WorldWideScience

Sample records for general regulatory mechanism

  1. Homopolymeric tracts represent a general regulatory mechanism in prokaryotes

    Directory of Open Access Journals (Sweden)

    Bowen Barbara M

    2010-02-01

    Full Text Available Abstract Background While, traditionally, regulation of gene expression can be grouped into transcriptional, translational, and post-translational mechanisms, some mechanisms of rapid genetic variation can also contribute to regulation of gene expression, e.g., phase variation. Results We show here that prokaryotes evolved to include homopolymeric tracts (HTs within coding genes as a system that allows for efficient gene inactivation. Analyses of 81 bacterial and 18 archaeal genomes showed that poly(A and poly(T HTs are overrepresented in these genomes and preferentially located at the 5' end of coding genes. Location of HTs at the 5' end is not driven by a preferential placement of aminoacids encoded by the AAA and TTT codons at the N-terminal of proteins. The inlA gene of the pathogen L. monocytogenes was used as a model to further study the role of HTs in reversible gene inactivation. In a number of L. monocytogenes strains, inlA harbors a 5' poly(A HT, which regularly shows frameshift mutation leading to expression of a truncated 8 aa InlA protein. Translational fusions of the inlA 5' end allowed us to estimate that the frequency of variation in this HT is about 1,000 fold higher than the estimated average point mutation frequency. Conclusions As frameshift mutations in HTs can occur at high frequencies and enable efficient gene inactivation, hypermutable HTs appear to represent a universal system for regulation of gene expression in prokaryotes. Combined with other studies indicating that HTs also enable rapid diversification of both coding and regulatory genetic sequences in eukaryotes, our data suggest that hypermutable HTs represent a general and rapid evolutionary mechanism facilitating adaptation and gene regulation across diverse organisms.

  2. Mechanics of Generalized Continua

    CERN Document Server

    Maugin, Gerard A

    2010-01-01

    In their 1909 publication "Theorie des corps deformables", Eugene and Francois Cosserat made a historic contribution to materials science by establishing the fundamental principles of the mechanics of generalized continua. The chapters collected in this volume showcase the many areas of continuum mechanics that grew out of the foundational work of the Cosserat brothers. The included contributions provide a detailed survey of the most recent theoretical developments in the field of generalized continuum mechanics. The diverse topics covered include: the properties of Cosserat media, m

  3. A study of bacterial gene regulatory mechanisms

    DEFF Research Database (Denmark)

    Hansen, Sabine

    the different regulatory mechanisms affect system dynamics. We have designed a synthetic gene regulatory network (GRN) in bacterial cells that enables us to study the dynamics of GRNs. The results presented in this PhD thesis show that model equations based on the established mechanisms of action of each...... of a particular type of regulatory mechanism. The synthetic system presented in this thesis is, to our knowledge, the first of its kind to allow a direct comparison of the dynamic behaviors of gene regulatory networks that employ different mechanisms of regulation. In addition to studying the dynamic behavior...... of GRNs this thesis also provided the first evidence of the sensor histidine kinase VC1831 being an additional player in the Vibrio cholerae quorum sensing (QS) GRN. Bacteria use a process of cell-cell communication called QS which enable the bacterial cells to collectively control their gene expression...

  4. Gene regulatory mechanisms in infected fish

    DEFF Research Database (Denmark)

    Schyth, Brian Dall; Hajiabadi, Seyed Amir Hossein Jalali; Kristensen, Lasse Bøgelund Juel

    2011-01-01

    This talk will highlight the regulatory mechanisms of gene expression especially the programmed form of mRNA decay which is known as RNA interference (RNAi) and how this and other mechanisms contribute to the regulation of genes involved in immunity. In the RNAi mechanism small double stranded RNA...... whole pathways for the fine-tuning of physiological states like immunological reaction. But miRNAs are themselves under control of regulatory sequences for their timed expression. We will give an example of the finding of two rainbow trout microRNAs, which are up-regulated in the liver during infection...

  5. Regulatory mechanisms link phenotypic plasticity to evolvability.

    Science.gov (United States)

    van Gestel, Jordi; Weissing, Franz J

    2016-04-18

    Organisms have a remarkable capacity to respond to environmental change. They can either respond directly, by means of phenotypic plasticity, or they can slowly adapt through evolution. Yet, how phenotypic plasticity links to evolutionary adaptability is largely unknown. Current studies of plasticity tend to adopt a phenomenological reaction norm (RN) approach, which neglects the mechanisms underlying plasticity. Focusing on a concrete question - the optimal timing of bacterial sporulation - we here also consider a mechanistic approach, the evolution of a gene regulatory network (GRN) underlying plasticity. Using individual-based simulations, we compare the RN and GRN approach and find a number of striking differences. Most importantly, the GRN model results in a much higher diversity of responsive strategies than the RN model. We show that each of the evolved strategies is pre-adapted to a unique set of unseen environmental conditions. The regulatory mechanisms that control plasticity therefore critically link phenotypic plasticity to the adaptive potential of biological populations.

  6. Major regulatory mechanisms involved in sperm motility.

    Science.gov (United States)

    Pereira, Rute; Sá, Rosália; Barros, Alberto; Sousa, Mário

    2017-01-01

    The genetic bases and molecular mechanisms involved in the assembly and function of the flagellum components as well as in the regulation of the flagellar movement are not fully understood, especially in humans. There are several causes for sperm immotility, of which some can be avoided and corrected, whereas other are related to genetic defects and deserve full investigation to give a diagnosis to patients. This review was performed after an extensive literature search on the online databases PubMed, ScienceDirect, and Web of Science. Here, we review the involvement of regulatory pathways responsible for sperm motility, indicating possible causes for sperm immotility. These included the calcium pathway, the cAMP-dependent protein kinase pathway, the importance of kinases and phosphatases, the function of reactive oxygen species, and how the regulation of cell volume and osmolarity are also fundamental components. We then discuss main gene defects associated with specific morphological abnormalities. Finally, we slightly discuss some preventive and treatments approaches to avoid development of conditions that are associated with unspecified sperm immotility. We believe that in the near future, with the development of more powerful techniques, the genetic causes of sperm immotility and the regulatory mechanisms of sperm motility will be better understand, thus enabling to perform a full diagnosis and uncover new therapies.

  7. Mechanisms of T regulatory cell function.

    Science.gov (United States)

    Askenasy, Nadir; Kaminitz, Ayelet; Yarkoni, Shai

    2008-05-01

    Regulatory T cells (Treg) play a pivotal role in tolerance to self-antigens and tissue grafts, and suppression of autoimmune reactions. These cells modulate the intensity and quality of immune reactions through attenuation of the cytolytic activities of reactive immune cells. Treg cells operate primarily at the site of inflammation where they modulate the immune reaction through three major mechanisms: a) direct killing of cytotoxic cells through cell-to-cell contact, b) inhibition of cytokine production by cytotoxic cells, in particular interleukin-2, c) direct secretion of immunomodulatory cytokines, in particular TGF-beta and interleukin-10. In addition to differential contributions of these mechanisms under variable inflammatory conditions, mechanistic complexity and diversity evolves from the diverse tasks performed by various Treg cell subsets in different stages of the immune reaction. Here we attempt to integrate the current experimental evidence to delineate the major suppressive pathways of Treg cells.

  8. Multiphoton imaging of renal regulatory mechanisms.

    Science.gov (United States)

    Peti-Peterdi, János; Toma, Ildikó; Sipos, Arnold; Vargas, Sarah L

    2009-04-01

    Most physiological functions of the kidneys, including the clearance of metabolic waste products, maintenance of body fluid, electrolyte homeostasis, and blood pressure, are achieved by complex interactions between multiple renal cell types and previously inaccessible structures in many organ parts that have been difficult to study. Multiphoton fluorescence microscopy offers a state-of-the-art imaging technique for deep optical sectioning of living tissues and organs with minimal deleterious effects. Dynamic regulatory processes and multiple functions in the intact kidney can be quantitatively visualized in real time, noninvasively, and with submicron resolution. This article reviews innovative multiphoton imaging technologies and their applications that provided the most complex, immediate, and dynamic portrayal of renal function-clearly depicting as well as analyzing the components and mechanisms involved in renal (patho)physiology.

  9. Regulatory capital requirements and bail in mechanisms

    NARCIS (Netherlands)

    Joosen, B.P.M.; Haentjens, M.; Wessels, B.

    2015-01-01

    With the introduction of the Capital Requirements Regulation (CRR) in the European Union, the qualitative requirements for bank regulatory capital have changed. These changes aim at implementing in Europe the Basel III principles for better bank capital that is able to absorb losses of banks,

  10. Regulatory capital requirements and bail in mechanisms

    NARCIS (Netherlands)

    Joosen, B.P.M.; Haentjens, M.; Wessels, B.

    2015-01-01

    With the introduction of the Capital Requirements Regulation (CRR) in the European Union, the qualitative requirements for bank regulatory capital have changed. These changes aim at implementing in Europe the Basel III principles for better bank capital that is able to absorb losses of banks, withou

  11. A study of bacterial gene regulatory mechanisms

    DEFF Research Database (Denmark)

    Hansen, Sabine

    regulator studied accurately reproduced the experimental data. Simulations of system dynamics reveals that even two step regulatory cascades significantly increase response times compared to direct allosteric regulation of a transcription factor. It is observed that while many system behaviors...... of GRNs this thesis also provided the first evidence of the sensor histidine kinase VC1831 being an additional player in the Vibrio cholerae quorum sensing (QS) GRN. Bacteria use a process of cell-cell communication called QS which enable the bacterial cells to collectively control their gene expression...

  12. Self-regulatory mechanisms governing gender development.

    Science.gov (United States)

    Bussey, K; Bandura, A

    1992-10-01

    This study tested predictions about development of gender-related thought and action from social cognitive theory. Children at 4 levels of gender constancy were assessed for their gender knowledge, personal gender standards, and gender-linked behavior under different situational conditions. Irrespective of gender constancy level, all children engaged in more same-sex than cross-sex typed behavior. Younger children reacted in a gender stereotypic manner to peers' gender-linked behavior but did not regulate their own behavior on the basis of personal gender standards. Older children exhibited substantial self-regulatory guidance based on personal standards. They expressed anticipatory self-approval for same-sex typed behavior and self-criticism for cross-sex typed behavior. Their anticipatory self-sanctions, in turn, predicted their actual gender-linked behavior. Neither gender knowledge nor gender constancy predicted gender-linked behavior. These results lend support to social cognitive theory that evaluation and regulation of gender-linked conduct shifts developmentally from anticipatory social sanctions to anticipatory self-sanctions rooted in personal standards.

  13. Plant Antifreeze Proteins and Their Expression Regulatory Mechanism

    Institute of Scientific and Technical Information of China (English)

    Lin Yuan-zhen; Lin Shan-zhi; Zhang Zhi-yi; Zhang Wei; Liu Wen-feng

    2005-01-01

    Low temperature is one of the major limiting environmental factors which constitutes the growth, development,productivity and distribution of plants. Over the past several years, the proteins and genes associated with freezing resistance of plants have been widely studied. The recent progress of domestic and foreign research on plant antifreeze proteins and the identification and characterization of plant antifreeze protein genes, especially on expression regulatory mechanism of plant antifreeze proteins are reviewed in this paper. Finally, some unsolved problems and the trend of research in physiological functions and gene expression regulatory mechanism of plant antifreeze proteins are discussed.

  14. Epigenetic regulatory mechanisms associated with infertility

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Madon, Prochi F; Parikh, Firuza R

    2010-01-01

    Infertility is a complex human condition and is known to be caused by numerous factors including genetic alterations and abnormalities. Increasing evidence from studies has associated perturbed epigenetic mechanisms with spermatogenesis and infertility. However, there has been no consensus...... on whether one or a collective of these altered states is responsible for the onset of infertility. Epigenetic alterations involve changes in factors that regulate gene expression without altering the physical sequence of DNA. Understanding these altered epigenetic states at the genomic level along...... with higher order organisation of chromatin in genes associated with infertility and pericentromeric regions of chromosomes, particularly 9 and Y, could further identify causes of idiopathic infertility. Determining the association between DNA methylation, chromatin state, and noncoding RNAs...

  15. Gene regulatory networks elucidating huanglongbing disease mechanisms.

    Science.gov (United States)

    Martinelli, Federico; Reagan, Russell L; Uratsu, Sandra L; Phu, My L; Albrecht, Ute; Zhao, Weixiang; Davis, Cristina E; Bowman, Kim D; Dandekar, Abhaya M

    2013-01-01

    Next-generation sequencing was exploited to gain deeper insight into the response to infection by Candidatus liberibacter asiaticus (CaLas), especially the immune disregulation and metabolic dysfunction caused by source-sink disruption. Previous fruit transcriptome data were compared with additional RNA-Seq data in three tissues: immature fruit, and young and mature leaves. Four categories of orchard trees were studied: symptomatic, asymptomatic, apparently healthy, and healthy. Principal component analysis found distinct expression patterns between immature and mature fruits and leaf samples for all four categories of trees. A predicted protein - protein interaction network identified HLB-regulated genes for sugar transporters playing key roles in the overall plant responses. Gene set and pathway enrichment analyses highlight the role of sucrose and starch metabolism in disease symptom development in all tissues. HLB-regulated genes (glucose-phosphate-transporter, invertase, starch-related genes) would likely determine the source-sink relationship disruption. In infected leaves, transcriptomic changes were observed for light reactions genes (downregulation), sucrose metabolism (upregulation), and starch biosynthesis (upregulation). In parallel, symptomatic fruits over-expressed genes involved in photosynthesis, sucrose and raffinose metabolism, and downregulated starch biosynthesis. We visualized gene networks between tissues inducing a source-sink shift. CaLas alters the hormone crosstalk, resulting in weak and ineffective tissue-specific plant immune responses necessary for bacterial clearance. Accordingly, expression of WRKYs (including WRKY70) was higher in fruits than in leaves. Systemic acquired responses were inadequately activated in young leaves, generally considered the sites where most new infections occur.

  16. Density-dependence as a size-independent regulatory mechanism

    NARCIS (Netherlands)

    De Vladar, H.P.

    2006-01-01

    The growth function of populations is central in biomathematics. The main dogma is the existence of density-dependence mechanisms, which can be modelled with distinct functional forms that depend on the size of the Population. One important class of regulatory functions is the theta-logistic, which

  17. Density-dependence as a size-independent regulatory mechanism

    NARCIS (Netherlands)

    De Vladar, H.P.

    2006-01-01

    The growth function of populations is central in biomathematics. The main dogma is the existence of density-dependence mechanisms, which can be modelled with distinct functional forms that depend on the size of the Population. One important class of regulatory functions is the theta-logistic, which

  18. General trends in the evolution of prokaryotic transcriptional regulatory networks.

    Science.gov (United States)

    Madan Babu, M; Balaji, S; Aravind, L

    2007-01-01

    Gene expression in organisms is controlled by regulatory proteins termed transcription factors, which recognize and bind to specific nucleotide sequences. Over the years, considerable information has accumulated on the regulatory interactions between transcription factors and their target genes in various model prokaryotes, such as Escherichia coli and Bacillus subtilis. This has allowed the representation of this information in the form of a directed graph, which is commonly referred to as the transcriptional regulatory network. The network representation provides us with an excellent conceptual framework to understand the structure of the transcriptional regulation, both at local and global levels of organization. Several studies suggest that the transcriptional network inferred from model organisms may be approximated by a scale-free topology, which in turn implies the presence of a relatively small group of highly connected regulators (hubs or global regulators). While the graph theoretical principles have been applied to infer various properties of such networks, there have been few studies that have actually investigated the evolution of the transcriptional regulatory networks across diverse organisms. Using recently developed computational methods that exploit various evolutionary principles, we have attempted to reconstruct and compare these networks across a wide-range of prokaryotes. This has provided several insights on the modification and diversification of network structures of various organisms in course of evolution. Firstly, we observed that target genes show a much higher level of conservation than their transcriptional regulators. This in turn suggested that the same set of functions could be differently controlled across diverse organisms, contributing significantly to their adaptive radiations. In particular, at the local level of network structure, organism-specific optimization of the transcription network has evolved primarily via tinkering

  19. Molecular regulatory mechanisms of osteoclastogenesis through cytoprotective enzymes

    Directory of Open Access Journals (Sweden)

    Hiroyuki Kanzaki

    2016-08-01

    Full Text Available It has been reported that reactive oxygen species (ROS, such as hydrogen peroxide and superoxide, take part in osteoclast differentiation as intra-cellular signaling molecules. The current assumed signaling cascade from RANK to ROS production is RANK, TRAF6, Rac1, and then Nox. The target molecules of ROS in RANKL signaling remain unclear; however, several reports support the theory that NF-κB signaling could be the crucial downstream signaling molecule of RANKL-mediated ROS signaling. Furthermore, ROS exert cytotoxic effects such as peroxidation of lipids and phospholipids and oxidative damage to proteins and DNA. Therefore, cells have several protective mechanisms against oxidative stressors that mainly induce cytoprotective enzymes and ROS scavenging. Three well-known mechanisms regulate cytoprotective enzymes including Nrf2-, FOXO-, and sirtuin-dependent mechanisms. Several reports have indicated a crosslink between FOXO- and sirtuin-dependent regulatory mechanisms. The agonists against the regulatory mechanisms are reported to induce these cytoprotective enzymes successfully. Some of them inhibit osteoclast differentiation and bone destruction via attenuation of intracellular ROS signaling. In this review article, we discuss the above topics and summarize the current information available on the relationship between cytoprotective enzymes and osteoclastogenesis.

  20. Molecular regulatory mechanisms of osteoclastogenesis through cytoprotective enzymes

    Science.gov (United States)

    Kanzaki, Hiroyuki; Shinohara, Fumiaki; Kanako, Itohiya; Yamaguchi, Yuuki; Fukaya, Sari; Miyamoto, Yutaka; Wada, Satoshi; Nakamura, Yoshiki

    2016-01-01

    It has been reported that reactive oxygen species (ROS), such as hydrogen peroxide and superoxide, take part in osteoclast differentiation as intra-cellular signaling molecules. The current assumed signaling cascade from RANK to ROS production is RANK, TRAF6, Rac1, and then Nox. The target molecules of ROS in RANKL signaling remain unclear; however, several reports support the theory that NF-κB signaling could be the crucial downstream signaling molecule of RANKL-mediated ROS signaling. Furthermore, ROS exert cytotoxic effects such as peroxidation of lipids and phospholipids and oxidative damage to proteins and DNA. Therefore, cells have several protective mechanisms against oxidative stressors that mainly induce cytoprotective enzymes and ROS scavenging. Three well-known mechanisms regulate cytoprotective enzymes including Nrf2-, FOXO-, and sirtuin-dependent mechanisms. Several reports have indicated a crosslink between FOXO- and sirtuin-dependent regulatory mechanisms. The agonists against the regulatory mechanisms are reported to induce these cytoprotective enzymes successfully. Some of them inhibit osteoclast differentiation and bone destruction via attenuation of intracellular ROS signaling. In this review article, we discuss the above topics and summarize the current information available on the relationship between cytoprotective enzymes and osteoclastogenesis. PMID:26795736

  1. Gene regulatory network inference using out of equilibrium statistical mechanics.

    Science.gov (United States)

    Benecke, Arndt

    2008-08-01

    Spatiotemporal control of gene expression is fundamental to multicellular life. Despite prodigious efforts, the encoding of gene expression regulation in eukaryotes is not understood. Gene expression analyses nourish the hope to reverse engineer effector-target gene networks using inference techniques. Inference from noisy and circumstantial data relies on using robust models with few parameters for the underlying mechanisms. However, a systematic path to gene regulatory network reverse engineering from functional genomics data is still impeded by fundamental problems. Recently, Johannes Berg from the Theoretical Physics Institute of Cologne University has made two remarkable contributions that significantly advance the gene regulatory network inference problem. Berg, who uses gene expression data from yeast, has demonstrated a nonequilibrium regime for mRNA concentration dynamics and was able to map the gene regulatory process upon simple stochastic systems driven out of equilibrium. The impact of his demonstration is twofold, affecting both the understanding of the operational constraints under which transcription occurs and the capacity to extract relevant information from highly time-resolved expression data. Berg has used his observation to predict target genes of selected transcription factors, and thereby, in principle, demonstrated applicability of his out of equilibrium statistical mechanics approach to the gene network inference problem.

  2. Ochratoxin A Producing Fungi, Biosynthetic Pathway and Regulatory Mechanisms.

    Science.gov (United States)

    Wang, Yan; Wang, Liuqing; Liu, Fei; Wang, Qi; Selvaraj, Jonathan Nimal; Xing, Fuguo; Zhao, Yueju; Liu, Yang

    2016-03-21

    Ochratoxin A (OTA), mainly produced by Aspergillus and Penicillum species, is one of the most important mycotoxin contaminants in agricultural products. It is detrimental to human health because of its nephrotoxicity, hepatotoxicity, carcinogenicity, teratogenicity, and immunosuppression. OTA structurally consists of adihydrocoumarin moiety linked with l-phenylalanine via an amide bond. OTA biosynthesis has been putatively hypothesized, although several contradictions exist on some processes of the biosynthetic pathway. We discuss recent information on molecular studies of OTA biosynthesis despite insufficient genetic background in detail. Accordingly, genetic regulation has also been explored with regard to the interaction between the regulators and the environmental factors. In this review, we focus on three aspects of OTA: OTA-producing strains, OTA biosynthetic pathway and the regulation mechanisms of OTA production. This can pave the way to assist in protecting food and feed from OTA contamination by understanding OTA biosynthetic pathway and regulatory mechanisms.

  3. Ochratoxin A Producing Fungi, Biosynthetic Pathway and Regulatory Mechanisms

    Science.gov (United States)

    Wang, Yan; Wang, Liuqing; Liu, Fei; Wang, Qi; Selvaraj, Jonathan Nimal; Xing, Fuguo; Zhao, Yueju; Liu, Yang

    2016-01-01

    Ochratoxin A (OTA), mainly produced by Aspergillus and Penicillum species, is one of the most important mycotoxin contaminants in agricultural products. It is detrimental to human health because of its nephrotoxicity, hepatotoxicity, carcinogenicity, teratogenicity, and immunosuppression. OTA structurally consists of adihydrocoumarin moiety linked with l-phenylalanine via an amide bond. OTA biosynthesis has been putatively hypothesized, although several contradictions exist on some processes of the biosynthetic pathway. We discuss recent information on molecular studies of OTA biosynthesis despite insufficient genetic background in detail. Accordingly, genetic regulation has also been explored with regard to the interaction between the regulators and the environmental factors. In this review, we focus on three aspects of OTA: OTA-producing strains, OTA biosynthetic pathway and the regulation mechanisms of OTA production. This can pave the way to assist in protecting food and feed from OTA contamination by understanding OTA biosynthetic pathway and regulatory mechanisms. PMID:27007394

  4. Regulatory focus and generalized trust: the impact of prevention-focused self-regulation on trusting others.

    Science.gov (United States)

    Keller, Johannes; Mayo, Ruth; Greifeneder, Rainer; Pfattheicher, Stefan

    2015-01-01

    The current research suggests that taking self-regulatory mechanisms into account provides insights regarding individuals' responses to threats in social interactions. In general, based on the notion that a prevention-focused orientation of self-regulation is associated with a need for security and a vigilant tendency to avoid losses and other types of negative events we advocate that a prevention-focused orientation, both as a disposition as well as a situationally induced state, lowers generalized trust, thus hindering cooperation within social interactions that entail threats. Specifically, we found that the more individuals' habitual self-regulatory orientation is dominated by a prevention focus, the less likely they are to score high on a self-report measure of generalized trust (Study 1), and to express trust in a trust game paradigm as manifested in lower sums of transferred money (Studies 2 and 3). Similar findings were found when prevention focus was situationally manipulated (Study 4). Finally, one possible factor underlying the impact of prevention-focused self-regulation on generalized trust was demonstrated as individuals with a special sensitivity to negative information were significantly affected by a subtle prevention focus manipulation (versus control condition) in that they reacted with reduced trust in the trust game (Study 5). In sum, the current findings document the crucial relevance of self-regulatory orientations as conceptualized in regulatory focus theory regarding generalized trust and responses to threats within a social interaction. The theoretical and applied implications of the findings are discussed.

  5. From continuum mechanics to general relativity

    CERN Document Server

    Boehmer, Christian G

    2014-01-01

    Using ideas from continuum mechanics we construct a theory of gravity. We show that this theory is equivalent to Einstein's theory of general relativity; it is also a much faster way of reaching general relativity than the conventional route. Our approach is simple and natural: we form a very general model and then apply two physical assumptions supported by experimental evidence. This easily reduces our construction to a model equivalent to general relativity. Finally, we suggest a simple way of modifying our theory to investigate non-standard space-time symmetries.

  6. Toxin-mediated gene regulatory mechanism in Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Hwang-Soo Joo

    2016-12-01

    Full Text Available The dangerous human pathogen Staphylococcus aureus relies heavily on toxins to cause disease, but toxin production can put a strong burden on the bacteria’s energy balance. Thus, controlling the synthesis of proteins solely needed in times of toxin production represents a way for the bacteria to avoid wasting energy. One hypothetical manner to accomplish this sort of regulation is by gene regulatory functions of the toxins themselves. There have been several reports about gene regulation by toxins in S. aureus, but these were never verified on the molecular level. In our study published in MBio [Joo et al., 7(5. pii: e01579-16], we show that phenol-soluble modulins (PSMs, important peptide toxins of S. aureus, release a repressor from the promoter of the operon encoding the toxin export system, thereby enabling toxin secretion. This study describes the first molecular regulatory mechanism exerted by an S. aureus toxin, setting a paradigmatic example of how S. aureus toxins may influence cell functions to adjust them to times of toxin production.

  7. Generalized statistical mechanics for superstatistical systems.

    Science.gov (United States)

    Beck, Christian

    2011-01-28

    Mesoscopic systems in a slowly fluctuating environment are often well described by superstatistical models. We develop a generalized statistical mechanics formalism for superstatistical systems, by mapping the superstatistical complex system onto a system of ordinary statistical mechanics with modified energy levels. We also briefly review recent examples of applications of the superstatistics concept for three very different subject areas, namely train delay statistics, turbulent tracer dynamics and cancer survival statistics.

  8. Generalized Plastic Mechanics and Its Application

    Institute of Scientific and Technical Information of China (English)

    Zheng Yingren; Kong Liang

    2006-01-01

    The development of geotechnical plasticity is reviewed and some problems of applying the classical plastic mechanics (CPM) to geomaterials are analyzed, and then CPM's three hypotheses not fitted the deformation mechanism of geomaterials are pointed out. By giving up the three hypotheses, a generalized plastic potential theory can be obtained from solid mechanics directly, and then the traditional plastic mechanics can be changed to a more generalized plastic mechanics, namely generalized plastic mechanics (GPM). The GPM adopts the component theory as theoretical base, so it can reflect the influence of transition of stress path. The unreasonable phenomena such as excessive dilatancy caused by adopting the normality-flow law can be avoided, and the error caused by the arbitrary assumption of plastic potential surfaces cannot be produced. The yield surface theory, hardening laws and stress-strain relations of GPM are given, and a GPM including the rotation of principal stress axes is also established. It is pointed out that the yield condition is a state parameter as well as a test parameter, and it can only be given by test. After the practical application, it is shown that the GPM cannot only be applied to the modeling theory of geomaterials but also to other fields of geomechanics such as limit analysis.

  9. Regulatory Mechanisms and Physiological Significance of Reelin Function.

    Science.gov (United States)

    Kohno, Takao

    2017-01-01

     Reelin is a large secreted glycoprotein that regulates embryonic neuronal lamination and adult synaptic function. Secreted Reelin binds to lipoprotein receptors expressed on neurons. The Reelin-receptor interaction induces phosphorylation of an intracellular adaptor protein Dab1, which is required for normal embryonic brain development and adult brain functions. It has been suggested that Reelin hypofunction plays a role in the pathogenesis of several neuropsychiatric diseases, such as schizophrenia, autism, and Alzheimer's disease. Thus upregulation of Reelin activity may ameliorate the symptoms of neuropsychiatric diseases. However, the regulatory mechanism underlying the functions of Reelin is largely unknown and there are no good animal models of Reelin malfunction; thus, causal relations between Reelin and neuropsychiatric diseases remain unclear. Recently, our studies have shown that proteolytic cleavage of the Reelin protein regulates its activity. Herein, we will review recent findings about relations between Reelin and Alzheimer's disease, and the mechanism underlying the regulation of Reelin function by proteolytic cleavage. Also, we will discuss the prospect of treating neuropsychiatric diseases by upregulation of Reelin activity.

  10. Generalized Borel transform technique in quantum mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Epele, L.N.; Fanchiotti, H.; Garcia Canal, C.A.; Marucho, M

    2003-03-13

    We present the Generalized Borel Transform (GBT). This new approach allows one to obtain approximate solutions of Laplace/Mellin transform valid in both, perturbative and non-perturbative regimes. We compare the results provided by the GBT for a solvable model of quantum mechanics with those provided by standard techniques, as the conventional Borel sum, or its modified versions. We found that our approach is very efficient for obtaining both the low and the high energy behavior of the model.

  11. Architecture and Molecular Mechanism of PAN, the Archaeal Proteasome Regulatory ATPase*

    Science.gov (United States)

    Medalia, Noa; Beer, Avital; Zwickl, Peter; Mihalache, Oana; Beck, Martin; Medalia, Ohad; Navon, Ami

    2009-01-01

    In Archaea, an hexameric ATPase complex termed PAN promotes proteins unfolding and translocation into the 20 S proteasome. PAN is highly homologous to the six ATPases of the eukaryotic 19 S proteasome regulatory complex. Thus, insight into the mechanism of PAN function may reveal a general mode of action mutual to the eukaryotic 19 S proteasome regulatory complex. In this study we generated a three-dimensional model of PAN from tomographic reconstruction of negatively stained particles. Surprisingly, this reconstruction indicated that the hexameric complex assumes a two-ring structure enclosing a large cavity. Assessment of distinct three-dimensional functional states of PAN in the presence of adenosine 5′-O-(thiotriphosphate) and ADP and in the absence of nucleotides outlined a possible mechanism linking nucleotide binding and hydrolysis to substrate recognition, unfolding, and translocation. A novel feature of the ATPase complex revealed in this study is a gate controlling the “exit port” of the regulatory complex and, presumably, translocation into the 20 S proteasome. Based on our structural and biochemical findings, we propose a possible model in which substrate binding and unfolding are linked to structural transitions driven by nucleotide binding and hydrolysis, whereas translocation into the proteasome only depends upon the presence of an unfolded substrate and binding but not hydrolysis of nucleotide. PMID:19363223

  12. Redox-switch regulatory mechanism of thiolase from Clostridium acetobutylicum.

    Science.gov (United States)

    Kim, Sangwoo; Jang, Yu-Sin; Ha, Sung-Chul; Ahn, Jae-Woo; Kim, Eun-Jung; Lim, Jae Hong; Cho, Changhee; Ryu, Yong Shin; Lee, Sung Kuk; Lee, Sang Yup; Kim, Kyung-Jin

    2015-09-22

    Thiolase is the first enzyme catalysing the condensation of two acetyl-coenzyme A (CoA) molecules to form acetoacetyl-CoA in a dedicated pathway towards the biosynthesis of n-butanol, an important solvent and biofuel. Here we elucidate the crystal structure of Clostridium acetobutylicum thiolase (CaTHL) in its reduced/oxidized states. CaTHL, unlike those from other aerobic bacteria such as Escherichia coli and Zoogloea ramegera, is regulated by the redox-switch modulation through reversible disulfide bond formation between two catalytic cysteine residues, Cys88 and Cys378. When CaTHL is overexpressed in wild-type C. acetobutylicum, butanol production is reduced due to the disturbance of acidogenic to solventogenic shift. The CaTHL(V77Q/N153Y/A286K) mutant, which is not able to form disulfide bonds, exhibits higher activity than wild-type CaTHL, and enhances butanol production upon overexpression. On the basis of these results, we suggest that CaTHL functions as a key enzyme in the regulation of the main metabolism of C. acetobutylicum through a redox-switch regulatory mechanism.

  13. Naturally occurring regulatory T cells: markers, mechanisms, and manipulation.

    Science.gov (United States)

    Schmetterer, Klaus G; Neunkirchner, Alina; Pickl, Winfried F

    2012-06-01

    Naturally occurring CD4(+)CD25(high) forkhead box protein 3 (FOXP3)(+) regulatory T cells (nTregs) are key mediators of immunity, which orchestrate and maintain tolerance to self and foreign antigens. In the recent 1.5 decades, a multitude of studies have aimed to define the phenotype and function of nTregs and to assess their therapeutic potential for modulating immune mediated disorders such as autoimmunity, allergy, and episodes of transplant rejection. In this review, we summarize the current knowledge on the biology of nTregs. We address the exact definition of nTregs by specific markers and combinations thereof, which is a prerequisite for the state-of-the-art isolation of defined nTreg populations. Furthermore, we discuss the mechanism by which nTregs mediate immunosuppression and how this knowledge might translate into novel therapeutic modalities. With first clinical studies of nTreg-based therapies being finished, questions concerning the reliable sources of nTregs are becoming more and more eminent. Consequently, approaches allowing conversion of CD4(+) T cells into nTregs by coculture with antigen-presenting cells, cytokines, and/or pharmacological agents are discussed. In addition, genetic engineering approaches for the generation of antigen-specific nTregs are described.

  14. Cis-regulatory elements: molecular mechanisms and evolutionary processes underlying divergence.

    Science.gov (United States)

    Wittkopp, Patricia J; Kalay, Gizem

    2011-12-06

    Cis-regulatory sequences, such as enhancers and promoters, control development and physiology by regulating gene expression. Mutations that affect the function of these sequences contribute to phenotypic diversity within and between species. With many case studies implicating divergent cis-regulatory activity in phenotypic evolution, researchers have recently begun to elucidate the genetic and molecular mechanisms that are responsible for cis-regulatory divergence. Approaches include detailed functional analysis of individual cis-regulatory elements and comparing mechanisms of gene regulation among species using the latest genomic tools. Despite the limited number of mechanistic studies published to date, this work shows how cis-regulatory activity can diverge and how studies of cis-regulatory divergence can address long-standing questions about the genetic mechanisms of phenotypic evolution.

  15. Symbiotic Nitrogen Fixation in Legume Nodules: Metabolism and Regulatory Mechanisms

    OpenAIRE

    Saad Sulieman; Lam-Son Phan Tran

    2014-01-01

    The special issue “Symbiotic Nitrogen Fixation in Legume Nodules: Metabolism and Regulatory Mechanisms” aims to investigate the physiological and biochemical advances in the symbiotic process with an emphasis on nodule establishment, development and functioning. The original research articles included in this issue provide important information regarding novel aspects of nodule metabolism and various regulatory pathways, which could have important future implications. This issue also included...

  16. Parsing regulatory DNA: General tasks, techniques, and the PhyloGibbs approach

    Indian Academy of Sciences (India)

    Rahul Siddharthan

    2007-08-01

    In this review, we discuss the general problem of understanding transcrip tional regulation from DNA sequence and prior information. The main tasks we discuss are predicting local regions of DNA, cis-regulatory modules (CRMs) that contain binding sites for transcription factors (TFs), and predicting individ ual binding sites. We review various existing methods, and then describe the approach taken by PhyloGibbs, a recent motif-finding algorithm that we developed to predict TF binding sites, and PhyloGibbs-MP, an extension to PhyloGibbs that tackles other tasks in regulatory genomics, particularly prediction of CRMs.

  17. General Auction Mechanism for Search Advertising

    CERN Document Server

    Aggarwal, Gagan; Pal, David; Pal, Martin

    2008-01-01

    In sponsored search, a number of advertising slots is available on a search results page, and have to be allocated among a set of advertisers competing to display an ad on the page. This gives rise to a bipartite matching market that is typically cleared by the way of an automated auction. Several auction mechanisms have been proposed, with variants of the Generalized Second Price (GSP) being widely used in practice. A rich body of work on bipartite matching markets builds upon the stable marriage model of Gale and Shapley and the assignment model of Shapley and Shubik. We apply insights from this line of research into the structure of stable outcomes and their incentive properties to advertising auctions. We model advertising auctions in terms of an assignment model with linear utilities, extended with bidder and item specific maximum and minimum prices. Auction mechanisms like the commonly used GSP or the well-known Vickrey-Clarke-Groves (VCG) are interpreted as simply computing a \\emph{bidder-optimal stabl...

  18. DMPD: The interferon regulatory factor family in host defense: mechanism of action. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17502370 The interferon regulatory factor family in host defense: mechanism of acti....html) (.csml) Show The interferon regulatory factor family in host defense: mechanism of action. PubmedID 1...7502370 Title The interferon regulatory factor family in host defense: mechanism

  19. Future research and therapeutic applications of human stem cells: general, regulatory, and bioethical aspects

    Directory of Open Access Journals (Sweden)

    Liras Antonio

    2010-12-01

    Full Text Available Abstract There is much to be investigated about the specific characteristics of stem cells and about the efficacy and safety of the new drugs based on this type of cells, both embryonic as adult stem cells, for several therapeutic indications (cardiovascular and ischemic diseases, diabetes, hematopoietic diseases, liver diseases. Along with recent progress in transference of nuclei from human somatic cells, as well as iPSC technology, has allowed availability of lineages of all three germ layers genetically identical to those of the donor patient, which permits safe transplantation of organ-tissue-specific adult stem cells with no immune rejection. The main objective is the need for expansion of stem cell characteristics to maximize stem cell efficacy (i.e. the proper selection of a stem cell and the efficacy (maximum effect and safety of stem cell derived drugs. Other considerations to take into account in cell therapy will be the suitability of infrastructure and technical staff, biomaterials, production costs, biobanks, biosecurity, and the biotechnological industry. The general objectives in the area of stem cell research in the next few years, are related to identification of therapeutic targets and potential therapeutic tests, studies of cell differentiation and physiological mechanisms, culture conditions of pluripotent stem cells and efficacy and safety tests for stem cell-based drugs or procedures to be performed in both animal and human models in the corresponding clinical trials. A regulatory framework will be required to ensure patient accessibility to products and governmental assistance for their regulation and control. Bioethical aspects will be required related to the scientific and therapeutic relevance and cost of cryopreservation over time, but specially with respect to embryos which may ultimately be used for scientific uses of research as source of embryonic stem cells, in which case the bioethical conflict may be further

  20. Transcriptional control of yeast ribosome biogenesis: A multifaceted role for general regulatory factors.

    Science.gov (United States)

    Bosio, Maria Cristina; Fermi, Beatrice; Dieci, Giorgio

    2017-08-08

    In Saccharomyces cerevisiae, a group of more than 200 co-regulated genes (Ribi genes) is involved in ribosome biogenesis. This regulon has recently been shown to rely on a small set of transcriptional regulators (mainly Abf1, but also Reb1, Tbf1 and Rap1) previously referred to as general regulatory factors (GRFs) because of their widespread binding and action at many promoters and other specialized genomic regions. Intriguingly, Abf1 binding to Ribi genes is differentially modulated in response to distinct nutrition signaling pathways. Such a dynamic promoter association has the potential to orchestrate both activation and repression of Ribi genes in synergy with neighboring regulatory sites and through the functional interplay of histone acetyltransferases and deacetylases.

  1. General description of the national regulatory framework; Descripcion general del marco regulatorio nacional

    Energy Technology Data Exchange (ETDEWEB)

    Basurto C, J. [Comision Nacional de Seguridad Nuclear y Salvaguardias, Dr. Jose Ma. Barragan No. 779, Col. Narvarte, 03020 Mexico D. F. (Mexico)

    2008-12-15

    Of the six existing hierarchy in the Mexican legal system, the first five of the Constitution of the Mexican Official Norms have a binding character, containing mandatory requirements to meet, while the sixth is not binding. The articles that have nuclear subject in the Mexican Constitution are 25, 27 and 28. At the same hierarchical level as the Constitution is the international treaties signed and ratified by our country, such as for example the Nuclear Safety Convention or the Convention on the Nuclear Materials Physical Protection. For the treaties negotiation process consists of a text adoption, the authentication which implies the final content signature and unalterable, the Senate approval and the consent submission, which implies the ratification and publication in the Federation Official Gazette. In the case of Mexican laws your proposition process includes an initiative, the analysis of the relevant committee, the discussion, approval, sanction, and with it the publication of the initiation force. The road can become very convoluted because some steps are recurrent, returning to the same level several times. Regulations whose purpose is to clarify, develop or explain the general principles contained in the laws that relate to more obtainable your application are subject to a similarly complicated process. First we developed a preliminary draft by the competent authority subject to revision and opinion of the respective institutions prior to submission to the Federal Executive. The final document is submitted to the latter project, which must be approved by the agencies involved, approved by the Federal Executive and finally published in the Federation Official Gazette, from which it launched its application. (Author)

  2. Structural imprints in vivo decode RNA regulatory mechanisms

    Science.gov (United States)

    Spitale, Robert C.; Flynn, Ryan A.; Zhang, Qiangfeng Cliff; Crisalli, Pete; Lee, Byron; Jung, Jong-Wha; Kuchelmeister, Hannes Y.; Batista, Pedro J.; Torre, Eduardo A.; Kool, Eric T.; Chang, Howard Y.

    2015-03-01

    Visualizing the physical basis for molecular behaviour inside living cells is a great challenge for biology. RNAs are central to biological regulation, and the ability of RNA to adopt specific structures intimately controls every step of the gene expression program. However, our understanding of physiological RNA structures is limited; current in vivo RNA structure profiles include only two of the four nucleotides that make up RNA. Here we present a novel biochemical approach, in vivo click selective 2'-hydroxyl acylation and profiling experiment (icSHAPE), which enables the first global view, to our knowledge, of RNA secondary structures in living cells for all four bases. icSHAPE of the mouse embryonic stem cell transcriptome versus purified RNA folded in vitro shows that the structural dynamics of RNA in the cellular environment distinguish different classes of RNAs and regulatory elements. Structural signatures at translational start sites and ribosome pause sites are conserved from in vitro conditions, suggesting that these RNA elements are programmed by sequence. In contrast, focal structural rearrangements in vivo reveal precise interfaces of RNA with RNA-binding proteins or RNA-modification sites that are consistent with atomic-resolution structural data. Such dynamic structural footprints enable accurate prediction of RNA-protein interactions and N6-methyladenosine (m6A) modification genome wide. These results open the door for structural genomics of RNA in living cells and reveal key physiological structures controlling gene expression.

  3. Beyond Quantum Mechanics and General Relativity

    CERN Document Server

    Gregori, Andrea

    2010-01-01

    In this note I present the main ideas of my proposal about the theoretical framework that could underlie, and therefore "unify", Quantum Mechanics and Relativity, and I briefly summarize the implications and predictions.

  4. Conservation of apoptosis as an immune regulatory mechanism: effects of cortisol and cortisone on carp lymphocytes.

    NARCIS (Netherlands)

    Weyts, F.A.A.; Verburg-van Kemenade, B.M.L.; Flik, G.; Lambert, J.G.D.; Wendelaar Bonga, S.E.

    1997-01-01

    This is the first study to show that apoptosis as an immune regulatory mechanism is conserved in fish, demonstrating its importance in maintaining immunological homeostasis. The data further show that this mechanism is subject to control by glucocorticosteroids. Carp plasma cortisol concentrations

  5. Conservation of apoptosis as an immune regulatory mechanism: effects of cortisol and cortisone on carp lymphocytes.

    NARCIS (Netherlands)

    Weyts, F.A.A.; Verburg-van Kemenade, B.M.L.; Flik, G.; Lambert, J.G.D.; Wendelaar Bonga, S.E.

    1997-01-01

    This is the first study to show that apoptosis as an immune regulatory mechanism is conserved in fish, demonstrating its importance in maintaining immunological homeostasis. The data further show that this mechanism is subject to control by glucocorticosteroids. Carp plasma cortisol concentrations i

  6. Design’s Mechanism -- General Morphological Analysis

    Science.gov (United States)

    2012-05-04

    and Melvin Webber, “Dilemmas in a General Theory of Planning,” Policy Sciences no. 4 (1973): 155-160. 13 Orson Scott Card, Ender’s Game (New York...34 Bibliography Barrera, Guillermo, interview by John Miller. ADM (RET) (2012). Card, Orson Scott . Ender’s Game. New York: Tor Books

  7. Apoptosis as a mechanism of T-regulatory cell homeostasis and suppression.

    Science.gov (United States)

    Yolcu, Esma S; Ash, Shifra; Kaminitz, Ayelet; Sagiv, Yuval; Askenasy, Nadir; Yarkoni, Shai

    2008-01-01

    Activation-induced cell death is a general mechanism of immune homeostasis through negative regulation of clonal expansion of activated immune cells. This mechanism is involved in the maintenance of self- and transplant tolerance through polarization of the immune responses. The Fas/Fas-ligand interaction is a major common executioner of apoptosis in lymphocytes, with a dual role in regulatory T cell (Treg) function: Treg cell homeostasis and Treg cell-mediated suppression. Sensitivity to apoptosis and the patterns of Treg-cell death are of outmost importance in immune homeostasis that affects the equilibrium between cytolytic and suppressor forces in activation and termination of immune activity. Naive innate (naturally occurring) Treg cells present variable sensitivities to apoptosis, related to their turnover rates in tissue under steady state conditions. Following activation, Treg cells are less sensitive to apoptosis than cytotoxic effector subsets. Their susceptibility to apoptosis is influenced by cytokines within the inflammatory environment (primarily interleukin-2), the mode of antigenic stimulation and the proliferation rates. Here, we attempt to resolve some controversies surrounding the sensitivity of Treg cells to apoptosis under various experimental conditions, to delineate the function of cell death in regulation of immunity.

  8. Sociocognitive self-regulatory mechanisms governing judgments of the acceptability and likelihood of sport cheating.

    Science.gov (United States)

    d'Arripe-Longueville, Fabienne; Corrion, Karine; Scoffier, Stéphanie; Roussel, Peggy; Chalabaev, Aïna

    2010-10-01

    This study extends previous psychosocial literature (Bandura et al., 2001, 2003) by examining a structural model of the self-regulatory mechanisms governing the acceptability and likelihood of cheating in a sport context. Male and female adolescents (N = 804), aged 15-20 years, took part in this study. Negative affective self-regulatory efficacy influenced the acceptability and likelihood of cheating through the mediating role of moral disengagement, in females and males. Affective efficacy positively influenced prosocial behavior through moral disengagement or through resistive self-regulatory efficacy and social efficacy, in both groups. The direct effects of affective efficacy on beliefs about cheating were only evident in females. These results extend the findings of Bandura et al. (2001, 2003) to the sport context and suggest that affective and resistive self-regulatory efficacy operate in concert in governing adolescents' moral disengagement and transgressive behaviors in sport.

  9. Regulatory mechanisms of the phasic respiratory activity in cricothyroid muscle.

    Science.gov (United States)

    Dejonckere, P H; Lebacq, J

    1984-01-01

    Phasic respiratory activity of the cricothyroid muscle has been investigated with electromyography in 15 normal subjects, and in 19 pathological cases with well defined neurological troubles. It appears that phasic respiratory activity in the cricothyroid muscle, probably centrally generated, is under control of a complex and intricate mechanisms, in which the nervus laryngeus superior, the nervus laryngeus inferior, the vagus nerve and cross connections all together intervene. Furthermore, a peripheral modulation related somehow to the resistance of the airways is present. Despite differences between animal species, it seems that qualitatively the same contributing elements are present in animals and humans.

  10. Regulatory mechanisms for glycogenolysis and K+ uptake in brain astrocytes.

    Science.gov (United States)

    DiNuzzo, Mauro; Mangia, Silvia; Maraviglia, Bruno; Giove, Federico

    2013-11-01

    Recent advances in brain energy metabolism support the notion that glycogen in astrocytes is necessary for the clearance of neuronally-released K(+) from the extracellular space. However, how the multiple metabolic pathways involved in K(+)-induced increase in glycogen turnover are regulated is only partly understood. Here we summarize the current knowledge about the mechanisms that control glycogen metabolism during enhanced K(+) uptake. We also describe the action of the ubiquitous Na(+)/K(+) ATPase for both ion transport and intracellular signaling cascades, and emphasize its importance in understanding the complex relation between glycogenolysis and K(+) uptake.

  11. Mechanics of extended masses in general relativity

    CERN Document Server

    Harte, Abraham I

    2011-01-01

    The "external" or "bulk" motion of extended bodies is studied in general relativity. Material objects of arbitrary shape, spin, internal composition, and velocity are allowed as long as the metric remains near a vacuum solution (with a possible cosmological constant). Under this restriction, physically reasonable linear and angular momenta are proposed that evolve as though they were the momenta of an extended test body moving in an effective vacuum metric. This result holds to all multipole orders. The portion of the physical metric that does not directly affect the motion is a slightly generalized form of the Detweiler-Whiting S-field originally introduced in the context of self-force. This serves only to (finitely) renormalize the "bare" multipole moments of the object's stress-energy tensor. The MiSaTaQu expression for the gravitational self-force is recovered as a simple application. A gravitational self-torque is obtained as well. Lastly, a certain exact result is derived that may provide a basis for un...

  12. Regulatory mechanisms of viral hepatitis B and C

    Indian Academy of Sciences (India)

    G Waris; A Siddiqui

    2003-04-01

    Of all the hepatitis viruses, only the hepatitis B virus (HBV) and hepatitis C virus (HCV) cause chronic hepatitis, which can progress to cirrhosis and hepatocellular carcinoma. In this review, we discuss how these two biologically diverse viruses use common pathways to induce oxidative stress and activation of key transcription factors, known to be involved in inflammatory processes in cells. Activation of NF-B and STAT-3 most likely contribute to the progression of viral infections to chronic hepatitis and liver oncogenesis associated with HBV and HCV infections. In this review, we focus on the mechanisms of action of HBx and HCV NS5A proteins in inducing intracellular events associated with the viral infections.

