is individually controlled with precision analog circuitry and is capable of single molecule measurements. Under electronic and software control, the IC was used to demonstrate the feasibility of creating and detecting lipid bilayers and biological nanopores using wild type α-hemolysin. The ability to dynamically create bilayers over each of the sensors will greatly accelerate pore development and pore mutation analysis. In addition, the noise performance of the IC was measured to be 30fA(rms). With this noise performance, single base detection of DNA was demonstrated using α-hemolysin. The data shows that a single molecule, electrical detection platform using biological nanopores can be operationalized and can ultimately scale to millions of sensors. Such a massively parallel platform will revolutionize molecular analysis and will completely change the field of molecular diagnostics in the future.

  6. Molecular signals that shape the integrative responses of the heat-acclimated phenotype.

    PubMed

    Horowitz, Michal; Kodesh, Einat

    2010-12-01

    The introduction of molecular biology to thermoregulation was delayed compared with its application in other research fields pertinent to human health and disease. Using principles from molecular biology, we revisited fundamental problems in integrative and environmental physiology and were able to explore new research horizons. Global genomic responses in tandem with an appropriate physiological experimental model are a good experimental design strategy that can unravel the molecular mechanisms underlying integrative thermoregulatory responses. In this way, dynamic adaptation models, with accentuated or diminished regulatory circuits, triggered by superimposition of novel stressors sharing similar protective pathways, have significant benefits. On the basis of this approach, we will discuss the molecular physiological linkage of heat acclimation alone or combined with exercise training and decipher stress-specific genes in the thermoregulatory circuits in the heart and skeletal muscles. Opposing/competing adaptive features are required for each of the above-mentioned physiological conditions. Aerobic training increases the capacity to store/use ATP. In contrast, the acclimated phenotype attempts to counteract excessive heat production. Nevertheless, both treatments augment muscle force generation. These changes are tissue-specific; in the exercise-trained rat heart, there is up-regulation of Ca2+-induced Ca2+ release mechanism genes, whereas in the skeletal muscle (soleus), the enrichment is found in genes involved in metabolism. The final issue discussed in this review is the possibility that heat shock proteins serve as consensus markers of heat stress. The role of the autonomic nervous system in their induction during heat stress and how they affect integrative body systems are described.

  7. Molecular signals that shape the integrative responses of the heat-acclimated phenotype.

    PubMed

    Horowitz, Michal; Kodesh, Einat

    2010-12-01

    The introduction of molecular biology to thermoregulation was delayed compared with its application in other research fields pertinent to human health and disease. Using principles from molecular biology, we revisited fundamental problems in integrative and environmental physiology and were able to explore new research horizons. Global genomic responses in tandem with an appropriate physiological experimental model are a good experimental design strategy that can unravel the molecular mechanisms underlying integrative thermoregulatory responses. In this way, dynamic adaptation models, with accentuated or diminished regulatory circuits, triggered by superimposition of novel stressors sharing similar protective pathways, have significant benefits. On the basis of this approach, we will discuss the molecular physiological linkage of heat acclimation alone or combined with exercise training and decipher stress-specific genes in the thermoregulatory circuits in the heart and skeletal muscles. Opposing/competing adaptive features are required for each of the above-mentioned physiological conditions. Aerobic training increases the capacity to store/use ATP. In contrast, the acclimated phenotype attempts to counteract excessive heat production. Nevertheless, both treatments augment muscle force generation. These changes are tissue-specific; in the exercise-trained rat heart, there is up-regulation of Ca2+-induced Ca2+ release mechanism genes, whereas in the skeletal muscle (soleus), the enrichment is found in genes involved in metabolism. The final issue discussed in this review is the possibility that heat shock proteins serve as consensus markers of heat stress. The role of the autonomic nervous system in their induction during heat stress and how they affect integrative body systems are described. PMID:20404766

  8. Meiotic chromosome synapsis and recombination in Arabidopsis thaliana: new ways of integrating cytological and molecular approaches.

    PubMed

    Sanchez-Moran, E; Armstrong, S J

    2014-06-01

    Meiosis is an evolutionary conserved mechanism that produces haploid gametes and is essential for the sexual reproduction of higher eukaryotes. Since the late nineteenth century, meiosis has been studied in plants due their large chromosomes compared with other organisms and due to advances in microscopy and cytological approaches. On the other hand, non-plant model organisms like budding yeast have been widely used recently in order to characterise the molecular and functional aspects of meiosis. Arabidopsis arose as a new meiotic model for plants during the last decade of the twentieth century. This emergence was sustained by different molecular and genetic advances, mainly by completing the full genome sequence in 2000. Since then, further development of molecular technologies and the cytological methodologies to analyse the meiotic dynamics in Arabidopsis have permitted researchers to establish plant meiosis at the forefront of international research. Some key plant meiotic recombination events have been established in Arabidopsis. These advances have placed researchers into the position to transfer their knowledge from this plant meiotic model to crops and are likely to have an impact on plant breeding and the development of agriculture in future years. PMID:24941912

  9. Convergence of Sampling Kirkwood-Buff Integrals of Aqueous Solutions with Molecular Dynamics Simulations.

    PubMed

    Ganguly, Pritam; van der Vegt, Nico F A

    2013-03-12

    We discuss two methods for calculating Kirkwood-Buff integrals (KBIs) of aqueous cosolvent solutions from molecular simulations. The first method is based on computing running integrals over radial distribution functions obtained from NVT or NpT simulations. The second, more recent method, originally introduced by Schnell et al. (J. Phys. Chem. B2011, 115, 10911), obtains the KBIs from direct analysis of particle number fluctuations in small, open subvolumes embedded in a larger reservoir as provided by the NVT (NpT) simulation cell. The thermodynamic limit is taken in the first method by using the plateau-values of the running KBIs for large distances, while in the second method an analytical finite-size scaling relation is applied to the KBIs of subvolumes of variable size. We find that direct analysis of particle number fluctuations at small scales provides more precise estimates of KBIs for methanol-water and urea-water solutions. Converged KBIs could, however, not be obtained from nanosecond time scale molecular dynamics simulations with either of the two methods. Based on 0.1 μs simulation trajectories of small and large system sizes time-converged KBIs were obtained with both methods. The running integral method suffers, however, from stronger finite-size artifacts than the sub-box method, also when empirical finite-size tail corrections are applied to the radial distribution functions.

  10. Molecular radiotherapy: The NUKFIT software for calculating the time-integrated activity coefficient

    SciTech Connect

    Kletting, P.; Schimmel, S.; Luster, M.; Kestler, H. A.; Hänscheid, H.; Fernández, M.; Lassmann, M.; Bröer, J. H.; Nosske, D.; Glatting, G.

    2013-10-15

    Purpose: Calculation of the time-integrated activity coefficient (residence time) is a crucial step in dosimetry for molecular radiotherapy. However, available software is deficient in that it is either not tailored for the use in molecular radiotherapy and/or does not include all required estimation methods. The aim of this work was therefore the development and programming of an algorithm which allows for an objective and reproducible determination of the time-integrated activity coefficient and its standard error.Methods: The algorithm includes the selection of a set of fitting functions from predefined sums of exponentials and the choice of an error model for the used data. To estimate the values of the adjustable parameters an objective function, depending on the data, the parameters of the error model, the fitting function and (if required and available) Bayesian information, is minimized. To increase reproducibility and user-friendliness the starting values are automatically determined using a combination of curve stripping and random search. Visual inspection, the coefficient of determination, the standard error of the fitted parameters, and the correlation matrix are provided to evaluate the quality of the fit. The functions which are most supported by the data are determined using the corrected Akaike information criterion. The time-integrated activity coefficient is estimated by analytically integrating the fitted functions. Its standard error is determined assuming Gaussian error propagation. The software was implemented using MATLAB.Results: To validate the proper implementation of the objective function and the fit functions, the results of NUKFIT and SAAM numerical, a commercially available software tool, were compared. The automatic search for starting values was successfully tested for reproducibility. The quality criteria applied in conjunction with the Akaike information criterion allowed the selection of suitable functions. Function fit

  11. Integration of Chinese medicine with Western medicine could lead to future medicine: molecular module medicine.

    PubMed

    Zhang, Chi; Zhang, Ge; Chen, Ke-ji; Lu, Ai-ping

    2016-04-01

    The development of an effective classification method for human health conditions is essential for precise diagnosis and delivery of tailored therapy to individuals. Contemporary classification of disease systems has properties that limit its information content and usability. Chinese medicine pattern classification has been incorporated with disease classification, and this integrated classification method became more precise because of the increased understanding of the molecular mechanisms. However, we are still facing the complexity of diseases and patterns in the classification of health conditions. With continuing advances in omics methodologies and instrumentation, we are proposing a new classification approach: molecular module classification, which is applying molecular modules to classifying human health status. The initiative would be precisely defining the health status, providing accurate diagnoses, optimizing the therapeutics and improving new drug discovery strategy. Therefore, there would be no current disease diagnosis, no disease pattern classification, and in the future, a new medicine based on this classification, molecular module medicine, could redefine health statuses and reshape the clinical practice.

  12. Molecular physiopathology of obesity-related diseases: multi-organ integration by GRK2.

    PubMed

    Lucas, Elisa; Cruces-Sande, Marta; Briones, Ana M; Salaices, Mercedes; Mayor, Federico; Murga, Cristina; Vila-Bedmar, Rocio

    2015-01-01

    Obesity is a worldwide problem that has reached epidemic proportions both in developed and developing countries. The excessive accumulation of fat poses a risk to health since it favours the development of metabolic alterations including insulin resistance and tissue inflammation, which further contribute to the progress of the complex pathological scenario observed in the obese. In this review we put together the different outcomes of fat accumulation and insulin resistance in the main insulin-responsive tissues, and discuss the role of some of the key molecular routes that control disease progression both in an organ-specific and also in a more systemic manner. In particular, we focus on the importance of studying the integrated regulation of different organs and pathways that contribute to the global pathophysiology of this condition with a specific emphasis on the role of emerging key molecular nodes such as the G protein-coupled receptor kinase 2 (GRK2) signalling hub.

  13. Future Directions in Pain Management: Integrating Anatomically Selective Delivery Techniques With Novel Molecularly Selective Agents.

    PubMed

    Pleticha, Josef; Maus, Timothy P; Beutler, Andreas S

    2016-04-01

    Treatment for chronic, locoregional pain ranks among the most prevalent unmet medical needs. The failure of systemic analgesic drugs, such as opioids, is often due to their off-target toxicity, development of tolerance, and abuse potential. Interventional pain procedures provide target specificity but lack pharmacologically selective agents with long-term efficacy. Gene therapy vectors are a new tool for the development of molecularly selective pain therapies, which have already been proved to provide durable analgesia in preclinical models. Taken together, advances in image-guided delivery and gene therapy may lead to a new class of dual selective analgesic treatments integrating the molecular selectivity of analgesic genes with the anatomic selectivity of interventional delivery techniques.

  14. Integrated Observations of ICME - Driven Substorm - Storm Evolution on 7 August 1998: Traditional and Non-Traditional Aspects.

    NASA Astrophysics Data System (ADS)

    Farrugia, C. J.; Sandholt, P. E.; Torbert, R. B.

    2015-12-01

    The aim of this study is to obtain an integrated view of substorm-storm evolution in relation to well-defined interplanetary (IP) conditions, and to identify traditional and non-traditional aspects of the DP1 and DP2 current systems during substorm activity. Specifically, we report a case study of substorm/storm evolution driven by an ICME from ground observations around the oval in relation to geoeffective IP parameters (Kan-Lee electric field, E-KL, and dynamic pressure, Pdyn), geomagnetic indices (AL, SYM-H and PCN) and satellite observations (from DMSP F13 and F14, Geotail, and GOES spacecraft). A sudden enhancement of E-KL at a southward turning of the IMF led to an initial transient phase (PCN-enhancement) followed by a persistent stage of solar wind-magnetosphere-ionosphere coupling. The persistent phase terminated abruptly at a steep E-KL reduction when the ICME magnetic field turned north after a 3-hour-long interval of enhanced E-KL. The persistent phase consisted of (i) a 45-min-long substorm growth phase (DP2 current) followed by (ii) a classical substorm onset (DP1 current) in the 0100 - 0300 MLT sector, (ii) a 30-min-long expansion phase, maximizing in the same sector, and (iii) a phase lasting for 1.5 hr of 10-15 min-long DP1 events in the 2100 - 2300 and 0400 - 0600 MLT sectors. In the morning sector the expansion phase was characterized by Ps6 pulsations and omega bands. The SYM-H evolution reached the level of a major storm after a 2.5-hour-long interval of E-KL ˜5 mV/m and elevated Pdyn in the substorm expansion phase. Magetosphere - Ionosphere (M - I) coupling during a localized electrojet event at 0500 MLT in the late stage of the substorm expansion is studied by ground - satellite conjunction data (Iceland - Geotail). The DP1 and DP2 components of geomagnetic activity are discussed in relation to M - I current systems and substorm current wedge morphology.

  15. Phase Behavior of Active Swimmers in Depletants: Molecular Dynamics and Integral Equation Theory

    NASA Astrophysics Data System (ADS)

    Das, Subir K.; Egorov, Sergei A.; Trefz, Benjamin; Virnau, Peter; Binder, Kurt

    2014-05-01

    We study the structure and phase behavior of a binary mixture where one of the components is self-propelling in nature. The interparticle interactions in the system are taken from the Asakura-Oosawa model for colloid-polymer mixtures for which the phase diagram is known. In the current model version, the colloid particles are made active using the Vicsek model for self-propelling particles. The resultant active system is studied by molecular dynamics methods and integral equation theory. Both methods produce results consistent with each other and demonstrate that the Vicsek model-based activity facilitates phase separation, thus, broadening the coexistence region.

  16. Phase behavior of active swimmers in depletants: molecular dynamics and integral equation theory.

    PubMed

    Das, Subir K; Egorov, Sergei A; Trefz, Benjamin; Virnau, Peter; Binder, Kurt

    2014-05-16

    We study the structure and phase behavior of a binary mixture where one of the components is self-propelling in nature. The interparticle interactions in the system are taken from the Asakura-Oosawa model for colloid-polymer mixtures for which the phase diagram is known. In the current model version, the colloid particles are made active using the Vicsek model for self-propelling particles. The resultant active system is studied by molecular dynamics methods and integral equation theory. Both methods produce results consistent with each other and demonstrate that the Vicsek model-based activity facilitates phase separation, thus, broadening the coexistence region. PMID:24877969

  17. Site-controlled Ag nanocrystals grown by molecular beam epitaxy-Towards plasmonic integration technology

    SciTech Connect

    Urbanczyk, Adam; Noetzel, Richard

    2012-12-15

    We demonstrate site-controlled growth of epitaxial Ag nanocrystals on patterned GaAs substrates by molecular beam epitaxy with high degree of long-range uniformity. The alignment is based on lithographically defined holes in which position controlled InAs quantum dots are grown. The Ag nanocrystals self-align preferentially on top of the InAs quantum dots. No such ordering is observed in the absence of InAs quantum dots, proving that the ordering is strain-driven. The presented technique facilitates the placement of active plasmonic nanostructures at arbitrarily defined positions enabling their integration into complex devices and plasmonic circuits.

  18. Using non-invasive molecular spectroscopic techniques to detect unique aspects of protein Amide functional groups and chemical properties of modeled forage from different sourced-origins

    NASA Astrophysics Data System (ADS)

    Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

    2016-03-01

    The non-invasive molecular spectroscopic technique-FT/IR is capable to detect the molecular structure spectral features that are associated with biological, nutritional and biodegradation functions. However, to date, few researches have been conducted to use these non-invasive molecular spectroscopic techniques to study forage internal protein structures associated with biodegradation and biological functions. The objectives of this study were to detect unique aspects and association of protein Amide functional groups in terms of protein Amide I and II spectral profiles and chemical properties in the alfalfa forage (Medicago sativa L.) from different sourced-origins. In this study, alfalfa hay with two different origins was used as modeled forage for molecular structure and chemical property study. In each forage origin, five to seven sources were analyzed. The molecular spectral profiles were determined using FT/IR non-invasive molecular spectroscopy. The parameters of protein spectral profiles included functional groups of Amide I, Amide II and Amide I to II ratio. The results show that the modeled forage Amide I and Amide II were centered at 1653 cm- 1 and 1545 cm- 1, respectively. The Amide I spectral height and area intensities were from 0.02 to 0.03 and 2.67 to 3.36 AI, respectively. The Amide II spectral height and area intensities were from 0.01 to 0.02 and 0.71 to 0.93 AI, respectively. The Amide I to II spectral peak height and area ratios were from 1.86 to 1.88 and 3.68 to 3.79, respectively. Our results show that the non-invasive molecular spectroscopic techniques are capable to detect forage internal protein structure features which are associated with forage chemical properties.

  19. Integrating open-source software applications to build molecular dynamics systems.

    PubMed

    Allen, Bruce M; Predecki, Paul K; Kumosa, Maciej

    2014-04-01

    Three open-source applications, NanoEngineer-1, packmol, and mis2lmp are integrated using an open-source file format to quickly create molecular dynamics (MD) cells for simulation. The three software applications collectively make up the open-source software (OSS) suite known as MD Studio (MDS). The software is validated through software engineering practices and is verified through simulation of the diglycidyl ether of bisphenol-a and isophorone diamine (DGEBA/IPD) system. Multiple simulations are run using the MDS software to create MD cells, and the data generated are used to calculate density, bulk modulus, and glass transition temperature of the DGEBA/IPD system. Simulation results compare well with published experimental and numerical results. The MDS software prototype confirms that OSS applications can be analyzed against real-world research requirements and integrated to create a new capability.

  20. Toward Integrated Molecular Diagnostic System (iMDx): Principles and Applications

    PubMed Central

    Park, Seung-min; Sabour, Andrew F.; Son, Jun Ho; Lee, Sang Hun

    2014-01-01

    Integrated molecular diagnostic systems (iMDx), which are automated, sensitive, specific, user-friendly, robust, rapid, easy-to-use, and portable, can revolutionize future medicine. This review will first focus on the components of sample extraction, preservation, and filtration necessary for all point-of-care devices to include for practical use. Subsequently, we will look for low-powered and precise methods for both sample amplification and signal transduction, going in-depth to the details behind their principles. The final field of total device integration and its application to the clinical field will also be addressed to discuss the practicality for future patient care. We envision that microfluidic systems hold the potential to breakthrough the number of problems brought into the field of medical diagnosis today. PMID:24759281

  1. Efficient molecular dynamics using geodesic integration and solvent–solute splitting

    PubMed Central

    Leimkuhler, Benedict

    2016-01-01

    We present an approach to Langevin dynamics in the presence of holonomic constraints based on decomposition of the system into components representing geodesic flow, constrained impulse and constrained diffusion. We show that a particular ordering of the components results in an integrator that is an order of magnitude more accurate for configurational averages than existing alternatives. Moreover, by combining the geodesic integration method with a solvent–solute force splitting, we demonstrate that stepsizes of at least 8 fs can be used for solvated biomolecules with high sampling accuracy and without substantially altering diffusion rates, approximately increasing by a factor of two the efficiency of molecular dynamics sampling for such systems. The methods described in this article are easily implemented using the standard apparatus of modern simulation codes. PMID:27279779

  2. Integrity of Prostate Tissue for Molecular Analysis After Robotic-Assisted Laparoscopic and Open Prostatectomy

    PubMed Central

    Best, Sara; Sawers, Youssef; Fu, Vivian X.; Almassi, Nima; Huang, Wei; Jarrard, David F.

    2009-01-01

    Objectives Tissue warm-ischemia time prior to fixation for pathological analysis has been linked to changes in cell morphology, as well as nucleic acid and protein integrity. Robotic-assisted laparoscopic prostatectomy(RALP) results in longer warm-ischemia times compared to open radical retropubic prostatectomy(RRP). To assess the effect of longer ischemia times on biomolecular integrity we analyzed DNA, RNA and protein collected from robotic and open prostatectomies. Methods Specimens obtained from 22 consecutive RALP (11) or RRP (11) operations were examined after H&E staining by light microscopy. To assess protein integrity, immunohistochemical staining for p63, E-cadherin, and AE1/AE3 was performed. DNA was assessed by gel analysis. An RNA integrity score was determined by microfluidic capillary electrophoresis and calculated based on the electropherogram and simulated gel view. Finally, epithelial cells were cultured on collagen-coated plates. Results No differences in clinicopathologic characteristics existed between groups with the exception of a significantly longer warm-ischemia time during RALP (82+/−23min) versus RRP (23+/−2min) (<0.001). Tissue integrity was suitable for the assessment of pathologic grade and stage for all samples. Protein and DNA analyses demonstrated no evidence of degradation in any samples. No significant differences in the RI scores were demonstrated between surgical approaches. Prostate epithelial cells were cultured successfully in 66% of RALP specimens. Conclusion Robotic prostatectomy, though it involves additional exposure to warm-ischemia, does not significantly affect histopathological characteristics or the biomolecular integrity of the specimen. Provided a rapid response occurs for tissue banking after specimen removal, molecular research studies utilizing prostate tissue harvested via RALP appear feasible. PMID:17826499

  3. Outbreak Control and Clinical, Pathological, and Epidemiological Aspects and Molecular Characterization of a Bovine Herpesvirus Type 5 on a Feedlot Farm in São Paulo State.

    PubMed

    Megid, Jane; Ferreira Vicente, Acácia; Appolinario, Camila Michele; Allendorf, Susan Dora; de Souza Ribeiro Mioni, Mateus; Gasparini Baraldi, Thaís; Cortez, Adriana; Bryan Heinemann, Marcos; Reinaldo Silva Fonseca, Clovis; Cristina Pelícia, Vanessa; Devidé Ribeiro, Bruna Leticia; Hiromi Okuda, Liria; Pituco, Edviges Maristela

    2015-01-01

    This paper describes the control, epidemiological, pathological, and molecular aspects of an outbreak of meningoencephalitis in calves due to bovine herpesvirus 5 at a feedlot with 540 animals in São Paulo State, Brazil. The introduction of new animals and contact between the resident animals and the introduced ones were most likely responsible for virus transmission. Bovine herpesvirus 1 vaccine was used, resulting in the efficacy of the outbreak control, although two bovine herpesvirus 1 positive animals, vaccinated and revaccinated, presented meningoencephalitis, thereby characterizing vaccinal failure.

  4. Preparation, Purification, and Secondary Structure Determination of Bacillus Circulans Xylanase. A Molecular Laboratory Incorporating Aspects of Molecular Biology, Biochemistry, and Biophysical Chemistry

    ERIC Educational Resources Information Center

    Russo, Sal; Gentile, Lisa

    2006-01-01

    A project module designed for biochemistry or cellular and molecular biology student which involves determining the secondary structure of Bacillus circulans xylanase (BCX) by circular dichroism (CD) spectroscopy under conditions that compromise its stabilizing intramolecular forces is described. The lab model enhanced students knowledge of the…

  5. Evaluation and molecular characterization of human adenovirus in drinking water supplies: viral integrity and viability assays

    PubMed Central

    2013-01-01

    Background Human adenoviruses (HAdVs) are the second-leading cause of childhood gastroenteritis worldwide. This virus is commonly found in environmental waters and is very resistant to water disinfection and environmental stressors, especially UV light inactivation. Molecular techniques, such as PCR-based methods (Polymerase Chain Reaction), are commonly used to detect and identify viral contamination in water, although PCR alone does not allow the discrimination between infectious and non-infectious viral particles. A combination of cell culture and PCR has allowed detection of infectious viruses that grow slowly or fail to produce cytopathic effects (CPE) in cell culture. This study aimed to assess the integrity and viability of human adenovirus (HAdV) in environmental water and evaluate circulating strains by molecular characterization in three sites of the water supply in Florianópolis, Santa Catarina Island, Brazil: Peri Lagoon water, spring source water, and water from the public water supply system. Methods Water samples were collected, concentrated and HAdV quantified by real-time PCR. Viral integrity was evaluated by enzymatic assay (DNase I) and infectivity by plaque assay (PA) and integrated cell culture using transcribed mRNA (ICC-RT-qPCR). Samples containing particles of infectious HAdV were selected for sequencing and molecular characterization. Results The analyzed sites contained 83, 66 and 58% undamaged HAdV particles (defined as those in which the genetic material is protected by the viral capsid) at Peri Lagoon, spring source water and public supply system water, respectively. Of these, 66% of the particles (by PA) and 75% (by ICC-RT-qPCR) HAdV were shown to be infectious, due to being undamaged in Peri Lagoon, 33% (by PA) and 58% (by ICC-RT-qPCR) in spring source water and 8% (by PA) and 25% (by ICC-RT-qPCR) in the public water supply system. ICC-RT-qPCR, a very sensitive and rapid technique, was able to detect as low as 1 × 102 HAd

  6. Integrating Nanostructured Artificial Receptors with Whispering Gallery Mode Optical Microresonators via Inorganic Molecular Imprinting Techniques

    PubMed Central

    Hammond, G. Denise; Vojta, Adam L.; Grant, Sheila A.; Hunt, Heather K.

    2016-01-01

    The creation of label-free biosensors capable of accurately detecting trace contaminants, particularly small organic molecules, is of significant interest for applications in environmental monitoring. This is achieved by pairing a high-sensitivity signal transducer with a biorecognition element that imparts selectivity towards the compound of interest. However, many environmental pollutants do not have corresponding biorecognition elements. Fortunately, biomimetic chemistries, such as molecular imprinting, allow for the design of artificial receptors with very high selectivity for the target. Here, we perform a proof-of-concept study to show how artificial receptors may be created from inorganic silanes using the molecular imprinting technique and paired with high-sensitivity transducers without loss of device performance. Silica microsphere Whispering Gallery Mode optical microresonators are coated with a silica thin film templated by a small fluorescent dye, fluorescein isothiocyanate, which serves as our model target. Oxygen plasma degradation and solvent extraction of the template are compared. Extracted optical devices are interacted with the template molecule to confirm successful sorption of the template. Surface characterization is accomplished via fluorescence and optical microscopy, ellipsometry, optical profilometry, and contact angle measurements. The quality factors of the devices are measured to evaluate the impact of the coating on device sensitivity. The resulting devices show uniform surface coating with no microstructural damage with Q factors above 106. This is the first report demonstrating the integration of these devices with molecular imprinting techniques, and could lead to new routes to biosensor creation for environmental monitoring. PMID:27314397

  7. Integrating Nanostructured Artificial Receptors with Whispering Gallery Mode Optical Microresonators via Inorganic Molecular Imprinting Techniques.

    PubMed

    Hammond, G Denise; Vojta, Adam L; Grant, Sheila A; Hunt, Heather K

    2016-01-01

    The creation of label-free biosensors capable of accurately detecting trace contaminants, particularly small organic molecules, is of significant interest for applications in environmental monitoring. This is achieved by pairing a high-sensitivity signal transducer with a biorecognition element that imparts selectivity towards the compound of interest. However, many environmental pollutants do not have corresponding biorecognition elements. Fortunately, biomimetic chemistries, such as molecular imprinting, allow for the design of artificial receptors with very high selectivity for the target. Here, we perform a proof-of-concept study to show how artificial receptors may be created from inorganic silanes using the molecular imprinting technique and paired with high-sensitivity transducers without loss of device performance. Silica microsphere Whispering Gallery Mode optical microresonators are coated with a silica thin film templated by a small fluorescent dye, fluorescein isothiocyanate, which serves as our model target. Oxygen plasma degradation and solvent extraction of the template are compared. Extracted optical devices are interacted with the template molecule to confirm successful sorption of the template. Surface characterization is accomplished via fluorescence and optical microscopy, ellipsometry, optical profilometry, and contact angle measurements. The quality factors of the devices are measured to evaluate the impact of the coating on device sensitivity. The resulting devices show uniform surface coating with no microstructural damage with Q factors above 10⁶. This is the first report demonstrating the integration of these devices with molecular imprinting techniques, and could lead to new routes to biosensor creation for environmental monitoring. PMID:27314397

  8. inTB - a data integration platform for molecular and clinical epidemiological analysis of tuberculosis

    PubMed Central

    2013-01-01

    Background Tuberculosis is currently the second highest cause of death from infectious diseases worldwide. The emergence of multi and extensive drug resistance is threatening to make tuberculosis incurable. There is growing evidence that the genetic diversity of Mycobacterium tuberculosis may have important clinical consequences. Therefore, combining genetic, clinical and socio-demographic data is critical to understand the epidemiology of this infectious disease, and how virulence and other phenotypic traits evolve over time. This requires dedicated bioinformatics platforms, capable of integrating and enabling analyses of this heterogeneous data. Results We developed inTB, a web-based system for integrated warehousing and analysis of clinical, socio-demographic and molecular data for Mycobacterium sp. isolates. As a database it can organize and display data from any of the standard genotyping methods (SNP, MIRU-VNTR, RFLP and spoligotype), as well as an extensive array of clinical and socio-demographic variables that are used in multiple countries to characterize the disease. Through the inTB interface it is possible to insert and download data, browse the database and search specific parameters. New isolates are automatically classified into strains according to an internal reference, and data uploaded or typed in is checked for internal consistency. As an analysis framework, the system provides simple, point and click analysis tools that allow multiple types of data plotting, as well as simple ways to download data for external analysis. Individual trees for each genotyping method are available, as well as a super tree combining all of them. The integrative nature of inTB grants the user the ability to generate trees for filtered subsets of data crossing molecular and clinical/socio-demografic information. inTB is built on open source software, can be easily installed locally and easily adapted to other diseases. Its design allows for use by research

  9. Integrating molecular and morphological approaches for characterizing parasite cryptic species: implications for parasitology.

    PubMed

    Nadler, Steven A; DE León, Gerardo Pérez-Ponce

    2011-11-01

    Herein we review theoretical and methodological considerations important for finding and delimiting cryptic species of parasites (species that are difficult to recognize using traditional systematic methods). Applications of molecular data in empirical investigations of cryptic species are discussed from an historical perspective, and we evaluate advantages and disadvantages of approaches that have been used to date. Developments concerning the theory and practice of species delimitation are emphasized because theory is critical to interpretation of data. The advantages and disadvantages of different molecular methodologies, including the number and kind of loci, are discussed relative to tree-based approaches for detecting and delimiting cryptic species. We conclude by discussing some implications that cryptic species have for research programmes in parasitology, emphasizing that careful attention to the theory and operational practices involved in finding, delimiting, and describing new species (including cryptic species) is essential, not only for fully characterizing parasite biodiversity and broader aspects of comparative biology such as systematics, evolution, ecology and biogeography, but to applied research efforts that strive to improve development and understanding of epidemiology, diagnostics, control and potential eradication of parasitic diseases.

  10. VitisNet: “Omics” Integration through Grapevine Molecular Networks

    PubMed Central

    Grimplet, Jérôme; Cramer, Grant R.; Dickerson, Julie A.; Mathiason, Kathy; Van Hemert, John; Fennell, Anne Y.

    2009-01-01

    Background Genomic data release for the grapevine has increased exponentially in the last five years. The Vitis vinifera genome has been sequenced and Vitis EST, transcriptomic, proteomic, and metabolomic tools and data sets continue to be developed. The next critical challenge is to provide biological meaning to this tremendous amount of data by annotating genes and integrating them within their biological context. We have developed and validated a system of Grapevine Molecular Networks (VitisNet). Methodology/Principal Findings The sequences from the Vitis vinifera (cv. Pinot Noir PN40024) genome sequencing project and ESTs from the Vitis genus have been paired and the 39,424 resulting unique sequences have been manually annotated. Among these, 13,145 genes have been assigned to 219 networks. The pathway sets include 88 “Metabolic”, 15 “Genetic Information Processing”, 12 “Environmental Information Processing”, 3 “Cellular Processes”, 21 “Transport”, and 80 “Transcription Factors”. The quantitative data is loaded onto molecular networks, allowing the simultaneous visualization of changes in the transcriptome, proteome, and metabolome for a given experiment. Conclusions/Significance VitisNet uses manually annotated networks in SBML or XML format, enabling the integration of large datasets, streamlining biological functional processing, and improving the understanding of dynamic processes in systems biology experiments. VitisNet is grounded in the Vitis vinifera genome (currently at 8x coverage) and can be readily updated with subsequent updates of the genome or biochemical discoveries. The molecular network files can be dynamically searched by pathway name or individual genes, proteins, or metabolites through the MetNet Pathway database and web-portal at http://metnet3.vrac.iastate.edu/. All VitisNet files including the manual annotation of the grape genome encompassing pathway names, individual genes, their genome identifier, and

  11. Structural aspects of the solvation shell of lysine and acetylated lysine: A Car-Parrinello and classical molecular dynamics investigation

    SciTech Connect

    Carnevale, V.; Raugei, S.

    2009-12-14

    Lysine acetylation is a post-translational modification, which modulates the affinity of protein-protein and/or protein-DNA complexes. Its crucial role as a switch in signaling pathways highlights the relevance of charged chemical groups in determining the interactions between water and biomolecules. A great effort has been recently devoted to assess the reliability of classical molecular dynamics simulations in describing the solvation properties of charged moieties. In the spirit of these investigations, we performed classical and Car-Parrinello molecular dynamics simulations on lysine and acetylated-lysine in aqueous solution. A comparative analysis between the two computational schemes is presented with a focus on the first solvation shell of the charged groups. An accurate structural analysis unveils subtle, yet statistically significant, differences which are discussed in connection to the significant electronic density charge transfer occurring between the solute and the surrounding water molecules.

  12. [Molecular and genetic aspects of interactions of the circadian clock and the energy-producing substrate metabolism in mammals].

    PubMed

    Podkolodnaia, O A

    2014-02-01

    The circadian clock system coordinates al the processes occurring in the body and controls the rhythmic pattern in metabolic system functioning. The reciprocal relationship between molecular and genetic systems of the circadian clock and the systems responsible for carbohydrate and lipid turnover provide fine tuning both of metabolic processes and the circadian clock regulation system, permitting the body to adapt to a variable environment. NAD-dependent enzymes, protein-kinases, and transcription regulators could serve as presumable molecular components, which are responsible for such a type of relationship. Genetic models and epidemiological studies demonstrate an association between mutations in the circadian clock genes with the risk of a disturbance of metabolic processes regulation, obesity development, and other maniifestations of metabolic syndrome.

  13. Topiramate-Induced Modulation of Hepatic Molecular Mechanisms: An Aspect for Its Anti-Insulin Resistant Effect

    PubMed Central

    El-Abhar, Hanan S.; Schaalan, Mona F.

    2012-01-01

    Topiramate is an antiepileptic drug known to ameliorate insulin resistance besides reducing body weight. Albeit liver plays a fundamental role in regulation of overall insulin resistance, yet the effect of topiramate on this organ is controversial and is not fully investigated. The current work aimed to study the potential hepatic molecular mechanistic cassette of the anti-insulin resistance effect of topiramate. To this end, male Wistar rats were fed high fat/high fructose diet (HFFD) for 10 weeks to induce obese, insulin resistant, hyperglycemic animals, but with no overt diabetes. Two HFFD-groups received oral topiramate, 40 or 100 mg/kg, for two weeks. Topiramate, on the hepatic molecular level, has opposed the high fat/high fructose diet effect, where it significantly increased adiponectin receptors, GLUT2, and tyrosine kinase activity, while decreased insulin receptor isoforms. Besides, it improved the altered glucose homeostasis and lipid profile, lowered the ALT level, caused subtle, yet significant decrease in TNF-α, and boosted adiponectin in a dose dependent manner. Moreover, topiramate decreased liver weight/, visceral fat weight/, and epididymal fat weight/body weight ratios. The study proved that insulin-resistance has an effect on hepatic molecular level and that the topiramate-mediated insulin sensitivity is ensued partly by modulation of hepatic insulin receptor isoforms, activation of tyrosine kinase, induction of GLUT2 and elevation of adiponectin receptors, as well as their ligand, adiponectin, besides its known improving effect on glucose tolerance and lipid homeostasis. PMID:22649556

  14. Integrative Taxonomy and Molecular Phylogeny of Genus Aplysina (Demospongiae: Verongida) from Mexican Pacific

    PubMed Central

    Cruz-Barraza, José Antonio; Carballo, José Luis; Rocha-Olivares, Axayacatl; Ehrlich, Hermann; Hog, Martin

    2012-01-01

    Integrative taxonomy provides a major approximation to species delimitation based on integration of different perspectives (e.g. morphology, biochemistry and DNA sequences). The aim of this study was to assess the relationships and boundaries among Eastern Pacific Aplysina species using morphological, biochemical and molecular data. For this, a collection of sponges of the genus Aplysina from the Mexican Pacific was studied on the basis of their morphological, chemical (chitin composition), and molecular markers (mitochondrial COI and nuclear ribosomal rDNA: ITS1-5.8-ITS2). Three morphological species were identified, two of which are new to science. A. clathrata sp. nov. is a yellow to yellow-reddish or -brownish sponge, characterized by external clathrate-like morphology; A. revillagigedi sp. nov. is a lemon yellow to green, cushion-shaped sometimes lobate sponge, characterized by conspicuous oscules, which are slightly elevated and usually linearly distributed on rims; and A. gerardogreeni a known species distributed along the Mexican Pacific coast. Chitin was identified as the main structural component within skeletons of the three species using FTIR, confirming that it is shared among Verongida sponges. Morphological differences were confirmed by DNA sequences from nuclear ITS1-5.8-ITS2. Mitochondrial COI sequences showed extremely low but diagnostic variability for Aplysina revillagigedi sp. nov., thus our results corroborate that COI has limited power for DNA-barcoding of sponges and should be complemented with other markers (e.g. rDNA). Phylogenetic analyses of Aplysina sequences from the Eastern Pacific and Caribbean, resolved two allopatric and reciprocally monophyletic groups for each region. Eastern Pacific species were grouped in general accordance with the taxonomic hypothesis based on morphological characters. An identification key of Eastern Pacific Aplysina species is presented. Our results constitute one of the first approximations to integrative

  15. Integrative taxonomy and molecular phylogeny of genus Aplysina (Demospongiae: Verongida) from Mexican Pacific.

    PubMed

    Cruz-Barraza, José Antonio; Carballo, José Luis; Rocha-Olivares, Axayacatl; Ehrlich, Hermann; Hog, Martin

    2012-01-01

    Integrative taxonomy provides a major approximation to species delimitation based on integration of different perspectives (e.g. morphology, biochemistry and DNA sequences). The aim of this study was to assess the relationships and boundaries among Eastern Pacific Aplysina species using morphological, biochemical and molecular data. For this, a collection of sponges of the genus Aplysina from the Mexican Pacific was studied on the basis of their morphological, chemical (chitin composition), and molecular markers (mitochondrial COI and nuclear ribosomal rDNA: ITS1-5.8-ITS2). Three morphological species were identified, two of which are new to science. A. clathrata sp. nov. is a yellow to yellow-reddish or -brownish sponge, characterized by external clathrate-like morphology; A. revillagigedi sp. nov. is a lemon yellow to green, cushion-shaped sometimes lobate sponge, characterized by conspicuous oscules, which are slightly elevated and usually linearly distributed on rims; and A. gerardogreeni a known species distributed along the Mexican Pacific coast. Chitin was identified as the main structural component within skeletons of the three species using FTIR, confirming that it is shared among Verongida sponges. Morphological differences were confirmed by DNA sequences from nuclear ITS1-5.8-ITS2. Mitochondrial COI sequences showed extremely low but diagnostic variability for Aplysina revillagigedi sp. nov., thus our results corroborate that COI has limited power for DNA-barcoding of sponges and should be complemented with other markers (e.g. rDNA). Phylogenetic analyses of Aplysina sequences from the Eastern Pacific and Caribbean, resolved two allopatric and reciprocally monophyletic groups for each region. Eastern Pacific species were grouped in general accordance with the taxonomic hypothesis based on morphological characters. An identification key of Eastern Pacific Aplysina species is presented. Our results constitute one of the first approximations to integrative

  16. Legal Aspects in Quebec of Integration of Students with Handicaps, Social Maladjustments or Learning Disabilities: A Changing Situation.