  13. General aspects of two-component regulatory circuits in bacteria: Domains, signals and roles.

    Science.gov (United States)

    Padilla-Vaca, Felipe; Mondragón-Jaimes, Verónica; Franco, Bernardo

    2016-08-09

    All living organisms are subject to changing environments, which must be sensed in order to respond swiftly and efficiently. Two-component systems (TCS) are signal transduction regulatory circuits based typically on a membrane bound sensor kinase and a cytoplasmic response regulator, that is activated through a histidine to aspartate phosphorelay reactions. Activated response regulator acts usually as a transcription factor. The best known examples were identified in bacteria, but they are also found in fungi, algae and plants. Thus far, they are not found in mammals. Regulatory circuits coupled to two-component systems exhibit a myriad of responses to environmental stimuli such as: redox potential, pH, specific metabolites, pressure, light and more recently to specific antimicrobial peptides that activate a sensor kinase responsible for expressing virulence factors through the active response regulator. In this review we explore general aspects on two-component systems that ultimately can play a role on virulence regulation, also the intriguing domain properties of the sensor kinases that can be a potential target for antimicrobial compounds. Only a handful of sensor kinases are extensively characterized, the vast majority belong to what we call 'the dark matter of bacterial signal transduction' since no known signal, structure and biochemical properties are available. Regulatory circuits from vertebrate pathogenic organisms can explain virulence in terms of either response to environmental factors or specific niche occupancy. Hopefully, knowledge on these signal transduction systems can lead to identify novel molecules that target two-component systems, since the increase of drug resistant microorganisms is worrisome.

  14. Unification of General Relativity and Quantum Mechanics

    CERN Document Server

    Widmer, H

    2005-01-01

    Physics cannot determine what mass is; it can only normalize it - by a given volume: one liter of water corresponds to one kilogram, and so does everything else that shows the same inertia or weight - whatever mass itself was. In the same manner physics is not able to explain inertia or gravity, or to specify the reasons for a constant speed of light, a fundament of special relativity, or the Einstein-De Broglie relations, the basis of quantum mechanics. Even its very core, the Schroedinger Equation, is introduced into the world of physics as a good guess. Would we picture the universe itself as a continuum in space-time all these questions are solved automatically.

  15. SUCROSE SYNTHASE: ELUCIDATION OF COMPLEX POST-TRANSLATIONAL REGULATORY MECHANISMS

    Energy Technology Data Exchange (ETDEWEB)

    Steven C. Huber

    2009-05-12

    Studies have focused on the enzyme sucrose synthase, which plays an important role in the metabolism of sucrose in seeds and tubers. There are three isoforms of SUS in maize, referred to as SUS1, SUS-SH1, and SUS2. SUS is generally considered to be tetrameric protein but recent evidence suggests that SUS can also occur as a dimeric protein. The formation of tetrameric SUS is regulated by sucrose concentration in vitro and this could also be an important factor in the cellular localization of the protein. We found that high sucrose concentrations, which promote tetramer formation, also inhibit the binding of SUS1 to actin filaments in vitro. Previously, high sucrose concentrations were shown to promote SUS association with the plasma membrane. The specific regions of the SUS molecule involved in oligomerization are not known, but we identified a region of the SUS1 moelcule by bioinformatic analysis that was predicted to form a coiled coil. We demonstrated that this sequence could, in fact, self-associate as predicted for a coiled coil, but truncation analysis with the full-length recombinant protein suggested that it was not responsible for formation of dimers or tetramers. However, the coiled coil may function in binding of other proteins to SUS1. Overall, sugar availability may differentially influence the binding of SUS to cellular structures, and these effects may be mediated by changes in the oligomeric nature of the enzyme.

  16. Photosynthesis Control: An underrated short-term regulatory mechanism essential for plant viability.

    Science.gov (United States)

    Colombo, Monica; Suorsa, Marjaana; Rossi, Fabio; Ferrari, Roberto; Tadini, Luca; Barbato, Roberto; Pesaresi, Paolo

    2016-01-01

    Regulation of photosynthetic electron transport provides efficient performance of oxygenic photosynthesis in plants. During the last 15 years, the molecular bases of various photosynthesis short-term regulatory processes have been elucidated, however the wild type-like phenotypes of mutants lacking of State Transitions, Non Photochemical Quenching, or Cyclic Electron Transport, when grown under constant light conditions, have also raised doubts about the acclimatory significance of these short-regulatory mechanisms on plant performance. Interestingly, recent studies performed by growing wild type and mutant plants under field conditions revealed a prominent role of State Transitions and Non Photochemical Quenching on plant fitness, with almost no effect on vegetative plant growth. Conversely, the analysis of plants lacking the regulation of electron transport by the cytochrome b6f complex, also known as Photosynthesis Control, revealed the fundamental role of this regulatory mechanism in the survival of young, developing seedlings under fluctuating light conditions.

  17. Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters

    Directory of Open Access Journals (Sweden)

    Farré Domènec

    2007-12-01

    Full Text Available Abstract Background The arrangement of regulatory motifs in gene promoters, or promoter architecture, is the result of mutation and selection processes that have operated over many millions of years. In mammals, tissue-specific transcriptional regulation is related to the presence of specific protein-interacting DNA motifs in gene promoters. However, little is known about the relative location and spacing of these motifs. To fill this gap, we have performed a systematic search for motifs that show significant bias at specific promoter locations in a large collection of housekeeping and tissue-specific genes. Results We observe that promoters driving housekeeping gene expression are enriched in particular motifs with strong positional bias, such as YY1, which are of little relevance in promoters driving tissue-specific expression. We also identify a large number of motifs that show positional bias in genes expressed in a highly tissue-specific manner. They include well-known tissue-specific motifs, such as HNF1 and HNF4 motifs in liver, kidney and small intestine, or RFX motifs in testis, as well as many potentially novel regulatory motifs. Based on this analysis, we provide predictions for 559 tissue-specific motifs in mouse gene promoters. Conclusion The study shows that motif positional bias is an important feature of mammalian proximal promoters and that it affects both general and tissue-specific motifs. Motif positional constraints define very distinct promoter architectures depending on breadth of expression and type of tissue.

  18. Engineering a General Education Program: Designing Mechanical Engineering General Education Courses

    Science.gov (United States)

    Fagette, Paul; Chen, Shih-Jiun; Baran, George R.; Samuel, Solomon P.; Kiani, Mohammad F.

    2013-01-01

    The Department of Mechanical Engineering at our institution created two engineering courses for the General Education Program that count towards second level general science credit (traditional science courses are first level). The courses were designed for the general student population based upon the requirements of our General Education Program…

  19. Engineering a General Education Program: Designing Mechanical Engineering General Education Courses

    Science.gov (United States)

    Fagette, Paul; Chen, Shih-Jiun; Baran, George R.; Samuel, Solomon P.; Kiani, Mohammad F.

    2013-01-01

    The Department of Mechanical Engineering at our institution created two engineering courses for the General Education Program that count towards second level general science credit (traditional science courses are first level). The courses were designed for the general student population based upon the requirements of our General Education Program…

  20. Functional Development of the Human Gastrointestinal Tract: Hormone- and Growth Factor-Mediated Regulatory Mechanisms

    Directory of Open Access Journals (Sweden)

    Daniel Ménard

    2004-01-01

    Full Text Available The present review focuses on the control of gastrointestinal (GI tract development. The first section addresses the differences in general mechanisms of GI development in humans versus rodents, highlighting that morphogenesis of specific digestive organs and the differentiation of digestive epithelia occur not only at different stages of ontogeny but also at different rates. The second section provides an overview of studies from the author's laboratory at the Université de Sherbrooke pertaining to the development of the human fetal small intestine and colon. While both segments share similar morphological and functional characteristics, they are nevertheless modulated by distinct regulatory mechanisms. Using the organ culture approach, the author and colleagues were able to establish that hormones and growth factors, such as glucocorticoids, epidermal growth factor, insulin and keratinocyte growth factor, not only exert differential effects within these two segments, they can also trigger opposite responses in comparison with animal models. In the third section, emphasis is placed on the functional development of human fetal stomach and its various epithelial cell types; in particular, the glandular chief cells responsible for the synthesis and secretion of gastric enzymes such as pepsinogen-5 and gastric lipase. Bearing in mind that limitations of available cell models have, until now, greatly impeded the comprehension of molecular mechanisms regulating human gastric epithelial cell functions, the last section focuses on new human gastric epithelial cell models recently developed in the author's laboratory. These models comprise a novel primary culture system of human fetal gastric epithelium including, for the first time, functional chief cells, and human gastric epithelium cell lines cloned from the parental NCI-N87 strain. These new cells lines could serve important applications in the study of pathogenic action and epithelial

  1. Generalization of Classical Statistical Mechanics to Quantum Mechanics and Stable Property of Condensed Matter

    CERN Document Server

    Huang, Y C; Zhang, N

    2004-01-01

    Classical statistical average values are generally generalized to average values of quantum mechanics, it is discovered that quantum mechanics is direct generalization of classical statistical mechanics, and we generally deduce both a general new continuous eigenvalue equation and a general discrete eigenvalue equation in quantum mechanics, and discover that a eigenvalue of quantum mechanics is just an extreme value of an operator in possibility distribution, the eigenvalue f is just classical observable quantity. A general classical statistical uncertain relation is further given, the general classical statistical uncertain relation is generally generalized to quantum uncertainty principle, the two lost conditions in classical uncertain relation and quantum uncertainty principle, respectively, are found. We generally expound the relations among uncertainty principle, singularity and condensed matter stability, discover that quantum uncertainty principle prevents from the appearance of singularity of the elec...

  2. Extensive Generalization of Statistical Mechanics Based on Incomplete Information Theory

    Directory of Open Access Journals (Sweden)

    Qiuping A. Wang

    2003-06-01

    Full Text Available Statistical mechanics is generalized on the basis of an additive information theory for incomplete probability distributions. The incomplete normalization is used to obtain generalized entropy . The concomitant incomplete statistical mechanics is applied to some physical systems in order to show the effect of the incompleteness of information. It is shown that this extensive generalized statistics can be useful for the correlated electron systems in weak coupling regime.

  3. Canonical symmetry properties of the constrained singular generalized mechanical system

    Institute of Scientific and Technical Information of China (English)

    李爱民; 江金环; 李子平

    2003-01-01

    Based on generalized Apell-Chetaev constraint conditions and to take the inherent constrains for singular Lagrangian into account, the generalized canonical equations for a general mechanical system with a singular higher-order Lagrangian and subsidiary constrains are formulated. The canonical symmetries in phase space for such a system are studied and Noether theorem and its inversion theorem in the generalized canonical formalism have been established.

  4. Canonical symmetry properties of the constrained singular generalized mechanical system

    Institute of Scientific and Technical Information of China (English)

    LiAi-Min; JiangJin-Huan; LiZi-Ping

    2003-01-01

    Based on generalized Apell-Chetaev constraint conditions and to take the inherent constrains for singular Lagrangian into account,the generalized canonical equations for a general mechanical system with a singular higher-order Lagrangian and subsidiary constrains are formulated. The canonical symmetries in phase space for such a system are studied and Noether theorem and its inversion theorem in the generalized canonical formalism have been established.

  5. BOOK REVIEW: Advanced Mechanics and General Relativity Advanced Mechanics and General Relativity

    Science.gov (United States)

    Louko, Jorma

    2011-04-01

    Joel Franklin's textbook `Advanced Mechanics and General Relativity' comprises two partially overlapping, partially complementary introductory paths into general relativity at advanced undergraduate level. Path I starts with the Lagrangian and Hamiltonian formulations of Newtonian point particle motion, emphasising the action principle and the connection between symmetries and conservation laws. The concepts are then adapted to point particle motion in Minkowski space, introducing Lorentz transformations as symmetries of the action. There follows a focused development of tensor calculus, parallel transport and curvature, using examples from Newtonian mechanics and special relativity, culminating in the field equations of general relativity. The Schwarzschild solution is analysed, including a detailed discussion of the tidal forces on a radially infalling observer. Basics of gravitational radiation are examined, highlighting the similarities to and differences from electromagnetic radiation. The final topics in Path I are equatorial geodesics in Kerr and the motion of a relativistic string in Minkowski space. Path II starts by introducing scalar field theory on Minkowski space as a limit of point masses connected by springs, emphasising the action principle, conservation laws and the energy-momentum tensor. The action principle for electromagnetism is introduced, and the coupling of electromagnetism to a complex scalar field is developed in a detailed and pedagogical fashion. A free symmetric second-rank tensor field on Minkowski space is introduced, and the action principle of general relativity is recovered from coupling the second-rank tensor to its own energy-momentum tensor. Path II then merges with Path I and, supplanted with judicious early selections from Path I, can proceed to the Schwarzschild solution. The choice of material in each path is logical and focused. A notable example in Path I is that Lorentz transformations in Minkowki space are introduced

  6. Deriving generalized variational principles in general mechanics by using Lagrangian multiplier method

    Institute of Scientific and Technical Information of China (English)

    梁立孚

    1999-01-01

    By using the involutory transformations, the classical variational principle——Hamiltonian principle of two kinds of variables in general mechanics is advanced and by using undetermined Lagrangian multiplier method, the generalized variational principles and generalized variational principles with subsidiary conditions are established. The stationary conditions of various kinds of variational principles are derived and the relational problems discussed.

  7. Regulatory mechanisms of immune tolerance in type 1 diabetes and their failures.

    Science.gov (United States)

    Kuhn, Chantal; Besançon, Alix; Lemoine, Sébastien; You, Sylvaine; Marquet, Cindy; Candon, Sophie; Chatenoud, Lucienne

    2016-07-01

    In this brief review we propose to discuss salient data showing the importance of immune regulatory mechanisms, and in particular of Treg, for the control of pathogenic anti-β-cell response in autoimmune diabetes. Disease progression that culminates with the massive destruction of insulin-secreting β-cells and advent of hyperglycemia and glycosuria tightly correlates with a functional deficit in immune regulation. Better dissection of the cellular and molecular mechanisms through which the immune system normally sustains tolerance to "self", and which become defective when autoimmune aggression is overt, is the only direct and robust way to learn how to harness these effectively, so as to restore immune tolerance in patients with insulin-dependent type 1 diabetes. No doubt that regulatory T cells are a privileged mechanism underlying this self-tolerance in the periphery. The discovery of the key role of the transcription factor FoxP3, represented the cornerstone leading to the great advances in the field we are witnessing today. Type 1 diabetes is certainly one of the prototypic T cell-mediated autoimmune diseases where immune regulatory mechanisms relying on specialized subsets of T cells have been the most thoroughly analyzed from the fundamental point of view and also largely exploited in a translational therapeutic perspective.

  8. Form invariance for systems of generalized classical mechanics

    Institute of Scientific and Technical Information of China (English)

    张毅; 梅凤翔

    2003-01-01

    This paper presents a form invariance of canonical equations for systems of generalized classical mechanics. According to the invariance of the form of differential equations of motion under the infinitesimal transformations, this paper gives the definition and criterion of the form invariance for generalized classical mechanical systems, and establishes relations between form invariance, Noether symmetry and Lie symmetry. At the end of the paper, an example is given to illustrate the application of the results.

  9. Two-Component Regulatory Systems – implication in the quorum sensing mechanisms and bacteriocin production in lactic acid bacteria

    Directory of Open Access Journals (Sweden)

    Lia–Mara Ditu

    2014-08-01

    Full Text Available For lactic acid bacteria, the mechanisms of quorum sensing and response are mediated by peptides or pheromones that interfere with the synthesis of antimicrobial peptides (AMP called bacteriocins, when these molecules reach a certain critical level of concentration. Generally, the synthesis and activity of pheromones is adjusted by means of a two-component regulatory system. The observation that some microorganisms, in particular lactic acid bacteria, produce bacteriocins according to the cell density, has led to the discovery of the involvement of QS mechanisms in the synthesis of these peptides. Bacteriocins synthesis is inducible, the process requiring the extracellular accumulation of peptides that functions as chemical messengers activators of bacteriocins synthesis. This minireview presents the molecular architecture and functions of two-component regulatory systems and ABC transporters implicated in the synthesis and secretion of nisin, one of the most studied bacteriocin. The elucidation of the intimate mechanisms of bacteriocins synthesis is equally of biotechnological and medical importance, opening interesting perspectives for the development of improved technologies for the production of bacteriocins with good yields, and also, for increasing the beneficial anti-infective roles of probiotic bacteria when administered in vivo.

  10. Quantum mechanical generalization of the balistic electron wind theory

    Science.gov (United States)

    Lacina, A.

    1980-06-01

    The Fiks' quasiclassical theory of the electron wind force is quantum mechanically generalized. Within the framework of this generalization the space dependence of the electron wind force is calculated in the vicinity of an interface between two media. It is found that quantum corrections may be comparable with or even greater than corresponding quasiclassical values.

  11. Noether's theory of generalized linear nonholonomic mechanical systems

    Institute of Scientific and Technical Information of China (English)

    Dong Wen-Shan; Huang Bao-Xin; Fang Jian-Hui

    2011-01-01

    By introducing the quasi-symmetry of the infinitesimal transformation of the transformation group Gr, the Noether's theorem and the Noether's inverse theorem for generalized linear nonholonomic mechanical systems are obtained in a generalized compound derivative space. An example is given to illustrate the application of the result.

  12. Exploring associations between self-regulatory mechanisms and neuropsychological functioning and driver behaviour after brain injury.

    Science.gov (United States)

    Rike, Per-Ola; Johansen, Hans J; Ulleberg, Pål; Lundqvist, Anna; Schanke, Anne-Kristine

    2016-04-11

    The objective of this prospective one-year follow-up study was to explore the associations between self-regulatory mechanisms and neuropsychological tests as well as baseline and follow-up ratings of driver behaviour. The participants were a cohort of subjects with stroke and traumatic brain injury (TBI) who were found fit to drive after a multi-disciplinary driver assessment (baseline). Baseline measures included neuropsychological tests and ratings of self-regulatory mechanisms, i.e., executive functions (Behavior Rating Inventory of Executive Function-Adult Version; BRIEF-A) and impulsive personality traits (UPPS Impulsive Behavior Scale). The participants rated pre-injury driving behaviour on the Driver Behaviour Qestionnaire (DBQ) retrospectively at baseline and after one year of post-injury driving (follow-up). Better performance on neuropsychological tests was significantly associated with more post-injury DBQ Violations. The BRIEF-A main indexes were significantly associated with baseline and follow-up ratings of DBQ Mistakes and follow-up DBQ Inattention. UPPS (lack of) Perseverance was significantly associated with baseline DBQ Inattention, whereas UPPS Urgency was significantly associated with baseline DBQ Inexperience and post-injury DBQ Mistakes. There were no significant changes in DBQ ratings from baseline (pre-injury) to follow-up (post-injury). It was concluded that neuropsychological functioning and self-regulatory mechanisms are related to driver behaviour. Some aspects of driver behaviour do not necessarily change after brain injury, reflecting the influence of premorbid driving behaviour or impaired awareness of deficits on post-injury driving behaviour. Further evidence is required to predict the role of self-regulatory mechanisms on driver behaviour and crashes or near misses.

  13. Expression pattern and transcriptional regulatory mechanism of noxa gene in grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Pei, Yongyan; Lu, Xiaonan; He, Libo; Wang, Hao; Zhang, Aidi; Li, Yongming; Huang, Rong; Liao, Lanjie; Zhu, Zuoyan; Wang, Yaping

    2015-12-01

    Noxa, a pro-apoptotic protein, plays an important role in cell apoptosis. The researches about noxa gene were concentrated in mammalians, whereas the role and transcriptional regulatory mechanism of noxa in fish were still unclear. In this study, the expression pattern and transcriptional regulatory mechanism of noxa gene in grass carp were analyzed. Noxa was constitutively expressed in all the examined tissues but the relative expression level differed. After exposure to grass carp reovirus (GCRV), mRNA expression level of noxa was down-regulated at the early phase whereas up-regulated at the late phase of infection. Luciferase assays showed that the promoter region -867 ∼ +107 of noxa had high activity and the region -678 ∼ -603 was important in the response to GCRV infection. By deleting the predicted transcription factor binding sites, transcription factors FOXO1 and CEBPβ were found important for noxa in response to GCRV infection. Moreover, the noxa promoter was biotin-labeled and incubated with nuclear extracts from GCRV infected cells. Mass spectrometry analysis showed that transcription factors FOXO1 and CEBPβ were also enriched in the combined proteins. Therefore, the results suggested that transcription factors FOXO1 and CEBPβ may play an important role in the regulation of noxa. Our study would provide new insight into the transcriptional regulatory mechanism of noxa in teleost fish.

  14. A qrr noncoding RNA deploys four different regulatory mechanisms to optimize quorum-sensing dynamics.

    Science.gov (United States)

    Feng, Lihui; Rutherford, Steven T; Papenfort, Kai; Bagert, John D; van Kessel, Julia C; Tirrell, David A; Wingreen, Ned S; Bassler, Bonnie L

    2015-01-15

    Quorum sensing is a cell-cell communication process that bacteria use to transition between individual and social lifestyles. In vibrios, homologous small RNAs called the Qrr sRNAs function at the center of quorum-sensing pathways. The Qrr sRNAs regulate multiple mRNA targets including those encoding the quorum-sensing regulatory components luxR, luxO, luxM, and aphA. We show that a representative Qrr, Qrr3, uses four distinct mechanisms to control its particular targets: the Qrr3 sRNA represses luxR through catalytic degradation, represses luxM through coupled degradation, represses luxO through sequestration, and activates aphA by revealing the ribosome binding site while the sRNA itself is degraded. Qrr3 forms different base-pairing interactions with each mRNA target, and the particular pairing strategy determines which regulatory mechanism occurs. Combined mathematical modeling and experiments show that the specific Qrr regulatory mechanism employed governs the potency, dynamics, and competition of target mRNA regulation, which in turn, defines the overall quorum-sensing response.

  15. General theory of genotype to phenotype mapping: derivation of epigenetic landscapes from N-node complex gene regulatory networks.

    Science.gov (United States)

    Villarreal, Carlos; Padilla-Longoria, Pablo; Alvarez-Buylla, Elena R

    2012-09-14

    We propose a systematic methodology to construct a probabilistic epigenetic landscape of cell-fate attainment associated with N-node Boolean genetic regulatory networks. The general derivation proposed here is exemplified with an Arabidopsis thaliana network underlying floral organ determination grounded on qualitative experimental data.

  16. Integration of general amino acid control and target of rapamycin (TOR) regulatory pathways in nitrogen assimilation in yeast.

    Science.gov (United States)

    Staschke, Kirk A; Dey, Souvik; Zaborske, John M; Palam, Lakshmi Reddy; McClintick, Jeanette N; Pan, Tao; Edenberg, Howard J; Wek, Ronald C

    2010-05-28

    Two important nutrient-sensing and regulatory pathways, the general amino acid control (GAAC) and the target of rapamycin (TOR), participate in the control of yeast growth and metabolism during changes in nutrient availability. Amino acid starvation activates the GAAC through Gcn2p phosphorylation of translation factor eIF2 and preferential translation of GCN4, a transcription activator. TOR senses nitrogen availability and regulates transcription factors such as Gln3p. We used microarray analyses to address the integration of the GAAC and TOR pathways in directing the yeast transcriptome during amino acid starvation and rapamycin treatment. We found that GAAC is a major effector of the TOR pathway, with Gcn4p and Gln3p each inducing a similar number of genes during rapamycin treatment. Although Gcn4p activates a common core of 57 genes, the GAAC directs significant variations in the transcriptome during different stresses. In addition to inducing amino acid biosynthetic genes, Gcn4p in conjunction with Gln3p activates genes required for the assimilation of secondary nitrogen sources such as gamma-aminobutyric acid (GABA). Gcn2p activation upon shifting to secondary nitrogen sources is suggested to occur by means of a dual mechanism. First, Gcn2p is induced by the release of TOR repression through a mechanism involving Sit4p protein phosphatase. Second, this eIF2 kinase is activated by select uncharged tRNAs, which were shown to accumulate during the shift to the GABA medium. This study highlights the mechanisms by which the GAAC and TOR pathways are integrated to recognize changing nitrogen availability and direct the transcriptome for optimal growth adaptation.

  17. Regulatory mechanisms for absenteeism in the health sector: a systematic review of strategies and their implementation

    Directory of Open Access Journals (Sweden)

    Kisakye AN

    2016-11-01

    Full Text Available Angela N Kisakye,1 Raymond Tweheyo,1 Freddie Ssengooba,1 George W Pariyo,2 Elizeus Rutebemberwa,1 Suzanne N Kiwanuka1 1Department of Health Policy Planning and Management, Makerere University School of Public Health, Kampala, Uganda; 2Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Background: A systematic review was undertaken to identify regulatory mechanisms aimed at mitigating health care worker absenteeism, to describe where and how they have been implemented as well as their possible effects. The goal was to propose potential policy options for managing the problem of absenteeism among human resources for health in low- and middle-income countries. Mechanisms described in this review are at the local workplace and broader national policy level. Methods: A comprehensive online search was conducted on EMBASE, CINAHL, PubMed, Google Scholar, Google, and Social Science Citation Index using MEDLINE search terms. Retrieved studies were uploaded onto reference manager and screened by two independent reviewers. Only publications in English were included. Data were extracted and synthesized according to the objectives of the review. Results: Twenty six of the 4,975 published articles retrieved were included. All were from high-income countries and covered all cadres of health workers. The regulatory mechanisms and possible effects include 1 organizational-level mechanisms being reported as effective in curbing absenteeism in low- and middle-income countries (LMICs; 2 prohibition of private sector activities in LMICs offering benefits but presenting a challenge for the government to monitor the health workforce; 3 contractual changes from temporary to fixed posts having been associated with no reduction in absenteeism and not being appropriate for LMICs; 4 multifaceted work interventions being implemented in most settings; 5 the possibility of using financial and incentive regulatory mechanisms

  18. Research on generalized optimization process for mechanical product

    Institute of Scientific and Technical Information of China (English)

    冯培恩; 邱清盈; 潘双夏; 董黎刚; 李善春

    1999-01-01

    The generalized optimization process for mechanical product is proposed which includes functional optimization phase, conceptual design optimization phase, technical design optimization phase (that is further divided into product modeling phase, optimization process scheduling phase, optimization modeling phase and multi-computer collaborative optimizing phase), and result analysis and evaluation phase. The characteristics of the generalized optimization are incarnated such as oriented to the design of entire system, whole process and overall performance of a product and combined with human intelligent and artificial intelligent optimization. The functions and the achieved strategies of each key phase in the generalized optimization process are discussed. A prototype of the generalized optimization supported system for mechanical product is preliminarily established.

  19. Noether-Lie Symmetry of Generalized Classical Mechanical Systems

    Institute of Scientific and Technical Information of China (English)

    JIA Wen-Zhi; ZHANG Xiao-Ni; WANG Shun-Jin; FANG Jian-Hui; WANG Peng; DING Ning

    2008-01-01

    In this paper, the Noether-Lie symmetry and conserved quantities of generalized classical mechanical system are studied. The definition and the criterion of the Noether Lie symmetry for the system under the general infinitesimal transformations of groups are given. The Noether conserved quantity and the Hojman conserved quantity deduced from the Noether-Lie symmetry are obtained. An example is given to illustrate the application of the results.

  20. Generalized Toda Mechanics Associated with Loop Algebra (ι)(Br)

    Institute of Scientific and Technical Information of China (English)

    YANG Zhan-Ying; ZHAO Liu; SHI Kang-Jie

    2005-01-01

    A class of generalization of Toda mechanics with long range interactions is constructed in this paper. These systems are associated with the loop algebras (ι)(Br) in the sense that their Lax matrices can be realized in terms of the c = 0 representations of the affine Lie algebras Br(1). We adopt a pair of ordered integers (m, n) to describe the Toda mechanics system when we present the equations of motion and the Hamiltonian structure. We also extract the classical r matrix which satisfy the classical Yang-Baxter relation. Such generalizations will become systems with noncommutative variables in the quantum case.

  1. Latent Tuberculosis: Models, Computational efforts and the Pathogen's regulatory mechanisms during dormancy

    Directory of Open Access Journals (Sweden)

    Gesham eMagombedze

    2013-08-01

    Full Text Available Latent tuberculosis is a clinical syndrome that occurs after an individual has been exposed to the Mycobacterium tuberculosis (Mtb bacillus, the infection has been established and an immune response has been generated to control the pathogen and force it into a quiescent state. Mtb can exit this quiescent state where it is unresponsive to treatment and elusive to the immune response, and enter a rapid replicating state, hence causing infection reactivation. It remains a grey area to understand how the pathogen causes a persistent infection and it is unclear whether the organism will be in a slow replicating state or a dormant non-replicating state. The ability of the pathogen to adapt to changing host immune response mechanisms, in which it is exposed to hypoxia, low pH, nitric oxide (NO, nutrient starvation and several other anti-microbial effectors, is associated with a high metabolic plasticity that enables it to metabolise under these different conditions. Adaptive gene regulatory mechanisms are thought to coordinate how the pathogen changes their metabolic pathways through mechanisms that sense changes in oxygen tension and other stress factors, hence stimulating the pathogen to make necessary adjustments to ensure survival. Here, we review studies that give insights into latency/dormancy regulatory mechanisms that enable infection persistence and pathogen adaptation to different stress conditions. We highlight what mathematical and computational models can do and what they should do to enhance our current understanding of TB latency.

  2. SYMMETRIES AND CONSERVED QUANTITIES FOR SYSTEMS OF GENERALIZED CLASSICAL MECHANICS

    Institute of Scientific and Technical Information of China (English)

    Zhang Yi; Shang Mei; Mei Feng-xiang

    2000-01-01

    In this paper, the symmetries and the conserved quantities for systemsof generalized classical mechanics are studied. First, the generalizedNoether's theorem and the generalized Noether's inverse theorem of thesystems are given, which are based upon the invariant properties of thecanonical action with respect to the action of the infinitesimaltransformation of r-parameter finite group of transformation; second,the Lie symmetries and conserved quantities of the systems are studiedin accordance with the Lie's theory of the invariance of differentialequations under the transformation of infinitesimal groups; and finally,the inner connection between the two kinds of symmetries of systems isdiscussed.

  3. Vibrational mechanics nonlinear dynamic effects, general approach, applications

    CERN Document Server

    Blekhman, Iliya I

    2000-01-01

    This important book deals with vibrational mechanics - the new, intensively developing section of nonlinear dynamics and the theory of nonlinear oscillations. It offers a general approach to the study of the effect of vibration on nonlinear mechanical systems.The book presents the mathematical apparatus of vibrational mechanics which is used to describe such nonlinear effects as the disappearance and appearance under vibration of stable positions of equilibrium and motions (i.e. attractors), the change of the rheological properties of the media, self-synchronization, self-balancing, the vibrat

  4. Using Xenopus Embryos to Study Transcriptional and Posttranscriptional Gene Regulatory Mechanisms of Intermediate Filaments.

    Science.gov (United States)

    Wang, Chen; Szaro, Ben G

    2016-01-01

    Intermediate filament genes exhibit highly regulated, tissue-specific patterns of expression during development and in response to injury. Identifying the responsible cis-regulatory gene elements thus holds great promise for revealing insights into fundamental gene regulatory mechanisms controlling tissue differentiation and repair. Because much of this regulation occurs in response to signals from surrounding cells, characterizing them requires a model system in which their activity can be tested within the context of an intact organism conveniently. We describe methods for doing so by injecting plasmid DNAs into fertilized Xenopus embryos. A prokaryotic element for site-specific recombination and two dual HS4 insulator elements flanking the reporter gene promote penetrant, promoter-typic expression that persists through early swimming tadpole stages, permitting the observation of fluorescent reporter protein expression in live embryos. In addition to describing cloning strategies for generating these plasmids, we present methods for coinjecting test and reference plasmids to identify the best embryos for analysis, for analyzing reporter protein and RNA expression, and for characterizing the trafficking of expressed reporter RNAs from the nucleus to polysomes. Thus, this system can be used to study the activities of cis-regulatory elements of intermediate filament genes at multiple levels of transcriptional and posttranscriptional control within an intact vertebrate embryo, from early stages of embryogenesis through later stages of organogenesis and tissue differentiation.

  5. Pseudoharmonic oscillator in quantum mechanics with a generalized uncertainty principle

    CERN Document Server

    Boukhellout, Abdelmalek

    2013-01-01

    The pseudoharmonic oscillator potential is studied in quantum mechanics with a generalized uncertainty relation characterized by the existence of a minimal length. By using the perturbative approach of Brau, we compute the correction to the energy spectrum in the first order of the minimal length parameter {\\beta}. The effect of the minimal length on the vibration-rotation of diatomic molecules is discussed.

  6. Biosafety, biosecurity and internationally mandated regulatory regimes: compliance mechanisms for education and global health security

    Science.gov (United States)

    Sture, Judi; Whitby, Simon; Perkins, Dana

    2015-01-01

    This paper highlights the biosafety and biosecurity training obligations that three international regulatory regimes place upon states parties. The duty to report upon the existence of such provisions as evidence of compliance is discussed in relation to each regime. We argue that such mechanisms can be regarded as building blocks for the development and delivery of complementary biosafety and biosecurity teaching and training materials. We show that such building blocks represent foundations upon which life and associated scientists – through greater awareness of biosecurity concerns – can better fulfil their responsibilities to guard their work from misuse in the future. PMID:24494580

  7. General mechanism for amplitude death in coupled systems.

    Science.gov (United States)

    Resmi, V; Ambika, G; Amritkar, R E

    2011-10-01

    We introduce a general mechanism for amplitude death in coupled synchronizable dynamical systems. It is known that when two systems are coupled directly, they can synchronize under suitable conditions. When an indirect feedback coupling through an environment or an external system is introduced in them, it is found to induce a tendency for antisynchronization. We show that, for sufficient strengths, these two competing effects can lead to amplitude death. We provide a general stability analysis that gives the threshold values for onset of amplitude death. We study in detail the nature of the transition to death in several specific cases and find that the transitions can be of two types--continuous and discontinuous. By choosing a variety of dynamics, for example, periodic, chaotic, hyperchaotic, and time-delay systems, we illustrate that this mechanism is quite general and works for different types of direct coupling, such as diffusive, replacement, and synaptic couplings, and for different damped dynamics of the environment.

  8. Distinct regulatory mechanisms act to establish and maintain Pax3 expression in the developing neural tube.

    Directory of Open Access Journals (Sweden)

    Steven Moore

    Full Text Available Pattern formation in developing tissues is driven by the interaction of extrinsic signals with intrinsic transcriptional networks that together establish spatially and temporally restricted profiles of gene expression. How this process is orchestrated at the molecular level by genomic cis-regulatory modules is one of the central questions in developmental biology. Here we have addressed this by analysing the regulation of Pax3 expression in the context of the developing spinal cord. Pax3 is induced early during neural development in progenitors of the dorsal spinal cord and is maintained as pattern is subsequently elaborated, resulting in the segregation of the tissue into dorsal and ventral subdivisions. We used a combination of comparative genomics and transgenic assays to define and dissect several functional cis-regulatory modules associated with the Pax3 locus. We provide evidence that the coordinated activity of two modules establishes and refines Pax3 expression during neural tube development. Mutational analyses of the initiating element revealed that in addition to Wnt signaling, Nkx family homeodomain repressors restrict Pax3 transcription to the presumptive dorsal neural tube. Subsequently, a second module mediates direct positive autoregulation and feedback to maintain Pax3 expression. Together, these data indicate a mechanism by which transient external signals are converted into a sustained expression domain by the activities of distinct regulatory elements. This transcriptional logic differs from the cross-repression that is responsible for the spatiotemporal patterns of gene expression in the ventral neural tube, suggesting that a variety of circuits are deployed within the neural tube regulatory network to establish and elaborate pattern formation.

  9. The new Australian after-hours general practice incentive payment mechanism: equity for rural general practice?

    Science.gov (United States)

    Neil, Amanda L; Nelson, Mark; Palmer, Andrew J

    2016-07-01

    In July 2015, a national scheme for after-hours incentive funding for general practices was re-introduced in Australia, 2-years after funding was transferred to regional primary health care organisations (Medicare Locals). The re-introduction was recommended in a 2014 review of after-hours primary care reflecting the "overwhelming desire" among general practice. Given the centrality of after-hours care provision in rural and remote practices identified in the review, we compare and contrast the current and historical after-hours incentive funding mechanisms focussing on fairness towards rural general practices. While there are similarities between the current and historical mechanisms, significant differences exist. The comparison is not straightforward. The major consistency is utilisation of practice standardised whole patient equivalents (SWPE) as the basis of funding, inherently favouring large urban general practices. This bias is expected to increase given a shift in focus from practices with no option but to provide 24/7 care to any practice providing 24/7 care; and an associated increased funding per SWPE. Differences primarily pertain to classification processes, in which the realities of rural service provision and recognition of regional support mechanisms are given minimal consideration. Rapid introduction of the new general practice after-hours incentive funding mechanism has led to inconsistencies and has exacerbated inherent biases, particularly inequity towards rural providers. Impact on morale and service provision in non-urban areas should be monitored.

  10. Concepts and mechanisms of generalized central nervous system arousal.

    Science.gov (United States)

    Pfaff, Donald; Ribeiro, Ana; Matthews, James; Kow, Lee-Ming

    2008-01-01

    A concept of generalized arousal of the CNS is presented and given an operational definition that leads to quantitative physical measures. Because this primitive arousal function underlies all motivated behavioral responses, cognitive functions, and emotional expression, disorders of generalized arousal can be associated with a large number of problems in medicine and public health, including vegetative states, attentional disorders, depression, occupational hazards, and problems with sleep and anesthesia. Some of its known mechanisms are briefly reviewed, at the levels of neuroanatomy, neurophysiology, and functional genomics. Generalized arousal contributes to the excitement and the activation of behaviors during specific arousal states. Data are summarized for four genomic/neurochemical systems through which changes in generalized arousal could affect sexual arousal, two of which heighten, and the other two of which reduce arousal.

  11. Generalized constitutive equations for piezo-actuated compliant mechanism

    Science.gov (United States)

    Cao, Junyi; Ling, Mingxiang; Inman, Daniel J.; Lin, Jin

    2016-09-01

    This paper formulates analytical models to describe the static displacement and force interactions between generic serial-parallel compliant mechanisms and their loads by employing the matrix method. In keeping with the familiar piezoelectric constitutive equations, the generalized constitutive equations of compliant mechanism represent the input-output displacement and force relations in the form of a generalized Hooke’s law and as analytical functions of physical parameters. Also significantly, a new model of output displacement for compliant mechanism interacting with piezo-stacks and elastic loads is deduced based on the generalized constitutive equations. Some original findings differing from the well-known constitutive performance of piezo-stacks are also given. The feasibility of the proposed models is confirmed by finite element analysis and by experiments under various elastic loads. The analytical models can be an insightful tool for predicting and optimizing the performance of a wide class of compliant mechanisms that simultaneously consider the influence of loads and piezo-stacks.

  12. Generalized Statistical Mechanics at the Onset of Chaos

    Directory of Open Access Journals (Sweden)

    Alberto Robledo

    2013-11-01

    Full Text Available Transitions to chaos in archetypal low-dimensional nonlinear maps offer real and precise model systems in which to assess proposed generalizations of statistical mechanics. The known association of chaotic dynamics with the structure of Boltzmann–Gibbs (BG statistical mechanics has suggested the potential verification of these generalizations at the onset of chaos, when the only Lyapunov exponent vanishes and ergodic and mixing properties cease to hold. There are three well-known routes to chaos in these deterministic dissipative systems, period-doubling, quasi-periodicity and intermittency, which provide the setting in which to explore the limit of validity of the standard BG structure. It has been shown that there is a rich and intricate behavior for both the dynamics within and towards the attractors at the onset of chaos and that these two kinds of properties are linked via generalized statistical-mechanical expressions. Amongst the topics presented are: (i permanently growing sensitivity fluctuations and their infinite family of generalized Pesin identities; (ii the emergence of statistical-mechanical structures in the dynamics along the routes to chaos; (iii dynamical hierarchies with modular organization; and (iv limit distributions of sums of deterministic variables. The occurrence of generalized entropy properties in condensed-matter physical systems is illustrated by considering critical fluctuations, localization transition and glass formation. We complete our presentation with the description of the manifestations of the dynamics at the transitions to chaos in various kinds of complex systems, such as, frequency and size rank distributions and complex network images of time series. We discuss the results.

  13. Fear Generalization and Anxiety: Behavioral and Neural Mechanisms.

    Science.gov (United States)

    Dunsmoor, Joseph E; Paz, Rony

    2015-09-01

    Fear can be an adaptive emotion that helps defend against potential danger. Classical conditioning models elegantly describe how animals learn which stimuli in the environment signal danger, but understanding how this learning is generalized to other stimuli that resemble aspects of a learned threat remains a challenge. Critically, the overgeneralization of fear to harmless stimuli or situations is a burden to daily life and characteristic of posttraumatic stress disorder and other anxiety disorders. Here, we review emerging evidence on behavioral and neural mechanisms of generalization of emotional learning with the goal of encouraging further research on generalization in anxiety disorders. We begin by placing research on fear generalization in a rich historical context of stimulus generalization dating back to Pavlov, which lays the foundation for theoretical and experimental approaches used today. We then transition to contemporary behavioral and neurobiological research on generalization of emotional learning in humans and nonhuman animals and discuss the factors that promote generalization on the one hand from discrimination on the other hand.

  14. Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms

    Science.gov (United States)

    Horikoshi, Momoko; Pasquali, Lorenzo; Wiltshire, Steven; Huyghe, Jeroen R.; Mahajan, Anubha; Asimit, Jennifer L.; Ferreira, Teresa; Locke, Adam E.; Robertson, Neil R.; Wang, Xu; Sim, Xueling; Fujita, Hayato; Hara, Kazuo; Young, Robin; Zhang, Weihua; Choi, Sungkyoung; Chen, Han; Kaur, Ismeet; Takeuchi, Fumihiko; Fontanillas, Pierre; Thuillier, Dorothée; Yengo, Loic; Below, Jennifer E.; Tam, Claudia H.T.; Wu, Ying; Abecasis, Gonçalo; Altshuler, David; Bell, Graeme I.; Blangero, John; Burtt, Noél P.; Duggirala, Ravindranath; Florez, Jose C.; Hanis, Craig L.; Seielstad, Mark; Atzmon, Gil; Chan, Juliana C.N.; Ma, Ronald C.W.; Froguel, Philippe; Wilson, James G.; Bharadwaj, Dwaipayan; Dupuis, Josee; Meigs, James B.; Cho, Yoon Shin; Park, Taesung; Kooner, Jaspal S.; Chambers, John C.; Saleheen, Danish; Kadowaki, Takashi; Tai, E. Shyong; Mohlke, Karen L.; Cox, Nancy J.; Ferrer, Jorge; Zeggini, Eleftheria; Kato, Norihiro; Teo, Yik Ying; Boehnke, Michael; McCarthy, Mark I.; Morris, Andrew P.

    2016-01-01

    To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised the variants most likely to drive each distinct association signal. We demonstrated that integration of these genetic fine-mapping data with genomic annotation can highlight potential causal regulatory elements in T2D-relevant tissues. These analyses provide insight into the mechanisms through which T2D association signals are mediated, and suggest future routes to understanding the biology of specific disease susceptibility loci. PMID:26911676

  15. The underlying molecular and network level mechanisms in the evolution of robustness in gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Mario Pujato

    Full Text Available Gene regulatory networks show robustness to perturbations. Previous works identified robustness as an emergent property of gene network evolution but the underlying molecular mechanisms are poorly understood. We used a multi-tier modeling approach that integrates molecular sequence and structure information with network architecture and population dynamics. Structural models of transcription factor-DNA complexes are used to estimate relative binding specificities. In this model, mutations in the DNA cause changes on two levels: (a at the sequence level in individual binding sites (modulating binding specificity, and (b at the network level (creating and destroying binding sites. We used this model to dissect the underlying mechanisms responsible for the evolution of robustness in gene regulatory networks. Results suggest that in sparse architectures (represented by short promoters, a mixture of local-sequence and network-architecture level changes are exploited. At the local-sequence level, robustness evolves by decreasing the probabilities of both the destruction of existent and generation of new binding sites. Meanwhile, in highly interconnected architectures (represented by long promoters, robustness evolves almost entirely via network level changes, deleting and creating binding sites that modify the network architecture.

  16. Newly Described Components and Regulatory Mechanisms of Circadian Clock Function in Arabidopsis thaliana

    Institute of Scientific and Technical Information of China (English)

    Manuel Adrián Troncoso-Ponce; Paloma Mas

    2012-01-01

    The circadian clock temporally coordinates plant growth and metabolism in close synchronization with the diurnal and seasonal environmental changes.Research over the last decade has identified a number of clock components and a variety of regulatory mechanisms responsible for the rhythmic oscillations in metabolic and physiological activities.At the core of the clock,transcriptional/translational feedback loops modulate the expression of a significant proportion of the genome.In this article,we briefly describe some of the very recent advances that have improved our understanding of clock organization and function in Arabidopsis thaliana.The new studies illustrate the role of clock protein complex formation on circadian gating of plant growth and identify alternative splicing as a new regulatory mechanism for clock function.Examination of key clock properties such as temperature compensation has also opened new avenues for functional research within the plant clockwork.The emerging connections between the circadian clock and metabolism,hormone signaling and response to biotic and abiotic stress also add new layers of complexity to the clock network and underscore the significance of the circadian clock regulating the daily life of plants.

  17. Generalized Mechanism of Field Emission from Nanostructured Semiconductor Film Cathodes

    Science.gov (United States)

    Wang, Ru-Zhi; Zhao, Wei; Yan, Hui

    2017-03-01

    Considering the effect of both the buffer layer and substrate, a series of ultrathin multilayered structure cathodes (UTMC) is constructed to simulate the field emission (FE) process of nanostructured semiconductor film cathodes (NSFCs). We find a generalized FE mechanism of the NSFCs, in which there are three distinct FE modes with the change of the applied field. Our results clearly show significant differences of FE between conventional emitters and nanofilm emitters, which the non-Fowler-Nordheim characteristics and the resonant FE will be inevitable for NSFCs. Moreover, the controllable FE can be realized by fine-tuning the quantum structure of NSFCs. The generalized mechanism of NSFCs presented here may be particularly useful for design high-speed and high-frequency vacuum nano-electronic devices.

  18. Generalized Dual Symmetry Mechanical Performance of Nano Magnetic Composite

    Institute of Scientific and Technical Information of China (English)

    Li Yong; Song Jian; Zhang Z.M

    2004-01-01

    Nano magnetic composite is a kind of heterogeneous material. Scientists found the symmetrical and dual symmetrical phenomena in its structure previously and we find the generalized dual symmetry mechanical performance in Nano Magnetic Composite and further establish the theory. The applicable nano magnetic composite structure is analyzed thoroughly and systematically. Such phenomena as serration and step dispersing distribution of bending stress and mirror reflection of interlaminar stress are thus found. Therefore, starting from the physical features of materials, Nano Magnetic Composite are analyzed on the basis of the understanding and application of the generalized dual symmetry mechanical performance. In addition, the design parameter is optimized to attain the goal of maximizing the use of materials, which is quite meaningful.

  19. Generalized Poisson processes in quantum mechanics and field theory

    Energy Technology Data Exchange (ETDEWEB)

    Combe, P.; Rodriguez, R. (Centre National de la Recherche Scientifique, 13 - Marseille (France). Faculte des Sciences de Luminy); Hoegh-Krohn, R.; Sirugue, M.; Sirugue-Collin, M.

    1981-11-01

    In section 2 we describe more carefully the generalized Poisson processes, giving a realization of the underlying probability space, and we characterize these processes by their characteristic functionals. Section 3 is devoted to the proof of the previous formula for quantum mechanical systems, with possibly velocity dependent potentials and in section 4 we give an application of the previous theory to some relativistic Bose field models.

  20. On General Volume-Preserving Mechanical Systems via Cohomology

    Institute of Scientific and Technical Information of China (English)

    ZHOU Bin; GUO Han-Ying; WU Ke

    2003-01-01

    We present the general form of equations that generate a volume-preserving flow on a symplectic manifold(Μ,ω) via the highest Euler-Lagrange cohomology. It is shown that for every volume-preserving fiow there are some 2-forms that play a similar role to the Hamiltonian in the Hamilton mechanics and the ordinary canonical equations with Hamiltonian H are included as a special case with a 2-form Hω/(n - 1).

  1. Plasticity-rigidity cycles: A general adaptation mechanism

    OpenAIRE

    Csermely, Peter

    2015-01-01

    Successful adaptation helped the emergence of complexity. Alternating plastic- and rigid-like states were recurrently considered to play a role in adaptive processes. However, this extensive knowledge remained fragmented. In this paper I describe plasticity-rigidity cycles as a general adaptation mechanism operating in molecular assemblies, assisted protein folding, cellular differentiation, learning, memory formation, creative thinking, as well as the organization of social groups and ecosys...

  2. Generalized stochastic profiling of transcriptional regulatory heterogeneities in tissues, tumors, and cultured cells

    OpenAIRE

    2013-01-01

    Single-cell variations in gene and protein expression are important during development and disease. Cell-to-cell heterogeneities can be directly inspected one cell at a time, but global methods are usually not sensitive enough to work with such a small amount of starting material. Here, we provide a detailed protocol for stochastic profiling, a method that infers single-cell regulatory heterogeneities by repeatedly sampling small collections of cells at random. Repeated stochastic sampling is...

  3. Innovation of a Regulatory Mechanism Modulating Semi-determinate Stem Growth through Artificial Selection in Soybean.

    Directory of Open Access Journals (Sweden)

    Yunfeng Liu

    2016-01-01

    Full Text Available It has been demonstrated that Terminal Flowering 1 (TFL1 in Arabidopsis and its functional orthologs in other plants specify indeterminate stem growth through their specific expression that represses floral identity genes in shoot apical meristems (SAMs, and that the loss-of-function mutations at these functional counterparts result in the transition of SAMs from the vegetative to reproductive state that is essential for initiation of terminal flowering and thus formation of determinate stems. However, little is known regarding how semi-determinate stems, which produce terminal racemes similar to those observed in determinate plants, are specified in any flowering plants. Here we show that semi-determinacy in soybean is modulated by transcriptional repression of Dt1, the functional ortholog of TFL1, in SAMs. Such repression is fulfilled by recently enabled spatiotemporal expression of Dt2, an ancestral form of the APETALA1/FRUITFULL orthologs, which encodes a MADS-box factor directly binding to the regulatory sequence of Dt1. In addition, Dt2 triggers co-expression of the putative SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (GmSOC1 in SAMs, where GmSOC1 interacts with Dt2, and also directly binds to the Dt1 regulatory sequence. Heterologous expression of Dt2 and Dt1 in determinate (tfl1 Arabidopsis mutants enables creation of semi-determinacy, but the same forms of the two genes in the tfl1 and soc1 background produce indeterminate stems, suggesting that Dt2 and SOC1 both are essential for transcriptional repression of Dt1. Nevertheless, the expression of Dt2 is unable to repress TFL1 in Arabidopsis, further demonstrating the evolutionary novelty of the regulatory mechanism underlying stem growth in soybean.

  4. Activation of counter-regulatory mechanisms in a rat renal acute rejection model

    Directory of Open Access Journals (Sweden)

    Salomon Daniel R

    2008-02-01

    Full Text Available Abstract Background Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation. Results We used a rat kidney transplantation model with strict transplant and sample preparation procedures to analyze genome wide changes in gene expression four days after syngeneic and allogeneic transplantation. Both interventions were associated with substantial changes in gene expression. After allogeneic transplantation, genes and pathways related to transport and metabolism were predominantly down-regulated consistent with rejection-mediated graft injury and dysfunction. Up-regulated genes were primarily related to the acute immune response including antigen presentation, T-cell receptor signaling, apoptosis, interferon signaling and complement cascades. We observed a cytokine and chemokine expression profile consistent with activation of a Th1-cell response. A novel finding was up-regulation of several regulatory and protective genes after allogeneic transplantation, specifically IL10, Bcl2a1, C4bpa, Ctla4, HO-1 and the SOCS family. Conclusion Our data indicate that in parallel with the predicted activation of immune response and tissue injury pathways, there is simultaneous activation of pathways for counter regulatory and protective mechanisms that would balance and limit the ongoing inflammatory/immune responses. The pathophysiological mechanisms behind and the clinical consequences of alterations in expression of these gene classes in acute rejection, injury and dysfunction vs. protection and immunoregulation, prompt further analyses and open new aspects for therapeutic approaches.

  5. Putting theory to the test: which regulatory mechanisms can drive realistic growth of a root?

    Directory of Open Access Journals (Sweden)

    Dirk De Vos

    2014-10-01

    Full Text Available In recent years there has been a strong development of computational approaches to mechanistically understand organ growth regulation in plants. In this study, simulation methods were used to explore which regulatory mechanisms can lead to realistic output at the cell and whole organ scale and which other possibilities must be discarded as they result in cellular patterns and kinematic characteristics that are not consistent with experimental observations for the Arabidopsis thaliana primary root. To aid in this analysis, a 'Uniform Longitudinal Strain Rule' (ULSR was formulated as a necessary condition for stable, unidirectional, symplastic growth. Our simulations indicate that symplastic structures are robust to differences in longitudinal strain rates along the growth axis only if these differences are small and short-lived. Whereas simple cell-autonomous regulatory rules based on counters and timers can produce stable growth, it was found that steady developmental zones and smooth transitions in cell lengths are not feasible. By introducing spatial cues into growth regulation, those inadequacies could be avoided and experimental data could be faithfully reproduced. Nevertheless, a root growth model based on previous polar auxin-transport mechanisms violates the proposed ULSR due to the presence of lateral gradients. Models with layer-specific regulation or layer-driven growth offer potential solutions. Alternatively, a model representing the known cross-talk between auxin, as the cell proliferation promoting factor, and cytokinin, as the cell differentiation promoting factor, predicts the effect of hormone-perturbations on meristem size. By down-regulating PIN-mediated transport through the transcription factor SHY2, cytokinin effectively flattens the lateral auxin gradient, at the basal boundary of the division zone, (thereby imposing the ULSR to signal the exit of proliferation and start of elongation. This model exploration underlines the

  6. Putting theory to the test: which regulatory mechanisms can drive realistic growth of a root?

    Science.gov (United States)

    De Vos, Dirk; Vissenberg, Kris; Broeckhove, Jan; Beemster, Gerrit T S

    2014-10-01

    In recent years there has been a strong development of computational approaches to mechanistically understand organ growth regulation in plants. In this study, simulation methods were used to explore which regulatory mechanisms can lead to realistic output at the cell and whole organ scale and which other possibilities must be discarded as they result in cellular patterns and kinematic characteristics that are not consistent with experimental observations for the Arabidopsis thaliana primary root. To aid in this analysis, a 'Uniform Longitudinal Strain Rule' (ULSR) was formulated as a necessary condition for stable, unidirectional, symplastic growth. Our simulations indicate that symplastic structures are robust to differences in longitudinal strain rates along the growth axis only if these differences are small and short-lived. Whereas simple cell-autonomous regulatory rules based on counters and timers can produce stable growth, it was found that steady developmental zones and smooth transitions in cell lengths are not feasible. By introducing spatial cues into growth regulation, those inadequacies could be avoided and experimental data could be faithfully reproduced. Nevertheless, a root growth model based on previous polar auxin-transport mechanisms violates the proposed ULSR due to the presence of lateral gradients. Models with layer-specific regulation or layer-driven growth offer potential solutions. Alternatively, a model representing the known cross-talk between auxin, as the cell proliferation promoting factor, and cytokinin, as the cell differentiation promoting factor, predicts the effect of hormone-perturbations on meristem size. By down-regulating PIN-mediated transport through the transcription factor SHY2, cytokinin effectively flattens the lateral auxin gradient, at the basal boundary of the division zone, (thereby imposing the ULSR) to signal the exit of proliferation and start of elongation. This model exploration underlines the value of

  7. Putting Theory to the Test: Which Regulatory Mechanisms Can Drive Realistic Growth of a Root?

    Science.gov (United States)

    De Vos, Dirk; Vissenberg, Kris; Broeckhove, Jan; Beemster, Gerrit T. S.

    2014-01-01

    In recent years there has been a strong development of computational approaches to mechanistically understand organ growth regulation in plants. In this study, simulation methods were used to explore which regulatory mechanisms can lead to realistic output at the cell and whole organ scale and which other possibilities must be discarded as they result in cellular patterns and kinematic characteristics that are not consistent with experimental observations for the Arabidopsis thaliana primary root. To aid in this analysis, a ‘Uniform Longitudinal Strain Rule’ (ULSR) was formulated as a necessary condition for stable, unidirectional, symplastic growth. Our simulations indicate that symplastic structures are robust to differences in longitudinal strain rates along the growth axis only if these differences are small and short-lived. Whereas simple cell-autonomous regulatory rules based on counters and timers can produce stable growth, it was found that steady developmental zones and smooth transitions in cell lengths are not feasible. By introducing spatial cues into growth regulation, those inadequacies could be avoided and experimental data could be faithfully reproduced. Nevertheless, a root growth model based on previous polar auxin-transport mechanisms violates the proposed ULSR due to the presence of lateral gradients. Models with layer-specific regulation or layer-driven growth offer potential solutions. Alternatively, a model representing the known cross-talk between auxin, as the cell proliferation promoting factor, and cytokinin, as the cell differentiation promoting factor, predicts the effect of hormone-perturbations on meristem size. By down-regulating PIN-mediated transport through the transcription factor SHY2, cytokinin effectively flattens the lateral auxin gradient, at the basal boundary of the division zone, (thereby imposing the ULSR) to signal the exit of proliferation and start of elongation. This model exploration underlines the value of

  8. Use of lactobacilli and their pheromone-based regulatory mechanism in gene expression and drug delivery.

    Science.gov (United States)

    Diep, D B; Mathiesen, G; Eijsink, V G H; Nes, I F

    2009-01-01

    Lactobacilli are common microorganisms in diverse vegetables and meat products and several of these are also indigenous inhabitants in the gastro-intestinal (GI) tract of humans and animals where they are believed to have health promoting effects on the host. One of the highly appreciated probiotic effects is their ability to inhibit the growth of pathogens by producing antimicrobial peptides, so-called bacteriocins. Production of some bacteriocins has been shown to be strictly regulated through a quorum-sensing based mechanism mediated by a secreted peptide-pheromone (also called induction peptide; IP), a membrane-located sensor (histidine protein kinase; HPK) and a cytoplasmic response regulator (RR). The interaction between an IP and its sensor, which is highly specific, leads to activation of the cognate RR which in turn binds to regulated promoters and activates gene expression. The HPKs and RRs are built up by conserved modules, and the signalling between them within a network is efficient and directional, and can easily be activated by exogenously added synthetic IPs. Consequently, components from such regulatory networks have successfully been exploited in construction of a number of inducible gene expression systems. In this review, we discuss some well-characterised quorum sensing networks involved in bacteriocin production in lactobacilli, with special focus on the use of the regulatory components in gene expression and on lactobacilli as potential delivery vehicle for therapeutic and vaccine purposes.

  9. The Role and Mechanisms of Double Negative Regulatory T Cells in the Suppression of Immune Responses

    Institute of Scientific and Technical Information of China (English)

    WenhaoChen; MeganS.Ford; KevinJ.Young; LiZhang

    2004-01-01

    Accumulating evidence has demonstrated that regulatory T (Treg) cells play an important role in the maintenance of immunologic self-tolerance and in down-regulating various immune responses. Thus, there has recently been an increasing interest in studying the biology of Treg cells as well as their potential application in treating immune diseases. Many types of Treg cell subsets have been reported in a variety of disease models.Among these subsets, αβ-TCR+CD3+CD4*CD8* double negative (DN) Treg cells are defined by their capability of inhibiting immune responses via directly killing effector T cells in an antigen specific fashion. Furthermore,DN Treg cells have been shown to develop regulatory activity after encountering specific antigens, partially mediated by the acquisition of MHC-peptide complexes from antigen presenting cells (APCs). The presentation of acquired alloantigens on DN T cells allows for the specific interaction between DN Treg cells and alloantigen reactive effector T cells. Once the DN Treg and target cells have come into contact, killing is then mediated by Fas/Fas-ligand interactions, and perhaps through other unidentified pathways. Further characterization of the functions, molecular expression and mechanisms of activation of DN Treg cells will help in the development of novel therapies to induce antigen specific tolerance to self and foreign antigens. Cellular & Molecular Immunology. 2004;1(5):328-335.

  10. The Role and Mechanisms of Double Negative Regulatory T Cells in the Suppression of Immune Responses

    Institute of Scientific and Technical Information of China (English)

    Wenhao Chen; Megan S. Ford; Kevin J. Young; Li Zhang

    2004-01-01

    Accumulating evidence has demonstrated that regulatory T (Treg) cells play an important role in the maintenance of immunologic self-tolerance and in down-regulating various immune responses. Thus, there has recently been an increasing interest in studying the biology of Treg cells as well as their potential application in treating immune diseases. Many types of Treg cell subsets have been reported in a variety of disease models.Among these subsets, αβ-TCR+CD3+CD4-CD8- double negative (DN) Treg cells are defined by their capability of inhibiting immune responses via directly killing effector T cells in an antigen specific fashion. Furthermore,DN Treg cells have been shown to develop regulatory activity after encountering specific antigens, partially mediated by the acquisition of MHC-peptide complexes from antigen presenting cells (APCs). The presentation of acquired alloantigens on DN T cells allows for the specific interaction between DN Treg cells and alloantigen reactive effector T cells. Once the DN Treg and target cells have come into contact, killing is then mediated by Fas/Fas-ligand interactions, and perhaps through other unidentified pathways. Further characterization of the functions, molecular expression and mechanisms of activation of DN Treg cells will help in the development of novel therapies to induce antigen specific tolerance to self and foreign antigens. Cellular & Molecular Immunology. 2004;1(5):328-335.

  11. Novel Regulatory Mechanisms of Pathogenicity and Virulence to Combat MDR in Candida albicans

    Directory of Open Access Journals (Sweden)

    Saif Hameed

    2013-01-01

    Full Text Available Continuous deployment of antifungals in treating infections caused by dimorphic opportunistic pathogen Candida albicans has led to the emergence of drug resistance resulting in cross-resistance to many unrelated drugs, a phenomenon termed multidrug resistance (MDR. Despite the current understanding of major factors which contribute to MDR mechanisms, there are many lines of evidence suggesting that it is a complex interplay of multiple factors which may be contributed by still unknown mechanisms. Coincidentally with the increased usage of antifungal drugs, the number of reports for antifungal drug resistance has also increased which further highlights the need for understanding novel molecular mechanisms which can be explored to combat MDR, namely, ROS, iron, hypoxia, lipids, morphogenesis, and transcriptional and signaling networks. Considering the worrying evolution of MDR and significance of C. albicans being the most prevalent human fungal pathogen, this review summarizes these new regulatory mechanisms which could be exploited to prevent MDR development in C. albicans as established from recent studies.

  12. The Regulatory Mechanisms of Tumor Suppressor P16INK4A and Relevance to Cancer†

    Science.gov (United States)

    Li, Junan; Poi, Ming Jye; Tsai, Ming-Daw

    2011-01-01

    P16INK4A (also known as P16 and MTS1), a protein consisting exclusively of four ankyrin repeats, is recognized as a tumor suppressor mainly due to the prevalence of genetic inactivation of the p16INK4A (or CDKN2A) gene in virtually all types of human cancers. However, it has also been shown that elevated expression (up-regulation) of P16 is involved in cellular senescence, aging, and cancer progression, indicating that the regulation of P16 is critical for its function. Here, we discuss the regulatory mechanisms of P16 function at the DNA level, the transcription level, and the posttranscriptional level, as well as their implications in the structure-function relationship of P16 and in human cancers. PMID:21619050

  13. Mechanistic Basis for Plant Responses to Drought Stress : Regulatory Mechanism of Abscisic Acid Signaling

    Science.gov (United States)

    Miyakawa, Takuya; Tanokura, Masaru

    The phytohormone abscisic acid (ABA) plays a key role in the rapid adaptation of plants to environmental stresses such as drought and high salinity. Accumulated ABA in plant cells promotes stomatal closure in guard cells and transcription of stress-tolerant genes. Our understanding of ABA responses dramatically improved by the discovery of both PYR/PYL/RCAR as a soluble ABA receptor and inhibitory complex of a protein phospatase PP2C and a protein kinase SnRK2. Moreover, several structural analyses of PYR/PYL/RCAR revealed the mechanistic basis for the regulatory mechanism of ABA signaling, which provides a rational framework for the design of alternative agonists in future.

  14. Regulatory mechanism of endothelin receptor B in the cerebral arteries after focal cerebral ischemia

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Thigarajah, Rushani; Edvinsson, Lars;

    2014-01-01

    drug targets to restore normal cerebral artery contractile function as part of successful neuroprotective therapy. METHODS: We have employed in vitro methods on human and rat cerebral arteries to study the regulatory mechanisms and the efficacy of target selective inhibitor, Mithramycin A (MitA...... arteries. RESULTS: Increased expression of specificity protein (Sp1) was observed in human and rat cerebral arteries after organ culture, strongly correlating with the ETBR upregulation. Similar observations were made in MCAO rats. Treatment with MitA, a Sp1 specific inhibitor, significantly downregulated...... vasoconstriction in focal cerebral ischemia via MEK-ERK signaling, which is also conserved in humans. The results show that MitA can effectively be used to block ETBR mediated vasoconstriction as a supplement to an existing ischemic stroke therapy....

  15. Systemic blood loss affects NF-kappa B regulatory mechanisms in the lungs.

    Science.gov (United States)

    Moine, P; Shenkar, R; Kaneko, D; Le Tulzo, Y; Abraham, E

    1997-07-01

    The nuclear regulatory factor (NF)-kappa B is activated in the lungs of patients with acute respiratory distress syndrome (ARDS). In experimental models of acute lung injury, activation of NF-kappa B contributes to the increased expression of immunoregulatory cytokines and other proinflammatory mediators in the lungs. Because of the important role that NF-kappa B activation appears to play in the development of acute lung injury, we examined cytoplasmic and nuclear NF-kappa B counterregulatory mechanisms in lung mononuclear cells, using a murine model in which inflammatory lung injury develops after blood loss. Sustained activation of NF-kappa B was present in lung mononuclear cells over the 4-h period after blood loss. The activation of NF-kappa B after hemorrhage was accompanied by alterations in levels of the NF-kappa B regulatory proteins I kappa B alpha and Bcl-3. Cytoplasmic and nuclear I kappa B alpha were increased and nuclear Bcl-3 was decreased during the first hour after blood loss, but, by 4 h posthemorrhage, cytoplasmic and nuclear I kappa B alpha levels were decreased and nuclear levels of Bcl-3 were increased. Inhibition of xanthine oxidase activity in otherwise unmanipulated unhemorrhaged mice resulted in increased levels of I kappa B alpha and decreased amounts of Bcl-3 in nuclear extracts from lung mononuclear cells. No changes in the levels of nuclear I kappa B alpha or Bcl-3 occurred after hemorrhage when xanthine oxidase activity was inhibited. These results demonstrate that blood loss, at least partly through xanthine oxidase-dependent mechanisms, produces alterations in the levels of both I kappa B alpha and Bcl-3 in lung mononuclear cell populations. The effects of hemorrhage on proteins that regulate activation of NF-kappa B may contribute to the frequent development of inflammatory lung injury in this setting.

  16. Distinct regulatory mechanisms of eukaryotic transcriptional activation by SAGA and TFIID.

    Science.gov (United States)

    Bhaumik, Sukesh R

    2011-02-01

    A growing number of human diseases are linked to abnormal gene expression which is largely controlled at the level of transcriptional initiation. The gene-specific activator promotes the initiation of transcription through its interaction with one or more components of the transcriptional initiation machinery, hence leading to stimulated transcriptional initiation or activation. However, all activator proteins do not target the same component(s) of the transcriptional initiation machinery. Rather, they can have different target specificities, and thus, can lead to distinct mechanisms of transcriptional activation. Two such distinct mechanisms of transcriptional activation in yeast are mediated by the SAGA (Spt-Ada-Gcn5-Acetyltransferase) and TFIID (Transcription factor IID) complexes, and are termed as "SAGA-dependent" and "TFIID-dependent" transcriptional activation, respectively. SAGA is the target of the activator in case of SAGA-dependent transcriptional activation, while the targeting of TFIID by the activator leads to TFIID-dependent transcriptional activation. Both the SAGA and TFIID complexes are highly conserved from yeast to human, and play crucial roles in gene activation among eukaryotes. The regulatory mechanisms of eukaryotic transcriptional activation by SAGA and TFIID are discussed here. This article is part of a Special Issue entitled The 26S Proteasome: When degradation is just not enough!

  17. TRIP: General computer algebra system for celestial mechanics

    Science.gov (United States)

    Laskar, J.; Gastineau, M.

    2012-10-01

    TRIP is an interactive computer algebra system that is devoted to perturbation series computations, and specially adapted to celestial mechanics. Its development started in 1988, as an upgrade of the special purpose FORTRAN routines elaborated by J. Laskar for the demonstration of the chaotic behavior of the Solar System. TRIP is a mature and efficient tool for handling multivariate generalized power series, and embeds two kernels, a symbolic and a numerical kernel. This numerical kernel communicates with Gnuplot or Grace to plot the graphics and allows one to plot the numerical evaluation of symbolic objects.

  18. A General Formulation for the Stiffness Matrix of Parallel Mechanisms

    CERN Document Server

    Quennouelle, Cyril

    2012-01-01

    Starting from the definition of a stiffness matrix, the authors present a new formulation of the Cartesian stiffness matrix of parallel mechanisms. The proposed formulation is more general than any other stiffness matrix found in the literature since it can take into account the stiffness of the passive joints, it can consider additional compliances in the joints or in the links and it remains valid for large displacements. Then, the validity, the conservative property, the positive definiteness and the relation with other formulations of stiffness matrices are discussed theoretically. Finally, a numerical example is given in order to illustrate the correctness of this matrix.

  19. Minimum length from quantum mechanics and classical general relativity.

    Science.gov (United States)

    Calmet, Xavier; Graesser, Michael; Hsu, Stephen D H

    2004-11-19

    We derive fundamental limits on measurements of position, arising from quantum mechanics and classical general relativity. First, we show that any primitive probe or target used in an experiment must be larger than the Planck length lP. This suggests a Planck-size minimum ball of uncertainty in any measurement. Next, we study interferometers (such as LIGO) whose precision is much finer than the size of any individual components and hence are not obviously limited by the minimum ball. Nevertheless, we deduce a fundamental limit on their accuracy of order lP. Our results imply a device independent limit on possible position measurements.

  20. Domain-general mechanisms of complex working memory span.

    Science.gov (United States)

    Chein, Jason M; Moore, Adam B; Conway, Andrew R A

    2011-01-01

    A new fMRI complex working memory span paradigm was used to identify brain regions making domain-general contributions to working memory task performance. For both verbal and spatial versions of the task, complex working memory span performance increased the activity in lateral prefrontal, anterior cingulate, and parietal cortices during the Encoding, Maintenance, and Coordination phase of task performance. Meanwhile, overlapping activity in anterior prefrontal and medial temporal lobe regions was associated with both verbal and spatial recall from working memory. These findings help to adjudicate several contested issues regarding the executive mechanisms of working memory, the separability of short-term and working memory in the verbal and spatial domains, and the relative contribution of short-term and long-term memory mechanisms to working memory capacity. The study also provides a vital bridge between psychometric and neuroimaging approaches to working memory, and constrains our understanding of how working memory may contribute to the broader landscape of cognitive performance.

  1. Opportunities to minimise animal use in pharmaceutical regulatory general toxicology: a cross-company review.

    Science.gov (United States)

    Sparrow, Susan S; Robinson, Sally; Bolam, Sue; Bruce, Christopher; Danks, Andy; Everett, David; Fulcher, Stephen; Hill, Rose E; Palmer, Helen; Scott, Elspeth W; Chapman, Kathryn L

    2011-11-01

    Toxicity studies in animals are carried out to identify the intrinsic hazard of a substance to support risk assessment for humans. In order to identify opportunities to minimise animal use in regulatory toxicology studies, a review of current study designs was carried out. Pharmaceutical companies and contract research organisations in the UK shared data and experience of standard toxicology studies (ranging from one to nine months duration) in rodents and non-rodents; and carcinogenicity studies in the rat and mouse. The data show that variation in study designs was primarily due to (i) the number of animals used in the main study groups, (ii) the use of animals in toxicokinetic (TK) satellite groups, and (iii) the use of animals in off-treatment recovery groups. The information has been used to propose a series of experimental designs where small adjustments could reduce animal use in practice, while maintaining the scientific objectives.

  2. NF-kappaB regulatory mechanisms in alveolar macrophages from patients with acute respiratory distress syndrome.

    Science.gov (United States)

    Moine, P; McIntyre, R; Schwartz, M D; Kaneko, D; Shenkar, R; Le Tulzo, Y; Moore, E E; Abraham, E

    2000-02-01

    Activation of the nuclear regulatory factor NF-kappaB occurs in the lungs of patients with the acute respiratory distress syndrome (ARDS) and may contribute to the increased expression of immunoregulatory cytokines and other proinflammatory mediators in this setting. Because of the important role that NF-kappaB activation appears to play in the development of acute lung injury, we examined cytoplasmic and nuclear NF-kapppaB counterregulatory mechanisms, involving IkappaB proteins, in alveolar macrophages obtained from 7 control patients without lung injury and 11 patients with established ARDS. Cytoplasmic levels of the NF-kappaB subunits p50, p65, and c-Rel were significantly decreased in alveolar macrophages from patients with ARDS, consistent with enhanced migration of liberated NF-kappaB dimers from the cytoplasm to the nucleus. Cytoplasmic and nuclear levels of IkappaBalpha were not significantly altered in alveolar macrophages from patients with established ARDS, compared with controls. In contrast, nuclear levels of Bcl-3 were significantly decreased in patients with ARDS compared with controls (P = 0.02). No IkappaBgamma, IkappaBbeta, or p105 proteins were detected in the cytoplasm of alveolar macrophages from control patients or patients with ARDS. The presence of activated NF-kappaB in alveolar macrophages from patients with established ARDS implies the presence of an ongoing stimulus for NF-kappaB activation. In this setting, appropriate counterregulatory mechanisms to normalize nuclear levels of NF-kappaB and to suppress NF-kappaB-mediated transcription, such as increased cytoplasmic and nuclear IkappaBalpha levels or decreased Bcl-3 levels, appeared to be induced. Nevertheless, even though counterregulatory mechanisms to NF-kappaB activation are activated in lung macrophages of patients with ARDS, NF-kappaB remains activated. These results suggest that fundamental abnormalities in transcriptional mechanisms involving NF-kappaB and important in the

  3. A model for the volume regulatory mechanism of the Airway Surface Layer

    Science.gov (United States)

    Lang, Michael; Rubinstein, Michael; Davis, C. William; Tarran, Robert; Boucher, Richard

    2006-03-01

    The airway surface layer (ASL) of a lung consists of two parts: a mucus layer with thickness of about 30 μm in contact with air and a periciliary layer (PCL) of about 7 μm below. Mucus collects dust and bacteria and is swept to throat by beating cilia, while riding on top of PCL. It is important that the thickness of PCL is matched with the length of cilia in order to optimize clearance of mucus. Decrease of PCL thickness would finally lead to an occlusion of the respiratory system. Experiments show that the height of PCL stays constant after removing mucus. When modifying height or composition of this open PCL by removing fluid or adding isotonic solution leads to the same final height of PCL. Thus, there must be a regulatory mechanism, that controls height, i.e. ASL volume. Additional experiments show that mechanical stimulus of the cells like shear leads to an increase of ASL volume, thus, the cell is able to actively adjust this volume. Based on these observations a class of models is introduced that describes the experiments and a specific minimum model for the given problem is proposed.

  4. A cell-regulatory mechanism involving feedback between contraction and tissue formation guides wound healing progression.

    Directory of Open Access Journals (Sweden)

    Clara Valero

    Full Text Available Wound healing is a process driven by cells. The ability of cells to sense mechanical stimuli from the extracellular matrix that surrounds them is used to regulate the forces that cells exert on the tissue. Stresses exerted by cells play a central role in wound contraction and have been broadly modelled. Traditionally, these stresses are assumed to be dependent on variables such as the extracellular matrix and cell or collagen densities. However, we postulate that cells are able to regulate the healing process through a mechanosensing mechanism regulated by the contraction that they exert. We propose that cells adjust the contraction level to determine the tissue functions regulating all main activities, such as proliferation, differentiation and matrix production. Hence, a closed-regulatory feedback loop is proposed between contraction and tissue formation. The model consists of a system of partial differential equations that simulates the evolution of fibroblasts, myofibroblasts, collagen and a generic growth factor, as well as the deformation of the extracellular matrix. This model is able to predict the wound healing outcome without requiring the addition of phenomenological laws to describe the time-dependent contraction evolution. We have reproduced two in vivo experiments to evaluate the predictive capacity of the model, and we conclude that there is feedback between the level of cell contraction and the tissue regenerated in the wound.

  5. Comprehensive population-based genome sequencing provides insight into hematopoietic regulatory mechanisms

    Science.gov (United States)

    Guo, Michael H.; Nandakumar, Satish K.; Ulirsch, Jacob C.; Zekavat, Seyedeh M.; Buenrostro, Jason D.; Natarajan, Pradeep; Salem, Rany M.; Chiarle, Roberto; Mitt, Mario; Kals, Mart; Pärn, Kalle; Fischer, Krista; Milani, Lili; Mägi, Reedik; Palta, Priit; Gabriel, Stacey B.; Metspalu, Andres; Lander, Eric S.; Kathiresan, Sekar; Hirschhorn, Joel N.; Esko, Tõnu; Sankaran, Vijay G.

    2017-01-01

    Genetic variants affecting hematopoiesis can influence commonly measured blood cell traits. To identify factors that affect hematopoiesis, we performed association studies for blood cell traits in the population-based Estonian Biobank using high-coverage whole-genome sequencing (WGS) in 2,284 samples and SNP genotyping in an additional 14,904 samples. Using up to 7,134 samples with available phenotype data, our analyses identified 17 associations across 14 blood cell traits. Integration of WGS-based fine-mapping and complementary epigenomic datasets provided evidence for causal mechanisms at several loci, including at a previously undiscovered basophil count-associated locus near the master hematopoietic transcription factor CEBPA. The fine-mapped variant at this basophil count association near CEBPA overlapped an enhancer active in common myeloid progenitors and influenced its activity. In situ perturbation of this enhancer by CRISPR/Cas9 mutagenesis in hematopoietic stem and progenitor cells demonstrated that it is necessary for and specifically regulates CEBPA expression during basophil differentiation. We additionally identified basophil count-associated variation at another more pleiotropic myeloid enhancer near GATA2, highlighting regulatory mechanisms for ordered expression of master hematopoietic regulators during lineage specification. Our study illustrates how population-based genetic studies can provide key insights into poorly understood cell differentiation processes of considerable physiologic relevance. PMID:28031487

  6. Up-regulation of miR-98 and unraveling regulatory mechanisms in gestational diabetes mellitus

    Science.gov (United States)

    Cao, Jing-Li; Zhang, Lu; Li, Jian; Tian, Shi; Lv, Xiao-Dan; Wang, Xue-Qin; Su, Xing; Li, Ying; Hu, Yi; Ma, Xu; Xia, Hong-Fei

    2016-01-01

    MiR-98 expression was up-regulated in kidney in response to early diabetic nephropathy in mouse and down-regulated in muscle in type 2 diabetes in human. However, the expression prolife and functional role of miR-98 in human gestational diabetes mellitus (GDM) remained unclear. Here, we investigated its expression and function in placental tissues from GDM patients and the possible molecular mechanisms. The results showed that miR-98 was up-regulated in placentas from GDM patients compared with normal placentas. MiR-98 over-expression increased global DNA methylational level and miR-98 knockdown reduced global DNA methylational level. Further investigation revealed that miR-98 could inhibit Mecp2 expression by binding the 3′-untranslated region (UTR) of methyl CpG binding protein 2 (Mecp2), and then led to the expression dysregulation of canonical transient receptor potential 3 (Trpc3), a glucose uptake related gene. More importantly, in vivo analysis found that the expression level of Mecp2 and Trpc3 in placental tissues from GDM patients, relative to the increase of miR-98, was diminished, especially for GDM patients over the age of 35 years. Collectively, up-regulation of miR-98 in the placental tissues of human GDM is linked to the global DNA methylation via targeting Mecp2, which may imply a novel regulatory mechanism in GDM. PMID:27573367

  7. Immunology Mechanism of CD4+ CD25 T Regulatory Cells Acting on Effector T Cells

    Institute of Scientific and Technical Information of China (English)

    FENGNing-han; WUHong-fei; WUJun; ZHANGWei; SUIYuan-gen; HEHou-guang; ZHANGChun-lei; ZHENGJun-song

    2004-01-01

    Objective: To detect the inhibiting co-stimulating molecule CTLA4 and cytokines secreted by Treg cells, and explore the immunology mechanism of T regulatory cells acting on effector T cells in co-cultured system(CCS) and separating-cultured system(SCS). Methods: Detecting the percentage of CTLA4 and CD28 expressed on the Treg ceils and effector T ceils, and then adding Treg cells to mixed lymphocyte reaction(MLR) system in CCS and TransWeil Milliceil-PCF SCS, at the same time, adding or not adding anti-IL-10 or anti-TGF.II1 to the reacting systems, examining the inhibitory capacity of Treg ceils exerting on the MLR. Results: Compared with effector T cells, Treg cells expressed higher level CTLA4 and secreted much more IL-10 and TGF-β(P<0.01). The inhibitory capacity of Treg cells co-cultured with effector T ceils is much stronger than that in separating cultured group(P<0.01). Moreover, the inhibiting rate of Treg ceils exerting on effector T ceils through secretin_g IL-10 was more powerful than that through secreting TGF-β1 (P<0.01). Coaclusion: Both ceil-to-ceil contact and cytokines secretion mechanisms are involved in CD4+ CD25+ Treg ceils operating function. However, the former is more important. Intresfingly, we for the first time pointfound that IL-10 plays more powerful roles than TGF-β1 in the cytokines secretion mechanism.

  8. Analysis of regulatory network involved in mechanical induction of embryonic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Xinan Zhang

    Full Text Available Embryonic stem cells are conventionally differentiated by modulating specific growth factors in the cell culture media. Recently the effect of cellular mechanical microenvironment in inducing phenotype specific differentiation has attracted considerable attention. We have shown the possibility of inducing endoderm differentiation by culturing the stem cells on fibrin substrates of specific stiffness. Here, we analyze the regulatory network involved in such mechanically induced endoderm differentiation under two different experimental configurations of 2-dimensional and 3-dimensional culture, respectively. Mouse embryonic stem cells are differentiated on an array of substrates of varying mechanical properties and analyzed for relevant endoderm markers. The experimental data set is further analyzed for identification of co-regulated transcription factors across different substrate conditions using the technique of bi-clustering. Overlapped bi-clusters are identified following an optimization formulation, which is solved using an evolutionary algorithm. While typically such analysis is performed at the mean value of expression data across experimental repeats, the variability of stem cell systems reduces the confidence on such analysis of mean data. Bootstrapping technique is thus integrated with the bi-clustering algorithm to determine sets of robust bi-clusters, which is found to differ significantly from corresponding bi-clusters at the mean data value. Analysis of robust bi-clusters reveals an overall similar network interaction as has been reported for chemically induced endoderm or endodermal organs but with differences in patterning between 2-dimensional and 3-dimensional culture. Such analysis sheds light on the pathway of stem cell differentiation indicating the prospect of the two culture configurations for further maturation.

  9. The problem of time quantum mechanics versus general relativity

    CERN Document Server

    Anderson, Edward

    2017-01-01

    This book is a treatise on time and on background independence in physics. It first considers how time is conceived of in each accepted paradigm of physics: Newtonian, special relativity, quantum mechanics (QM) and general relativity (GR). Substantial differences are moreover uncovered between what is meant by time in QM and in GR. These differences jointly source the Problem of Time: Nine interlinked facets which arise upon attempting concurrent treatment of the QM and GR paradigms, as is required in particular for a background independent theory of quantum gravity. A sizeable proportion of current quantum gravity programs - e.g. geometrodynamical and loop quantum gravity approaches to quantum GR, quantum cosmology, supergravity and M-theory - are background independent in this sense. This book's foundational topic is thus furthermore of practical relevance in the ongoing development of quantum gravity programs. This book shows moreover that eight of the nine facets of the Problem of Time already occur upon ...

  10. General theory for the mechanics of confined microtubule asters

    Science.gov (United States)

    Ma, Rui; Laan, Liedewij; Dogterom, Marileen; Pavin, Nenad; Jülicher, Frank

    2014-01-01

    In cells, dynamic microtubules organize into asters or spindles to assist positioning of organelles. Two types of forces are suggested to contribute to the positioning process: (i) microtubule-growth based pushing forces; and (ii) motor protein mediated pulling forces. In this paper, we present a general theory to account for aster positioning in a confinement of arbitrary shape. The theory takes account of microtubule nucleation, growth, catastrophe, slipping, as well as interaction with cortical force generators. We calculate microtubule distributions and forces acting on microtubule organizing centers in a sphere and in an ellipsoid. Positioning mechanisms based on both pushing forces and pulling forces can be distinguished in our theory for different parameter regimes or in different geometries. In addition, we investigate positioning of microtubule asters in the case of asymmetric distribution of motors. This analysis enables us to characterize situations relevant for Caenorrhabditis elegans embryos.

  11. Reconciling Local Realism with Quantum Mechanics: The Generalized BCHSH Inequalities

    CERN Document Server

    Garola, C; Garola, Claudio; Sozzo, Sandro

    2007-01-01

    Most physicists uphold that the tests of the Bell-Clauser, Horne, Shimony and Holt (BCHSH) inequalities confirm quantum mechanics (QM) and refute local realism. Some scholars, however, criticize this conviction, yet maintaining that QM conflicts with local realism. At variance with both viewpoints one of the authors has recently worked out an extended semantic realism (ESR) model which shows that, if quantum probabilities are interpreted as conditional rather than absolute probabilities, a picture of the microworld can be constructed that is simultaneously consistent with local realism and QM. We show here that the BCHSH inequalities must be replaced, within the ESR model, by more general inequalities. These depend on parameters (detection probabilities) which may be such that the inequalities are never violated by quantum expectation values. The condition that no violation occurs implies the existence of upper bounds on detection probabilities, which makes the ESR model falsifiable. These results admit an in...

  12. Regulatory mechanism of protein metabolic pathway during the differentiation process of chicken male germ cell.

    Science.gov (United States)

    Li, Dong; Zuo, Qisheng; Lian, Chao; Zhang, Lei; Shi, Qingqing; Zhang, Zhentao; Wang, Yingjie; Ahmed, Mahmoud F; Tang, Beibei; Xiao, Tianrong; Zhang, Yani; Li, Bichun

    2015-08-01

    We explored the regulatory mechanism of protein metabolism during the differentiation process of chicken male germ cells and provide a basis for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro. We sequenced the transcriptome of embryonic stem cells, primordial germ cells, and spermatogonial stem cells with RNA sequencing (RNA-Seq), bioinformatics analysis methods, and detection of the key genes by quantitative reverse transcription PCR (qRT-PCR). Finally, we found 16 amino acid metabolic pathways enriched in the biological metabolism during the differentiation process of embryonic stem cells to primordial germ cells and 15 amino acid metabolic pathways enriched in the differentiation stage of primordial germ cells to spermatogonial stem cells. We found three pathways, arginine-proline metabolic pathway, tyrosine metabolic pathway, and tryptophan metabolic pathway, significantly enriched in the whole differentiation process of embryonic stem cells to spermatogonial stem cells. Moreover, for these three pathways, we screened key genes such as NOS2, ADC, FAH, and IDO. qRT-PCR results showed that the expression trend of these genes were the same to RNA-Seq. Our findings showed that the three pathways and these key genes play an important role in the differentiation process of embryonic stem cells to male germ cells. These results provide basic information for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro.

  13. Secretion and regulatory mechanism of leptin during pregnancy in the golden hamster (Mesocricetus auratus)

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The aim of this study is to investigate the secretion pattern and regulatory mechanism of leptin during pregnancy in the golden hamster (Mesocricetus auratus). 100 pregnant golden hamsters were separated into 16 groups and the serum was sampled daily throughout gestation for the leptin assay. Results indicated that a gestational leptin profile existed during pregnancy in the golden hamster. To investigate if endocrine conditions during pregnancy contribute to this gestational leptin profile, serums collected during different reproductive stages were added to the adipocyte culture medium. Results showed that sera collected from all reproductive stages have significant stimulating effect on the secretion of leptin as compared with the control (P 0.05). However, sera from mid and late pregnancy significantly stimulate leptin secretion as compared with the cycling sera (P < 0.01). Serum collected on day 15 of pregnancy have the strongest stimulating effect on leptin secretion compared with sera collected on day 8 (P < 0.0001) and day 12 (P < 0.001) of the pregnancy. But after the extraction of steroid hormones, sera collected during different reproductive stages have the same effect on leptin secretion in vitro. Further study showed that dexamethason, progesterone and insulin stimulated while estradiol suppressed leptin secretion in vitro. Our results suggested that steroid hormones (or other steroid factors) have significant regulating effect on the leptin secretion during pregnancy and they may be the most important contributors of the gestational leptin profile in the golden hamster.

  14. The Characteristics and Regulatory Mechanisms of Superoxide Generation from eNOS Reductase Domain.

    Directory of Open Access Journals (Sweden)

    Hu Peng

    Full Text Available In addition to superoxide (O2.- generation from nitric oxide synthase (NOS oxygenase domain, a new O2.- generation site has been identified in the reductase domain of inducible NOS (iNOS and neuronal NOS (nNOS. Cysteine S-glutathionylation in eNOS reductase domain also induces O2.- generation from eNOS reductase domain. However, the characteristics and regulatory mechanism of the O2.- generation from NOS reductase domain remain unclear. We cloned and purified the wild type bovine eNOS (WT eNOS, a mutant of Serine 1179 replaced with aspartic acid eNOS (S1179D eNOS, which mimics the negative charge caused by phosphorylationand truncated eNOS reductase domain (eNOS RD. Both WT eNOS and S1179D eNOS generated significant amount of O2.- in the absence of BH4 and L-arginine. The capacity of O2.- generation from S1179D eNOS was significantly higher than that of WT eNOS (1.74:1. O2.- generation from both WT eNOS and S1179D eNOS were not completely inhibited by 100nM tetrahydrobiopterin(BH4. This BH4 un-inhibited O2.- generation from eNOS was blocked by 10mM flavoprotein inhibitor, diphenyleneiodonium (DPI. Purified eNOS reductase domain protein confirmed that this BH4 un-inhibited O2.- generation originates at the FMN or FAD/NADPH binding site of eNOS reductase domain. DEPMPO-OOH adduct EPR signals and NADPH consumptions analyses showed that O2.- generation from eNOS reductase domain was regulated by Serine 1179 phosphorylation and DPI, but not by L-arginine, BH4 or calmodulin (CaM. In addition to the heme center of eNOS oxygenase domain, we confirmed another O2.- generation site in the eNOS reductase domain and characterized its regulatory properties.

  15. Characterization of the regulatory mechanisms of activating transcription factor 3 by hypertrophic stimuli in rat cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Elina Koivisto

    Full Text Available AIMS: Activating transcription factor 3 (ATF3 is a stress-activated immediate early gene suggested to have both detrimental and cardioprotective role in the heart. Here we studied the mechanisms of ATF3 activation by hypertrophic stimuli and ATF3 downstream targets in rat cardiomyocytes. METHODS AND RESULTS: When neonatal rat cardiomyocytes were exposed to endothelin-1 (ET-1, 100 nM and mechanical stretching in vitro, maximal increase in ATF3 expression occurred at 1 hour. Inhibition of extracellular signal-regulated kinase (ERK by PD98059 decreased ET-1- and stretch-induced increase of ATF3 protein but not ATF3 mRNA levels, whereas protein kinase A (PKA inhibitor H89 attenuated both ATF3 mRNA transcription and protein expression in response to ET-1 and stretch. To characterize further the regulatory mechanisms upstream of ATF3, p38 mitogen-activated protein kinase (MAPK signaling was investigated using a gain-of-function approach. Adenoviral overexpression of p38α, but not p38β, increased ATF3 mRNA and protein levels as well as DNA binding activity. To investigate the role of ATF3 in hypertrophic process, we overexpressed ATF3 by adenovirus-mediated gene transfer. In vitro, ATF3 gene delivery attenuated the mRNA transcription of interleukin-6 (IL-6 and plasminogen activator inhibitor-1 (PAI-1, and enhanced nuclear factor-κB (NF-κB and Nkx-2.5 DNA binding activities. Reduced PAI-1 expression was also detected in vivo in adult rat heart by direct intramyocardial adenovirus-mediated ATF3 gene delivery. CONCLUSIONS: These data demonstrate that ATF3 activation by ET-1 and mechanical stretch is partly mediated through ERK and cAMP-PKA pathways, whereas p38 MAPK pathway is involved in ATF3 activation exclusively through p38α isoform. ATF3 activation caused induction of modulators of the inflammatory response NF-κB and Nkx-2.5, as well as attenuation of pro-fibrotic and pro-inflammatory proteins IL-6 and PAI-1, suggesting cardioprotective role

  16. Regulatory forum opinion piece: blind reading of histopathology slides in general toxicology studies.

    Science.gov (United States)

    Neef, Natasha; Nikula, Kristen J; Francke-Carroll, Sabine; Boone, Laura

    2012-06-01

    With the intention of reducing bias, a recent European Food Safety Authority draft guidance document included a recommendation for blinded evaluation of histopathology slides in general toxicology studies (EFSA 2011). Although blinding as to treatment status reduces bias in many types of scientific experiment and is sometimes also appropriate in toxicologic pathology (Holland and Holland 2011), it is most unlikely to help achieve the overall goal of improved human safety when used for routine histopathology evaluation of tissues in general toxicology studies. This is the case because (1) blinding is not applicable to the inductive reasoning process used to identify test article effects in the tissues and would dramatically reduce the chances of these being successfully identified; and (2) in any case, the bias that would be reduced by blinding is actually a bias favoring diagnosis of a toxicological hazard and a conservative safety evaluation, which is appropriate in this context. Other unintended consequences of blinding histopathology evaluation include reductions in sensitivity for a variety of additional reasons and increased subjectivity of the pathology data.

  17. Integrating Factors and Conservation Theorems of Lagrangian Equations for Nonconservative Mechanical System in Generalized Classical Mechanics

    Institute of Scientific and Technical Information of China (English)

    QIAO Yong-Fen; ZHAO Shu-Hong

    2006-01-01

    The conservation theorems of the generalized Lagrangian equations for nonconservative mechanical system are studied by using method of integrating factors. Firstly, the differential equations of motion of system are given, and the definition of integrating factors is given. Next, the necessary conditions for the existence of the conserved quantity are studied in detail. Finally, the conservation theorem and its inverse for the system are established, and an example is given to illustrate the application of the result.

  18. Mutational analysis of structural elements in a class-I cyclic di-GMP riboswitch to elucidate its regulatory mechanism.

    Science.gov (United States)

    Inuzuka, Saki; Nishimura, Kei-Ichiro; Kakizawa, Hitoshi; Fujita, Yuki; Furuta, Hiroyuki; Matsumura, Shigeyoshi; Ikawa, Yoshiya

    2016-09-01

    The Vc2 riboswitch possesses an aptamer domain belonging to the class-I c-di-GMP riboswitch family. This domain has been analysed and the molecular mechanism by which it recognizes the c-di-GMP ligand has been elucidated. On the other hand, the regulatory mechanism of the full-length Vc2 riboswitch to control its downstream open reading frame (ORF) remains largely unknown. In this study, we performed in vivo reporter assays and in vitro biochemical analyses of the full-length riboswitch and its aptamer domain. We evaluated the results of in vivo and in vitro analyses to elucidate the regulatory mechanism of the Vc2 riboswitch. The present results suggest that recognition of c-di-GMP ligand by the Vc2 riboswitch aptamer domain downregulates expression of its downstream ORF primarily at the translational level.

  19. Heart Rate Variability: New Perspectives on Physiological Mechanisms, Assessment of Self-regulatory Capacity, and Health risk.

    Science.gov (United States)

    McCraty, Rollin; Shaffer, Fred

    2015-01-01

    Heart rate variability, the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operates on different time scales to adapt to environmental and psychological challenges. This article briefly reviews neural regulation of the heart and offers some new perspectives on mechanisms underlying the very low frequency rhythm of heart rate variability. Interpretation of heart rate variability rhythms in the context of health risk and physiological and psychological self-regulatory capacity assessment is discussed. The cardiovascular regulatory centers in the spinal cord and medulla integrate inputs from higher brain centers with afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. We also discuss the intrinsic cardiac nervous system and the heart-brain connection pathways, through which afferent information can influence activity in the subcortical, frontocortical, and motor cortex areas. In addition, the use of real-time HRV feedback to increase self-regulatory capacity is reviewed. We conclude that the heart's rhythms are characterized by both complexity and stability over longer time scales that reflect both physiological and psychological functional status of these internal self-regulatory systems.

  20. General aspects of solid on liquid growth mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Laux, E; Charmet, J; Haquette, H; Banakh, O; Jeandupeux, L; Graf, B; Keppner, H, E-mail: Herbert.Keppner@he-arc.c [University of Applied Science Arc, Eplatures-Grise 17, CH-2300 La Chaux-de-Fonds (Switzerland)

    2009-08-01

    Liquids, in general, tend to have a lower density as solids and therefore it is not straightforward to deposit solid over liquids in a way that the liquid becomes hermetically sealed under the solid layer. The authors review that several phenomena that can easily be observed in nature are only due to particular anomalies and solid on liquid is rather an exception as the rule. Natural solid on liquid systems are lacking of thermal, mechanical or chemical stability. It is not surprising, that one is not at all used thinking about to e.g. replace the gate oxide in a thin film transistor by a thin film of oil, or, to find in other microsystems functional liquids between a stack of thin solid films. However, once this becomes a serious option, a large variety of new Microsystems with new functionalities can be easily designed. In another paper (this conference and [1]) the authors pioneered that the polymer Parylene (poly(p-xylylene)) can be deposited on liquids coming already quite close to the above mentioned vision. In this paper the authors ask if one can synthesize other solid on liquid systems and surprisingly conclude, based on experimental evidence, that solid on liquid deposition seems to rather be the rule and not the exception.

  1. One interpretation for both Quantum Mechanics and General Relativity

    Energy Technology Data Exchange (ETDEWEB)

    Halewijn, Ewoud

    2014-07-01

    In reconciling General Relativity with Quantum Mechanics, it is challenging to resolve the combined mathematical equations and to find an interpretation that makes sense ontologically. Such an interpretation has been developed by quantizing descriptive components in both the theories and other views. The resulting micro-components have been re-integrated within the scope of known gaps between science and 'the real world'. The odd peculiarities in these theories have been made look 'normal' by fully untraditionally answering fundamental questions. The interpretation is suggesting that we define time as a discrete operator and its eigenvalues as constraints on space-time manifolds, in order to reconcile the mathematical equations. Outside the mathematical arena we suggest reconsidering the concepts of Black Holes, the Big Bang, the epistemological problem of perception in philosophy and the supposed clash between scientific and the spiritual worldviews. It is concluded that developing one consistent ontological interpretation for both theorie is possible. It is a weird story, but it is making powerful suggestions for reviewing some of our fundamental convictions.