    ERIC Educational Resources Information Center

    Dore, Robert; Wagner, Serge; Dore, Isabelle

    2001-01-01

    This article examines the current situation and evolution of school integration policies in Quebec and the influence of court decisions on these policies. Variations across Canada are discussed, particularly the differences between English-language school boards, who integrate many more students with intellectual disability, and French-speaking…

  17. Assessing the potential of surface-immobilized molecular logic machines for integration with solid state technology.

    PubMed

    Dunn, Katherine E; Trefzer, Martin A; Johnson, Steven; Tyrrell, Andy M

    2016-08-01

    Molecular computation with DNA has great potential for low power, highly parallel information processing in a biological or biochemical context. However, significant challenges remain for the field of DNA computation. New technology is needed to allow multiplexed label-free readout and to enable regulation of molecular state without addition of new DNA strands. These capabilities could be provided by hybrid bioelectronic systems in which biomolecular computing is integrated with conventional electronics through immobilization of DNA machines on the surface of electronic circuitry. Here we present a quantitative experimental analysis of a surface-immobilized OR gate made from DNA and driven by strand displacement. The purpose of our work is to examine the performance of a simple representative surface-immobilized DNA logic machine, to provide valuable information for future work on hybrid bioelectronic systems involving DNA devices. We used a quartz crystal microbalance to examine a DNA monolayer containing approximately 5×10(11)gatescm(-2), with an inter-gate separation of approximately 14nm, and we found that the ensemble of gates took approximately 6min to switch. The gates could be switched repeatedly, but the switching efficiency was significantly degraded on the second and subsequent cycles when the binding site for the input was near to the surface. Otherwise, the switching efficiency could be 80% or better, and the power dissipated by the ensemble of gates during switching was approximately 0.1nWcm(-2), which is orders of magnitude less than the power dissipated during switching of an equivalent array of transistors. We propose an architecture for hybrid DNA-electronic systems in which information can be stored and processed, either in series or in parallel, by a combination of molecular machines and conventional electronics. In this architecture, information can flow freely and in both directions between the solution-phase and the underlying electronics

  18. Assessing the potential of surface-immobilized molecular logic machines for integration with solid state technology.

    PubMed

    Dunn, Katherine E; Trefzer, Martin A; Johnson, Steven; Tyrrell, Andy M

    2016-08-01

    Molecular computation with DNA has great potential for low power, highly parallel information processing in a biological or biochemical context. However, significant challenges remain for the field of DNA computation. New technology is needed to allow multiplexed label-free readout and to enable regulation of molecular state without addition of new DNA strands. These capabilities could be provided by hybrid bioelectronic systems in which biomolecular computing is integrated with conventional electronics through immobilization of DNA machines on the surface of electronic circuitry. Here we present a quantitative experimental analysis of a surface-immobilized OR gate made from DNA and driven by strand displacement. The purpose of our work is to examine the performance of a simple representative surface-immobilized DNA logic machine, to provide valuable information for future work on hybrid bioelectronic systems involving DNA devices. We used a quartz crystal microbalance to examine a DNA monolayer containing approximately 5×10(11)gatescm(-2), with an inter-gate separation of approximately 14nm, and we found that the ensemble of gates took approximately 6min to switch. The gates could be switched repeatedly, but the switching efficiency was significantly degraded on the second and subsequent cycles when the binding site for the input was near to the surface. Otherwise, the switching efficiency could be 80% or better, and the power dissipated by the ensemble of gates during switching was approximately 0.1nWcm(-2), which is orders of magnitude less than the power dissipated during switching of an equivalent array of transistors. We propose an architecture for hybrid DNA-electronic systems in which information can be stored and processed, either in series or in parallel, by a combination of molecular machines and conventional electronics. In this architecture, information can flow freely and in both directions between the solution-phase and the underlying electronics

  19. Accelerating ab initio path integral molecular dynamics with multilevel sampling of potential surface

    SciTech Connect

    Geng, Hua Y.

    2015-02-15

    A multilevel approach to sample the potential energy surface in a path integral formalism is proposed. The purpose is to reduce the required number of ab initio evaluations of energy and forces in ab initio path integral molecular dynamics (AI-PIMD) simulation, without compromising the overall accuracy. To validate the method, the internal energy and free energy of an Einstein crystal are calculated and compared with the analytical solutions. As a preliminary application, we assess the performance of the method in a realistic model—the FCC phase of dense atomic hydrogen, in which the calculated result shows that the acceleration rate is about 3 to 4-fold for a two-level implementation, and can be increased up to 10 times if extrapolation is used. With only 16 beads used for the ab initio potential sampling, this method gives a well converged internal energy. The residual error in pressure is just about 3 GPa, whereas it is about 20 GPa for a plain AI-PIMD calculation with the same number of beads. The vibrational free energy of the FCC phase of dense hydrogen at 300 K is also calculated with an AI-PIMD thermodynamic integration method, which gives a result of about 0.51 eV/proton at a density of r{sub s}=0.912.

  20. Integration of molecular and enzymatic catalysts on graphene for biomimetic generation of antithrombotic species

    NASA Astrophysics Data System (ADS)

    Xue, Teng; Peng, Bo; Xue, Min; Zhong, Xing; Chiu, Chin-Yi; Yang, Si; Qu, Yongquan; Ruan, Lingyan; Jiang, Shan; Dubin, Sergey; Kaner, Richard B.; Zink, Jeffrey I.; Meyerhoff, Mark E.; Duan, Xiangfeng; Huang, Yu

    2014-02-01

    The integration of multiple synergistic catalytic systems can enable the creation of biocompatible enzymatic mimics for cascading reactions under physiologically relevant conditions. Here we report the design of a graphene-haemin-glucose oxidase conjugate as a tandem catalyst, in which graphene functions as a unique support to integrate molecular catalyst haemin and enzymatic catalyst glucose oxidase for biomimetic generation of antithrombotic species. Monomeric haemin can be conjugated with graphene through π-π interactions to function as an effective catalyst for the oxidation of endogenous L-arginine by hydrogen peroxide. Furthermore, glucose oxidase can be covalently linked onto graphene for local generation of hydrogen peroxide through the oxidation of blood glucose. Thus, the integrated graphene-haemin-glucose oxidase catalysts can readily enable the continuous generation of nitroxyl, an antithrombotic species, from physiologically abundant glucose and L-arginine. Finally, we demonstrate that the conjugates can be embedded within polyurethane to create a long-lasting antithrombotic coating for blood-contacting biomedical devices.

  1. Integration of molecular and enzymatic catalysts on graphene for biomimetic generation of antithrombotic species.

    PubMed

    Xue, Teng; Peng, Bo; Xue, Min; Zhong, Xing; Chiu, Chin-Yi; Yang, Si; Qu, Yongquan; Ruan, Lingyan; Jiang, Shan; Dubin, Sergey; Kaner, Richard B; Zink, Jeffrey I; Meyerhoff, Mark E; Duan, Xiangfeng; Huang, Yu

    2014-01-01

    The integration of multiple synergistic catalytic systems can enable the creation of biocompatible enzymatic mimics for cascading reactions under physiologically relevant conditions. Here we report the design of a graphene-haemin-glucose oxidase conjugate as a tandem catalyst, in which graphene functions as a unique support to integrate molecular catalyst haemin and enzymatic catalyst glucose oxidase for biomimetic generation of antithrombotic species. Monomeric haemin can be conjugated with graphene through π-π interactions to function as an effective catalyst for the oxidation of endogenous L-arginine by hydrogen peroxide. Furthermore, glucose oxidase can be covalently linked onto graphene for local generation of hydrogen peroxide through the oxidation of blood glucose. Thus, the integrated graphene-haemin-glucose oxidase catalysts can readily enable the continuous generation of nitroxyl, an antithrombotic species, from physiologically abundant glucose and L-arginine. Finally, we demonstrate that the conjugates can be embedded within polyurethane to create a long-lasting antithrombotic coating for blood-contacting biomedical devices. PMID:24518643

  2. Integrated microfluidic tmRNA purification and real-time NASBA device for molecular diagnostics.

    PubMed

    Dimov, Ivan K; Garcia-Cordero, Jose L; O'Grady, Justin; Poulsen, Claus R; Viguier, Caroline; Kent, Lorcan; Daly, Paul; Lincoln, Bryan; Maher, Majella; O'Kennedy, Richard; Smith, Terry J; Ricco, Antonio J; Lee, Luke P

    2008-12-01

    We demonstrate the first integrated microfluidic tmRNA purification and nucleic acid sequence-based amplification (NASBA) device incorporating real-time detection. The real-time amplification and detection step produces pathogen-specific response in < 3 min from the chip-purified RNA from 100 lysed bacteria. On-chip RNA purification uses a new silica bead immobilization method. On-chip amplification uses custom-designed high-selectivity primers and real-time detection uses molecular beacon fluorescent probe technology; both are integrated on-chip with NASBA. Present in all bacteria, tmRNA (10Sa RNA) includes organism-specific identification sequences, exhibits unusually high stability relative to mRNA, and has high copy number per organism; the latter two factors improve the limit of detection, accelerate time-to-positive response, and suit this approach ideally to the detection of small numbers of bacteria. Device efficacy was demonstrated by integrated on-chip purification, amplification, and real-time detection of 100 E. coli bacteria in 100 microL of crude lysate in under 30 min for the entire process.

  3. Integration of molecular and enzymatic catalysts on graphene for biomimetic generation of antithrombotic species

    PubMed Central

    Xue, Teng; Peng, Bo; Xue, Min; Zhong, Xing; Chiu, Chin-Yi; Yang, Si; Qu, Yongquan; Ruan, Lingyan; Jiang, Shan; Dubin, Sergey; Kaner, Richard B.; Zink, Jeffrey I.; Meyerhoff, Mark E.; Duan, Xiangfeng; Huang, Yu

    2014-01-01

    The integration of multiple synergistic catalytic systems can enable the creation of biocompatible enzymatic mimics for cascading reactions under physiologically relevant conditions. Here we report the design of a graphene–haemin–glucose oxidase conjugate as a tandem catalyst, in which graphene functions as a unique support to integrate molecular catalyst haemin and enzymatic catalyst glucose oxidase for biomimetic generation of antithrombotic species. Monomeric haemin can be conjugated with graphene through π–π interactions to function as an effective catalyst for the oxidation of endogenous L-arginine by hydrogen peroxide. Furthermore, glucose oxidase can be covalently linked onto graphene for local generation of hydrogen peroxide through the oxidation of blood glucose. Thus, the integrated graphene–haemin–glucose oxidase catalysts can readily enable the continuous generation of nitroxyl, an antithrombotic species, from physiologically abundant glucose and L-arginine. Finally, we demonstrate that the conjugates can be embedded within polyurethane to create a long-lasting antithrombotic coating for blood-contacting biomedical devices. PMID:24518643

  4. Some interesting aspects of physisorption stay-time measurements obtained using molecular-beam techniques. [on Ni surface

    NASA Technical Reports Server (NTRS)

    Wilmoth, R. G.; Fisher, S. S.

    1974-01-01

    Stay-time distributions have been obtained for Xe physisorbing on polycrystalline nickel as a function of the target temperature using a pulsed molecular-beam technique. Some interesting effects due to ion bombardment of the surface using He, Ar, and Xe ions are presented. Measured detector signal shapes are found to deviate from those predicted for first-order desorption with velocities corresponding to Maxwellian effusion at the surface temperature. Evidence is found for interaction between beam pulse adsorption and steady-state adsorption of beam species background atoms.

  5. Molecular characterization and morphological aspects of Myxobolus parvus (Myxozoa) from Liza saliens (Mugilidae) off the Turkish Black Sea coasts.

    PubMed

    Özer, A; Gürkanlı, C T; Özkan, H; Acar, G; Çiftçi, Y; Yurakhno, V

    2016-09-01

    Members of the phylum Myxozoa are among the most cosmopolitan parasites of fish, and the genus Myxobolus is the largest within the class Myxosporea in freshwater and marine environment from all over the world. Myxobolus parvus has been reported from mainly mugilid fishes from different localities including the Black Sea. Leaping mullet Liza saliens collected by fishermen off Sinop coasts of the Black Sea in the period between September 2014 and December 2015 was investigated for myxosporean parasites using conventional methods. M. parvus Schulman, 1962 was the only Myxobolus species identified and it was found in the gills, gall bladder, kidney tubules, and inside several cysts located on the lower jaw of examined fish in the present study. Morphometric data and all details of parasitic infection were determined and presented in tables and illustrated in figures. Molecular characterization was also conducted to reveal its position within Myxosporea. Two M. parvus samples from gills and kidney showed the same haplotype and appeared in the same sub-lineage with marine Myxobolus species. The closest haplotypes to M. parvus were Triactinomyxon sp. and Endocapsa sp. which are the actinosporeans forms of unknown myxozoan species. These data are the first in molecular characterization of M. parvus, its occurrence in lower jaw of leaping mullet along with its infection prevalence values off the Turkish Black Sea coasts. PMID:27198509

  6. Molecular Features of Triple Negative Breast Cancer: Microarray Evidence and Further Integrated Analysis

    PubMed Central

    Chen, Weicai; Wu, Huisheng; Yuan, Zishan; Wang, Kun; Li, Guojin; Sun, Jie; Yu, Limin

    2015-01-01

    Purpose Breast cancer is a heterogeneous disease usually including four molecular subtypes such as luminal A, luminal B, HER2-enriched, and triple-negative breast cancer (TNBC). TNBC is more aggressive than other breast cancer subtypes. Despite major advances in ER-positive or HER2-amplified breast cancer, there is no targeted agent currently available for TNBC, so it is urgent to identify new potential therapeutic targets for TNBC. Methods We first used microarray analysis to compare gene expression profiling between TNBC and non-TNBC. Furthermore an integrated analysis was conducted based on our own and published data, leading to more robust, reproducible and accurate predictions. Additionally, we performed qRT-PCR in breast cancer cell lines to verify the findings in integrated analysis. Results After searching Gene Expression Omnibus database (GEO), two microarray studies were obtained according to the inclusion criteria. The integrated analysis was conducted, including 30 samples of TNBC and 77 samples of non-TNBC. 556 genes were found to be consistently differentially expressed (344 up-regulated genes and 212 down-regulated genes in TNBC). Functional annotation for these differentially expressed genes (DEGs) showed that the most significantly enriched Gene Ontology (GO) term for molecular functions was protein binding (GO: 0005515, P = 6.09E-21), while that for biological processes was signal transduction (GO: 0007165, P = 9.46E-08), and that for cellular component was cytoplasm (GO: 0005737, P = 2.09E-21). The most significant pathway was Pathways in cancer (P = 6.54E-05) based on Kyoto Encyclopedia of Genes and Genomes (KEGG). DUSP1 (Degree = 21), MYEOV2 (Degree = 15) and UQCRQ (Degree = 14) were identified as the significant hub proteins in the protein-protein interaction (PPI) network. Five genes were selected to perform qRT-PCR in seven breast cancer cell lines, and qRT-PCR results showed that the expression pattern of selected genes in TNBC lines and

  7. Molecular Aspects of Structure, Gating, and Physiology of pH-Sensitive Background K2P and Kir K+-Transport Channels

    PubMed Central

    Sepúlveda, Francisco V.; Pablo Cid, L.; Teulon, Jacques; Niemeyer, María Isabel

    2015-01-01

    K+ channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K+ channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique features with important consequences for the gating mechanisms. Important tasks of these channels are discussed in kidney physiology and disease, K+ homeostasis in the brain by Kir channel-equipped glia, and central functions in the hearing mechanism in the inner ear and in acid secretion by parietal cells in the stomach. K2P channels fulfill a crucial part in central chemoreception probably by virtue of their pH sensitivity and are central to adrenal secretion of aldosterone. Finally, some unorthodox behaviors of the selectivity filters of K2P channels might explain their normal and pathological functions. Although a great deal has been learned about structure, molecular details of gating, and physiological functions of K2P and Kir K+-transport channels, this has been only scratching at the surface. More molecular and animal studies are clearly needed to deepen our knowledge. PMID:25540142

  8. Molecular aspects of structure, gating, and physiology of pH-sensitive background K2P and Kir K+-transport channels.

    PubMed

    Sepúlveda, Francisco V; Pablo Cid, L; Teulon, Jacques; Niemeyer, María Isabel

    2015-01-01

    K(+) channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K(+) channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique features with important consequences for the gating mechanisms. Important tasks of these channels are discussed in kidney physiology and disease, K(+) homeostasis in the brain by Kir channel-equipped glia, and central functions in the hearing mechanism in the inner ear and in acid secretion by parietal cells in the stomach. K2P channels fulfill a crucial part in central chemoreception probably by virtue of their pH sensitivity and are central to adrenal secretion of aldosterone. Finally, some unorthodox behaviors of the selectivity filters of K2P channels might explain their normal and pathological functions. Although a great deal has been learned about structure, molecular details of gating, and physiological functions of K2P and Kir K(+)-transport channels, this has been only scratching at the surface. More molecular and animal studies are clearly needed to deepen our knowledge.

  9. From Research to Operations: Integrating Components of an Advanced Diagnostic System with an Aspect-Oriented Framework

    NASA Technical Reports Server (NTRS)

    Fletcher, Daryl P.; Alena, Richard L.; Akkawi, Faisal; Duncavage, Daniel P.

    2004-01-01

    This paper presents some of the challenges associated with bringing software projects from the research world into an operationa1 environment. While the core functional components of research-oriented software applications can have great utility in an operational setting, these applications often lack aspects important in an operational environment such as logging and security. Furthermore, these stand-alone applications, sometimes developed in isolation from one another, can produce data products useful to other applications in a software ecosystem.

  10. Proton transfer dynamics in the propionic acid dimer from path integral molecular dynamics calculations.

    PubMed

    Durlak, Piotr; Latajka, Zdzisław

    2011-09-01

    The double proton transfer process in the cyclic dimer of propionic acid in the gas phase was studied using a path integral molecular dynamics method. Structures, energies and proton trajectories were determined. Very large amplitude motions of the skeleton of a propionic acid molecule were observed during the simulations, and almost free rotation of the C(2)H(5) group around the C(α)-C bond. A double-well symmetric potential with a very small energy barrier was determined from the free energy profile for the proton motions. Infrared spectra for different isotopomers were calculated, and comparative vibrational analysis was performed. The vibrational results from CPMD appear to be in qualitative agreement with the experimental ones. PMID:21213001

  11. Bulk and integrated acousto-optic spectrometers for molecular astronomy with heterodyne spectrometers

    NASA Technical Reports Server (NTRS)

    Chin, G.; Buhl, D.; Florez, J. M.

    1981-01-01

    A survey of acousto-optic spectrometers for molecular astronomy is presented, noting a technique of combining the acoustic bending of a collimated coherent light beam with a Bragg cell followed by an array of sensitive photodetectors. This acousto-optic spectrometer has a large bandwidth, a large number of channels, high resolution, and is energy efficient. Receiver development has concentrated on high-frequency heterodyne systems for the study of the chemical composition of the interstellar medium. RF spectrometers employing acousto-optic diffraction cells are described. Acousto-optic techniques have been suggested for applications to electronic warfare, electronic countermeasures and electronic support systems. Plans to use integrated optics for the further miniaturization of acousto-optic spectrometers are described. Bulk acousto-optic spectrometers with 300 MHz and 1 GHz bandwidths are being developed for use in the back-end of high-frequency heterodyne receivers for astronomical research.

  12. A Critical Analysis of Rejection in Vascularized Composite Allotransplantation: Clinical, Cellular and Molecular Aspects, Current Challenges, and Novel Concepts

    PubMed Central

    Sarhane, Karim A.; Tuffaha, Sami H.; Broyles, Justin M.; Ibrahim, Amir E.; Khalifian, Saami; Baltodano, Pablo; Santiago, Gabriel F.; Alrakan, Mohammed; Ibrahim, Zuhaib

    2013-01-01

    Advances in microsurgical techniques and immunomodulatory protocols have contributed to the expansion of vascularized composite allotransplantation (VCA) with very encouraging immunological, functional, and cosmetic results. Rejection remains however a major hurdle that portends serious threats to recipients. Rejection features in VCA have been described in a number of studies, and an international consensus on the classification of rejection was established. Unfortunately, current available diagnostic methods carry many shortcomings that, in certain cases, pose a great diagnostic challenge to physicians especially in borderline rejection cases. In this review, we revisit the features of acute skin rejection in hand and face transplantation at the clinical, cellular, and molecular levels. The multiple challenges in diagnosing rejection and in defining chronic and antibody-mediated rejection in VCA are then presented, and we finish by analyzing current research directions and novel concepts aiming at improving available diagnostic measures. PMID:24324470

  13. Equilibrium fractionation of H and O isotopes in water from path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Pinilla, Carlos; Blanchard, Marc; Balan, Etienne; Ferlat, Guillaume; Vuilleumier, Rodolphe; Mauri, Francesco

    2014-06-01

    The equilibrium fractionation factor between two phases is of importance for the understanding of many planetary and environmental processes. Although thermodynamic equilibrium can be achieved between minerals at high temperature, many natural processes involve reactions between liquids or aqueous solutions and solids. For crystals, the fractionation factor α can be theoretically determined using a statistical thermodynamic approach based on the vibrational properties of the phases. These calculations are mostly performed in the harmonic approximation, using empirical or ab-initio force fields. In the case of aperiodic and dynamic systems such as liquids or solutions, similar calculations can be done using finite-size molecular clusters or snapshots obtained from molecular dynamics (MD) runs. It is however difficult to assess the effect of these approximate models on the isotopic fractionation properties. In this work we present a systematic study of the calculation of the D/H and 18O/16O equilibrium fractionation factors in water for the liquid/vapour and ice/vapour phases using several levels of theory within the simulations. Namely, we use a thermodynamic integration approach based on Path Integral MD calculations (PIMD) and an empirical potential model of water. Compared with standard MD, PIMD takes into account quantum effects in the thermodynamic modeling of systems and the exact fractionation factor for a given potential can be obtained. We compare these exact results with those of modeling strategies usually used, which involve the mapping of the quantum system on its harmonic counterpart. The results show the importance of including configurational disorder for the estimation of isotope fractionation in liquid phases. In addition, the convergence of the fractionation factor as a function of parameters such as the size of the simulated system and multiple isotope substitution is analyzed, showing that isotope fractionation is essentially a local effect in

  14. Dating primate divergences through an integrated analysis of palaeontological and molecular data.

    PubMed

    Wilkinson, Richard D; Steiper, Michael E; Soligo, Christophe; Martin, Robert D; Yang, Ziheng; Tavaré, Simon

    2011-01-01

    Estimation of divergence times is usually done using either the fossil record or sequence data from modern species. We provide an integrated analysis of palaeontological and molecular data to give estimates of primate divergence times that utilize both sources of information. The number of preserved primate species discovered in the fossil record, along with their geological age distribution, is combined with the number of extant primate species to provide initial estimates of the primate and anthropoid divergence times. This is done by using a stochastic forwards-modeling approach where speciation and fossil preservation and discovery are simulated forward in time. We use the posterior distribution from the fossil analysis as a prior distribution on node ages in a molecular analysis. Sequence data from two genomic regions (CFTR on human chromosome 7 and the CYP7A1 region on chromosome 8) from 15 primate species are used with the birth-death model implemented in mcmctree in PAML to infer the posterior distribution of the ages of 14 nodes in the primate tree. We find that these age estimates are older than previously reported dates for all but one of these nodes. To perform the inference, a new approximate Bayesian computation (ABC) algorithm is introduced, where the structure of the model can be exploited in an ABC-within-Gibbs algorithm to provide a more efficient analysis.

  15. Molecular classification based on apomorphic amino acids (Arthropoda, Hexapoda): Integrative taxonomy in the era of phylogenomics

    PubMed Central

    Wu, Hao-Yang; Wang, Yan-Hui; Xie, Qiang; Ke, Yun-Ling; Bu, Wen-Jun

    2016-01-01

    With the great development of sequencing technologies and systematic methods, our understanding of evolutionary relationships at deeper levels within the tree of life has greatly improved over the last decade. However, the current taxonomic methodology is insufficient to describe the growing levels of diversity in both a standardised and general way due to the limitations of using only morphological traits to describe clades. Herein, we propose the idea of a molecular classification based on hierarchical and discrete amino acid characters. Clades are classified based on the results of phylogenetic analyses and described using amino acids with group specificity in phylograms. Practices based on the recently published phylogenomic datasets of insects together with 15 de novo sequenced transcriptomes in this study demonstrate that such a methodology can accommodate various higher ranks of taxonomy. Such an approach has the advantage of describing organisms in a standard and discrete way within a phylogenetic framework, thereby facilitating the recognition of clades from the view of the whole lineage, as indicated by PhyloCode. By combining identification keys and phylogenies, the molecular classification based on hierarchical and discrete characters may greatly boost the progress of integrative taxonomy. PMID:27312960

  16. Integrating atomistic molecular dynamics simulations, experiments, and network analysis to study protein dynamics: strength in unity

    PubMed Central

    Papaleo, Elena

    2015-01-01

    In the last years, we have been observing remarkable improvements in the field of protein dynamics. Indeed, we can now study protein dynamics in atomistic details over several timescales with a rich portfolio of experimental and computational techniques. On one side, this provides us with the possibility to validate simulation methods and physical models against a broad range of experimental observables. On the other side, it also allows a complementary and comprehensive view on protein structure and dynamics. What is needed now is a better understanding of the link between the dynamic properties that we observe and the functional properties of these important cellular machines. To make progresses in this direction, we need to improve the physical models used to describe proteins and solvent in molecular dynamics, as well as to strengthen the integration of experiments and simulations to overcome their own limitations. Moreover, now that we have the means to study protein dynamics in great details, we need new tools to understand the information embedded in the protein ensembles and in their dynamic signature. With this aim in mind, we should enrich the current tools for analysis of biomolecular simulations with attention to the effects that can be propagated over long distances and are often associated to important biological functions. In this context, approaches inspired by network analysis can make an important contribution to the analysis of molecular dynamics simulations. PMID:26075210

  17. Integrating atomistic molecular dynamics simulations, experiments, and network analysis to study protein dynamics: strength in unity.

    PubMed

    Papaleo, Elena

    2015-01-01

    In the last years, we have been observing remarkable improvements in the field of protein dynamics. Indeed, we can now study protein dynamics in atomistic details over several timescales with a rich portfolio of experimental and computational techniques. On one side, this provides us with the possibility to validate simulation methods and physical models against a broad range of experimental observables. On the other side, it also allows a complementary and comprehensive view on protein structure and dynamics. What is needed now is a better understanding of the link between the dynamic properties that we observe and the functional properties of these important cellular machines. To make progresses in this direction, we need to improve the physical models used to describe proteins and solvent in molecular dynamics, as well as to strengthen the integration of experiments and simulations to overcome their own limitations. Moreover, now that we have the means to study protein dynamics in great details, we need new tools to understand the information embedded in the protein ensembles and in their dynamic signature. With this aim in mind, we should enrich the current tools for analysis of biomolecular simulations with attention to the effects that can be propagated over long distances and are often associated to important biological functions. In this context, approaches inspired by network analysis can make an important contribution to the analysis of molecular dynamics simulations.

  18. Molecular classification based on apomorphic amino acids (Arthropoda, Hexapoda): Integrative taxonomy in the era of phylogenomics.

    PubMed

    Wu, Hao-Yang; Wang, Yan-Hui; Xie, Qiang; Ke, Yun-Ling; Bu, Wen-Jun

    2016-06-17

    With the great development of sequencing technologies and systematic methods, our understanding of evolutionary relationships at deeper levels within the tree of life has greatly improved over the last decade. However, the current taxonomic methodology is insufficient to describe the growing levels of diversity in both a standardised and general way due to the limitations of using only morphological traits to describe clades. Herein, we propose the idea of a molecular classification based on hierarchical and discrete amino acid characters. Clades are classified based on the results of phylogenetic analyses and described using amino acids with group specificity in phylograms. Practices based on the recently published phylogenomic datasets of insects together with 15 de novo sequenced transcriptomes in this study demonstrate that such a methodology can accommodate various higher ranks of taxonomy. Such an approach has the advantage of describing organisms in a standard and discrete way within a phylogenetic framework, thereby facilitating the recognition of clades from the view of the whole lineage, as indicated by PhyloCode. By combining identification keys and phylogenies, the molecular classification based on hierarchical and discrete characters may greatly boost the progress of integrative taxonomy.

  19. QwikMD — Integrative Molecular Dynamics Toolkit for Novices and Experts

    PubMed Central

    Ribeiro, João V.; Bernardi, Rafael C.; Rudack, Till; Stone, John E.; Phillips, James C.; Freddolino, Peter L.; Schulten, Klaus

    2016-01-01

    The proper functioning of biomolecules in living cells requires them to assume particular structures and to undergo conformational changes. Both biomolecular structure and motion can be studied using a wide variety of techniques, but none offers the level of detail as do molecular dynamics (MD) simulations. Integrating two widely used modeling programs, namely NAMD and VMD, we have created a robust, user-friendly software, QwikMD, which enables novices and experts alike to address biomedically relevant questions, where often only molecular dynamics simulations can provide answers. Performing both simple and advanced MD simulations interactively, QwikMD automates as many steps as necessary for preparing, carrying out, and analyzing simulations while checking for common errors and enabling reproducibility. QwikMD meets also the needs of experts in the field, increasing the efficiency and quality of their work by carrying out tedious or repetitive tasks while enabling easy control of every step. Whether carrying out simulations within the live view mode on a small laptop or performing complex and large simulations on supercomputers or Cloud computers, QwikMD uses the same steps and user interface. QwikMD is freely available by download on group and personal computers. It is also available on the cloud at Amazon Web Services. PMID:27216779

  20. QwikMD — Integrative Molecular Dynamics Toolkit for Novices and Experts

    NASA Astrophysics Data System (ADS)

    Ribeiro, João V.; Bernardi, Rafael C.; Rudack, Till; Stone, John E.; Phillips, James C.; Freddolino, Peter L.; Schulten, Klaus

    2016-05-01

    The proper functioning of biomolecules in living cells requires them to assume particular structures and to undergo conformational changes. Both biomolecular structure and motion can be studied using a wide variety of techniques, but none offers the level of detail as do molecular dynamics (MD) simulations. Integrating two widely used modeling programs, namely NAMD and VMD, we have created a robust, user-friendly software, QwikMD, which enables novices and experts alike to address biomedically relevant questions, where often only molecular dynamics simulations can provide answers. Performing both simple and advanced MD simulations interactively, QwikMD automates as many steps as necessary for preparing, carrying out, and analyzing simulations while checking for common errors and enabling reproducibility. QwikMD meets also the needs of experts in the field, increasing the efficiency and quality of their work by carrying out tedious or repetitive tasks while enabling easy control of every step. Whether carrying out simulations within the live view mode on a small laptop or performing complex and large simulations on supercomputers or Cloud computers, QwikMD uses the same steps and user interface. QwikMD is freely available by download on group and personal computers. It is also available on the cloud at Amazon Web Services.

  1. QwikMD - Integrative Molecular Dynamics Toolkit for Novices and Experts.

    PubMed

    Ribeiro, João V; Bernardi, Rafael C; Rudack, Till; Stone, John E; Phillips, James C; Freddolino, Peter L; Schulten, Klaus

    2016-05-24

    The proper functioning of biomolecules in living cells requires them to assume particular structures and to undergo conformational changes. Both biomolecular structure and motion can be studied using a wide variety of techniques, but none offers the level of detail as do molecular dynamics (MD) simulations. Integrating two widely used modeling programs, namely NAMD and VMD, we have created a robust, user-friendly software, QwikMD, which enables novices and experts alike to address biomedically relevant questions, where often only molecular dynamics simulations can provide answers. Performing both simple and advanced MD simulations interactively, QwikMD automates as many steps as necessary for preparing, carrying out, and analyzing simulations while checking for common errors and enabling reproducibility. QwikMD meets also the needs of experts in the field, increasing the efficiency and quality of their work by carrying out tedious or repetitive tasks while enabling easy control of every step. Whether carrying out simulations within the live view mode on a small laptop or performing complex and large simulations on supercomputers or Cloud computers, QwikMD uses the same steps and user interface. QwikMD is freely available by download on group and personal computers. It is also available on the cloud at Amazon Web Services.

  2. Towards an Integrative Morpho-molecular Classification of the Collodaria (Polycystinea, Radiolaria).

    PubMed

    Biard, Tristan; Pillet, Loïc; Decelle, Johan; Poirier, Camille; Suzuki, Noritoshi; Not, Fabrice

    2015-07-01

    Collodaria are ubiquitous and abundant marine radiolarian (Rhizaria) protists. They occur as either large colonies or solitary specimens, and, unlike most radiolarians, some taxa lack silicified structures. Collodarians are known to play an important role in oceanic food webs as both active predators and hosts of symbiotic microalgae, yet very little is known about their diversity and evolution. Taxonomic delineation of collodarians is challenging and only a few species have been genetically characterized. Here we investigated collodarian diversity using phylogenetic analyses of both nuclear small (18S) and large (28S) subunits of the ribosomal DNA, including 124 new sequences from 75 collodarians sampled worldwide. The resulting molecular phylogeny was compared to morphology-based classification. Our analyses distinguished the monophyletic clade of skeleton-less and spicule-bearing Sphaerozoidae from the sister clades Collosphaeridae (skeleton-bearing) and Collophidiidae (skeleton-less), while the Thalassicollidae was not retrieved as a monophyletic clade. Detailed morphological examination with electron microscopy combined with molecular analyses revealed many discrepancies, such as a mix between solitary and colonial species, co-existence of skeleton-less and skeleton-bearing specimens within the Collosphaeridae, as well as complex intraspecific variability in silicified structures. Such observations challenge a morphology-based classification and highlight the pertinence of an integrative taxonomic approach to study collodarian diversity.

  3. Heterogeneity revealed by integrated genomic analysis uncovers a molecular switch in malignant uveal melanoma.

    PubMed

    de Lange, Mark J; van Pelt, Sake I; Versluis, Mieke; Jordanova, Ekaterina S; Kroes, Wilma G M; Ruivenkamp, Claudia; van der Burg, Sjoerd H; Luyten, Grégorius P M; van Hall, Thorbald; Jager, Martine J; van der Velden, Pieter A

    2015-11-10

    Gene expression profiles as well as genomic imbalances are correlated with disease progression in uveal melanoma (UM). We integrated expression and genomic profiles to obtain insight into the oncogenic mechanisms in development and progression of UM. We used tumor tissue from 64 enucleated eyes of UM patients for profiling. Mutations and genomic imbalances were quantified with digital PCR to study tumor heterogeneity and molecular pathogenesis. Gene expression analysis divided the UM panel into three classes. Class I presented tumors with a good prognosis and a distinct genomic make up that is characterized by 6p gain. The UM with a bad prognosis were subdivided into class IIa and class IIb. These classes presented similar survival risks but could be distinguished by tumor heterogeneity. Class IIa presented homogeneous tumors while class IIb tumors, on average, contained 30% of non-mutant cells. Tumor heterogeneity coincided with expression of a set of immune genes revealing an extensive immune infiltrate in class IIb tumors. Molecularly, class IIa and IIb presented the same genomic configuration and could only be distinguished by 8q copy number. Moreover, UM establish in the void of the immune privileged eye indicating that in IIb tumors the infiltrate is attracted by the UM. Combined our data show that chromosome 8q contains the locus that causes the immune phentotype of UM. UM thereby provides an unique opportunity to study immune attraction by tumors. PMID:26462151

  4. Integrating responsible conduct of research education into undergraduate biochemistry and molecular biology laboratory curricula.

    PubMed

    Hendrickson, Tamara L

    2015-01-01

    Recently, a requirement for directed responsible conduct in research (RCR) education has become a priority in the United States and elsewhere. In the US, both the National Institutes of Health and the National Science Foundation require RCR education for all students who are financially supported by federal awards. The guidelines produced by these agencies offer useful templates for the introduction of RCR materials into courses worldwide. Many academic programs already offer courses or workshops in RCR for their graduate students and for undergraduate science majors and/or researchers. Introducing RCR into undergraduate biochemistry and molecular biology laboratory curricula is another, highly practical way that students can be exposed to these important topics. In fact, a strong argument can be made for integrating RCR into laboratory courses because these classes often introduce students to a scientific environment like that they might encounter in their careers after graduation. This article focuses on general strategies for incorporating explicit RCR education into biochemistry and molecular biology laboratory coursework using the topics suggested by NIH as a starting point.

  5. QwikMD - Integrative Molecular Dynamics Toolkit for Novices and Experts.

    PubMed

    Ribeiro, João V; Bernardi, Rafael C; Rudack, Till; Stone, John E; Phillips, James C; Freddolino, Peter L; Schulten, Klaus

    2016-01-01

    The proper functioning of biomolecules in living cells requires them to assume particular structures and to undergo conformational changes. Both biomolecular structure and motion can be studied using a wide variety of techniques, but none offers the level of detail as do molecular dynamics (MD) simulations. Integrating two widely used modeling programs, namely NAMD and VMD, we have created a robust, user-friendly software, QwikMD, which enables novices and experts alike to address biomedically relevant questions, where often only molecular dynamics simulations can provide answers. Performing both simple and advanced MD simulations interactively, QwikMD automates as many steps as necessary for preparing, carrying out, and analyzing simulations while checking for common errors and enabling reproducibility. QwikMD meets also the needs of experts in the field, increasing the efficiency and quality of their work by carrying out tedious or repetitive tasks while enabling easy control of every step. Whether carrying out simulations within the live view mode on a small laptop or performing complex and large simulations on supercomputers or Cloud computers, QwikMD uses the same steps and user interface. QwikMD is freely available by download on group and personal computers. It is also available on the cloud at Amazon Web Services. PMID:27216779

  6. Integrating Survey and Molecular Approaches to Better Understand Wildlife Disease Ecology

    PubMed Central

    Cowled, Brendan D.; Ward, Michael P.; Laffan, Shawn W.; Galea, Francesca; Garner, M. Graeme; MacDonald, Anna J.; Marsh, Ian; Muellner, Petra; Negus, Katherine; Quasim, Sumaiya; Woolnough, Andrew P.; Sarre, Stephen D.

    2012-01-01

    Infectious wildlife diseases have enormous global impacts, leading to human pandemics, global biodiversity declines and socio-economic hardship. Understanding how infection persists and is transmitted in wildlife is critical for managing diseases, but our understanding is limited. Our study aim was to better understand how infectious disease persists in wildlife populations by integrating genetics, ecology and epidemiology approaches. Specifically, we aimed to determine whether environmental or host factors were stronger drivers of Salmonella persistence or transmission within a remote and isolated wild pig (Sus scrofa) population. We determined the Salmonella infection status of wild pigs. Salmonella isolates were genotyped and a range of data was collected on putative risk factors for Salmonella transmission. We a priori identified several plausible biological hypotheses for Salmonella prevalence (cross sectional study design) versus transmission (molecular case series study design) and fit the data to these models. There were 543 wild pig Salmonella observations, sampled at 93 unique locations. Salmonella prevalence was 41% (95% confidence interval [CI]: 37–45%). The median Salmonella DICE coefficient (or Salmonella genetic similarity) was 52% (interquartile range [IQR]: 42–62%). Using the traditional cross sectional prevalence study design, the only supported model was based on the hypothesis that abundance of available ecological resources determines Salmonella prevalence in wild pigs. In the molecular study design, spatial proximity and herd membership as well as some individual risk factors (sex, condition score and relative density) determined transmission between pigs. Traditional cross sectional surveys and molecular epidemiological approaches are complementary and together can enhance understanding of disease ecology: abundance of ecological resources critical for wildlife influences Salmonella prevalence, whereas Salmonella transmission is driven by

  7. Ab initio path-integral molecular dynamics and the quantum nature of hydrogen bonds

    NASA Astrophysics Data System (ADS)

    Yexin, Feng; Ji, Chen; Xin-Zheng, Li; Enge, Wang

    2016-01-01

    The hydrogen bond (HB) is an important type of intermolecular interaction, which is generally weak, ubiquitous, and essential to life on earth. The small mass of hydrogen means that many properties of HBs are quantum mechanical in nature. In recent years, because of the development of computer simulation methods and computational power, the influence of nuclear quantum effects (NQEs) on the structural and energetic properties of some hydrogen bonded systems has been intensively studied. Here, we present a review of these studies by focussing on the explanation of the principles underlying the simulation methods, i.e., the ab initio path-integral molecular dynamics. Its extension in combination with the thermodynamic integration method for the calculation of free energies will also be introduced. We use two examples to show how this influence of NQEs in realistic systems is simulated in practice. Project supported by the National Natural Science Foundation of China (Grant Nos. 11275008, 91021007, and 10974012) and the China Postdoctoral Science Foundation (Grant No. 2014M550005).

  8. Integrative Molecular Profiling Reveals Asparagine Synthetase Is a Target in Castration-Resistant Prostate Cancer

    PubMed Central

    Sircar, Kanishka; Huang, Heng; Hu, Limei; Cogdell, David; Dhillon, Jasreman; Tzelepi, Vassiliki; Efstathiou, Eleni; Koumakpayi, Ismaël H.; Saad, Fred; Luo, Dijun; Bismar, Tarek A.; Aparicio, Ana; Troncoso, Patricia; Navone, Nora; Zhang, Wei

    2013-01-01

    The identification of new and effective therapeutic targets for the lethal, castration-resistant stage of prostate cancer (CRPC) has been challenging because of both the paucity of adequate frozen tissues and a lack of integrated molecular analysis. Therefore, in this study, we performed a genome-wide analysis of DNA copy number alterations from 34 unique surgical CRPC specimens and 5 xenografts, with matched transcriptomic profiling of 25 specimens. An integrated analysis of these data revealed that the asparagine synthetase (ASNS) gene showed a gain in copy number and was overexpressed at the transcript level. The overexpression of ASNS was validated by analyzing other public CRPC data sets. ASNS protein expression, as detected by reverse-phase protein lysate array, was tightly correlated with gene copy number. In addition, ASNS protein expression, as determined by IHC analysis, was associated with progression to a therapy-resistant disease state in TMAs that included 77 castration-resistant and 40 untreated prostate cancer patient samples. Knockdown of ASNS by small-interfering RNAs in asparagine-deprived media led to growth inhibition in both androgen-responsive (ie, LNCaP) and castration-resistant (ie, C4-2B) prostate cancer cell lines and in cells isolated from a CRPC xenograft (ie, MDA PCa 180-30). Together, our results suggest that ASNS is up-regulated in cases of CRPC and that depletion of asparagine using ASNS inhibitors will be a novel strategy for targeting CRPC cells. PMID:22245216

  9. Accurate and efficient integration for molecular dynamics simulations at constant temperature and pressure.

    PubMed

    Lippert, Ross A; Predescu, Cristian; Ierardi, Douglas J; Mackenzie, Kenneth M; Eastwood, Michael P; Dror, Ron O; Shaw, David E

    2013-10-28

    In molecular dynamics simulations, control over temperature and pressure is typically achieved by augmenting the original system with additional dynamical variables to create a thermostat and a barostat, respectively. These variables generally evolve on timescales much longer than those of particle motion, but typical integrator implementations update the additional variables along with the particle positions and momenta at each time step. We present a framework that replaces the traditional integration procedure with separate barostat, thermostat, and Newtonian particle motion updates, allowing thermostat and barostat updates to be applied infrequently. Such infrequent updates provide a particularly substantial performance advantage for simulations parallelized across many computer processors, because thermostat and barostat updates typically require communication among all processors. Infrequent updates can also improve accuracy by alleviating certain sources of error associated with limited-precision arithmetic. In addition, separating the barostat, thermostat, and particle motion update steps reduces certain truncation errors, bringing the time-average pressure closer to its target value. Finally, this framework, which we have implemented on both general-purpose and special-purpose hardware, reduces software complexity and improves software modularity.

  10. Biosilica: Molecular Biology, Biochemistry and Function in Demosponges as well as its Applied Aspects for Tissue Engineering.

    PubMed

    Wang, Xiaohong; Schröder, Heinz C; Wiens, Matthias; Schloßmacher, Ute; Müller, Werner E G

    2012-01-01

    Biomineralization, biosilicification in particular (i.e. the formation of biogenic silica, SiO(2)), has become an exciting source of inspiration for the development of novel bionic approaches following 'nature as model'. Siliceous sponges are unique among silica-forming organisms in their ability to catalyze silica formation using a specific enzyme termed silicatein. In this study, we review the present state of knowledge on silicatein-mediated 'biosilica' formation in marine demosponges, the involvement of further molecules in silica metabolism and their potential applications in nano-biotechnology and bio-medicine. While most forms of multicellular life have developed a calcium-based skeleton, a few specialized organisms complement their body plan with silica. Only sponges (phylum Porifera) are able to polymerize silica enzymatically mediated in order to generate massive siliceous skeletal elements (spicules) during a unique reaction, at ambient temperature and pressure. During this biomineralization process (i.e. biosilicification), hydrated, amorphous silica is deposited within highly specialized sponge cells, ultimately resulting in structures that range in size from micrometres to metres. This peculiar phenomenon has been comprehensively studied in recent years, and in several approaches, the molecular background was explored to create tools that might be employed for novel bioinspired biotechnological and biomedical applications. Thus, it was discovered that spiculogenesis is mediated by the enzyme silicatein and starts intracellularly. The resulting silica nanoparticles fuse and subsequently form concentric lamellar layers around a central protein filament, consisting of silicatein and the scaffold protein silintaphin-1. Once the growing spicule is extruded into the extracellular space, it obtains final size and shape. Again, this process is mediated by silicatein and silintaphin-1/silintaphin-1, in combination with other molecules such as galectin and

  11. The eukaryotic cell originated in the integration and redistribution of hyperstructures from communities of prokaryotic cells based on molecular complementarity.

    PubMed

    Norris, Vic; Root-Bernstein, Robert

    2009-06-04

    In the "ecosystems-first" approach to the origins of life, networks of non-covalent assemblies of molecules (composomes), rather than individual protocells, evolved under the constraints of molecular complementarity. Composomes evolved into the hyperstructures of modern bacteria. We extend the ecosystems-first approach to explain the origin of eukaryotic cells through the integration of mixed populations of bacteria. We suggest that mutualism and symbiosis resulted in cellular mergers entailing the loss of redundant hyperstructures, the uncoupling of transcription and translation, and the emergence of introns and multiple chromosomes. Molecular complementarity also facilitated integration of bacterial hyperstructures to perform cytoskeletal and movement functions.

  12. Evolutionary history of the PER3 variable number of tandem repeats (VNTR): idiosyncratic aspect of primate molecular circadian clock.

    PubMed

    Sabino, Flávia Cal; Ribeiro, Amanda Oliveira; Tufik, Sérgio; Torres, Laila Brito; Oliveira, José Américo; Mello, Luiz Eugênio Araújo Moraes; Cavalcante, Jeferson Souza; Pedrazzoli, Mario

    2014-01-01

    The PER3 gene is one of the clock genes, which function in the core mammalian molecular circadian system. A variable number of tandem repeats (VNTR) locus in the 18th exon of this gene has been strongly associated to circadian rhythm phenotypes and sleep organization in humans, but it has not been identified in other mammals except primates. To better understand the evolution and the placement of the PER3 VNTR in a phylogenetical context, the present study enlarges the investigation about the presence and the structure of this variable region in a large sample of primate species and other mammals. The analysis of the results has revealed that the PER3 VNTR occurs exclusively in simiiforme primates and that the number of copies of the primitive unit ranges from 2 to 11 across different primate species. Two transposable elements surrounding the 18th exon of PER3 were found in primates with published genome sequences, including the tarsiiforme Tarsius syrichta, which lacks the VNTR. These results suggest that this VNTR may have evolved in a common ancestor of the simiiforme branch and that the evolutionary copy number differentiation of this VNTR may be associated with primate simiiformes sleep and circadian phenotype patterns.

  13. The Molecular Crosstalk between the MET Receptor Tyrosine Kinase and the DNA Damage Response — Biological and Clinical Aspects

    PubMed Central

    Medová, Michaela; Aebersold, Daniel M.; Zimmer, Yitzhak

    2013-01-01

    Radiation therapy remains an imperative treatment modality for numerous malignancies. Enduring significant technical achievements both on the levels of treatment planning and radiation delivery have led to improvements in local control of tumor growth and reduction in healthy tissue toxicity. Nevertheless, resistance mechanisms, which presumably also involve activation of DNA damage response signaling pathways that eventually may account for loco-regional relapse and consequent tumor progression, still remain a critical problem. Accumulating data suggest that signaling via growth factor receptor tyrosine kinases, which are aberrantly expressed in many tumors, may interfere with the cytotoxic impact of ionizing radiation via the direct activation of the DNA damage response, leading eventually to so-called tumor radioresistance. The aim of this review is to overview the current known data that support a molecular crosstalk between the hepatocyte growth factor receptor tyrosine kinase MET and the DNA damage response. Apart of extending well established concepts over MET biology beyond its function as a growth factor receptor, these observations directly relate to the role of its aberrant activity in resistance to DNA damaging agents, such as ionizing radiation, which are routinely used in cancer therapy and advocate tumor sensitization towards DNA damaging agents in combination with MET targeting. PMID:24378750

  14. Conflicting processes in the extinction of conditioned taste aversion: behavioral and molecular aspects of latency, apparent stagnation, and spontaneous recovery.

    PubMed

    Berman, Diego E; Hazvi, Shoshi; Stehberg, Jimmy; Bahar, Amir; Dudai, Yadin

    2003-01-01

    The study of experimental extinction and of the spontaneous recovery of the extinguished memory could cast light on neurobiological mechanisms by which internal representations compete to control behavior. In this work, we use a combination of behavioral and molecular methods to dissect subprocesses of experimental extinction of conditioned taste aversion (CTA). Extinction of CTA becomes apparent only 90 min after the extinction trial. This latency is insensitive to muscarinic and beta-adrenergic modulation and to protein synthesis inhibition in the insular cortex (IC). Immediately afterwards, however, the extinguishing trace becomes sensitive to beta-adrenergic blockade and protein synthesis inhibition. The subsequent kinetics and magnitude of extinction depend on whether a spaced or massed extinction protocol is used. A massed protocol is highly effective in the short run, but results in apparent stagnation of extinction in the long-run, which conceals fast spontaneous recovery of the preextinguished trace. This recovery can be truncated by a beta-adrenergic agonist or a cAMP analog in the insular cortex, suggesting that spontaneous overtaking of the behavioral control by the original association is regulated at least in part by beta-adrenergic input, probably operating via the cAMP cascade, long after the offset of the conditioned stimulus. Hence, the performance of the subject in experimental extinction is the sum total of multiple, sometimes conflicting, time-dependent processes.

  15. Evolutionary History of the PER3 Variable Number of Tandem Repeats (VNTR): Idiosyncratic Aspect of Primate Molecular Circadian Clock

    PubMed Central

    Sabino, Flávia Cal; Ribeiro, Amanda Oliveira; Tufik, Sérgio; Torres, Laila Brito; Oliveira, José Américo; Mello, Luiz Eugênio Araújo Moraes; Cavalcante, Jeferson Souza; Pedrazzoli, Mario

    2014-01-01

    The PER3 gene is one of the clock genes, which function in the core mammalian molecular circadian system. A variable number of tandem repeats (VNTR) locus in the 18th exon of this gene has been strongly associated to circadian rhythm phenotypes and sleep organization in humans, but it has not been identified in other mammals except primates. To better understand the evolution and the placement of the PER3 VNTR in a phylogenetical context, the present study enlarges the investigation about the presence and the structure of this variable region in a large sample of primate species and other mammals. The analysis of the results has revealed that the PER3 VNTR occurs exclusively in simiiforme primates and that the number of copies of the primitive unit ranges from 2 to 11 across different primate species. Two transposable elements surrounding the 18th exon of PER3 were found in primates with published genome sequences, including the tarsiiforme Tarsius syrichta, which lacks the VNTR. These results suggest that this VNTR may have evolved in a common ancestor of the simiiforme branch and that the evolutionary copy number differentiation of this VNTR may be associated with primate simiiformes sleep and circadian phenotype patterns. PMID:25222750

  16. Dynamic aspects of antibody:oligosaccharide complexes characterized by molecular dynamics simulations and saturation transfer difference nuclear magnetic resonance.

    PubMed

    Theillet, François-Xavier; Frank, Martin; Vulliez-Le Normand, Brigitte; Simenel, Catherine; Hoos, Sylviane; Chaffotte, Alain; Bélot, Frédéric; Guerreiro, Catherine; Nato, Farida; Phalipon, Armelle; Mulard, Laurence A; Delepierre, Muriel

    2011-12-01

    Carbohydrates are likely to maintain significant conformational flexibility in antibody (Ab):carbohydrate complexes. As demonstrated herein for the protective monoclonal Ab (mAb) F22-4 recognizing the Shigella flexneri 2a O-antigen (O-Ag) and numerous synthetic oligosaccharide fragments thereof, the combination of molecular dynamics simulations and nuclear magnetic resonance saturation transfer difference experiments, supported by physicochemical analysis, allows us to determine the binding epitope and its various contributions to affinity without using any modified oligosaccharides. Moreover, the methods used provide insights into ligand flexibility in the complex, thus enabling a better understanding of the Ab affinities observed for a representative set of synthetic O-Ag fragments. Additionally, these complementary pieces of information give evidence to the ability of the studied mAb to recognize internal as well as terminal epitopes of its cognate polysaccharide antigen. Hence, we show that an appropriate combination of computational and experimental methods provides a basis to explore carbohydrate functional mimicry and receptor binding. The strategy may facilitate the design of either ligands or carbohydrate recognition domains, according to needed improvements of the natural carbohydrate:receptor properties. PMID:21610193

  17. Dynamic aspects of antibody:oligosaccharide complexes characterized by molecular dynamics simulations and saturation transfer difference nuclear magnetic resonance.

    PubMed

    Theillet, François-Xavier; Frank, Martin; Vulliez-Le Normand, Brigitte; Simenel, Catherine; Hoos, Sylviane; Chaffotte, Alain; Bélot, Frédéric; Guerreiro, Catherine; Nato, Farida; Phalipon, Armelle; Mulard, Laurence A; Delepierre, Muriel

    2011-12-01

    Carbohydrates are likely to maintain significant conformational flexibility in antibody (Ab):carbohydrate complexes. As demonstrated herein for the protective monoclonal Ab (mAb) F22-4 recognizing the Shigella flexneri 2a O-antigen (O-Ag) and numerous synthetic oligosaccharide fragments thereof, the combination of molecular dynamics simulations and nuclear magnetic resonance saturation transfer difference experiments, supported by physicochemical analysis, allows us to determine the binding epitope and its various contributions to affinity without using any modified oligosaccharides. Moreover, the methods used provide insights into ligand flexibility in the complex, thus enabling a better understanding of the Ab affinities observed for a representative set of synthetic O-Ag fragments. Additionally, these complementary pieces of information give evidence to the ability of the studied mAb to recognize internal as well as terminal epitopes of its cognate polysaccharide antigen. Hence, we show that an appropriate combination of computational and experimental methods provides a basis to explore carbohydrate functional mimicry and receptor binding. The strategy may facilitate the design of either ligands or carbohydrate recognition domains, according to needed improvements of the natural carbohydrate:receptor properties.

  18. The Integration of Select Aspects of Educational Foundations as Applied to Health Care Education: A Religious Perspective

    ERIC Educational Resources Information Center

    Fredericks, Marcel; Kondellas, Bill; Fredericks, Janet; Langer, Michael; Ross, Michael W. V.

    2013-01-01

    The purpose of this paper is to establish the necessity to fully and effectively integrate the sub-disciplines of educational foundations, such as psychology and philosophy, in addition to the natural and social sciences, within medical and health-related educational programs. This is particularly pertinent in Catholic and other religiously…

  19. Identification, clinical aspects, susceptibility pattern, and molecular epidemiology of beta-haemolytic group G Streptococcus anginosus group isolates from central Taiwan.

    PubMed

    Chang, Yi-Cheng; Lo, Hsueh-Hsia

    2013-07-01

    No literature is available on the prevalence and clinical aspects of beta-haemolytic group G Streptococcus anginosus group in central Taiwan. In this study, we used 16S rRNA gene sequencing and 16S-23S rDNA intergenic spacer sequencing (where necessary) as the gold standard for molecular identification. Twenty-seven S. anginosus group isolates were identified from 273 beta-haemolytic GGS isolates collected from patients in central Taiwan between February 2007 and August 2011. Of the 27 isolates, 22 were S. anginosus and 5 were Streptococcus constellatus. The 3 commercial methods, Rapid ID 32 Strep, API 20 Strep, and Vitek 2 GP card, identified 77.8%, 40.7%, and 37.0% of S. anginosus group isolates, respectively, with acceptable %ID or probability level. All the S. constellatus isolates possessed the lmb gene (encoding laminin-binding protein); however, none of the S. anginosus isolates possessed this gene. All the 27 isolates were susceptible to penicillin. Five S. anginosus group isolates (18.5%) were resistant to erythromycin. The resistance genes, ermB and mefA, were detected in 3 (2 S. anginosus and 1 S. constellatus) and 2 (2 S. anginosus) isolates, respectively. Pulsed field gel electrophoresis showed that most S. anginosus group isolates were genetically diverse. This is the first study to evaluate 3 commercial methods for the identification of beta-haemolytic group G S. anginosus group species, and only the Rapid ID 32 Strep system showed considerable ability. The clinical aspects, susceptibility pattern, and molecular epidemiology of beta-haemolytic group G S. anginosus group isolates from central Taiwan were also first presented.

  20. Cytochrome P450 polymorphism--molecular, metabolic and pharmacogenetic aspects. I. Mechanisms of activity of cytochrome P450 monooxygenases.

    PubMed

    Pachecka, Jan; Tomaszewski, Piotr; Kubiak-Tomaszewska, Grazyna

    2008-01-01

    Cytochrome P450, initially perceived as a type of cell pigment, was soon identified as a hemoprotein with an enzymatic activity characteristic for monooxygenases with an affinity for differentiated endo- or exogenous substrates, including drugs. So far in the human organism 58 CYP isoenzymes belonging to 18 families have been described. Most from the CYP monooxygenases superfamily turned out to be integral elements of hepatocytic reticular monooxygenase complexes which also contain NADPH-dependent cytochrome P450 reductase (CPR). Later investigations indicated the possibility of the participation in electron transport for reticular CYP isoenzymes, alternative NADH-dependent reticular system composed of cytochrome b5 reductase (CBR) and cytochrome b5. The demonstration of the activity of some CYP superfamily isoenzymes not only in hepatocytes but also in many other cells of the human organism, numerous plant and animal tissues and even in cells of fungi, protists and prokaryotes has contributed to the significantly increased understanding of the role of CYP in biological systems. In addition, some CYP isoenzymes were found to be characteristic for the inner mitochondrial membrane monooxygenase complexes which contain NADPH-dependent adrenodoxin reductase (AR) and adrenodoxin (Ad), which is identical with ferredoxin-1 (Fd-1) and hepatoredoxin (Hd).

  1. Proton transport in triflic acid hydrates studied via path integral car-parrinello molecular dynamics.

    PubMed

    Hayes, Robin L; Paddison, Stephen J; Tuckerman, Mark E

    2009-12-31

    The mono-, di-, and tetrahydrates of trifluoromethanesulfonic acid, which contain characteristic H(3)O(+), H(5)O(2)(+), and H(9)O(4)(+) structures, provide model systems for understanding proton transport in materials with high perfluorosulfonic acid density such as perfluorosulfonic acid membranes commonly employed in hydrogen fuel cells. Ab initio molecular dynamics simulations indicate that protons in these solids are predisposed to transfer to the water most strongly bound to sulfonate groups via a Grotthuss-type mechanism, but quickly return to the most solvated defect structure either due to the lack of a nearby species to stabilize the new defect or a preference for the proton to be maximally hydrated. Path integral molecular dynamics of the mono- and dihydrate reveal significant quantum effects that facilitate proton transfer to the "presolvated" water or SO(3)(-) in the first solvation shell and increase the Zundel character of all the defects. These trends are quantified in free energy profiles for each bonding environment. Hydrogen bonding criteria for HOH-OH(2) and HOH-O(3)S are extracted from the two-dimensional potential of mean force. The quantum radial distribution function, radius of gyration, and root-mean-square displacement position correlation function show that the protonic charge is distributed over two or more water molecules. Metastable structural defects with one excess proton shared between two sulfonate groups and another Zundel or Eigen type cation defect are found for the mono- and dihydrate but not for the tetrahydrate crystal. Results for the tetrahydrate native crystal exhibit minor differences at 210 and 250 K. IR spectra are calculated for all native and stable defect structures. Graph theory techniques are used to characterize the chain lengths and ring sizes in the hydrogen bond network. Low conductivities when limited water is present may be attributable to trapping of protons between SO(3)(-) groups and the increased

  2. Molecularly Imprinted Polymer Integrated with a Surface Acoustic Wave Technique for Detection of Sulfamethizole.

    PubMed

    Ayankojo, Akinrinade George; Tretjakov, Aleksei; Reut, Jekaterina; Boroznjak, Roman; Öpik, Andres; Rappich, Jörg; Furchner, Andreas; Hinrichs, Karsten; Syritski, Vitali

    2016-01-19

    The synergistic effect of combining molecular imprinting and surface acoustic wave (SAW) technologies for the selective and label-free detection of sulfamethizole as a model antibiotic in aqueous environment was demonstrated. A molecularly imprinted polymer (MIP) for sulfamethizole (SMZ) selective recognition was prepared in the form of a homogeneous thin film on the sensing surfaces of SAW chip by oxidative electropolymerization of m-phenylenediamine (mPD) in the presence of SMZ, acting as a template. Special attention was paid to the rational selection of the functional monomer using computational and spectroscopic approaches. SMZ template incorporation and its subsequent release from the polymer was supported by IR microscopic measurements. Precise control of the thicknesses of the SMZ-MIP and respective nonimprinted reference films (NIP) was achieved by correlating the electrical charge dosage during electrodeposition with spectroscopic ellipsometry measurements in order to ensure accurate interpretation of label-free responses originating from the MIP modified sensor. The fabricated SMZ-MIP films were characterized in terms of their binding affinity and selectivity toward the target by analyzing the binding kinetics recorded using the SAW system. The SMZ-MIPs had SMZ binding capacity approximately more than eight times higher than the respective NIP and were able to discriminate among structurally similar molecules, i.e., sulfanilamide and sulfadimethoxine. The presented approach for the facile integration of a sulfonamide antibiotic-sensing layer with SAW technology allowed observing the real-time binding events of the target molecule at nanomolar concentration levels and could be potentially suitable for cost-effective fabrication of a multianalyte chemosensor for analysis of hazardous pollutants in an aqueous environment. PMID:26704414

  3. Molecularly Imprinted Polymer Integrated with a Surface Acoustic Wave Technique for Detection of Sulfamethizole.

    PubMed

    Ayankojo, Akinrinade George; Tretjakov, Aleksei; Reut, Jekaterina; Boroznjak, Roman; Öpik, Andres; Rappich, Jörg; Furchner, Andreas; Hinrichs, Karsten; Syritski, Vitali

    2016-01-19

    The synergistic effect of combining molecular imprinting and surface acoustic wave (SAW) technologies for the selective and label-free detection of sulfamethizole as a model antibiotic in aqueous environment was demonstrated. A molecularly imprinted polymer (MIP) for sulfamethizole (SMZ) selective recognition was prepared in the form of a homogeneous thin film on the sensing surfaces of SAW chip by oxidative electropolymerization of m-phenylenediamine (mPD) in the presence of SMZ, acting as a template. Special attention was paid to the rational selection of the functional monomer using computational and spectroscopic approaches. SMZ template incorporation and its subsequent release from the polymer was supported by IR microscopic measurements. Precise control of the thicknesses of the SMZ-MIP and respective nonimprinted reference films (NIP) was achieved by correlating the electrical charge dosage during electrodeposition with spectroscopic ellipsometry measurements in order to ensure accurate interpretation of label-free responses originating from the MIP modified sensor. The fabricated SMZ-MIP films were characterized in terms of their binding affinity and selectivity toward the target by analyzing the binding kinetics recorded using the SAW system. The SMZ-MIPs had SMZ binding capacity approximately more than eight times higher than the respective NIP and were able to discriminate among structurally similar molecules, i.e., sulfanilamide and sulfadimethoxine. The presented approach for the facile integration of a sulfonamide antibiotic-sensing layer with SAW technology allowed observing the real-time binding events of the target molecule at nanomolar concentration levels and could be potentially suitable for cost-effective fabrication of a multianalyte chemosensor for analysis of hazardous pollutants in an aqueous environment.

  4. On-chip magnetic separation of superparamagnetic beads for integrated molecular analysis

    NASA Astrophysics Data System (ADS)

    Florescu, Octavian; Wang, Kevan; Au, Patrick; Tang, Jimmy; Harris, Eva; Beatty, P. Robert; Boser, Bernhard E.

    2010-03-01

    We have demonstrated a postprocessed complementary metal oxide semiconductor (CMOS) integrated circuit (IC) capable of on-chip magnetic separation, i.e., removing via magnetic forces the nonspecifically bound magnetic beads from the detection area on the surface of the chip. Initially, 4.5 μm wide superparamagnetic beads sedimenting out of solution due to gravity were attracted to the detection area by a magnetic concentration force generated by flowing current through a conductor embedded in the IC. After sedimentation, the magnetic beads that did not bind strongly to the functionalized surface of the IC through a specific biochemical complex were removed by a magnetic separation force generated by flowing current through another conductor placed laterally to the detection area. As the spherical bead pivoted on the surface of the chip, the lateral magnetic force was further amplified by mechanical leveraging, and 50 mA of current flowing through the separation conductor placed 18 μm away from the bead resulted in 7.5 pN of tensile force on the biomolecular tether immobilizing the bead. This force proved high enough to break nonspecific interactions while leaving specific antibody-antigen bonds intact. A sandwich capture immunoassay on purified human immunoglobulin G showed strong correlation with a control enzyme linked immunosorbent assay and a detection limit of 10 ng/ml or 70 pM. The beads bound to the detection area after on-chip magnetic separation were detected optically. To implement a fully integrated molecular diagnostics platform, the on-chip magnetic separation functionality presented in this work can be readily combine with state-of-the art CMOS-based magnetic bead detection technology.

  5. Prototype of integrated pseudo-dynamic crosstalk network for cancer molecular mechanism.

    PubMed

    Wu, Shinq-Jen; Chen, Wei-Yong; Chou, Chia-Hsien; Wu, Cheng-Tao

    2013-05-01

    In this study, we attempted to solve two important challenges in systems biology. First, although the Michaelis-Menten (MM) model provides local kinetic information, it is hard to generalize MM models to model a large system because increasingly large amounts of experimental data are necessary for the parameter identification. In addition, it is not possible to develop an MM model that provides information about the strength of the interactions in the system. Second, although the dynamic simulation of various signal transduction pathways is important in cancer research, it is impossible to theoretically derive a mathematical model to describe the cancer molecular mechanism. Predictive computational approaches can be used to analyze the dynamics of a system and to determine the dysfunction of a regulatory process. In this report, we first propose a pseudo-dynamic pathway to describe protein interactions in an MM system. We then discuss the dynamic behavior of two large-scale systems (antigrowth-signal-induced cell cycle and apoptotic-signal-transduction mechanism). These two systems were constructed through the in-series and organic integration, respectively, of MM modules with Petri net modules; moreover, more than 30% additional reactions were added during this integration step. We then described an extremely large multi-stream system (growth signal transduction); however, the analysis of this system to obtain dynamic predictions is critical but appears impossible. Thus, we introduced a fuzzy concept that can be used to develop a physically realizable model prototype. In the future, through step-by-step in vivo modifications, researchers will be able to develop a complete model of cancer metabolism to achieve accurate predictions. PMID:23454229

  6. An integral equation and simulation study of hydrogen inclusions in a molecular crystal of short-capped nanotubes

    NASA Astrophysics Data System (ADS)

    Lomba, Enrique; Bores, Cecilia; Notario, Rafael; Sánchez-Gil, V.

    2016-09-01

    In this work we have assessed the ability of a recently proposed three-dimensional integral equation approach to describe the explicit spatial distribution of molecular hydrogen confined in a crystal formed by short-capped nanotubes of C50 H10. To that aim we have resorted to extensive molecular simulation calculations whose results have been compared with our three-dimensional integral equation approximation. We have first tested the ability of a single C50 H10 nanocage for the encapsulation of H2 by means of molecular dynamics simulations, in particular using targeted molecular dynamics to estimate the binding Gibbs energy of a host hydrogen molecule inside the nanocage. Then, we have investigated the adsorption isotherm of the nanocage crystal using grand canonical Monte Carlo simulations in order to evaluate the maximum load of molecular hydrogen. For a packing close to the maximum load explicit hydrogen density maps and density profiles have been determined using molecular dynamics simulations and the three-dimensional Ornstein–Zernike equation with a hypernetted chain closure. In these conditions of extremely tight confinement the theoretical approach has shown to be able to reproduce the three-dimensional structure of the adsorbed fluid with accuracy down to the finest details.

  7. An integral equation and simulation study of hydrogen inclusions in a molecular crystal of short-capped nanotubes.

    PubMed

    Lomba, Enrique; Bores, Cecilia; Notario, Rafael; Sánchez-Gil, V

    2016-09-01

    In this work we have assessed the ability of a recently proposed three-dimensional integral equation approach to describe the explicit spatial distribution of molecular hydrogen confined in a crystal formed by short-capped nanotubes of C50 H10. To that aim we have resorted to extensive molecular simulation calculations whose results have been compared with our three-dimensional integral equation approximation. We have first tested the ability of a single C50 H10 nanocage for the encapsulation of H2 by means of molecular dynamics simulations, in particular using targeted molecular dynamics to estimate the binding Gibbs energy of a host hydrogen molecule inside the nanocage. Then, we have investigated the adsorption isotherm of the nanocage crystal using grand canonical Monte Carlo simulations in order to evaluate the maximum load of molecular hydrogen. For a packing close to the maximum load explicit hydrogen density maps and density profiles have been determined using molecular dynamics simulations and the three-dimensional Ornstein-Zernike equation with a hypernetted chain closure. In these conditions of extremely tight confinement the theoretical approach has shown to be able to reproduce the three-dimensional structure of the adsorbed fluid with accuracy down to the finest details. PMID:27367179

  8. An integral equation and simulation study of hydrogen inclusions in a molecular crystal of short-capped nanotubes

    NASA Astrophysics Data System (ADS)

    Lomba, Enrique; Bores, Cecilia; Notario, Rafael; Sánchez-Gil, V.

    2016-09-01

    In this work we have assessed the ability of a recently proposed three-dimensional integral equation approach to describe the explicit spatial distribution of molecular hydrogen confined in a crystal formed by short-capped nanotubes of C50 H10. To that aim we have resorted to extensive molecular simulation calculations whose results have been compared with our three-dimensional integral equation approximation. We have first tested the ability of a single C50 H10 nanocage for the encapsulation of H2 by means of molecular dynamics simulations, in particular using targeted molecular dynamics to estimate the binding Gibbs energy of a host hydrogen molecule inside the nanocage. Then, we have investigated the adsorption isotherm of the nanocage crystal using grand canonical Monte Carlo simulations in order to evaluate the maximum load of molecular hydrogen. For a packing close to the maximum load explicit hydrogen density maps and density profiles have been determined using molecular dynamics simulations and the three-dimensional Ornstein-Zernike equation with a hypernetted chain closure. In these conditions of extremely tight confinement the theoretical approach has shown to be able to reproduce the three-dimensional structure of the adsorbed fluid with accuracy down to the finest details.

  9. Molecular architecture of the 26S proteasome holocomplex determined by an integrative approach

    PubMed Central

    Lasker, Keren; Förster, Friedrich; Bohn, Stefan; Walzthoeni, Thomas; Villa, Elizabeth; Unverdorben, Pia; Beck, Florian; Aebersold, Ruedi; Sali, Andrej; Baumeister, Wolfgang

    2012-01-01

    The 26S proteasome is at the executive end of the ubiquitin-proteasome pathway for the controlled degradation of intracellular proteins. While the structure of its 20S core particle (CP) has been determined by X-ray crystallography, the structure of the 19S regulatory particle (RP), which recruits substrates, unfolds them, and translocates them to the CP for degradation, has remained elusive. Here, we describe the molecular architecture of the 26S holocomplex determined by an integrative approach based on data from cryoelectron microscopy, X-ray crystallography, residue-specific chemical cross-linking, and several proteomics techniques. The “lid” of the RP (consisting of Rpn3/5/6/7/8/9/11/12) is organized in a modular fashion. Rpn3/5/6/7/9/12 form a horseshoe-shaped heterohexamer, which connects to the CP and roofs the AAA-ATPase module, positioning the Rpn8/Rpn11 heterodimer close to its mouth. Rpn2 is rigid, supporting the lid, while Rpn1 is conformationally variable, positioned at the periphery of the ATPase ring. The ubiquitin receptors Rpn10 and Rpn13 are located in the distal part of the RP, indicating that they were recruited to the complex late in its evolution. The modular structure of the 26S proteasome provides insights into the sequence of events prior to the degradation of ubiquitylated substrates. PMID:22307589

  10. Integration of Morphological Data into Molecular Phylogenetic Analysis: Toward the Identikit of the Stylasterid Ancestor.

    PubMed

    Puce, Stefania; Pica, Daniela; Schiaparelli, Stefano; Negrisolo, Enrico

    2016-01-01

    Stylasteridae is a hydroid family including 29 worldwide-distributed genera, all provided with a calcareous skeleton. They are abundant in shallow and deep waters and represent an important component of marine communities. In the present paper, we studied the evolution of ten morphological characters, currently used in stylasterid taxonomy, using a phylogenetic approach. Our results indicate that stylasterid morphology is highly plastic and that many events of independent evolution and reversion have occurred. Our analysis also allows sketching a possible identikit of the stylasterid ancestor. It had calcareous skeleton, reticulate-granular coenosteal texture, polyps randomly arranged, gastrostyle, and dactylopore spines, while lacking a gastropore lip and dactylostyles. If the ancestor had single or double/multiple chambered gastropore tube is uncertain. These data suggest that the ancestor was similar to the extant genera Cyclohelia and Stellapora. Our investigation is the first attempt to integrate molecular and morphological information to clarify the stylasterid evolutionary scenario and represents the first step to infer the stylasterid ancestor morphology. PMID:27537333

  11. On the Intramolecular Hydrogen Bond in Solution: Car-Parrinello and Path Integral Molecular Dynamics Perspective.

    PubMed

    Dopieralski, Przemyslaw; Perrin, Charles L; Latajka, Zdzislaw

    2011-11-01

    The issue of the symmetry of short, low-barrier hydrogen bonds in solution is addressed here with advanced ab initio simulations of a hydrogen maleate anion in different environments, starting with the isolated anion, going through two crystal structures (sodium and potassium salts), then to an aqueous solution, and finally in the presence of counterions. By Car-Parrinello and path integral molecular dynamics simulations, it is demonstrated that the position of the proton in the intramolecular hydrogen bond of an aqueous hydrogen maleate anion is entirely related to the solvation pattern around the oxygen atoms of the intramolecular hydrogen bond. In particular, this anion has an asymmetric hydrogen bond, with the proton always located on the oxygen atom that is less solvated, owing to the instantaneous solvation environment. Simulations of water solutions of hydrogen maleate ion with two different counterions, K(+) and Na(+), surprisingly show that the intramolecular hydrogen-bond potential in the case of the Na(+) salt is always asymmetric, regardless of the hydrogen bonds to water, whereas for the K(+) salt, the potential for H motion depends on the location of the K(+). It is proposed that repulsion by the larger and more hydrated K(+) is weaker than that by Na(+) and competitive with solvation by water. PMID:26598249

  12. Critical zone study in Korea: integration of hydrogeology, mineralogy, sedimentology and molecular biogeochemistry

    NASA Astrophysics Data System (ADS)

    Lee, J. Y.; Kwon, K.; Jo, K. N.; Lee, J. S.

    2015-12-01

    Critical Zone (CZ) is the topmost layer of the Earth ranging from the vegetation canopy down to the soil, groundwater, and bedrock that sustains our ecosystem including human life. This CZ is being greatly influenced by the climate change and anthropogenic forces. We introduce the Critical Zone Frontier Research Laboratory (CFRL), a critical zone research lab recently funded by the Korean government for 2015-2020. The objective of CFRL is to unravel the relationships between climate and CZ changes to propose a prediction model for future responses of CZ to climate change. For this ultimate goal, we establish multiple CZ observatories in Kangwon areas and investigate soil, groundwater, and cave environments by integration of hydrogeology, mineralogy, sedimentology and molecular biogeochemistry. This study will enhance our understanding about CZ and local resolution of a climate change model. This research is financially supported by the Basic Research Laboratory Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning.

  13. Determination of the protonation state of the Asp dyad: conventional molecular dynamics versus thermodynamic integration.

    PubMed

    Huang, Jinfeng; Zhu, Yali; Sun, Bin; Yao, Yuan; Liu, Junjun

    2016-03-01

    The protonation state of the Asp dyad is important as it can reveal enzymatic mechanisms, and the information this provides can be used in the development of drugs for proteins such as memapsin 2 (BACE-1), HIV-1 protease, and rennin. Conventional molecular dynamics (MD) simulations have been successfully used to determine the preferred protonation state of the Asp dyad. In the present work, we demonstrate that the results obtained from conventional MD simulations can be greatly influenced by the particular force field applied or the values used for control parameters. In principle, free-energy changes between possible protonation states can be used to determine the protonation state. We show that protonation state prediction by the thermodynamic integration (TI) method is insensitive to force field version or to the cutoff for calculating nonbonded interactions (a control parameter). In the present study, the protonation state of the Asp dyad predicted by TI calculations was the same regardless of the force field and cutoff value applied. Contrary to the intuition that conventional MD is more efficient, our results clearly show that the TI method is actually more efficient and more reliable for determining the protonation state of the Asp dyad.

  14. Integrated systems analysis reveals a molecular network underlying autism spectrum disorders

    PubMed Central

    Li, Jingjing; Shi, Minyi; Ma, Zhihai; Zhao, Shuchun; Euskirchen, Ghia; Ziskin, Jennifer; Urban, Alexander; Hallmayer, Joachim; Snyder, Michael

    2014-01-01

    Autism is a complex disease whose etiology remains elusive. We integrated previously and newly generated data and developed a systems framework involving the interactome, gene expression and genome sequencing to identify a protein interaction module with members strongly enriched for autism candidate genes. Sequencing of 25 patients confirmed the involvement of this module in autism, which was subsequently validated using an independent cohort of over 500 patients. Expression of this module was dichotomized with a ubiquitously expressed subcomponent and another subcomponent preferentially expressed in the corpus callosum, which was significantly affected by our identified mutations in the network center. RNA-sequencing of the corpus callosum from patients with autism exhibited extensive gene mis-expression in this module, and our immunochemical analysis showed that the human corpus callosum is predominantly populated by oligodendrocyte cells. Analysis of functional genomic data further revealed a significant involvement of this module in the development of oligodendrocyte cells in mouse brain. Our analysis delineates a natural network involved in autism, helps uncover novel candidate genes for this disease and improves our understanding of its molecular pathology. PMID:25549968

  15. Silicon sample holder for molecular beam epitaxy on pre-fabricated integrated circuits

    NASA Technical Reports Server (NTRS)

    Hoenk, Michael E. (Inventor); Grunthaner, Paula J. (Inventor); Grunthaner, Frank J. (Inventor)

    1994-01-01

    The sample holder of the invention is formed of the same semiconductor crystal as the integrated circuit on which the molecular beam expitaxial process is to be performed. In the preferred embodiment, the sample holder comprises three stacked micro-machined silicon wafers: a silicon base wafer having a square micro-machined center opening corresponding in size and shape to the active area of a CCD imager chip, a silicon center wafer micro-machined as an annulus having radially inwardly pointing fingers whose ends abut the edges of and center the CCD imager chip within the annulus, and a silicon top wafer micro-machined as an annulus having cantilevered membranes which extend over the top of the CCD imager chip. The micro-machined silicon wafers are stacked in the order given above with the CCD imager chip centered in the center wafer and sandwiched between the base and top wafers. The thickness of the center wafer is about 20% less than the thickness of the CCD imager chip. Preferably, four titanium wires, each grasping the edges of the top and base wafers, compress all three wafers together, flexing the cantilever fingers of the top wafer to accommodate the thickness of the CCD imager chip, acting as a spring holding the CCD imager chip in place.