  2. [Research Progress of NOS3 Participation in Regulatory Mechanisms of Cardiovascular Diseases].

    Science.gov (United States)

    Sun, Ting; Chi, Qingjia; Wang, Guixue

    2016-02-01

    Cardiovascular disease has been a major threat to human's health and lives for many years. It is of great importance to explore the mechanisms and develop strategies to prevent the pathogenesis. Generally, cardiovascular disease is associated with endothelial dysfunction, which is closely related to the nitric oxide (NO)-mediated vasodilatation. The release of NO is regulated by NOS3 gene in mammals' vascular system. A great deal of evidences have shown that the polymorphism and epigenetic of NOS3 gene play vital roles in the pathological process of cardiovascular disease. To gain insights into the role of NOS3 in the cardiovascular diseases, we reviewed the molecular mechanisms underlying the development of cardiovascular diseases in this paper, including the uncoupling of NOS3 protein, epigenetic and polymorphism of NOS3 gene. The review can also offer possible strategies to prevent and treat cardiovascular diseases.

  3. microRNA regulatory mechanism by which PLLA aligned nanofibers influence PC12 cell differentiation

    Science.gov (United States)

    Yu, Yadong; Lü, Xiaoying; Ding, Fei

    2015-08-01

    Objective. Aligned nanofibers (AFs) are regarded as promising biomaterials in nerve tissue engineering. However, a full understanding of the biocompatibility of AFs at the molecular level is still challenging. Therefore, the present study focused on identifying the microRNA (miRNA)-mediated regulatory mechanism by which poly-L-lactic acid (PLLA) AFs influence PC12 cell differentiation. Approach. Firstly, the effects of PLLA random nanofibers (RFs)/AFs and PLLA films (control) on the biological responses of PC12 cells that are associated with neuronal differentiation were examined. Then, SOLiD sequencing and cDNA microarray were employed to profile the expressions of miRNAs and mRNAs. The target genes of the misregulated miRNAs were predicted and compared with the mRNA profile data. Functions of the matched target genes (the intersection between the predicted target genes and the experimentally-determined, misregulated genes) were analyzed. Main results. The results revealed that neurites spread in various directions in control and RF groups. In the AF group, most neurites extended in parallel with each other. The glucose consumption and lactic acid production in the RF and AF groups were higher than those in the control group. Compared with the control group, 42 and 94 miRNAs were significantly dysregulated in the RF and AF groups, respectively. By comparing the predicted target genes with the mRNA profile data, five and 87 matched target genes were found in the RF and AF groups, respectively. Three of the matched target genes in the AF group were found to be associated with neuronal differentiation, whereas none had this association in the RF group. The PLLA AFs induced the dysregulation of miRNAs that regulate many biological functions, including axonal guidance, lipid metabolism and long-term potentiation. In particular, two miRNA-matched target gene-biological function modules associated with neuronal differentiation were identified as follows: (1) miR-23b, mi

  4. RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins Involved in a Posttranscriptional Iron Regulatory Mechanism

    Science.gov (United States)

    Figueroa-Angulo, Elisa E.; Calla-Choque, Jaeson S.; Mancilla-Olea, Maria Inocente; Arroyo, Rossana

    2015-01-01

    Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs) that interact with an iron responsive element (IRE) located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis. PMID:26703754

  5. Regulatory Mechanisms of the Molecular Pathways in Fibrosis Induced by MicroRNAs

    Institute of Scientific and Technical Information of China (English)

    Cui Yang; Si-Dao Zheng; Hong-Jin Wu; Shao-Jun Chen

    2016-01-01

    Objective:MicroRNAs (miRNAs or miRs) play critical roles in the fibrotic process in different organs.We summarized the latest research progress on the roles and mechanisms of miRNAs in the regulation of the molecular signaling pathways involved in fibrosis.Data Sources:Papers published in English from January 2010 to August 2015 were selected from the PubMed and Web of Science databases using the search terms "microRNA","miR","transforming growth factor β","tgf β","mitogen-activated protein kinase","mapk","integrin","p38","c-Jun NH2-terminal kinase","jnk","extracellular signal-regulated kinase","erk",and "fibrosis".Study Selection:Articles were obtained and reviewed to analyze the regulatory effects of miRNAs on molecular signaling pathways involved in the fibrosis.Results:Recent evidence has shown that miRNAs are involved in regulating fibrosis by targeting different substrates in the molecular processes that drive fibrosis,such as immune cell sensitization,effector cell activation,and extracellular matrix remodeling.Moreover,several important molecular signaling pathways involve in fibrosis,such as the transforming growth factor-beta (TGF-β) pathway,mitogen-activated protein kinase (MAPK) pathways,and the integrin pathway are regulated by miRNAs.Third,regulation of the fibrotic pathways induced by miRNAs is found in many other tissues in addition to the heart,lung,liver,and kidney.Interestingly,the actions of many drugs on the human body are also induced by miRNAs.It is encouraging that the fibrotic process can be blocked or reversed by targeting specific miRNAs and their signaling pathways,thereby protecting the structures and functions of different organs.Conclusions:miRNAs not only regulate molecular signaling pathways in fibrosis but also serve as potential targets of novel therapeutic interventions for fibrosing diseases.

  6. Genome-wide analysis of the salmonella Fis regulon and its regulatory mechanism on pathogenicity islands.

    Directory of Open Access Journals (Sweden)

    Hui Wang

    Full Text Available Fis, one of the most important nucleoid-associated proteins, functions as a global regulator of transcription in bacteria that has been comprehensively studied in Escherichia coli K12. Fis also influences the virulence of Salmonella enterica and pathogenic E. coli by regulating their virulence genes, however, the relevant mechanism is unclear. In this report, using combined RNA-seq and chromatin immunoprecipitation (ChIP-seq technologies, we first identified 1646 Fis-regulated genes and 885 Fis-binding targets in the S. enterica serovar Typhimurium, and found a Fis regulon different from that in E. coli. Fis has been reported to contribute to the invasion ability of S. enterica. By using cell infection assays, we found it also enhances the intracellular replication ability of S. enterica within macrophage cell, which is of central importance for the pathogenesis of infections. Salmonella pathogenicity islands (SPI-1 and SPI-2 are crucial for the invasion and survival of S. enterica in host cells. Using mutation and overexpression experiments, real-time PCR analysis, and electrophoretic mobility shift assays, we demonstrated that Fis regulates 63 of the 94 Salmonella pathogenicity island (SPI-1 and SPI-2 genes, by three regulatory modes: i binds to SPI regulators in the gene body or in upstream regions; ii binds to SPI genes directly to mediate transcriptional activation of themselves and downstream genes; iii binds to gene encoding OmpR which affects SPI gene expression by controlling SPI regulators SsrA and HilD. Our results provide new insights into the impact of Fis on SPI genes and the pathogenicity of S. enterica.

  7. Vpu Mediates Depletion of Interferon Regulatory Factor 3 during HIV Infection by a Lysosome-Dependent Mechanism

    OpenAIRE

    Doehle, Brian P.; Chang, Kristina; Rustagi, Arjun; McNevin, John; McElrath, M. Juliana; Gale, Michael

    2012-01-01

    HIV has evolved sophisticated mechanisms to avoid restriction by intracellular innate immune defenses that otherwise serve to control acute viral infection and virus dissemination. Innate defenses are triggered when pattern recognition receptor (PRR) proteins of the host cell engage pathogen-associated molecule patterns (PAMPs) present in viral products. Interferon regulatory factor 3 (IRF3) plays a central role in PRR signaling of innate immunity to drive the expression of type I interferon ...

  8. Regulatory mechanisms in arterial hypertension: role of microRNA in pathophysiology and therapy.

    Science.gov (United States)

    Klimczak, Dominika; Jazdzewski, Krystian; Kuch, Marek

    2017-02-01

    Multiple factors underlie the pathophysiology of hypertension, involving endothelial dysregulation, vascular smooth muscle dysfunction, increased oxidative stress, sympathetic nervous system activation and altered renin -angiotensin -aldosterone regulatory activity. A class of non-coding RNA called microRNA, consisting of 17-25 nucleotides, exert regulatory function over these processes. This paper summarizes the currently available data from preclinical and clinical studies on miRNA in the development of hypertension as well as the impact of anti-hypertensive treatment on their plasma expression. We present microRNAs' characteristics, their biogenesis and role in the regulation of blood pressure together with their potential diagnostic and therapeutic application in clinical practice.

  9. IMPAIRED REGULATORY MECHANISMS OF THE mTOR SIGNALING PATHWAY IN OSTEOARTHROSIS

    Directory of Open Access Journals (Sweden)

    Elena Vasilyevna Chetina

    2012-01-01

    Full Text Available Objective: to study the pattern of impaired regulatory mechanisms of the mammalian target of rapamycin (TOR signaling pathway, by monitoring gene expression in the blood of patients with osteoarthrosis (OA at different stages of the disease. Subjects and methods. The study covered 33 outpatients with OA, 14 patients with this condition prior to knee joint endoprosthesis, and 27 healthy individuals (controls (mean age 58.0+7.4, 56.5+8.9, and 55.0+8.3 years, respectively. Total RNA was isolated from their blood and used to determine the level of gene expression by a real-time polymerase chain reaction for AMP-activated protein kinase (AMPK, hypoxia-inducible factor-1α (HIF1α, the rate-limiting proteins of the hexosamine signaling pathway — glutamine-fructose-6-phosphate amidotransferase and acetylglucosaminyltransferase, as well as the glucose transporter GLUT1 and steps 6 and 7 glycolytic pathway components — glucose-6-phosphate dehydrogenase and phosphoglycerate kinase-1, respectively; the lipogenesis-related genes — fatty acid synthase (FAS and the activity of the pentose phosphate pathway — glucose-6-phosphate dehydrogenase in the blood of patients with OA at different stages of the disease. Results. Analysis of gene expressions showed that in the OA patients with a low expression of the mTOR gene (a LOW subgroup, the expression of AGT and GLUT1 genes proved to be significantly lower and that of the AMPK gene was higher than in the healthy individuals. In the OA patients with a high expression of the mTOR gene (a HIGH subgroup, the expression of all the genes under study was much higher, except for the FAS gene; moreover, the greatest expression excess as compared to the controls was observed for the AMPK and HIFlα genes. In the patients with endstage disease (an ES subgroup, the expression of all the study genes, including the FAS gene, turned out to be higher than in the healthy individuals. Conclusion. The development of OA is

  10. Regulatory Mechanisms of the Molecular Pathways in Fibrosis Induced by MicroRNAs

    Science.gov (United States)

    Yang, Cui; Zheng, Si-Dao; Wu, Hong-Jin; Chen, Shao-Jun

    2016-01-01

    Objective: MicroRNAs (miRNAs or miRs) play critical roles in the fibrotic process in different organs. We summarized the latest research progress on the roles and mechanisms of miRNAs in the regulation of the molecular signaling pathways involved in fibrosis. Data Sources: Papers published in English from January 2010 to August 2015 were selected from the PubMed and Web of Science databases using the search terms “microRNA”, “miR”, “transforming growth factor β”, “tgf β”, “mitogen-activated protein kinase”, “mapk”, “integrin”, “p38”, “c-Jun NH2-terminal kinase”, “jnk”, “extracellular signal-regulated kinase”, “erk”, and “fibrosis”. Study Selection: Articles were obtained and reviewed to analyze the regulatory effects of miRNAs on molecular signaling pathways involved in the fibrosis. Results: Recent evidence has shown that miRNAs are involved in regulating fibrosis by targeting different substrates in the molecular processes that drive fibrosis, such as immune cell sensitization, effector cell activation, and extracellular matrix remodeling. Moreover, several important molecular signaling pathways involve in fibrosis, such as the transforming growth factor-beta (TGF-β) pathway, mitogen-activated protein kinase (MAPK) pathways, and the integrin pathway are regulated by miRNAs. Third, regulation of the fibrotic pathways induced by miRNAs is found in many other tissues in addition to the heart, lung, liver, and kidney. Interestingly, the actions of many drugs on the human body are also induced by miRNAs. It is encouraging that the fibrotic process can be blocked or reversed by targeting specific miRNAs and their signaling pathways, thereby protecting the structures and functions of different organs. Conclusions: miRNAs not only regulate molecular signaling pathways in fibrosis but also serve as potential targets of novel therapeutic interventions for fibrosing diseases. PMID:27647197

  11. Regulatory framework and development perspectives of the mechanism of public participation in the management of Russia’s forests

    Directory of Open Access Journals (Sweden)

    Nikolay Mikhaylovich Shmatkov

    2014-03-01

    Full Text Available The article dwells on the current state of the regulatory framework of the Russian Federation and the mechanism of public participation in forest management. The examples of addressing the problems of public participation in forest management in individual regions are disclosed. The article deals with the issues concerning the provision of in-interests of the local population through the voluntary forest certification system under the FSC scheme. Recommendations on improving the mechanism of public participation in solving the forest management issues are suggested

  12. Generalized contexts and consistent histories in quantum mechanics

    Science.gov (United States)

    Losada, Marcelo; Laura, Roberto

    2014-05-01

    We analyze a restriction of the theory of consistent histories by imposing that a valid description of a physical system must include quantum histories which satisfy the consistency conditions for all states. We prove that these conditions are equivalent to imposing the compatibility conditions of our formalism of generalized contexts. Moreover, we show that the theory of consistent histories with the consistency conditions for all states and the formalism of generalized context are equally useful representing expressions which involve properties at different times.

  13. Generalized variational principles of three kinds of variables in general mechanic

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In this paper, by using the involutory transformations, the stationary conditions of two kinds of variables are transformed into basic equations of three kinds of variables. According to the corresponding relations between general forces and general displacements, the basic equations are multiplied by corresponding virtual quantities, added algebraically, and then integrated with time. Thus, the generalized variational principles of three kinds of variables in holonomic systems and nonholonomic systems are established. As an example, the generalized variational principles are applied to elastodynamics. Finally, some related problems are discussed.

  14. Generalized statistical mechanics approaches to earthquakes and tectonics.

    Science.gov (United States)

    Vallianatos, Filippos; Papadakis, Giorgos; Michas, Georgios

    2016-12-01

    Despite the extreme complexity that characterizes the mechanism of the earthquake generation process, simple empirical scaling relations apply to the collective properties of earthquakes and faults in a variety of tectonic environments and scales. The physical characterization of those properties and the scaling relations that describe them attract a wide scientific interest and are incorporated in the probabilistic forecasting of seismicity in local, regional and planetary scales. Considerable progress has been made in the analysis of the statistical mechanics of earthquakes, which, based on the principle of entropy, can provide a physical rationale to the macroscopic properties frequently observed. The scale-invariant properties, the (multi) fractal structures and the long-range interactions that have been found to characterize fault and earthquake populations have recently led to the consideration of non-extensive statistical mechanics (NESM) as a consistent statistical mechanics framework for the description of seismicity. The consistency between NESM and observations has been demonstrated in a series of publications on seismicity, faulting, rock physics and other fields of geosciences. The aim of this review is to present in a concise manner the fundamental macroscopic properties of earthquakes and faulting and how these can be derived by using the notions of statistical mechanics and NESM, providing further insights into earthquake physics and fault growth processes.

  15. General Review of Tinnitus Prevalence, Mechanisms, Effects, and Management

    Science.gov (United States)

    Henry, James A.; Dennis, Kyle C.; Schechter, Martin A.

    2005-01-01

    Tinnitus is an increasing health concern across all strata of the general population. Although an abundant amount of literature has addressed the many facets of tinnitus, wide-ranging differences in professional beliefs and attitudes persist concerning its clinical management. These differences are detrimental to tinnitus patients because the…

  16. Endocannabinoids are involved in male vertebrate reproduction: regulatory mechanisms at central and gonadal level

    Directory of Open Access Journals (Sweden)

    Patrizia eBovolin

    2014-04-01

    Full Text Available Endocannabinoids are natural lipids regulating a large array of physiological functions and behaviors in vertebrates. The endocannabinoid system is highly conserved in evolution and comprises several specific receptors (type-1 and type-2 cannabinoid receptors, their endogenous ligands (e.g. anandamide and 2-arachidonoylglycerol, and a number of biosynthetic and degradative enzymes. In the last few years, endocannabinoids have been described as critical signals in the control of male and female reproduction at multiple levels: centrally, by targeting hypothalamic Gonadotropin-Releasing-Hormone secreting neurons and pituitary, and locally, with direct effects on the gonads. These functions are supported by the extensive localization of cannabinoid receptors and endocannabinoid metabolic enzymes at different levels of the hypothalamic-pituitary-gonadal axis in mammals, as well as bonyfish and amphibians. In vivo and in vitro studies indicate that endocannabinoids centrally regulate gonadal functions by modulating the Gonadotropin Releasing Hormone-gonadotropin-steroid network through direct and indirect mechanisms. Several proofs of local endocannabinoid regulation have been found in the testis and male genital tracts, since endocannabinoids control Sertoli and Leydig cells activity, germ cell progression, as well as the acquisition of sperm functions. A comparative approach usually is a key step in the study of physiological events leading to the building of a general model. Thus, in this review we summarize the action of endocannabinoids at different levels of the male reproductive axis, with special emphasis, where appropriate, on data from non-mammalian vertebrates.

  17. Seasonality of reproduction in mammals: intimate regulatory mechanisms and practical implications.

    Science.gov (United States)

    Chemineau, P; Guillaume, D; Migaud, M; Thiéry, J C; Pellicer-Rubio, M T; Malpaux, B

    2008-07-01

    Farm mammals generally express seasonal variations in their production traits, thus inducing changing availability of fresh derived animal products (meat, milk and cheese) or performances (horses). This is due to a more or less marked seasonal birth distribution in sheep and goats, in horses but not cattle. Birth peak occurs at the end of winter-early spring, the most favourable period for the progeny to survive. Most species show seasonal variations in their ovulation frequency (presence or absence of ovulation), spermatogenic activity (from moderate decrease to complete absence of sperm production), gamete quality (variations in fertilization rates and embryo survival), and also sexual behaviour. The intimate mechanism involved is a complex combination of endogenous circannual rhythm driven and synchronized by light and melatonin. Profound and long-term neuroendocrine changes involving different neuromediator systems were described to play a role in these processes. In most species artificial photoperiodic treatments consisting of extra-light during natural short days (in sheep and goats and mares) or melatonin during long days (in sheep and goats) are extensively used to either adjust the breeding season to animal producer needs and/or to completely overcome seasonal variations of sperm production in artificial insemination centres. Pure light treatments (without melatonin), especially when applied in open barns, could be considered as non-invasive ones which fully respect animal welfare. Genetic selection could be one of the future ways to decrease seasonality in sheep and goats.

  18. The quantum mechanics based on a general kinetic energy

    CERN Document Server

    Wei, Yuchuan

    2016-01-01

    In this paper, we introduce the Schrodinger equation with a general kinetic energy operator. The conservation law is proved and the probability continuity equation is deducted in a general sense. Examples with a Hermitian kinetic energy operator include the standard Schrodinger equation, the relativistic Schrodinger equation, the fractional Schrodinger equation, the Dirac equation, and the deformed Schrodinger equation. We reveal that the Klein-Gordon equation has a hidden non-Hermitian kinetic energy operator. The probability continuity equation with sources indicates that there exists a different way of probability transportation, which is probability teleportation. An average formula is deducted from the relativistic Schrodinger equation, the Dirac equation, and the K-G equation.

  19. Generalized space and linear momentum operators in quantum mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Bruno G. da, E-mail: bruno.costa@ifsertao-pe.edu.br [Instituto Federal de Educação, Ciência e Tecnologia do Sertão Pernambucano, Campus Petrolina, BR 407, km 08, 56314-520 Petrolina, Pernambuco (Brazil); Instituto de Física, Universidade Federal da Bahia, R. Barão de Jeremoabo s/n, 40170-115 Salvador, Bahia (Brazil); Borges, Ernesto P., E-mail: ernesto@ufba.br [Instituto de Física, Universidade Federal da Bahia, R. Barão de Jeremoabo s/n, 40170-115 Salvador, Bahia (Brazil)

    2014-06-15

    We propose a modification of a recently introduced generalized translation operator, by including a q-exponential factor, which implies in the definition of a Hermitian deformed linear momentum operator p{sup ^}{sub q}, and its canonically conjugate deformed position operator x{sup ^}{sub q}. A canonical transformation leads the Hamiltonian of a position-dependent mass particle to another Hamiltonian of a particle with constant mass in a conservative force field of a deformed phase space. The equation of motion for the classical phase space may be expressed in terms of the generalized dual q-derivative. A position-dependent mass confined in an infinite square potential well is shown as an instance. Uncertainty and correspondence principles are analyzed.

  20. Presenting particle physics and quantum mechanics to the general public

    CERN Document Server

    Strauss, J

    2015-01-01

    The job of a physicist is to describe Nature. General features, hypotheses and theories help to describe physics phenomena at a more abstract, fundamental level, and are sometimes tacitly assigned some sort of real existence; doing so appears to be of little harm in most of classical physics. However, missing any tangible connection to everyday experience, one better always bears in mind the descriptive nature of any efforts to grasp the quantum. And elementary particles interact in the quantum world, of course. When communicating the world of elementary particles to the general public, the Bayesian approach of an ever ongoing updating of the depiction of reality turns out to be virtually indispensable. The human experience of providing a series of increasingly better descriptions generates plenty of personal pleasures, for researchers as well as for amateurs. A suggestive analogy for improving our understanding of the world, even the seemingly paradoxical quantum world, may be found in recent insight into ho...

  1. Activation of Vago by interferon regulatory factor (IRF) suggests an interferon system-like antiviral mechanism in shrimp.

    Science.gov (United States)

    Li, Chaozheng; Li, Haoyang; Chen, Yixiao; Chen, Yonggui; Wang, Sheng; Weng, Shao-Ping; Xu, Xiaopeng; He, Jianguo

    2015-10-13

    There is a debate on whether invertebrates possess an antiviral immunity similar to the interferon (IFN) system of vertebrates. The Vago gene from arthropods encodes a viral-activated secreted peptide that restricts virus infection through activating the JAK-STAT pathway and is considered to be a cytokine functionally similar to IFN. In this study, the first crustacean IFN regulatory factor (IRF)-like gene was identified in Pacific white shrimp, Litopenaeus vannamei. The L. vannamei IRF showed similar protein nature to mammalian IRFs and could be activated during virus infection. As a transcriptional regulatory factor, L. vannamei IRF could activate the IFN-stimulated response element (ISRE)-containing promoter to regulate the expression of mammalian type I IFNs and initiate an antiviral state in mammalian cells. More importantly, IRF could bind the 5'-untranslated region of L. vannamei Vago4 gene and activate its transcription, suggesting that shrimp Vago may be induced in a similar manner to that of IFNs and supporting the opinion that Vago might function as an IFN-like molecule in invertebrates. These suggested that shrimp might possess an IRF-Vago-JAK/STAT regulatory axis, which is similar to the IRF-IFN-JAK/STAT axis of vertebrates, indicating that invertebrates might possess an IFN system-like antiviral mechanism.

  2. Chiral Recognition Mechanisms in Enantiomers Separations: A General View

    Science.gov (United States)

    Berthod, Alain

    In 1858, Louis Pasteur, the first to accomplish the separation of two enantiomers wrote: “Most natural organic products, the essential products of life, are asymmetric and possess such asymmetry that they are not superimposable on their image. This establishes perhaps the only well-marked line of demarcation that can at present be drawn between the chemistry of dead matter and the chemistry of living matter.” Enantiomers have exactly the same properties in isotropic conditions. They behave differently only in anisotropic conditions. Chiral-chiral interactions are needed for enantiomeric separations. The fundamental mechanisms for chiral separations are listed along with the commercially available chiral selectors. Two chemometric examples are commented: one on quantitative structure enantioselectivity relationship and the second one on linear solvation energy relationships. It is shown that the solvents used in the mobile phase may play the most critical role in the chiral mechanism.

  3. General mechanism for helium blistering involving displaced atom transport

    Energy Technology Data Exchange (ETDEWEB)

    McDonell, W.R.

    1979-01-01

    A mechanism developed to account for formation of vertically elongated blisters in high displacement environments produced by /sup 252/Cf alpha particles and fission fragments has been extended to formation of done-shaped blisters in the low displacement environments produced by simple helium ion beams. In this mechanism, transport of displaced atoms to relieve compressive stresses in the helium-implanted layer allows interconnections of small, subsurface bubbles to form the blister cavity. The same transport may cause thickening of the blister caps at low implantation energies. The transition from dome-shaped to vertically elongated blistering occurs between the 300 and 3000 displacements per helium atom produced by simple helium ions and /sup 252/Cf radiations respectively.

  4. Mechanisms of diabetic autoimmunity: II--Is diabetes a central or peripheral disorder of effector and regulatory cells?

    Science.gov (United States)

    Askenasy, Nadir

    2016-02-01

    Two competing hypotheses aiming to explain the onset of autoimmune reactions are discussed in the context of genetic and environmental predisposition to type 1 diabetes (T1D). The first hypothesis has evolved along characterization of the mechanisms of self-discrimination and attributes diabetic autoimmunity to escape of reactive T cells from central regulation in the thymus. The second considers frequent occurrence of autoimmune reactions within the immune homunculus, which are adequately suppressed by regulatory T cells originating from the thymus, and occasionally, insufficient suppression results in autoimmunity. Besides thymic dysfunction, deregulation of both effector and suppressor cells can in fact result from homeostatic aberrations at the peripheral level during initial stages of evolution of adaptive immunity. Pathogenic cells sensitized in the islets are efficiently expanded in the target tissue and pancreatic lymph nodes of lymphopenic neonates. In parallel, the same mechanisms of peripheral sensitization contribute to tolerization through education of naïve/effector T cells and expansion of regulatory T cells. Experimental evidence presented for each individual mechanism implies that T1D may result from a primary effector or suppressor immune abnormality. Disturbed self-tolerance leading to T1D may well result from peripheral deregulation of innate and adaptive immunity, with variable contribution of central thymic dysfunction.

  5. Some scientific reflections on possible mechanisms of general anaesthesia.

    Science.gov (United States)

    Carmody, J J

    2009-03-01

    The challenge to achieve a gestalt understanding of general anaesthesia is really dependent upon an understanding of the elusive concept of consciousness. Until very recently, anaesthesia has been understood to depend fundamentally on the lipid solubility of anaesthetic agents, unsurprisingly a misleading view which has followed from the greater simplicity of lipid chemistry compared with protein chemistry and, it is contended here, from a serious misunderstanding of the older experimental data. Nonetheless, because an over-simplistic view of lipids pertains in much pharmacological thinking about anaesthesia, this paper devotes some attention to potentially relevant aspects of lipid function and also to concepts of anaesthesia which are based on the properties of intracellular and extracellular water. It is argued that the more correct pharmacological explanation is likely to be action at hydrophobic sites of crucial functional molecules, most plausibly protein molecules: empirical data which support such actions are presented and considered. Anaesthetic actions on a range of such proteins are discussed, with the emphasis on general neurophysiological principles, with the intent of avoiding the mire into which detailed consideration of actions at specific sites of putative function in the central nervous system can lead. Those experimentally-documented actions include influences on the proteins which constitute the Na(+)-ion conductance channels in axonal membranes (which are the basis for action potentials); on the Ca(2+)-ion channels which are crucial for neurotransmitter secretion from nerve terminals; on the properties of the ion channels in the post-synaptic membranes of the neurons which are the targets for transmitter action; on components of the "second messenger" systems of target neurons; as well as actions on metabolically significant enzymes (notably cytochrome P450). The overall argument is that the concept of anaesthetic actions on lipids should be

  6. A new type of adiabatic invariants for nonconservative systems of generalized classical mechanics

    Institute of Scientific and Technical Information of China (English)

    Zhang Yi

    2006-01-01

    The perturbations to symmetries and adiabatic invariants for nonconservative systems of generalized classical mechanics are studied. The exact invariant in the form of Hojman from a particular Lie symmetry for an undisturbed system of generalized mechanics is given. Based on the concept of high-order adiabatic invariant in generalized mechanics, the perturbation to Lie symmetry for the system under the action of small disturbance is investigated, and a new adiabatic invariant for the nonconservative system of generalized classical mechanics is obtained, which can be called the Hojman adiabatic invariant. An example is also given to illustrate the application of the results.

  7. Mosaic gene network modelling identified new regulatory mechanisms in HCV infection.

    Science.gov (United States)

    Popik, Olga V; Petrovskiy, Evgeny D; Mishchenko, Elena L; Lavrik, Inna N; Ivanisenko, Vladimir A

    2016-06-15

    Modelling of gene networks is widely used in systems biology to study the functioning of complex biological systems. Most of the existing mathematical modelling techniques are useful for analysis of well-studied biological processes, for which information on rates of reactions is available. However, complex biological processes such as those determining the phenotypic traits of organisms or pathological disease processes, including pathogen-host interactions, involve complicated cross-talk between interacting networks. Furthermore, the intrinsic details of the interactions between these networks are often missing. In this study, we developed an approach, which we call mosaic network modelling, that allows the combination of independent mathematical models of gene regulatory networks and, thereby, description of complex biological systems. The advantage of this approach is that it allows us to generate the integrated model despite the fact that information on molecular interactions between parts of the model (so-called mosaic fragments) might be missing. To generate a mosaic mathematical model, we used control theory and mathematical models, written in the form of a system of ordinary differential equations (ODEs). In the present study, we investigated the efficiency of this method in modelling the dynamics of more than 10,000 simulated mosaic regulatory networks consisting of two pieces. Analysis revealed that this approach was highly efficient, as the mean deviation of the dynamics of mosaic network elements from the behaviour of the initial parts of the model was less than 10%. It turned out that for construction of the control functional, data on perturbation of one or two vertices of the mosaic piece are sufficient. Further, we used the developed method to construct a mosaic gene regulatory network including hepatitis C virus (HCV) as the first piece and the tumour necrosis factor (TNF)-induced apoptosis and NF-κB induction pathways as the second piece. Thus

  8. General frost growth mechanism on solid substrates with different stiffness.

    Science.gov (United States)

    Petit, Julien; Bonaccurso, Elmar

    2014-02-01

    Preventing or delaying frost formation on surfaces is of significant importance in many aspects of our daily life. Despite many efforts and improvements recently achieved in the design of new icephobic materials and substrates, not all proposed solutions are universally applicable and frost formation still remains a problem in need of further flexible solutions. In this respect, we propose to take benefit from the tunable viscoelastic properties of soft polymer gel substrates, since they are known to strongly influence the dropwise condensation process of water, and to investigate condensation frosting on them. Using polymer gels with different stiffness and a hard substrate as a reference, we demonstrate their ability to delay frost formation compared to recent results reported in the literature on other solid substrates and in particular on superhydrophobic surfaces. By investigating the frost front propagation we singled out a general behavior of its dynamic evolution consisting of two processes presenting two different time scales. This general growth appears to be independent of experimental conditions as well as substrate stiffness.

  9. General coarse-grained red blood cell models: I. Mechanics

    OpenAIRE

    FEDOSOV, DMITRY A.; Caswell, Bruce; Karniadakis, George E.

    2009-01-01

    We present a rigorous procedure to derive coarse-grained red blood cell (RBC) models, which lead to accurate mechanical properties of realistic RBCs. Based on a semi-analytic theory linear and non-linear elastic properties of the RBC membrane can be matched with those obtained in optical tweezers stretching experiments. In addition, we develop a nearly stress-free model which avoids a number of pitfalls of existing RBC models, such as non-biconcave equilibrium shape and dependence of RBC mech...

  10. Study of General health, resiliency, and defense mechanisms in patients with migraine headache

    Directory of Open Access Journals (Sweden)

    Alireza Aghayusefi

    2013-06-01

    Full Text Available Background: Migraine is a neurological disease that the etiology, several factors affect its onset or its exacerbation. One of the factors affecting disease is psychological factors such as defense mechanisms, resiliency, and general health. This study assessed the relationship between general health, resiliency, and general defense mechanisms, and also predicts the general health of people with migraine headaches that have a high resiliency and use mature defense mechanisms. Material and Methods: 50 women with migraine headache in the city of Bushehr using defense mechanisms, resiliency, and general health questionnaires were studied. For statistical analysis, Pearson correlation and multiple regression tests were used by SPSS 17 software. Results: The results showed that most of the defense mechanisms of migraine sufferers are Immature and Neuroticism. There is significant negative correlation between the deterioration of general health and resiliency as well as the mature defense mechanism (p=0/003, and also there is a significant positive correlation between this deterioration with neuroticism (p=0/040 and immature defense mechanisms (p=0/041. On the other hand there is significant negative correlation between resiliencies with immature (p=0/009 and neuroticism defense mechanisms (p=0/04, and also with mature defense mechanism has a significant positive correlation (p=0/003. Also, as more people use the mature defense mechanism, their deterioration of general health will be reduced, but this relationship will be stronger with the presence of resiliency. So migraine people use the mature defense mechanisms with high resiliency will have more favorable general health (less deterioration of general health. Conclusion: This study showed that migraine patients use the mature defense mechanisms with high resiliency will have more favorable general health (less deterioration of general health.

  11. Brain-derived neurotrophic factor enhances calcium regulatory mechanisms in human airway smooth muscle.

    Directory of Open Access Journals (Sweden)

    Amard J Abcejo

    Full Text Available Neurotrophins (NTs, which play an integral role in neuronal development and function, have been found in non-neuronal tissue (including lung, but their role is still under investigation. Recent reports show that NTs such as brain-derived neurotrophic factor (BDNF as well as NT receptors are expressed in human airway smooth muscle (ASM. However, their function is still under investigation. We hypothesized that NTs regulate ASM intracellular Ca(2+ ([Ca(2+](i by altered expression of Ca(2+ regulatory proteins. Human ASM cells isolated from lung samples incidental to patient surgery were incubated for 24 h (overnight in medium (control or 1 nM BDNF in the presence vs. absence of inhibitors of signaling cascades (MAP kinases; PI3/Akt; NFκB. Measurement of [Ca(2+](i responses to acetylcholine (ACh and histamine using the Ca(2+ indicator fluo-4 showed significantly greater responses following BDNF exposure: effects that were blunted by pathway inhibitors. Western analysis of whole cell lysates showed significantly higher expression of CD38, Orai1, STIM1, IP(3 and RyR receptors, and SERCA following BDNF exposure, effects inhibited by inhibitors of the above cascades. The functional significance of BDNF effects were verified by siRNA or pharmacological inhibition of proteins that were altered by this NT. Overall, these data demonstrate that NTs activate signaling pathways in human ASM that lead to enhanced [Ca(2+](i responses via increased regulatory protein expression, thus enhancing airway contractility.

  12. General review of tinnitus: prevalence, mechanisms, effects, and management.

    Science.gov (United States)

    Henry, James A; Dennis, Kyle C; Schechter, Martin A

    2005-10-01

    Tinnitus is an increasing health concern across all strata of the general population. Although an abundant amount of literature has addressed the many facets of tinnitus, wide-ranging differences in professional beliefs and attitudes persist concerning its clinical management. These differences are detrimental to tinnitus patients because the management they receive is based primarily on individual opinion (which can be biased) rather than on medical consensus. It is thus vitally important for the tinnitus professional community to work together to achieve consensus. To that end, this article provides a broad-based review of what is presently known about tinnitus, including prevalence, associated factors, theories of pathophysiology, psychological effects, effects on disability and handicap, workers' compensation issues, clinical assessment, and various forms of treatment. This summary of fundamental information has relevance to both clinical and research arenas.

  13. General Relativistic Effects in the Core Collapse Supernova Mechanism

    CERN Document Server

    Bruenn, S W; Mezzacappa, A

    2001-01-01

    We apply our recently developed code for spherically symmetric, fully general relativistic (GR) Lagrangian hydrodynamics and multigroup flux-limited diffusion neutrino transport to examine the effects of GR on the hydrodynamics and transport during collapse, bounce, and the critical shock reheating phase of core collapse supernovae. Comparisons of models computed with GR versus Newtonian hydrodynamics show that collapse to bounce takes slightly less time in the GR limit, and that the shock propagates slightly farther out in radius before receding. After a secondary quasistatic rise in the shock radius, the shock radius declines considerably more rapidly in the GR simulations than in the corresponding Newtonian simulations. During the shock reheating phase, core collapse computed with GR hydrodynamics results in a substantially more compact structure from the center out to the stagnated shock. The inflow speed of material behind the shock is also increased. Comparisons also show that the luminosity and rms ene...

  14. General principles in the interpretation of quantum mechanics

    CERN Document Server

    Blood, Casey

    2009-01-01

    The three major theoretical principles of quantum mechanics relevant to its interpretation are: (T1), linearity; (T2), invariance under certain groups; and (T3) the orthogonality and isolation of the different branches of the state vector. These three imply the particle-like properties of mass, energy, momentum, spin, charge, and locality are actually properties of the state vector; and this in turn implies there is no evidence for the existence of particles. Experimentally there is no evidence for collapse (E1) and theoretically linearity prohibits collapse. One also has the experimentally verified probability law (E2), which is found to rule out the many-worlds interpretation. The failure of these three major interpretation, particles, collapse, and many-worlds, apparently implies an acceptable interpretation must be based on perception. Rather than being a separate principle, probability follows in this interpretation from a weak assumption on perception plus the combinatorics when an experiment is run man...

  15. Comparative analysis of mutant plants impaired in the main regulatory mechanisms of photosynthetic light reactions - From biophysical measurements to molecular mechanisms.

    Science.gov (United States)

    Tikkanen, Mikko; Rantala, Sanna; Grieco, Michele; Aro, Eva-Mari

    2017-03-01

    Chlorophyll (chl) fluorescence emission by photosystem II (PSII) and light absorption by P700 reaction center chl a of photosystem I (PSI) provide easy means to probe the function of the photosynthetic machinery. The exact relationship between the measured optical variables and the molecular processes have, however, remained elusive. Today, the availability of mutants with distinct molecular characterization of photosynthesis regulatory processes should make it possible to gain further insights into this relationship, yet a systematic comparative analysis of such regulatory mutants has been missing. Here we have systematically compared the behavior of Dual-PAM fluorescence and P700 variables from well-characterized photosynthesis regulation mutants. The analysis revealed a very convincing relationship between the given molecular deficiency in the photosynthetic apparatus and the original fluorescence and P700 signals obtained by using varying intensities of actinic light and by applying a saturating pulse. Importantly, the specific information on the underlying molecular mechanism, present in these authentic signals of a given photosynthesis mutant, was largely nullified when using the commonly accepted parameters that are based on further treatment of the original signals. Understanding the unique relationship between the investigated molecular process of photosynthesis and the measured variable is an absolute prerequisite for comprehensive interpretation of fluorescence and P700 measurements. The data presented here elucidates the relationships between the main regulatory mechanisms controlling the photosynthetic light reactions and the variables obtained by fluorescence and P700 measurements. It is discussed how the full potential of optical photosynthesis measurements can be utilized in investigation of a given molecular mechanism. Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  16. Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress

    KAUST Repository

    Yun, Kil-Young

    2010-01-25

    Background: The transcriptional regulatory network involved in low temperature response leading to acclimation has been established in Arabidopsis. In japonica rice, which can only withstand transient exposure to milder cold stress (10C), an oxidative-mediated network has been proposed to play a key role in configuring early responses and short-term defenses. The components, hierarchical organization and physiological consequences of this network were further dissected by a systems-level approach.Results: Regulatory clusters responding directly to oxidative signals were prominent during the initial 6 to 12 hours at 10C. Early events mirrored a typical oxidative response based on striking similarities of the transcriptome to disease, elicitor and wounding induced processes. Targets of oxidative-mediated mechanisms are likely regulated by several classes of bZIP factors acting on as1/ocs/TGA-like element enriched clusters, ERF factors acting on GCC-box/JAre-like element enriched clusters and R2R3-MYB factors acting on MYB2-like element enriched clusters.Temporal induction of several H2O2-induced bZIP, ERF and MYB genes coincided with the transient H2O2spikes within the initial 6 to 12 hours. Oxidative-independent responses involve DREB/CBF, RAP2 and RAV1 factors acting on DRE/CRT/rav1-like enriched clusters and bZIP factors acting on ABRE-like enriched clusters. Oxidative-mediated clusters were activated earlier than ABA-mediated clusters.Conclusion: Genome-wide, physiological and whole-plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress and developmental responses leads to modulated growth and vigor maintenance contributing to a delay of plastic injuries. 2010 Yun et al; licensee BioMed Central Ltd.

  17. A meta-analysis of caloric restriction gene expression profiles to infer common signatures and regulatory mechanisms.

    Science.gov (United States)

    Plank, Michael; Wuttke, Daniel; van Dam, Sipko; Clarke, Susan A; de Magalhães, João Pedro

    2012-04-01

    Caloric restriction, a reduction in calorie intake without malnutrition, retards age-related degeneration and extends lifespan in several organisms. CR induces multiple changes, yet its underlying mechanisms remain poorly understood. In this work, we first performed a meta-analysis of microarray CR studies in mammals and identified genes and processes robustly altered due to CR. Our results reveal a complex array of CR-induced changes and we re-identified several genes and processes previously associated with CR, such as growth hormone signalling, lipid metabolism and immune response. Moreover, our results highlight novel associations with CR, such as retinol metabolism and copper ion detoxification, as well as hint of a strong effect of CR on circadian rhythms that in turn may contribute to metabolic changes. Analyses of our signatures by integrating co-expression data, information on genetic mutants, and transcription factor binding site analysis revealed candidate regulators of transcriptional modules in CR. Our results hint at a transcriptional module involved in sterol metabolism regulated by Srebf1. A putative regulatory role of Ppara was also identified. Overall, our conserved molecular signatures of CR provide a comprehensive picture of CR-induced changes and help understand its regulatory mechanisms.

  18. Horizon Quantum Mechanics of Generalized Uncertainty Principle Black Holes

    CERN Document Server

    Manfredi, Luciano

    2016-01-01

    We study the Horizon Wavefunction (HWF) description of a generalized uncertainty principle inspired metric that admits sub-Planckian black holes, where the black hole mass $m$ is replaced by $M = m\\left( 1 + \\frac{\\beta}{2} \\frac{M_{\\rm Pl}^2}{m^2} \\right)$. Considering the case of a wave-packet shaped by a Gaussian distribution, we compute the HWF and the probability ${\\cal {P}}_{BH}$ that the source is a (quantum) black hole, i.e., that it lies within its horizon radius. The case $\\beta0$, where a minimum in ${\\cal {P}}_{BH}$ is encountered, thus meaning that every particle has some probability of decaying to a black hole. Furthermore, for sufficiently large $\\beta$ we find that every particle is a quantum black hole, in agreement with the intuitive effect of increasing $\\beta$, which creates larger $M$ and $R_{H}$ terms. This is likely due to a "dimensional reduction" feature of the model, where the black hole characteristics for sub-Planckian black holes mimic those in $(1+1)$-dimensions and the horizon s...

  19. A general theory of mechanical instabilities in soft solids

    Science.gov (United States)

    Hohlfeld, Evan; Mahadevan, L.

    2011-03-01

    Some instabilities in soft solids, e.g. buckling and wrinkling, can be detected in linearized analysis. Surprisingly, linearly stable configurations can still have nonlinear instabilities with strictly zero energy barrier. Two examples are cavitation (formation of voids) and sulcification (formation of sharply creased free surface folds), wherein singularities nucleate and grow when a critical strain is achieved. Here we present the first general theory of stability in nonlinearly elastic materials. The theory predicts when singularities spontaneously form, irrespective of linearized analysis, and how these can be controlled with geometry. Such ``hidden'' instabilities arise from the scale-free geometric and constitutive nonlinearities common in soft materials, and can be understood as scale symmetry breaking processes in simple cases. More deeply, even buckling and wrinkling can be traced back to scale-free linear instabilities (loss of ellipticity at an interface) as was first explained by M. A. Biot. We illustrate the theory with simulations and experiments on sulcification. Time allowing we will also discuss fracture and delamination.

  20. Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity.

    Science.gov (United States)

    Xu, Xiang; Zhao, Jingyue; Xu, Zhen; Peng, Baozhen; Huang, Qiuhua; Arnold, Eddy; Ding, Jianping

    2004-08-06

    Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, and regulation of the enzymatic activity of IDHs is crucial for their biological functions. Bacterial IDHs are reversibly regulated by phosphorylation of a strictly conserved serine residue at the active site. Eukaryotic NADP-dependent IDHs (NADP-IDHs) have been shown to have diverse important biological functions; however, their regulatory mechanism remains unclear. Structural studies of human cytosolic NADP-IDH (HcIDH) in complex with NADP and in complex with NADP, isocitrate, and Ca2+ reveal three biologically relevant conformational states of the enzyme that differ substantially in the structure of the active site and in the overall structure. A structural segment at the active site that forms a conserved alpha-helix in all known NADP-IDH structures assumes a loop conformation in the open, inactive form of HcIDH; a partially unraveled alpha-helix in the semi-open, intermediate form; and an alpha-helix in the closed, active form. The side chain of Asp279 of this segment occupies the isocitrate-binding site and forms hydrogen bonds with Ser94 (the equivalent of the phosphorylation site in bacterial IDHs) in the inactive form and chelates the metal ion in the active form. The structural data led us to propose a novel self-regulatory mechanism for HcIDH that mimics the phosphorylation mechanism used by the bacterial homologs, consistent with biochemical and biological data. This mechanism might be applicable to other eukaryotic NADP-IDHs. The results also provide insights into the recognition and specificity of substrate and cofactor by eukaryotic NADP-IDHs.

  1. Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs.

    Directory of Open Access Journals (Sweden)

    Huizheng Wang

    Full Text Available BACKGROUND: Polyhydroxyalkanoates (PHAs have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC, which belongs to (R-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic. METHODOLOGY/PRINCIPAL FINDINGS: We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC. CONCLUSIONS/SIGNIFICANCE: The data in our study reveal the regulatory mechanism of an (R-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  2. Discovery of Novel Splice Variants and Regulatory Mechanisms for Microsomal Triglyceride Transfer Protein in Human Tissues

    Science.gov (United States)

    Suzuki, Takashi; Swift, Larry L.

    2016-01-01

    Microsomal triglyceride transfer protein (MTP) is a unique lipid transfer protein essential for the assembly of triglyceride-rich lipoproteins by the liver and intestine. Previous studies in mice identified a splice variant of MTP with an alternate first exon. Splice variants of human MTP have not been reported. Using PCR approaches we have identified two splice variants in human tissues, which we have named MTP-B and MTP-C. MTP-B has a unique first exon (Ex1B) located 10.5 kb upstream of the first exon (Ex1A) for canonical MTP (MTP-A); MTP-C contains both first exons for MTP-A and MTP-B. MTP-B was found in a number of tissues, whereas MTP-C was prominent in brain and testis. MTP-B does not encode a protein; MTP-C encodes the same protein encoded by MTP-A, although MTP-C translation is strongly inhibited by regulatory elements within its 5′-UTR. Using luciferase assays, we demonstrate that the promoter region upstream of exon 1B is quite adequate to drive expression of MTP. We conclude that alternate splicing plays a key role in regulating cellular MTP levels by introducing distinct promoter regions and unique 5′-UTRs, which contain elements that alter translation efficiency, enabling the cell to optimize MTP activity. PMID:27256115

  3. Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer.

    Science.gov (United States)

    Roche, T E; Hiromasa, Y

    2007-04-01

    The fraction of pyruvate dehydrogenase complex (PDC) in the active form is reduced by the activities of dedicated PD kinase isozymes (PDK1, PDK2, PDK3 and PDK4). Via binding to the inner lipoyl domain (L2) of the dihydrolipoyl acetyltransferase (E2 60mer), PDK rapidly access their E2-bound PD substrate. The E2-enhanced activity of the widely distributed PDK2 is limited by dissociation of ADP from its C-terminal catalytic domain, and this is further slowed by pyruvate binding to the N-terminal regulatory (R) domain. Via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation. Activation of PDC by synthetic PDK inhibitors binding at the pyruvate or lipoyl binding sites decreased damage during heart ischemia and lowered blood glucose in insulin-resistant animals. PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate.

  4. 论食品安全奖励机制%Regulatory Mechanism for Food Safety

    Institute of Scientific and Technical Information of China (English)

    施吉龙

    2014-01-01

    In recent years, food safety issues have become increasingly prominent. Despite repeated adjustments of government regulators and its functions, it is still unable to curb the frequent occurrence of food safety incidents. Considering its reason, we will find that we are too over-reliancing on government power, and do not take advantage of market regulation and the role of social cohabitation. In order to alleviate or even to a certain extent to solve the current food security dilemma , we attempts to construct food safety incentives, and improve food safety regulatory system.%近年来,食品安全问题日渐突出。政府监管机构和职能虽经多次调整,但仍无法遏制食品安全事故的频繁发生。究其原因,在于过分依赖政府权力,而没有有效利用市场监管和社会共治的效用。本文试图通过建构食品安全奖励机制,完善食品安全监管制度以缓解甚至一定程度上解决当前食品安全困境。

  5. A Generalized Nonlocal Calculus with Application to the Peridynamics Model for Solid Mechanics

    OpenAIRE

    Alali, Bacim; Liu, Kuo; Gunzburger, Max

    2014-01-01

    A nonlocal vector calculus was introduced in [2] that has proved useful for the analysis of the peridynamics model of nonlocal mechanics and nonlocal diffusion models. A generalization is developed that provides a more general setting for the nonlocal vector calculus that is independent of particular nonlocal models. It is shown that general nonlocal calculus operators are integral operators with specific integral kernels. General nonlocal calculus properties are developed, including nonlocal...