  16. Integration of Morphological Data into Molecular Phylogenetic Analysis: Toward the Identikit of the Stylasterid Ancestor

    PubMed Central

    Puce, Stefania; Pica, Daniela; Schiaparelli, Stefano; Negrisolo, Enrico

    2016-01-01

    Stylasteridae is a hydroid family including 29 worldwide-distributed genera, all provided with a calcareous skeleton. They are abundant in shallow and deep waters and represent an important component of marine communities. In the present paper, we studied the evolution of ten morphological characters, currently used in stylasterid taxonomy, using a phylogenetic approach. Our results indicate that stylasterid morphology is highly plastic and that many events of independent evolution and reversion have occurred. Our analysis also allows sketching a possible identikit of the stylasterid ancestor. It had calcareous skeleton, reticulate-granular coenosteal texture, polyps randomly arranged, gastrostyle, and dactylopore spines, while lacking a gastropore lip and dactylostyles. If the ancestor had single or double/multiple chambered gastropore tube is uncertain. These data suggest that the ancestor was similar to the extant genera Cyclohelia and Stellapora. Our investigation is the first attempt to integrate molecular and morphological information to clarify the stylasterid evolutionary scenario and represents the first step to infer the stylasterid ancestor morphology. PMID:27537333

  17. Integration of legal aspects and human rights approach in palliative care delivery-the Nyeri Hospice model.

    PubMed

    Musyoki, David; Gichohi, Sarafina; Ritho, Johnson; Ali, Zipporah; Kinyanjui, Asaph; Muinga, Esther

    2016-01-01

    Palliative care is patient and family-centred care that optimises quality of life by anticipating, preventing, and treating suffering. Open Society Foundation public health program (2011) notes that people facing life-threatening illnesses are deeply vulnerable: often in severe physical pain, worried about death, incapacitation, or the fate of their loved ones. Legal issues can increase stress for patients and families and make coping harder, impacting on the quality of care. In the absence of a clear legal provision expressly recognising palliative care in Kenya, providers may face numerous legal and ethical dilemmas that affect the availability, accessibility, and delivery of palliative care services and commodities. In order to ensure positive outcomes from patients, their families, and providers, palliative care services should be prioritised by all and includes advocating for the integration of legal support into those services. Palliative care service providers should be able to identify the various needs of patients and their families including specific issues requiring legal advice and interventions. Access to legal services remains a big challenge in Kenya, with limited availability of specialised legal services for health-related legal issues. An increased awareness of the benefits of legal services in palliative care will drive demand for easily accessible and more affordable direct legal services to address legal issues for a more holistic approach to quality palliative care. PMID:27563351

  18. Integration of legal aspects and human rights approach in palliative care delivery—the Nyeri Hospice model

    PubMed Central

    Musyoki, David; Gichohi, Sarafina; Ritho, Johnson; Ali, Zipporah; Kinyanjui, Asaph; Muinga, Esther

    2016-01-01

    Palliative care is patient and family-centred care that optimises quality of life by anticipating, preventing, and treating suffering. Open Society Foundation public health program (2011) notes that people facing life-threatening illnesses are deeply vulnerable: often in severe physical pain, worried about death, incapacitation, or the fate of their loved ones. Legal issues can increase stress for patients and families and make coping harder, impacting on the quality of care. In the absence of a clear legal provision expressly recognising palliative care in Kenya, providers may face numerous legal and ethical dilemmas that affect the availability, accessibility, and delivery of palliative care services and commodities. In order to ensure positive outcomes from patients, their families, and providers, palliative care services should be prioritised by all and includes advocating for the integration of legal support into those services. Palliative care service providers should be able to identify the various needs of patients and their families including specific issues requiring legal advice and interventions. Access to legal services remains a big challenge in Kenya, with limited availability of specialised legal services for health-related legal issues. An increased awareness of the benefits of legal services in palliative care will drive demand for easily accessible and more affordable direct legal services to address legal issues for a more holistic approach to quality palliative care. PMID:27563351

  19. Proton transport in triflic acid pentahydrate studied via ab initio path integral molecular dynamics.

    PubMed

    Hayes, Robin L; Paddison, Stephen J; Tuckerman, Mark E

    2011-06-16

    Trifluoromethanesulfonic acid hydrates provide a well-defined system to study proton dissociation and transport in perfluorosulfonic acid membranes, typically used as the electrolyte in hydrogen fuel cells, in the limit of minimal water. The triflic acid pentahydrate crystal (CF(3)SO(3)H·5H(2)O) is sufficiently aqueous that it contains an extended three-dimensional water network. Despite it being extended, however, long-range proton transport along the network is structurally unfavorable and would require considerable rearrangement. Nevertheless, the triflic acid pentahydrate crystal system can provide a clear picture of the preferred locations of local protonic defects in the water network, which provides insights about related structures in the disordered, low-hydration environment of perfluorosulfonic acid membranes. Ab initio molecular dynamics simulations reveal that the proton defect is most likely to transfer to the closest water that has the expected presolvation and only contains water in its first solvation shell. Unlike the tetrahydrate of triflic acid (CF(3)SO(3)H·4H(2)O), there is no evidence of the proton preferentially transferring to a water molecule bridging two of the sulfonate groups. However, this could be an artifact of the crystal structure since the only such water molecule is separated from the proton by long O-O distances. Hydrogen bonding criteria, using the two-dimensional potential of mean force, are extracted. Radial distribution functions, free energy profiles, radii of gyration, and the root-mean-square displacement computed from ab initio path integral molecular dynamics simulations reveal that quantum effects do significantly extend the size of the protonic defect and increase the frequency of proton transfer events by nearly 15%. The calculated IR spectra confirm that the dominant protonic defect mostly exists as an Eigen cation but contains some Zundel ion characteristics. Chain lengths and ring sizes determined from the

  20. New Biogeographic insight into Bauhinia s.l. (Leguminosae): integration from fossil records and molecular analyses

    PubMed Central

    2014-01-01

    Background Given that most species that have ever existed on earth are extinct, it stands to reason that the evolutionary history can be better understood with fossil taxa. Bauhinia is a typical genus of pantropical intercontinental disjunction among the Asian, African, and American continents. Geographic distribution patterns are better recognized when fossil records and molecular sequences are combined in the analyses. Here, we describe a new macrofossil species of Bauhinia from the Upper Miocene Xiaolongtan Formation in Wenshan County, Southeast Yunnan, China, and elucidate the biogeographic significance through the analyses of molecules and fossils. Results Morphometric analysis demonstrates that the leaf shapes of B. acuminata, B. championii, B. chalcophylla, B. purpurea, and B. podopetala closely resemble the leaf shapes of the new finding fossil. Phylogenetic relationships among the Bauhinia species were reconstructed using maximum parsimony and Bayesian inference, which inferred that species in Bauhinia species are well-resolved into three main groups. Divergence times were estimated by the Bayesian Markov chain Monte Carlo (MCMC) method under a relaxed clock, and inferred that the stem diversification time of Bauhinia was ca. 62.7 Ma. The Asian lineage first diverged at ca. 59.8 Ma, followed by divergence of the Africa lineage starting during the late Eocene, whereas that of the neotropical lineage starting during the middle Miocene. Conclusions Hypotheses relying on vicariance or continental history to explain pantropical disjunct distributions are dismissed because they require mostly Palaeogene and older tectonic events. We suggest that Bauhinia originated in the middle Paleocene in Laurasia, probably in Asia, implying a possible Tethys Seaway origin or an “Out of Tropical Asia”, and dispersal of legumes. Its present pantropical disjunction resulted from disruption of the boreotropical flora by climatic cooling after the Paleocene-Eocene Thermal

  1. A Computational Systems Biology Software Platform for Multiscale Modeling and Simulation: Integrating Whole-Body Physiology, Disease Biology, and Molecular Reaction Networks

    PubMed Central

    Eissing, Thomas; Kuepfer, Lars; Becker, Corina; Block, Michael; Coboeken, Katrin; Gaub, Thomas; Goerlitz, Linus; Jaeger, Juergen; Loosen, Roland; Ludewig, Bernd; Meyer, Michaela; Niederalt, Christoph; Sevestre, Michael; Siegmund, Hans-Ulrich; Solodenko, Juri; Thelen, Kirstin; Telle, Ulrich; Weiss, Wolfgang; Wendl, Thomas; Willmann, Stefan; Lippert, Joerg

    2011-01-01

    Today, in silico studies and trial simulations already complement experimental approaches in pharmaceutical R&D and have become indispensable tools for decision making and communication with regulatory agencies. While biology is multiscale by nature, project work, and software tools usually focus on isolated aspects of drug action, such as pharmacokinetics at the organism scale or pharmacodynamic interaction on the molecular level. We present a modeling and simulation software platform consisting of PK-Sim® and MoBi® capable of building and simulating models that integrate across biological scales. A prototypical multiscale model for the progression of a pancreatic tumor and its response to pharmacotherapy is constructed and virtual patients are treated with a prodrug activated by hepatic metabolization. Tumor growth is driven by signal transduction leading to cell cycle transition and proliferation. Free tumor concentrations of the active metabolite inhibit Raf kinase in the signaling cascade and thereby cell cycle progression. In a virtual clinical study, the individual therapeutic outcome of the chemotherapeutic intervention is simulated for a large population with heterogeneous genomic background. Thereby, the platform allows efficient model building and integration of biological knowledge and prior data from all biological scales. Experimental in vitro model systems can be linked with observations in animal experiments and clinical trials. The interplay between patients, diseases, and drugs and topics with high clinical relevance such as the role of pharmacogenomics, drug–drug, or drug–metabolite interactions can be addressed using this mechanistic, insight driven multiscale modeling approach. PMID:21483730

  2. A new approach to calculate charge carrier transport mobility in organic molecular crystals from imaginary time path integral simulations

    SciTech Connect

    Song, Linze; Shi, Qiang

    2015-05-07

    We present a new non-perturbative method to calculate the charge carrier mobility using the imaginary time path integral approach, which is based on the Kubo formula for the conductivity, and a saddle point approximation to perform the analytic continuation. The new method is first tested using a benchmark calculation from the numerical exact hierarchical equations of motion method. Imaginary time path integral Monte Carlo simulations are then performed to explore the temperature dependence of charge carrier delocalization and mobility in organic molecular crystals (OMCs) within the Holstein and Holstein-Peierls models. The effects of nonlocal electron-phonon interaction on mobility in different charge transport regimes are also investigated.

  3. Car-Parrinello and path integral molecular dynamics study of the hydrogen bond in the chloroacetic acid dimer system

    NASA Astrophysics Data System (ADS)

    Durlak, Piotr; Morrison, Carole A.; Middlemiss, Derek S.; Latajka, Zdzislaw

    2007-08-01

    We have studied the double proton transfer (DPT) reaction in the cyclic dimer of chloroacetic acid using both classical and path integral Car-Parrinello molecular dynamics. We also attempt to quantify the errors in the potential energy surface that arise from the use of a pure density functional. In the classical dynamics a clear reaction mechanism can be identified, where asynchronized DPT arises due to coupling between the O-H stretching oscillator and several low energy intermolecular vibrational modes. This mechanism is considerably altered when quantum tunneling is permitted in the simulation. The introduction of path integrals leads to considerable changes in the thermally averaged molecular geometry, leading to shorter and more centered hydrogen bond linkages.

  4. Molecular and Integrative Physiological Effects of Isoflurane Anesthesia: The Paradigm of Cardiovascular Studies in Rodents using Magnetic Resonance Imaging.

    PubMed

    Constantinides, Christakis; Murphy, Kathy

    2016-01-01

    To-this-date, the exact molecular, cellular, and integrative physiological mechanisms of anesthesia remain largely unknown. Published evidence indicates that anesthetic effects are multifocal and occur in a time-dependent and coordinated manner, mediated via central, local, and peripheral pathways. Their effects can be modulated by a range of variables, and their elicited end-effect on the integrative physiological response is highly variable. This review summarizes the major cellular and molecular sites of anesthetic action with a focus on the paradigm of isoflurane (ISO) - the most commonly used anesthetic nowadays - and its use in prolonged in vivo rodent studies using imaging modalities, such as magnetic resonance imaging (MRI). It also presents established evidence for normal ranges of global and regional physiological cardiac function under ISO, proposes optimal, practical methodologies relevant to the use of anesthetic protocols for MRI and outlines the beneficial effects of nitrous oxide supplementation. PMID:27525256

  5. Molecular and Integrative Physiological Effects of Isoflurane Anesthesia: The Paradigm of Cardiovascular Studies in Rodents using Magnetic Resonance Imaging

    PubMed Central

    Constantinides, Christakis; Murphy, Kathy

    2016-01-01

    To-this-date, the exact molecular, cellular, and integrative physiological mechanisms of anesthesia remain largely unknown. Published evidence indicates that anesthetic effects are multifocal and occur in a time-dependent and coordinated manner, mediated via central, local, and peripheral pathways. Their effects can be modulated by a range of variables, and their elicited end-effect on the integrative physiological response is highly variable. This review summarizes the major cellular and molecular sites of anesthetic action with a focus on the paradigm of isoflurane (ISO) – the most commonly used anesthetic nowadays – and its use in prolonged in vivo rodent studies using imaging modalities, such as magnetic resonance imaging (MRI). It also presents established evidence for normal ranges of global and regional physiological cardiac function under ISO, proposes optimal, practical methodologies relevant to the use of anesthetic protocols for MRI and outlines the beneficial effects of nitrous oxide supplementation. PMID:27525256

  6. Path integral molecular dynamics within the grand canonical-like adaptive resolution technique: Simulation of liquid water

    SciTech Connect

    Agarwal, Animesh Delle Site, Luigi

    2015-09-07

    Quantum effects due to the spatial delocalization of light atoms are treated in molecular simulation via the path integral technique. Among several methods, Path Integral (PI) Molecular Dynamics (MD) is nowadays a powerful tool to investigate properties induced by spatial delocalization of atoms; however, computationally this technique is very demanding. The above mentioned limitation implies the restriction of PIMD applications to relatively small systems and short time scales. One of the possible solutions to overcome size and time limitation is to introduce PIMD algorithms into the Adaptive Resolution Simulation Scheme (AdResS). AdResS requires a relatively small region treated at path integral level and embeds it into a large molecular reservoir consisting of generic spherical coarse grained molecules. It was previously shown that the realization of the idea above, at a simple level, produced reasonable results for toy systems or simple/test systems like liquid parahydrogen. Encouraged by previous results, in this paper, we show the simulation of liquid water at room conditions where AdResS, in its latest and more accurate Grand-Canonical-like version (GC-AdResS), is merged with two of the most relevant PIMD techniques available in the literature. The comparison of our results with those reported in the literature and/or with those obtained from full PIMD simulations shows a highly satisfactory agreement.

  7. Detection of bacteria and fungi and assessment of the molecular aspects and resistance of Escherichia coli isolated from confiscated passerines intended for reintroduction programs.

    PubMed

    Braconaro, Patricia; Saidenberg, André B S; Benites, Nilson R; Zuniga, Eveline; da Silva, Adriana M J; Sanches, Thais C; Zwarg, Ticiana; Brandão, Paulo E; Melville, Priscilla A

    2015-11-01

    Many native bird species are currently considered rare in Brazil because they have been indiscriminately collected by animal traffickers and commercialized, leading to dwindling numbers in their natural habitats. Confiscated animals are at times destined for reintroduction programs that must ensure these animals do not pose a risk to native populations. Healthy or sick wild passerines may carry a great diversity of microorganisms. Therefore, knowledge of the sanitary status of confiscated animals destined for reintroduction is critical to assess whether these animals act as microorganism carriers and to investigate the epidemiology of transmissible diseases, a crucial aspect for animal and human health preservation. This study examined the occurrence of aerobic and facultative anaerobic bacteria and fungi in cloacal swabs collected from wild confiscated passerines intended for reintroduction programs. In vitro susceptibility tests of the most frequent isolates as well as studies of the molecular aspects of Escherichia coli isolates were also performed. There was microorganism growth in 62.5% of 253 samples. The microorganisms that were most frequently isolated were Staphylococcus spp. (15.0%), Micrococcus spp. (11.5%), E. coli (10.7%) and Klebsiella spp. (10.7%). Fifteen bacteria genera and seven fungi genera were isolated. Multidrug-resistance to antimicrobials was observed in Staphylococcus spp., Micrococcus spp., E. coli and Klebsiella spp. isolates. The high occurrence of Enterobacteria observed is possibly related to the sanitary conditions in which confiscated animals are usually kept. One E. coli sample (out of 27 isolates) was positive for the S-fimbrial adhesion encoding gene (sfa). Considering the low occurrence of genes that encode virulence factors, confiscated passerines may represent a low risk for the potential transmission of EPEC, APEC, UPEC and NMEC isolates to other animals or humans. The potential risk of intra- or inter-specific transmission of

  8. Synthesis, structure, DFT calculations, electrochemistry, fluorescence, DNA binding and molecular docking aspects of a novel oxime based ligand and its palladium(II) complex.

    PubMed

    Bandyopadhyay, Nirmalya; Pradhan, Ankur Bikash; Das, Suman; Lu, Liping; Zhu, Miaoli; Chowdhury, Shubhamoy; Naskar, Jnan Prakash

    2016-07-01

    A novel oxime based ligand, phenyl-(pyridine-2-yl-hydrazono)-acetaldehyde oxime (LH), and its palladium(II) complex (1) have been synthesised and spectroscopically characterised. The ligand crystallizes in the monoclinic space group (P21/c). The X-ray crystal structure of the ligand shows that it forms a hydrogen bonded helical network. The ligand has been characterised by C, H and N microanalyses, (1)H and (13)C NMR, ESI-MS, FT-IR and UV-Vis spectral measurements. Geometry optimizations at the level of DFT show that the Pd(II) centre is nested in a square-planar 'N3Cl' coordination chromophore. The diamagnetic palladium complex has been characterised by C, H and N microanalyses, FAB-MS, FT-IR, UV-Vis spectra and molar electrical conductivity measurements. The observed electronic spectrum of 1 correlates with our theoretical findings as evaluated through TD-DFT. 1 displays quasi-reversible Pd(II)/Pd(III) and Pd(III)/Pd(IV) redox couples in its CV in acetonitrile. 1 is nine-fold more emissive with respect to the binding ligand. Biophysical studies have been carried out to show the DNA binding aspects of both the ligand and complex. The binding constants for the ligand and complex were found to be 3.93×10(4) and 1.38×10(3)M(-1) respectively. To have an insight into the mode of binding of LH and 1 with CT DNA a hydrodynamic study was also undertaken. The mode of binding has also been substantiated through molecular docking. A promising groove binding efficacy has been revealed for the ligand. PMID:27179300

  9. Significance and integration of molecular diagnostics in the framework of veterinary practice.

    PubMed

    Aranaz, Alicia

    2015-01-01

    The field of molecular diagnostics in veterinary practice is rapidly evolving. An array of molecular techniques of different complexity is available to facilitate the fast and specific diagnosis of animal diseases. The choice for the adequate technique is dependent on the mission and attributions of the laboratory and requires both a knowledge of the molecular biology basis and of its limitations. The ability to quickly detect pathogens and their characteristics would allow for precise decision-making and target measures such as prophylaxis, appropriate therapy, and biosafety plans to control disease outbreaks. In practice, taking benefit of the huge amount of data that can be obtained using molecular techniques highlights the need of collaboration between veterinarians in the laboratory and practitioners.

  10. All-organic microelectromechanical systems integrating specific molecular recognition--a new generation of chemical sensors.

    PubMed

    Ayela, Cédric; Dubourg, Georges; Pellet, Claude; Haupt, Karsten

    2014-09-01

    Cantilever-type all-organic microelectromechanical systems based on molecularly imprinted polymers for specific analyte recognition are used as chemical sensors. They are produced by a simple spray-coating-shadow-masking process. Analyte binding to the cantilever generates a measurable change in its resonance frequency. This allows label-free detection by direct mass sensing of low-molecular-weight analytes at nanomolar concentrations.

  11. ATOMIC AND MOLECULAR PHYSICS: Integral Reduction Arising in Double Transfer and Excitation Amplitude

    NASA Astrophysics Data System (ADS)

    Zerarka, A.; Soukeur, A.; Bensalah, N.

    2010-03-01

    The purpose of this article is to develop an integral derived from the double transfer and excitation theory. The reduced form of this integral, so obtained, can serve in the computation of the transition amplitude which is from numerical point of view difficult to implement. This amplitude is of great interest in the resonant and non resonant transfer and excitation (RTE and NTE) processes.

  12. Extended molecular Ornstein-Zernike integral equation for fully anisotropic solute molecules: Formulation in a rectangular coordinate system

    NASA Astrophysics Data System (ADS)

    Ishizuka, Ryosuke; Yoshida, Norio

    2013-08-01

    An extended molecular Ornstein-Zernike (XMOZ) integral equation is formulated to calculate the spatial distribution of solvent around a solute of arbitrary shape and solid surfaces. The conventional MOZ theory employs spherical harmonic expansion technique to treat the molecular orientation of components of solution. Although the MOZ formalism is fully exact analytically, the truncation of the spherical harmonic expansion requires at a finite order for numerical calculation and causes the significant error for complex molecules. The XMOZ integral equation is the natural extension of the conventional MOZ theory to a rectangular coordinate system, which is free from the truncation of spherical harmonic expansion with respect to solute orientation. In order to show its applicability, we applied the XMOZ theory to several systems using the hypernetted-chain (HNC) and Kovalenko-Hirata approximations. The quality of results obtained within our theory is discussed by comparison with values from the conventional MOZ theory, molecular dynamics simulation, and three-dimensional reference interaction site model theory. The spatial distributions of water around the complex of non-charged sphere and dumbbell were calculated. Using this system, the approximation level of the XMOZ and other methods are discussed. To assess our theory, we also computed the excess chemical potentials for three realistic molecules (water, methane, and alanine dipeptide). We obtained the qualitatively reasonable results by using the XMOZ/HNC theory. The XMOZ theory covers a wide variety of applications in solution chemistry as a useful tool to calculate solvation thermodynamics.

  13. Final Report. DOE Computational Nanoscience Project DE-FG02-03ER46096: Integrated Multiscale Modeling of Molecular Computing Devices

    SciTech Connect

    Cummings, Peter

    2009-11-15

    The document is the final report of the DOE Computational Nanoscience Project DE-FG02-03ER46096: Integrated Multiscale Modeling of Molecular Computing Devices. It included references to 62 publications that were supported by the grant.

  14. A hybrid framework of first principles molecular orbital calculations and a three-dimensional integral equation theory for molecular liquids: multi-center molecular Ornstein-Zernike self-consistent field approach.

    PubMed

    Kido, Kentaro; Kasahara, Kento; Yokogawa, Daisuke; Sato, Hirofumi

    2015-07-01

    In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein-Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM-SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple SN2 reaction (Cl(-) + CH3Cl → ClCH3 + Cl(-)) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF.

  15. A hybrid framework of first principles molecular orbital calculations and a three-dimensional integral equation theory for molecular liquids: Multi-center molecular Ornstein–Zernike self-consistent field approach

    SciTech Connect

    Kido, Kentaro; Kasahara, Kento; Yokogawa, Daisuke; Sato, Hirofumi

    2015-07-07

    In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein–Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM-SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple S{sub N}2 reaction (Cl{sup −} + CH{sub 3}Cl → ClCH{sub 3} + Cl{sup −}) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF.

  16. Analytically reduced form of multicenter integrals from Gaussian transforms. [in atomic and molecular physics

    NASA Technical Reports Server (NTRS)

    Straton, Jack C.

    1989-01-01

    The four-dimensional Fourier-Feynman transformations previously used in analytically reducing the general class of integrals containing multicenter products of 1s hydrogenic orbitals, Coulomb or Yukawa potentials, and plane waves, are replaced by the one-dimensional Gaussian transformation. This reduces the previously required double-diagonalization of the quadratic form of the multicenter integrals to only one diagonalization, yielding a simpler reduced form of the integral. The present work also extends the result to include all s states and pairs of states with l not equal to zero summed over the m quantum number.

  17. Double path integral method for obtaining the mobility of the one-dimensional charge transport in molecular chain.

    PubMed

    Yoo-Kong, Sikarin; Liewrian, Watchara

    2015-12-01

    We report on a theoretical investigation concerning the polaronic effect on the transport properties of a charge carrier in a one-dimensional molecular chain. Our technique is based on the Feynman's path integral approach. Analytical expressions for the frequency-dependent mobility and effective mass of the carrier are obtained as functions of electron-phonon coupling. The result exhibits the crossover from a nearly free particle to a heavily trapped particle. We find that the mobility depends on temperature and decreases exponentially with increasing temperature at low temperature. It exhibits large polaronic-like behaviour in the case of weak electron-phonon coupling. These results agree with the phase transition (A.S. Mishchenko et al., Phys. Rev. Lett. 114, 146401 (2015)) of transport phenomena related to polaron motion in the molecular chain. PMID:26701710

  18. Ki-67 proliferation index but not mitotic thresholds integrates the molecular prognostic stratification of lower grade gliomas

    PubMed Central

    Duregon, Eleonora; Bertero, Luca; Pittaro, Alessandra; Soffietti, Riccardo; Rudà, Roberta; Trevisan, Morena; Papotti, Mauro; Ventura, Laura; Senetta, Rebecca; Cassoni, Paola

    2016-01-01

    Despite several molecular signatures for “lower grade diffuse gliomas” (LGG) have been identified, WHO grade still remains a cornerstone of treatment guidelines. Mitotic count bears a crucial role in its definition, although limited by the poor reproducibility of standard Hematoxylin & Eosin (H&E) evaluation. Phospho-histone-H3 (PHH3) and Ki-67 have been proposed as alternative assays of cellular proliferation. Therefore in the present series of 141 LGG, the molecular characterization (namely IDH status, 1p/19q co-deletion and MGMT promoter methylation) was integrated with the tumor “proliferative trait” (conventional H&E or PHH3-guided mitotic count and Ki-67 index) in term of prognosis definition. Exclusively high PHH3 and Ki-67 values were predictor of poor prognosis (log rank test, P = 0.0281 for PHH3 and P = 0.032 for Ki-67), unlike standard mitotic count. Based on Cox proportional hazard regression analyses, among all clinical (age), pathological (PHH3 and Ki-67) and molecular variables (IDH, 1p/19q codeletion and MGMT methylation) with a prognostic relevance at univariate survival analysis, only IDH expression (P = 0.001) and Ki-67 proliferation index (P = 0.027) proved to be independent prognostic factors. In addition, stratifying by IDH expression status, high Ki-67 retained its prognostic relevance uniquely in the IDH negative patient (P = 0.029) doubling their risk of death (hazard ratio = 2.27). Overall, PHH3 immunostaining is the sole reliable method with a prognostic value to highlight mitotic figures in LGG. Ki-67 proliferation index exceeds PHH3 mitotic count as a predictor of patient's prognosis, and should be integrated with molecular markers in a comprehensive grading system for LGG. PMID:27049832

  19. Ki-67 proliferation index but not mitotic thresholds integrates the molecular prognostic stratification of lower grade gliomas.

    PubMed

    Duregon, Eleonora; Bertero, Luca; Pittaro, Alessandra; Soffietti, Riccardo; Rudà, Roberta; Trevisan, Morena; Papotti, Mauro; Ventura, Laura; Senetta, Rebecca; Cassoni, Paola

    2016-04-19

    Despite several molecular signatures for "lower grade diffuse gliomas" (LGG) have been identified, WHO grade still remains a cornerstone of treatment guidelines. Mitotic count bears a crucial role in its definition, although limited by the poor reproducibility of standard Hematoxylin & Eosin (H&E) evaluation. Phospho-histone-H3 (PHH3) and Ki-67 have been proposed as alternative assays of cellular proliferation. Therefore in the present series of 141 LGG, the molecular characterization (namely IDH status, 1p/19q co-deletion and MGMT promoter methylation) was integrated with the tumor "proliferative trait" (conventional H&E or PHH3-guided mitotic count and Ki-67 index) in term of prognosis definition. Exclusively high PHH3 and Ki-67 values were predictor of poor prognosis (log rank test, P = 0.0281 for PHH3 and P = 0.032 for Ki-67), unlike standard mitotic count. Based on Cox proportional hazard regression analyses, among all clinical (age), pathological (PHH3 and Ki-67) and molecular variables (IDH, 1p/19q codeletion and MGMT methylation) with a prognostic relevance at univariate survival analysis, only IDH expression (P = 0.001) and Ki-67 proliferation index (P = 0.027) proved to be independent prognostic factors. In addition, stratifying by IDH expression status, high Ki-67 retained its prognostic relevance uniquely in the IDH negative patient (P = 0.029) doubling their risk of death (hazard ratio = 2.27). Overall, PHH3 immunostaining is the sole reliable method with a prognostic value to highlight mitotic figures in LGG. Ki-67 proliferation index exceeds PHH3 mitotic count as a predictor of patient's prognosis, and should be integrated with molecular markers in a comprehensive grading system for LGG. PMID:27049832

  20. ATOMIC AND MOLECULAR PHYSICS: Lifetime Measurement of Cold Atoms in an Integrating Sphere

    NASA Astrophysics Data System (ADS)

    Zhang, Wen-Zhuo; Wang, Xu-Cheng; Cheng, Hua-Dong; Xiao, Ling; Liu, Liang; Wang, Yu-Zhu

    2009-08-01

    We present an experimental measurement of the lifetime of the cold 87Rb atoms in an integrating sphere. The atoms are cooled by the diffuse light which is generated by the diffuse reflection of laser beams in the integrating sphere. Our result shows that the lifetime is primarily determined by the free fall of the cold 87Rb atoms, and its half-life can reach 40 ms, which is suitable for many experiments, especially for a cold atom clock.

  1. Configurational entropy of protein: A combined approach based on molecular simulation and integral-equation theory of liquids

    NASA Astrophysics Data System (ADS)

    Chong, Song-Ho; Ham, Sihyun

    2011-03-01

    We report the recent development of a theoretical method to calculate the protein configurational entropy in explicit solvent from statistical properties of the solvent-averaged protein potential energy surface. This method can be implemented by combining molecular simulation and integral-equation theory of liquids. Our method does not assume Gaussian distribution of protein configurations, and can be applied to unfolded or misfolded states of protein in which an average protein structure is not well defined. An illustrative application is made to misfolded state of 42-residue amyloid beta protein in water.

  2. A new approach to calculate charge carrier transport mobility in organic molecular crystals from imaginary time path integral simulations.

    PubMed

    Song, Linze; Shi, Qiang

    2015-05-01

    We present a new non-perturbative method to calculate the charge carrier mobility using the imaginary time path integral approach, which is based on the Kubo formula for the conductivity, and a saddle point approximation to perform the analytic continuation. The new method is first tested using a benchmark calculation from the numerical exact hierarchical equations of motion method. Imaginary time path integral Monte Carlo simulations are then performed to explore the temperature dependence of charge carrier delocalization and mobility in organic molecular crystals (OMCs) within the Holstein and Holstein-Peierls models. The effects of nonlocal electron-phonon interaction on mobility in different charge transport regimes are also investigated. PMID:25956086

  3. Integrating Internet Assignments into a Biochemistry/Molecular Biology Laboratory Course

    ERIC Educational Resources Information Center

    Kaspar, Roger L.

    2002-01-01

    A main challenge in educating undergraduate students is to introduce them to the Internet and to teach them how to effectively use it in research. To this end, an Internet assignment was developed that introduces students to websites related to biomedical research at the beginning of a biochemistry/molecular biology laboratory course. The basic…

  4. Using Biocatalysis to Integrate Organic Chemistry into a Molecular Biology Laboratory Course

    ERIC Educational Resources Information Center

    Beers, Mande; Archer, Crystal; Feske, Brent D.; Mateer, Scott C.

    2012-01-01

    Current cutting-edge biomedical investigation requires that the researcher have an operational understanding of several diverse disciplines. Biocatalysis is a field of science that operates at the crossroads of organic chemistry, biochemistry, microbiology, and molecular biology, and provides an excellent model for interdisciplinary research. We…

  5. An Inquiry-Infused Introductory Biology Laboratory That Integrates Mendel's Pea Phenotypes with Molecular Mechanisms

    ERIC Educational Resources Information Center

    Kudish, Philip; Schlag, Erin; Kaplinsky, Nicholas J.

    2015-01-01

    We developed a multi-week laboratory in which college-level introductory biology students investigate Mendel's stem length phenotype in peas. Students collect, analyze and interpret convergent evidence from molecular and physiological techniques. In weeks 1 and 2, students treat control and experimental plants with Gibberellic Acid (GA) to…

  6. An Integrated Visualization and Basic Molecular Modeling Laboratory for First-Year Undergraduate Medicinal Chemistry

    ERIC Educational Resources Information Center

    Hayes, Joseph M.

    2014-01-01

    A 3D model visualization and basic molecular modeling laboratory suitable for first-year undergraduates studying introductory medicinal chemistry is presented. The 2 h practical is embedded within a series of lectures on drug design, target-drug interactions, enzymes, receptors, nucleic acids, and basic pharmacokinetics. Serving as a teaching aid…

  7. The Need for Novel Informatics Tools for Integrating and Planning Research in Molecular and Cellular Cognition

    ERIC Educational Resources Information Center

    Silva, Alcino J.; Müller, Klaus-Robert

    2015-01-01

    The sheer volume and complexity of publications in the biological sciences are straining traditional approaches to research planning. Nowhere is this problem more serious than in molecular and cellular cognition, since in this neuroscience field, researchers routinely use approaches and information from a variety of areas in neuroscience and other…

  8. Integration of Culture-Based and Molecular Analysis of a Complex Sponge-Associated Bacterial Community

    PubMed Central

    Vicente, Jan; Pittiglio, Raquel; Ravel, Jacques; Hill, Russell T.

    2014-01-01

    The bacterial communities of sponges have been studied using molecular techniques as well as culture-based techniques, but the communities described by these two methods are remarkably distinct. Culture-based methods describe communities dominated by Proteobacteria, and Actinomycetes while molecular methods describe communities dominated by predominantly uncultivated groups such as the Chloroflexi, Acidobacteria, and Acidimicrobidae. In this study, we used a wide range of culture media to increase the diversity of cultivable bacteria from the closely related giant barrel sponges, Xestospongia muta collected from the Florida Keys, Atlantic Ocean and Xestospongia testudinaria, collected from Indonesia, Pacific Ocean. Over 400 pure cultures were isolated and identified from X. muta and X. testudinaria and over 90 bacterial species were represented. Over 16,000 pyrosequences were analyzed and assigned to 976 OTUs. We employed both cultured-based methods and pyrosequencing to look for patterns of overlap between the culturable and molecular communities. Only one OTU was found in both the molecular and culturable communities, revealing limitations inherent in both approaches. PMID:24618773

  9. SCIENCE RESULTS INTEGRATION. BRINGING MOLECULAR BIOLOGY TECHNIQUES TO REGIONAL WATER MONITORING PROGRAMS

    EPA Science Inventory

    EPA's Office of Research and Development (ORD) develops innovative methods for use in environmental monitoring and assessment by scientists in Regions, states, and Tribes. Molecular-biology-based methods are not yet established in the environmental monitoring "tool box". SRI (Sci...

  10. Molecular mechanisms of ionic liquid cytotoxicity probed by an integrated experimental and computational approach

    DOE PAGES

    Yoo, Brian; Jing, Benxin; Jones, Stuart E.; Lamberti, Gary A.; Zhu, Yingxi; Shah, Jindal K.; Maginn, Edward J.

    2016-02-02

    Ionic liquids (ILs) are salts that remain liquid down to low temperatures, and sometimes well below room temperature. ILs have been called “green solvents” because of their extraordinarily low vapor pressure and excellent solvation power, but ecotoxicology studies have shown that some ILs exhibit greater toxicity than traditional solvents. A fundamental understanding of the molecular mechanisms responsible for IL toxicity remains elusive. Here we show that one mode of IL toxicity on unicellular organisms is driven by swelling of the cell membrane. Cytotoxicity assays, confocal laser scanning microscopy, and molecular simulations reveal that IL cations nucleate morphological defects in themore » microbial cell membrane at concentrations near the half maximal effective concentration (EC50) of several microorganisms. Lastly, cytotoxicity increases with increasing alkyl chain length of the cation due to the ability of the longer alkyl chain to more easily embed in, and ultimately disrupt, the cell membrane.« less

  11. Molecular mechanisms of ionic liquid cytotoxicity probed by an integrated experimental and computational approach

    PubMed Central

    Yoo, Brian; Jing, Benxin; Jones, Stuart E.; Lamberti, Gary A.; Zhu, Yingxi; Shah, Jindal K.; Maginn, Edward J.

    2016-01-01

    Ionic liquids (ILs) are salts that remain liquid down to low temperatures, and sometimes well below room temperature. ILs have been called “green solvents” because of their extraordinarily low vapor pressure and excellent solvation power, but ecotoxicology studies have shown that some ILs exhibit greater toxicity than traditional solvents. A fundamental understanding of the molecular mechanisms responsible for IL toxicity remains elusive. Here we show that one mode of IL toxicity on unicellular organisms is driven by swelling of the cell membrane. Cytotoxicity assays, confocal laser scanning microscopy, and molecular simulations reveal that IL cations nucleate morphological defects in the microbial cell membrane at concentrations near the half maximal effective concentration (EC50) of several microorganisms. Cytotoxicity increases with increasing alkyl chain length of the cation due to the ability of the longer alkyl chain to more easily embed in, and ultimately disrupt, the cell membrane. PMID:26831599

  12. Integration and scaling of UV-B radiation effects on plants: from molecular interactions to whole plant responses.

    PubMed

    Suchar, Vasile Alexandru; Robberecht, Ronald

    2016-07-01

    A process based model integrating the effects of UV-B radiation to molecular level processes and their consequences to whole plant growth and development was developed from key parameters in the published literature. Model simulations showed that UV-B radiation induced changes in plant metabolic and/or photosynthesis rates can result in plant growth inhibitions. The costs of effective epidermal UV-B radiation absorptive compounds did not result in any significant changes in plant growth, but any associated metabolic costs effectively reduced the potential plant biomass. The model showed significant interactions between UV-B radiation effects and temperature and any factor leading to inhibition of photosynthetic production or plant growth during the midday, but the effects were not cumulative for all factors. Vegetative growth were significantly delayed in species that do not exhibit reproductive cycles during a growing season, but vegetative growth and reproductive yield in species completing their life cycle in one growing season did not appear to be delayed more than 2-5 days, probably within the natural variability of the life cycles for many species. This is the first model to integrate the effects of increased UV-B radiation through molecular level processes and their consequences to whole plant growth and development. PMID:27547319

  13. Design and construction of a first-generation high-throughput integrated robotic molecular biology platform for bioenergy applications.

    PubMed

    Hughes, Stephen R; Butt, Tauseef R; Bartolett, Scott; Riedmuller, Steven B; Farrelly, Philip

    2011-08-01

    The molecular biological techniques for plasmid-based assembly and cloning of gene open reading frames are essential for elucidating the function of the proteins encoded by the genes. High-throughput integrated robotic molecular biology platforms that have the capacity to rapidly clone and express heterologous gene open reading frames in bacteria and yeast and to screen large numbers of expressed proteins for optimized function are an important technology for improving microbial strains for biofuel production. The process involves the production of full-length complementary DNA libraries as a source of plasmid-based clones to express the desired proteins in active form for determination of their functions. Proteins that were identified by high-throughput screening as having desired characteristics are overexpressed in microbes to enable them to perform functions that will allow more cost-effective and sustainable production of biofuels. Because the plasmid libraries are composed of several thousand unique genes, automation of the process is essential. This review describes the design and implementation of an automated integrated programmable robotic workcell capable of producing complementary DNA libraries, colony picking, isolating plasmid DNA, transforming yeast and bacteria, expressing protein, and performing appropriate functional assays. These operations will allow tailoring microbial strains to use renewable feedstocks for production of biofuels, bioderived chemicals, fertilizers, and other coproducts for profitable and sustainable biorefineries.

  14. Designing molecular complexes using free-energy derivatives from liquid-state integral equation theory

    NASA Astrophysics Data System (ADS)

    Mrugalla, Florian; Kast, Stefan M.

    2016-09-01

    Complex formation between molecules in solution is the key process by which molecular interactions are translated into functional systems. These processes are governed by the binding or free energy of association which depends on both direct molecular interactions and the solvation contribution. A design goal frequently addressed in pharmaceutical sciences is the optimization of chemical properties of the complex partners in the sense of minimizing their binding free energy with respect to a change in chemical structure. Here, we demonstrate that liquid-state theory in the form of the solute-solute equation of the reference interaction site model provides all necessary information for such a task with high efficiency. In particular, computing derivatives of the potential of mean force (PMF), which defines the free-energy surface of complex formation, with respect to potential parameters can be viewed as a means to define a direction in chemical space toward better binders. We illustrate the methodology in the benchmark case of alkali ion binding to the crown ether 18-crown-6 in aqueous solution. In order to examine the validity of the underlying solute-solute theory, we first compare PMFs computed by different approaches, including explicit free-energy molecular dynamics simulations as a reference. Predictions of an optimally binding ion radius based on free-energy derivatives are then shown to yield consistent results for different ion parameter sets and to compare well with earlier, orders-of-magnitude more costly explicit simulation results. This proof-of-principle study, therefore, demonstrates the potential of liquid-state theory for molecular design problems.

  15. Designing molecular complexes using free-energy derivatives from liquid-state integral equation theory.

    PubMed

    Mrugalla, Florian; Kast, Stefan M

    2016-09-01

    Complex formation between molecules in solution is the key process by which molecular interactions are translated into functional systems. These processes are governed by the binding or free energy of association which depends on both direct molecular interactions and the solvation contribution. A design goal frequently addressed in pharmaceutical sciences is the optimization of chemical properties of the complex partners in the sense of minimizing their binding free energy with respect to a change in chemical structure. Here, we demonstrate that liquid-state theory in the form of the solute-solute equation of the reference interaction site model provides all necessary information for such a task with high efficiency. In particular, computing derivatives of the potential of mean force (PMF), which defines the free-energy surface of complex formation, with respect to potential parameters can be viewed as a means to define a direction in chemical space toward better binders. We illustrate the methodology in the benchmark case of alkali ion binding to the crown ether 18-crown-6 in aqueous solution. In order to examine the validity of the underlying solute-solute theory, we first compare PMFs computed by different approaches, including explicit free-energy molecular dynamics simulations as a reference. Predictions of an optimally binding ion radius based on free-energy derivatives are then shown to yield consistent results for different ion parameter sets and to compare well with earlier, orders-of-magnitude more costly explicit simulation results. This proof-of-principle study, therefore, demonstrates the potential of liquid-state theory for molecular design problems.

  16. Designing molecular complexes using free-energy derivatives from liquid-state integral equation theory

    NASA Astrophysics Data System (ADS)

    Mrugalla, Florian; Kast, Stefan M.

    2016-09-01

    Complex formation between molecules in solution is the key process by which molecular interactions are translated into functional systems. These processes are governed by the binding or free energy of association which depends on both direct molecular interactions and the solvation contribution. A design goal frequently addressed in pharmaceutical sciences is the optimization of chemical properties of the complex partners in the sense of minimizing their binding free energy with respect to a change in chemical structure. Here, we demonstrate that liquid-state theory in the form of the solute–solute equation of the reference interaction site model provides all necessary information for such a task with high efficiency. In particular, computing derivatives of the potential of mean force (PMF), which defines the free-energy surface of complex formation, with respect to potential parameters can be viewed as a means to define a direction in chemical space toward better binders. We illustrate the methodology in the benchmark case of alkali ion binding to the crown ether 18-crown-6 in aqueous solution. In order to examine the validity of the underlying solute–solute theory, we first compare PMFs computed by different approaches, including explicit free-energy molecular dynamics simulations as a reference. Predictions of an optimally binding ion radius based on free-energy derivatives are then shown to yield consistent results for different ion parameter sets and to compare well with earlier, orders-of-magnitude more costly explicit simulation results. This proof-of-principle study, therefore, demonstrates the potential of liquid-state theory for molecular design problems.

  17. MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment.

    PubMed

    Kumar, Sudhir; Tamura, Koichiro; Nei, Masatoshi

    2004-06-01

    With its theoretical basis firmly established in molecular evolutionary and population genetics, the comparative DNA and protein sequence analysis plays a central role in reconstructing the evolutionary histories of species and multigene families, estimating rates of molecular evolution, and inferring the nature and extent of selective forces shaping the evolution of genes and genomes. The scope of these investigations has now expanded greatly owing to the development of high-throughput sequencing techniques and novel statistical and computational methods. These methods require easy-to-use computer programs. One such effort has been to produce Molecular Evolutionary Genetics Analysis (MEGA) software, with its focus on facilitating the exploration and analysis of the DNA and protein sequence variation from an evolutionary perspective. Currently in its third major release, MEGA3 contains facilities for automatic and manual sequence alignment, web-based mining of databases, inference of the phylogenetic trees, estimation of evolutionary distances and testing evolutionary hypotheses. This paper provides an overview of the statistical methods, computational tools, and visual exploration modules for data input and the results obtainable in MEGA.

  18. Integrating Bibliographic Software, Database Searching, and Molecular Modeling in an Introductory Biology Course

    ERIC Educational Resources Information Center

    Priore, Charles F., Jr.; Giannini, John L.

    2007-01-01

    Librarians instruct students where to find information, but rarely demonstrate its management, while faculty have difficulty incorporating real-time laboratory experience with library research. This paper focuses on the development of a hands-on biology laboratory experiment in an introductory course that integrates bibliographic software into the…

  19. Multi-study Integration of Brain Cancer Transcriptomes Reveals Organ-Level Molecular Signatures

    PubMed Central

    Sung, Jaeyun; Kim, Pan-Jun; Ma, Shuyi; Funk, Cory C.; Magis, Andrew T.; Wang, Yuliang; Hood, Leroy; Geman, Donald; Price, Nathan D.

    2013-01-01

    We utilized abundant transcriptomic data for the primary classes of brain cancers to study the feasibility of separating all of these diseases simultaneously based on molecular data alone. These signatures were based on a new method reported herein – Identification of Structured Signatures and Classifiers (ISSAC) – that resulted in a brain cancer marker panel of 44 unique genes. Many of these genes have established relevance to the brain cancers examined herein, with others having known roles in cancer biology. Analyses on large-scale data from multiple sources must deal with significant challenges associated with heterogeneity between different published studies, for it was observed that the variation among individual studies often had a larger effect on the transcriptome than did phenotype differences, as is typical. For this reason, we restricted ourselves to studying only cases where we had at least two independent studies performed for each phenotype, and also reprocessed all the raw data from the studies using a unified pre-processing pipeline. We found that learning signatures across multiple datasets greatly enhanced reproducibility and accuracy in predictive performance on truly independent validation sets, even when keeping the size of the training set the same. This was most likely due to the meta-signature encompassing more of the heterogeneity across different sources and conditions, while amplifying signal from the repeated global characteristics of the phenotype. When molecular signatures of brain cancers were constructed from all currently available microarray data, 90% phenotype prediction accuracy, or the accuracy of identifying a particular brain cancer from the background of all phenotypes, was found. Looking forward, we discuss our approach in the context of the eventual development of organ-specific molecular signatures from peripheral fluids such as the blood. PMID:23935471

  20. Planar lipid bilayers containing gramicidin A as a molecular sensing system based on an integrated current.

    PubMed

    Nishio, Masato; Shoji, Atsushi; Sugawara, Masao

    2012-01-01

    The channel activity of gramicidin A in free-standing planar lipid bilayers with different charges of polar head groups and various lengths of hydrocarbon tails were analyzed in terms of the channel conductance, the lifetime of channel events and the magnitude of integrated currents. The channel activity of gramicidin A in lipid bilayers is tunable by adjusting the membrane composition. The in situ coupling of the anti-BSA antibody as a model protein to the amine moiety of phosphatidylethanolamine (PE) in a lipid bilayer by the amine coupling method allowed us to design an antigen (BSA)-sensitive interface, in which the integrated current, rather than the frequency of channel event, can be used as an analytical signal. The potential of the present system for highly sensitive and selective detection of BSA at 10(-9) g/mL level is demonstrated.

  1. Efficient Calculation of Free Energy Differences Associated with Isotopic Substitution Using Path-Integral Molecular Dynamics.

    PubMed

    Marsalek, Ondrej; Chen, Pei-Yang; Dupuis, Romain; Benoit, Magali; Méheut, Merlin; Bačić, Zlatko; Tuckerman, Mark E

    2014-04-01

    The problem of computing free energy differences due to isotopic substitution in chemical systems is discussed. The shift in the equilibrium properties of a system upon isotopic substitution is a purely quantum mechanical effect that can be quantified using the Feynman path integral approach. In this paper, we explore two developments that lead to a highly efficient path integral scheme. First, we employ a mass switching function inspired by the work of Ceriotti and Markland [ J. Chem. Phys. 2013, 138, 014112] that is based on the inverse square root of the mass and which leads to a perfectly constant free energy derivative with respect to the switching parameter in the harmonic limit. We show that even for anharmonic systems, this scheme allows a single-point thermodynamic integration approach to be used in the construction of free energy differences. In order to improve the efficiency of the calculations even further, however, we derive a set of free energy derivative estimators based on the fourth-order scheme of Takahashi and Imada [ J. Phys. Soc. Jpn. 1984, 53, 3765]. The Takahashi-Imada procedure generates a primitive fourth-order estimator that allows the number of imaginary time slices in the path-integral approach to be reduced substantially. However, as with all primitive estimators, its convergence is plagued by numerical noise. In order to alleviate this problem, we derive a fourth-order virial estimator based on a transferring of the difference between second- and fourth-order primitive estimators, which remains relatively constant as a function of the number of configuration samples, to the second-order virial estimator. We show that this new estimator converges as smoothly as the second-order virial estimator but requires significantly fewer imaginary time points. PMID:26580362

  2. Communication: Phase diagram of C{sub 36} by atomistic molecular dynamics and thermodynamic integration through coexistence regions

    SciTech Connect

    Abramo, M. C.; Caccamo, C. Costa, D.; Munaò, G.

    2014-09-07

    We report an atomistic molecular dynamics determination of the phase diagram of a rigid-cage model of C{sub 36}. We first show that free energies obtained via thermodynamic integrations along isotherms displaying “van der Waals loops,” are fully reproduced by those obtained via isothermal-isochoric integration encompassing only stable states. We find that a similar result also holds for isochoric paths crossing van der Waals regions of the isotherms, and for integrations extending to rather high densities where liquid-solid coexistence can be expected to occur. On such a basis we are able to map the whole phase diagram of C{sub 36}, with resulting triple point and critical temperatures about 1770 K and 2370 K, respectively. We thus predict a 600 K window of existence of a stable liquid phase. Also, at the triple point density, we find that the structural functions and the diffusion coefficient maintain a liquid-like character down to 1400–1300 K, this indicating a wide region of possible supercooling. We discuss why all these features might render possible the observation of the melting of C{sub 36} fullerite and of its liquid state, at variance with what previously experienced for C{sub 60}.

  3. A hybrid approach to survival model building using integration of clinical and molecular information in censored data.

    PubMed

    Choi, Ickwon; Kattan, Michael W; Wells, Brian J; Yu, Changhong

    2012-01-01

    In medical society, the prognostic models, which use clinicopathologic features and predict prognosis after a certain treatment, have been externally validated and used in practice. In recent years, most research has focused on high dimensional genomic data and small sample sizes. Since clinically similar but molecularly heterogeneous tumors may produce different clinical outcomes, the combination of clinical and genomic information, which may be complementary, is crucial to improve the quality of prognostic predictions. However, there is a lack of an integrating scheme for clinic-genomic models due to the P ≥ N problem, in particular, for a parsimonious model. We propose a methodology to build a reduced yet accurate integrative model using a hybrid approach based on the Cox regression model, which uses several dimension reduction techniques, L₂ penalized maximum likelihood estimation (PMLE), and resampling methods to tackle the problem. The predictive accuracy of the modeling approach is assessed by several metrics via an independent and thorough scheme to compare competing methods. In breast cancer data studies on a metastasis and death event, we show that the proposed methodology can improve prediction accuracy and build a final model with a hybrid signature that is parsimonious when integrating both types of variables.

  4. Expression of endogenous para-retroviral genes and molecular analysis of the integration events in its plant host Dahlia variabilis.

    PubMed

    Eid, S; Pappu, H R

    2014-02-01

    The dahlia (Dahlia variabilis) genome contains an endogenous pararetrovirus sequence (EPRS) tentatively designated as DvEPRS. The DvEPRS shares genome structure and organization that is typical of members of the Caulimovirus genus. Studies were carried out to better understand the nature of this integration and to determine the gene expression of this DvEPRS. Genomic Southern hybridization showed multiple and random integration events of the DvEPRS in the dahlia genome. To investigate the presence of DvEPRS transcripts, RT-PCR was done on DNase-treated total RNA from DvEPRS-infected dahlia plants. Results showed the expression of open reading frames I, V, and VI. Direct PCR from sap extracts produced more intense DNA amplicons of Dahlia mosaic virus and Dahlia common mosaic virus which are believed to exist as typical episomal caulimoviruses, whereas significantly less intense amplicon was seen in case of DvEPRS in comparison with internal transcribed spacer region of dahlias amplicon. The DvEPRS in wild and cultivated species of Dahlia offer a model system to study the molecular events underlying the ecology, evolution and spread of DvEPRS within natural and managed ecosystems and the factors affecting integration of these EPRS in the plant genome. PMID:24258394

  5. Molecular profiling of marine fauna: integration of omics with environmental assessment of the world's oceans.

    PubMed

    Veldhoen, Nik; Ikonomou, Michael G; Helbing, Caren C

    2012-02-01

    Many species that contribute to the commercial and ecological richness of our marine ecosystems are harbingers of environmental change. The ability of organisms to rapidly detect and respond to changes in the surrounding environment represents the foundation for application of molecular profiling technologies towards marine sentinel species in an attempt to identify signature profiles that may reside within the transcriptome, proteome, or metabolome and that are indicative of a particular environmental exposure event. The current review highlights recent examples of the biological information obtained for marine sentinel teleosts, mammals, and invertebrates. While in its infancy, such basal information can provide a systems biology framework in the detection and evaluation of environmental chemical contaminant effects on marine fauna. Repeated evaluation across different seasons and local marine environs will lead to discrimination between signature profiles representing normal variation within the complex milieu of environmental factors that trigger biological response in a given sentinel species and permit a greater understanding of normal versus anthropogenic-associated modulation of biological pathways, which prove detrimental to marine fauna. It is anticipated that incorporation of contaminant-specific molecular signatures into current risk assessment paradigms will lead to enhanced wildlife management strategies that minimize the impacts of our industrialized society on marine ecosystems. PMID:22036265

  6. An integrative molecular and genomic analysis of pediatric hemispheric low-grade gliomas: an update.

    PubMed

    Lassaletta, Alvaro; Zapotocky, Michal; Bouffet, Eric; Hawkins, Cynthia; Tabori, Uri

    2016-10-01

    Hemispheric low-grade gliomas account for the second most common location in pediatric low-grade gliomas (PLGGs) after the cerebellum. The pathological spectrum includes gangliogliomas, dysembryoplastic neuroepithelial tumors (DNETs), diffuse astrocytomas, pilocytic astrocytomas, and pleomorphic xanthoastrocytomas (PXAs), among others. Clinically, hemispheric PLGGs represent a well-recognized cause of intractable epilepsy in children and adolescents. With an excellent long-term outcome, surgery remains the cornerstone and patients with gross total resection typically do not need any further therapies. The recent literature about hemispheric PLGGs was reviewed to provide an up-to-date overview of the molecular and cell biology of these tumors. Hemispheric PLGGs can harbor multiple alterations involving BRAFV600E, FGFR, NTRK, MYB/MYBL1, IDH, and BRAF-KIAA1549 fusions. However, the clinical significance of most of these alterations is still to be defined. The role of RAS/MAPK mutations and other alterations in hemispheric PLGGs is of interest from diagnostic, prognostic, and therapeutic perspectives. Molecular testing for these tumors should be encouraged, since the findings can have an important impact not only in prognosis but also in therapeutic strategies. PMID:27659822

  7. Extension of the AMBER molecular dynamics software to Intel's Many Integrated Core (MIC) architecture

    NASA Astrophysics Data System (ADS)

    Needham, Perri J.; Bhuiyan, Ashraf; Walker, Ross C.

    2016-04-01

    We present an implementation of explicit solvent particle mesh Ewald (PME) classical molecular dynamics (MD) within the PMEMD molecular dynamics engine, that forms part of the AMBER v14 MD software package, that makes use of Intel Xeon Phi coprocessors by offloading portions of the PME direct summation and neighbor list build to the coprocessor. We refer to this implementation as pmemd MIC offload and in this paper present the technical details of the algorithm, including basic models for MPI and OpenMP configuration, and analyze the resultant performance. The algorithm provides the best performance improvement for large systems (>400,000 atoms), achieving a ∼35% performance improvement for satellite tobacco mosaic virus (1,067,095 atoms) when 2 Intel E5-2697 v2 processors (2 ×12 cores, 30M cache, 2.7 GHz) are coupled to an Intel Xeon Phi coprocessor (Model 7120P-1.238/1.333 GHz, 61 cores). The implementation utilizes a two-fold decomposition strategy: spatial decomposition using an MPI library and thread-based decomposition using OpenMP. We also present compiler optimization settings that improve the performance on Intel Xeon processors, while retaining simulation accuracy.

  8. Extension of the AMBER molecular dynamics software to Intel's Many Integrated Core (MIC) architecture

    NASA Astrophysics Data System (ADS)

    Needham, Perri J.; Bhuiyan, Ashraf; Walker, Ross C.

    2016-04-01

    We present an implementation of explicit solvent particle mesh Ewald (PME) classical molecular dynamics (MD) within the PMEMD molecular dynamics engine, that forms part of the AMBER v14 MD software package, that makes use of Intel Xeon Phi coprocessors by offloading portions of the PME direct summation and neighbor list build to the coprocessor. We refer to this implementation as pmemd MIC offload and in this paper present the technical details of the algorithm, including basic models for MPI and OpenMP configuration, and analyze the resultant performance. The algorithm provides the best performance improvement for large systems (>400,000 atoms), achieving a ˜35% performance improvement for satellite tobacco mosaic virus (1,067,095 atoms) when 2 Intel E5-2697 v2 processors (2 ×12 cores, 30M cache, 2.7 GHz) are coupled to an Intel Xeon Phi coprocessor (Model 7120P-1.238/1.333 GHz, 61 cores). The implementation utilizes a two-fold decomposition strategy: spatial decomposition using an MPI library and thread-based decomposition using OpenMP. We also present compiler optimization settings that improve the performance on Intel Xeon processors, while retaining simulation accuracy.

  9. Integrative analysis revealed the molecular mechanism underlying RBM10-mediated splicing regulation

    PubMed Central

    Wang, Yongbo; Gogol-Döring, Andreas; Hu, Hao; Fröhler, Sebastian; Ma, Yunxia; Jens, Marvin; Maaskola, Jonas; Murakawa, Yasuhiro; Quedenau, Claudia; Landthaler, Markus; Kalscheuer, Vera; Wieczorek, Dagmar; Wang, Yang; Hu, Yuhui; Chen, Wei

    2013-01-01

    RBM10 encodes an RNA binding protein. Mutations in RBM10 are known to cause multiple congenital anomaly syndrome in male humans, the TARP syndrome. However, the molecular function of RBM10 is unknown. Here we used PAR-CLIP to identify thousands of binding sites of RBM10 and observed significant RBM10–RNA interactions in the vicinity of splice sites. Computational analyses of binding sites as well as loss-of-function and gain-of-function experiments provided evidence for the function of RBM10 in regulating exon skipping and suggested an underlying mechanistic model, which could be subsequently validated by minigene experiments. Furthermore, we demonstrated the splicing defects in a patient carrying an RBM10 mutation, which could be explained by disrupted function of RBM10 in splicing regulation. Overall, our study established RBM10 as an important regulator of alternative splicing, presented a mechanistic model for RBM10-mediated splicing regulation and provided a molecular link to understanding a human congenital disorder. PMID:24000153

  10. Using biocatalysis to integrate organic chemistry into a molecular biology laboratory course.

    PubMed

    Beers, Mande; Archer, Crystal; Feske, Brent D; Mateer, Scott C

    2012-01-01

    Current cutting-edge biomedical investigation requires that the researcher have an operational understanding of several diverse disciplines. Biocatalysis is a field of science that operates at the crossroads of organic chemistry, biochemistry, microbiology, and molecular biology, and provides an excellent model for interdisciplinary research. We have developed an inquiry-based module that uses the mutagenesis of the yeast reductase, YDL124w, to study the bioorganic synthesis of the taxol side-chain, a pharmacologically important molecule. Using related structures, students identify regions they think will affect enzyme stereoselective, design and generate site-specific mutants, and then characterize the effect of these changes on enzyme activity. This laboratory activity gives our students experience, working in a scientific discipline outside of biology and exposes them to techniques and equipment they do not normally work with in a molecular biology course. These inter-disciplinary experiences not only show the relevance of other sciences to biology, but also give our students the ability to communicate more effectively with scientists outside their discipline.

  11. Integrating Art.

    ERIC Educational Resources Information Center

    BCATA Journal for Art Teachers, 1991

    1991-01-01

    These articles focus on art as a component of interdisciplinary integration. (1) "Integrated Curriculum and the Visual Arts" (Anna Kindler) considers various aspects of integration and implications for art education. (2) "Integration: The New Literacy" (Tim Varro) illustrates how the use of technology can facilitate cross-curricular integration.…

  12. Lab-on-a-CD: A Fully Integrated Molecular Diagnostic System.

    PubMed

    Kong, Ling X; Perebikovsky, Alexandra; Moebius, Jacob; Kulinsky, Lawrence; Madou, Marc

    2016-06-01

    The field of centrifugal microfluidics has experienced tremendous growth during the past 15 years, especially in applications such as lab-on-a-disc (LoD) diagnostics. The strength of LoD systems lies in its potential for development into fully integrated sample-to-answer analysis systems. This review highlights the technologies necessary to develop the next generation of these systems. In addition to outlining valving and other fluid-handling operations, we discuss the recent advances and future outlook in four categories of LoD processes: reagent storage, sample preparation, nucleic acid amplification, and analyte detection strategies.

  13. Sequencing and beyond: integrating molecular ‘omics for microbial community profiling

    PubMed Central

    Franzosa, Eric A.; Hsu, Tiffany; Sirota-Madi, Alexandra; Shafquat, Afrah; Abu-Ali, Galeb; Morgan, Xochitl C.

    2016-01-01

    High-throughput DNA sequencing has proven invaluable for investigating diverse environmental and host-associated microbial communities. In this Review, we discuss emerging strategies for microbial community analysis that complement and expand traditional metagenomic profiling. These include novel DNA sequencing strategies for identifying strain-level microbial variation and community temporal dynamics; measuring additional multi'omic data types that better capture community functional activity, such as transcriptomics, proteomics, and metabolomics; and combining multiple forms of multi'omic data in an integrated framework. We highlight studies in which the multi'omics approach has led to improved mechanistic models of microbial community structure and function. PMID:25915636

  14. Fast computation of molecular random phase approximation correlation energies using resolution of the identity and imaginary frequency integration

    NASA Astrophysics Data System (ADS)

    Eshuis, Henk; Yarkony, Julian; Furche, Filipp

    2010-06-01

    The random phase approximation (RPA) is an increasingly popular post-Kohn-Sham correlation method, but its high computational cost has limited molecular applications to systems with few atoms. Here we present an efficient implementation of RPA correlation energies based on a combination of resolution of the identity (RI) and imaginary frequency integration techniques. We show that the RI approximation to four-index electron repulsion integrals leads to a variational upper bound to the exact RPA correlation energy if the Coulomb metric is used. Auxiliary basis sets optimized for second-order Møller-Plesset (MP2) calculations are well suitable for RPA, as is demonstrated for the HEAT [A. Tajti et al., J. Chem. Phys. 121, 11599 (2004)] and MOLEKEL [F. Weigend et al., Chem. Phys. Lett. 294, 143 (1998)] benchmark sets. Using imaginary frequency integration rather than diagonalization to compute the matrix square root necessary for RPA, evaluation of the RPA correlation energy requires O(N4 log N) operations and O(N3) storage only; the price for this dramatic improvement over existing algorithms is a numerical quadrature. We propose a numerical integration scheme that is exact in the two-orbital case and converges exponentially with the number of grid points. For most systems, 30-40 grid points yield μH accuracy in triple zeta basis sets, but much larger grids are necessary for small gap systems. The lowest-order approximation to the present method is a post-Kohn-Sham frequency-domain version of opposite-spin Laplace-transform RI-MP2 [J. Jung et al., Phys. Rev. B 70, 205107 (2004)]. Timings for polyacenes with up to 30 atoms show speed-ups of two orders of magnitude over previous implementations. The present approach makes it possible to routinely compute RPA correlation energies of systems well beyond 100 atoms, as is demonstrated for the octapeptide angiotensin II.

  15. Integrated atomistic chemical imaging and reactive force field molecular dynamic simulations on silicon oxidation

    SciTech Connect

    Dumpala, Santoshrupa; Broderick, Scott R.; Rajan, Krishna; Khalilov, Umedjon; Neyts, Erik C.; Duin, Adri C. T. van; Provine, J; Howe, Roger T.

    2015-01-05

    In this paper, we quantitatively investigate with atom probe tomography, the effect of temperature on the interfacial transition layer suboxide species due to the thermal oxidation of silicon. The chemistry at the interface was measured with atomic scale resolution, and the changes in chemistry and intermixing at the interface were identified on a nanometer scale. We find an increase of suboxide (SiOx) concentration relative to SiO{sub 2} and increased oxygen ingress with elevated temperatures. Our experimental findings are in agreement with reactive force field molecular dynamics simulations. This work demonstrates the direct comparison between atom probe derived chemical profiles and atomistic-scale simulations for transitional interfacial layer of suboxides as a function of temperature.

  16. Performance evaluation of integrating detectors for near-infrared fluorescence molecular imaging

    NASA Astrophysics Data System (ADS)

    Zhu, Banghe; Rasmussen, John C.; Sevick-Muraca, Eva M.

    2014-05-01

    Although there has been a plethora of devices advanced for clinical translation, there has been no standards to compare and determine the optical device for fluorescence molecular imaging. In this work, we compare different CCD configurations using a solid phantom developed to mimic pM - fM concentrations of near-infrared fluorescent dyes in tissues. Our results show that intensified CCD systems (ICCDs) offer greater contrast at larger signal-tonoise ratios (SNRs) in comparison to their un-intensified CCD systems operated at clinically reasonable, sub-second acquisition times. Furthermore, we compared our investigational ICCD device to the commercial NOVADAQ SPY system, demonstrating different performance in both SNR and contrast.

  17. Toward integration of in vivo molecular computing devices: successes and challenges

    PubMed Central

    Hayat, Sikander; Hinze, Thomas

    2008-01-01

    The computing power unleashed by biomolecule based massively parallel computational units has been the focus of many interdisciplinary studies that couple state of the art ideas from mathematical logic, theoretical computer science, bioengineering, and nanotechnology to fulfill some computational task. The output can influence, for instance, release of a drug at a specific target, gene expression, cell population, or be a purely mathematical entity. Analysis of the results of several studies has led to the emergence of a general set of rules concerning the implementation and optimization of in vivo computational units. Taking two recent studies on in vivo computing as examples, we discuss the impact of mathematical modeling and simulation in the field of synthetic biology and on in vivo computing. The impact of the emergence of gene regulatory networks and the potential of proteins acting as “circuit wires” on the problem of interconnecting molecular computing device subunits is also highlighted. PMID:19404433

  18. An integrated molecular modeling approach for in silico design of new tetracyclic derivatives as ALK inhibitors.

    PubMed

    Peddi, Saikiran Reddy; Sivan, Sree Kanth; Manga, Vijjulatha

    2016-10-01

    Anaplastic lymphoma kinase (ALK), a promising therapeutic target for treatment of human cancers, is a receptor tyrosine kinase that instigates the activation of several signal transduction pathways. In the present study, in silico methods have been employed in order to explore the structural features and functionalities of a series of tetracyclic derivatives displaying potent inhibitory activity toward ALK. Initially docking was performed using GLIDE 5.6 to probe the bioactive conformation of all the compounds and to understand the binding modes of inhibitors. The docking results revealed that ligand interaction with Met 1199 plays a crucial role in binding of inhibitors to ALK. Further to establish a robust 3D-QSAR model using CoMFA and CoMSIA methods, the whole dataset was divided into three splits. Model obtained from Split 3 showed high accuracy ([Formula: see text] of 0.700 and 0.682, [Formula: see text] of 0.971 and 0.974, [Formula: see text] of 0.673 and 0.811, respectively for CoMFA and CoMSIA). The key structural requirements for enhancing the inhibitory activity were derived from CoMFA and CoMSIA contours in combination with site map analysis. Substituting small electronegative groups at Position 8 by replacing either morpholine or piperidine rings and maintaining hydrophobic character at Position 9 in tetracyclic derivatives can enhance the inhibitory potential. Finally, we performed molecular dynamics simulations in order to investigate the stability of protein ligand interactions and MM/GBSA calculations to compare binding free energies of co-crystal ligand and newly designed molecule N1. Based on the coherence of outcome of various molecular modeling studies, a set of 11 new molecules having potential predicted inhibitory activity were designed. PMID:26758803

  19. An integrated molecular modeling approach for in silico design of new tetracyclic derivatives as ALK inhibitors.

    PubMed

    Peddi, Saikiran Reddy; Sivan, Sree Kanth; Manga, Vijjulatha

    2016-10-01

    Anaplastic lymphoma kinase (ALK), a promising therapeutic target for treatment of human cancers, is a receptor tyrosine kinase that instigates the activation of several signal transduction pathways. In the present study, in silico methods have been employed in order to explore the structural features and functionalities of a series of tetracyclic derivatives displaying potent inhibitory activity toward ALK. Initially docking was performed using GLIDE 5.6 to probe the bioactive conformation of all the compounds and to understand the binding modes of inhibitors. The docking results revealed that ligand interaction with Met 1199 plays a crucial role in binding of inhibitors to ALK. Further to establish a robust 3D-QSAR model using CoMFA and CoMSIA methods, the whole dataset was divided into three splits. Model obtained from Split 3 showed high accuracy ([Formula: see text] of 0.700 and 0.682, [Formula: see text] of 0.971 and 0.974, [Formula: see text] of 0.673 and 0.811, respectively for CoMFA and CoMSIA). The key structural requirements for enhancing the inhibitory activity were derived from CoMFA and CoMSIA contours in combination with site map analysis. Substituting small electronegative groups at Position 8 by replacing either morpholine or piperidine rings and maintaining hydrophobic character at Position 9 in tetracyclic derivatives can enhance the inhibitory potential. Finally, we performed molecular dynamics simulations in order to investigate the stability of protein ligand interactions and MM/GBSA calculations to compare binding free energies of co-crystal ligand and newly designed molecule N1. Based on the coherence of outcome of various molecular modeling studies, a set of 11 new molecules having potential predicted inhibitory activity were designed.

  20. Molecular divergence and species delimitation of the cultivated oyster mushrooms: integration of IGS1 and ITS.

    PubMed

    Avin, Farhat Ahmadi; Bhassu, Subha; Tan, Yee Shin; Shahbazi, Pedram; Vikineswary, Sabaratnam

    2014-01-01

    Identification of edible mushrooms particularly Pleurotus genus has been restricted due to various obstacles. The present study attempted to use the combination of two variable regions of IGS1 and ITS for classifying the economically cultivated Pleurotus species. Integration of the two regions proved a high ability that not only could clearly distinguish the species but also served sufficient intraspecies variation. Phylogenetic tree (IGS1+ITS) showed seven distinct clades, each clade belonging to a separate species group. Moreover, the species differentiation was tested by AMOVA and the results were reconfirmed by presenting appropriate amounts of divergence (91.82% among and 8.18% within the species). In spite of achieving a proper classification of species by combination of IGS1 and ITS sequences, the phylogenetic tree showed the misclassification of the species of P. nebrodensis and P. eryngii var. ferulae with other strains of P. eryngii. However, the constructed median joining (MJ) network could not only differentiate between these species but also offer a profound perception of the species' evolutionary process. Eventually, due to the sufficient variation among and within species, distinct sequences, simple amplification, and location between ideal conserved ribosomal genes, the integration of IGS1 and ITS sequences is recommended as a desirable DNA barcode. PMID:24587752

  1. Molecular Divergence and Species Delimitation of the Cultivated Oyster Mushrooms: Integration of IGS1 and ITS

    PubMed Central

    Bhassu, Subha; Tan, Yee Shin; Vikineswary, Sabaratnam

    2014-01-01

    Identification of edible mushrooms particularly Pleurotus genus has been restricted due to various obstacles. The present study attempted to use the combination of two variable regions of IGS1 and ITS for classifying the economically cultivated Pleurotus species. Integration of the two regions proved a high ability that not only could clearly distinguish the species but also served sufficient intraspecies variation. Phylogenetic tree (IGS1 + ITS) showed seven distinct clades, each clade belonging to a separate species group. Moreover, the species differentiation was tested by AMOVA and the results were reconfirmed by presenting appropriate amounts of divergence (91.82% among and 8.18% within the species). In spite of achieving a proper classification of species by combination of IGS1 and ITS sequences, the phylogenetic tree showed the misclassification of the species of P. nebrodensis and P. eryngii var. ferulae with other strains of P. eryngii. However, the constructed median joining (MJ) network could not only differentiate between these species but also offer a profound perception of the species' evolutionary process. Eventually, due to the sufficient variation among and within species, distinct sequences, simple amplification, and location between ideal conserved ribosomal genes, the integration of IGS1 and ITS sequences is recommended as a desirable DNA barcode. PMID:24587752

  2. Transformation of Chloroplast Ribosomal RNA Genes in Chlamydomonas: Molecular and Genetic Characterization of Integration Events

    PubMed Central

    Newman, S. M.; Boynton, J. E.; Gillham, N. W.; Randolph-Anderson, B. L.; Johnson, A. M.; Harris, E. H.

    1990-01-01

    Transformation of chloroplast ribosomal RNA (rRNA) genes in Chlamydomonas has been achieved by the biolistic process using cloned chloroplast DNA fragments carrying mutations that confer antibiotic resistance. The sites of exchange employed during the integration of the donor DNA into the recipient genome have been localized using a combination of antibiotic resistance mutations in the 16S and 23S rRNA genes and restriction fragment length polymorphisms that flank these genes. Complete or nearly complete replacement of a region of the chloroplast genome in the recipient cell by the corresponding sequence from the donor plasmid was the most common integration event. Exchange events between the homologous donor and recipient sequences occurred preferentially near the vector:insert junctions. Insertion of the donor rRNA genes and flanking sequences into one inverted repeat of the recipient genome was followed by intramolecular copy correction so that both copies of the inverted repeat acquired identical sequences. Increased frequencies of rRNA gene transformants were achieved by reducing the copy number of the chloroplast genome in the recipient cells and by decreasing the heterology between donor and recipient DNA sequences flanking the selectable markers. In addition to producing bona fide chloroplast rRNA transformants, the biolistic process induced mutants resistant to low levels of streptomycin, typical of nuclear mutations in Chlamydomonas. PMID:1981764

  3. Molecular beam epitaxy growth of SrO buffer layers on graphite and graphene for the integration of complex oxides

    NASA Astrophysics Data System (ADS)

    Ahmed, Adam S.; Wen, Hua; Ohta, Taisuke; Pinchuk, Igor V.; Zhu, Tiancong; Beechem, Thomas; Kawakami, Roland K.

    2016-08-01

    We report the successful growth of high-quality SrO films on highly-ordered pyrolytic graphite (HOPG) and single-layer graphene by molecular beam epitaxy. The SrO layers have (001) orientation as confirmed by X-ray diffraction (XRD) while atomic force microscopy measurements show continuous pinhole-free films having rms surface roughness of <1.5 Å. Transport measurements of exfoliated graphene after SrO deposition show a strong dependence between the Dirac point and Sr oxidation. Subsequently, the SrO is leveraged as a buffer layer for more complex oxide integration via the demonstration of (001) oriented SrTiO3 grown atop a SrO/HOPG stack.

  4. Molecular beam epitaxy growth of SrO buffer layers on graphite and graphene for the integration of complex oxides

    DOE PAGES

    Ahmed, Adam S.; Wen, Hua; Ohta, Taisuke; Pinchuk, Igor V.; Zhu, Tiancong; Beechem, Thomas; Kawakami, Roland K.

    2016-04-27

    Here, we report the successful growth of high-quality SrO films on highly-ordered pyrolytic graphite (HOPG) and single-layer graphene by molecular beam epitaxy. The SrO layers have (001) orientation as confirmed by X-ray diffraction (XRD) while atomic force microscopy measurements show continuous pinhole-free films having rms surface roughness of <1.5 Å. Moreover, transport measurements of exfoliated graphene, after SrO deposition, show a strong dependence between the Dirac point and Sr oxidation. As a result, the SrO is leveraged as a buffer layer for more complex oxide integration via the demonstration of (001) oriented SrTiO3 grown atop a SrO/HOPG stack.

  5. Low-temperature phases of dense hydrogen and deuterium by first-principles path-integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Torrent, Marc; Geneste, Gregory

    2012-02-01

    The low-temperature phases of dense hydrogen and deuterium have been investigated using first-principles path-integral molecular dynamics, a technique that we have recently implemented in the ABINIT code and that allows to account for the quantum fluctuations of atomic nuclei. A massively parallelized scheme is applied to produce trajectories of several tens of thousands steps using a 64-atom supercell and a Trotter number of 64. The so-called phases I, II and III are studied and compared to the structures proposed in the literature. The quantum fluctuations produce configurational disorder and are shown to systematically enhance the symmetry of the system: a continuous gain of symmetry in the angular density of probability of the molecules is found from classical particles to quantum D2 and finally to quantum H2. Particular emphasis is made on the ``broken-symmetry'' phase (phase II).

  6. Integrated Testing of a 4-Bed Molecular Sieve, Air-Cooled Temperature Swing Adsorption Compressor, and Sabatier Engineering Development Unit

    NASA Technical Reports Server (NTRS)

    Knox, James C.; Miller, Lee; Campbell, Melissa; Mulloth, Lila; Varghese, Mini

    2006-01-01

    Accumulation and subsequent compression of carbon dioxide that is removed from the space cabin are two important processes involved in a closed-loop air revitalization scheme of the International Space Station (ISS). The 4-Bed Molecular Sieve (4BMS) of ISS currently operates in an open loop mode without a compressor. The Sabatier Engineering Development Unit (EDU) processes waste CO2 to provide water to the crew. This paper reports the integrated 4BMS, air-cooled Temperature Swing Adsorption Compressor (TSAC), and Sabatier EDU testing. The TSAC prototype was developed at NASA Ames Research Center (ARC). The 4BMS was modified to a functionally flight-like condition at NASA Marshall Space Flight Center (MSFC). Testing was conducted at MSFC. The paper provides details of the TSAC operation at various CO2 loadings and corresponding performance of the 4BMS and Sabatier.

  7. Crosslinking and Mass Spectrometry: An Integrated Technology to Understand the Structure and Function of Molecular Machines.

    PubMed

    Leitner, Alexander; Faini, Marco; Stengel, Florian; Aebersold, Ruedi

    2016-01-01

    In recent years, chemical crosslinking of protein complexes and the identification of crosslinked residues by mass spectrometry (XL-MS; sometimes abbreviated as CX-MS) has become an important technique bridging mass spectrometry (MS) and structural biology. By now, XL-MS is well established and supported by publicly available resources as a convenient and versatile part of the structural biologist's toolbox. The combination of XL-MS with cryo-electron microscopy (cryo-EM) and/or integrative modeling is particularly promising to study the topology and structure of large protein assemblies. Among the targets studied so far are proteasomes, ribosomes, polymerases, chromatin remodelers, and photosystem complexes. Here we provide an overview of recent advances in XL-MS, the current state of the field, and a cursory outlook on future challenges. PMID:26654279

  8. Crosslinking and Mass Spectrometry: An Integrated Technology to Understand the Structure and Function of Molecular Machines.

    PubMed

    Leitner, Alexander; Faini, Marco; Stengel, Florian; Aebersold, Ruedi

    2016-01-01

    In recent years, chemical crosslinking of protein complexes and the identification of crosslinked residues by mass spectrometry (XL-MS; sometimes abbreviated as CX-MS) has become an important technique bridging mass spectrometry (MS) and structural biology. By now, XL-MS is well established and supported by publicly available resources as a convenient and versatile part of the structural biologist's toolbox. The combination of XL-MS with cryo-electron microscopy (cryo-EM) and/or integrative modeling is particularly promising to study the topology and structure of large protein assemblies. Among the targets studied so far are proteasomes, ribosomes, polymerases, chromatin remodelers, and photosystem complexes. Here we provide an overview of recent advances in XL-MS, the current state of the field, and a cursory outlook on future challenges.