  6. Elements of nonlinear quantum mechanics (Part II): Triple bracket generalization of quantum mechanics

    OpenAIRE

    Czachor, Marek

    1994-01-01

    A new version of NLQM is formulated in terms of the generalized Nambu dynamics. The generalization is free from the difficulties of earlier approaches. The paper is a second part of "Elements of NLQM (I): NL Schrodinger equation and two-level atoms".

  7. Regulatory mechanisms differ in UMP kinases from gram-negative and gram-positive bacteria.

    Science.gov (United States)

    Evrin, Cécile; Straut, Monica; Slavova-Azmanova, Neli; Bucurenci, Nadia; Onu, Adrian; Assairi, Liliane; Ionescu, Mihaela; Palibroda, Nicolae; Bârzu, Octavian; Gilles, Anne-Marie

    2007-03-09

    In this work, we examined the regulation by GTP and UTP of the UMP kinases from eight bacterial species. The enzyme from Gram-positive organisms exhibited cooperative kinetics with ATP as substrate. GTP decreased this cooperativity and increased the affinity for ATP. UTP had the opposite effect, as it decreased the enzyme affinity for ATP. The nucleotide analogs 5-bromo-UTP and 5-iodo-UTP were 5-10 times stronger inhibitors than the parent compound. On the other hand, UMP kinases from the Gram-negative organisms did not show cooperativity in substrate binding and catalysis. Activation by GTP resulted mainly from the reversal of inhibition caused by excess UMP, and inhibition by UTP was accompanied by a strong increase in the apparent K(m) for UMP. Altogether, these results indicate that, depending on the bacteria considered, GTP and UTP interact with different enzyme recognition sites. In Gram-positive bacteria, GTP and UTP bind to a single site or largely overlapping sites, shifting the T R equilibrium to either the R or T form, a scenario corresponding to almost all regulatory proteins, commonly called K systems. In Gram-negative organisms, the GTP-binding site corresponds to the unique allosteric site of the Gram-positive bacteria. In contrast, UTP interacts cooperatively with a site that overlaps the catalytic center, i.e. the UMP-binding site and part of the ATP-binding site. These characteristics make UTP an original regulator of UMP kinases from Gram-negative organisms, beyond the common scheme of allosteric control.

  8. Effect of radiologic contrast media on cell volume regulatory mechanisms in human red blood cells.

    Science.gov (United States)

    Galtung, Hilde Kanli; Sørlundsengen, Vibeke; Sakariassen, Kjell S; Benestad, Haakon B

    2002-08-01

    The authors performed this study to evaluate cell volume regulation in human red blood cells (RBCs) after incubation in solutions of three contrast media: iohexol (830 mOsm), ioxaglate (520 mOsm), and iodixanol (300 mOsm). Whole blood sampled from six healthy subjects was exposed to Ringer solutions containing 25% or 5% vol/vol iohexol (final osmolality, 440 or 340 mOsm, respectively), ioxaglate (final osmolality, 395 or 335 mOsm, respectively), iodixanol (final osmolality, 330 or 315 mOsm, respectively), or NaCl (control solutions with the same osmolality as that of the contrast media). In some experiments, control RBCs were subjected to a hyposmotic solution (100 mOsm). RBC volumes were obtained with a Coulter counter. The RBCs showed normal regulatory cell shrinkage after hyposmotically induced swelling. All 25% vol/vol contrast material solutions and their control solutions induced RBC shrinkage (range, 6% +/- 1 [standard error] to 22% +/- 3). The same was true for cells exposed to 5% vol/vol contrast material (range, 4% +/- 1 to 7% +/- 1). The shrinkage phase was followed by cell swelling (10% +/- 2 to 20% +/- 2 for 25% contrast material and their control solutions and 8% +/- 1 to 15% +/- 2 for 5% contrast material and their control solutions). No contrast material-exposed RBCs increased their volumes to the level reached with their control solutions. RBCs exposed to hyperosmotic iohexol, ioxaglate, or iodixanol solutions shrank and then swelled. The degree of shrinkage and subsequent swelling could not be explained simply with the osmolality of the test solutions. Physicochemical properties of the contrast media must be involved, putatively affecting electrolyte fluxes over the RBC membrane. Possible targets of these effects are the K+/Cl- symporter, K+ channels, and the Na+/K+/Cl- symporter.

  9. Unraveling the regulatory mechanisms underlying tissue-dependent genetic variation of gene expression

    NARCIS (Netherlands)

    Fu, Jingyuan; Wolfs, Marcel G M; Deelen, Patrick; Westra, Harm Jan; Fehrmann, Rudolf S N; te Meerman, Gerhardus; Buurman, Wim A; Rensen, Sander S M; Groen, Hendricus; Weersma, Rinse K; van den Berg, Leonard H; Veldink, Jan; Ophoff, Roel A; Snieder, Harold; van Heel, David; Jansen, Ritsert C; Hofker, Marten H; Wijmenga, Cisca; Franke, Lude

    2012-01-01

    It is known that genetic variants can affect gene expression, but it is not yet completely clear through what mechanisms genetic variation mediate this expression. We therefore compared the cis-effect of single nucleotide polymorphisms (SNPs) on gene expression between blood samples from 1,240 human

  10. [Regulatory role of mechanical stress response in cellular function: development of new drugs and tissue engineering].

    Science.gov (United States)

    Momose, Kazutaka; Matsuda, Takehisa; Oike, Masahiro; Obara, Kazuo; Laher, Ismail; Sugiura, Seiryo; Ohata, Hisayuki; Nakayama, Koichi

    2003-02-01

    The investigation of mechanotransduction in the cardiovascular system is essentially important for elucidating the cellular and molecular mechanisms involved in not only the maintenance of hemodynamic homeostasis but also etiology of cardiovascular diseases including arteriosclerosis. The present review summarizes the latest research performed by six academic groups, and presented at the 75th Annual Meeting of the Japanese Pharmacological Society. Technology of cellular biomechanics is also required for research and clinical application of a vascular hybrid tissue responding to pulsatile stress. 1) Vascular tissue engineering: Design of pulsatile stress-responsive scaffold and in vivo vascular wall reconstruction (T. Matsuda); 2) Cellular mechanisms of mechanosensitive calcium transients in vascular endothelium (M. Oike et al.); 3) Cross-talk of stimulation with fluid flow and lysophosphatidic acid in vascular endothelial cells (K. Momose et al.); 4) Mechanotransduction of vascular smooth muscles: Rate-dependent stretch-induced protein phosphorylations and contractile activation (K. Obara et al.); 5) Lipid mediators in vascular myogenic tone (I. Laher et al.); and 6) Caldiomyocyte regulates its mechanical output in response to mechanical load (S. Sugiura et al.).

  11. c-myc in whitefish (Coregonus lavaretus): structure, expression, and insights into possible posttranscriptional regulatory mechanism.

    Science.gov (United States)

    Brzuzan, P; Kramer, C; Łakomiak, A; Jakimiuk, E; Florczyk, M; Woźny, M

    2015-10-01

    c-myc has a crucial function in growth control, differentiation, and apoptosis of vertebrate cells. Despite the important role of c-myc in mediating the biological effects, studies of c-myc gene expression and factors that control it in organisms other than mammals, such as fish, have been rare. In the current study, we asked whether c-myc mRNA of whitefish, a feasible organism for pollution monitoring in aquatic systems and a model in toxicological research, contains activity sites for regulatory motifs in its 5'- and 3'-UTRs, similar to those found in mammals. We were particularly interested in whether miRNA-34, a known negative regulator of c-myc's in mammals, is able to regulate c-myc in fish. To answer these questions, we determined the mRNA sequence of whitefish c-myc and inferred the structure of the protein that it codes for. We found that the active sites of mRNA and structures of the inferred c-myc protein are similar to those found in mammals and other fish. Remarkably, levels of c-myc mRNA expression were very high in ovaries compared to other tissues of whitefish, thus corroborating previous data in fish. Using bioinformatic searches on c-myc 3'-UTR, we confirmed the presence of two miRNA-34a (miR-34a) response elements. Luciferase reporter assay showed that activity of reporters containing either the miR response elements or entire c-myc 3'-UTR was significantly reduced (p c-myc gene silencing by profiling the expression of both genes in livers of whitefish treated for 8, 24, 48 h with MC-LR, a potent c-myc inducer in mammals. Although the difference was only significant at p = 0.08, the expression of c-myc mRNA in challenged whitefish after 24 h of the treatment was notably higher than that in livers of control fish. Concurrently, we noticed slight but significant up-regulation of miR-34a after 24 and 48 h of the challenge (p c-myc mRNA levels and miR-34a expression. Together, these results suggest that miR-34a might regulate c-myc gene

  12. Boosters of a therapeutic HIV-1 vaccine induce divergent T cell responses related to regulatory mechanisms.

    Science.gov (United States)

    Lind, Andreas; Brekke, Kristin; Sommerfelt, Maja; Holmberg, Jens O; Aass, Hans Christian D; Baksaas, Ingebjørg; Sørensen, Birger; Dyrhol-Riise, Anne Ma; Kvale, Dag

    2013-09-23

    Therapeutic human immunodeficiency virus (HIV) vaccines aim to reduce disease progression by inducing HIV-specific T cells. Vacc-4x are peptides derived from conserved domains within HIV-1 p24 Gag. Previously, Vacc-4x induced T cell responses in 90% of patients which were associated with reduced viral loads. Here we evaluate the effects of Vacc-4x boosters on T cell immunity and immune regulation seven years after primary immunization. Twenty-five patients on effective antiretroviral therapy received two Vacc-4x doses four weeks apart and were followed for 16 weeks. Vacc-4x T cell responses were measured by proliferation (CFSE), INF-γ, CD107a, Granzyme B, Delayed-Type Hypersensitivity test (DTH) and cytokines and chemokines (Luminex). Functional regulation of Vacc-4x-specific T cell proliferation was estimated in vitro using anti-IL-10 and anti-TGF-ß monoclonal antibodies. Vacc-4x-specific CD8(+) T cell proliferation increased in 80% after either the first (64%) or second (16%) booster. Only 40% remained responders after two boosters with permanently increased Vacc-4x-specific proliferative responses (p=0.005) and improved CD8(+) T cell degranulation, IFN-γ production and DTH. At baseline, responders had higher CD8(+) T cell degranulation (p=0.05) and CD4(+) INF-γ production (p=0.01), whereas non-responders had higher production of proinflammatory TNF-α, IL-1α and IL-1ß (p<0.045) and regulatory IL-10 (p=0.07). Notably, IL-10 and TGF-ß mediated downregulation of Vacc-4x-specific CD8(+) T cell proliferation increased only in non-responders (p<0.001). Downregulation during the study correlated to higher PD-1 expression on Vacc-4x-specific CD8(+) T cells (r=0.44, p=0.037), but was inversely correlated to changes in Vacc4x-specific CD8(+) T cell proliferation (r=-0.52, p=0.012). These findings show that Vacc-4x boosters can improve T cell responses in selected patients, but also induce vaccine-specific downregulation of T cell responses in others. Broad

  13. Transport mechanism and regulatory properties of the human amino acid transporter ASCT2 (SLC1A5).

    Science.gov (United States)

    Scalise, Mariafrancesca; Pochini, Lorena; Panni, Simona; Pingitore, Piero; Hedfalk, Kristina; Indiveri, Cesare

    2014-11-01

    The kinetic mechanism of the transport catalyzed by the human glutamine/neutral amino acid transporter hASCT2 over-expressed in P. pastoris was determined in proteoliposomes by pseudo-bi-substrate kinetic analysis of the Na(+)-glutamineex/glutaminein transport reaction. A random simultaneous mechanism resulted from the experimental analysis. Purified functional hASCT2 was chemically cross-linked to a stable dimeric form. The oligomeric structure correlated well with the kinetic mechanism of transport. Half-saturation constants (Km) of the transporter for the other substrates Ala, Ser, Asn and Thr were measured both on the external and internal side. External Km were much lower than the internal ones confirming the asymmetry of the transporter. The electric nature of the transport reaction was determined imposing a negative inside membrane potential generated by K(+) gradients in the presence of valinomycin. The transport reaction resulted to be electrogenic and the electrogenicity originated from external Na(+). Internal Na(+) exerted a stimulatory effect on the transport activity which could be explained by a regulatory, not a counter-transport, effect. Native and deglycosylated hASCT2 extracted from HeLa showed the same transport features demonstrating that the glycosyl moiety has no role in transport function. Both in vitro and in vivo interactions of hASCT2 with the scaffold protein PDZK1 were revealed.

  14. Mechanisms of autoimmunity in the non-obese diabetic mouse: effector/regulatory cell equilibrium during peak inflammation.

    Science.gov (United States)

    Askenasy, Nadir

    2016-04-01

    Immune imbalance in autoimmune disorders such as type 1 diabetes may originate from aberrant activities of effector cells or dysfunction of suppressor cells. All possible defective mechanisms have been proposed for diabetes-prone species: (i) quantitative dominance of diabetogenic cells and decreased numbers of regulatory T cells, (ii) excessive aggression of effectors and defective function of suppressors, (iii) perturbed interaction between effector and suppressor cells, and (iv) variations in sensitivity to negative regulation. The experimental evidence available to date presents conflicting information on these mechanisms, with identification of perturbed equilibrium on the one hand and negation of critical role of each mechanism in propagation of diabetic autoimmunity on the other hand. In our analysis, there is no evidence that inherent abnormalities in numbers and function of effector and suppressor T cells are responsible for the immune imbalance responsible for propagation of type 1 diabetes as a chronic inflammatory process. Possibly, the experimental tools for investigation of these features of immune activity are still underdeveloped and lack sufficient resolution, in the presence of the extensive biological viability and functional versatility of effector and suppressor elements.

  15. Transcriptome profiling of a curdlan-producing Agrobacterium reveals conserved regulatory mechanisms of exopolysaccharide biosynthesis

    Directory of Open Access Journals (Sweden)

    Ruffing Anne M

    2012-02-01

    Full Text Available Abstract Background The ability to synthesize exopolysaccharides (EPS is widespread among microorganisms, and microbial EPS play important roles in biofilm formation, pathogen persistence, and applications in the food and medical industries. Although it is well established that EPS synthesis is invariably in response to environmental cues, it remains largely unknown how various environmental signals trigger activation of the biochemical synthesis machinery. Results We report here the transcriptome profiling of Agrobacterium sp. ATCC 31749, a microorganism that produces large amounts of a glucose polymer known as curdlan under nitrogen starvation. Transcriptome analysis revealed a nearly 100-fold upregulation of the curdlan synthesis operon upon transition to nitrogen starvation, thus establishing the prominent role that transcriptional regulation plays in the EPS synthesis. In addition to known mechanisms of EPS regulation such as activation by c-di-GMP, we identify novel mechanisms of regulation in ATCC 31749, including RpoN-independent NtrC regulation and intracellular pH regulation by acidocalcisomes. Furthermore, we show evidence that curdlan synthesis is also regulated by conserved cell stress responses, including polyphosphate accumulation and the stringent response. In fact, the stringent response signal, pppGpp, appears to be indispensible for transcriptional activation of curdlan biosynthesis. Conclusions This study identifies several mechanisms regulating the synthesis of curdlan, an EPS with numerous applications. These mechanisms are potential metabolic engineering targets for improving the industrial production of curdlan from Agrobacterium sp. ATCC 31749. Furthermore, many of the genes identified in this study are highly conserved across microbial genomes, and we propose that the molecular elements identified in this study may serve as universal regulators of microbial EPS synthesis.

  16. Lamins, laminopathies and disease mechanisms: Possible role for proteasomal degradation of key regulatory proteins

    Indian Academy of Sciences (India)

    Veena K Parnaik; Pankaj Chaturvedi; B H Muralikrishna

    2011-08-01

    Lamins are major structural proteins of the nucleus and are essential for nuclear integrity and organization of nuclear functions. Mutations in the human lamin genes lead to highly degenerative genetic diseases that affect a number of different tissues such as muscle, adipose or neuronal tissues, or cause premature ageing syndromes. New findings on the role of lamins in cellular signalling pathways, as well as in ubiquitin-mediated proteasomal degradation, have given important insights into possible mechanisms of pathogenesis.

  17. Neural mechanisms supporting the extraction of general knowledge across episodic memories

    NARCIS (Netherlands)

    Sweegers, C.C.G.; Takashima, A.; Fernández, G.; Talamini, L.M.

    2014-01-01

    General knowledge acquisition entails the extraction of statistical regularities from the environment. At high levels of complexity, this may involve the extraction, and consolidation, of associative regularities across event memories. The underlying neural mechanisms would likely involve a

  18. Neural mechanisms supporting the extraction of general knowledge across episodic memories

    NARCIS (Netherlands)

    Sweegers, C.C.; Takashima, A.; Fernandez, G.S.E.; Talamini, L.M.

    2014-01-01

    General knowledge acquisition entails the extraction of statistical regularities from the environment. At high levels of complexity, this may involve the extraction, and consolidation, of associative regularities across event memories. The underlying neural mechanisms would likely involve a hippocam

  19. The cytoplasmic poly(A) polymerases GLD-2 and GLD-4 promote general gene expression via distinct mechanisms.

    Science.gov (United States)

    Nousch, Marco; Yeroslaviz, Assa; Habermann, Bianca; Eckmann, Christian R

    2014-10-01

    Post-transcriptional gene regulation mechanisms decide on cellular mRNA activities. Essential gatekeepers of post-transcriptional mRNA regulation are broadly conserved mRNA-modifying enzymes, such as cytoplasmic poly(A) polymerases (cytoPAPs). Although these non-canonical nucleotidyltransferases efficiently elongate mRNA poly(A) tails in artificial tethering assays, we still know little about their global impact on poly(A) metabolism and their individual molecular roles in promoting protein production in organisms. Here, we use the animal model Caenorhabditis elegans to investigate the global mechanisms of two germline-enriched cytoPAPs, GLD-2 and GLD-4, by combining polysome profiling with RNA sequencing. Our analyses suggest that GLD-2 activity mediates mRNA stability of many translationally repressed mRNAs. This correlates with a general shortening of long poly(A) tails in gld-2-compromised animals, suggesting that most if not all targets are stabilized via robust GLD-2-mediated polyadenylation. By contrast, only mild polyadenylation defects are found in gld-4-compromised animals and few mRNAs change in abundance. Interestingly, we detect a reduced number of polysomes in gld-4 mutants and GLD-4 protein co-sediments with polysomes, which together suggest that GLD-4 might stimulate or maintain translation directly. Our combined data show that distinct cytoPAPs employ different RNA-regulatory mechanisms to promote gene expression, offering new insights into translational activation of mRNAs.

  20. [Research progress in biofilm formation and regulatory mechanism of Campylobacter jejuni].

    Science.gov (United States)

    Wu, Qingping; Zhong, Xian; Zhang, Jumei

    2016-02-04

    Biofilm of Campylobacter jejuni was formed by cross-linking its extracellular secretion, polysaccharides, various extracellular proteins, nucleic acids etc to enhance its survival in hostile environments, especially for detergents, antibiotics and disinfectants. This paper elaborated C. jejuni biofilm formation and regulation mechanisms in the surface properties of the media, temperatures, gas environment, the regulation of gene etc, also analysed and discussed a variety of biofilm removal practical applications. We hope it can provide a reference for studies on biofilm control of C. jejuni.

  1. Disruption of long-range gene regulation in human genetic disease: a kaleidoscope of general principles, diverse mechanisms and unique phenotypic consequences.

    Science.gov (United States)

    Bhatia, Shipra; Kleinjan, Dirk A

    2014-07-01

    The precise control of gene expression programs is crucial for the establishment of the diverse gene activity patterns required for the correct development, patterning and differentiation of the myriad of cell types within an organism. The crucial importance of non-coding regions of the genome in the control of gene regulation is well established and depends on a diverse group of sequence fragments called cis-regulatory elements that reside in these regions. Advances in novel genome-wide techniques have greatly increased the ability to identify potential regulatory elements. In contrast, their functional characterisation and the determination of their diverse modes of action remain a major bottleneck. Greater knowledge of gene expression control is of major importance for human health as disruption of gene regulation has become recognised as a significant cause of human disease. Appreciation of the role of cis-regulatory polymorphism in natural variation and susceptibility to common disease is also growing. While novel techniques such as GWAS and NGS provide the ability to collect large genomic datasets, the challenge for the twenty-first century will be to extract the relevant sequences and how to investigate the functional consequences of disease-associated changes. Here, we review how studies of transcriptional control at selected paradigm disease gene loci have revealed general principles of cis-regulatory logic and regulatory genome organisation, yet also demonstrate how the variety of mechanisms can combine to result in unique phenotypic outcomes. Integration of these principles with the emerging wealth of genome-wide data will provide enhanced insight into the workings of our regulatory genome.

  2. Novel Sinorhizobium meliloti quorum sensing positive and negative regulatory feedback mechanisms respond to phosphate availability.

    Science.gov (United States)

    McIntosh, Matthew; Meyer, Stefan; Becker, Anke

    2009-12-01

    The Sin quorum sensing system of Sinorhizobium meliloti depends upon at least three genes, sinR, sinI and expR, and N-acyl homoserine lactones (AHLs) as signals to regulate multiple processes in its free-living state in the rhizosphere and in the development towards symbiosis with its plant host. In this study, we have characterized novel mechanisms of transcription control through which the system regulates itself. At low AHL levels a positive feedback loop activates expression of sinI (AHL synthase), resulting in amplification of AHL levels. At high AHL levels, expression of sinI is reduced by a negative feedback loop. These feedback mechanisms are mediated by the LuxR-type regulators ExpR and SinR. Expression of sinR and expR is regulated by ExpR in the presence of AHLs. A novel ExpR binding site in the promoter of sinR is responsible for the reduction of expression of this gene. In addition, expression of sinR, upon which sinI expression is dependent, is induced by phoB during growth under phosphate-limiting conditions. This indicates that this response ensures quorum sensing in phosphate-restricted growth.

  3. Subchromoplast sequestration of carotenoids affects regulatory mechanisms in tomato lines expressing different carotenoid gene combinations.

    Science.gov (United States)

    Nogueira, Marilise; Mora, Leticia; Enfissi, Eugenia M A; Bramley, Peter M; Fraser, Paul D

    2013-11-01

    Metabolic engineering of the carotenoid pathway in recent years has successfully enhanced the carotenoid contents of crop plants. It is now clear that only increasing biosynthesis is restrictive, as mechanisms to sequestrate these increased levels in the cell or organelle should be exploited. In this study, biosynthetic pathway genes were overexpressed in tomato (Solanum lycopersicum) lines and the effects on carotenoid formation and sequestration revealed. The bacterial Crt carotenogenic genes, independently or in combination, and their zygosity affect the production of carotenoids. Transcription of the pathway genes was perturbed, whereby the tissue specificity of transcripts was altered. Changes in the steady state levels of metabolites in unrelated sectors of metabolism were found. Of particular interest was a concurrent increase of the plastid-localized lipid monogalactodiacylglycerol with carotenoids along with membranous subcellular structures. The carotenoids, proteins, and lipids in the subchromoplast fractions of the transgenic tomato fruit with increased carotenoid content suggest that cellular structures can adapt to facilitate the sequestration of the newly formed products. Moreover, phytoene, the precursor of the pathway, was identified in the plastoglobule, whereas the biosynthetic enzymes were in the membranes. The implications of these findings with respect to novel pathway regulation mechanisms are discussed.

  4. Regulatory mechanisms and clinical perspectives of miR-34a in cancer

    Directory of Open Access Journals (Sweden)

    Lei Li

    2014-01-01

    Full Text Available MicroRNAs (miRNAs are evolutionarily conserved, endogenous, noncoding RNA molecules of about 22-24 nucleotides in length that repress gene expression at the posttranscriptional level. MiR-34a plays an important role in the initiation, progression, and therapy of cancer. In addition, the miR-34a expression has also been identified as a diagnostic and prognostic cancer signature. This article introduces the roles of miR-34a in cancer development, metastasis as well as its mechanism of actions on target genes and the functional outcomes of its actions on radio-sensitivity. The paper ends with a brief perspective to the future of miR-34a.

  5. Ocean warming and acidification modulate energy budget and gill ion regulatory mechanisms in Atlantic cod (Gadus morhua).

    Science.gov (United States)

    Kreiss, C M; Michael, K; Lucassen, M; Jutfelt, F; Motyka, R; Dupont, S; Pörtner, H-O

    2015-10-01

    Ocean warming and acidification are threatening marine ecosystems. In marine animals, acidification is thought to enhance ion regulatory costs and thereby baseline energy demand, while elevated temperature also increases baseline metabolic rate. Here we investigated standard metabolic rates (SMR) and plasma parameters of Atlantic cod (Gadus morhua) after 3-4 weeks of exposure to ambient and future PCO2 levels (550, 1200 and 2200 µatm) and at two temperatures (10, 18 °C). In vivo branchial ion regulatory costs were studied in isolated, perfused gill preparations. Animals reared at 18 °C responded to increasing CO2 by elevating SMR, in contrast to specimens at 10 °C. Isolated gills at 10 °C and elevated PCO2 (≥1200 µatm) displayed increased soft tissue mass, in parallel to increased gill oxygen demand, indicating an increased fraction of gill in whole animal energy budget. Altered gill size was not found at 18 °C, where a shift in the use of ion regulation mechanisms occurred towards enhanced Na(+)/H(+)-exchange and HCO3 (-) transport at high PCO2 (2200 µatm), paralleled by higher Na(+)/K(+)-ATPase activities. This shift did not affect total gill energy consumption leaving whole animal energy budget unaffected. Higher Na(+)/K(+)-ATPase activities in the warmth might have compensated for enhanced branchial permeability and led to reduced plasma Na(+) and/or Cl(-) concentrations and slightly lowered osmolalities seen at 18 °C and 550 or 2200 µatm PCO2 in vivo. Overall, the gill as a key ion regulation organ seems to be highly effective in supporting the resilience of cod to effects of ocean warming and acidification.

  6. Integrating factors and conservation theorem for holonomic nonconservative dynamical systems in generalized classical mechanics

    Institute of Scientific and Technical Information of China (English)

    乔永芬; 张耀良; 韩广才

    2002-01-01

    In this paper, we present a general approach to the construction of conservation laws for generalized classical dynamical systems. Firstly, we give the definition of integrating factors and, secondly, we study in detail the necessary conditions for the existence of conserved quantities. Then we establish the conservation theorem and its inverse for the Hamilton's canonical equations of motion of holonomic nonconservative dynamical systems in generalized classical mechanics. Finally, we give an example to illustrate the application of the results.

  7. Gene Regulatory Mechanisms Underlying the Spatial and Temporal Regulation of Target-Dependent Gene Expression in Drosophila Neurons.

    Directory of Open Access Journals (Sweden)

    Anthony J E Berndt

    2015-12-01

    Full Text Available Neuronal differentiation often requires target-derived signals from the cells they innervate. These signals typically activate neural subtype-specific genes, but the gene regulatory mechanisms remain largely unknown. Highly restricted expression of the FMRFa neuropeptide in Drosophila Tv4 neurons requires target-derived BMP signaling and a transcription factor code that includes Apterous. Using integrase transgenesis of enhancer reporters, we functionally dissected the Tv4-enhancer of FMRFa within its native cellular context. We identified two essential but discrete cis-elements, a BMP-response element (BMP-RE that binds BMP-activated pMad, and a homeodomain-response element (HD-RE that binds Apterous. These cis-elements have low activity and must be combined for Tv4-enhancer activity. Such combinatorial activity is often a mechanism for restricting expression to the intersection of cis-element spatiotemporal activities. However, concatemers of the HD-RE and BMP-RE cis-elements were found to independently generate the same spatiotemporal expression as the Tv4-enhancer. Thus, the Tv4-enhancer atypically combines two low-activity cis-elements that confer the same output from distinct inputs. The activation of target-dependent genes is assumed to 'wait' for target contact. We tested this directly, and unexpectedly found that premature BMP activity could not induce early FMRFa expression; also, we show that the BMP-insensitive HD-RE cis-element is activated at the time of target contact. This led us to uncover a role for the nuclear receptor, seven up (svp, as a repressor of FMRFa induction prior to target contact. Svp is normally downregulated immediately prior to target contact, and we found that maintaining Svp expression prevents cis-element activation, whereas reducing svp gene dosage prematurely activates cis-element activity. We conclude that the target-dependent FMRFa gene is repressed prior to target contact, and that target-derived BMP

  8. Experimental and theoretical investigation of mechanical disturbances in epoxy-impregnated superconducting coils. 1. General introduction

    Energy Technology Data Exchange (ETDEWEB)

    Iwasa, Y. (Massachusetts Inst. of Tech., Cambridge (USA). Francis Bitter National Magnet Lab.; Massachusetts Inst. of Tech., Cambridge (USA). Plasma Fusion Center)

    1985-06-01

    The paper gives a general introduction to the three papers which follow. A brief discussion of the origins and mechanisms of mechanical disturbances within the windings of high performance superconducting magnets is followed by a short summary of each of the three papers.

  9. The Mechanics of Spacetime - A Solid Mechanics Perspective on the Theory of General Relativity

    CERN Document Server

    Tenev, T G

    2016-01-01

    We present an elastic constitutive model of General Relativity where we identify the vacuum of three-dimensional space with a Cosmic Fabric embedded in four-dimensional spacetime and having a small thickness along the time dimension. We show a correspondence between the gravitational phenomena described by General Relativity and the kinematic and kinetic properties of the Cosmic Fabric. We propose, in agreement with modern cosmological observations (Collier, 2012; Perlmutter et al., 1999; Riess et al., 1998) and with theoretical results from Quantum Field Theory (Rugh and Zinkernagel, 2002), that the space vacuum is really not a vacuum in the purest sense but is a Cosmic Fabric that has energy density and as such mass density. We further propose that the Cosmic Fabric deforms due to matter in space, which acts as inclusions, in a manner analogous to the deformation of a conventional thin plate (Efrati et al., 2008). By introducing a constitutive model for General Relativity, we lay the groundwork for subseque...

  10. Desenho e funcionamento dos mecanismos de controle e accountability das agências reguladoras brasileiras: semelhanças e diferenças Design and operation of the Brazilian regulatory agencies' control and accountability mechanisms: similarities and differences

    National Research Council Canada - National Science Library

    Marcos Vinicius Pó; Fernando Luiz Abrucio

    2006-01-01

    ... agências reguladoras provoca na accountability do Estado brasileiro.This article studies the design and operation of the regulatory agencies' control and accountability mechanisms, underlining...

  11. The regulatory mechanism of fungal elicitor-induced secondary metabolite biosynthesis in medical plants.

    Science.gov (United States)

    Zhai, Xin; Jia, Min; Chen, Ling; Zheng, Cheng-Jian; Rahman, Khalid; Han, Ting; Qin, Lu-Ping

    2017-03-01

    A wide range of external stress stimuli trigger plant cells to undergo complex network of reactions that ultimately lead to the synthesis and accumulation of secondary metabolites. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. Throughout evolution, endophytic fungi, an important constituent in the environment of medicinal plants, have known to form long-term stable and mutually beneficial symbiosis with medicinal plants. The endophytic fungal elicitor can rapidly and specifically induce the expression of specific genes in medicinal plants which can result in the activation of a series of specific secondary metabolic pathways resulting in the significant accumulation of active ingredients. Here we summarize the progress made on the mechanisms of fungal elicitor including elicitor signal recognition, signal transduction, gene expression and activation of the key enzymes and its application. This review provides guidance on studies which may be conducted to promote the efficient synthesis and accumulation of active ingredients by the endogenous fungal elicitor in medicinal plant cells, and provides new ideas and methods of studying the regulation of secondary metabolism in medicinal plants.

  12. A competitive regulatory mechanism discriminates between juxtaposed splice sites and pri-miRNA structures.

    Science.gov (United States)

    Mattioli, Chiara; Pianigiani, Giulia; Pagani, Franco

    2013-10-01

    We have explored the functional relationships between spliceosome and Microprocessor complex activities in a novel class of microRNAs (miRNAs), named Splice site Overlapping (SO) miRNAs, whose pri-miRNA hairpins overlap splice sites. We focused on the evolutionarily conserved SO miR-34b, and we identified two indispensable elements for recognition of its 3' splice site: a branch point located in the hairpin and a downstream purine-rich exonic splicing enhancer. In minigene systems, splicing inhibition owing to exonic splicing enhancer deletion or AG 3'ss mutation increases miR-34b levels. Moreover, small interfering-mediated silencing of Drosha and/or DGCR8 improves splicing efficiency and abolishes miR-34b production. Thus, the processing of this 3' SO miRNA is regulated in an antagonistic manner by the Microprocessor and the spliceosome owing to competition between these two machineries for the nascent transcript. We propose that this novel mechanism is commonly used to regulate the relative amount of SO miRNA and messenger RNA produced from primary transcripts.

  13. Social dominance-related major urinary proteins and the regulatory mechanism in mice.

    Science.gov (United States)

    Guo, Huifen; Fang, Qi; Huo, Ying; Zhang, Yaohua; Zhang, Jianxu

    2015-11-01

    Major urinary proteins (MUPs) have been proven to be non-volatile male pheromones in mice. Here, we aimed to elucidate the relationship between MUPs and dominance hierarchy, and the underlying molecular mechanisms. Dominance-submission relationship was established by chronic dyadic encountering. We found that at the urinary protein level and hepatic mRNA level, the expression of major MUPs, including Mup20, was enhanced in dominant males compared with subordinate males, indicating that MUPs might signal the social status of male mice. Meanwhile, the mRNA level of hepatic corticotropin releasing hormone receptor 2 (CRHR2) was higher in subordinate male mice than in dominant male mice. Castration also enhanced the expression of CRHR2, but suppressed that of MUPs. CRHR2 agonist treatment reduced the expression of MUPs in liver. However, male social status failed to exert significant influence on serum testosterone and corticosterone as well as the mRNA expression of their receptors. These findings reveal that some MUPs, especially Mup20, might constitute potential dominance pheromones and could be downregulated by hepatic CRHR2, which is possibly independent of androgen or corticosterone systems.

  14. Tuning of redox regulatory mechanisms, reactive oxygen species and redox homeostasis under salinity stress

    Directory of Open Access Journals (Sweden)

    Hossain eSazzad

    2016-05-01

    Full Text Available Soil salinity is a crucial environmental constraint which limits biomass production at many sites on a global scale. Saline growth conditions cause osmotic and ionic imbalances, oxidative stress and perturb metabolism, e.g. the photosynthetic electron flow. The plant ability to tolerate salinity is determined by multiple biochemical and physiological mechanisms protecting cell functions, in particular by regulating proper water relations and maintaining ion homeostasis. Redox homeostasis is a fundamental cell property. Its regulation includes control of reactive oxygen species (ROS generation, sensing deviation from and readjustment of the cellular redox state. All these redox related functions have been recognized as decisive factors in salinity acclimation and adaptation. This review focuses on the core response of plants to overcome the challenges of salinity stress through regulation of ROS generation and detoxification systems and to maintain redox homeostasis. Emphasis is given to the role of NADH oxidase (RBOH, alternative oxidase (AOX, the plastid terminal oxidase (PTOX and the malate valve with the malate dehydrogenase isoforms under salt stress. Overwhelming evidence assigns an essential auxiliary function of ROS and redox homeostasis to salinity acclimation of plants.

  15. The Mechanisms of Water Exchange: The Regulatory Roles of Multiple Interactions in Social Wasps.

    Directory of Open Access Journals (Sweden)

    Devanshu Agrawal

    Full Text Available Evolutionary benefits of task fidelity and improving information acquisition via multiple transfers of materials between individuals in a task partitioned system have been shown before, but in this paper we provide a mechanistic explanation of these phenomena. Using a simple mathematical model describing the individual interactions of the wasps, we explain the functioning of the common stomach, an information center, which governs construction behavior and task change. Our central hypothesis is a symmetry between foragers who deposit water and foragers who withdraw water into and out of the common stomach. We combine this with a trade-off between acceptance and resistance to water transfer. We ultimately derive a mathematical function that relates the number of interactions that foragers complete with common stomach wasps during a foraging cycle. We use field data and additional model assumptions to calculate values of our model parameters, and we use these to explain why the fullness of the common stomach stabilizes just below 50 percent, why the average number of successful interactions between foragers and the wasps forming the common stomach is between 5 and 7, and why there is a variation in this number of interactions over time. Our explanation is that our proposed water exchange mechanism places natural bounds on the number of successful interactions possible, water exchange is set to optimize mediation of water through the common stomach, and the chance that foragers abort their task prematurely is very low.

  16. Phosphorylation regulates myo-inositol-3-phosphate synthase: a novel regulatory mechanism of inositol biosynthesis.

    Science.gov (United States)

    Deranieh, Rania M; He, Quan; Caruso, Joseph A; Greenberg, Miriam L

    2013-09-13

    myo-Inositol-3-phosphate synthase (MIPS) plays a crucial role in inositol homeostasis. Transcription of the coding gene INO1 is highly regulated. However, regulation of the enzyme is not well defined. We previously showed that MIPS is indirectly inhibited by valproate, suggesting that the enzyme is post-translationally regulated. Using (32)Pi labeling and phosphoamino acid analysis, we show that yeast MIPS is a phosphoprotein. Mass spectrometry analysis identified five phosphosites, three of which are conserved in the human MIPS. Analysis of phosphorylation-deficient and phosphomimetic site mutants indicated that the three conserved sites in yeast (Ser-184, Ser-296, and Ser-374) and humans (Ser-177, Ser-279, and Ser-357) affect MIPS activity. Both S296A and S296D yeast mutants and S177A and S177D human mutants exhibited decreased enzymatic activity, suggesting that a serine residue is critical at that location. The phosphomimetic mutations S184D (human S279D) and S374D (human S357D) but not the phosphodeficient mutations decreased activity, suggesting that phosphorylation of these two sites is inhibitory. The double mutation S184A/S374A caused an increase in MIPS activity, conferred a growth advantage, and partially rescued sensitivity to valproate. Our findings identify a novel mechanism of regulation of inositol synthesis by phosphorylation of MIPS.

  17. Symmetry of Hamiltonian and conserved quantity for a system of generalized classical mechanics

    Institute of Scientific and Technical Information of China (English)

    Zhang Yi

    2011-01-01

    This paper focuses on a new symmetry of Hamiltonian and its conserved quantity for a system of generalized classical mechanics. The differential equations of motion of the system are established. The definition and the criterion of the symmetry of Hamiltonian of the system are given. A conserved quantity directly derived from the symmetry of Hamiltonian of the generalized classical mechanical system is given. Since a Hamilton system is a special case of the generalized classical mechanics, the results above are equally applicable to the Hamilton system. The results of the paper are the generalization of a theorem known for the existing nonsingular equivalent Lagrangian. Finally, two examples are given to illustrate the application of the results.

  18. Vpu mediates depletion of interferon regulatory factor 3 during HIV infection by a lysosome-dependent mechanism.

    Science.gov (United States)

    Doehle, Brian P; Chang, Kristina; Rustagi, Arjun; McNevin, John; McElrath, M Juliana; Gale, Michael

    2012-08-01

    HIV has evolved sophisticated mechanisms to avoid restriction by intracellular innate immune defenses that otherwise serve to control acute viral infection and virus dissemination. Innate defenses are triggered when pattern recognition receptor (PRR) proteins of the host cell engage pathogen-associated molecule patterns (PAMPs) present in viral products. Interferon regulatory factor 3 (IRF3) plays a central role in PRR signaling of innate immunity to drive the expression of type I interferon (IFN) and interferon-stimulated genes (ISGs), including a variety of HIV restriction factors, that serve to limit viral replication directly and/or program adaptive immunity. Productive infection of T cells by HIV is dependent upon the targeted proteolysis of IRF3 that occurs through a virus-directed mechanism that results in suppression of innate immune defenses. However, the mechanisms by which HIV controls innate immune signaling and IRF3 function are not defined. Here, we examined the innate immune response induced by HIV strains identified through their differential control of PRR signaling. We identified viruses that, unlike typical circulating HIV strains, lack the ability to degrade IRF3. Our studies show that IRF3 regulation maps specifically to the HIV accessory protein Vpu. We define a molecular interaction between Vpu and IRF3 that redirects IRF3 to the endolysosome for proteolytic degradation, thus allowing HIV to avoid the innate antiviral immune response. Our studies reveal that Vpu is an important IRF3 regulator that supports acute HIV infection through innate immune suppression. These observations define the Vpu-IRF3 interface as a novel target for therapeutic strategies aimed at enhancing the immune response to HIV.

  19. Vpu Mediates Depletion of Interferon Regulatory Factor 3 during HIV Infection by a Lysosome-Dependent Mechanism

    Science.gov (United States)

    Doehle, Brian P.; Chang, Kristina; Rustagi, Arjun; McNevin, John; McElrath, M. Juliana

    2012-01-01

    HIV has evolved sophisticated mechanisms to avoid restriction by intracellular innate immune defenses that otherwise serve to control acute viral infection and virus dissemination. Innate defenses are triggered when pattern recognition receptor (PRR) proteins of the host cell engage pathogen-associated molecule patterns (PAMPs) present in viral products. Interferon regulatory factor 3 (IRF3) plays a central role in PRR signaling of innate immunity to drive the expression of type I interferon (IFN) and interferon-stimulated genes (ISGs), including a variety of HIV restriction factors, that serve to limit viral replication directly and/or program adaptive immunity. Productive infection of T cells by HIV is dependent upon the targeted proteolysis of IRF3 that occurs through a virus-directed mechanism that results in suppression of innate immune defenses. However, the mechanisms by which HIV controls innate immune signaling and IRF3 function are not defined. Here, we examined the innate immune response induced by HIV strains identified through their differential control of PRR signaling. We identified viruses that, unlike typical circulating HIV strains, lack the ability to degrade IRF3. Our studies show that IRF3 regulation maps specifically to the HIV accessory protein Vpu. We define a molecular interaction between Vpu and IRF3 that redirects IRF3 to the endolysosome for proteolytic degradation, thus allowing HIV to avoid the innate antiviral immune response. Our studies reveal that Vpu is an important IRF3 regulator that supports acute HIV infection through innate immune suppression. These observations define the Vpu-IRF3 interface as a novel target for therapeutic strategies aimed at enhancing the immune response to HIV. PMID:22593165

  20. Electrical stimulation of the substantia nigra reticulata : Detection of neuronal extracellular GABA in the ventromedial thalamus and its regulatory mechanism using microdialysis in awake rats

    NARCIS (Netherlands)

    Timmerman, W; Westerink, BHC

    1997-01-01

    A combination of electrical stimulation and microdialysis was used to study the nigrothalamic gamma aminobutyric acid (GABA)ergic system and its regulatory mechanisms in awake rats. Extracellular GABA levels in the ventromedial nucleus of the thalamus were detected in S-min fractions collected befor

  1. Cis- and trans-regulatory mechanisms of gene expression in the ASJ sensory neuron of Caenorhabditis elegans

    NARCIS (Netherlands)

    M. González-Barrios (María); J.C. Fierro-González (Juan Carlos); E. Krpelanova (Eva); J.A. Mora-Lorca (José Antonio); J. Rafael Pedrajas (José); X. Peñate (Xenia); S. Chavez (Sebastián); P. Swoboda (Peter); G. Jansen (Gert); A. Miranda-Vizuet (Antonio)

    2015-01-01

    textabstractThe identity of a given cell type is determined by the expression of a set of genes sharing common cis-regulatory motifs and being regulated by shared transcription factors. Here, we identify cis and trans regulatory elements that drive gene expression in the bilateral sensory neuron ASJ

  2. Auxin Response Factor SlARF2 Is an Essential Component of the Regulatory Mechanism Controlling Fruit Ripening in Tomato.

    Science.gov (United States)

    Hao, Yanwei; Hu, Guojian; Breitel, Dario; Liu, Mingchun; Mila, Isabelle; Frasse, Pierre; Fu, Yongyao; Aharoni, Asaph; Bouzayen, Mondher; Zouine, Mohamed

    2015-12-01

    Ethylene is the main regulator of climacteric fruit ripening, by contrast the putative role of other phytohormones in this process remains poorly understood. The present study brings auxin signaling components into the mechanism regulating tomato fruit ripening through the functional characterization of Auxin Response Factor2 (SlARF2) which encodes a downstream component of auxin signaling. Two paralogs, SlARF2A and SlARF2B, are found in the tomato genome, both displaying a marked ripening-associated expression but distinct responsiveness to ethylene and auxin. Down-regulation of either SlARF2A or SlARF2B resulted in ripening defects while simultaneous silencing of both genes led to severe ripening inhibition suggesting a functional redundancy among the two ARFs. Tomato fruits under-expressing SlARF2 produced less climacteric ethylene and exhibited a dramatic down-regulation of the key ripening regulators RIN, CNR, NOR and TAGL1. Ethylene treatment failed to reverse the non-ripening phenotype and the expression of ethylene signaling and biosynthesis genes was strongly altered in SlARF2 down-regulated fruits. Although both SlARF proteins are transcriptional repressors the data indicate they work as positive regulators of tomato fruit ripening. Altogether, the study defines SlARF2 as a new component of the regulatory network controlling the ripening process in tomato.

  3. Auxin Response Factor SlARF2 Is an Essential Component of the Regulatory Mechanism Controlling Fruit Ripening in Tomato.

    Directory of Open Access Journals (Sweden)

    Yanwei Hao

    2015-12-01

    Full Text Available Ethylene is the main regulator of climacteric fruit ripening, by contrast the putative role of other phytohormones in this process remains poorly understood. The present study brings auxin signaling components into the mechanism regulating tomato fruit ripening through the functional characterization of Auxin Response Factor2 (SlARF2 which encodes a downstream component of auxin signaling. Two paralogs, SlARF2A and SlARF2B, are found in the tomato genome, both displaying a marked ripening-associated expression but distinct responsiveness to ethylene and auxin. Down-regulation of either SlARF2A or SlARF2B resulted in ripening defects while simultaneous silencing of both genes led to severe ripening inhibition suggesting a functional redundancy among the two ARFs. Tomato fruits under-expressing SlARF2 produced less climacteric ethylene and exhibited a dramatic down-regulation of the key ripening regulators RIN, CNR, NOR and TAGL1. Ethylene treatment failed to reverse the non-ripening phenotype and the expression of ethylene signaling and biosynthesis genes was strongly altered in SlARF2 down-regulated fruits. Although both SlARF proteins are transcriptional repressors the data indicate they work as positive regulators of tomato fruit ripening. Altogether, the study defines SlARF2 as a new component of the regulatory network controlling the ripening process in tomato.

  4. Transcriptome profiling reveals the regulatory mechanism underlying pollination dependent and parthenocarpic fruit set mainly mediated by auxin and gibberellin.

    Science.gov (United States)

    Tang, Ning; Deng, Wei; Hu, Guojian; Hu, Nan; Li, Zhengguo

    2015-01-01

    Fruit set is a key process for crop production in tomato which occurs after successful pollination and fertilization naturally. However, parthenocarpic fruit development can be uncoupled from fertilization triggered by exogenous auxin or gibberellins (GAs). Global transcriptome knowledge during fruit initiation would help to characterize the molecular mechanisms by which these two hormones regulate pollination-dependent and -independent fruit set. In this work, digital gene expression tag profiling (DGE) technology was applied to compare the transcriptomes from pollinated and 2, 4-D/GA3-treated ovaries. Activation of carbohydrate metabolism, cell division and expansion as well as the down-regulation of MADS-box is a comprehensive regulatory pathway during pollination-dependent and parthenocarpic fruit set. The signaling cascades of auxin and GA are significantly modulated. The feedback regulations of Aux/IAAs and DELLA genes which functioned to fine-tune auxin and GA response respectively play fundamental roles in triggering fruit initiation. In addition, auxin regulates GA synthesis via up-regulation of GA20ox1 and down-regulation of KNOX. Accordingly, the effect of auxin on fruit set is mediated by GA via ARF2 and IAA9 down-regulation, suggesting that both pollination-dependent and parthenocarpic fruit set depend on the crosstalk between auxin and GA. This study characterizes the transcriptomic features of ovary development and more importantly unravels the integral roles of auxin and GA on pollination-dependent and parthenocarpic fruit set.

  5. Regulatory Mechanisms of the Ihh/PTHrP Signaling Pathway in Fibrochondrocytes in Entheses of Pig Achilles Tendon

    Directory of Open Access Journals (Sweden)

    Xuesong Han

    2016-01-01

    Full Text Available This study is aimed at exploring the effect of stress stimulation on the proliferation and differentiation of fibrochondrocytes in entheses mediated via the Indian hedgehog (Ihh/parathyroid hormone-related protein (PTHrP signaling pathway. Differential stress stimulation on fibrochondrocytes in entheses was imposed. Gene expression and protein levels of signaling molecules including collagen type I (Col I, Col II, Col X, Ihh, and PTHrP in the cytoplasm of fibrochondrocytes were detected. Ihh signal blocking group was set up using Ihh signaling pathway-specific blocking agent cyclopamine. PTHrP enhancement group was set up using PTHrP reagent. Ihh/PTHrP double intervention group, as well as control group, was included to study the regulatory mechanisms of the Ihh/PTHrP signaling pathway in fibrochondrocytes. Under low cyclic stress tensile (CTS, PTHrP, Col I, and Col II gene expression and protein synthesis increased. Under high CTS, Ihh and Col X gene expression and protein synthesis increased. Blocking Ihh signaling with cyclopamine resulted in reduced PTHrP gene expression and protein synthesis and increased Col X gene expression and protein synthesis. Ihh and PTHrP coregulate fibrochondrocyte proliferation and differentiation in entheses through negative feedback regulation. Fibrochondrocyte is affected by the CTS. This phenomenon is regulated by stress stimulation through the Ihh/PTHrP signaling pathway.