  9. THE MOLECULAR PATHOLOGY OF MELANOMA: AN INTEGRATED TAXONOMY OF MELANOCYTIC NEOPLASIA

    PubMed Central

    Bastian, Boris C.

    2016-01-01

    Melanomas are comprised of multiple biologically distinct categories, which differ in cell of origin, age of onset, clinical and histologic presentation, pattern of metastasis, ethnic distribution, causative role of UV radiation, predisposing germ line alterations, mutational processes, and patterns of somatic mutations. Neoplasms are initiated by gain of function mutations in one of several primary oncogenes, typically leading to benign melanocytic nevi with characteristic histologic features. The progression of nevi is restrained by multiple tumor suppressive mechanisms. Secondary genetic alterations override these barriers and promote intermediate or overtly malignant tumors along distinct progression trajectories. The current knowledge about pathogenesis, clinical, histological and genetic features of primary melanocytic neoplasms is reviewed and integrated into a taxonomic framework. PMID:24460190

  10. Molecular determinant modulates thermal recovery kinetics and structural integrity of the bacterial BLUF photoreceptor.

    PubMed

    Tanwar, Meenakshi; Nahar, Smita; Gulati, Sahil; Veetil, Sindhu Kandoth; Kateriya, Suneel

    2016-07-01

    BLUF domains are flavin-based photoreceptors which receive the blue light signal and are involved in the sensory transduction. We report a short BLUF photoreceptor (SnfB) in Stenotrophomonas sp. We have investigated photodynamic properties of C terminus truncated and several mutated SnfB proteins. Deletion of the extended C-terminal residues alters the thermal recovery kinetics and also affects the integrity of the SnfB protein. Mutagenesis studies demonstrated that the conserved residues within and outside the flavin-binding pocket also regulates the photocycle properties of the protein. These studies suggest that the C-terminal residues outside the BLUF domain can tune the photodynamic properties of the BLUF protein. PMID:27230699

  11. Integrative Genomics Reveals Novel Molecular Pathways and Gene Networks for Coronary Artery Disease

    PubMed Central

    Mäkinen, Ville-Petteri; Civelek, Mete; Meng, Qingying; Zhang, Bin; Zhu, Jun; Levian, Candace; Huan, Tianxiao; Segrè, Ayellet V.; Ghosh, Sujoy; Vivar, Juan; Nikpay, Majid; Stewart, Alexandre F. R.; Nelson, Christopher P.; Willenborg, Christina; Erdmann, Jeanette; Blakenberg, Stefan; O'Donnell, Christopher J.; März, Winfried; Laaksonen, Reijo; Epstein, Stephen E.; Kathiresan, Sekar; Shah, Svati H.; Hazen, Stanley L.; Reilly, Muredach P.; Lusis, Aldons J.; Samani, Nilesh J.; Schunkert, Heribert; Quertermous, Thomas; McPherson, Ruth; Yang, Xia; Assimes, Themistocles L.

    2014-01-01

    The majority of the heritability of coronary artery disease (CAD) remains unexplained, despite recent successes of genome-wide association studies (GWAS) in identifying novel susceptibility loci. Integrating functional genomic data from a variety of sources with a large-scale meta-analysis of CAD GWAS may facilitate the identification of novel biological processes and genes involved in CAD, as well as clarify the causal relationships of established processes. Towards this end, we integrated 14 GWAS from the CARDIoGRAM Consortium and two additional GWAS from the Ottawa Heart Institute (25,491 cases and 66,819 controls) with 1) genetics of gene expression studies of CAD-relevant tissues in humans, 2) metabolic and signaling pathways from public databases, and 3) data-driven, tissue-specific gene networks from a multitude of human and mouse experiments. We not only detected CAD-associated gene networks of lipid metabolism, coagulation, immunity, and additional networks with no clear functional annotation, but also revealed key driver genes for each CAD network based on the topology of the gene regulatory networks. In particular, we found a gene network involved in antigen processing to be strongly associated with CAD. The key driver genes of this network included glyoxalase I (GLO1) and peptidylprolyl isomerase I (PPIL1), which we verified as regulatory by siRNA experiments in human aortic endothelial cells. Our results suggest genetic influences on a diverse set of both known and novel biological processes that contribute to CAD risk. The key driver genes for these networks highlight potential novel targets for further mechanistic studies and therapeutic interventions. PMID:25033284

  12. Path integral molecular dynamics method based on a pair density matrix approximation: An algorithm for distinguishable and identical particle systems

    NASA Astrophysics Data System (ADS)

    Miura, Shinichi; Okazaki, Susumu

    2001-09-01

    In this paper, the path integral molecular dynamics (PIMD) method has been extended to employ an efficient approximation of the path action referred to as the pair density matrix approximation. Configurations of the isomorphic classical systems were dynamically sampled by introducing fictitious momenta as in the PIMD based on the standard primitive approximation. The indistinguishability of the particles was handled by a pseudopotential of particle permutation that is an extension of our previous one [J. Chem. Phys. 112, 10 116 (2000)]. As a test of our methodology for Boltzmann statistics, calculations have been performed for liquid helium-4 at 4 K. We found that the PIMD with the pair density matrix approximation dramatically reduced the computational cost to obtain the structural as well as dynamical (using the centroid molecular dynamics approximation) properties at the same level of accuracy as that with the primitive approximation. With respect to the identical particles, we performed the calculation of a bosonic triatomic cluster. Unlike the primitive approximation, the pseudopotential scheme based on the pair density matrix approximation described well the bosonic correlation among the interacting atoms. Convergence with a small number of discretization of the path achieved by this approximation enables us to construct a method of avoiding the problem of the vanishing pseudopotential encountered in the calculations by the primitive approximation.

  13. Accurate path integral molecular dynamics simulation of ab-initio water at near-zero added cost

    NASA Astrophysics Data System (ADS)

    Elton, Daniel; Fritz, Michelle; Soler, José; Fernandez-Serra, Marivi

    It is now established that nuclear quantum motion plays an important role in determining water's structure and dynamics. These effects are important to consider when evaluating DFT functionals and attempting to develop better ones for water. The standard way of treating nuclear quantum effects, path integral molecular dynamics (PIMD), multiplies the number of energy/force calculations by the number of beads, which is typically 32. Here we introduce a method whereby PIMD can be incorporated into a DFT molecular dynamics simulation at virtually zero cost. The method is based on the cluster (many body) expansion of the energy. We first subtract the DFT monomer energies, using a custom DFT-based monomer potential energy surface. The evolution of the PIMD beads is then performed using only the more-accurate Partridge-Schwenke monomer energy surface. The DFT calculations are done using the centroid positions. Various bead thermostats can be employed to speed up the sampling of the quantum ensemble. The method bears some resemblance to multiple timestep algorithms and other schemes used to speed up PIMD with classical force fields. We show that our method correctly captures some of key effects of nuclear quantum motion on both the structure and dynamics of water. We acknowledge support from DOE Award No. DE-FG02-09ER16052 (D.E.) and DOE Early Career Award No. DE-SC0003871 (M.V.F.S.).

  14. Integrating a Numerical Taxonomic Method and Molecular Phylogeny for Species Delimitation of Melampsora Species (Melampsoraceae, Pucciniales) on Willows in China.

    PubMed

    Zhao, Peng; Wang, Qing-Hong; Tian, Cheng-Ming; Kakishima, Makoto

    2015-01-01

    The species in genus Melampsora are the causal agents of leaf rust diseases on willows in natural habitats and plantations. However, the classification and recognition of species diversity are challenging because morphological characteristics are scant and morphological variation in Melampsora on willows has not been thoroughly evaluated. Thus, the taxonomy of Melampsora species on willows remains confused, especially in China where 31 species were reported based on either European or Japanese taxonomic systems. To clarify the species boundaries of Melampsora species on willows in China, we tested two approaches for species delimitation inferred from morphological and molecular variations. Morphological species boundaries were determined based on numerical taxonomic analyses of morphological characteristics in the uredinial and telial stages by cluster analysis and one-way analysis of variance. Phylogenetic species boundaries were delineated based on the generalized mixed Yule-coalescent (GMYC) model analysis of the sequences of the internal transcribed spacer (ITS1 and ITS2) regions including the 5.8S and D1/D2 regions of the large nuclear subunit of the ribosomal RNA gene. Numerical taxonomic analyses of 14 morphological characteristics recognized in the uredinial-telial stages revealed 22 morphological species, whereas the GMYC results recovered 29 phylogenetic species. In total, 17 morphological species were in concordance with the phylogenetic species and 5 morphological species were in concordance with 12 phylogenetic species. Both the morphological and molecular data supported 14 morphological characteristics, including 5 newly recognized characteristics and 9 traditionally emphasized characteristics, as effective for the differentiation of Melampsora species on willows in China. Based on the concordance and discordance of the two species delimitation approaches, we concluded that integrative taxonomy by using both morphological and molecular variations was

  15. Integrating a Numerical Taxonomic Method and Molecular Phylogeny for Species Delimitation of Melampsora Species (Melampsoraceae, Pucciniales) on Willows in China

    PubMed Central

    Zhao, Peng; Wang, Qing-Hong; Tian, Cheng-Ming; Kakishima, Makoto

    2015-01-01

    The species in genus Melampsora are the causal agents of leaf rust diseases on willows in natural habitats and plantations. However, the classification and recognition of species diversity are challenging because morphological characteristics are scant and morphological variation in Melampsora on willows has not been thoroughly evaluated. Thus, the taxonomy of Melampsora species on willows remains confused, especially in China where 31 species were reported based on either European or Japanese taxonomic systems. To clarify the species boundaries of Melampsora species on willows in China, we tested two approaches for species delimitation inferred from morphological and molecular variations. Morphological species boundaries were determined based on numerical taxonomic analyses of morphological characteristics in the uredinial and telial stages by cluster analysis and one-way analysis of variance. Phylogenetic species boundaries were delineated based on the generalized mixed Yule-coalescent (GMYC) model analysis of the sequences of the internal transcribed spacer (ITS1 and ITS2) regions including the 5.8S and D1/D2 regions of the large nuclear subunit of the ribosomal RNA gene. Numerical taxonomic analyses of 14 morphological characteristics recognized in the uredinial-telial stages revealed 22 morphological species, whereas the GMYC results recovered 29 phylogenetic species. In total, 17 morphological species were in concordance with the phylogenetic species and 5 morphological species were in concordance with 12 phylogenetic species. Both the morphological and molecular data supported 14 morphological characteristics, including 5 newly recognized characteristics and 9 traditionally emphasized characteristics, as effective for the differentiation of Melampsora species on willows in China. Based on the concordance and discordance of the two species delimitation approaches, we concluded that integrative taxonomy by using both morphological and molecular variations was

  16. Equilibrium magnesium isotope fractionation between aqueous Mg2+ and carbonate minerals: Insights from path integral molecular dynamics

    NASA Astrophysics Data System (ADS)

    Pinilla, Carlos; Blanchard, Marc; Balan, Etienne; Natarajan, Suresh K.; Vuilleumier, Rodolphe; Mauri, Francesco

    2015-08-01

    The theoretical determination of the isotopic fractionation between an aqueous solution and a mineral is of utmost importance in Earth sciences. While for crystals, it is well established that equilibrium isotopic fractionation factors can be calculated using a statistical thermodynamic approach based on the vibrational properties, several theoretical methods are currently used to model ions in aqueous solution. In this work, we present a systematic study to determine the reduced partition function ratio (β-factor) of aqueous Mg2+ using several levels of theory within the simulations. In particular, using an empirical force field, we compare and discuss the performance of the exact results obtained from path integral molecular dynamics (PIMD) simulations, with respect to the more traditional methods based on vibrational properties and the cluster approximation. The results show the importance of including configurational disorder for the estimation of the equilibrium isotope fractionation factor. We also show that using the vibrational frequencies computed from snapshots taken from equilibrated classical molecular dynamics represents a good approximation for the study of aqueous ions. Based on these conclusions, the β-factor of aqueous Mg2+ have been estimated from a Car-Parrinello molecular dynamics (CPMD) simulation with an ab initio force field, and combined with the β-factors of carbonate minerals (magnesite, dolomite, calcite and aragonite). Mg β-factor of Mg-bearing aragonite, calculated here for the first time, displays a lower value than the three other carbonate minerals. This is explained by a strong distortion of the cationic site leading to a decrease of the coordination number during Ca-Mg substitution. Overall, the equilibrium magnesium isotope fractionation factors between aqueous Mg2+ and carbonate minerals that derive from this methodological study support the previous theoretical results obtained from embedded cluster models.

  17. Integrating a Numerical Taxonomic Method and Molecular Phylogeny for Species Delimitation of Melampsora Species (Melampsoraceae, Pucciniales) on Willows in China.

    PubMed

    Zhao, Peng; Wang, Qing-Hong; Tian, Cheng-Ming; Kakishima, Makoto

    2015-01-01

    The species in genus Melampsora are the causal agents of leaf rust diseases on willows in natural habitats and plantations. However, the classification and recognition of species diversity are challenging because morphological characteristics are scant and morphological variation in Melampsora on willows has not been thoroughly evaluated. Thus, the taxonomy of Melampsora species on willows remains confused, especially in China where 31 species were reported based on either European or Japanese taxonomic systems. To clarify the species boundaries of Melampsora species on willows in China, we tested two approaches for species delimitation inferred from morphological and molecular variations. Morphological species boundaries were determined based on numerical taxonomic analyses of morphological characteristics in the uredinial and telial stages by cluster analysis and one-way analysis of variance. Phylogenetic species boundaries were delineated based on the generalized mixed Yule-coalescent (GMYC) model analysis of the sequences of the internal transcribed spacer (ITS1 and ITS2) regions including the 5.8S and D1/D2 regions of the large nuclear subunit of the ribosomal RNA gene. Numerical taxonomic analyses of 14 morphological characteristics recognized in the uredinial-telial stages revealed 22 morphological species, whereas the GMYC results recovered 29 phylogenetic species. In total, 17 morphological species were in concordance with the phylogenetic species and 5 morphological species were in concordance with 12 phylogenetic species. Both the morphological and molecular data supported 14 morphological characteristics, including 5 newly recognized characteristics and 9 traditionally emphasized characteristics, as effective for the differentiation of Melampsora species on willows in China. Based on the concordance and discordance of the two species delimitation approaches, we concluded that integrative taxonomy by using both morphological and molecular variations was

  18. A path integral molecular dynamics study of the hyperfine coupling constants of the muoniated and hydrogenated acetone radicals

    NASA Astrophysics Data System (ADS)

    Oba, Yuki; Kawatsu, Tsutomu; Tachikawa, Masanori

    2016-08-01

    The on-the-fly ab initio density functional path integral molecular dynamics (PIMD) simulations, which can account for both the nuclear quantum effect and thermal effect, were carried out to evaluate the structures and "reduced" isotropic hyperfine coupling constants (HFCCs) for muoniated and hydrogenated acetone radicals (2-muoxy-2-propyl and 2-hydoxy-2-propyl) in vacuo. The reduced HFCC value from a simple geometry optimization calculation without both the nuclear quantum effect and thermal effect is -8.18 MHz, and that by standard ab initio molecular dynamics simulation with only the thermal effect and without the nuclear quantum effect is 0.33 MHz at 300 K, where these two methods cannot distinguish the difference between muoniated and hydrogenated acetone radicals. In contrast, the reduced HFCC value of the muoniated acetone radical by our PIMD simulation is 32.1 MHz, which is about 8 times larger than that for the hydrogenated radical of 3.97 MHz with the same level of calculation. We have found that the HFCC values are highly correlated with the local molecular structures; especially, the Mu—O bond length in the muoniated acetone radical is elongated due to the large nuclear quantum effect of the muon, which makes the expectation value of the HFCC larger. Although our PIMD result calculated in vacuo is about 4 times larger than the measured experimental value in aqueous solvent, the ratio of these HFCC values between muoniated and hydrogenated acetone radicals in vacuo is in reasonable agreement with the ratio of the experimental values in aqueous solvent (8.56 MHz and 0.9 MHz); the explicit presence of solvent molecules has a major effect on decreasing the reduced muon HFCC of in vacuo calculations for the quantitative reproduction.

  19. Craniometric variation in the Aleutians: integrating morphological, molecular, spatial, and temporal data.

    PubMed

    Ousley, Stephen D; Jones, Erica B

    2010-12-01

    Several hypotheses have been put forward about the origins and evolution of the inhabitants of the Aleutian Islands. Both Hrdlička [The Aleutian and Commander Islands and Their Inhabitants (Philadelphia: Wistar Institute of Anatomy and Biology, 1945)] and Laughlin ["The Alaska gateway viewed from the Aleutian Islands," in Papers on the Physical Anthropology of the American Indian, W. S. Laughlin, ed. (New York: Viking Fund, 1951), 98-126] analyzed cranial morphology and came to somewhat different conclusions using a typological approach and limited analytical methods. Subsequent investigations using morphological data have not significantly improved our understanding of Aleut prehistory. More recently, radiocarbon dating and mitochondrial DNA analyses have shed light on Aleut genetic variation and changes over time, but better morphological methods using multivariate statistical analysis have not yet been used. We analyzed craniometric data using multivariate procedures and found that Aleuts demonstrate significant changes in cranial morphology over time, and these changes correspond to Hrdlička's observations but may not necessarily reflect in-migration. The morphological changes were concentrated in the very aspects of morphology that are easily observable and that Hrdlička most often measured, namely, cranial length, breadth, and height, but they were obscured when craniometric variation as a whole was analyzed. Also, we found that the morphological changes over time were not related to the changes in haplogroup frequencies over time, suggesting that migration into the Aleutians did not play a significant role in producing the morphological changes. However, craniometric variability apparently increases over time, suggesting in-migration, localized selection, and/or greater environmental heterogeneity. Our results contradict Laughlin's observations but may be more in line with his hypothesis of in situ evolutionary changes absent gene flow. In addition to

  20. Integrating molecular, phenotypic and environmental data to elucidate patterns of crocodile hybridization in Belize

    PubMed Central

    Hekkala, Evon R.; Platt, Steven G.; Thorbjarnarson, John B.; Rainwater, Thomas R.; Tessler, Michael; Cunningham, Seth W.; Twomey, Christopher; Amato, George

    2015-01-01

    The genus Crocodylus comprises 12 currently recognized species, many of which can be difficult to differentiate phenotypically. Interspecific hybridization among crocodiles is known to occur in captivity and has been documented between some species in the wild. The identification of hybrid individuals is of importance for management and monitoring of crocodilians, many of which are Convention on International Trade in Endangered Species (CITES) listed. In this study, both mitochondrial and nuclear DNA markers were evaluated for their use in confirming a suspected hybrid zone between American crocodile (Crocodylus acutus) and Morelet’s crocodile (Crocodylus moreletii) populations in southern Belize where individuals and nests exhibiting atypical phenotypic features had previously been observed. Patterns observed in both phenotypic and molecular data indicate possible behavioural and ecological characteristics associated with hybridization events. The results of the combined analyses found that the majority of suspected hybrid samples represent crosses between female C. acutus and male C. moreletii. Phenotypic data could statistically identify hybrids, although morphological overlap between hybrids and C. moreletii reduced reliability of identification based solely on field characters. Ecologically, C. acutus was exclusively found in saline waters, whereas hybrids and C. moreletii were largely absent in these conditions. A hypothesized correlation between unidirectional hybridization and destruction of C. acutus breeding habitats warrants additional research. PMID:26473062

  1. Integrating molecular, phenotypic and environmental data to elucidate patterns of crocodile hybridization in Belize.

    PubMed

    Hekkala, Evon R; Platt, Steven G; Thorbjarnarson, John B; Rainwater, Thomas R; Tessler, Michael; Cunningham, Seth W; Twomey, Christopher; Amato, George

    2015-09-01

    The genus Crocodylus comprises 12 currently recognized species, many of which can be difficult to differentiate phenotypically. Interspecific hybridization among crocodiles is known to occur in captivity and has been documented between some species in the wild. The identification of hybrid individuals is of importance for management and monitoring of crocodilians, many of which are Convention on International Trade in Endangered Species (CITES) listed. In this study, both mitochondrial and nuclear DNA markers were evaluated for their use in confirming a suspected hybrid zone between American crocodile (Crocodylus acutus) and Morelet's crocodile (Crocodylus moreletii) populations in southern Belize where individuals and nests exhibiting atypical phenotypic features had previously been observed. Patterns observed in both phenotypic and molecular data indicate possible behavioural and ecological characteristics associated with hybridization events. The results of the combined analyses found that the majority of suspected hybrid samples represent crosses between female C. acutus and male C. moreletii. Phenotypic data could statistically identify hybrids, although morphological overlap between hybrids and C. moreletii reduced reliability of identification based solely on field characters. Ecologically, C. acutus was exclusively found in saline waters, whereas hybrids and C. moreletii were largely absent in these conditions. A hypothesized correlation between unidirectional hybridization and destruction of C. acutus breeding habitats warrants additional research. PMID:26473062

  2. Assessing the role of cladogenesis in macroevolution by integrating fossil and molecular evidence

    PubMed Central

    Strotz, Luke C.; Allen, Andrew P.

    2013-01-01

    Assessing the extent to which population subdivision during cladogenesis is necessary for long-term phenotypic evolution is of fundamental importance in a broad range of biological disciplines. Differentiating cladogenesis from anagenesis, defined as evolution within a species, has generally been hampered by dating precision, insufficient fossil data, and difficulties in establishing a direct link between morphological changes detectable in the fossil record and biological species. Here we quantify the relative frequencies of cladogenesis and anagenesis for macroperforate planktic Foraminifera, which arguably have the most complete fossil record currently available, to address this question. Analyzing this record in light of molecular evidence, while taking into account the precision of fossil dating techniques, we estimate that the fraction of speciation events attributable to anagenesis is <19% during the Cenozoic era (last 65 Myr) and <10% during the Neogene period (last 23 Myr). Our central conclusion—that cladogenesis is the predominant mode by which new planktic Foraminifera taxa become established at macroevolutionary time scales—differs markedly from the conclusion reached in a recent study based solely on fossil data. These disparate findings demonstrate that interpretations of macroevolutionary dynamics in the fossil record can be fundamentally altered in light of genetic evidence. PMID:23378632

  3. Nitrate uptake along the maize primary root: an integrated physiological and molecular approach.

    PubMed

    Sorgonà, Agostino; Lupini, Antonio; Mercati, Francesco; Di Dio, Luigi; Sunseri, Francesco; Abenavoli, Maria Rosa

    2011-07-01

    The spatial variability of the nitrate (NO₃-) uptake along the maize primary root axis was investigated at physiological and molecular levels. Net NO₃- uptake rate (NNUR) and its kinetic parameters, together with the gene expression of a high-affinity NO₃- transporter (NRT2.1), were evaluated. The activity and the expression of plasma membrane H⁺ -ATPase (PM H⁺ -ATPase), key enzyme in plant nutrition, were also analysed. The NNUR showed a heterogeneous spatial pattern along the root, where the regions closer to the root tip early exhibited higher capacity to absorb NO₃- than the basal regions, because of a higher maximum NNUR and faster induction of the inducible high-affinity transport system (iHATS), the presence of the high-affinity transport system (HATS) also at external NO₃- concentrations >100 µm and an improved NO₃- transport because of lower K(m) values. ZmNRT2.1 transcript abundances were not spatially correlated with NNUR, suggesting that post-translational effects or NAR2 protein co-expression could be involved. By contrast, PM H⁺ -ATPase displayed a similar spatial-temporal pattern as that of nitrate uptake, resulting in higher activity in the root tip than in the basal regions. Increased activities of the enzyme after nitrate supply resulted in enhanced expression of MAH3 and MAH4, PM H⁺ -ATPase subfamily II genes, while MAH1 was not expressed. PMID:21410710

  4. An integrated view of molecular changes, histopathology and outcomes in kidney transplants.

    PubMed

    Halloran, P F; de Freitas, D G; Einecke, G; Famulski, K S; Hidalgo, L G; MengeL, M; Reeve, J; Sellares, J; Sis, B

    2010-10-01

    Data-driven approaches to deteriorating kidney transplants, incorporating histologic, molecular and HLA antibody findings, have created a new understanding of transplant pathology and why transplants fail. Transplant dysfunction is best understood in terms of three elements: diseases, the active injury-repair response and the cumulative burden of injury. Progression to failure is mainly attributable to antibody-mediated rejection, nonadherence and glomerular disease. Antibody-mediated rejection usually develops late due to de novo HLA antibodies, particularly anti-class II, and is often C4d negative. Pure treated T cell-mediated rejection does not predispose to graft loss because it responds well, even with endothelialitis, but it may indicate nonadherence. The cumulative burden of injury results in atrophy-fibrosis (nephron loss), arterial fibrous intimal thickening and arteriolar hyalinosis, but these are not progressive without ongoing disease/injury, and do not explain progression. Calcineurin inhibitor toxicity has been overestimated because burden-of-injury lesions invite this default diagnosis when diseases such as antibody-mediated rejection are missed. Disease/injury triggers a stereotyped active injury-repair response, including de-differentiation, cell cycling and apoptosis. The active injury-repair response is the strongest correlate of organ function and future progression to failure, but should always prompt a search for the initiating injury or disease.

  5. Integration of molecular functions at the ecosystemic level: breakthroughs and future goals of environmental genomics and post-genomics

    PubMed Central

    Vandenkoornhuyse, Philippe; Dufresne, Alexis; Quaiser, Achim; Gouesbet, Gwenola; Binet, Françoise; Francez, André-Jean; Mahé, Stéphane; Bormans, Myriam; Lagadeuc, Yvan; Couée, Ivan

    2010-01-01

    Environmental genomics and genome-wide expression approaches deal with large-scale sequence-based information obtained from environmental samples, at organismal, population or community levels. To date, environmental genomics, transcriptomics and proteomics are arguably the most powerful approaches to discover completely novel ecological functions and to link organismal capabilities, organism–environment interactions, functional diversity, ecosystem processes, evolution and Earth history. Thus, environmental genomics is not merely a toolbox of new technologies but also a source of novel ecological concepts and hypotheses. By removing previous dichotomies between ecophysiology, population ecology, community ecology and ecosystem functioning, environmental genomics enables the integration of sequence-based information into higher ecological and evolutionary levels. However, environmental genomics, along with transcriptomics and proteomics, must involve pluridisciplinary research, such as new developments in bioinformatics, in order to integrate high-throughput molecular biology techniques into ecology. In this review, the validity of environmental genomics and post-genomics for studying ecosystem functioning is discussed in terms of major advances and expectations, as well as in terms of potential hurdles and limitations. Novel avenues for improving the use of these approaches to test theory-driven ecological hypotheses are also explored. PMID:20426792

  6. Assessment of sperm nucleus integrity in infertile men: a novel research field for anthropology in the molecular era.

    PubMed

    Lavranos, Giagkos; Manolakou, Panagiota; Katsiki, Evangelia; Angelopoulou, Roxani

    2013-12-01

    Anthropology has always been particularly interested in the origin of human life and the development towards adulthood. Although originally working with skeletal measurements and bio-morphological markers in modern populations, it has now entered the growing field of applied molecular biology. This relatively recent advance allows the detailed study of major events in human development and senescence. For instance, sperm DNA integrity and chromatin re-organization are crucial factors for fertilization and embryo development. Clinical researchers have developed improved methods for the evaluation of DNA integrity and protaminosis in sperm nuclei, such as the TUNEL and the CMA3 assays. DNA damage in spermatozoal nuclei is detected using the TUNEL assay which depends on the specific enzymatic reaction of TdT with the end strand breaks of DNA. Protaminosis in spermatozoal nucleus is evaluated using CMA3 assay, which is based on the in situ competition between CMA3 and protamines. Such measurements may provide useful data on human reproductive health, aiding the explanation of demographic differences across the world.

  7. A Fully Integrated Paperfluidic Molecular Diagnostic Chip for the Extraction, Amplification, and Detection of Nucleic Acids from Clinical Samples

    PubMed Central

    Rodriguez, Natalia M.; Wong, Winnie S.; Liu, Lena; Dewar, Rajan; Klapperich, Catherine M.

    2016-01-01

    Paper diagnostics have successfully been employed to detect the presence of antigens or small molecules in clinical samples through immunoassays; however, the detection of many disease targets relies on the much higher sensitivity and specificity achieved via nucleic acid amplification tests (NAAT). The steps involved in NAAT have recently begun to be explored in paper matrices, and our group, among others, has reported on paper-based extraction, amplification, and detection of DNA and RNA targets. Here, we integrate these paper-based NAAT steps onto a single paperfluidic chip in a modular, foldable system that allows for fully integrated fluidic handling from sample to result. We showcase the functionality of the chip by combining nucleic acid isolation, isothermal amplification, and lateral flow detection of human papillomavirus (HPV) 16 DNA directly from crude cervical specimens in under 1 hour for rapid, early detection of cervical cancer. The chip is made entirely of paper and adhesive sheets, making it low-cost, portable, and disposable, and offering the potential for a point-of-care molecular diagnostic platform even in remote and resource-limited settings. PMID:26785636

  8. A New Integrated Approach to Taxonomy: The Fusion of Molecular and Morphological Systematics with Type Material in Benthic Foraminifera.

    PubMed

    Roberts, Angela; Austin, William; Evans, Katharine; Bird, Clare; Schweizer, Magali; Darling, Kate

    2016-01-01

    A robust and consistent taxonomy underpins the use of fossil material in palaeoenvironmental research and long-term assessment of biodiversity. This study presents a new integrated taxonomic protocol for benthic foraminifera by unequivocally reconciling the traditional taxonomic name to a specific genetic type. To implement this protocol, a fragment of the small subunit ribosomal RNA (SSU rRNA) gene is used in combination with 16 quantitative morphometric variables to fully characterise the benthic foraminiferal species concept of Elphidium williamsoni Haynes, 1973. A combination of live contemporary topotypic specimens, original type specimens and specimens of genetic outliers were utilised in this study. Through a series of multivariate statistical tests we illustrate that genetically characterised topotype specimens are morphologically congruent with both the holotype and paratype specimens of E. williamsoni Haynes, 1973. We present the first clear link between morphologically characterised type material and the unique SSU rRNA genetic type of E. williamsoni. This example provides a standard framework for the benthic foraminifera which bridges the current discontinuity between molecular and morphological lines of evidence, allowing integration with the traditional Linnaean roots of nomenclature to offer a new prospect for taxonomic stability. PMID:27388271

  9. A New Integrated Approach to Taxonomy: The Fusion of Molecular and Morphological Systematics with Type Material in Benthic Foraminifera

    PubMed Central

    Roberts, Angela; Austin, William; Evans, Katharine; Bird, Clare; Schweizer, Magali; Darling, Kate

    2016-01-01

    A robust and consistent taxonomy underpins the use of fossil material in palaeoenvironmental research and long-term assessment of biodiversity. This study presents a new integrated taxonomic protocol for benthic foraminifera by unequivocally reconciling the traditional taxonomic name to a specific genetic type. To implement this protocol, a fragment of the small subunit ribosomal RNA (SSU rRNA) gene is used in combination with 16 quantitative morphometric variables to fully characterise the benthic foraminiferal species concept of Elphidium williamsoni Haynes, 1973. A combination of live contemporary topotypic specimens, original type specimens and specimens of genetic outliers were utilised in this study. Through a series of multivariate statistical tests we illustrate that genetically characterised topotype specimens are morphologically congruent with both the holotype and paratype specimens of E. williamsoni Haynes, 1973. We present the first clear link between morphologically characterised type material and the unique SSU rRNA genetic type of E. williamsoni. This example provides a standard framework for the benthic foraminifera which bridges the current discontinuity between molecular and morphological lines of evidence, allowing integration with the traditional Linnaean roots of nomenclature to offer a new prospect for taxonomic stability. PMID:27388271

  10. Studies of complex biological systems with applications to molecular medicine: the need to integrate transcriptomic and proteomic approaches.

    PubMed

    Silvestri, Elena; Lombardi, Assunta; de Lange, Pieter; Glinni, Daniela; Senese, Rosalba; Cioffi, Federica; Lanni, Antonia; Goglia, Fernando; Moreno, Maria

    2011-01-01

    Omics approaches to the study of complex biological systems with potential applications to molecular medicine are attracting great interest in clinical as well as in basic biological research. Genomics, transcriptomics and proteomics are characterized by the lack of an a priori definition of scope, and this gives sufficient leeway for investigators (a) to discern all at once a globally altered pattern of gene/protein expression and (b) to examine the complex interactions that regulate entire biological processes. Two popular platforms in "omics" are DNA microarrays, which measure messenger RNA transcript levels, and proteomic analyses, which identify and quantify proteins. Because of their intrinsic strengths and weaknesses, no single approach can fully unravel the complexities of fundamental biological events. However, an appropriate combination of different tools could lead to integrative analyses that would furnish new insights not accessible through one-dimensional datasets. In this review, we will outline some of the challenges associated with integrative analyses relating to the changes in metabolic pathways that occur in complex pathophysiological conditions (viz. ageing and altered thyroid state) in relevant metabolically active tissues. In addition, we discuss several new applications of proteomic analysis to the investigation of mitochondrial activity.

  11. Changes in DNA damage, molecular integrity, and copy number for plastid DNA and mitochondrial DNA during maize development

    PubMed Central

    Kumar, Rachana A.; Oldenburg, Delene J.; Bendich, Arnold J.

    2014-01-01

    The amount and structural integrity of organellar DNAs change during plant development, although the mechanisms of change are poorly understood. Using PCR-based methods, we quantified DNA damage, molecular integrity, and genome copy number for plastid and mitochondrial DNAs of maize seedlings. A DNA repair assay was also used to assess DNA impediments. During development, DNA damage increased and molecules with impediments that prevented amplification by Taq DNA polymerase increased, with light causing the greatest change. DNA copy number values depended on the assay method, with standard real-time quantitative PCR (qPCR) values exceeding those determined by long-PCR by 100- to 1000-fold. As the organelles develop, their DNAs may be damaged in oxidative environments created by photo-oxidative reactions and photosynthetic/respiratory electron transfer. Some molecules may be repaired, while molecules with unrepaired damage may be degraded to non-functional fragments measured by standard qPCR but not by long-PCR. PMID:25261192

  12. [Investigation of molecular machine that integrates microtubules depolymerization and chromosomes movement in mitosis].

    PubMed

    Volkov, V A; Ataullakhanov, F I

    2013-02-01

    The main goal of a dividing cell is to distribute its genetic material equally between two daughter cells. Each of the two sister chromatids comprising each chromosome should go into one of the daughter cells. This is possible thanks to polar protein polymers called microtubules, which form a structure called "spindle" during mitosis. Microtubules are one of the basic elements of the cytoskeleton, but at the same time they are highly dynamic. Minus ends of the microtubules attach to the two poles of the spindle, while their plus ends are constantly growing or shrinking, and are also able to attach to the chromosomes and to move them. Chromosomes attach to the microtubule ends with a special protein super-complex called kinetochore. Each sister chromatid in a pair attaches to the microtubules emanating from a corresponding spindle pole. Kinetochores are attached to the dynamic plus ends of the microtubules, but tubulin subunits are still able to attach and detach to these attached ends. One of the most important questions in mitosis is understanding of the mechanism that allows such attachment to be stable (since unstable attachments lead to chromosome loss and aneuploidy) yet dynamic (arrest of the microtubule dynamics stops mitosis). More than 100 proteins comprising the kinetochore are known today, but there is no clear mechanical view on the molecular machine that forms kinetochore-microtubule attachment. The difficulties in understanding this mechanism are due to the variety of theoretical views on the principle of such machine, as well as limited number of biochemically isolated candidates to test these hypotheses experimentally. Therefore, investigation of the properties of putative couplers of microtubule depolymerization and chromosome movement is an important task.

  13. Deciphering the origin of the 2012 cholera epidemic in Guinea by integrating epidemiological and molecular analyses.

    PubMed

    Rebaudet, Stanislas; Mengel, Martin A; Koivogui, Lamine; Moore, Sandra; Mutreja, Ankur; Kande, Yacouba; Yattara, Ousmane; Sarr Keita, Véronique; Njanpop-Lafourcade, Berthe-Marie; Fournier, Pierre-Edouard; Garnotel, Eric; Keita, Sakoba; Piarroux, Renaud

    2014-06-01

    Cholera is typically considered endemic in West Africa, especially in the Republic of Guinea. However, a three-year lull period was observed from 2009 to 2011, before a new epidemic struck the country in 2012, which was officially responsible for 7,350 suspected cases and 133 deaths. To determine whether cholera re-emerged from the aquatic environment or was rather imported due to human migration, a comprehensive epidemiological and molecular survey was conducted. A spatiotemporal analysis of the national case databases established Kaback Island, located off the southern coast of Guinea, as the initial focus of the epidemic in early February. According to the field investigations, the index case was found to be a fisherman who had recently arrived from a coastal district of neighboring Sierra Leone, where a cholera outbreak had recently occurred. MLVA-based genotype mapping of 38 clinical Vibrio cholerae O1 El Tor isolates sampled throughout the epidemic demonstrated a progressive genetic diversification of the strains from a single genotype isolated on Kaback Island in February, which correlated with spatial epidemic spread. Whole-genome sequencing characterized this strain as an "atypical" El Tor variant. Furthermore, genome-wide SNP-based phylogeny analysis grouped the Guinean strain into a new clade of the third wave of the seventh pandemic, distinct from previously analyzed African strains and directly related to a Bangladeshi isolate. Overall, these results highly suggest that the Guinean 2012 epidemic was caused by a V. cholerae clone that was likely imported from Sierra Leone by an infected individual. These results indicate the importance of promoting the cross-border identification and surveillance of mobile and vulnerable populations, including fishermen, to prevent, detect and control future epidemics in the region. Comprehensive epidemiological investigations should be expanded to better understand cholera dynamics and improve disease control

  14. Actin Immobilization on Chitin for Purifying Myosin II: A Laboratory Exercise That Integrates Concepts of Molecular Cell Biology and Protein Chemistry

    ERIC Educational Resources Information Center

    de Souza, Marcelle Gomes; Grossi, Andre Luiz; Pereira, Elisangela Lima Bastos; da Cruz, Carolina Oliveira; Mendes, Fernanda Machado; Cameron, Luiz Claudio; Paiva, Carmen Lucia Antao

    2008-01-01

    This article presents our experience on teaching biochemical sciences through an innovative approach that integrates concepts of molecular cell biology and protein chemistry. This original laboratory exercise is based on the preparation of an affinity chromatography column containing F-actin molecules immobilized on chitin particles for purifying…

  15. Comparative molecular developmental aspects of the mammalian- and the avian lungs, and the insectan tracheal system by branching morphogenesis: recent advances and future directions

    PubMed Central

    2012-01-01

    Gas exchangers fundamentally form by branching morphogenesis (BM), a mechanistically profoundly complex process which derives from coherent expression and regulation of multiple genes that direct cell-to-cell interactions, differentiation, and movements by signaling of various molecular morphogenetic cues at specific times and particular places in the developing organ. Coordinated expression of growth-instructing factors determines sizes and sites where bifurcation occurs, by how much a part elongates before it divides, and the angle at which branching occurs. BM is essentially induced by dualities of factors where through feedback- or feed forward loops agonists/antagonists are activated or repressed. The intricate transactions between the development orchestrating molecular factors determine the ultimate phenotype. From the primeval time when the transformation of unicellular organisms to multicellular ones occurred by systematic accretion of cells, BM has been perpetually conserved. Canonical signalling, transcriptional pathways, and other instructive molecular factors are commonly employed within and across species, tissues, and stages of development. While much still remain to be elucidated and some of what has been reported corroborated and reconciled with rest of existing data, notable progress has in recent times been made in understanding the mechanism of BM. By identifying and characterizing the morphogenetic drivers, and markers and their regulatory dynamics, the elemental underpinnings of BM have been more precisely explained. Broadening these insights will allow more effective diagnostic and therapeutic interventions of developmental abnormalities and pathologies in pre- and postnatal lungs. Conservation of the molecular factors which are involved in the development of the lung (and other branched organs) is a classic example of nature’s astuteness in economically utilizing finite resources. Once purposefully formed, well-tested and tried ways and

  16. Selective detection of gas-phase TNT by integrated optical waveguide spectrometry using molecularly imprinted sol-gel sensing films.