  6. Comparative study between transcriptionally- and translationally-acting adenine riboswitches reveals key differences in riboswitch regulatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Jean-François Lemay

    2011-01-01

    Full Text Available Many bacterial mRNAs are regulated at the transcriptional or translational level by ligand-binding elements called riboswitches. Although they both bind adenine, the adenine riboswitches of Bacillus subtilis and Vibrio vulnificus differ by controlling transcription and translation, respectively. Here, we demonstrate that, beyond the obvious difference in transcriptional and translational modulation, both adenine riboswitches exhibit different ligand binding properties and appear to operate under different regulation regimes (kinetic versus thermodynamic. While the B. subtilis pbuE riboswitch fully depends on co-transcriptional binding of adenine to function, the V. vulnificus add riboswitch can bind to adenine after transcription is completed and still perform translation regulation. Further investigation demonstrates that the rate of transcription is critical for the B. subtilis pbuE riboswitch to perform efficiently, which is in agreement with a co-transcriptional regulation. Our results suggest that the nature of gene regulation control, that is transcription or translation, may have a high importance in riboswitch regulatory mechanisms.

  7. Reactive oxygen species regulatory mechanisms associated with rapid response of MC3T3-E1 cells for vibration stress

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ling; Gan, Xueqi; Zhu, Zhuoli; Yang, Yang; He, Yuting; Yu, Haiyang, E-mail: yhyang6812@scu.edu.cn

    2016-02-12

    Although many previous studies have shown that refractory period-dependent memory effect of vibration stress is anabolic for skeletal homeostasis, little is known about the rapid response of osteoblasts simply derived from vibration itself. In view of the potential role of reactive oxygen species (ROS) in mediating differentiated activity of osteoblasts, whether and how ROS regulates the rapid effect of vibration deserve to be demonstrated. Our findings indicated that MC3T3-E1 cells underwent decreased gene expression of Runx2, Col-I and ALP and impaired ALP activity accompanied by increased mitochondrial fission immediately after vibration loading. Moreover, we also revealed the involvement of ERK-Drp1 signal transduction in ROS regulatory mechanisms responsible for the rapid effect of vibration stress. - Highlights: • ROS contributed to the rapid response of MC3T3-E1 cells for vibration stress. • Imbalance of mitochondrial dynamics were linked to the LMHFV-derived rapid response. • The role of ERK-Drp1 signal pathway in the LMHFV-derived osteoblast rapid response.

  8. The function of the RNA-binding protein TEL1 in moss reveals ancient regulatory mechanisms of shoot development.

    Science.gov (United States)

    Vivancos, Julien; Spinner, Lara; Mazubert, Christelle; Charlot, Florence; Paquet, Nicolas; Thareau, Vincent; Dron, Michel; Nogué, Fabien; Charon, Céline

    2012-03-01

    The shoot represents the basic body plan in land plants. It consists of a repeated structure composed of stems and leaves. Whereas vascular plants generate a shoot in their diploid phase, non-vascular plants such as mosses form a shoot (called the gametophore) in their haploid generation. The evolution of regulatory mechanisms or genetic networks used in the development of these two kinds of shoots is unclear. TERMINAL EAR1-like genes have been involved in diploid shoot development in vascular plants. Here, we show that disruption of PpTEL1 from the moss Physcomitrella patens, causes reduced protonema growth and gametophore initiation, as well as defects in gametophore development. Leafy shoots formed on ΔTEL1 mutants exhibit shorter stems with more leaves per shoot, suggesting an accelerated leaf initiation (shortened plastochron), a phenotype shared with the Poaceae vascular plants TE1 and PLA2/LHD2 mutants. Moreover, the positive correlation between plastochron length and leaf size observed in ΔTEL1 mutants suggests a conserved compensatory mechanism correlating leaf growth and leaf initiation rate that would minimize overall changes in plant biomass. The RNA-binding protein encoded by PpTEL1 contains two N-terminus RNA-recognition motifs, and a third C-terminus non-canonical RRM, specific to TEL proteins. Removal of the PpTEL1 C-terminus (including this third RRM) or only 16-18 amino acids within it seriously impairs PpTEL1 function, suggesting a critical role for this third RRM. These results show a conserved function of the RNA-binding PpTEL1 protein in the regulation of shoot development, from early ancestors to vascular plants, that depends on the third TEL-specific RRM.

  9. Prefrontal and Striatal Glutamate Differently Relate to Striatal Dopamine: Potential Regulatory Mechanisms of Striatal Presynaptic Dopamine Function?

    Science.gov (United States)

    Gleich, Tobias; Deserno, Lorenz; Lorenz, Robert Christian; Boehme, Rebecca; Pankow, Anne; Buchert, Ralph; Kühn, Simone; Heinz, Andreas; Schlagenhauf, Florian; Gallinat, Jürgen

    2015-07-01

    Theoretical and animal work has proposed that prefrontal cortex (PFC) glutamate inhibits dopaminergic inputs to the ventral striatum (VS) indirectly, whereas direct VS glutamatergic afferents have been suggested to enhance dopaminergic inputs to the VS. In the present study, we aimed to investigate relationships of glutamate and dopamine measures in prefrontostriatal circuitries of healthy humans. We hypothesized that PFC and VS glutamate, as well as their balance, are differently associated with VS dopamine. Glutamate concentrations in the left lateral PFC and left striatum were assessed using 3-Tesla proton magnetic resonance spectroscopy. Striatal presynaptic dopamine synthesis capacity was measured by fluorine-18-l-dihydroxyphenylalanine (F-18-FDOPA) positron emission tomography. First, a negative relationship was observed between glutamate concentrations in lateral PFC and VS dopamine synthesis capacity (n = 28). Second, a positive relationship was revealed between striatal glutamate and VS dopamine synthesis capacity (n = 26). Additionally, the intraindividual difference between PFC and striatal glutamate concentrations correlated negatively with VS dopamine synthesis capacity (n = 24). The present results indicate an involvement of a balance in PFC and striatal glutamate in the regulation of VS dopamine synthesis capacity. This notion points toward a potential mechanism how VS presynaptic dopamine levels are kept in a fine-tuned range. A disruption of this mechanism may account for alterations in striatal dopamine turnover as observed in mental diseases (e.g., in schizophrenia). The present work demonstrates complementary relationships between prefrontal and striatal glutamate and ventral striatal presynaptic dopamine using human imaging measures: a negative correlation between prefrontal glutamate and presynaptic dopamine and a positive relationship between striatal glutamate and presynaptic dopamine are revealed. The results may reflect a regulatory role

  10. Multistructure index in revealing complexity of regulatory mechanisms of human cardiovascular system at rest and orthostatic stress in healthy humans

    Science.gov (United States)

    Makowiec, Danuta; Graff, Beata; Struzik, Zbigniew R.

    2017-02-01

    Biological regulation is sufficiently complex to pose an enduring challenge for characterization of both its equilibrium and transient non-equilibrium dynamics. Two univariate but coupled observables, heart rate and systolic blood pressure, are commonly characterized in the benchmark example of the human cardiovascular regulatory system. Asymmetric distributions of accelerations and decelerations of heart rate, as well as rises and falls in systolic blood pressure, recorded in humans during a head-up tilt test provide insights into the dynamics of cardiovascular response to a rapid, controlled deregulation of the system's homeostasis. The baroreflex feedback loop is assumed to be the fundamental physiological mechanism for ensuring homeostatic blood supply to distant organs at rest and during orthostatic stress, captured in a classical beat-to-beat autoregressive model of baroreflex by de Boer et al. (1987). For model corroboration, a multistructure index statistic is proposed, seamlessly evaluating the size spectrum of magnitudes of neural reflexes such as baroreflex, responsible for maintaining the homeostatic dynamics. The multistructure index exposes a distinctly different dynamics of multiscale asymmetry between results obtained from real-life signals recorded from healthy subjects and those simulated using both the classical and perturbed versions of the model. Nonlinear effects observed suggest the pronounced presence of complex mechanisms resulting from baroreflex regulation when a human is at rest, which is aggravated in the system's response to orthostatic stress. Using our methodology of multistructure index, we therefore show a marked difference between model and real-life scenarios, which we attribute to multiscale asymmetry of non-linear origin in real-life signals, which we are not reproducible by the classical model.

  11. Cis and trans regulatory mechanisms control AP2-mediated B cell receptor endocytosis via select tyrosine-based motifs.

    Directory of Open Access Journals (Sweden)

    Kathleen Busman-Sahay

    Full Text Available Following antigen recognition, B cell receptor (BCR-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2 is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding YxxØ motifs, including four that are present within two immunoreceptor tyrosine-based activation motifs (ITAMs. Using a combination of in vitro and in situ approaches, we establish that the sole mediator of AP2-dependent BCR internalization is the membrane proximal ITAM YxxØ motif in CD79b, which is a major target of mutation in ABC DLBCL. In addition, we establish that BCR internalization can be regulated at a minimum of two different levels: regulation of YxxØ AP2 binding in cis by downstream ITAM-embedded DCSM and QTAT regulatory elements and regulation in trans by the partner cytoplasmic domain of the CD79 heterodimer. Beyond establishing the basic rules governing BCR internalization, these results illustrate an underappreciated role for ITAM residues in controlling clathrin-dependent endocytosis and highlight the complex mechanisms that control the activity of AP2 binding motifs in this receptor system.

  12. Regulatory mechanisms that prevent re-initiation of DNA replication can be locally modulated at origins by nearby sequence elements.

    Directory of Open Access Journals (Sweden)

    Christopher D Richardson

    2014-06-01

    Full Text Available Eukaryotic cells must inhibit re-initiation of DNA replication at each of the thousands of origins in their genome because re-initiation can generate genomic alterations with extraordinary frequency. To minimize the probability of re-initiation from so many origins, cells use a battery of regulatory mechanisms that reduce the activity of replication initiation proteins. Given the global nature of these mechanisms, it has been presumed that all origins are inhibited identically. However, origins re-initiate with diverse efficiencies when these mechanisms are disabled, and this diversity cannot be explained by differences in the efficiency or timing of origin initiation during normal S phase replication. This observation raises the possibility of an additional layer of replication control that can differentially regulate re-initiation at distinct origins. We have identified novel genetic elements that are necessary for preferential re-initiation of two origins and sufficient to confer preferential re-initiation on heterologous origins when the control of re-initiation is partially deregulated. The elements do not enhance the S phase timing or efficiency of adjacent origins and thus are specifically acting as re-initiation promoters (RIPs. We have mapped the two RIPs to ∼ 60 bp AT rich sequences that act in a distance- and sequence-dependent manner. During the induction of re-replication, Mcm2-7 reassociates both with origins that preferentially re-initiate and origins that do not, suggesting that the RIP elements can overcome a block to re-initiation imposed after Mcm2-7 associates with origins. Our findings identify a local level of control in the block to re-initiation. This local control creates a complex genomic landscape of re-replication potential that is revealed when global mechanisms preventing re-replication are compromised. Hence, if re-replication does contribute to genomic alterations, as has been speculated for cancer cells, some

  13. Non-Noether Conserved Quantity of Poincaré-Chetaev Equations of a Generalized Classical Mechanics

    Institute of Scientific and Technical Information of China (English)

    ZHANG Peng-Yu; FANG Jian-Hui; WANG Peng; DING Ning

    2006-01-01

    In the present paper the Lie symmetrical non-Noether conserved quantity of the Poincaré-Chetaev equations of a generalized classical mechanics under the general infinitesimal transformations of Lie groups is discussed. First, we establish the determining equations of Lie symmetry of the equations. Second, the Lie symmetrical non-Noether conserved quantity of the equations is deduced. Finally, an example is given to illustrate the application of the results.

  14. A New Conservation Law Derived from Mei Symmetry for the System of Generalized Classical Mechanics

    Institute of Scientific and Technical Information of China (English)

    ZHANGYi

    2004-01-01

    A new conservation theorem derived directly from Mei symmetry of the generalized classical mechanical system is presented. First, the differential equations of motion of the system are established, and the definition and criterion of Mei symmetry for the system of generalized classical mechanics are given, which are based upon the invariance of dynamical functions under irdinitesimal transformations. Second, the condition under which a Mei symmetry can lead to a new conservation law is obtained and the form of the conservation law is presented. And finadly, an example is given to illustrate the application of the results.

  15. A New Conservation Law Derived from Mei Symmetry for the System of Generalized Classical Mechanics

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yi

    2004-01-01

    A new conservation theorem derived directly from Mei symmetry of the generalized classical mechanical system is presented. First, the differential equations of motion of the system are established, and the definition and criterion of Mei symmetry for the system of generalized classical mechanics are given, which are based upon the invariance of dynamical functions under infinitesimal transformations. Second, the condition under which a Mei symmetry can lead to a new conservation law is obtained and the form of the conservation law is presented. And finally, an example is given to illustrate the application of the results.

  16. A Generalized Kawasaki-Type Dynamics with Spin-Pair Redistribution Mechanism

    Institute of Scientific and Technical Information of China (English)

    朱建阳; 朱涵

    2002-01-01

    We generalize Kawasaki's dynamics, spin-pair exchange mechanism, to a spin-pair redistribution mechanism,and we present a normalized redistribution probability. As an application, we treat the one-dimensional kinetic Gaussian model and obtain the exact diffusion equation and the temperature-dependent diffusion coefficient. We find that the diffusion process can slow down infinitely near the critical point and obtain the critical dynamic exponent z = 2 that is independent of the assumed mechanism, either Glauber-type or Kawasaki-type.

  17. The lateral pressure profile in membranes: a physical mechanism of general anesthesia.

    Science.gov (United States)

    Cantor, R S

    1998-11-23

    1. A lipid-mediated mechanism of general anesthesia is suggested and investigated using lattice statistical thermodynamics. 2. Anesthetics are predicted to shift the distribution of lateral pressure within a lipid bilayer, and thus alter the mechanical work required to open ion channel proteins, if channel opening is accompanied by a non-uniform change in cross-sectional area of the protein. 3. Calculations based on this mechanical thermodynamic hypothesis yield qualitative agreement with anesthetic potency at clinical anesthetic membrane concentrations, and predict the alkanol cutoff and anomalously low potencies of strongly hydrophobic molecules with little attraction for the aqueous interface, such as perfluorocarbons.

  18. A general mechanism for intracellular toxicity of metal-containing nanoparticles

    KAUST Repository

    Sabella, Stefania

    2014-04-09

    The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment-where particles are abundantly internalized-is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a "lysosome-enhanced Trojan horse effect" since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments. The Royal Society of Chemistry 2014.

  19. STATISTICAL-MECHANICAL ENTROPY OF THE GENERAL STATIC BLACK HOLE DUE TO ELECTROMAGNETIC FIELD

    Institute of Scientific and Technical Information of China (English)

    JING JI-LIANG; YAN MU-LIN

    2000-01-01

    Statistical-mechanical entropy arising from the electromagnetic field in the general four-dimensional static blackhole spacetime is investigated by means of the "brick wall" model. An expression for the entropy is obtained and some examples are considered. The results show that the entropy arising from the electromagnetic field is exactly twice the one for a massless scalar field.

  20. Speech and music shape the listening brain: Evidence for shared domain-general mechanisms

    NARCIS (Netherlands)

    Asaridou, S.S.; McQueen, J.M.

    2013-01-01

    Are there bi-directional influences between speech perception and music perception? An answer to this question is essential for understanding the extent to which the speech and music that we hear are processed by domain-general auditory processes and/or by distinct neural auditory mechanisms. This r

  1. Speech and music shape the listening brain: Evidence for shared domain-general mechanisms

    NARCIS (Netherlands)

    Asaridou, S.S.; McQueen, J.M.

    2013-01-01

    Are there bi-directional influences between speech perception and music perception? An answer to this question is essential for understanding the extent to which the speech and music that we hear are processed by domain-general auditory processes and/or by distinct neural auditory mechanisms. This r

  2. A general theorem on the transition probabilities of a quantum mechanical system with spatial degeneracy

    NARCIS (Netherlands)

    Tolhoek, H.A.; Groot, S.R. de

    1949-01-01

    In the general case of a quantum mechanical system with a Hamiltonian that is invariant for rotations spatial degeneracy will exist. So the initial state must be characterized except by the energy also by e.g. the magnetic quantum number. Both for emission of light and electrons plus neutrinos (ß-ra

  3. Speech and music shape the listening brain: Evidence for shared domain-general mechanisms

    NARCIS (Netherlands)

    Asaridou, S.S.; McQueen, J.M.

    2013-01-01

    Are there bi-directional influences between speech perception and music perception? An answer to this question is essential for understanding the extent to which the speech and music that we hear are processed by domain-general auditory processes and/or by distinct neural auditory mechanisms. This

  4. Bacillus subtilis as a platform for molecular characterisation of regulatory mechanisms of Enterococcus faecalis resistance against cell wall antibiotics.

    Science.gov (United States)

    Fang, Chong; Stiegeler, Emanuel; Cook, Gregory M; Mascher, Thorsten; Gebhard, Susanne

    2014-01-01

    To combat antibiotic resistance of Enterococcus faecalis, a better understanding of the molecular mechanisms, particularly of antibiotic detection, signal transduction and gene regulation is needed. Because molecular studies in this bacterium can be challenging, we aimed at exploiting the genetically highly tractable Gram-positive model organism Bacillus subtilis as a heterologous host. Two fundamentally different regulators of E. faecalis resistance against cell wall antibiotics, the bacitracin sensor BcrR and the vancomycin-sensing two-component system VanSB-VanRB, were produced in B. subtilis and their functions were monitored using target promoters fused to reporter genes (lacZ and luxABCDE). The bacitracin resistance system BcrR-BcrAB of E. faecalis was fully functional in B. subtilis, both regarding regulation of bcrAB expression and resistance mediated by the transporter BcrAB. Removal of intrinsic bacitracin resistance of B. subtilis increased the sensitivity of the system. The lacZ and luxABCDE reporters were found to both offer sensitive detection of promoter induction on solid media, which is useful for screening of large mutant libraries. The VanSB-VanRB system displayed a gradual dose-response behaviour to vancomycin, but only when produced at low levels in the cell. Taken together, our data show that B. subtilis is a well-suited host for the molecular characterization of regulatory systems controlling resistance against cell wall active compounds in E. faecalis. Importantly, B. subtilis facilitates the careful adjustment of expression levels and genetic background required for full functionality of the introduced regulators.

  5. Bacillus subtilis as a platform for molecular characterisation of regulatory mechanisms of Enterococcus faecalis resistance against cell wall antibiotics.

    Directory of Open Access Journals (Sweden)

    Chong Fang

    Full Text Available To combat antibiotic resistance of Enterococcus faecalis, a better understanding of the molecular mechanisms, particularly of antibiotic detection, signal transduction and gene regulation is needed. Because molecular studies in this bacterium can be challenging, we aimed at exploiting the genetically highly tractable Gram-positive model organism Bacillus subtilis as a heterologous host. Two fundamentally different regulators of E. faecalis resistance against cell wall antibiotics, the bacitracin sensor BcrR and the vancomycin-sensing two-component system VanSB-VanRB, were produced in B. subtilis and their functions were monitored using target promoters fused to reporter genes (lacZ and luxABCDE. The bacitracin resistance system BcrR-BcrAB of E. faecalis was fully functional in B. subtilis, both regarding regulation of bcrAB expression and resistance mediated by the transporter BcrAB. Removal of intrinsic bacitracin resistance of B. subtilis increased the sensitivity of the system. The lacZ and luxABCDE reporters were found to both offer sensitive detection of promoter induction on solid media, which is useful for screening of large mutant libraries. The VanSB-VanRB system displayed a gradual dose-response behaviour to vancomycin, but only when produced at low levels in the cell. Taken together, our data show that B. subtilis is a well-suited host for the molecular characterization of regulatory systems controlling resistance against cell wall active compounds in E. faecalis. Importantly, B. subtilis facilitates the careful adjustment of expression levels and genetic background required for full functionality of the introduced regulators.

  6. Review: Regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH synthesis and release in photoperiodic animals

    Directory of Open Access Journals (Sweden)

    Kazuyoshi eTsutsui

    2013-04-01

    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R, GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin and glucocorticoids, to control avian and mammalian reproduction.

  7. Functional Analysis of In-frame Indel ARID1A Mutations Reveals New Regulatory Mechanisms of Its Tumor Suppressor Functions

    Directory of Open Access Journals (Sweden)

    Bin Guan

    2012-10-01

    Full Text Available AT-rich interactive domain 1A (ARID1A has emerged as a new tumor suppressor in which frequent somatic mutations have been identified in several types of human cancers. Although most ARID1A somatic mutations are frame-shift or nonsense mutations that contribute to mRNA decay and loss of protein expression, 5% of ARID1A mutations are in-frame insertions or deletions (indels that involve only a small stretch of peptides. Naturally occurring in-frame indel mutations provide unique and useful models to explore the biology and regulatory role of ARID1A. In this study, we analyzed indel mutations identified in gynecological cancers to determine how these mutations affect the tumor suppressor function of ARID1A. Our results demonstrate that all in-frame mutants analyzed lost their ability to inhibit cellular proliferation or activate transcription of CDKN1A, which encodes p21, a downstream effector of ARID1A. We also showed that ARID1A is a nucleocytoplasmic protein whose stability depends on its subcellular localization. Nuclear ARID1A is less stable than cytoplasmic ARID1A because ARID1A is rapidly degraded by the ubiquitin-proteasome system in the nucleus. In-frame deletions affecting the consensus nuclear export signal reduce steady-state protein levels of ARID1A. This defect in nuclear exportation leads to nuclear retention and subsequent degradation. Our findings delineate a mechanism underlying the regulation of ARID1A subcellular distribution and protein stability and suggest that targeting the nuclear ubiquitin-proteasome system can increase the amount of the ARID1A protein in the nucleus and restore its tumor suppressor functions.

  8. Regulatory mechanism of pyrrolidine dithiocarbamate is mediated by nuclear factor-κB and inhibits neutrophil accumulation in ARDS mice.

    Science.gov (United States)

    Wang, Hongman; Xu, Lisheng; Zhao, Jiping; Wang, Donghui; Guo, Ranran; Wang, Junfei; Gong, Wenbin; Liu, Tian; Zhang, Yuanyuan; Dong, Liang

    2014-08-01

    The aim of the present study was to investigate the regulatory mechanism of nuclear factor (NF)-κB on polymorphonuclear neutrophil (PMN) accumulation and the inflammatory response in lung tissues with acute respiratory distress syndrome (ARDS), as well as the therapeutic effect of pyrrolidine dithiocarbamate (PDTC). Mouse models of ARDS were established by intraperitoneal injection of lipopolysaccharide (LPS). BALB/c mice were divided into control, LPS and PDTC + LPS groups. The expression of PMN adhesion molecules, CD11b/CD18 and intercellular adhesion molecule-1 (ICAM-1), were detected by immunohistochemistry, while the protein expression levels of NF-κB p65 in the lung tissue were analyzed by western blot analysis. In addition, flow cytometry was used to investigate the apoptosis rate of PMNs in the bronchoalveolar fluid, and the expression levels of interleukin (IL)-1β, IL-8 and tumor necrosis factor (TNF)-α and myeloperoxidase (MPO) activity were also determined. Following an intraperitoneal injection of LPS, alveolar septum rupture, pulmonary interstitial hyperemia and PMN infiltration in the alveolar was observed. The protein expression of p65 in the pulmonary cytoplasm decreased, while the expression of p65 in the nucleus increased. The levels of IL-8, IL-1β and TNF-α increased and the high expression status was maintained for 24 h. As the time increased, CD11b/CD18 and ICAM-1 expression increased, as well as MPO activity, while the apoptosis of PMNs was delayed. Compared with the LPS group, the expression of p65 in the pulmonary cytoplasm and the PMN apoptosis rate increased following PDTC intervention, while the expression of p65 in the nucleus decreased, as well as the expression levels of the cytokines and MPO activity. Therefore, PDTC reduced the production of inflammatory cytokines via the NF-κB pathway, which reduced the activation of PMNs in the lung tissue and promoted PMN apoptosis.

  9. Regulation of the CDP-choline pathway by sterol regulatory element binding proteins involves transcriptional and post-transcriptional mechanisms.

    Science.gov (United States)

    Ridgway, Neale D; Lagace, Thomas A

    2003-06-15

    The synthesis of phosphatidylcholine (PtdCho) by the CDP-choline pathway is under the control of the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CCT). Sterol regulatory element binding proteins (SREBPs) have been proposed to regulate CCT at the transcriptional level, or via the synthesis of lipid activators or substrates of the CDP-choline pathway. To assess the contributions of these two mechanisms, we examined CCTalpha expression and PtdCho synthesis by the CDP-choline pathway in cholesterol and fatty acid auxotrophic CHO M19 cells inducibly expressing constitutively active nuclear forms of SREBP1a or SREBP2. Induction of either SREBP resulted in increased expression of mRNAs for sterol-regulated genes, elevated fatty acid and cholesterol synthesis (>10-50-fold) and increased PtdCho synthesis (2-fold). CCTalpha mRNA was increased 2-fold by enforced expression of SREBP1a or SREBP2. The resultant increase in CCTalpha protein and activity (2-fold) was restricted primarily to the soluble fraction of cells, and increased CCTalpha activity in vivo was not detected. Inhibition of the synthesis of fatty acids or their CoA esters by cerulenin or triacsin C respectively following SREBP induction effectively blocked the accompanying elevation in PtdCho synthesis. Thus PtdCho synthesis was driven by increased synthesis of fatty acids or a product thereof. These data show that transcriptional activation of CCTalpha is modest relative to that of other SREBP-regulated genes, and that stimulation of PtdCho synthesis by SREBPs in CHO cells is due primarily to increased fatty acid synthesis.

  10. Modeling of hysteresis in gene regulatory networks.

    Science.gov (United States)

    Hu, J; Qin, K R; Xiang, C; Lee, T H

    2012-08-01

    Hysteresis, observed in many gene regulatory networks, has a pivotal impact on biological systems, which enhances the robustness of cell functions. In this paper, a general model is proposed to describe the hysteretic gene regulatory network by combining the hysteresis component and the transient dynamics. The Bouc-Wen hysteresis model is modified to describe the hysteresis component in the mammalian gene regulatory networks. Rigorous mathematical analysis on the dynamical properties of the model is presented to ensure the bounded-input-bounded-output (BIBO) stability and demonstrates that the original Bouc-Wen model can only generate a clockwise hysteresis loop while the modified model can describe both clockwise and counter clockwise hysteresis loops. Simulation studies have shown that the hysteresis loops from our model are consistent with the experimental observations in three mammalian gene regulatory networks and two E.coli gene regulatory networks, which demonstrate the ability and accuracy of the mathematical model to emulate natural gene expression behavior with hysteresis. A comparison study has also been conducted to show that this model fits the experiment data significantly better than previous ones in the literature. The successful modeling of the hysteresis in all the five hysteretic gene regulatory networks suggests that the new model has the potential to be a unified framework for modeling hysteresis in gene regulatory networks and provide better understanding of the general mechanism that drives the hysteretic function.

  11. Regulatory mechanisms for abnormal expression of the human breast cancer specific gene 1 in breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    LU; Aiping; LI; Qing; LIU; Jingwen

    2006-01-01

    Breast cancer-specific gene 1 (BCSG1), also referred as synuclein γ, was originally isolated from a human breast cancer cDNA library and the protein is mainly localized to presynaptic terminals in the nervous system. BCSG1 is not expressed in normal or benign breast lesions, but expressed at an extremely high level in the vast majority of the advanced staged breast carcinomas and ovarian carcinomas. Overexpression of BCSG1 in cancer cells led to significant increase in cell proliferation, motility and invasiveness, and metastasis. To elucidate the molecular mechanism and regulation for abnormal transcription of BCSG1, a variety of BCSG1 promoter luciferase reporters were constructed including 3' end deleted sequences, Sp1 deleted, and activator protein-1 (AP1) domains mutated. Transient transfection assay was used to detect the transcriptional activation of BCSG1 promoters. Results showed that the Sp1 sequence in 5'-flanking region was involved in the basal transcriptional activities of BCSG1 without cell-type specificity. In comparison to pGL3-1249, the reporter activities of pGL3-1553 in BCSG1-negative MCF-7 cells and pGL3-1759 in HepG2 cells were notably decreased. Mutations at AP1 sites in BCSG1 intron 1 significantly reduced the promoter activity in all cell lines. Transcription factors, c-jun, c-fos and cyclin AMP-responsive element binding (CREB) protein, could markedly enhance the promoter activities. Thus, our results suggest that the abnormal expression of BCSG1 in breast cancer cells is likely regulated by multiple mechanisms. The 5' flanking region of BCSG1 provides the basal transcriptional activity without cell type specificity. A critical promoter element involved in abnormal expression of BCSG1 presents in the first exon. The cell type specificity of BCSG1 transcription is probably affected through intronic cis-regulatory sequences. AP1 domains in the first intron play an important role in control of BCSG1 transcription.

  12. To Gate, or Not to Gate: Regulatory Mechanisms for Intercellular Protein Transport and Virus Movement in Plants

    Institute of Scientific and Technical Information of China (English)

    Shoko Ueki; Vitaly Citovsky

    2011-01-01

    Cell-to-cell signal transduction is vital for orchestrating the whole-body physiology of multi-cellular organisms,and many endogenous macromolecules,proteins,and nucleic acids function as such transported signals.In plants,many of these molecules are transported through plasmodesmata (Pd),the cell wall-spanning channel structures that interconnect plant cells.Furthermore,Pd also act as conduits for cell-to-cell movement of most plant viruses that have evolved to pirate these channels to spread the infection.Pd transport is presumed to be highly selective,and only a limited repertoire of molecules is transported through these channels.Recent studies have begun to unravel mechanisms that actively regulate the opening of the Pd channel to allow traffic.This macromolecular transport between cells comprises two consecutive steps:intracellular targeting to Pd and translocation through the channel to the adjacent cell.Here,we review the current knowledge of molecular species that are transported though Pd and the mechanisms that control this traffic.Generally,Pd traffic can occur by passive diffusion through the trans-Pd cytoplasm or through the membrane/lumen of the trans-Pd ER,or by active transport that includes protein-protein interactions.It is this latter mode of Pd transport that is involved in intercellular traffic of most signal molecules and is regulated by distinct and sometimes interdependent mechanisms,which represent the focus of this article.

  13. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  14. A general methodology for mobility analysis of mechanisms based on constraint screw theory

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    It is well known that the traditional Grübler-Kutzbach formula fails to calculate the mobility of some classical mechanisms or many modern parallel robots,and this situation seriously hampers mechani-cal innovation.To seek an efficient and universal method for mobility calculation has been a heated topic in the sphere of mechanism.The modified Grübler-Kutzbach criterion proposed by us achieved success in calculating the mobility of a lot of highly complicated mechanisms,especially the mobility of all recent parallel mechanisms listed by Gogu,and the Bennett mechanism known for its particular difficulty.With wide applications of the criterion,a systematic methodology has recently formed.This paper systematically presents the methodology based on the screw theory for the first time and ana-lyzes six representative puzzling mechanisms.In addition,the methodology is convenient for judgment of the instantaneous or full-cycle mobility,and has become an effective and general method of great scientific value and practical significance.In the first half,this paper introduces the basic screw theory,then it presents the effective methodology formed within this decade.The second half of this paper presents how to apply the methodology by analyzing the mobility of several puzzling mechanisms.Finally,this paper contrasts and analyzes some different methods and interprets the essential reason for validity of our methodology.

  15. A general methodology for mobility analysis of mechanisms based on constraint screw theory

    Institute of Scientific and Technical Information of China (English)

    HUANG Zhen; LIU JingFang; ZENG DaXing

    2009-01-01

    It is well known that the traditional Grubler-Kutzbach formula fails to calculate the mobility of some classical mechanisms or many modern parallel robots, and this situation seriously hampers mechani-cal innovation. To seek an efficient and universal method for mobility calculation has been a heated topic in the sphere of mechanism. The modified Grubler-Kutzbach criterion proposed by us achieved success in calculating the mobility of a lot of highly complicated mechanisms, especially the mobility of all recent parallel mechanisms listed by Gogu, and the Bennett mechanism known for its particular difficulty. With wide applications of the criterion, a systematic methodology has recently formed. This paper systematically presents the methodology based on the screw theory for the first time and ana-lyzes six representative puzzling mechanisms. In addition, the methodology is convenient for judgment of the instantaneous or full-cycle mobility, and has become an effective and general method of great scientific value and practical significance. In the first half, this paper introduces the basic screw theory,then it presents the effective methodology formed within this decade. The second half of this paperpresents how to apply the methodology by analyzing the mobility of several puzzling mechanisms.Finally, this paper contrasts and analyzes some different methods and interprets the essential reason for validity of our methodology.

  16. Mathematica® for Theoretical Physics Electrodynamics, Quantum Mechanics, General Relativity and Fractals

    CERN Document Server

    Baumann, Gerd

    2005-01-01

    Mathematica for Theoretical Physics: Electrodynamics, Quantum Mechanics, General Relativity, and Fractals This second edition of Baumann's Mathematica® in Theoretical Physics shows readers how to solve physical problems and deal with their underlying theoretical concepts while using Mathematica® to derive numeric and symbolic solutions. Each example and calculation can be evaluated by the reader, and the reader can change the example calculations and adopt the given code to related or similar problems. The second edition has been completely revised and expanded into two volumes: The first volume covers classical mechanics and nonlinear dynamics. Both topics are the basis of a regular mechanics course. The second volume covers electrodynamics, quantum mechanics, relativity, and fractals and fractional calculus. New examples have been added and the representation has been reworked to provide a more interactive problem-solving presentation. This book can be used as a textbook or as a reference work, by student...

  17. General N=2 supersymmetric quantum mechanical model: Supervariable approach to its off-shell nilpotent symmetries

    Energy Technology Data Exchange (ETDEWEB)

    Krishna, S., E-mail: skrishna.bhu@gmail.com [Physics Department, Centre of Advanced Studies, Banaras Hindu University (BHU), Varanasi-221 005 (India); Shukla, A., E-mail: ashukla038@gmail.com [Physics Department, Centre of Advanced Studies, Banaras Hindu University (BHU), Varanasi-221 005 (India); Malik, R.P., E-mail: rpmalik1995@gmail.com [Physics Department, Centre of Advanced Studies, Banaras Hindu University (BHU), Varanasi-221 005 (India); DST-CIMS, Faculty of Science, BHU-Varanasi-221 005 (India)

    2014-12-15

    Using the supersymmetric (SUSY) invariant restrictions on the (anti-)chiral supervariables, we derive the off-shell nilpotent symmetries of the general one (0+1)-dimensional N=2 SUSY quantum mechanical (QM) model which is considered on a (1, 2)-dimensional supermanifold (parametrized by a bosonic variable t and a pair of Grassmannian variables θ and θ-bar with θ{sup 2}=(θ-bar){sup 2}=0,θ(θ-bar)+(θ-bar)θ=0). We provide the geometrical meanings to the two SUSY transformations of our present theory which are valid for any arbitrary type of superpotential. We express the conserved charges and Lagrangian of the theory in terms of the supervariables (that are obtained after the application of SUSY invariant restrictions) and provide the geometrical interpretation for the nilpotency property and SUSY invariance of the Lagrangian for the general N=2 SUSY quantum theory. We also comment on the mathematical interpretation of the above symmetry transformations. - Highlights: • A novel method has been proposed for the derivation of N=2 SUSY transformations. • General N=2 SUSY quantum mechanical (QM) model with a general superpotential, is considered. • The above SUSY QM model is generalized onto a (1, 2)-dimensional supermanifold. • SUSY invariant restrictions are imposed on the (anti-)chiral supervariables. • Geometrical meaning of the nilpotency property is provided.

  18. Probing the chemical mechanism and critical regulatory amino acid residues of Drosophila melanogaster arylalkylamine N-acyltransferase like 2.

    Science.gov (United States)

    Dempsey, Daniel R; Carpenter, Anne-Marie; Ospina, Santiago Rodriguez; Merkler, David J

    2015-11-01

    Arylalkylamine N-acyltransferase like 2 (AANATL2) catalyzes the formation of N-acylarylalkylamides from the corresponding acyl-CoA and arylalkylamine. The N-acylation of biogenic amines in Drosophila melanogaster is a critical step for the inactivation of neurotransmitters, cuticle sclerotization, and melatonin biosynthesis. In addition, D. melanogaster has been used as a model system to evaluate the biosynthesis of fatty acid amides: a family of potent cell signaling lipids. We have previously showed that AANATL2 catalyzes the formation of N-acylarylakylamides, including long-chain N-acylserotonins and N-acyldopamines. Herein, we define the kinetic mechanism for AANATL2 as an ordered sequential mechanism with acetyl-CoA binding first followed by tyramine to generate the ternary complex prior to catalysis. Bell shaped kcat,app - acetyl-CoA and (kcat/Km)app - acetyl-CoA pH-rate profiles identified two apparent pKa,app values of ∼7.4 and ∼8.9 that are critical to catalysis, suggesting the AANATL2-catalyzed formation of N-acetyltyramine occurs through an acid/base chemical mechanism. Site-directed mutagenesis of a conserved glutamate that corresponds to the catalytic base for other D. melanogaster AANATL enzymes did not produce a substantial depression in the kcat,app value nor did it abolish the pKa,app value attributed to the general base in catalysis (pKa ∼7.4). These data suggest that AANATL2 catalyzes the formation of N-acylarylalkylamides using either different catalytic residues or a different chemical mechanism relative to other D. melanogaster AANATL enzymes. In addition, we constructed other site-directed mutants of AANATL2 to help define the role of targeted amino acids in substrate binding and/or enzyme catalysis.

  19. Disturbance due to mechanical and thermal sources in a generalized thermo-microstretch elastic half space

    Indian Academy of Sciences (India)

    Rajneesh Kumar; Sunita Deswal

    2001-12-01

    Disturbances caused by impulsive concentrated mechanical and thermal sources in a homogeneous, isotropic generalized thermo-microstretch elastic medium are studied by the use of Laplace-Hankel transform techniques. The integral transforms are inverted using a numerical technique. Analytical expressions for displacement components, stress, couple stress, microstress and temperature field are derived for different models of generalized thermoelasticity and illustrated graphically. These results for stresses and displacements can be used in estimating the effects of a surface pressure wave. Stretch and micropolar effects on various expressions obtained analytically are also depicted graphically.

  20. Over-constraint and a unified mobility method for general spatial mechanisms part 1: Essential principle

    Science.gov (United States)

    Zeng, Daxing; Lu, Wenjuan; Huang, Zhen

    2015-09-01

    Compared with the parallel mechanisms, the mobility analysis of the general multi-loop spatial mechanisms(GMSMs) is more difficult to obtain correct results. The reason is that its multi-loop is formed through several times of closings and there also exists motion coupling even strong coupling, where the over-constraints are concealed. However, the mobility analysis for this kind of mechanisms has been paid few attentions. A new systemic methodology for analyzing mobility is proposed for GMSMs also based on the screw theory. The key issue for mobility analysis is to recognize the over-constraint. Firstly, three theorems are given and point out: the reason and site of over-constraint occurrence, calculating the number of over-constraints by the screw theory, and how to analyze the over-constraints for a single-loop mechanism as well. Then, three closing forms for GMSMs are proposed including rigid closure, movable closure and dynamic closure, and for the three different forms the different analysis methods are also given. Especially, for the most difficult issue of GMSMs with the multi-loop closure in many times and the inevitable motion coupling, two important methods are proposed: "recognizing over-constraints by analyzing relative movement" and "recognizing over-constraints by virtual loop". The two methods are well used to solve the issue. Above-mentioned principles are not only systematic and effective but also unified. They provide a theoretical basis for the general multi-loop spatial mechanisms.

  1. A general mechanism for intracellular toxicity of metal-containing nanoparticles

    Science.gov (United States)

    Sabella, Stefania; Carney, Randy P.; Brunetti, Virgilio; Malvindi, Maria Ada; Al-Juffali, Noura; Vecchio, Giuseppe; Janes, Sam M.; Bakr, Osman M.; Cingolani, Roberto; Stellacci, Francesco; Pompa, Pier Paolo

    2014-05-01

    The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment - where particles are abundantly internalized - is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a ``lysosome-enhanced Trojan horse effect'' since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments.The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment - where

  2. Hamiltonian formulation of generalized quantum dynamics——Quantum mechanical problem

    Institute of Scientific and Technical Information of China (English)

    吴宁; 阮图南

    1997-01-01

    The Hamiltonian formulation of the usual complex quantum mechanics in the theory of generalized quantum dynamics is discussed. After the total trace Lagrangian, total trace Hamiltonian and two kinds of Poisson brackets are introduced, both the equations of motion of some total trace functionals which are expressed by total trace Poisson brackets and the equations of motion of some operators which are expressed by the without-total-trace Poisson brackets are obtained. Then a set of basic equations of motion of the usual complex quantum mechanics are obtained, which are also expressed by the Poisson brackets and total trace Hamiltonian in the generalized quantum dynamics. The set of equations of motion are consistent with the corresponding Heisenberg equations.

  3. General Formula for the Efficiency of Quantum-Mechanical Analog of the Carnot Engine

    Directory of Open Access Journals (Sweden)

    Sumiyoshi Abe

    2013-04-01

    Full Text Available An analog of the Carnot engine reversibly operating within the framework of pure-state quantum mechanics is discussed. A general formula is derived for the efficiency of such an engine with an arbitrary confining potential. Its expression is given in terms of an energy spectrum and shows how the efficiency depends on a potential as the analog of a working material in thermodynamics, in general. This non-universal nature results from the fact that there exists no analog of the second law of thermodynamics in pure-state quantum mechanics where the von Neumann entropy identically vanishes. A special class of spectra, which leads to a common form of the efficiency, is identified.

  4. Kinetic behavior of the general modifier mechanism of Botts and Morales with non-equilibrium binding

    CERN Document Server

    Jia, Chen; Qian, Min-Ping; Jiang, Da-Quan; Zhang, Yu-Ping

    2010-01-01

    In this paper, we thoroughly investigate the kinetic behavior of the general modifier mechanism of Botts and Morales at both equilibrium steady state assuming equilibrium substrate- and modifier-binding steps and non-equilibrium steady state (NESS) without assuming equilibrium binding steps. We introduce the net flux into discussion and propose a method which gains a strong advantage over early approaches involving King-Atman method and even the numerical computations in dealing with the cyclic reaction systems. Using this new approach, the expression of product rate at NESS gives clear biophysical significance. Moreover, we classify the kinetic behavior of the modifier into three categories, namely hyperbolic behavior, bell-shaped behavior, and switching behavior. It turns out that a modifier cannot be regarded as overall activator or inhibitor when the reaction system is not at equilibrium. The switching-behaved modifier may convert between activator and inhibitor via the general modifier mechanism when the...

  5. Contrasting evolutionary dynamics of the developmental regulator PAX9, among bats, with evidence for a novel post-transcriptional regulatory mechanism.

    Directory of Open Access Journals (Sweden)

    Caleb D Phillips

    Full Text Available Morphological evolution can be the result of natural selection favoring modification of developmental signaling pathways. However, little is known about the genetic basis of such phenotypic diversity. Understanding these mechanisms is difficult for numerous reasons, yet studies in model organisms often provide clues about the major developmental pathways involved. The paired-domain gene, PAX9, is known to be a key regulator of development, particularly of the face and teeth. In this study, using a comparative genetics approach, we investigate PAX9 molecular evolution among mammals, focusing on craniofacially diversified (Phyllostomidae and conserved (Vespertilionidae bat families, and extend our comparison to other orders of mammal. Open-reading frame analysis disclosed signatures of selection, in which a small percentage of residues vary, and lineages acquire different combinations of variation through recurrent substitution and lineage specific changes. A few instances of convergence for specific residues were observed between morphologically convergent bat lineages. Bioinformatic analysis for unknown PAX9 regulatory motifs indicated a novel post-transcriptional regulatory mechanism involving a Musashi protein. This regulation was assessed through fluorescent reporter assays and gene knockdowns. Results are compatible with the hypothesis that the number of Musashi binding-elements in PAX9 mRNA proportionally regulates protein translation rate. Although a connection between morphology and binding element frequency was not apparent, results indicate this regulation would vary among craniofacially divergent bat species, but be static among conserved species. Under this model, Musashi's regulatory control of alternative human PAX9 isoforms would also vary. The presence of Musashi-binding elements within PAX9 of all mammals examined, chicken, zebrafish, and the fly homolog of PAX9, indicates this regulatory mechanism is ancient, originating basal

  6. Perturbation to Lie Symmetry and Adiabatic Invariants for General Holonomic Mechanical Systems

    Institute of Scientific and Technical Information of China (English)

    DING Ning; FANG Jian-Hui; WANG Peng; ZHANG Xiao-Ni

    2007-01-01

    Based on the concept of adiabatic invariant, the perturbation to the Lie symmetry and adiabatic invariants for general holonomic mechanical systems are studied. The exact invariants induced directly from the Lie symmetry of the system without perturbation are given. The perturbation to the Lie symmetry is discussed and the adiabatic invariants that have the different form from that in [Act. Phys. Sin. 55 (2006) 3236 (in Chinese)] of the perturbed system, are obtained.

  7. Nonlinear generalized functions and nonlinear numerical simulations in fluid and solid continuum mechanics

    OpenAIRE

    Colombeau, J. F.

    2007-01-01

    We present numerical techniques based on generalized functions adapted to nonlinear calculations. They concern main numerical engineering problems ruled by-or issued from-nonlinear equations of continuum mechanics. The aim of this text is to invite the readers in applying these techniques in their own work without significant prerequisites by presenting their use on a sample of elementary applications from engineering. Pure mathematicians can read it easily since the numerical techniques are ...

  8. Neural mechanisms supporting the extraction of general knowledge across episodic memories.

    Science.gov (United States)

    Sweegers, Carly C G; Takashima, Atsuko; Fernández, Guillén; Talamini, Lucia M

    2014-02-15

    General knowledge acquisition entails the extraction of statistical regularities from the environment. At high levels of complexity, this may involve the extraction, and consolidation, of associative regularities across event memories. The underlying neural mechanisms would likely involve a hippocampo-neocortical dialog, as proposed previously for system-level consolidation. To test these hypotheses, we assessed possible differences in consolidation between associative memories containing cross-episodic regularities and unique associative memories. Subjects learned face-location associations, half of which responded to complex regularities regarding the combination of facial features and locations, whereas the other half did not. Importantly, regularities could only be extracted over hippocampus-encoded, associative aspects of the items. Memory was assessed both immediately after encoding and 48 h later, under fMRI acquisition. Our results suggest that processes related to system-level reorganization occur preferentially for regular associations across episodes. Moreover, the build-up of general knowledge regarding regular associations appears to involve the coordinated activity of the hippocampus and mediofrontal regions. The putative cross-talk between these two regions might support a mechanism for regularity extraction. These findings suggest that the consolidation of cross-episodic regularities may be a key mechanism underlying general knowledge acquisition.

  9. Boron Stress Activates the General Amino Acid Control Mechanism and Inhibits Protein Synthesis

    Science.gov (United States)

    Uluisik, Irem; Kaya, Alaattin; Fomenko, Dmitri E.; Karakaya, Huseyin C.; Carlson, Bradley A.; Gladyshev, Vadim N.; Koc, Ahmet

    2011-01-01

    Boron is an essential micronutrient for plants, and it is beneficial for animals. However, at high concentrations boron is toxic to cells although the mechanism of this toxicity is not known. Atr1 has recently been identified as a boron efflux pump whose expression is upregulated in response to boron treatment. Here, we found that the expression of ATR1 is associated with expression of genes involved in amino acid biosynthesis. These mechanisms are strictly controlled by the transcription factor Gcn4 in response to boron treatment. Further analyses have shown that boron impaired protein synthesis by promoting phosphorylation of eIF2α in a Gcn2 kinase dependent manner. The uncharged tRNA binding domain (HisRS) of Gcn2 is necessary for the phosphorylation of eIF2α in the presence of boron. We postulate that boron exerts its toxic effect through activation of the general amino acid control system and inhibition of protein synthesis. Since the general amino acid control pathway is conserved among eukaryotes, this mechanism of boron toxicity may be of general importance. PMID:22114689

  10. Boron stress activates the general amino acid control mechanism and inhibits protein synthesis.

    Directory of Open Access Journals (Sweden)

    Irem Uluisik

    Full Text Available Boron is an essential micronutrient for plants, and it is beneficial for animals. However, at high concentrations boron is toxic to cells although the mechanism of this toxicity is not known. Atr1 has recently been identified as a boron efflux pump whose expression is upregulated in response to boron treatment. Here, we found that the expression of ATR1 is associated with expression of genes involved in amino acid biosynthesis. These mechanisms are strictly controlled by the transcription factor Gcn4 in response to boron treatment. Further analyses have shown that boron impaired protein synthesis by promoting phosphorylation of eIF2α in a Gcn2 kinase dependent manner. The uncharged tRNA binding domain (HisRS of Gcn2 is necessary for the phosphorylation of eIF2α in the presence of boron. We postulate that boron exerts its toxic effect through activation of the general amino acid control system and inhibition of protein synthesis. Since the general amino acid control pathway is conserved among eukaryotes, this mechanism of boron toxicity may be of general importance.

  11. Communication: Maximum caliber is a general variational principle for nonequilibrium statistical mechanics.

    Science.gov (United States)

    Hazoglou, Michael J; Walther, Valentin; Dixit, Purushottam D; Dill, Ken A

    2015-08-07

    There has been interest in finding a general variational principle for non-equilibrium statistical mechanics. We give evidence that Maximum Caliber (Max Cal) is such a principle. Max Cal, a variant of maximum entropy, predicts dynamical distribution functions by maximizing a path entropy subject to dynamical constraints, such as average fluxes. We first show that Max Cal leads to standard near-equilibrium results—including the Green-Kubo relations, Onsager's reciprocal relations of coupled flows, and Prigogine's principle of minimum entropy production—in a way that is particularly simple. We develop some generalizations of the Onsager and Prigogine results that apply arbitrarily far from equilibrium. Because Max Cal does not require any notion of "local equilibrium," or any notion of entropy dissipation, or temperature, or even any restriction to material physics, it is more general than many traditional approaches. It also applicable to flows and traffic on networks, for example.

  12. Multidimensional Generalized Functions in Aeroacoustics and Fluid Mechanics. Part 1; Basic Concepts and Operations

    Science.gov (United States)

    Farassat, Fereidoun; Myers, Michael K.

    2011-01-01

    This paper is the first part of a three part tutorial on multidimensional generalized functions (GFs) and their applications in aeroacoustics and fluid mechanics. The subject is highly fascinating and essential in many areas of science and, in particular, wave propagation problems. In this tutorial, we strive to present rigorously and clearly the basic concepts and the tools that are needed to use GFs in applications effectively and with ease. We give many examples to help the readers in understanding the mathematical ideas presented here. The first part of the tutorial is on the basic concepts of GFs. Here we define GFs, their properties and some common operations on them. We define the important concept of generalized differentiation and then give some interesting elementary and advanced examples on Green's functions and wave propagation problems. Here, the analytic power of GFs in applications is demonstrated with ease and elegance. Part 2 of this tutorial is on the diverse applications of generalized derivatives (GDs). Part 3 is on generalized Fourier transformations and some more advanced topics. One goal of writing this tutorial is to convince readers that, because of their powerful operational properties, GFs are absolutely essential and useful in engineering and physics, particularly in aeroacoustics and fluid mechanics.

  13. Distinct regulatory mechanisms of the human ferritin gene by hypoxia and hypoxia mimetic cobalt chloride at the transcriptional and post-transcriptional levels.

    Science.gov (United States)

    Huang, Bo-Wen; Miyazawa, Masaki; Tsuji, Yoshiaki

    2014-12-01

    Cobalt chloride has been used as a hypoxia mimetic because it stabilizes hypoxia inducible factor-1α (HIF1-α) and activates gene transcription through a hypoxia responsive element (HRE). However, differences between hypoxia and hypoxia mimetic cobalt chloride in gene regulation remain elusive. Expression of ferritin, the major iron storage protein, is regulated at the transcriptional and posttranscriptional levels through DNA and RNA regulatory elements. Here we demonstrate that hypoxia and cobalt chloride regulate ferritin heavy chain (ferritin H) expression by two distinct mechanisms. Both hypoxia and cobalt chloride increased HIF1-α but a putative HRE in the human ferritin H gene was not activated. Instead, cobalt chloride but not hypoxia activated ferritin H transcription through an antioxidant responsive element (ARE), to which Nrf2 was recruited. Intriguingly, cobalt chloride downregulated ferritin H protein expression while it upregulated other ARE-regulated antioxidant genes in K562 cells. Further characterization demonstrated that cobalt chloride increased interaction between iron regulatory proteins (IRP1 and IRP2) and iron responsive element (IRE) in the 5'UTR of ferritin H mRNA, resulting in translational block of the accumulated ferritin H mRNA. In contrast, hypoxia had marginal effect on ferritin H transcription but increased its translation through decreased IRP1-IRE interaction. These results suggest that hypoxia and hypoxia mimetic cobalt chloride employ distinct regulatory mechanisms through the interplay between DNA and mRNA elements at the transcriptional and post-transcriptional levels.

  14. Folding to Curved Surfaces: A Generalized Design Method and Mechanics of Origami-based Cylindrical Structures

    Science.gov (United States)

    Wang, Fei; Gong, Haoran; Chen, Xi; Chen, C. Q.

    2016-01-01

    Origami structures enrich the field of mechanical metamaterials with the ability to convert morphologically and systematically between two-dimensional (2D) thin sheets and three-dimensional (3D) spatial structures. In this study, an in-plane design method is proposed to approximate curved surfaces of interest with generalized Miura-ori units. Using this method, two combination types of crease lines are unified in one reprogrammable procedure, generating multiple types of cylindrical structures. Structural completeness conditions of the finite-thickness counterparts to the two types are also proposed. As an example of the design method, the kinematics and elastic properties of an origami-based circular cylindrical shell are analysed. The concept of Poisson’s ratio is extended to the cylindrical structures, demonstrating their auxetic property. An analytical model of rigid plates linked by elastic hinges, consistent with numerical simulations, is employed to describe the mechanical response of the structures. Under particular load patterns, the circular shells display novel mechanical behaviour such as snap-through and limiting folding positions. By analysing the geometry and mechanics of the origami structures, we extend the design space of mechanical metamaterials and provide a basis for their practical applications in science and engineering. PMID:27624892

  15. Folding to Curved Surfaces: A Generalized Design Method and Mechanics of Origami-based Cylindrical Structures

    Science.gov (United States)

    Wang, Fei; Gong, Haoran; Chen, Xi; Chen, C. Q.

    2016-09-01

    Origami structures enrich the field of mechanical metamaterials with the ability to convert morphologically and systematically between two-dimensional (2D) thin sheets and three-dimensional (3D) spatial structures. In this study, an in-plane design method is proposed to approximate curved surfaces of interest with generalized Miura-ori units. Using this method, two combination types of crease lines are unified in one reprogrammable procedure, generating multiple types of cylindrical structures. Structural completeness conditions of the finite-thickness counterparts to the two types are also proposed. As an example of the design method, the kinematics and elastic properties of an origami-based circular cylindrical shell are analysed. The concept of Poisson’s ratio is extended to the cylindrical structures, demonstrating their auxetic property. An analytical model of rigid plates linked by elastic hinges, consistent with numerical simulations, is employed to describe the mechanical response of the structures. Under particular load patterns, the circular shells display novel mechanical behaviour such as snap-through and limiting folding positions. By analysing the geometry and mechanics of the origami structures, we extend the design space of mechanical metamaterials and provide a basis for their practical applications in science and engineering.

  16. Folding to Curved Surfaces: A Generalized Design Method and Mechanics of Origami-based Cylindrical Structures.

    Science.gov (United States)

    Wang, Fei; Gong, Haoran; Chen, Xi; Chen, C Q

    2016-09-14

    Origami structures enrich the field of mechanical metamaterials with the ability to convert morphologically and systematically between two-dimensional (2D) thin sheets and three-dimensional (3D) spatial structures. In this study, an in-plane design method is proposed to approximate curved surfaces of interest with generalized Miura-ori units. Using this method, two combination types of crease lines are unified in one reprogrammable procedure, generating multiple types of cylindrical structures. Structural completeness conditions of the finite-thickness counterparts to the two types are also proposed. As an example of the design method, the kinematics and elastic properties of an origami-based circular cylindrical shell are analysed. The concept of Poisson's ratio is extended to the cylindrical structures, demonstrating their auxetic property. An analytical model of rigid plates linked by elastic hinges, consistent with numerical simulations, is employed to describe the mechanical response of the structures. Under particular load patterns, the circular shells display novel mechanical behaviour such as snap-through and limiting folding positions. By analysing the geometry and mechanics of the origami structures, we extend the design space of mechanical metamaterials and provide a basis for their practical applications in science and engineering.

  17. α -Actinin TvACTN3 of Trichomonas vaginalis is an RNA-binding protein that could participate in its posttranscriptional iron regulatory mechanism.

    Science.gov (United States)

    Calla-Choque, Jaeson Santos; Figueroa-Angulo, Elisa Elvira; Ávila-González, Leticia; Arroyo, Rossana

    2014-01-01

    Trichomonas vaginalis is a sexually transmitted flagellated protist parasite responsible for trichomoniasis. This parasite is dependent on high levels of iron, favoring its growth and multiplication. Iron also differentially regulates some trichomonad virulence properties by unknown mechanisms. However, there is evidence to support the existence of gene regulatory mechanisms at the transcriptional and posttranscriptional levels that are mediated by iron concentration in T. vaginalis. Thus, the goal of this study was to identify an RNA-binding protein in T. vaginalis that interacts with the tvcp4 RNA stem-loop structure, which may participate in a posttranscriptional iron regulatory mechanism mediated by RNA-protein interactions. We performed RNA electrophoretic mobility shift assay (REMSA) and supershift, UV cross-linking, Northwestern blot, and western blot (WB) assays using cytoplasmic protein extracts from T. vaginalis with the tvcp4 RNA hairpin structure as a probe. We identified a 135-kDa protein isolated by the UV cross-linking assays as α-actinin 3 (TvACTN3) by MALDI-TOF-MS that was confirmed by LS-MS/MS and de novo sequencing. TvACTN3 is a cytoplasmic protein that specifically binds to hairpin RNA structures from trichomonads and humans when the parasites are grown under iron-depleted conditions. Thus, TvACTN3 could participate in the regulation of gene expression by iron in T. vaginalis through a parallel posttranscriptional mechanism similar to that of the IRE/IRP system.

  18. 77 FR 55517 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2012-09-10

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a.... Introduction On May 24, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the... General Counsel, Securities Industry and Financial Markets Association, dated June 26, 2012...

  19. An approach for mechanical fault classification based on generalized discriminant analysis

    Institute of Scientific and Technical Information of China (English)

    LI Wei-hua; SHI Tie-lin; YANG Shu-zi

    2006-01-01

    To deal with pattern classification of complicated mechanical faults,an approach to multi-faults classification based on generalized discriminant analysis is presented.Compared with linear discriminant analysis (LDA),generalized discriminant analysis (GDA),one of nonlinear discriminant analysis methods,is more suitable for classifying the linear non-separable problem.The connection and difference between KPCA (Kernel Principal Component Analysis) and GDA is discussed.KPCA is good at detection of machine abnormality while GDA performs well in multi-faults classification based on the collection of historical faults symptoms.When the proposed method is applied to air compressor condition classification and gear fault classification,an excellent performance in complicated multi-faults classification is presented.

  20. The Statistical Mechanics of Random Set Packing and a Generalization of the Karp-Sipser Algorithm

    Directory of Open Access Journals (Sweden)

    C. Lucibello

    2014-01-01

    Full Text Available We analyse the asymptotic behaviour of random instances of the maximum set packing (MSP optimization problem, also known as maximum matching or maximum strong independent set on hypergraphs. We give an analytic prediction of the MSPs size using the 1RSB cavity method from statistical mechanics of disordered systems. We also propose a heuristic algorithm, a generalization of the celebrated Karp-Sipser one, which allows us to rigorously prove that the replica symmetric cavity method prediction is exact for certain problem ensembles and breaks down when a core survives the leaf removal process. The e-phenomena threshold discovered by Karp and Sipser, marking the onset of core emergence and of replica symmetry breaking, is elegantly generalized to Cs=e/(d-1 for one of the ensembles considered, where d is the size of the sets.

  1. Extended Network Generalized Entanglement Theory: therapeutic mechanisms, empirical predictions, and investigations.

    Science.gov (United States)

    Hyland, Michael E

    2003-12-01

    Extended Network Generalized Entanglement Theory (Entanglement Theory for short) combines two earlier theories based on complexity theory and quantum mechanics. The theory's assumptions are: the body is a complex, self-organizing system (the extended network) that self-organizes so as to achieve genetically defined patterns (where patterns include morphologic as well as lifestyle patterns). These pattern-specifying genes require feedback that is provided by generalized quantum entanglement. Additionally, generalized entanglement has evolved as a form of communication between people (and animals) and can be used in healing. Entanglement Theory suggests that several processes are involved in complementary and alternative medicine (CAM). Direct subtle therapy creates network change either through lifestyle management, some manual therapies, and psychologically mediated effects of therapy. Indirect subtle therapy is a process of entanglement with other people or physical entities (e.g., remedies, healing sites). Both types of subtle therapy create two kinds of information within the network--either that the network is more disregulated than it is and the network then compensates for this error, or as a guide for network change leading to healing. Most CAM therapies involve a combination of indirect and direct therapies, making empirical evaluation complex. Empirical predictions from this theory are contrasted with those from two other possible mechanisms of healing: (1) psychologic processes and (2) mechanisms involving electromagnetic influence between people (biofield/energy medicine). Topics for empirical study include a hyperfast communication system, the phenomenology of entanglement, predictors of outcome in naturally occurring clinical settings, and the importance of therapist and patient characteristics to outcome.

  2. Nuclear Regulatory Commission information digest

    Energy Technology Data Exchange (ETDEWEB)

    None,

    1990-03-01

    The Nuclear Regulatory Commission information digest provides summary information regarding the US Nuclear Regulatory Commission, its regulatory responsibilities, and areas licensed by the commission. This is an annual publication for the general use of the NRC Staff and is available to the public. The digest is divided into two parts: the first presents an overview of the US Nuclear Regulatory Commission and the second provides data on NRC commercial nuclear reactor licensees and commercial nuclear power reactors worldwide.

  3. Joint Action: Mental Representations, Shared Information and General Mechanisms for Coordinating with Others

    Science.gov (United States)

    Vesper, Cordula; Abramova, Ekaterina; Bütepage, Judith; Ciardo, Francesca; Crossey, Benjamin; Effenberg, Alfred; Hristova, Dayana; Karlinsky, April; McEllin, Luke; Nijssen, Sari R. R.; Schmitz, Laura; Wahn, Basil

    2017-01-01

    In joint action, multiple people coordinate their actions to perform a task together. This often requires precise temporal and spatial coordination. How do co-actors achieve this? How do they coordinate their actions toward a shared task goal? Here, we provide an overview of the mental representations involved in joint action, discuss how co-actors share sensorimotor information and what general mechanisms support coordination with others. By deliberately extending the review to aspects such as the cultural context in which a joint action takes place, we pay tribute to the complex and variable nature of this social phenomenon. PMID:28101077

  4. Instantons in four-Fermi term broken supersymmetric quantum mechanics with general potential

    Energy Technology Data Exchange (ETDEWEB)

    Hatzinikitas, Agapitos; Smyrnakis, Ioannis [University of Crete, Department of Applied Mathematics, L. Knosou-Ambelokipi, 71409 Iraklio, Crete (Greece)

    2004-01-09

    We have shown here how to find an integral representation for the solution of the Euclidean equations of motion of a quantum mechanical point particle in a general potential and in the presence of a four-Fermi term. The classical action in this theory depends explicitly on a set of four fermionic collective coordinates. The corrections to the classical action due to the presence of fermions are of topological nature in the sense that they depend only on the values of the fields at the boundary points {tau} {yields} {+-} {infinity}. As an application, the quantum mechanical sine-Gordon model with a four-Fermi term is solved explicitly and the corrections to the classical action are computed.

  5. General beliefs about the world as defensive mechanisms against death anxiety.

    Science.gov (United States)

    Hui, Victoria Ka-Ying; Bond, Michael Harris; Ng, Timmy Sze Wing

    Death ideation and death anxiety represent the cognitive and affective dimensions of death attitudes, respectively. General beliefs about the world are proposed to be useful defensive mechanisms protecting persons against the death anxiety provoked by death ideation. SEM is employed to test the proposed mediation model, using a sample of 133 Hong Kong Chinese university students. Results showed that death ideation was significantly and inversely linked to belief in social cynicism, reward for application, and fate control. Moreover, higher levels of belief in fate control and lower levels of religiosity predicted greater death anxiety. Only belief in fate control partially mediated the relationship between death ideation and death anxiety. Discussion focused on how social axioms serve as useful defensive mechanisms against death anxiety.

  6. Entropy theorems in classical mechanics, general relativity, and the gravitational two-body problem

    Science.gov (United States)

    Oltean, Marius; Bonetti, Luca; Spallicci, Alessandro D. A. M.; Sopuerta, Carlos F.

    2016-09-01

    In classical Hamiltonian theories, entropy may be understood either as a statistical property of canonical systems or as a mechanical property, that is, as a monotonic function of the phase space along trajectories. In classical mechanics, there are theorems which have been proposed for proving the nonexistence of entropy in the latter sense. We explicate, clarify, and extend the proofs of these theorems to some standard matter (scalar and electromagnetic) field theories in curved spacetime, and then we show why these proofs fail in general relativity; due to properties of the gravitational Hamiltonian and phase space measures, the second law of thermodynamics holds. As a concrete application, we focus on the consequences of these results for the gravitational two-body problem, and in particular, we prove the noncompactness of the phase space of perturbed Schwarzschild-Droste spacetimes. We thus identify the lack of recurring orbits in phase space as a distinct sign of dissipation and hence entropy production.

  7. Toxicity of graphene-family nanoparticles: a general review of the origins and mechanisms.

    Science.gov (United States)

    Ou, Lingling; Song, Bin; Liang, Huimin; Liu, Jia; Feng, Xiaoli; Deng, Bin; Sun, Ting; Shao, Longquan

    2016-10-31

    Due to their unique physicochemical properties, graphene-family nanomaterials (GFNs) are widely used in many fields, especially in biomedical applications. Currently, many studies have investigated the biocompatibility and toxicity of GFNs in vivo and in intro. Generally, GFNs may exert different degrees of toxicity in animals or cell models by following with different administration routes and penetrating through physiological barriers, subsequently being distributed in tissues or located in cells, eventually being excreted out of the bodies. This review collects studies on the toxic effects of GFNs in several organs and cell models. We also point out that various factors determine the toxicity of GFNs including the lateral size, surface structure, functionalization, charge, impurities, aggregations, and corona effect ect. In addition, several typical mechanisms underlying GFN toxicity have been revealed, for instance, physical destruction, oxidative stress, DNA damage, inflammatory response, apoptosis, autophagy, and necrosis. In these mechanisms, (toll-like receptors-) TLR-, transforming growth factor β- (TGF-β-) and tumor necrosis factor-alpha (TNF-α) dependent-pathways are involved in the signalling pathway network, and oxidative stress plays a crucial role in these pathways. In this review, we summarize the available information on regulating factors and the mechanisms of GFNs toxicity, and propose some challenges and suggestions for further investigations of GFNs, with the aim of completing the toxicology mechanisms, and providing suggestions to improve the biological safety of GFNs and facilitate their wide application.

  8. A statistical mechanical approach for the computation of the climatic response to general forcings

    Science.gov (United States)

    Lucarini, V.; Sarno, S.

    2011-01-01

    The climate belongs to the class of non-equilibrium forced and dissipative systems, for which most results of quasi-equilibrium statistical mechanics, including the fluctuation-dissipation theorem, do not apply. In this paper we show for the first time how the Ruelle linear response theory, developed for studying rigorously the impact of perturbations on general observables of non-equilibrium statistical mechanical systems, can be applied with great success to analyze the climatic response to general forcings. The crucial value of the Ruelle theory lies in the fact that it allows to compute the response of the system in terms of expectation values of explicit and computable functions of the phase space averaged over the invariant measure of the unperturbed state. We choose as test bed a classical version of the Lorenz 96 model, which, in spite of its simplicity, has a well-recognized prototypical value as it is a spatially extended one-dimensional model and presents the basic ingredients, such as dissipation, advection and the presence of an external forcing, of the actual atmosphere. We recapitulate the main aspects of the general response theory and propose some new general results. We then analyze the frequency dependence of the response of both local and global observables to perturbations having localized as well as global spatial patterns. We derive analytically several properties of the corresponding susceptibilities, such as asymptotic behavior, validity of Kramers-Kronig relations, and sum rules, whose main ingredient is the causality principle. We show that all the coefficients of the leading asymptotic expansions as well as the integral constraints can be written as linear function of parameters that describe the unperturbed properties of the system, such as its average energy. Some newly obtained empirical closure equations for such parameters allow to define such properties as an explicit function of the unperturbed forcing parameter alone for a

  9. A statistical mechanical approach for the computation of the climatic response to general forcings

    Directory of Open Access Journals (Sweden)

    V. Lucarini

    2011-01-01

    Full Text Available The climate belongs to the class of non-equilibrium forced and dissipative systems, for which most results of quasi-equilibrium statistical mechanics, including the fluctuation-dissipation theorem, do not apply. In this paper we show for the first time how the Ruelle linear response theory, developed for studying rigorously the impact of perturbations on general observables of non-equilibrium statistical mechanical systems, can be applied with great success to analyze the climatic response to general forcings. The crucial value of the Ruelle theory lies in the fact that it allows to compute the response of the system in terms of expectation values of explicit and computable functions of the phase space averaged over the invariant measure of the unperturbed state. We choose as test bed a classical version of the Lorenz 96 model, which, in spite of its simplicity, has a well-recognized prototypical value as it is a spatially extended one-dimensional model and presents the basic ingredients, such as dissipation, advection and the presence of an external forcing, of the actual atmosphere. We recapitulate the main aspects of the general response theory and propose some new general results. We then analyze the frequency dependence of the response of both local and global observables to perturbations having localized as well as global spatial patterns. We derive analytically several properties of the corresponding susceptibilities, such as asymptotic behavior, validity of Kramers-Kronig relations, and sum rules, whose main ingredient is the causality principle. We show that all the coefficients of the leading asymptotic expansions as well as the integral constraints can be written as linear function of parameters that describe the unperturbed properties of the system, such as its average energy. Some newly obtained empirical closure equations for such parameters allow to define such properties as an explicit function of the unperturbed forcing

  10. Supercritical super-Brownian motion with a general branching mechanism and travelling waves

    CERN Document Server

    Kyprianou, A E; Murillo-Salas, A; Ren, Y -X

    2010-01-01

    We consider the classical problem of existence, uniqueness and asymptotics of monotone solutions to the travelling wave equation associated to the parabolic semi-group equation of a super-Brownian motion with a general branching mechanism. Whilst we are strongly guided by the probabilistic reasoning of Kyprianou (2004) for branching Brownian motion, the current paper offers a number of new insights. Our analysis incorporates the role of Seneta-Heyde norming which, in the current setting, draws on classical work of Grey (1974). We give a pathwise explanation of Evans' immortal particle picture (the spine decomposition) which uses the Dynkin-Kuznetsov N-measure as a key ingredient. Moreover, in the spirit of Neveu's stopping lines we make repeated use of Dynkin's exit measures. Additional complications arise from the general nature of the branching mechanism. As a consequence of the analysis we also offer an exact X(log X)^2 moment dichotomy for the almost sure convergence of the so-called derivative martingale...

  11. Building functional groups of marine benthic macroinvertebrates on the basis of general community assembly mechanisms

    Science.gov (United States)

    Alexandridis, Nikolaos; Bacher, Cédric; Desroy, Nicolas; Jean, Fred

    2017-03-01

    The accurate reproduction of the spatial and temporal dynamics of marine benthic biodiversity requires the development of mechanistic models, based on the processes that shape macroinvertebrate communities. The modelled entities should, accordingly, be able to adequately represent the many functional roles that are performed by benthic organisms. With this goal in mind, we applied the emergent group hypothesis (EGH), which assumes functional equivalence within and functional divergence between groups of species. The first step of the grouping involved the selection of 14 biological traits that describe the role of benthic macroinvertebrates in 7 important community assembly mechanisms. A matrix of trait values for the 240 species that occurred in the Rance estuary (Brittany, France) in 1995 formed the basis for a hierarchical classification that generated 20 functional groups, each with its own trait values. The functional groups were first evaluated based on their ability to represent observed patterns of biodiversity. The two main assumptions of the EGH were then tested, by assessing the preservation of niche attributes among the groups and the neutrality of functional differences within them. The generally positive results give us confidence in the ability of the grouping to recreate functional diversity in the Rance estuary. A first look at the emergent groups provides insights into the potential role of community assembly mechanisms in shaping biodiversity patterns. Our next steps include the derivation of general rules of interaction and their incorporation, along with the functional groups, into mechanistic models of benthic biodiversity.

  12. Exact Descriptions of General Relativity Derived from Newtonian Mechanics within Curved Geometries

    Science.gov (United States)

    Savickas, David

    2015-04-01

    General relativity and Newtonian mechanics are shown to be exactly related when Newton's second law is written in a curved geometry by using the physical components of a vector as is defined in tensor calculus. By replacing length within the momentum's velocity by the vector metric in a curved geometry the second law can then be shown to be exactly identical to the geodesic equation of motion occurring in general relativity. When time's vector direction is constant, as similarly occurs in Newtonian mechanics, this equation can be reduced to a curved three-dimensional equation of motion that yields the the Schwarzschild equations of motion for an isolated particle. They can be used to describe gravitational behavior for any array of masses for which the Newtonian gravitational potential is known, and is shown to describe a mass particle's behavior in the gravitational field of a thin mass-rod. This use of Newton's laws allows relativistic behavior to be described in a physically comprehensible manner. D. Savickas, Int. J. Mod. Phys. D 23 1430018, (2014).

  13. Algebraic solution for the forward displacement analysis of the general 6-6 stewart mechanism

    Science.gov (United States)

    Wei, Feng; Wei, Shimin; Zhang, Ying; Liao, Qizheng

    2016-01-01

    The solution for the forward displacement analysis(FDA) of the general 6-6 Stewart mechanism(i.e., the connection points of the moving and fixed platforms are not restricted to lying in a plane) has been extensively studied, but the efficiency of the solution remains to be effectively addressed. To this end, an algebraic elimination method is proposed for the FDA of the general 6-6 Stewart mechanism. The kinematic constraint equations are built using conformal geometric algebra(CGA). The kinematic constraint equations are transformed by a substitution of variables into seven equations with seven unknown variables. According to the characteristic of anti-symmetric matrices, the aforementioned seven equations can be further transformed into seven equations with four unknown variables by a substitution of variables using the Gröbner basis. Its elimination weight is increased through changing the degree of one variable, and sixteen equations with four unknown variables can be obtained using the Gröbner basis. A 40th-degree univariate polynomial equation is derived by constructing a relatively small-sized 9´9 Sylvester resultant matrix. Finally, two numerical examples are employed to verify the proposed method. The results indicate that the proposed method can effectively improve the efficiency of solution and reduce the computational burden because of the small-sized resultant matrix.

  14. Generalization of classical mechanics for nuclear motions on nonadiabatically coupled potential energy surfaces in chemical reactions.

    Science.gov (United States)

    Takatsuka, Kazuo

    2007-10-18

    Classical trajectory study of nuclear motion on the Born-Oppenheimer potential energy surfaces is now one of the standard methods of chemical dynamics. In particular, this approach is inevitable in the studies of large molecular systems. However, as soon as more than a single potential energy surface is involved due to nonadiabatic coupling, such a naive application of classical mechanics loses its theoretical foundation. This is a classic and fundamental issue in the foundation of chemistry. To cope with this problem, we propose a generalization of classical mechanics that provides a path even in cases where multiple potential energy surfaces are involved in a single event and the Born-Oppenheimer approximation breaks down. This generalization is made by diagonalization of the matrix representation of nuclear forces in nonadiabatic dynamics, which is derived from a mixed quantum-classical representation of the electron-nucleus entangled Hamiltonian [Takatsuka, K. J. Chem. Phys. 2006, 124, 064111]. A manifestation of quantum fluctuation on a classical subsystem that directly contacts with a quantum subsystem is discussed. We also show that the Hamiltonian thus represented gives a theoretical foundation to examine the validity of the so-called semiclassical Ehrenfest theory (or mean-field theory) for electron quantum wavepacket dynamics, and indeed, it is pointed out that the electronic Hamiltonian to be used in this theory should be slightly modified.

  15. Simulated scaling method for localized enhanced sampling and simultaneous "alchemical" free energy simulations: a general method for molecular mechanical, quantum mechanical, and quantum mechanical/molecular mechanical simulations.

    Science.gov (United States)

    Li, Hongzhi; Fajer, Mikolai; Yang, Wei

    2007-01-14

    A potential scaling version of simulated tempering is presented to efficiently sample configuration space in a localized region. The present "simulated scaling" method is developed with a Wang-Landau type of updating scheme in order to quickly flatten the distributions in the scaling parameter lambdam space. This proposal is meaningful for a broad range of biophysical problems, in which localized sampling is required. Besides its superior capability and robustness in localized conformational sampling, this simulated scaling method can also naturally lead to efficient "alchemical" free energy predictions when dual-topology alchemical hybrid potential is applied; thereby simultaneously, both of the chemically and conformationally distinct portions of two end point chemical states can be efficiently sampled. As demonstrated in this work, the present method is also feasible for the quantum mechanical and quantum mechanical/molecular mechanical simulations.

  16. Positive and Negative Regulatory Mechanisms for Fine-Tuning Cellularity and Functions of Medullary Thymic Epithelial Cells

    Science.gov (United States)

    Akiyama, Taishin; Tateishi, Ryosuke; Akiyama, Nobuko; Yoshinaga, Riko; Kobayashi, Tetsuya J.

    2015-01-01

    Self-tolerant T cells and regulatory T cells develop in the thymus. A wide variety of cell–cell interactions in the thymus is required for the differentiation, proliferation, and repertoire selection of T cells. Various secreted and cell surface molecules expressed in thymic epithelial cells (TECs) mediate these processes. Moreover, cytokines expressed by cells of hematopoietic origin regulate the cellularity of TECs. Tumor necrosis factor (TNF) family RANK ligand, lymphotoxin, and CD40 ligand, expressed in T cells and innate lymphoid cells (ILCs), promote the differentiation and proliferation of medullary TECs (mTECs) that play critical roles in the induction of immune tolerance. A recent study suggests that interleukin-22 (IL-22) produced by ILCs promotes regeneration of TECs after irradiation. Intriguingly, tumor growth factor-β and osteoprotegerin limit cellularity of mTECs, thereby attenuating regulatory T cell generation. We will review recent insights into the molecular basis for cell–cell interactions regulating differentiation and proliferation of mTECs and also discuss about a perspective on use of mathematical models for understanding this complicated system. PMID:26441966

  17. Mass Spectrometric Analysis of TRPM6 and TRPM7 Phosphorylation Reveals Regulatory Mechanisms of the Channel-Kinases

    Science.gov (United States)

    Cai, Na; Bai, Zhiyong; Nanda, Vikas; Runnels, Loren W.

    2017-01-01

    TRPM7 and TRPM6 were the first identified bifunctional channels to contain their own kinase domains, but how these channel-kinases are regulated is poorly understood. Previous studies identified numerous phosphorylation sites on TRPM7, but very little is known about TRPM6 phosphorylation or sites on TRPM7 transphosphorylated by TRPM6. Our mass spectrometric analysis of homomeric and heteromeric TRPM7 and TRPM6 channels identified phosphorylation sites on both proteins, as well as several prominent sites on TRPM7 that are commonly modified through autophosphorylation and transphosphorylation by TRPM6. We conducted a series of amino acid substitution analyses and identified S1777, in TRPM7’s catalytic domain, and S1565, in TRPM7’s exchange domain that mediates kinase dimerization, as potential regulatory sites. The phosphomimetic S1777D substitution disrupted catalytic activity, most likely by causing an electrostatic perturbation at the active site. The S1565D phosphomimetic substitution also inactivated the kinase but did so without interfering with kinase dimerization. Molecular modeling indicates that phosphorylation of S1565 is predicted to structurally affect TRPM7’s functionally conserved N/D loop, which is thought to influence the access of substrate to the active site pocket. We propose that phosphorylation of S1565 within the exchange domain functions as a regulatory switch to control TRPM7 catalytic activity. PMID:28220887

  18. A General Mechanism for the Propagation of Mutational Effects in Proteins.

    Science.gov (United States)

    Rajasekaran, Nandakumar; Suresh, Swaathiratna; Gopi, Soundhararajan; Raman, Karthik; Naganathan, Athi N

    2017-01-10

    Mutations in the hydrophobic interior of proteins are generally thought to weaken the interactions only in their immediate neighborhood. This forms the basis of protein engineering-based studies of folding mechanism and function. However, mutational work on diverse proteins has shown that distant residues are thermodynamically coupled, with the network of interactions within the protein acting as signal conduits, thus raising an intriguing paradox. Are mutational effects localized, and if not, is there a general rule for the extent of percolation and the functional form of this propagation? We explore these questions from multiple perspectives in this work. Perturbation analysis of interaction networks within proteins and microsecond long molecular dynamics simulations of several aliphatic mutants of ubiquitin reveal strong evidence of the distinct alteration of distal residue-residue communication networks. We find that mutational effects consistently propagate into the second shell of the altered site (even up to 15-20 Å) in proportion to the perturbation magnitude and dissipate exponentially with a decay distance constant of ∼4-5 Å. We also report evidence for this phenomenon from published experimental nuclear magnetic resonance data that strikingly resemble predictions from network theory and molecular dynamics simulations. Reformulating these observations onto a statistical mechanical model, we reproduce the stability changes of 375 mutations from 19 single-domain proteins. Our work thus reveals a robust energy dissipation-cum-signaling mechanism in the interaction network within proteins, quantifies the partitioning of destabilization energetics around the mutation neighborhood, and presents a simple theoretical framework for modeling the allosteric effects of point mutations.

  19. Bottom-Up and Top-Down Mechanisms of General Anesthetics Modulate Different Dimensions of Consciousness.

    Science.gov (United States)

    Mashour, George A; Hudetz, Anthony G

    2017-01-01

    There has been controversy regarding the precise mechanisms of anesthetic-induced unconsciousness, with two salient approaches that have emerged within systems neuroscience. One prominent approach is the "bottom up" paradigm, which argues that anesthetics suppress consciousness by modulating sleep-wake nuclei and neural circuits in the brainstem and diencephalon that have evolved to control arousal states. Another approach is the "top-down" paradigm, which argues that anesthetics suppress consciousness by modulating the cortical and thalamocortical circuits involved in the integration of neural information. In this article, we synthesize these approaches by mapping bottom-up and top-down mechanisms of general anesthetics to two distinct but inter-related dimensions of consciousness: level and content. We show how this explains certain empirical observations regarding the diversity of anesthetic drug effects. We conclude with a more nuanced discussion of how levels and contents of consciousness interact to generate subjective experience and what this implies for the mechanisms of anesthetic-induced unconsciousness.

  20. Bottom-Up and Top-Down Mechanisms of General Anesthetics Modulate Different Dimensions of Consciousness

    Science.gov (United States)

    Mashour, George A.; Hudetz, Anthony G.

    2017-01-01

    There has been controversy regarding the precise mechanisms of anesthetic-induced unconsciousness, with two salient approaches that have emerged within systems neuroscience. One prominent approach is the “bottom up” paradigm, which argues that anesthetics suppress consciousness by modulating sleep-wake nuclei and neural circuits in the brainstem and diencephalon that have evolved to control arousal states. Another approach is the “top-down” paradigm, which argues that anesthetics suppress consciousness by modulating the cortical and thalamocortical circuits involved in the integration of neural information. In this article, we synthesize these approaches by mapping bottom-up and top-down mechanisms of general anesthetics to two distinct but inter-related dimensions of consciousness: level and content. We show how this explains certain empirical observations regarding the diversity of anesthetic drug effects. We conclude with a more nuanced discussion of how levels and contents of consciousness interact to generate subjective experience and what this implies for the mechanisms of anesthetic-induced unconsciousness. PMID:28676745

  1. Rapid Enhancement in General Relativistic Precession Rates due to Kozai Mechanism in Solar System Bodies

    Science.gov (United States)

    Sekhar, Aswin; Asher, David; Morbidelli, Alessandro; Werner, Stephanie; Vaubaillon, Jeremie; Li, Gongjie

    2017-06-01

    Two well known phenomena in orbital dynamics associated with low perihelion distance bodies are general relativistic (GR) precession and Lidov-Kozai (LK) oscillations.In this work, we are interested to identify bodies evolving in the near future (i.e. thousands of years in this case) into rapid sungrazing and sun colliding phases and undergoing inclination flips, due to LK like oscillations and being GR active at the same time. We find that LK mechanism leads to secular lowering of perihelion distance which in turn leads to a huge increase in GR precession of the argument of pericentre depending on the initial orbital elements. This in turn gives feedback to the LK mechanism as the eccentricity, inclination and argument of pericentre in Kozai cycles are closely correlated. In this work, we find real examples of solar system bodies which show rapid enhancement in GR precession rates due to LK like oscillations and there are cases where GR precession rate peaks to about 60 times that of the GR precession of Mercury thus showing the strength and complementary nature between these two dynamical phenomena.An analytical treatment is done on few bodies to understand the difference in their orbital evolution in the context of LK mechanism with and without GR precession term by incorporating suitable Hamiltonian dynamics. This result is subsequently matched using numerical integrations to find direct correlations. Real solar system bodies showing both GR precession and LK like oscillations are identified using compiled observational records from IAU-Minor Planet Center, Cometary Catalogue, IAU-Meteor Data Center and performing analytical plus numerical tests on them. This intermediate state (where GR and LK effects are comparable and co-exist) brings up the interesting possibility of drastic changes in GR precession rates during orbital evolution due to sungrazing and sun colliding phases induced by the LK like mechanism, thus combining both these important effects in a

  2. Regulatory considerations for biosimilars

    Directory of Open Access Journals (Sweden)

    Ranjani Nellore

    2010-01-01

    Full Text Available Currently there is considerable interest in the legislative debate around generic biological drugs or "biosimilars" in the EU and US due to the large, lucrative market that it offers to the industry. While some countries have issued a few regulatory guidelines as well as product specific requirements, there is no general consensus as to a single, simple mechanism similar to the bioequivalence determination that leads to approval of generic small molecules all over the world. The inherent complex nature of the molecules, along with complicated manufacturing and analytical techniques to characterize them make it difficult to rely on a single human pharmacokinetic study for assurance of safety and efficacy. In general, the concept of comparability has been used for evaluation of the currently approved "similar" biological where a step by step assessment on the quality, preclinical and clinical aspects is made. In India, the focus is primarily on the availability and affordability of life-saving drugs. In this context every product needs to be evaluated on its own merit irrespective of the innovator brand. The formation of the National Biotechnology Regulatory Authority may provide a step in the right direction for regulation of these complex molecules. However, in order to have an efficient machinery for initial approval and ongoing oversight with a country-specific focus, cooperation with international authorities for granting approvals and continuous risk-benefit review is essential. Several steps are still needed for India to be perceived as a country that leads the world in providing quality biological products.

  3. The Born-Infeld vortices induced from a generalized Higgs mechanism.

    Science.gov (United States)

    Han, Xiaosen

    2016-04-01

    We construct self-dual Born-Infeld vortices induced from a generalized Higgs mechanism. Two specific models of the theory are of focused interest where the Higgs potential is either of a |ϕ|(4)- or |ϕ|(6)-type. For the |ϕ|(4)-model, we obtain a sharp existence and uniqueness theorem for doubly periodic and planar vortices. For doubly periodic solutions, a necessary and sufficient condition for the existence is explicitly derived in terms of the vortex number, the Born-Infeld parameter, and the size of the periodic lattice domain. For the |ϕ|(6)-model, we show that both topological and non-topological vortices are present. This new phenomenon distinguishes the model from the classical Born-Infeld-Higgs theory studied earlier in the literature. A series of results regarding doubly periodic, topological, and non-topological vortices in the |ϕ|(6)-model are also established.

  4. General quantum-mechanical setting for field-antifield formalism as a hyper-gauge theory

    CERN Document Server

    Batalin, Igor A

    2016-01-01

    A general quantum-mechanical setting is proposed for the field-antifield formalism as a unique hyper-gauge theory in the field-antifield space. We formulate a Schr\\"{o}dinger-type equation to describe the quantum evolution in a "current time" purely formal in its nature. The corresponding Hamiltonian is defined in the form of a supercommutator of the delta-operator with a hyper-gauge Fermion. The initial wave function is restricted to be annihilated with the delta-operator. The Schr\\"{o}dinger's equation is resolved in a closed form of the path integral, whose action contains the symmetric Weyl's symbol of the Hamiltonian. We take the path integral explicitly in the case of being a hyper-gauge Fermion an arbitrary function rather than an operator.

  5. General quantum-mechanical setting for field-antifield formalism as a hyper-gauge theory

    Science.gov (United States)

    Batalin, Igor A.; Lavrov, Peter M.

    2016-09-01

    A general quantum-mechanical setting is proposed for the field-antifield formalism as a unique hyper-gauge theory in the field-antifield space. We formulate a Schr\\"odinger-type equation to describe the quantum evolution in a "current time" purely formal in its nature. The corresponding Hamiltonian is defined in the form of a supercommutator of the delta-operator with a hyper-gauge Fermion. The initial wave function is restricted to be annihilated with the delta-operator. The Schr\\"odinger's equation is resolved in a closed form of the path integral, whose action contains the symmetric Weyl's symbol of the Hamiltonian. We take the path integral explicitly in the case of being a hyper-gauge Fermion an arbitrary function rather than an operator.

  6. Conceptual tensions between quantum mechanics and general relativity Are there experimental consequences?

    CERN Document Server

    Chiao, R Y

    2003-01-01

    One of the conceptual tensions between quantum mechanics (QM) and general relativity (GR) arises from the clash between the spatial nonseparability of entangled states in QM, and the complete spatial separability of all physical systems in GR, i.e., between the nonlocality implied by the superposition principle, and the locality implied by the equivalence principle. Possible experimental consequences of this conceptual tension will be discussed for macroscopically entangled, coherent quantum fluids, such as superconductors, superfluids, atomic Bose-Einstein condensates, and quantum Hall fluids, interacting with tidal and gravitational radiation fields. A minimal-coupling rule, which arises from the electron spin coupled to curved spacetime, leads to an interaction between electromagnetic (EM) and gravitational (GR) radiation fields mediated by a quantum Hall fluid. This suggests the possibility of a quantum transducer action, in which EM waves are convertible to GR waves, and vice versa.

  7. Conceptual tensions between quantum mechanics and general relativity Are there experimental consequences?

    CERN Document Server

    Chiao, R Y

    2002-01-01

    One of the conceptual tensions between quantum mechanics (QM) and general relativity (GR) arises from the clash between the spatial nonseparability} of entangled states in QM, and the complete spatial separability of all physical systems in GR, i.e., between the nonlocality implied by the superposition principle, and the locality implied by the equivalence principle. Possible experimental consequences of this conceptual tension will be discussed for macroscopically entangled, coherent quantum fluids, such as superconductors, superfluids, atomic Bose-Einstein condensates, and quantum Hall fluids, interacting with tidal and gravitational radiation fields. A minimal-coupling rule, which arises from the electron spin coupled to curved spacetime, leads to an interaction between electromagnetic (EM) and gravitational (GR) radiation fields mediated by a quantum Hall fluid. This suggests the possibility of a quantum transducer action, in which EM waves are convertible to GR waves, and vice versa.

  8. Speech and music shape the listening brain: evidence for shared domain-general mechanisms

    Directory of Open Access Journals (Sweden)

    Salomi S. Asaridou

    2013-06-01

    Full Text Available Are there bi-directional influences between speech perception and music perception? An answer to this question is essential for understanding the extent to which the speech and music that we hear are processed by domain-general auditory processes and/or by distinct neural auditory mechanisms. This review summarizes a large body of behavioral and neuroscientific findings which suggest that the musical experience of trained musicians does modulate speech processing, and a sparser set of data, largely on pitch processing, which suggest in addition that linguistic experience, in particular learning a tone language, modulates music processing. Although research has focused mostly on music on speech effects, we argue that both directions of influence need to be studied, and conclude that the picture which thus emerges is one of mutual interaction across domains. In particular, it is not simply that experience with spoken language has some effects on music perception, and vice versa, but that because of shared domain-general subcortical and cortical networks, experiences in both domains influence behavior in both domains.

  9. Generalized Lagrangian-Path Representation of Non-Relativistic Quantum Mechanics

    Science.gov (United States)

    Tessarotto, Massimo; Cremaschini, Claudio

    2016-08-01

    In this paper a new trajectory-based representation to non-relativistic quantum mechanics is formulated. This is ahieved by generalizing the notion of Lagrangian path (LP) which lies at the heart of the deBroglie-Bohm " pilot-wave" interpretation. In particular, it is shown that each LP can be replaced with a statistical ensemble formed by an infinite family of stochastic curves, referred to as generalized Lagrangian paths (GLP). This permits the introduction of a new parametric representation of the Schrödinger equation, denoted as GLP-parametrization, and of the associated quantum hydrodynamic equations. The remarkable aspect of the GLP approach presented here is that it realizes at the same time also a new solution method for the N-body Schrödinger equation. As an application, Gaussian-like particular solutions for the quantum probability density function (PDF) are considered, which are proved to be dynamically consistent. For them, the Schrödinger equation is reduced to a single Hamilton-Jacobi evolution equation. Particular solutions of this type are explicitly constructed, which include the case of free particles occurring in 1- or N-body quantum systems as well as the dynamics in the presence of suitable potential forces. In all these cases the initial Gaussian PDFs are shown to be free of the spreading behavior usually ascribed to quantum wave-packets, in that they exhibit the characteristic feature of remaining at all times spatially-localized.

  10. General equilibrium effects of a supply side GHG mitigation option under the Clean Development Mechanism.

    Science.gov (United States)

    Timilsina, Govinda R; Shrestha, Ram M

    2006-09-01

    The Clean Development Mechanism (CDM) under the Kyoto Protocol to the United Nations Framework Convention on Climate Change is considered a key instrument to encourage developing countries' participation in the mitigation of global climate change. Reduction of greenhouse gas (GHG) emissions through the energy supply and demand side activities are the main options to be implemented under the CDM. This paper analyses the general equilibrium effects of a supply side GHG mitigation option-the substitution of thermal power with hydropower--in Thailand under the CDM. A static multi-sector general equilibrium model has been developed for the purpose of this study. The key finding of the study is that the substitution of electricity generation from thermal power plants with that from hydropower plants would increase economic welfare in Thailand. The supply side option would, however, adversely affect the gross domestic product (GDP) and the trade balance. The percentage changes in economic welfare, GDP and trade balance increase with the level of substitution and the price of certified emission reduction (CER) units.

  11. Matrix elements for sum of power-law potentials in quantum mechanic using generalized hypergeometric functions

    Directory of Open Access Journals (Sweden)

    Ma'zoozeh E. Abu-Amra

    2008-04-01

    Full Text Available In this paper we derive close form for the matrix elements for $hat H=-Delta +V$, where $V$ is a pure power-law potential. We use trial functions of the form $$ psi _n(r= sqrt{{frac{2eta ^{gamma/2}(gamma _n} {n!Gamma(gamma }}} r^{gamma - 1/2} e^{-frac{sqrt{eta }}{2}r^q} _pF_1 ( -n,a_2,ldots ,a_p;gamma;sqrt {eta } r^q, $$ for $eta, q,gamma >0$ to obtain the matrix elements for $hat H$. These formulas are then optimized with respect to variational parameters $eta ,q$ and $gamma $ to obtain accurate upper bounds for the given nonsolvable eigenvalue problem in quantum mechanics. Moreover, we write the matrix elements in terms of the generalized hypergeomtric functions. These results are generalization of those found earlier in [2], [8-16] for power-law potentials. Applications and comparisons with earlier work are presented.

  12. General duality for Abelian-group-valued statistical-mechanics models

    Energy Technology Data Exchange (ETDEWEB)

    Caracciolo, Sergio [Dip. di Fisica and INFN, Universita degli Studi di Milano, via Celoria 16, I-20133 Milan (Italy); Sportiello, Andrea [Dip. di Fisica and INFN, Universita degli Studi di Milano, via Celoria 16, I-20133 Milan (Italy)

    2004-07-30

    We introduce a general class of statistical-mechanics models, taking values in an Abelian group, which includes examples of both spin and gauge models, both ordered and disordered. The model is described by a set of 'variables' and a set of 'interactions'. Each interaction is associated with a linear combination of variables; these are summarized in a matrix J. A Gibbs factor is associated with each variable (one-body term) and with each interaction. Then we introduce a duality transformation for systems in this class. The duality exchanges the Abelian group with its dual, the Gibbs factors with their Fourier transforms and the interactions with the variables. High (low) couplings in the interaction terms are mapped into low (high) couplings in the one-body terms. If the matrix J is interpreted as a vector representation of a matroid, duality exchanges the matroid with its dual. We discuss some physical examples. The main idea is to generalize the known models up to eventually include randomness into the pattern of interaction. We introduce and study a random Gaussian model, a random Potts-like model and a random variant of discrete scalar QED. Although the classical procedure as given by Kramers and Wannier does not extend in a natural way to such a wider class of systems, our weaker procedure applies to these models, too. We shortly describe the consequence of duality for each example.

  13. Speech and music shape the listening brain: evidence for shared domain-general mechanisms

    Science.gov (United States)

    Asaridou, Salomi S.; McQueen, James M.

    2013-01-01

    Are there bi-directional influences between speech perception and music perception? An answer to this question is essential for understanding the extent to which the speech and music that we hear are processed by domain-general auditory processes and/or by distinct neural auditory mechanisms. This review summarizes a large body of behavioral and neuroscientific findings which suggest that the musical experience of trained musicians does modulate speech processing, and a sparser set of data, largely on pitch processing, which suggest in addition that linguistic experience, in particular learning a tone language, modulates music processing. Although research has focused mostly on music on speech effects, we argue that both directions of influence need to be studied, and conclude that the picture which thus emerges is one of mutual interaction across domains. In particular, it is not simply that experience with spoken language has some effects on music perception, and vice versa, but that because of shared domain-general subcortical and cortical networks, experiences in both domains influence behavior in both domains. PMID:23761776

  14. Experimental and finite element analysis of fracture criterion in general yielding fracture mechanics

    Indian Academy of Sciences (India)

    D M Kulkarni; Ravi Prakash; A N Kumar

    2002-12-01

    Efforts made over the last three decades to understand the fracture behaviour of structural materials in elastic and elasto-plastic fracture mechanics are numerous, whereas investigations related to fracture behaviour of materials in thin sheets or general yielding fracture regimes are limited in number. Engineering simulative tests are being used to characterize formability and drawability of sheet metals. However, these tests do not assure consistency in quality of sheet metal products. The prevention of failure in stressed structural components currently requires fracture mechanics based design parameters like critical load, critical crack-tip opening displacement or fracture toughness. The present attempt would aim to fulfill this gap and generate more information thereby increased understanding on fracture behaviour of sheet metals. In the present investigation, using a recently developed technique for determining fracture criteria in sheet metals, results are generated on critical CTOD and fracture toughness. Finite element analysis was performed to support the results on various fracture parameters. The differences are within 1 to 4%. At the end it is concluded that magnitude of critical CTOD and/or critical load can be used as a fracture criterion for thin sheets.