    PubMed

    Walker, Natalie R; Linman, Matthew J; Timmers, Margaret M; Dean, Stacey L; Burkett, Colleen M; Lloyd, Julie A; Keelor, Joel D; Baughman, Brandi M; Edmiston, Paul L

    2007-06-12

    A chemical sensor was developed to detect the explosive 2,4,6-trinitrotoluene (TNT) utilizing planar integrated optical waveguide (IOW) attenuated total reflection spectrometry. Submicron thick films of organically modified sol-gel polymers were deposited on the waveguide surface as the sensing layer. Sol-gels were molecularly imprinted for TNT using covalently bound template molecules linked to the matrix through 1 or 2 carbamate linkages. Upon chemical cleavage of the template and displacement of the TNT-like pendant groups from the matrix, shape-selective binding sites were created that possess a primary amine group. The amine was used to deprotonate bound TNT yielding an anionic form that absorbs visible light. Binding of TNT and subsequent conversion to the anion results in the attenuation of light propagating through the waveguide, thus creating a spectrophotometric device. Sensitivity can be achieved by taking advantage of the substantial pathlength provided by the use of single mode IOWs. The limit-of-detection to gas-phase TNT was found to be five parts-per-billion (ppbV) in ambient air at a flow rate of 40 mL min(-1) given a 60 s sampling time. The sensor is highly selective for TNT due to the selectivity of binding site recognition of TNT and the subsequent generation of the TNT anion. Response to TNT is not reversible which results in an integrating sensor device which, in theory, can improve the ability to detect small amounts of the explosive if the exposure time is sufficient in length.

  17. Förster resonant energy transfer from an inorganic quantum well to a molecular material: Unexplored aspects, losses, and implications to applications

    SciTech Connect

    Itskos, G.; Othonos, A.; Choulis, S. A.; Iliopoulos, E.

    2015-12-07

    A systematic investigation of Förster resonant energy transfer (FRET) is reported within a hybrid prototype structure based on nitride single quantum well (SQW) donors and light emitting polymer acceptors. Self-consistent Schrödinger-Poisson modeling and steady-state and time-resolved photoluminescence experiments were initially employed to investigate the influence of a wide structural parameter space on the emission quantum yield of the nitride component. The optimized SQW heterostructures were processed into hybrid structures with spin-casted overlayers of polyfluorenes. The influence of important unexplored aspects of the inorganic heterostructure such as SQW confinement, content, and doping on the dipole-dipole coupling was probed. Competing mechanisms to the FRET process associated with interfacial recombination and charge transfer have been studied and their implications to device applications exploiting FRET across heterointerfaces have been discussed.

  18. Molecular mechanism of Spinocerebellar Ataxia type 6: glutamine repeat disorder, channelopathy and transcriptional dysregulation. The multifaceted aspects of a single mutation.

    PubMed

    Giunti, Paola; Mantuano, Elide; Frontali, Marina; Veneziano, Liana

    2015-01-01

    Spinocerebellar Ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative disease characterized by late onset, slowly progressive, mostly pure cerebellar ataxia. It is one of three allelic disorders associated to CACNA1A gene, coding for the Alpha1 A subunit of P/Q type calcium channel Cav2.1 expressed in the brain, particularly in the cerebellum. The other two disorders are Episodic Ataxia type 2 (EA2), and Familial Hemiplegic Migraine type 1 (FHM1). These disorders show distinct phenotypes that often overlap but have different pathogenic mechanisms. EA2 and FHM1 are due to mutations causing, respectively, a loss and a gain of channel function. SCA6, instead, is associated with short expansions of a polyglutamine stretch located in the cytoplasmic C-terminal tail of the protein. This domain has a relevant role in channel regulation, as well as in transcription regulation of other neuronal genes; thus the SCA6 CAG repeat expansion results in complex pathogenic molecular mechanisms reflecting the complex Cav2.1 C-terminus activity. We will provide a short review for an update on the SCA6 molecular mechanism.

  19. A derivation of centroid molecular dynamics and other approximate time evolution methods for path integral centroid variables

    NASA Astrophysics Data System (ADS)

    Jang, Seogjoo; Voth, Gregory A.

    1999-08-01

    Several methods to approximately evolve path integral centroid variables in real time are presented in this paper, the first of which, the centroid molecular dynamics (CMD) method, is recast into the new formalism of the preceding paper and thereby derived. The approximations involved in the CMD method are thus fully characterized by mathematical derivations. Additional new approaches are also presented: centroid Hamiltonian dynamics (CHD), linearized quantum dynamics (LQD), and a perturbative correction of the LQD method (PT-LQD). The CHD method is shown to be a variation of the CMD method which conserves the approximate time dependent centroid Hamiltonian. The LQD method amounts to a linear approximation for the quantum Liouville equation, while the PT-LQD method includes a perturbative correction to the LQD method. All of these approaches are then tested for the equilibrium position correlation functions of three different one-dimensional nondissipative model systems, and it is shown that certain quantum effects are accounted for by all of them, while others, such as the long time coherence characteristic of low-dimensional nondissipative systems, are not. The CMD method is found to be consistently better than the LQD method, while the PT-LQD method improves the latter and is better than the CMD method in most cases. The CHD method gives results complementary to those of the CMD method.

  20. Investigating the Complex Chemistry of Functional Energy Storage Systems: The Need for an Integrative, Multiscale (Molecular to Mesoscale) Perspective

    PubMed Central

    2016-01-01

    Electric energy storage systems such as batteries can significantly impact society in a variety of ways, including facilitating the widespread deployment of portable electronic devices, enabling the use of renewable energy generation for local off grid situations and providing the basis of highly efficient power grids integrated with energy production, large stationary batteries, and the excess capacity from electric vehicles. A critical challenge for electric energy storage is understanding the basic science associated with the gap between the usable output of energy storage systems and their theoretical energy contents. The goal of overcoming this inefficiency is to achieve more useful work (w) and minimize the generation of waste heat (q). Minimization of inefficiency can be approached at the macro level, where bulk parameters are identified and manipulated, with optimization as an ultimate goal. However, such a strategy may not provide insight toward the complexities of electric energy storage, especially the inherent heterogeneity of ion and electron flux contributing to the local resistances at numerous interfaces found at several scale lengths within a battery. Thus, the ability to predict and ultimately tune these complex systems to specific applications, both current and future, demands not just parametrization at the bulk scale but rather specific experimentation and understanding over multiple length scales within the same battery system, from the molecular scale to the mesoscale. Herein, we provide a case study examining the insights and implications from multiscale investigations of a prospective battery material, Fe3O4. PMID:27413781

  1. MutAid: Sanger and NGS Based Integrated Pipeline for Mutation Identification, Validation and Annotation in Human Molecular Genetics

    PubMed Central

    Pandey, Ram Vinay; Pabinger, Stephan; Kriegner, Albert; Weinhäusel, Andreas

    2016-01-01

    Traditional Sanger sequencing as well as Next-Generation Sequencing have been used for the identification of disease causing mutations in human molecular research. The majority of currently available tools are developed for research and explorative purposes and often do not provide a complete, efficient, one-stop solution. As the focus of currently developed tools is mainly on NGS data analysis, no integrative solution for the analysis of Sanger data is provided and consequently a one-stop solution to analyze reads from both sequencing platforms is not available. We have therefore developed a new pipeline called MutAid to analyze and interpret raw sequencing data produced by Sanger or several NGS sequencing platforms. It performs format conversion, base calling, quality trimming, filtering, read mapping, variant calling, variant annotation and analysis of Sanger and NGS data under a single platform. It is capable of analyzing reads from multiple patients in a single run to create a list of potential disease causing base substitutions as well as insertions and deletions. MutAid has been developed for expert and non-expert users and supports four sequencing platforms including Sanger, Illumina, 454 and Ion Torrent. Furthermore, for NGS data analysis, five read mappers including BWA, TMAP, Bowtie, Bowtie2 and GSNAP and four variant callers including GATK-HaplotypeCaller, SAMTOOLS, Freebayes and VarScan2 pipelines are supported. MutAid is freely available at https://sourceforge.net/projects/mutaid. PMID:26840129

  2. Path integral Monte Carlo study of hydrogen tunneling effect on dielectric properties of molecular crystal 5-Bromo-9-hydroxyphenalenone

    NASA Astrophysics Data System (ADS)

    Otaki, Hiroki; Ando, Koji

    2015-01-01

    The dielectric properties of proton(H)-deuteron(D) mixed crystals of the hydrogen-bonded material 5-Bromo-9-hydroxyphenalenone are studied using a novel path integral Monte Carlo (PIMC) method that takes account of the dipole induction effect depending on the relative proton configurations in the surrounding molecules. The induced dipole is evaluated using the fragment molecular orbital method with electron correlation included by second-order Møller-Plesset perturbation theory and long-range corrected density functional theory. The results show a greater influence of Csbnd H ⋯O intermolecular weak hydrogen bonding on the induction than for results evaluated with the Hartree-Fock method. The induction correction is incorporated into the PIMC simulations with a model Hamiltonian that consists of long-range dipolar interactions and a transverse term describing proton tunneling. The relationship between the calculated phase transition temperature and H/D mixing ratio is consistent with the experimental phase diagram, indicating that the balance between the proton tunneling and the collective ordering is appropriately described.

  3. MutAid: Sanger and NGS Based Integrated Pipeline for Mutation Identification, Validation and Annotation in Human Molecular Genetics.

    PubMed

    Pandey, Ram Vinay; Pabinger, Stephan; Kriegner, Albert; Weinhäusel, Andreas

    2016-01-01

    Traditional Sanger sequencing as well as Next-Generation Sequencing have been used for the identification of disease causing mutations in human molecular research. The majority of currently available tools are developed for research and explorative purposes and often do not provide a complete, efficient, one-stop solution. As the focus of currently developed tools is mainly on NGS data analysis, no integrative solution for the analysis of Sanger data is provided and consequently a one-stop solution to analyze reads from both sequencing platforms is not available. We have therefore developed a new pipeline called MutAid to analyze and interpret raw sequencing data produced by Sanger or several NGS sequencing platforms. It performs format conversion, base calling, quality trimming, filtering, read mapping, variant calling, variant annotation and analysis of Sanger and NGS data under a single platform. It is capable of analyzing reads from multiple patients in a single run to create a list of potential disease causing base substitutions as well as insertions and deletions. MutAid has been developed for expert and non-expert users and supports four sequencing platforms including Sanger, Illumina, 454 and Ion Torrent. Furthermore, for NGS data analysis, five read mappers including BWA, TMAP, Bowtie, Bowtie2 and GSNAP and four variant callers including GATK-HaplotypeCaller, SAMTOOLS, Freebayes and VarScan2 pipelines are supported. MutAid is freely available at https://sourceforge.net/projects/mutaid.

  4. Fast and General Method To Predict the Physicochemical Properties of Druglike Molecules Using the Integral Equation Theory of Molecular Liquids.

    PubMed

    Palmer, David S; Mišin, Maksim; Fedorov, Maxim V; Llinas, Antonio

    2015-09-01

    We report a method to predict physicochemical properties of druglike molecules using a classical statistical mechanics based solvent model combined with machine learning. The RISM-MOL-INF method introduced here provides an accurate technique to characterize solvation and desolvation processes based on solute-solvent correlation functions computed by the 1D reference interaction site model of the integral equation theory of molecular liquids. These functions can be obtained in a matter of minutes for most small organic and druglike molecules using existing software (RISM-MOL) (Sergiievskyi, V. P.; Hackbusch, W.; Fedorov, M. V. J. Comput. Chem. 2011, 32, 1982-1992). Predictions of caco-2 cell permeability and hydration free energy obtained using the RISM-MOL-INF method are shown to be more accurate than the state-of-the-art tools for benchmark data sets. Due to the importance of solvation and desolvation effects in biological systems, it is anticipated that the RISM-MOL-INF approach will find many applications in biophysical and biomedical property prediction. PMID:26212723

  5. Investigating the Complex Chemistry of Functional Energy Storage Systems: The Need for an Integrative, Multiscale (Molecular to Mesoscale) Perspective.

    PubMed

    Abraham, Alyson; Housel, Lisa M; Lininger, Christianna N; Bock, David C; Jou, Jeffrey; Wang, Feng; West, Alan C; Marschilok, Amy C; Takeuchi, Kenneth J; Takeuchi, Esther S

    2016-06-22

    Electric energy storage systems such as batteries can significantly impact society in a variety of ways, including facilitating the widespread deployment of portable electronic devices, enabling the use of renewable energy generation for local off grid situations and providing the basis of highly efficient power grids integrated with energy production, large stationary batteries, and the excess capacity from electric vehicles. A critical challenge for electric energy storage is understanding the basic science associated with the gap between the usable output of energy storage systems and their theoretical energy contents. The goal of overcoming this inefficiency is to achieve more useful work (w) and minimize the generation of waste heat (q). Minimization of inefficiency can be approached at the macro level, where bulk parameters are identified and manipulated, with optimization as an ultimate goal. However, such a strategy may not provide insight toward the complexities of electric energy storage, especially the inherent heterogeneity of ion and electron flux contributing to the local resistances at numerous interfaces found at several scale lengths within a battery. Thus, the ability to predict and ultimately tune these complex systems to specific applications, both current and future, demands not just parametrization at the bulk scale but rather specific experimentation and understanding over multiple length scales within the same battery system, from the molecular scale to the mesoscale. Herein, we provide a case study examining the insights and implications from multiscale investigations of a prospective battery material, Fe3O4. PMID:27413781

  6. Ricebase: a breeding and genetics platform for rice, integrating individual molecular markers, pedigrees and whole-genome-based data.

    PubMed

    Edwards, J D; Baldo, A M; Mueller, L A

    2016-01-01

    Ricebase (http://ricebase.org) is an integrative genomic database for rice (Oryza sativa) with an emphasis on combining datasets in a way that maintains the key links between past and current genetic studies. Ricebase includes DNA sequence data, gene annotations, nucleotide variation data and molecular marker fragment size data. Rice research has benefited from early adoption and extensive use of simple sequence repeat (SSR) markers; however, the majority of rice SSR markers were developed prior to the latest rice pseudomolecule assembly. Interpretation of new research using SNPs in the context of literature citing SSRs requires a common coordinate system. A new pipeline, using a stepwise relaxation of stringency, was used to map SSR primers onto the latest rice pseudomolecule assembly. The SSR markers and experimentally assayed amplicon sizes are presented in a relational database with a web-based front end, and are available as a track loaded in a genome browser with links connecting the browser and database. The combined capabilities of Ricebase link genetic markers, genome context, allele states across rice germplasm and potentially user curated phenotypic interpretations as a community resource for genetic discovery and breeding in rice. PMID:27515824

  7. Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes: molecular insight into sex-specific processes and translational repression.

    PubMed

    Lasonder, Edwin; Rijpma, Sanna R; van Schaijk, Ben C L; Hoeijmakers, Wieteke A M; Kensche, Philip R; Gresnigt, Mark S; Italiaander, Annet; Vos, Martijn W; Woestenenk, Rob; Bousema, Teun; Mair, Gunnar R; Khan, Shahid M; Janse, Chris J; Bártfai, Richárd; Sauerwein, Robert W

    2016-07-27

    Sexual differentiation of malaria parasites into gametocytes in the vertebrate host and subsequent gamete fertilization in mosquitoes is essential for the spreading of the disease. The molecular processes orchestrating these transitions are far from fully understood. Here, we report the first transcriptome analysis of male and female Plasmodium falciparum gametocytes coupled with a comprehensive proteome analysis. In male gametocytes there is an enrichment of proteins involved in the formation of flagellated gametes; proteins involved in DNA replication, chromatin organization and axoneme formation. On the other hand, female gametocytes are enriched in proteins required for zygote formation and functions after fertilization; protein-, lipid- and energy-metabolism. Integration of transcriptome and proteome data revealed 512 highly expressed maternal transcripts without corresponding protein expression indicating large scale translational repression in P. falciparum female gametocytes for the first time. Despite a high degree of conservation between Plasmodium species, 260 of these 'repressed transcripts' have not been previously described. Moreover, for some of these genes, protein expression is only reported in oocysts and sporozoites indicating that repressed transcripts can be partitioned into short- and long-term storage. Finally, these data sets provide an essential resource for identification of vaccine/drug targets and for further mechanistic studies. PMID:27298255

  8. Fast and General Method To Predict the Physicochemical Properties of Druglike Molecules Using the Integral Equation Theory of Molecular Liquids.

    PubMed

    Palmer, David S; Mišin, Maksim; Fedorov, Maxim V; Llinas, Antonio

    2015-09-01

    We report a method to predict physicochemical properties of druglike molecules using a classical statistical mechanics based solvent model combined with machine learning. The RISM-MOL-INF method introduced here provides an accurate technique to characterize solvation and desolvation processes based on solute-solvent correlation functions computed by the 1D reference interaction site model of the integral equation theory of molecular liquids. These functions can be obtained in a matter of minutes for most small organic and druglike molecules using existing software (RISM-MOL) (Sergiievskyi, V. P.; Hackbusch, W.; Fedorov, M. V. J. Comput. Chem. 2011, 32, 1982-1992). Predictions of caco-2 cell permeability and hydration free energy obtained using the RISM-MOL-INF method are shown to be more accurate than the state-of-the-art tools for benchmark data sets. Due to the importance of solvation and desolvation effects in biological systems, it is anticipated that the RISM-MOL-INF approach will find many applications in biophysical and biomedical property prediction.

  9. Ricebase: a breeding and genetics platform for rice, integrating individual molecular markers, pedigrees and whole-genome-based data

    PubMed Central

    Edwards, J. D.; Baldo, A. M.; Mueller, L. A.

    2016-01-01

    Ricebase (http://ricebase.org) is an integrative genomic database for rice (Oryza sativa) with an emphasis on combining datasets in a way that maintains the key links between past and current genetic studies. Ricebase includes DNA sequence data, gene annotations, nucleotide variation data and molecular marker fragment size data. Rice research has benefited from early adoption and extensive use of simple sequence repeat (SSR) markers; however, the majority of rice SSR markers were developed prior to the latest rice pseudomolecule assembly. Interpretation of new research using SNPs in the context of literature citing SSRs requires a common coordinate system. A new pipeline, using a stepwise relaxation of stringency, was used to map SSR primers onto the latest rice pseudomolecule assembly. The SSR markers and experimentally assayed amplicon sizes are presented in a relational database with a web-based front end, and are available as a track loaded in a genome browser with links connecting the browser and database. The combined capabilities of Ricebase link genetic markers, genome context, allele states across rice germplasm and potentially user curated phenotypic interpretations as a community resource for genetic discovery and breeding in rice. PMID:27515824

  10. Investigating the Complex Chemistry of Functional Energy Storage Systems: The Need for an Integrative, Multiscale (Molecular to Mesoscale) Perspective.

    PubMed

    Abraham, Alyson; Housel, Lisa M; Lininger, Christianna N; Bock, David C; Jou, Jeffrey; Wang, Feng; West, Alan C; Marschilok, Amy C; Takeuchi, Kenneth J; Takeuchi, Esther S

    2016-06-22

    Electric energy storage systems such as batteries can significantly impact society in a variety of ways, including facilitating the widespread deployment of portable electronic devices, enabling the use of renewable energy generation for local off grid situations and providing the basis of highly efficient power grids integrated with energy production, large stationary batteries, and the excess capacity from electric vehicles. A critical challenge for electric energy storage is understanding the basic science associated with the gap between the usable output of energy storage systems and their theoretical energy contents. The goal of overcoming this inefficiency is to achieve more useful work (w) and minimize the generation of waste heat (q). Minimization of inefficiency can be approached at the macro level, where bulk parameters are identified and manipulated, with optimization as an ultimate goal. However, such a strategy may not provide insight toward the complexities of electric energy storage, especially the inherent heterogeneity of ion and electron flux contributing to the local resistances at numerous interfaces found at several scale lengths within a battery. Thus, the ability to predict and ultimately tune these complex systems to specific applications, both current and future, demands not just parametrization at the bulk scale but rather specific experimentation and understanding over multiple length scales within the same battery system, from the molecular scale to the mesoscale. Herein, we provide a case study examining the insights and implications from multiscale investigations of a prospective battery material, Fe3O4.

  11. Integrated microfluidic system with automatic sampling for permanent molecular and antigen-based detection of CBRNE-related pathogens

    NASA Astrophysics Data System (ADS)

    Becker, Holger; Schattschneider, Sebastian; Klemm, Richard; Hlawatsch, Nadine; Gärtner, Claudia

    2015-03-01

    The continuous monitoring of the environment for lethal pathogens is a central task in the field of biothreat detection. Typical scenarios involve air-sampling in locations such as public transport systems or large public events and a subsequent analysis of the samples by a portable instrument. Lab-on-a-chip technologies are one of the promising technological candidates for such a system. We have developed an integrated microfluidic system with automatic sampling for the detection of CBRNE-related pathogens. The chip contains a two-pronged analysis strategy, on the one hand an immunological track using antibodies immobilized on a frit and a subsequent photometric detection, on the other hand a molecular biology approach using continuous-flow PCR with a fluorescence end-point detection. The cartridge contains two-component molded rotary valve to allow active fluid control and switching between channels. The accompanying instrument contains all elements for fluidic and valve actuation, thermal control, as well as the two detection modalities. Reagents are stored in dedicated reagent packs which are connected directly to the cartridge. With this system, we have been able to demonstrate the detection of a variety of pathogen species.

  12. Many-electron aspects of molecular promotion in ion-atom collisions - Production of core-excited states of Li in Li/+/-He collisions

    NASA Technical Reports Server (NTRS)

    Elston, S. B.; Vane, C. R.; Schumann, S.

    1979-01-01

    Production of core-excited autoionizing states of neutral Li having configurations of the form 1snln(prime)l(prime) has been observed over the impact-energy range from 10-50 keV. Although the results for production of all such states is remarkably consistent with a quasi-molecular-excitation model proposed by Stolterfoht and Leithaeuser (1976), production of individual lines in the observed spectra exhibits collision-velocity dependencies indicative of considerably more complex processes, including processes which appear to be inherently two-electron in nature. Excitation functions are presented for (1s2s/2/)/2/S, 1s(2s2p/3/P)/2/P, 1s(2s2p/1/P)/2/P, and (1s2p/2/)/2/D core-excited state of Li and for total core excitation.

  13. (Molecular studies of functional aspects of higher plant mitochrondria): Annual progress report covering the period August 1, 1987--March 15, 1988

    SciTech Connect

    Siedow, J.N.

    1988-01-01

    A 13 kDa protein, encoded by a gene specifically associated with the mitochondrial genome of Zea maize containing the cms-T trait, has been correlated susceptibility of maize to infection by the fungal pathogen, Biopolaris maydis, race T. Additional work had indicated that mitochondria from cms-T plants were specifically sensitive to BmT toxin produced by this fungus, such that addition of BmT toxin to cms-T maize mitochondria induced a massive leakage of low molecular weight. The gene encoding the 13 kDa polypeptide (urf13-T) was cloned into E. coli using the pATH-3 expression vector under control of the trp promoter.

  14. Regulatory aspects

    NASA Astrophysics Data System (ADS)

    Stern, Arthur M.

    1986-07-01

    At this time, there is no US legislation that is specifically aimed at regulating the environmental release of genetically engineered organisms or their modified components, either during the research and development stage or during application. There are some statutes, administered by several federal agencies, whose language is broad enough to allow the extension of intended coverage to include certain aspects of biotechnology. The one possible exception is FIFRA, which has already brought about the registration of several natural microbial pesticides but which also has provision for requiring the registration of “strain improved” microbial pesticides. Nevertheless, there may be gaps in coverage even if all pertinent statutes were to be actively applied to the control of environmental release of genetically modified substances. The decision to regulate biotechnology under TSCA was justified, in part, on the basis of its intended role as a gap-filling piece of environmental legislation. The advantage of regulating biotechnology under TSCA is that this statute, unlike others, is concerned with all media of exposure (air, water, soil, sediment, biota) that may pose health and environmental hazards. Experience may show that extending existing legislation to regulate biotechnology is a poor compromise compared to the promulgation of new legislation specifically designed for this purpose. It appears that many other countries are ultimately going to take the latter course to regulate biotechnology.

  15. Theoretical aspects of immunity.

    PubMed

    Deem, Michael W; Hejazi, Pooya

    2010-01-01

    The immune system recognizes a myriad of invading pathogens and their toxic products. It does so with a finite repertoire of antibodies and T cell receptors. We here describe theories that quantify the dynamics of the immune system. We describe how the immune system recognizes antigens by searching the large space of receptor molecules. We consider in some detail the theories that quantify the immune response to influenza and dengue fever. We review theoretical descriptions of the complementary evolution of pathogens that occurs in response to immune system pressure. Methods including bioinformatics, molecular simulation, random energy models, and quantum field theory contribute to a theoretical understanding of aspects of immunity.

  16. Apportioning sources of organic matter in streambed sediments: an integrated molecular and compound-specific stable isotope approach.

    PubMed

    Cooper, Richard J; Pedentchouk, Nikolai; Hiscock, Kevin M; Disdle, Paul; Krueger, Tobias; Rawlins, Barry G

    2015-07-01

    clearly demonstrate the effectiveness of an integrated molecular and stable isotope analysis for quantitatively apportioning, with uncertainty, plant-specific organic matter contributions to streambed sediments via a Bayesian mixing model approach. PMID:25817221

  17. Molecular Aspects of the Interaction of Iminium and Alkanolamine Forms of the Anticancer Alkaloid Chelerythrine with Plasma Protein Bovine Serum Albumin.

    PubMed

    Bhuiya, Sutanwi; Pradhan, Ankur Bikash; Haque, Lucy; Das, Suman

    2016-01-14

    The interaction between a quaternary benzophenanthridine alkaloid chelerythrine (herein after, CHL) and bovine serum albumin (herein after, BSA) was probed by employing various spectroscopic tools and isothermal titration calorimetry (ITC). Fluorescence studies revealed that the binding affinity of the alkanolamine form of the CHL is higher compared to the iminium counterpart. This was further established by fluorescence polarization anisotropy measurement and ITC. Fluorescence quenching study along with time-resolved fluorescence measurements establish that both forms of CHL quenched the fluorescence intensity of BSA through the mechanism of static quenching. Site selective binding and molecular modeling studies revealed that the alkaloid binds predominantly in the BSA subdomain IIA by electrostatic and hydrophobic forces. From Forster resonance energy transfer (FRET) studies, the average distances between the protein donor and the alkaloid acceptor were found to be 2.71 and 2.30 nm between tryptophan (Trp) 212 (donor) and iminium and alkanolamine forms (acceptor), respectively. Circular dichroism (CD) study demonstrated that the α-helical organization of the protein is reduced due to binding with CHL along with an increase in the coiled structure. This is indicative of a small but definitive partial unfolding of the protein. Thermodynamic parameters obtained from ITC experiments revealed that the interaction is favored by negative enthalpy change and positive entropy change. PMID:26653994

  18. Molecular aspects of the Eu3+/Eu2+ redox reaction at the interface between a molten salt and a metallic electrode

    NASA Astrophysics Data System (ADS)

    Pounds, Michael A.; Salanne, Mathieu; Madden, Paul A.

    2015-09-01

    We perform molecular dynamics simulations of a system consisting of Eu3+ and Eu2+ species dissolved in a high-temperature KCl electrolyte between two metallic electrodes. The interaction potential includes ion polarisation effects, and a constant electric potential is maintained within the electrodes by allowing the atomic charges to fluctuate in response to the environment. This setup allows us to study the electrochemical Eu3+/Eu2+ reaction in the framework of Marcus theory. Numerous studies have pointed to the highly structured nature of ionic liquids and molten salts close to solid surfaces which is not accounted for in the conventional mean-field description of this interface that underpins the theories of electrochemical reaction rates. Here we examine the influence on the kinetics of the charge-transfer event of the electrical potential across the electrode-electrolyte interface and on the effect of the presence of charged surface on the coordination structure and energetics of the ions in the region important for the charge-transfer event.

  19. Molecular dynamics simulations and structure-based network analysis reveal structural and functional aspects of G-protein coupled receptor dimer interactions.

    PubMed

    Baltoumas, Fotis A; Theodoropoulou, Margarita C; Hamodrakas, Stavros J

    2016-06-01

    A significant amount of experimental evidence suggests that G-protein coupled receptors (GPCRs) do not act exclusively as monomers but also form biologically relevant dimers and oligomers. However, the structural determinants, stoichiometry and functional importance of GPCR oligomerization remain topics of intense speculation. In this study we attempted to evaluate the nature and dynamics of GPCR oligomeric interactions. A representative set of GPCR homodimers were studied through Coarse-Grained Molecular Dynamics simulations, combined with interface analysis and concepts from network theory for the construction and analysis of dynamic structural networks. Our results highlight important structural determinants that seem to govern receptor dimer interactions. A conserved dynamic behavior was observed among different GPCRs, including receptors belonging in different GPCR classes. Specific GPCR regions were highlighted as the core of the interfaces. Finally, correlations of motion were observed between parts of the dimer interface and GPCR segments participating in ligand binding and receptor activation, suggesting the existence of mechanisms through which dimer formation may affect GPCR function. The results of this study can be used to drive experiments aimed at exploring GPCR oligomerization, as well as in the study of transmembrane protein-protein interactions in general.

  20. The genetic basis of inherited anomalies of the teeth. Part 1: clinical and molecular aspects of non-syndromic dental disorders.

    PubMed

    Bailleul-Forestier, Isabelle; Molla, Muriel; Verloes, Alain; Berdal, Ariane

    2008-01-01

    The genetic control of dental development represents a complex series of events, which can very schematically be divided in two pathways: specification of type, size and position of each dental organ, and specific processes for the formation of enamel and dentin. Several genes linked with early tooth positioning and development, belong to signalling pathways and have morphogenesis regulatory functions in morphogenesis of other organs where they are associated with the signalling pathways. Their mutations often show pleïotropic effects beyond dental morphogenesis resulting in syndromic developmental disorders. Some genes affecting early tooth development (MSX1, AXIN2) are associated with tooth agenesis and systemic features (cleft palate, colorectal cancer). By contrast, genes involved in enamel (AMELX, ENAM, MMP20, and KLK4) and dentin (DSPP) structures are highly specific for tooth. Mutations in these genes have been identified as causes of amelogenesis imperfecta, dentinogenesis imperfecta, dentin dysplasias and anomalies of teeth number (hypo-, oligo and anodontia), which only partially overlap with the classical phenotypic classifications of dental disorders. This review of genetic basis of inherited anomalies describes, in this first paper, the molecular bases and clinical features of inherited non-syndromic teeth disorders. And in a second part, the review focus on genetic syndromes with dental involvement. PMID:18499550

  1. An RNA Sequencing Transcriptome Analysis Reveals Novel Insights into Molecular Aspects of the Nitrate Impact on the Nodule Activity of Medicago truncatula1[W

    PubMed Central

    Cabeza, Ricardo; Koester, Beke; Liese, Rebecca; Lingner, Annika; Baumgarten, Vanessa; Dirks, Jan; Salinas-Riester, Gabriela; Pommerenke, Claudia; Dittert, Klaus; Schulze, Joachim

    2014-01-01

    The mechanism through which nitrate reduces the activity of legume nodules is controversial. The objective of the study was to follow Medicago truncatula nodule activity after nitrate provision continuously and to identify molecular mechanisms, which down-regulate the activity of the nodules. Nodule H2 evolution started to decline after about 4 h of nitrate application. At that point in time, a strong shift in nodule gene expression (RNA sequencing) had occurred (1,120 differentially expressed genes). The most pronounced effect was the down-regulation of 127 genes for nodule-specific cysteine-rich peptides. Various other nodulins were also strongly down-regulated, in particular all the genes for leghemoglobins. In addition, shifts in the expression of genes involved in cellular iron allocation and mitochondrial ATP synthesis were observed. Furthermore, the expression of numerous genes for the formation of proteins and glycoproteins with no obvious function in nodules (e.g. germins, patatin, and thaumatin) was strongly increased. This occurred in conjunction with an up-regulation of genes for proteinase inhibitors, in particular those containing the Kunitz domain. The additionally formed proteins might possibly be involved in reducing nodule oxygen permeability. Between 4 and 28 h of nitrate exposure, a further reduction in nodule activity occurred, and the number of differentially expressed genes almost tripled. In particular, there was a differential expression of genes connected with emerging senescence. It is concluded that nitrate exerts rapid and manifold effects on nitrogenase activity. A certain degree of nitrate tolerance might be achieved when the down-regulatory effect on late nodulins can be alleviated. PMID:24285852

  2. Morphological and molecular aspects of immobilization-induced muscle atrophy in rats at different stages of postnatal development: the role of autophagy.

    PubMed

    Foresto, Camila Silva; Paula-Gomes, Sílvia; Silveira, Wilian Assis; Graça, Flávia Aparecida; Kettelhut, Isis do Carmo; Gonçalves, Dawit Albieiro Pinheiro; Mattiello-Sverzut, Ana Claudia

    2016-09-01

    Muscle loss occurs following injury and immobilization in adulthood and childhood, which impairs the rehabilitation process; however, far fewer studies have been conducted analyzing atrophic response in infants. This work investigated first the morphological and molecular mechanisms involved in immobilization-induced atrophy in soleus muscles from rats at different stages of postnatal development [i.e., weanling (WR) and adult (AR) rats] and, second, the role of autophagy in regulating muscle plasticity during immobilization. Hindlimb immobilization for 10 days reduced muscle mass and fiber cross-sectional area, with more pronounced atrophy in WR, and induced slow-to-fast fiber switching. These effects were accompanied by a decrease in markers of protein synthesis and an increase in autophagy. The ubiquitin (Ub)-ligase MuRF1 and the ubiquitinated proteins were upregulated by immobilization in AR while the autolyzed form of μ-calpain was increased in WR. To further explore the role of autophagy in muscle abnormalities, AR were concomitantly immobilized and treated with colchicine, which blocks autophagosome-lysosome fusion. Colchicine-treated immobilized muscles had exacerbated atrophy and presented degenerative features. Despite Igf1/Akt signaling was downregulated in immobilized muscles from both age groups, Foxo1 and 4 phosphorylation was increased in WR. In the same group of animals, Foxo1 acetylation and Foxo1 and 4 content was increased and decreased, respectively. Our data show that muscle disorders induced by 10-day-immobilization occur in both age-dependent and -independent manners, an understanding that may optimize treatment outcomes in infants. We also provide further evidence that the strong inhibition of autophagy may be ineffective for treating muscle atrophy. PMID:27445301

  3. Graviresponse and its regulation from the aspect of molecular levels in higher plants: growth and development, and auxin polar transport in etiolated pea seedlings under microgravity.

    PubMed

    Miyamoto, Kensuke; Hoshino, Tomoki; Hitotsubashi, Reiko; Tanimoto, Eiichi; Ueda, Junichi

    2003-10-01

    In STS-95 space experiments we have demonstrated that microgravity conditions resulted in automorphosis in etiolated pea (Pisum sativum L. cv. Alaska) seedlings (Ueda et al. 1999). Automorphosis-like growth and development in etiolated pea seedlings were also induced under simulated microgravity conditions on a 3-dimensional (3-D) clinostat, epicotyls being the most oriented toward the direction far from the cotyledons. Detail analysis of epicotyl bending revealed that within 36 h after watering, no significant difference in growth direction of epicotyls was observed in between seedlings grown on the 3-D clinostat and under 1 g conditions, differential growth near the cotyledonary node resulting in epicotyl bending of ca. 45 degrees toward the direction far from the cotyledons. Thereafter epicotyls continued to grow almost straightly keeping this orientation on the 3-D clinostat. On the other hand, the growth direction in etiolated seedlings changed to antigravity direction by negative gravitropic response under 1 g conditions. Automorphological epicotyl bending was also phenocopied by the application of auxin polar transport inhibitors such as 9-hydroxyfluorene-9-carboxylic acid, N-(1-naphtyl)phthalamic acid and 2,3,5-triiodobenzoic acid. These results together with the fact that auxin polar transport activity in etiolated pea epicotyls was substantially reduced in space suggested that reduced auxin polar transport is closely related to automorphosis. Strenuous efforts to learn how gravity contributes to the auxin polar transport in etiolated pea epicotyls in molecular bases resulted in successful identification of PsPIN2 and PsAUX1 encoding putative auxin-efflux and influx carrier proteins, respectively. Based on the results of these gene expression under simulated microgravity conditions, a possible role of PsPIN2 and PsAUX1 genes for auxin polar transport in etiolated pea seedlings will be discussed. PMID:14676393

  4. Efficient multiple-time-step integrators with distance-based force splitting for particle-mesh-Ewald molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Qian, Xiaoliang; Schlick, Tamar

    2002-04-01

    We develop an efficient multiple-time-step force splitting scheme for particle-mesh-Ewald molecular dynamics simulations. Our method exploits smooth switch functions effectively to regulate direct and reciprocal space terms for the electrostatic interactions. The reciprocal term with the near field contributions removed is assigned to the slow class; the van der Waals and regulated particle-mesh-Ewald direct-space terms, each associated with a tailored switch function, are assigned to the medium class. All other bonded terms are assigned to the fast class. This versatile protocol yields good stability and accuracy for Newtonian algorithms, with temperature and pressure coupling, as well as for Langevin dynamics. Since the van der Waals interactions need not be cut at short distances to achieve moderate speedup, this integrator represents an enhancement of our prior multiple-time-step implementation for microcanonical ensembles. Our work also tests more rigorously the stability of such splitting schemes, in combination with switching methodology. Performance of the algorithms is optimized and tested on liquid water, solvated DNA, and solvated protein systems over 400 ps or longer simulations. With a 6 fs outer time step, we find computational speedup ratios of over 6.5 for Newtonian dynamics, compared with 0.5 fs single-time-step simulations. With modest Langevin damping, an outer time step of up to 16 fs can be used with a speedup ratio of 7.5. Theoretical analyses in our appendices produce guidelines for choosing the Langevin damping constant and show the close relationship among the leapfrog Verlet, velocity Verlet, and position Verlet variants.

  5. Integrated Analysis of Metabolite and Transcript Levels Reveals the Metabolic Shifts That Underlie Tomato Fruit Development and Highlight Regulatory Aspects of Metabolic Network Behavior1[W

    PubMed Central

    Carrari, Fernando; Baxter, Charles; Usadel, Björn; Urbanczyk-Wochniak, Ewa; Zanor, Maria-Ines; Nunes-Nesi, Adriano; Nikiforova, Victoria; Centero, Danilo; Ratzka, Antje; Pauly, Markus; Sweetlove, Lee J.; Fernie, Alisdair R.

    2006-01-01

    Tomato (Solanum lycopersicum) is a well-studied model of fleshy fruit development and ripening. Tomato fruit development is well understood from a hormonal-regulatory perspective, and developmental changes in pigment and cell wall metabolism are also well characterized. However, more general aspects of metabolic change during fruit development have not been studied despite the importance of metabolism in the context of final composition of the ripe fruit. In this study, we quantified the abundance of a broad range of metabolites by gas chromatography-mass spectrometry, analyzed a number of the principal metabolic fluxes, and in parallel analyzed transcriptomic changes during tomato fruit development. Metabolic profiling revealed pronounced shifts in the abundance of metabolites of both primary and secondary metabolism during development. The metabolite changes were reflected in the flux analysis that revealed a general decrease in metabolic activity during ripening. However, there were several distinct patterns of metabolite profile, and statistical analysis demonstrated that metabolites in the same (or closely related) pathways changed in abundance in a coordinated manner, indicating a tight regulation of metabolic activity. The metabolite data alone allowed investigations of likely routes through the metabolic network, and, as an example, we analyze the operational feasibility of different pathways of ascorbate synthesis. When combined with the transcriptomic data, several aspects of the regulation of metabolism during fruit ripening were revealed. First, it was apparent that transcript abundance was less strictly coordinated by functional group than metabolite abundance, suggesting that posttranslational mechanisms dominate metabolic regulation. Nevertheless, there were some correlations between specific transcripts and metabolites, and several novel associations were identified that could provide potential targets for manipulation of fruit compositional traits

  6. Molecular aspects, genomic arrangement and immune responsive mRNA expression profiles of two CXC chemokine receptor homologs (CXCR1 and CXCR2) from rock bream, Oplegnathus fasciatus.

    PubMed

    Umasuthan, Navaneethaiyer; Wan, Qiang; Revathy, Kasthuri Saranya; Whang, Ilson; Noh, Jae Koo; Kim, Seokryel; Park, Myoung-Ae; Lee, Jehee

    2014-09-01

    The CXCR1 and CXCR2 are the prototypical receptors and are the only known receptors for mammalian ELR+ (Glu-Leu-Arg) CXC chemokines, including CXCL8 (interleukin 8). These receptors transduce the ELR+ chemokine signals and operate the downstream signaling pathways in inflammation and innate immunity. In this study, we report the identification and characterization of CXCR1 and CXCR2 genes from rock bream fish (OfCXCR1 and OfCXCR2) at the molecular level. The cDNA and genomic DNA sequences of the OfCXCR1 and OfCXCR2 were identified from a transcriptome library and a custom-constructed BAC library, respectively. Both OfCXCR genes consisted of two exons, separated by an intron. The 5'-flanking regions of OfCXCR genes possessed multiple putative transcription factor binding sites related to immune response. The coding sequences of OfCXCR1 and OfCXCR2 encoded putative peptides of 355 and 360 amino acids (aa), respectively. The deduced aa sequences of OfCXCR1 and OfCXCR2 comprised of a G-protein coupled receptors (GPCR) family 1 profile with a GPCR signature and a DRY motif. In addition, seven conserved transmembrane regions were predicted in both OfCXCRs. While our multiple alignment study revealed the functionally significant conserved elements of the OfCXCR1 and OfCXCR2, phylogeny analyses further confirmed their position in teleost sub clade, in which they manifested an evolutionary relatedness with other fish counterparts. Based on comparative analyses, teleost CXC chemokine receptors appear to be distinct from their non-fish orthologs in terms of evolution (both CXCR1 and CXCR2) and genomic organization (CXCR2). Quantitative real-time PCR (qPCR) detected the transcripts of OfCXCR1 and OfCXCR2 in eleven examined tissues, with higher levels in head kidney, kidney and spleen highlighting their crucial importance in immunity. In vitro stimulation of peripheral blood leukocytes (PBLs) with concanavalin A (Con A) resulted in modulation of OfCXCR2 transcription, but not

  7. Car-Parrinello and path integral molecular dynamics study of the hydrogen bonds in 2-acetyl-1,8-dihydroxy-3,6-dimethylnaphthalene

    NASA Astrophysics Data System (ADS)

    Durlak, Piotr; Latajka, Zdzisław

    2010-10-01

    Theoretical studies of the structure and proton motion in the intramolecular O-H…O hydrogen bonds in 2-acetyl-1,8-dihydroxy-3,6-dimethylnapthlane were carried out at the DFT and molecular dynamics levels. Geometry optimization at the PBE1PBE/6-311++G(2d,2p) level demonstrate the existence of two tautomers on the potential energy surface. Dynamics of proton motion in intramolecular hydrogen bonds was investigated in vacuo at 100 K using Car-Parrinello and path integral molecular dynamics. For the strong intramolecular hydrogen bond very large delocalization of bridging proton is noted, especially in the path integral simulation where quantum effects are taken into account. No tautomerism was found for this intramolecular hydrogen bond.

  8. Mid-infrared integrated optics: versatile hot embossing of mid-infrared glasses for on-chip planar waveguides for molecular sensing

    NASA Astrophysics Data System (ADS)

    Seddon, Angela B.; Abdel-Moneim, Nabil S.; Zhang, Lian; Pan, Wei J.; Furniss, David; Mellor, Christopher J.; Kohoutek, Tomas; Orava, Jiri; Wagner, Tomas; Benson, Trevor M.

    2014-07-01

    The versatility of hot embossing for shaping photonic components on-chip for mid-infrared (IR) integrated optics, using a hard mold, is demonstrated. Hot embossing via fiber-on-glass (FOG), thermally evaporated films, and radio frequency (RF)-sputtered films on glass are described. Mixed approaches of combined plasma etching and hot embossing increase the versatility still further for engineering optical circuits on a single platform. Application of these methodologies for fabricating molecular-sensing devices on-chip is discussed with a view to biomedical sensing. Future prospects for using photonic integration for the new field of mid-IR molecular sensing are appraised. Also, common methods of measuring waveguide optical loss are critically compared, regarding their susceptibility to artifacts which tend artificially to depress, or enhance, the waveguide optical loss.

  9. A Car-Parrinello and path integral molecular dynamics study of the intramolecular lithium bond in the lithium 2-pyridyl-N-oxide acetate.

    PubMed

    Durlak, Piotr; Latajka, Zdzisław; Berski, Sławomir

    2009-07-14

    Lithium bonding in lithium 2-pyridyl-N-oxide acetate has been investigated using classic Car-Parrinello molecular dynamics (CPMD) and the path integral approach [path integrals molecular dynamics (PIMD)]. The simulations have been performed in 300 K. Structures, energies, and lithium trajectories have been determined. The CPMD results show that the lithium atom is generally equidistant between heavy atoms in the (O...Li...O) bridge. Applying quantum effects through the PIMD leads to similar conclusion. The theoretical lithium 2-pyridyl-N-oxide acetate infrared spectrum has also been determined using the CPMD calculations. This shows very good agreement with available experimental results and reproduces well the broad low-frequency band observed experimentally. In order to gain deeper understanding of the nature of the lithium bonding topological analysis of the electron localization function has been applied.

  10. A Car-Parrinello and path integral molecular dynamics study of the intramolecular lithium bond in the lithium 2-pyridyl-N-oxide acetate

    NASA Astrophysics Data System (ADS)

    Durlak, Piotr; Latajka, Zdzisław; Berski, Sławomir

    2009-07-01

    Lithium bonding in lithium 2-pyridyl-N-oxide acetate has been investigated using classic Car-Parrinello molecular dynamics (CPMD) and the path integral approach [path integrals molecular dynamics (PIMD)]. The simulations have been performed in 300 K. Structures, energies, and lithium trajectories have been determined. The CPMD results show that the lithium atom is generally equidistant between heavy atoms in the (O⋯Li⋯O) bridge. Applying quantum effects through the PIMD leads to similar conclusion. The theoretical lithium 2-pyridyl-N-oxide acetate infrared spectrum has also been determined using the CPMD calculations. This shows very good agreement with available experimental results and reproduces well the broad low-frequency band observed experimentally. In order to gain deeper understanding of the nature of the lithium bonding topological analysis of the electron localization function has been applied.

  11. Aspects of the integration of 3D buildings models with database. (Polish Title: Aspekty integracji modeli 3D budynków z bazą danych opisowych)

    NASA Astrophysics Data System (ADS)

    Kraszewski, B.

    2013-12-01

    In recent years in Poland for many cities 3D models were created. These developments mainly building models which contain only geometric information were included. However, it is advisable to extend the functionality and spectrum of applications of these models by adding to them information from existing databases. In this article the integration of 3D building models with databases were presented. Two methods of connection of both sets of data were analyzed. First was based on independent connection CAD model with database file and the second was integrated both types of data in CityGML structure. The capabilities of both methods on example 3D data were examined. The 3D data interior and exterior part of building were included. Based on analyzes it was found that the first connection methods used ODBC interface was more friendly for user, because integration could be done in CAD software usually used to 3D models creation. This method to connection used unique identifier MSLINK definited for all database records. The structure of connected database allowed to connect together individual attribute to set of date (tables) collected in different department of institution. The CityGML standard allowed saving not only descriptive information, but also describe semantic and topology of the objects. This format on creation stage request from user a knowledge about specific recording structure based on XML code. In CityGML standard default attributes for individual spatial objects were defined. The values for this attributes in specific code list were determined. In both presented methods it was allowed to add user attributes

  12. Medicinal Chemistry and Molecular Modeling: An Integration to Teach Drug Structure-Activity Relationship and the Molecular Basis of Drug Action

    ERIC Educational Resources Information Center

    Carvalho, Ivone; Borges, Aurea D. L.; Bernardes, Lilian S. C.

    2005-01-01

    The use of computational chemistry and the protein data bank (PDB) to understand and predict the chemical and molecular basis involved in the drug-receptor interactions is discussed. A geometrical and chemical overview of the great structural similarity in the substrate and inhibitor is provided.

  13. Integrating the molecular background of targeted therapy and immunotherapy in lung cancer: a way to explore the impact of mutational landscape on tumor immunogenicity

    PubMed Central

    Pilotto, Sara; Molina-Vila, Miguel Angel; Karachaliou, Niki; Carbognin, Luisa; Viteri, Santiago; González-Cao, Maria; Bria, Emilio; Tortora, Giampaolo

    2015-01-01

    The results of randomized clinical trials employing immune checkpoint inhibitors for pre-treated advanced non-small-cell lung cancer (NSCLC) have recently revolutionised the standard available option for this disease setting. Nevertheless, the validation of reliable predictive biomarkers, able to define that proportion of patients most likely to benefit from immunotherapy, represents a crucial and still unsolved issue. This intensive research aimed at selecting potentially predictive biomarkers for immunotherapy is developed together with a wide range of analyses investigating the molecular profiling of lung cancer, leading to the spontaneous question of how these two parallel aspects of the same disease may coexist and influence one another. The potential impact of the mutational landscape of lung cancer on tumor immunogenicity (in both oncogene-addicted and molecularly unselected disease) will be explored and discussed in this review in order to begin to answer the unsolved questions. PMID:26798581

  14. Integrating the molecular background of targeted therapy and immunotherapy in lung cancer: a way to explore the impact of mutational landscape on tumor immunogenicity.

    PubMed

    Pilotto, Sara; Molina-Vila, Miguel Angel; Karachaliou, Niki; Carbognin, Luisa; Viteri, Santiago; González-Cao, Maria; Bria, Emilio; Tortora, Giampaolo; Rosell, Rafael

    2015-12-01

    The results of randomized clinical trials employing immune checkpoint inhibitors for pre-treated advanced non-small-cell lung cancer (NSCLC) have recently revolutionised the standard available option for this disease setting. Nevertheless, the validation of reliable predictive biomarkers, able to define that proportion of patients most likely to benefit from immunotherapy, represents a crucial and still unsolved issue. This intensive research aimed at selecting potentially predictive biomarkers for immunotherapy is developed together with a wide range of analyses investigating the molecular profiling of lung cancer, leading to the spontaneous question of how these two parallel aspects of the same disease may coexist and influence one another. The potential impact of the mutational landscape of lung cancer on tumor immunogenicity (in both oncogene-addicted and molecularly unselected disease) will be explored and discussed in this review in order to begin to answer the unsolved questions.

  15. Integrative physiology of coronary microcirculation.

    PubMed

    Kajiya, F; Goto, M

    1999-06-01

    Coronary microvessels play a crucial role for mechanoenergetic interaction between blood flow and myocardial function, which is not uniform transmurally. Thus, highly organized vascular regulations are required for matching local blood flow with myocardial energy requirement. Recently, new technologies to investigate in vivo coronary microcirculation with new knowledge of the signaling molecules for vascular regulation have revolutionized our abilities to understand the integrative regulation of coronary microcirculation. In this review, the mechanical aspects of the interaction between coronary blood flow and myocardium, coronary arte-rial tree and its roles in myocardial blood flow regulation, hierarchical and dynamic control of coronary flow, capillary network and function, function of venous drainage system, and molecular and cellular aspects of integrative coronary blood flow regulation are discussed, focusing on their integrational roles in maintaining coronary microvascular function and cell signaling.

  16. Extending molecular simulation time scales: Parallel in time integrations for high-level quantum chemistry and complex force representations.

    PubMed

    Bylaska, Eric J; Weare, Jonathan Q; Weare, John H

    2013-08-21

    Parallel in time simulation algorithms are presented and applied to conventional molecular dynamics (MD) and ab initio molecular dynamics (AIMD) models of realistic complexity. Assuming that a forward time integrator, f (e.g., Verlet algorithm), is available to propagate the system from time ti (trajectory positions and velocities xi = (ri, vi)) to time ti + 1 (xi + 1) by xi + 1 = fi(xi), the dynamics problem spanning an interval from t0[ellipsis (horizontal)]tM can be transformed into a root finding problem, F(X) = [xi - f(x(i - 1)]i = 1, M = 0, for the trajectory variables. The root finding problem is solved using a variety of root finding techniques, including quasi-Newton and preconditioned quasi-Newton schemes that are all unconditionally convergent. The algorithms are parallelized by assigning a processor to each time-step entry in the columns of F(X). The relation of this approach to other recently proposed parallel in time methods is discussed, and the effectiveness of various approaches to solving the root finding problem is tested. We demonstrate that more efficient dynamical models based on simplified interactions or coarsening time-steps provide preconditioners for the root finding problem. However, for MD and AIMD simulations, such preconditioners are not required to obtain reasonable convergence and their cost must be considered in the performance of the algorithm. The parallel in time algorithms developed are tested by applying them to MD and AIMD simulations of size and complexity similar to those encountered in present day applications. These include a 1000 Si atom MD simulation using Stillinger-Weber potentials, and a HCl + 4H2O AIMD simulation at the MP2 level. The maximum speedup (serial execution/timeparallel execution time) obtained by parallelizing the Stillinger-Weber MD simulation was nearly 3.0. For the AIMD MP2 simulations, the algorithms achieved speedups of up to 14.3. The parallel in time algorithms can be implemented in a

  17. Extending molecular simulation time scales: Parallel in time integrations for high-level quantum chemistry and complex force representations

    NASA Astrophysics Data System (ADS)

    Bylaska, Eric J.; Weare, Jonathan Q.; Weare, John H.

    2013-08-01

    Parallel in time simulation algorithms are presented and applied to conventional molecular dynamics (MD) and ab initio molecular dynamics (AIMD) models of realistic complexity. Assuming that a forward time integrator, f (e.g., Verlet algorithm), is available to propagate the system from time ti (trajectory positions and velocities xi = (ri, vi)) to time ti + 1 (xi + 1) by xi + 1 = fi(xi), the dynamics problem spanning an interval from t0…tM can be transformed into a root finding problem, F(X) = [xi - f(x(i - 1)]i = 1, M = 0, for the trajectory variables. The root finding problem is solved using a variety of root finding techniques, including quasi-Newton and preconditioned quasi-Newton schemes that are all unconditionally convergent. The algorithms are parallelized by assigning a processor to each time-step entry in the columns of F(X). The relation of this approach to other recently proposed parallel in time methods is discussed, and the effectiveness of various approaches to solving the root finding problem is tested. We demonstrate that more efficient dynamical models based on simplified interactions or coarsening time-steps provide preconditioners for the root finding problem. However, for MD and AIMD simulations, such preconditioners are not required to obtain reasonable convergence and their cost must be considered in the performance of the algorithm. The parallel in time algorithms developed are tested by applying them to MD and AIMD simulations of size and complexity similar to those encountered in present day applications. These include a 1000 Si atom MD simulation using Stillinger-Weber potentials, and a HCl + 4H2O AIMD simulation at the MP2 level. The maximum speedup (serial execution time/parallel execution time) obtained by parallelizing the Stillinger-Weber MD simulation was nearly 3.0. For the AIMD MP2 simulations, the algorithms achieved speedups of up to 14.3. The parallel in time algorithms can be implemented in a distributed computing

  18. Extending molecular simulation time scales: Parallel in time integrations for high-level quantum chemistry and complex force representations

    SciTech Connect

    Bylaska, Eric J.; Weare, Jonathan Q.; Weare, John H.

    2013-08-21

    Parallel in time simulation algorithms are presented and applied to conventional molecular dynamics (MD) and ab initio molecular dynamics (AIMD) models of realistic complexity. Assuming that a forward time integrator, f (e.g., Verlet algorithm), is available to propagate the system from time t{sub i} (trajectory positions and velocities x{sub i} = (r{sub i}, v{sub i})) to time t{sub i+1} (x{sub i+1}) by x{sub i+1} = f{sub i}(x{sub i}), the dynamics problem spanning an interval from t{sub 0}…t{sub M} can be transformed into a root finding problem, F(X) = [x{sub i} − f(x{sub (i−1})]{sub i} {sub =1,M} = 0, for the trajectory variables. The root finding problem is solved using a variety of root finding techniques, including quasi-Newton and preconditioned quasi-Newton schemes that are all unconditionally convergent. The algorithms are parallelized by assigning a processor to each time-step entry in the columns of F(X). The relation of this approach to other recently proposed parallel in time methods is discussed, and the effectiveness of various approaches to solving the root finding problem is tested. We demonstrate that more efficient dynamical models based on simplified interactions or coarsening time-steps provide preconditioners for the root finding problem. However, for MD and AIMD simulations, such preconditioners are not required to obtain reasonable convergence and their cost must be considered in the performance of the algorithm. The parallel in time algorithms developed are tested by applying them to MD and AIMD simulations of size and complexity similar to those encountered in present day applications. These include a 1000 Si atom MD simulation using Stillinger-Weber potentials, and a HCl + 4H{sub 2}O AIMD simulation at the MP2 level. The maximum speedup ((serial execution time)/(parallel execution time) ) obtained by parallelizing the Stillinger-Weber MD simulation was nearly 3.0. For the AIMD MP2 simulations, the algorithms achieved speedups of up

  19. Extending molecular simulation time scales: Parallel in time integrations for high-level quantum chemistry and complex force representations

    SciTech Connect

    Bylaska, Eric J.; Weare, Jonathan Q.; Weare, John H.

    2013-08-21

    Parallel in time simulation algorithms are presented and applied to conventional molecular dynamics (MD) and ab initio molecular dynamics (AIMD) models of realistic complexity. Assuming that a forward time integrator, f , (e.g. Verlet algorithm) is available to propagate the system from time ti (trajectory positions and velocities xi = (ri; vi)) to time ti+1 (xi+1) by xi+1 = fi(xi), the dynamics problem spanning an interval from t0 : : : tM can be transformed into a root finding problem, F(X) = [xi - f (x(i-1)]i=1;M = 0, for the trajectory variables. The root finding problem is solved using a variety of optimization techniques, including quasi-Newton and preconditioned quasi-Newton optimization schemes that are all unconditionally convergent. The algorithms are parallelized by assigning a processor to each time-step entry in the columns of F(X). The relation of this approach to other recently proposed parallel in time methods is discussed and the effectiveness of various approaches to solving the root finding problem are tested. We demonstrate that more efficient dynamical models based on simplified interactions or coarsening time-steps provide preconditioners for the root finding problem. However, for MD and AIMD simulations such preconditioners are not required to obtain reasonable convergence and their cost must be considered in the performance of the algorithm. The parallel in time algorithms developed are tested by applying them to MD and AIMD simulations of size and complexity similar to those encountered in present day applications. These include a 1000 Si atom MD simulation using Stillinger-Weber potentials, and a HCl+4H2O AIMD simulation at the MP2 level. The maximum speedup obtained by parallelizing the Stillinger-Weber MD simulation was nearly 3.0. For the AIMD MP2 simulations the algorithms achieved speedups of up to 14.3. The parallel in time algorithms can be implemented in a distributed computing environment using very slow TCP/IP networks. Scripts

  20. Integrating the cell stress response: a new view of molecular chaperones as immunological and physiological homeostatic regulators.

    PubMed

    Henderson, Brian

    2010-01-01

    The response of cells to stress was first documented in the 1960s and 1970s and the molecular nature of the families of proteins that subserve this vital response, the molecular chaperones, were identified and subjected to critical study in the period from the late 1980s. This resulted in the rapidly advancing new field of protein folding and its role in cellular function. Emerging at the same time, but initially largely ignored, were reports that molecular chaperones could be released by cells and exist on the outer plasma membrane or in the body fluids. These secreted molecular chaperones were found to have intercellular signalling functions. There is now a growing body of evidence to support the hypothesis that molecular chaperones have properties ascribed to the Roman god Janus, the god of gates, doors, beginnings and endings, whose two faces point in different directions. Molecular chaperones appear to have one set of key functions within the cell and, potentially, a separate set of functions when they exist on the cell surface or in the various fluid phases of the body. Thus, it is a likely hypothesis that secreted molecular chaperones act as an additional level of homeostatic control possibly linking cellular stress to physiological systems such as the immune system. This review concentrates on three key molecular chaperones: Hsp10, Hsp60 and the Hsp70 family for which most information is available. An important consideration is the role that these proteins may play in human disease and in the treatment of human disease.

  1. [The medical aspects of the rehabilitation of patients with congenital heart defects and the problems of their social integration into modern society].

    PubMed

    Gritsenko, V V; Likhnitskaia, I I; Mochalov, O Iu; Miroshkina, V M

    1997-01-01

    Treatment of 500 patients was used as a basis for the development of a complex stepwise programme of rehabilitation of patients with congenital heart diseases (CHD). It was noted that for a valuable social integration of people with CHD into the modern society it was necessary to perform not only the indicated, adequate and timely operations but also the inescapable measures for the improvement of their physical and psychophysiological adaptation. The following job in remote periods of observations of the patients operated upon must take into account its conformity to functional possibilities of energy expenditure for the chosen occupation and should be effected with the individually accessible (or indicated) level of the physical tension taken into consideration. PMID:9235748

  2. Effects of high hydrostatic pressure on Escherichia coli ultrastructure, membrane integrity and molecular composition as assessed by FTIR spectroscopy and microscopic imaging techniques.

    PubMed

    Prieto-Calvo, María; Prieto, Miguel; López, Mercedes; Alvarez-Ordóñez, Avelino

    2014-12-18

    High hydrostatic pressure (HHP) is a novel food processing technology that is considered as an attractive alternative to conventional heat treatments for the preservation of foods, due to its lethal effects on pathogenic and spoilage microorganisms, while causing minor effects on food quality and sensorial attributes. This study is aimed at investigating how HHP treatments at varying intensities in the range 50-900 MPa affect the viability, membrane integrity, ultrastructure and molecular composition of Escherichia coli. Results of membrane integrity tests (measurement of cellular leakage and monitoring of propidium iodide uptake through fluorescence microscopy) and ultrastructural observations by transmission electron microscopy demonstrated that HHP gave rise to cellular enlargement, membrane damage or detachment, DNA and protein denaturation and loss of intracellular contents. Fourier-transform infrared (FTIR) spectroscopy analyses evidenced minor changes in molecular composition in response to high pressures, which were mostly observed on the spectral region w4 (1200-900 cm-1), mainly informative of carbohydrates and polysaccharides of the cell wall. These findings suggest that exposure of E. coli cells to HHP causes alterations in their physical integrity while producing minor modifications in biochemical cellular composition. The current study increases the knowledge on the mechanisms of E. coli inactivation by HHP and provides valuable information for the design of more effective food preservation regimes based on the integration of mild HHP in combination with other food preservation strategies into a multi-target hurdle technology approach.

  3. Scale bridging in molecular simulation. Recurrent problems and current options

    NASA Astrophysics Data System (ADS)

    Hartmann, Carsten; Delle Site, Luigi

    2015-09-01

    Multiscale and multiphysics approaches have become an integral part of the molecular modeling and simulation toolbox and are used to attack various real-world problems that would be out of reach without these techniques. This special topics issue is devoted to a critical appraisal of some of the most popular scale bridging techniques for molecular simulation. It features regular articles and a "Discussion and Debate" section, in which experts in the field discuss specific articles and general aspects of scale bridging techniques.

  4. Review of current chemoinformatic tools for modeling important aspects of CYPs-mediated drug metabolism. Integrating metabolism data with other biological profiles to enhance drug discovery.

    PubMed

    Speck-Planche, Alejandro; Cordeiro, Maria Natalia Dias Soeiro

    2014-01-01

    The study of the metabolism of xenobiotics by the human body is an essential stage in the complex and expensive process of drug discovery, being one of the main causes of disapproval and/or withdrawal of drugs. Regarding this, enzymes known as cytochromes P450 (CYPs) play a very decisive role in the biotransformation of many chemicals. For this reason, the use of chemoinformatics to predict and /or analyze from different points of view CYPs-mediated drug metabolism, can help to reduce time and financial resources. This work is focused on the most remarkable advances in the last 5 years of the chemoinformatics tools towards the virtual analysis of CYPsmediated drug metabolism. First, a brief section is dedicated to the applicability of chemoinformatics in different areas associated with drug metabolism. Then, both the models for prediction of CYPs substrates and those allowing the assessment of sites of metabolism (SOM) are discussed. At the same time, the principal limitations of the current chemoinformatic tools are pointed out. Finally, and taking into account that metabolism is an essential step in the whole process of designing any drug, we introduce here as a case of study, the first multitasking model for quantitative-structure biological effect relationships (mtk-QSBER). The purpose of this model is to integrate different types of biological profiles such as ADMET (absorption, distribution, metabolism, excretion, toxicity) profiles and antistaphylococci activities. The mtk-QSBER model was created by employing a heterogeneous dataset of more than 66000 cases tested in 6510 different experimental conditions. The model displayed a total accuracy higher than 94%. To the best of our knowledge, this is the first attempt to complement metabolism assays with other relevant biological data in order to speed up the discovery of efficacious antistaphylococci agents. PMID:24909424

  5. Novel aspects of grapevine response to phytoplasma infection investigated by a proteomic and phospho-proteomic approach with data integration into functional networks

    PubMed Central

    2013-01-01

    analysis showed that the general main category “response to stimulus” was over-represented in both infected and recovered plants but, in the latter, the specific child category “response to biotic stimulus” was no longer found, suggesting a return to steady-state levels for those proteins specifically required for defence against pathogens. Conclusions Proteomic data were integrated into biological networks and their interactions were represented through a hypothetical model, showing the effects of protein modulation on primary metabolic ways and related secondary pathways. By following a multiplex-staining approach, we obtained new data on grapevine proteome pathways that specifically change at the phosphorylation level during phytoplasma infection and following recovery, focusing for the first time on phosphoproteome changes during pathogen infection in this host. PMID:23327683

  6. Integrating In Silico Prediction Methods, Molecular Docking, and Molecular Dynamics Simulation to Predict the Impact of ALK Missense Mutations in Structural Perspective

    PubMed Central

    Priya Doss, C. George; Chen, Luonan

    2014-01-01

    Over the past decade, advancements in next generation sequencing technology have placed personalized genomic medicine upon horizon. Understanding the likelihood of disease causing mutations in complex diseases as pathogenic or neutral remains as a major task and even impossible in the structural context because of its time consuming and expensive experiments. Among the various diseases causing mutations, single nucleotide polymorphisms (SNPs) play a vital role in defining individual's susceptibility to disease and drug response. Understanding the genotype-phenotype relationship through SNPs is the first and most important step in drug research and development. Detailed understanding of the effect of SNPs on patient drug response is a key factor in the establishment of personalized medicine. In this paper, we represent a computational pipeline in anaplastic lymphoma kinase (ALK) for SNP-centred study by the application of in silico prediction methods, molecular docking, and molecular dynamics simulation approaches. Combination of computational methods provides a way in understanding the impact of deleterious mutations in altering the protein drug targets and eventually leading to variable patient's drug response. We hope this rapid and cost effective pipeline will also serve as a bridge to connect the clinicians and in silico resources in tailoring treatments to the patients' specific genotype. PMID:25054154

  7. [Molecular-genetic aspects of neurofibromatosis].

    PubMed

    Hulsebos, T J

    1997-03-29

    Two forms of neurofibromatosis, type 1 (NF1) and type 2 (NF2) are connected with genes localized on chromosomes 17 and 22, respectively. The genes that are inactivated in neurofibromatosis code for the proteins neurofibromine and merline, respectively. Since inactivation leads to neoplasia, they are called tumour suppressor genes. Neurofibromine shows resemblances to proteins that serve to inactivate oncogenes. Merline has a relationship with proteins that connect the cytoskeleton and the cell membrane. The precise function of the proteins is still unknown. The NF1 gene is characterized by extraordinarily high sensitivity to mutation; half the NF1 patients have not inherited the disease. In the familial form of neurofibromatosis, a mutated gene is inherited and the normal allele in the tumour is inactivated, making tumour growth possible. In the sporadic form of neurofibromatosis, both normal alleles are inactivated locally in the tissue so that a tumour develops in that place. PMID:9190537

  8. The molecular aspects of personalized anticancer treatment

    NASA Astrophysics Data System (ADS)

    Cherdyntseva, N.; Litviakov, N.; Ivanova, F.; Denisov, E.; Gervas, P.; Cherdyntsev, E.

    2016-08-01

    Only 25% of cancer patients, on average, benefit from therapy. Even in the cases of complete clinical response the tumor progression is an event of high level expectation. The main reasons for tumor progression are: intratumor heterogeneity resulted from clonal evolution, drug resistance, and tumor-promoting microenvironment. The reprogramming of microenvironmental stromal-inflammatory components is expected to allow tumor phenotype reversion. So, to find the new effective markers of tumor progression, drug response and targets for therapy, it could be promising to take into account the tumor-microenvironment heterogeneity and tumor clonal evolution.

  9. Olmsted syndrome: clinical, molecular and therapeutic aspects.

    PubMed

    Duchatelet, Sabine; Hovnanian, Alain

    2015-03-17

    Olmsted syndrome (OS) is a rare genodermatosis classically characterized by the combination of bilateral mutilating transgredient palmoplantar keratoderma (PPK) and periorificial keratotic plaques, but which shows considerable clinical heterogeneity. The disease starts usually at birth or in early childhood. About 73 cases have been reported worldwide. OS is observed in both sexes, although male cases are more frequent. The most suggestive symptoms associate PPK with pseudoainhum and periorificial keratotic plaques. Frequently associated features include hair and nail abnormalities, leukokeratosis, corneal default and recurrent infections. Pain and itching are variable but can be severe. Most of reported OS cases are sporadic, although familial cases with different mode of inheritance were also described. Mutations in TRPV3 (Transient receptor potential vanilloid-3) gene have recently been identified as a cause of autosomal dominant (gain-of-function mutations) or recessive OS. Mutations in MBTPS2 (membrane-bound transcription factor protease, site 2) gene were identified in a recessive X-linked form. The diagnosis relies mainly on clinical features associating severe PPK and periorificial keratotic plaques, but can be challenging in patients with incomplete phenotype or atypical features. OS has to be differentiated from other severe forms of PPK including Vohwinkel, Clouston, Papillon-Lefèvre or Haim-Munk syndromes, Mal de Meleda, pachyonychia congenita, Tyrosinemia type II and acrodermatitis enteropathica. When differential diagnoses are difficult to exclude, genetic studies are essential to search for a TRPV3 or MBTPS2 mutation. However, additional genes remain to be identified. No specific and satisfactory therapy is currently available for OS. Current treatments of hyperkeratosis (mainly emollients, keratolytics, retinoids or corticosteroids), either topical or systemic, are symptomatic and offer only temporary partial relief. Specific management of pain and itching is important to reduce the morbidity of the disease. The disease is debilitating and progressive keratoderma and auto-amputation of digits can prevent patients from grasping and walking, and confine them to a wheelchair. New therapeutic options are therefore crucial and are expected from a better understanding of the disease mechanisms. The use of TRPV3 antagonists would represent such a targeted and potentially powerful strategy.

  10. Molecular and industrial aspects of glucose isomerase.

    PubMed Central

    Bhosale, S H; Rao, M B; Deshpande, V V

    1996-01-01

    Glucose isomerase (GI) (D-xylose ketol-isomerase; EC. 5.3.1.5) catalyzes the reversible isomerization of D-glucose and D-xylose to D-fructose and D-xylulose, respectively. The enzyme has the largest market in the food industry because of its application in the production of high-fructose corn syrup (HFCS). HFCS, an equilibrium mixture of glucose and fructose, is 1.3 times sweeter than sucrose and serves as a sweetener for use by diabetics. Interconversion of xylose to xylulose by GI serves a nutritional requirement in saprophytic bacteria and has a potential application in the bioconversion of hemicellulose to ethanol. The enzyme is widely distributed in prokaryotes. Intensive research efforts are directed toward improving its suitability for industrial application. Development of microbial strains capable of utilizing xylan-containing raw materials for growth or screening for constitutive mutants of GI is expected to lead to discontinuation of the use of xylose as an inducer for the production of the enzyme. Elimination of Co2+ from the fermentation medium is desirable for avoiding health problems arising from human consumption of HFCS. Immobilization of GI provides an efficient means for its easy recovery and reuse and lowers the cost of its use. X-ray crystallographic and genetic engineering studies support a hydride shift mechanism for the action of GI. Cloning of GI in homologous as well as heterologous hosts has been carried out, with the prime aim of overproducing the enzyme and deciphering the genetic organization of individual genes (xylA, xylB, and xylR) in the xyl operon of different microorganisms. The organization of xylA and xylB seems to be highly conserved in all bacteria. The two genes are transcribed from the same strand in Escherichia coli and Bacillus and Lactobacillus species, whereas they are transcribed divergently on different strands in Streptomyces species. A comparison of the xylA sequences from several bacterial sources revealed the presence of two signature sequences, VXW(GP)GREG(YSTAE)E and (LIVM)EPKPX(EQ)P. The use of an inexpensive inducer in the fermentation medium devoid of Co2+ and redesigning of a tailor-made GI with increased thermostability, higher affinity for glucose, and lower pH optimum will contribute significantly to the development of an economically feasible commercial process for enzymatic isomerization of glucose to fructose. Manipulation of the GI gene by site-directed mutagenesis holds promise that a GI suitable for biotechnological applications will be produced in the foreseeable future. PMID:8801434

  11. Intra- and Interdimer Transfer Integrals Effectively Modified by Pulsed and Continuous-Wave Lasers for Controlling Charge Transfers in Molecular Crystals

    NASA Astrophysics Data System (ADS)

    Nishioka, Keita; Yonemitsu, Kenji

    2014-02-01

    We theoretically study the field-intensity dependence of charge transfers driven by continuous-wave and pulsed lasers in a two-dimensional crystal consisting of molecular dimers by numerically solving the time-dependent Schrödinger equation for an extended Hubbard model. Generally, electronic transfer integrals are regarded as renormalized when an oscillating external field is applied, as far as the electronic dynamics averaged over the oscillation period is concerned. The cases where effective transfer integrals vanish are known as dynamic localization. Interdimer charge transfers driven by continuous-wave lasers are thus governed by effective interdimer transfer integrals. After the field is switched off, the dynamic localization is no longer relevant. Then, we show that interdimer charge transfers driven by pulsed lasers of energy resonant with an intradimer transition are governed by an effective intradimer transfer integral. The total-energy increment depends on how the intradimer transfer integral is renormalized. The same holds for interdimer charge transfers. This interdimer dynamics governed by effective intradimer parameters is evident even for one- and two-cycle pulses, suggesting possible control of photoinduced charge-order melting.

  12. Molecular Plasmonics.

    PubMed

    Wilson, Andrew J; Willets, Katherine A

    2016-06-12

    In this review, we survey recent advances in the field of molecular plasmonics beyond the traditional sensing modality. Molecular plasmonics is explored in the context of the complex interaction between plasmon resonances and molecules and the ability of molecules to support plasmons self-consistently. First, spectroscopic changes induced by the interaction between molecular and plasmonic resonances are discussed, followed by examples of how tuning molecular properties leads to active molecular plasmonic systems. Next, the role of the position and polarizability of a molecular adsorbate on surface-enhanced Raman scattering signals is examined experimentally and theoretically. Finally, we introduce recent research focused on using molecules as plasmonic materials. Each of these examples is intended to highlight the role of molecules as integral components in coupled molecule-plasmon systems, as well as to show the diversity of applications in molecular plasmonics.

  13. Molecular Plasmonics

    NASA Astrophysics Data System (ADS)

    Wilson, Andrew J.; Willets, Katherine A.

    2016-06-01

    In this review, we survey recent advances in the field of molecular plasmonics beyond the traditional sensing modality. Molecular plasmonics is explored in the context of the complex interaction between plasmon resonances and molecules and the ability of molecules to support plasmons self-consistently. First, spectroscopic changes induced by the interaction between molecular and plasmonic resonances are discussed, followed by examples of how tuning molecular properties leads to active molecular plasmonic systems. Next, the role of the position and polarizability of a molecular adsorbate on surface-enhanced Raman scattering signals is examined experimentally and theoretically. Finally, we introduce recent research focused on using molecules as plasmonic materials. Each of these examples is intended to highlight the role of molecules as integral components in coupled molecule-plasmon systems, as well as to show the diversity of applications in molecular plasmonics.

  14. Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers.

    PubMed

    Korshunov, Andrey; Ryzhova, Marina; Hovestadt, Volker; Bender, Sebastian; Sturm, Dominik; Capper, David; Meyer, Jochen; Schrimpf, Daniel; Kool, Marcel; Northcott, Paul A; Zheludkova, Olga; Milde, Till; Witt, Olaf; Kulozik, Andreas E; Reifenberger, Guido; Jabado, Nada; Perry, Arie; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Jones, David T W

    2015-05-01

    Pediatric glioblastoma (pedGBM) is amongst the most common malignant brain tumors of childhood and carries a dismal prognosis. In contrast to adult GBM, few molecular prognostic markers for the pediatric counterpart have been established. We, therefore, investigated the prognostic significance of genomic and epigenetic alterations through molecular analysis of 202 pedGBM (1-18 years) with comprehensive clinical annotation. Routinely prepared formalin-fixed paraffin-embedded tumor samples were assessed for genome-wide DNA methylation profiles, with known candidate genes screened for alterations via direct sequencing or FISH. Unexpectedly, a subset of histologically diagnosed GBM (n = 40, 20 %) displayed methylation profiles similar to those of either low-grade gliomas or pleomorphic xanthoastrocytomas (PXA). These tumors showed a markedly better prognosis, with molecularly PXA-like tumors frequently harboring BRAF V600E mutations and 9p21 (CDKN2A) homozygous deletion. The remaining 162 tumors with pedGBM molecular signatures comprised four subgroups: H3.3 G34-mutant (15 %), H3.3/H3.1 K27-mutant (43 %), IDH1-mutant (6 %), and H3/IDH wild-type (wt) GBM (36 %). These subgroups were associated with specific cytogenetic aberrations, MGMT methylation patterns and clinical outcomes. Analysis of follow-up data identified a set of biomarkers feasible for use in risk stratification: pedGBM with any oncogene amplification and/or K27M mutation (n = 124) represents a particularly unfavorable group, with 3-year overall survival (OS) of 5 %, whereas tumors without these markers (n = 38) define a more favorable group (3-year OS ~70 %).Combined with the lower grade-like lesions, almost 40 % of pedGBM cases had distinct molecular features associated with a more favorable outcome. This refined prognostication method for pedGBM using a molecular risk algorithm may allow for improved therapeutic choices and better planning of clinical trial stratification for this otherwise devastating

  15. Structure and Dynamics of the Instantaneous Water/Vapor Interface Revisited by Path-Integral and Ab Initio Molecular Dynamics Simulations.

    PubMed

    Kessler, Jan; Elgabarty, Hossam; Spura, Thomas; Karhan, Kristof; Partovi-Azar, Pouya; Hassanali, Ali A; Kühne, Thomas D

    2015-08-01

    The structure and dynamics of the water/vapor interface is revisited by means of path-integral and second-generation Car-Parrinello ab initio molecular dynamics simulations in conjunction with an instantaneous surface definition [Willard, A. P.; Chandler, D. J. Phys. Chem. B 2010, 114, 1954]. In agreement with previous studies, we find that one of the OH bonds of the water molecules in the topmost layer is pointing out of the water into the vapor phase, while the orientation of the underlying layer is reversed. Therebetween, an additional water layer is detected, where the molecules are aligned parallel to the instantaneous water surface.

  16. Molecular beam epitaxy of InAs nanowires in SiO2 nanotube templates: challenges and prospects for integration of III–Vs on Si

    NASA Astrophysics Data System (ADS)

    Vukajlovic-Plestina, Jelena; Dubrovskii, Vladimir G.; Tütüncuoǧlu, Gözde; Potts, Heidi; Ricca, Ruben; Meyer, Frank; Matteini, Federico; Leran, Jean-Baptiste; Morral, Anna Fontcuberta i.

    2016-11-01

    Guided growth of semiconductor nanowires in nanotube templates has been considered as a potential platform for reproducible integration of III–Vs on silicon or other mismatched substrates. Herein, we report on the challenges and prospects of molecular beam epitaxy of InAs nanowires in SiO2/Si nanotube templates. We show how and under which conditions the nanowire growth is initiated by In-assisted vapor–liquid–solid growth enabled by the local conditions inside the nanotube template. The conditions for high yield of vertical nanowires are investigated in terms of the nanotube depth, diameter and V/III flux ratios. We present a model that further substantiates our findings. This work opens new perspectives for monolithic integration of III–Vs on the silicon platform enabling new applications in the electronics, optoelectronics and energy harvesting arena.

  17. Design and construction of a first-generation high-throughput integrated robotic molecular biology platform for bioenergy applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The molecular biological techniques for plasmid-based assembly and cloning of gene open reading frames are essential for elucidating the function of the proteins encoded by the genes. These techniques involve the production of full-length cDNA libraries as a source of plasmid-based clones to expres...