  15. Entropy theorems in classical mechanics, general relativity, and the gravitational two-body problem

    CERN Document Server

    Oltean, Marius; Spallicci, Alessandro D A M; Sopuerta, Carlos F

    2016-01-01

    In classical Hamiltonian theories, entropy may be understood either as a statistical property of canonical systems, or as a mechanical property, that is, as a monotonic function of the phase space along trajectories. In classical mechanics, there are theorems which have been proposed for proving the non-existence of entropy in the latter sense. We explicate, clarify and extend the proofs of these theorems to some standard matter (scalar and electromagnetic) field theories in curved spacetime, and then we show why these proofs fail in general relativity; due to properties of the gravitational Hamiltonian and phase space measures, the second law of thermodynamics holds. As a concrete application, we focus on the consequences of these results for the gravitational two-body problem, and in particular, we prove the non-compactness of the phase space of perturbed Schwarzschild-Droste spacetimes. We thus identify the lack of recurring orbits in phase space as a distinct sign of dissipation and hence entropy producti...

  16. [General functional state (tonus) of the brain and conditioned reflexes as the mechanisms of it's regulation].

    Science.gov (United States)

    Khananashvili, M M

    2008-01-01

    The article is dedicated to P.S. Kupalov, due to his 120 Anniversary. P.S. Kupalov was the disciple of I.P. Pavlov and his nearest collaborator. Right after I.P. Pavlov, he was at the head of the Institute of Experimental Medicine in St-Petersburg, where he developed a number of new ideas, concerning conditioned reflexes. Thus, he discovered shortened conditioned reflexes--central mechanisms of regulation of general functional state of the brain, and he created, on the base of the studies of unlimited motor activity in animals using his own method of situational conditioned reflexes, the conception of situational conditioned reflexes. P.S. Kupalov found out a number of new explanations for development of experimental neuroses and determined their mechanisms, as well. He was the one among the first disciples of I.P. Pavlov, who indicated at the complex structural-functional organization of conditioned reflexes, and he played the great part for the creation of modern theory about the nature of behavior, based on conditioned reflexes. The most important theses of P.S. Kupalov's conception, which is of great cognitive significance at the moment, as well as some results of the studies by his disciples and followers, developing the ideas of P.S. Kupalov, are presented in the article.

  17. Post-translational hydroxylation by 2OG/Fe(II-dependent oxygenases as a novel regulatory mechanism in bacteria

    Directory of Open Access Journals (Sweden)

    Laura M van Staalduinen

    2015-01-01

    Full Text Available Protein hydroxylation has been well-studied in eukaryotic systems. The structural importance of hydroxylation of specific proline and lysine residues during collagen biosynthesis is well established while, recently, key roles for post-translational hydroxylation in signalling and degradation pathways have been discovered. The function of hydroxylation in signalling is highlighted by its role in the hypoxic response of eukaryotic cells, where oxygen dependent hydroxylation of the hypoxia inducible transcription factor both targets it for degradation and blocks its activation. In contrast, the role of protein hydroxylation has been largely understudied in prokaryotes. Recently, an evolutionarily conserved class of ribosomal oxygenases (ROX that catalyze the hydroxylation of specific residues in the ribosome has been identified in bacteria. ROX activity has been linked to cell growth, and has been found to have a direct impact on bulk protein translation. This discovery of ribosomal protein hydroxylation in bacteria could lead to new therapeutic targets for regulating bacterial growth, as well as, shed light on new prokaryotic hydroxylation signalling pathways. In this review, recent structural and functional studies will be highlighted and discussed, underscoring the regulatory potential of post-translational hydroxylation in bacteria.

  18. Regulatory guidance document

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM`s evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7.

  19. A Fresh Look at Potential Mechanisms of Change in Applied Relaxation for Generalized Anxiety Disorder: A Case Series

    Science.gov (United States)

    Hayes-Skelton, Sarah A.; Usmani, Aisha; Lee, Jonathan K.; Roemer, Lizabeth; Orsillo, Susan M.

    2012-01-01

    Applied relaxation (AR), which involves noticing early signs of anxiety and responding with a relaxation response, is an empirically supported treatment for generalized anxiety disorder (GAD). However, research on hypothesized mechanisms of AR (e.g., reduced muscle tension) has been mixed, making it likely that additional mechanisms are…

  20. 自我效能感对心理弹性影响的实证研究%An Empirical Study of Effects of General and Regulatory Emotional Self-Efficacy on Stress Resilience

    Institute of Scientific and Technical Information of China (English)

    刘燊; 李丹丹; 张林

    2015-01-01

    This paper investigated 300 undergraduates in questionnaire to examine the effects of general self-efficacy and regulatory emotional self-efficacy on stress resilience. The results showed that there were significantly positive correlations between general self-efficacy, regulatory emotional self-efficacy and stress resilience; and regulatory emotional self-efficacy completely mediated the relationship between general self-efficacy and stress resilience.%运用问卷调查法,以300名大学生为研究对象,探讨一般自我效能感和情绪调节自我效能感对大学生心理弹性的影响。研究发现:一般自我效能感与情绪调节自我效能感、心理弹性之间均有显著的正相关,情绪调节自我效能感与心理弹性之间有显著的正相关;情绪调节自我效能感在一般自我效能感对心理弹性的影响之间具有完全中介作用。

  1. BOOK REVIEW: Mathematica for Theoretical Physics: Electrodynamics, Quantum Mechanics, General Relativity and Fractals

    Science.gov (United States)

    Heusler, Stefan

    2006-12-01

    The main focus of the second, enlarged edition of the book Mathematica for Theoretical Physics is on computational examples using the computer program Mathematica in various areas in physics. It is a notebook rather than a textbook. Indeed, the book is just a printout of the Mathematica notebooks included on the CD. The second edition is divided into two volumes, the first covering classical mechanics and nonlinear dynamics, the second dealing with examples in electrodynamics, quantum mechanics, general relativity and fractal geometry. The second volume is not suited for newcomers because basic and simple physical ideas which lead to complex formulas are not explained in detail. Instead, the computer technology makes it possible to write down and manipulate formulas of practically any length. For researchers with experience in computing, the book contains a lot of interesting and non-trivial examples. Most of the examples discussed are standard textbook problems, but the power of Mathematica opens the path to more sophisticated solutions. For example, the exact solution for the perihelion shift of Mercury within general relativity is worked out in detail using elliptic functions. The virial equation of state for molecules' interaction with Lennard-Jones-like potentials is discussed, including both classical and quantum corrections to the second virial coefficient. Interestingly, closed solutions become available using sophisticated computing methods within Mathematica. In my opinion, the textbook should not show formulas in detail which cover three or more pages—these technical data should just be contained on the CD. Instead, the textbook should focus on more detailed explanation of the physical concepts behind the technicalities. The discussion of the virial equation would benefit much from replacing 15 pages of Mathematica output with 15 pages of further explanation and motivation. In this combination, the power of computing merged with physical intuition

  2. Functional anatomy and ion regulatory mechanisms of the antennal gland in a semi-terrestrial crab, Ocypode stimpsoni

    Directory of Open Access Journals (Sweden)

    Jyuan-Ru Tsai

    2014-05-01

    Full Text Available Brachyuran crabs from diverse habitats show great differences in their osmoregulatory processes, especially in terms of the structural and physiological characteristics of the osmoregulatory organs. In crustaceans, the antennal glands are known to be important in osmoregulation, and they play a functional role analogous to that of the vertebrate kidney. Nevertheless, the detailed structure and function of the antennal glands in different species have rarely been described. The aim of this study is to investigate the role of the antennal gland in ion regulation by examining the ultrastructure of the cells and the distribution of the ion regulatory proteins in each cell type in the antennal gland of a semi-terrestrial crab. The results showed that Na+, K+-ATPase activity significantly increased in the antennal gland after a 4-day acclimation in dilute seawater and returned to its original (day 0 level after 7 days. Three major types of cells were identified in the antennal gland, including coelomic cells (COEs, labyrinthine cells (LBRs and end-labyrinthine cells (ELBRs. The proximal tubular region (PT and distal tubular region (DT of the antennal gland consist of LBRs and COEs, whereas the end tubular region (ET consists of all three types of cells, with fewer COEs and more ELBRs. We found a non-uniform distribution of NKA immunoreactivity, with increasing intensity from the proximal to the distal regions of the antennal gland. We summarise our study with a proposed model for the urine reprocessing pathway and the role of each cell type or segment of the antennal gland.

  3. Control of liver size by RNAi-mediated multiplex knockdown and its application for discovery of regulatory mechanisms

    Science.gov (United States)

    Yin, Hao; Bogorad, Roman L.; Barnes, Carmen; Walsha, Stephen; Zhuang, Iris; Nonaka, Hidenori; Ruda, Vera; Kuchimanchi, Satya; Nechev, Lubomir; Akinc, Akin; Xue, Wen; Zerial, Marino; Langer, Robert; Anderson, Daniel G.; Koteliansky, Victor

    2017-01-01

    Background and aims The Hippo pathway controls organ size through a negative regulation of the transcription co-activator Yap1. The overexpression of hyperactive mutant Yap1 or deletion of key components in the Hippo pathway leads to increased organ size in different species. Analysis of interactions of this pathway with other cellular signals corroborating organ size control is limited in part due to the difficulties associated with development of rodent models. Methods Here, we develop a new model of reversible induction of the liver size in mice using siRNA-nanoparticles targeting two kinases of Hippo pathway, namely, mammalian Ste20 family kinases 1 and 2 (Mst1 and Mst2), and an upstream regulator, neurofibromatosis type II (NF2). Results The triple siRNAs nanoparticle-induced hepatomegaly in mice phenocopies one observed with Mst1-/- Mst2-/- liver-specific depletion, as shown by extensive proliferation of hepatocytes and activation of Yap1. The simultaneous co-treatment with a fourth siRNA nanoparticle against Yap1 fully blocked the liver growth. Hippo pathway-induced liver enlargement is associated with p53 activation, evidenced by its accumulation in the nuclei and upregulation of its target genes. Moreover, injections of the triple siRNAs nanoparticle in p53LSL/LSL mice shows that livers lacking p53 expression grow faster and exceed the size of livers in p53 wild type animals, indicating a role of p53 in controlling Yap1-induced liver growth. Conclusion Our data show that siRNA-nanoparticulate manipulation of gene expression can provide the reversible control of organ size in adult animals, which presents a new avenue for the investigation of complex regulatory networks in liver. PMID:26658687

  4. Autophagy Regulatory Network - a systems-level bioinformatics resource for studying the mechanism and regulation of autophagy.

    Science.gov (United States)

    Türei, Dénes; Földvári-Nagy, László; Fazekas, Dávid; Módos, Dezső; Kubisch, János; Kadlecsik, Tamás; Demeter, Amanda; Lenti, Katalin; Csermely, Péter; Vellai, Tibor; Korcsmáros, Tamás

    2015-01-01

    Autophagy is a complex cellular process having multiple roles, depending on tissue, physiological, or pathological conditions. Major post-translational regulators of autophagy are well known, however, they have not yet been collected comprehensively. The precise and context-dependent regulation of autophagy necessitates additional regulators, including transcriptional and post-transcriptional components that are listed in various datasets. Prompted by the lack of systems-level autophagy-related information, we manually collected the literature and integrated external resources to gain a high coverage autophagy database. We developed an online resource, Autophagy Regulatory Network (ARN; http://autophagy-regulation.org), to provide an integrated and systems-level database for autophagy research. ARN contains manually curated, imported, and predicted interactions of autophagy components (1,485 proteins with 4,013 interactions) in humans. We listed 413 transcription factors and 386 miRNAs that could regulate autophagy components or their protein regulators. We also connected the above-mentioned autophagy components and regulators with signaling pathways from the SignaLink 2 resource. The user-friendly website of ARN allows researchers without computational background to search, browse, and download the database. The database can be downloaded in SQL, CSV, BioPAX, SBML, PSI-MI, and in a Cytoscape CYS file formats. ARN has the potential to facilitate the experimental validation of novel autophagy components and regulators. In addition, ARN helps the investigation of transcription factors, miRNAs and signaling pathways implicated in the control of the autophagic pathway. The list of such known and predicted regulators could be important in pharmacological attempts against cancer and neurodegenerative diseases.

  5. Neural mechanisms of symptom improvements in generalized anxiety disorder following mindfulness training☆☆☆

    Science.gov (United States)

    Hölzel, Britta K.; Hoge, Elizabeth A.; Greve, Douglas N.; Gard, Tim; Creswell, J. David; Brown, Kirk Warren; Barrett, Lisa Feldman; Schwartz, Carl; Vaitl, Dieter; Lazar, Sara W.

    2013-01-01

    Mindfulness training aims to impact emotion regulation. Generalized anxiety disorder (GAD) symptoms can be successfully addressed through mindfulness-based interventions. This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training. Furthermore, we compared brain activation between GAD patients and healthy participants at baseline. 26 patients with a current DSM-IV GAD diagnosis were randomized to an 8-week Mindfulness Based Stress Reduction (MBSR, N = 15) or a stress management education (SME, N = 11) active control program. 26 healthy participants were included for baseline comparisons. BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions. At baseline, GAD patients showed higher amygdala activation than healthy participants in response to neutral, but not angry faces, suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients. In patients, amygdala activation in response to neutral faces decreased following both interventions. BOLD response in ventrolateral prefrontal regions (VLPFC) showed greater increase in MBSR than SME participants. Functional connectivity between amygdala and PFC regions increased significantly pre- to post-intervention within the MBSR, but not SME group. Both, change in VLPFC activation and amygdala–prefrontal connectivity were correlated with change in Beck Anxiety Inventory (BAI) scores, suggesting clinical relevance of these changes. Amygdala–prefrontal connectivity turned from negative coupling (typically seen in down-regulation of emotions), to positive coupling; potentially suggesting a unique mechanism of mindfulness. Findings suggest that in GAD, mindfulness training leads to changes in fronto-limbic areas crucial for the regulation of emotion; these changes correspond with reported symptom improvements. PMID:24179799

  6. Potential of acute phase proteins as predictor of postpartum uterine infections during transition period and its regulatory mechanism in dairy cattle

    Directory of Open Access Journals (Sweden)

    A. Manimaran

    2016-01-01

    Full Text Available Among the various systemic reactions against infection or injury, the acute phase response is the cascade of reaction and mostly coordinated by cytokines-mediated acute phase proteins (APPs production. Since APPs are sensitive innate immune molecules, they are useful for early detection of inflammation in bovines and believed to be better discriminators than routine hematological parameters. Therefore, the possibility of using APPs as a diagnostic and prognostic marker of inflammation in major bovine health disorders including postpartum uterine infection has been explored by many workers. In this review, we discussed specifically importance of postpartum uterine infection, the role of energy balance in uterine infections and potential of APPs as a predictor of postpartum uterine infections during the transition period and its regulatory mechanism in dairy cattle.

  7. 基因表达调控机制--操纵子模型的确立%The establishment of genetic regulatory mechanisms-operon model

    Institute of Scientific and Technical Information of China (English)

    向义和

    2013-01-01

    笔者介绍了基因表达调控机制--操纵子模型建立的过程:诱导物和阻遏物的发现及对其性质的研究;调节基因和操纵基因的发现及对其性能的分析;操纵子模型建立和实验验证。%The establishment of genetic regulatory mechanisms-operon model is introduced. The key events include the discovery of inducer, repressor, regulator gene and operator, the study of their properties, the establishment of operon model and the evidence of experiment.

  8. Effects of the local resonance on the wave propagation in periodic frame structures: generalized Newtonian mechanics.

    Science.gov (United States)

    Chesnais, Céline; Boutin, Claude; Hans, Stéphane

    2012-10-01

    This work is devoted to the study of the wave propagation in infinite two-dimensional structures made up of the periodic repetition of frames. Such materials are highly anisotropic and, because of lack of bracing, can present a large contrast between the shear and compression deformabilities. Moreover, when the thickness to length ratio of the frame elements is small, these elements can resonate in bending at low frequencies when compressional waves propagate in the structure. The frame size being small compared to the wavelength of the compressional waves, the homogenization method of periodic discrete media is extended to situations with local resonance, and it is applied to identify the macroscopic behavior at the leading order. In particular, the local resonance in bending leads to an effective mass different from the real mass and to the generalization of the Newtonian mechanics at the macroscopic scale. Consequently, compressional waves become dispersive and frequency bandgaps occur. The physical origin of these phenomena at the microscopic scale is also presented. Finally, a method is proposed for the design of such materials.

  9. Generalized Toda Mechanics Associated with Classical Lie Algebras and Their Reductions

    Institute of Scientific and Technical Information of China (English)

    ZHAO Liu; LIU Wang-Yun; YANG Zhan-Ying

    2004-01-01

    For any classical Lie algebra g, we construct a family of integrable generalizations of Toda mechanics labeled a pair of ordered integers (m, n). The universal form of the Lax pair, equations of motion, Hamiltonian as well as Poisson brackets areprovided, and explicit examples for g = Br, Cr,Dr with m, n ≤ 3 are also given. For all m, n, it is shown that the dynamics of the (m, n - 1)- and the (m - 1, n)-Toda chains are natural reductions of that of the (m, n)-chain,and for m = n, there is also a family of symmetrically reduced Toda systems, the (m, m)sym-Toda systems, which are also integrable. In the quantum case, all (m,n)-Toda systems with m > 1 or n > 1 describe the dynamics of standard Toda variables coupled to noncommutative variables. Except for the symmetrically reduced cases, the integrability for all (m, n)-Toda systems survive after quantization.

  10. Stepwise Versus Concerted Mechanisms in General-Base Catalysis by Serine Proteases.

    Science.gov (United States)

    Uritsky, Neta; Shokhen, Michael; Albeck, Amnon

    2016-01-26

    General-base catalysis in serine proteases still poses mechanistic challenges despite decades of research. Whether proton transfer from the catalytic Ser to His and nucleophilic attack on the substrate are concerted or stepwise is still under debate, even for the classical Asp-His-Ser catalytic triad. To address these key catalytic steps, the transformation of the Michaelis complex to tetrahedral complex in the covalent inhibition of two prototype serine proteases was studied: chymotrypsin (with the catalytic triad) inhibition by a peptidyl trifluoromethane and GlpG rhomboid (with Ser-His dyad) inhibition by an isocoumarin derivative. The sampled MD trajectories of averaged pKa  values of catalytic residues were QM calculated by the MD-QM/SCRF(VS) method on molecular clusters simulating the active site. Differences between concerted and stepwise mechanisms are controlled by the dynamically changing pKa  values of the catalytic residues as a function of their progressively reduced water exposure, caused by the incoming ligand.

  11. The general mechanisms of Cu cluster formation in the processes of condensation from the gas phase

    Indian Academy of Sciences (India)

    I V Chepkasov; Yu Ya Gafner; S L Gafner; S P Bardakhanov

    2015-06-01

    Technological applications of metallic clusters impose very strict requirements for particle size, shape, structure and defect density. Such geometrical characteristics of nanoparticles are mainly determined by the process of their growth. This work represents the basic mechanisms of cluster formation from the gas phase that has been studied on the example of copper. The process of Cu nanoclusters synthesis has been studied by the moleculardynamics method based on tight-binding potentials. It has been shown that depending on the size and temperature of the initial nanoclusters the process of nanoparticle formation can pass through different basic scenarios. The general conditions of different types of particles formation have been defined and clear dependence of the cluster shape from collision temperature of initial conglomerates has been shown. The simulation results demonstrate a very good agreement with the available experimental data. Thus, it has been shown that depending on the specific application of the synthesized particles or in electronics, where particles of a small size with a spherical shape are required, or in catalytic reactions, where the main factor of effectiveness is the maximum surface area with the help of temperature of the system it is possible to get the realization of a certain frequency of this or that scenario of the shape formation of nanocrystalline particles.

  12. Mechanisms for Creating a Psychologically Safe Learning Environment in an Educational Institution of General Education

    Directory of Open Access Journals (Sweden)

    Leonova O.I.,

    2014-11-01

    Full Text Available At the moment the question of how to create and maintain the psychological safety of the educational environment of the school is not sufficiently studied. Meanwhile, there has been proved its positive effect on the psychological health of students, their emotional and personal well-being, the formation of a meta-subjective and personal educational outcomes. This paper describes a study the purpose of which was to examine and verify empiricaly the features of management activities in the educational organization to create a psychologically safe learning environment. We studied personality traits of the Head of an educational organization by the procedure "Troubleshooting leadership abilities" (E. Zharikova, E. Krushelnytsky, techniques "Diagnosis of the level of burnout" (V.V. Boyko, methods of self-management style assessment (A.V. Agrashenkova, modified by E.P. Ilyin, and methods for rapid assessment of health, activity, mood (SAN. We proposed mechanisms to solve the problem of creating a comfortable and safe learning environment in the educational organization of general education

  13. 肺纤维化的信号转导分子调控机制%Signaling molecular regulatory mechanisms of pulmonary fibrosis

    Institute of Scientific and Technical Information of China (English)

    余杰; 毛丽君; 赵金垣

    2015-01-01

    肺纤维化是一组各种原因所导致肺组织损伤的致命性疾病,主要表现为成纤维细胞增殖分化与胶原沉积.肺纤维化的分子机制主要集中于纤维化的始动因素以及成肌纤维母细胞的增殖分化;研究显示整个肺纤维化过程接受细胞因子网络与细胞内信号转导中的调控机制;阐明肺纤维化分子调控机制有利于抗纤维化治疗的开展.%Pulmonary fibrosis is a kind of lethal lung tissue injury diseases caused by various etiologies,with the main performance of fibroblast proliferation and collagen deposition.The molecular mechanisms of pulmonary fibrosis mainly focus on the initiating factors of the fibrosis and the myofibroblast proliferation and differentiation.Studies show that the whole course of pulmonary fibrosis is regulated by the mechanisms of cytokine networks and intracellular signal transduction.The research on molecular regulatory mechanisms of pulmonary fibrosis can be beneficial to the development of anti fibrosis therapy.

  14. Immune-Regulatory Mechanisms of Classical and Experimental Multiple Sclerosis Drugs: A Special Focus on Helminth-Derived Treatments.

    Science.gov (United States)

    Peón, Alberto N; Terrazas, Luis I

    2016-01-01

    Multiple sclerosis (MS) is the most prevalent autoimmune disease affecting the central nervous system (CNS). Its pathophysiology is centered on neuron myelin sheath destruction in a manner largely dependent upon CD4+/CD8+ T-cell autoreactivity against myelin antigens, inducing Th1/Th17 pathogenic responses with the resulting production of free radicals and soluble mediators that exhibit the effector mechanisms of neurodegeneration. The immune response responsible for this disease is complex and challenges modern medicine. Consequently, many experimental therapies have been proposed in addition to the classical array of immunoregulatory/ immunosuppressive drugs that are normally used to treat MS. In this review, we will describe the effects and mechanisms of action of widely used disease-modifying MS drugs as well as those of select treatments that are currently in the experimental phase. Special emphasis is placed on helminth-derived immunoregulators, as some of them have shown promising results. Additionally, we will compare the mechanisms of action of both the MS drugs and the helminth-derived treatments to discuss the potential importance of some signaling pathways in the control of MS.

  15. Mechanism of Regulatory Effect of MicroRNA-206 on Connexin 43 in Distant Metastasis of Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Zi-Jing Lin; Jia Ming; Lu Yang; Jun-Ze Du; Ning Wang; Hao-Jun Luo

    2016-01-01

    Background: MicroRNA-206 (miR-206) and connexin 43 (Cx43) are related with the distant metastasis of breast cancer.It remains unclear whether the regulatory effect of miR-206 on Cx43 is involved in metastasis of breast cancer.Methods: Using quantitative real-time polymerase chain reaction and Western blot, the expressions of miR-206 and Cx43 were determined in breast cancer tissues, hepatic and pulmonary metastasis (PM), and cell lines (MCF-10A, MCF-7, and MDA-MB-231).MCF-7/MDA-M-231 cells were transfected with lentivirus-shRNA vectors to enhance/inhibit miR-206, and then Cx43 expression was observed.Cell counting kit-8 assay and Transwell method were used to detect their changes in proliferation, migration, and invasion activity.The mutant plasmids of Cx43-3' untranslated region (3'UTR) at position 478-484 and position 1609-1615 were constructed.Luciferase reporter assay was performed to observe the effects of miR-206 on luciferase expression of different mutant plasmids and to confirm the potential binding sites of Cx43.Results: Cx43 protein expression in hepatic and PM was significantly higher than that in the primary tumor, while no significant difference was showed in messenger RNA (mRNA) expression.MiR-206 mRNA expression in hepatic and PM was significantly lower than that in the primary tumor.Cx43 mRNA and protein levels, as well as cell proliferation, migration, and invasion capabilities, were all significantly improved in MDA-MB-231 cells after reducing miR-206 expression but decreased in MCF-7 cells after elevating miR-206 expression, which demonstrated a significantly negative correlation between miR-206 and Cx43 expression (P =0.03).MiR-206 can drastically decrease Cx43 expression of MCF-7 cells but exerts no effects on Cx43 expression in 293 cells transfected with the Cx43 coding region but the lack of Cx43-3'UTR, suggesting that Cx43-3'UTR may be the key in Cx43 regulated by miR-206.Luciferase expression showed that the inhibition efficiency was

  16. Regulatory mechanism on enhancing protein synthesis in skeletal muscles of cold exposed fresh water fish (Channa punctata)

    OpenAIRE

    Md Shahidul Haque; Md. Asraful Haque; Swapan Kumar Roy; M M H Khan; Md Mosharrof Hossain

    2014-01-01

    Channa punctata varieties of fish are energetic and survive in critical environment although the molecular mechanism is not known. They were exposed to cold (4–8 °C) for 30 min, 1 h, 2 h and 4 h and the total protein contents in the liver were not significantly changed up to 4 h of cold exposure while a significantly increased protein level in the skeletal muscle was noted and maximal at 2 h. Groups of fish were exposed to Na2HAsO4 to examine its role on cold-induced protein synthesis in the ...

  17. Complementary vascular and matrix regulatory pathways underlie the beneficial mechanism of action of sorafenib in liver fibrosis

    Science.gov (United States)

    Thabut, Dominique; Routray, Chittaranjan; Lomberk, Gwen; Shergill, Uday; Glaser, Kevin; Huebert, Robert; Patel, Leena; Masyuk, Tetyana; Blechacz, Boris; Vercnocke, Andrew; Ritman, Erik; Ehman, Richard; Urrutia, Raul; Shah, Vijay

    2011-01-01

    Background Paracrine signaling between hepatic stellate cells (HSC) and liver endothelial cells (LEC) modulates fibrogenesis, angiogenesis, and portal hypertension. However, mechanisms regulating these processes are not fully defined. Sorafenib is a receptor tyrosine kinase inhibitor that blocks growth factor signaling in tumor cells but also displays important and not yet fully characterized effects on liver nonparenchymal cells including HSC and LEC. The aim of this study was to test the hypothesis that sorafenib influences paracrine signaling between HSC and LEC and thereby regulates matrix and vascular changes associated with chronic liver injury. Results Complementary magnetic resonance elastography, micro-CT, and histochemical analyses indicate that sorafenib attenuates the changes in both matrix and vascular compartments that occur in response to bile-duct ligation induced liver injury in rats. Cell biology studies demonstrate that sorafenib markedly reduces cell to cell apposition and junctional complexes, thus reducing the proximity typically observed between these sinusoidal barrier cells. At the molecular level, sorafenib down-regulates angiopoietin-1 and fibronectin, both released by HSC in a manner dependent on the transcription factor KLF6, suggesting that this pathway underlies both matrix and vascular changes associated with chronic liver disease. Conclusion Collectively, our results demonstrate that sorafenib inhibits both matrix restructuring and vascular remodeling that accompany chronic liver diseases and characterize cell and molecular mechanisms underlying this effect. These data may help to refine future therapies for advanced gastrointestinal and liver diseases characterized by abundant fibrosis and neovascularization. PMID:21567441

  18. Regulatory mechanism on enhancing protein synthesis in skeletal muscles of cold exposed fresh water fish (Channa punctata

    Directory of Open Access Journals (Sweden)

    Md. Shahidul Haque

    2014-06-01

    Full Text Available Channa punctata varieties of fish are energetic and survive in critical environment although the molecular mechanism is not known. They were exposed to cold (4–8 °C for 30 min, 1 h, 2 h and 4 h and the total protein contents in the liver were not significantly changed up to 4 h of cold exposure while a significantly increased protein level in the skeletal muscle was noted and maximal at 2 h. Groups of fish were exposed to Na2HAsO4 to examine its role on cold-induced protein synthesis in the skeletal muscle and the increased protein in the skeletal muscle was reduced significantly. The results appear to indicate that cold acclimation induces a metabolic change involving cellular protein content tissue specifically and arsenic might be involved in impairment of the cold-induced effect. To clarify the molecular mechanism, groups of fish exposed to cold for 1 h and 2 h had significantly increased RNA in the skeletal muscle compared to control fish, however, a higher level was found after 2 h of treatment and the enhanced RNA induced by cold was almost completely prevented by Na2HAsO4. Our findings will give a new insight into the survival process of this species while toxic arsenic prevents this cellular bioprocess.

  19. First Insights into the Subterranean Crustacean Bathynellacea Transcriptome: Transcriptionally Reduced Opsin Repertoire and Evidence of Conserved Homeostasis Regulatory Mechanisms

    Science.gov (United States)

    Kim, Bo-Mi; Kang, Seunghyun; Ahn, Do-Hwan; Kim, Jin-Hyoung; Ahn, Inhye; Lee, Chi-Woo; Cho, Joo-Lae; Min, Gi-Sik; Park, Hyun

    2017-01-01

    Bathynellacea (Crustacea, Syncarida, Parabathynellidae) are subterranean aquatic crustaceans that typically inhabit freshwater interstitial spaces (e.g., groundwater) and are occasionally found in caves and even hot springs. In this study, we sequenced the whole transcriptome of Allobathynella bangokensis using RNA-seq. De novo sequence assembly produced 74,866 contigs including 28,934 BLAST hits. Overall, the gene sequences were most similar to those of the waterflea Daphnia pulex. In the A. bangokensis transcriptome, no opsin or related sequences were identified, and no contig aligned to the crustacean visual opsins and non-visual opsins (i.e. arthropsins, peropsins, and melaopsins), suggesting potential regressive adaptation to the dark environment. However, A. bangokensis expressed conserved gene family sets, such as heat shock proteins and those related to key innate immunity pathways and antioxidant defense systems, at the transcriptional level, suggesting that this species has evolved adaptations involving molecular mechanisms of homeostasis. The transcriptomic information of A. bangokensis will be useful for investigating molecular adaptations and response mechanisms to subterranean environmental conditions. PMID:28107438

  20. 77 FR 59702 - Promoting U.S. EC Regulatory Compatibility

    Science.gov (United States)

    2012-09-28

    ... Promoting U.S. EC Regulatory Compatibility AGENCY: Office of the United States Trade Representative. ACTION... greater transatlantic regulatory compatibility generally. Concrete ideas on how greater compatibility... and EC invite your views on how to promote greater transatlantic regulatory compatibility...

  1. Alveolar recruiting maneuver in dogs under general anesthesia: effects on alveolar ventilation, gas exchange, and respiratory mechanics.

    Science.gov (United States)

    Staffieri, F; De Monte, V; De Marzo, C; Scrascia, F; Crovace, A

    2010-06-01

    The aim of this study was to evaluate the effects of a recruiting maneuver (RM) on lung aeration, gas exchange, and respiratory mechanics during general anesthesia in mechanically ventilated dogs. A thoracic computed tomography (CT) scan, an arterial blood sample, and measurement of respiratory mechanics were performed 10 min before (baseline) and both 5 and 30 min after a vital capacity RM in 10 dogs under general anesthesia. The RM was performed by inflating the lung at 40 cm H(2)O for 20 s. Lung aeration was estimated by analyzing the radiographic attenuation of the CT images. Lung aeration and gas exchange improved significantly 5 min after the RM compared to baseline and returned to values similar to baseline by 30 min. Static lung compliance was not significantly affected by the RM. An RM induces a temporary improvement in lung function in healthy dogs under general anesthesia.

  2. Regulatory mechanisms for 3'-end alternative splicing and polyadenylation of the Glial Fibrillary Acidic Protein, GFAP, transcript

    DEFF Research Database (Denmark)

    Blechingberg, Jenny; Lykke-Andersen, Søren; Jensen, Torben Heick

    2007-01-01

    molecular mechanisms participating in alternative GFAP expression. Usage of a polyadenylation signal within the alternatively spliced exon 7a is essential to generate the GFAP kappa and GFAP kappa transcripts. The GFAP kappa mRNA is distinct from GFAP epsilon mRNA given that it also includes intron 7a......The glial fibrillary acidic protein, GFAP, forms the intermediate cytoskeleton in cells of the glial lineage. Besides the common GFAP alpha transcript, the GFAP epsilon and GFAP kappa transcripts are generated by alternative mRNA 3'-end processing. Here we use a GFAP minigene to characterize...... (PTB) protein enhanced both exon 7a polyadenylation and exon 7a splicing. Finally, increasing transcription by the VP16 trans-activator did not affect the frequency of use of the exon 7a polyadenylation signal whereas the exon 7a splicing frequency was decreased. Our data suggest a model...

  3. Regulatory Mechanisms of a Highly Pectinolytic Mutant of Penicillium occitanis and Functional Analysis of a Candidate Gene in the Plant Pathogen Fusarium oxysporum

    Directory of Open Access Journals (Sweden)

    Gustavo Bravo-Ruiz

    2017-09-01

    Full Text Available Penicillium occitanis is a model system for enzymatic regulation. A mutant strain exhibiting constitutive overproduction of different pectinolytic enzymes both under inducing (pectin or repressing conditions (glucose was previously isolated after chemical mutagenesis. In order to identify the molecular basis of this regulatory mechanism, the genomes of the wild type and the derived mutant strain were sequenced and compared, providing the first reference genome for this species. We used a phylogenomic approach to compare P. occitanis with other pectinolytic fungi and to trace expansions of gene families involved in carbohydrate degradation. Genome comparison between wild type and mutant identified seven mutations associated with predicted proteins. The most likely candidate was a mutation in a highly conserved serine residue of a conserved fungal protein containing a GAL4-like Zn2Cys6 binuclear cluster DNA-binding domain and a fungus-specific transcription factor regulatory middle homology region. To functionally characterize the role of this candidate gene, the mutation was recapitulated in the predicted orthologue Fusarium oxysporum, a vascular wilt pathogen which secretes a wide array of plant cell wall degrading enzymes, including polygalacturonases, pectate lyases, xylanases and proteases, all of which contribute to infection. However, neither the null mutant nor a mutant carrying the analogous point mutation exhibited a deregulation of pectinolytic enzymes. The availability, annotation and phylogenomic analysis of the P. occitanis genome sequence represents an important resource for understanding the evolution and biology of this species, and sets the basis for the discovery of new genes of biotechnological interest for the degradation of complex polysaccharides.

  4. Research progress on regulatory mechanism of liver cancer stem cells%肝癌干细胞调控机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    王旭; 王超

    2014-01-01

    肿瘤干细胞学说认为,肝癌的复发和转移主要与肝癌干细胞密切相关.以手术为主的传统治疗肝癌的方法只是杀死了大量快速增殖的肿瘤细胞,并未清除起决定性作用的肝癌干细胞,故术后极易复发转移.调控肝癌干细胞的信号通路及因子较多,如Wnt/β-catenin通路、TGF-β通路、Notch通路、Hedgehog通路、乙型肝炎病毒等.表观遗传学在肝癌干细胞调控机制中的作用亦很重要.深入研究肝癌干细胞的调控机制,可为防止肝癌的复发和转移提供新的治疗依据.%The theory of cancer stem cells proposed that recurrence and metastasis of liver cancer are closely related to liver cancer stem cells.The traditional surgical treatment of liver cancer simply kills those rapidly proliferating tunor cells instead of eliminating hepatic cancer stem cells which play decisive role in recurrence and metastasis.As far as people have concerned,there are many signaling pathways and regulatory factors modulating liver cancer stem cells,such as the Wnt/β-catenin pathway,TGF-β pathway,Notch pathway,Hedgehog pathway,hepatitis B virus,as well as epigenetics.Further studies on regulatory mechanisms of liver cancer stem cells are of great significance,in hope of providing new evidence for treatment and prevention of recurrence and metastasis of liver cancer.

  5. A mathematical model of cancer stem cell driven tumor initiation: implications of niche size and loss of homeostatic regulatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Sara N Gentry

    Full Text Available Hierarchical organized tissue structures, with stem cell driven cell differentiation, are critical to the homeostatic maintenance of most tissues, and this underlying cellular architecture is potentially a critical player in the development of a many cancers. Here, we develop a mathematical model of mutation acquisition to investigate how deregulation of the mechanisms preserving stem cell homeostasis contributes to tumor initiation. A novel feature of the model is the inclusion of both extrinsic and intrinsic chemical signaling and interaction with the niche to control stem cell self-renewal. We use the model to simulate the effects of a variety of types and sequences of mutations and then compare and contrast all mutation pathways in order to determine which ones generate cancer cells fastest. The model predicts that the sequence in which mutations occur significantly affects the pace of tumorigenesis. In addition, tumor composition varies for different mutation pathways, so that some sequences generate tumors that are dominated by cancerous cells with all possible mutations, while others are primarily comprised of cells that more closely resemble normal cells with only one or two mutations. We are also able to show that, under certain circumstances, healthy stem cells diminish due to the displacement by mutated cells that have a competitive advantage in the niche. Finally, in the event that all homeostatic regulation is lost, exponential growth of the cancer population occurs in addition to the depletion of normal cells. This model helps to advance our understanding of how mutation acquisition affects mechanisms that influence cell-fate decisions and leads to the initiation of cancers.

  6. Favorable genomic environments for cis-regulatory evolution: A novel theoretical framework.

    Science.gov (United States)

    Maeso, Ignacio; Tena, Juan J

    2016-09-01

    Cis-regulatory changes are arguably the primary evolutionary source of animal morphological diversity. With the recent explosion of genome-wide comparisons of the cis-regulatory content in different animal species is now possible to infer general principles underlying enhancer evolution. However, these studies have also revealed numerous discrepancies and paradoxes, suggesting that the mechanistic causes and modes of cis-regulatory evolution are still not well understood and are probably much more complex than generally appreciated. Here, we argue that the mutational mechanisms and genomic regions generating new regulatory activities must comply with the constraints imposed by the molecular properties of cis-regulatory elements (CREs) and the organizational features of long-range chromatin interactions. Accordingly, we propose a new integrative evolutionary framework for cis-regulatory evolution based on two major premises for the origin of novel enhancer activity: (i) an accessible chromatin environment and (ii) compatibility with the 3D structure and interactions of pre-existing CREs. Mechanisms and DNA sequences not fulfilling these premises, will be less likely to have a measurable impact on gene expression and as such, will have a minor contribution to the evolution of gene regulation. Finally, we discuss current comparative cis-regulatory data under the light of this new evolutionary model, and propose that the two most prominent mechanisms for the evolution of cis-regulatory changes are the overprinting of ancestral CREs and the exaptation of transposable elements.

  7. A novel regulatory mechanism of the mitochondrial Ca2+ uniporter revealed by the p38 mitogen-activated protein kinase inhibitor SB202190.

    Science.gov (United States)

    Montero, Mayte; Lobaton, Carmen D; Moreno, Alfredo; Alvarez, Javier

    2002-12-01

    It is widely acknowledged that mitochondrial Ca2+ uptake modulates the cytosolic [Ca2+] ([Ca2+]c) acting as a transient Ca2+ buffer. In addition, mitochondrial [Ca2+] ([Ca2+]M) regulates the rate of respiration and may trigger opening of the permeability transition pore and start apoptosis. However, no mechanism for the physiological regulation of mitochondrial Ca2+ uptake has been described. We show here that SB202190, an inhibitor of p38 mitogen-activated protein (MAP) kinase, strongly stimulates ruthenium red-sensitive mitochondrial Ca2+ uptake, both in intact and in permeabilized HeLa cells. The [Ca2+]M peak induced by agonists was increased about fourfold in the presence of the inhibitor, with a concomitant reduction in the [Ca2+]c peak. The stimulation occurred fast and was rapidly reversible. In addition, experiments in permeabilized cells perfused with controlled [Ca2+] showed that SB202190 stimulated mitochondrial Ca2+ uptake by more than 10-fold, but only in the physiological [Ca2+]c range (1-4 mM). Other structurally related p38 MAP kinase inhibitors (SB203580, PD169316, or SB220025) produced little or no effect. Our data suggest that in HeLa cells, a protein kinase sensitive to SB202190 tonically inhibits the mitochondrial Ca2+ uniporter. This novel regulatory mechanism may be of paramount importance to modulate mitochondrial Ca2+ uptake under different physiopathological conditions.

  8. 血脑屏障中P-糖蛋白的调节机制%Regulatory mechanisms of P-glycoprotein at the blood-brain barrier

    Institute of Scientific and Technical Information of China (English)

    王玉璘; 王少峡; 郭虹; 胡利民

    2011-01-01

    P-糖蛋白属于ABC转运蛋白超家族.它在脑微血管中大量表达,限制毒性物质和大量治疗中枢神经系统的药物进入脑内,因此弄清P-糖蛋白在血脑屏障中的调节机制对疾病的治疗尤为重要.该文总结了P-糖蛋白基本结构、分布、功能,并讨论了P-糖蛋白在血脑屏障中调节机制的研究进展.%P-glycoprotein (P-gp) belongs to the adenosine triphosphate( ATP )-binding cassette( ABC ) proteins, which is present in the microvessels in the brain, so it can prevent cytotoxic compounds and large amount of CNS agents entering the brain. Thus, it is important to find out the mechanisms that regulate P-gp function and expression in the blood-brain barier for pharmcotherapy. In this review, the structure, tissue distribution and the function of P-glycoprotein were reviewed, focusing on the research advances of regulatory mechanisms at the bloodbrain barrier.

  9. Insights into the mechanism of FTY720 and compatibility with regulatory T cells for the inhibition of graft-versus-host disease (GVHD).

    Science.gov (United States)

    Taylor, Patricia A; Ehrhardt, Michael J; Lees, Christopher J; Tolar, Jakub; Weigel, Brenda J; Panoskaltsis-Mortari, Angela; Serody, Jonathan S; Brinkmann, Volker; Blazar, Bruce R

    2007-11-01

    The immunomodulator FTY720 (FTY) has been shown to be beneficial in experimental models of organ transplantation and autoimmunity. We show that FTY significantly inhibited but did not prevent graft-versus-host disease (GVHD) in lethally irradiated or nonirradiated allogeneic recipients. Although most studies implicate prevention of lymphocyte egress from lymphoid organs as the primary mechanism of action, our data indicate that FTY effects on the host are more likely to be responsible for GVHD inhibition. FTY reduced splenic CD11c+ cells by 50%, and similarly reduced CD4+ and CD8+ T-cell responder frequencies in the spleen early after transplantation. Imaging of GFP+ effectors indicated that FTY modified donor effector T-cell migration to secondary lymphoid organs, but did not uniformly trap T cells in lymph nodes or prevent early effector migration to GVHD parenchymal target organs. Administration of FTY only prior to transplantation inhibited GVHD, indicating that the primary function of FTY may be targeted to host cells. FTY was additive with regulatory T cells for GVHD inhibition. FTY slightly impaired but did not abrogate a graft-versus-leukemia (GVL) effect against C1498, a myeloid leukemia. Our data further define the mechanisms of action and provide insight as to the potential clinical uses of FTY in allogeneic bone marrow transplant recipients.

  10. The RNA-mediated, asymmetric ring regulatory mechanism of the transcription termination Rho helicase decrypted by time-resolved nucleotide analog interference probing (trNAIP).

    Science.gov (United States)

    Soares, Emilie; Schwartz, Annie; Nollmann, Marcello; Margeat, Emmanuel; Boudvillain, Marc

    2014-08-01

    Rho is a ring-shaped, ATP-dependent RNA helicase/translocase that dissociates transcriptional complexes in bacteria. How RNA recognition is coupled to ATP hydrolysis and translocation in Rho is unclear. Here, we develop and use a new combinatorial approach, called time-resolved Nucleotide Analog Interference Probing (trNAIP), to unmask RNA molecular determinants of catalytic Rho function. We identify a regulatory step in the translocation cycle involving recruitment of the 2'-hydroxyl group of the incoming 3'-RNA nucleotide by a Rho subunit. We propose that this step arises from the intrinsic weakness of one of the subunit interfaces caused by asymmetric, split-ring arrangement of primary RNA tethers around the Rho hexamer. Translocation is at highest stake every seventh nucleotide when the weak interface engages the incoming 3'-RNA nucleotide or breaks, depending on RNA threading constraints in the Rho pore. This substrate-governed, 'test to run' iterative mechanism offers a new perspective on how a ring-translocase may function or be regulated. It also illustrates the interest and versatility of the new trNAIP methodology to unveil the molecular mechanisms of complex RNA-based systems.

  11. Study of the main regulatory mechanisms to encourage renewable and alternative energy applied internationally and in Brazil; Estudo dos principais mecanismos regulatorios de incentivo as fontes renovaveis e alternativas de energia aplicados internacionalmente e no Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Juliana M.C.; Cavaliero, Carla Kazue Nakao [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Fac. de Engenharia Mecanica. Dept. de Energia], Emails: jumcm@fem.unicamp.br, cavaliero@fem.unicamp.br

    2009-07-01

    The investment in renewable and alternative energy sources has been stimulated by some countries in Europe and Americas through the introduction of encouragement regulatory mechanisms. This paper considers the most important international mechanisms such as Feed-in System, Tender System and Quota System with green certificates. In Brazil, there are three regulatory mechanisms in course: PROINFA, the 1. Tender of Renewable and 1. Tender Reserve. The carried out preliminary analysis made possible to classify PROINFA as a mechanism similar to Feed-in, while the auction of Renewable and Reserve are more like an auction system. This article points out the differences and similarities between the instruments and gives a preliminary analysis of their effectiveness, emphasizing national mechanisms, especially regarding the criteria for capacity increase and cost reduction of the technological bands, such as for biomass and small hydroelectric. (author)

  12. Voltammetric current oscillations due to general and pitting corrosion of tantalum: Implications for electrochemical-mechanical planarization

    Energy Technology Data Exchange (ETDEWEB)

    Sulyma, Christopher M. [Department of Physics, Clarkson University, Potsdam, NY 13699-5820 (United States); Roy, Dipankar, E-mail: samoy@clarkson.ed [Department of Physics, Clarkson University, Potsdam, NY 13699-5820 (United States)

    2010-09-15

    Anodic corrosion of Ta is examined for potential applications in electrochemical-mechanical planarization (ECMP) of diffusion barriers. This strategy involves electro-oxidation of Ta in the presence of NO{sub 3}{sup -} (or Br{sup -}) to form mechanically weak surface-oxide films, followed by mechanical removal of the latter. The voltammetric currents exhibit oscillatory behaviour with frequencies that are signature attributes of localised pitting by Br{sup -} or general surface corrosion by NO{sub 3}{sup -}. SEM, voltammetry, and impedance spectroscopy are used to probe these corrosion mechanisms. Apart from their relevance for ECMP, the results also address certain fundamental aspects of pitting and general corrosion of valve metals.

  13. See the forest for the trees: Whole-plant allocation patterns and regulatory mechanisms in Norway spruce

    Science.gov (United States)

    Huang, Jianbei; Behrendt, Thomas; Hammerbacher, Almuth; Weinhold, Alexander; Hellén, Heidi; Reichelt, Michael; Wisthaler, Armin; Dam, Nicole; Trumbore, Susan; Hartmann, Henrik

    2017-04-01

    acetone) decreased whereas monoterpene and sesquiterpene emissions slightly increased with decreasing [CO2]. Our experimental design provides an excellent platform for studying control mechanisms of C allocation. The range of C availabilities applied in our study will allow partitioning compensatory mechanisms (e.g., up-regulation of C storage due to sugar signalling at high C availability) from evolutionary programming (e.g., storage formation to increase long-term survival at expense of other functions with decreasing C availability). Such partitioning is corroborated via phytohormone and transcriptome analysis, and results will hopefully be available at the time of presentation.

  14. Prediction of regulatory elements

    DEFF Research Database (Denmark)

    Sandelin, Albin

    2008-01-01

    Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet-lab...

  15. Acupuncture Alleviates Colorectal Hypersensitivity and Correlates with the Regulatory Mechanism of TrpV1 and p-ERK

    Directory of Open Access Journals (Sweden)

    Shao-Jun Wang

    2012-01-01

    Full Text Available Here we used a mouse model of zymosan-induced colorectal hypersensitivity, a similar model of IBS in our previous work, to evaluate the effectiveness of the different number of times of acupuncture and elucidate its potential mechanism of EA treatment. Colorectal distension (CRD tests show that intracolonic zymosan injection does, while saline injection does not, induce a typical colorectal hypersensitivity. EA treatment at classical acupoints Zusanli (ST36 and Shangjuxu (ST37 in both hind limbs for 15 min slightly attenuated and significantly blunted the hypersensitive responses after first and fifth acupunctures, respectively, to colorectal distention in zymosan treatment mice, but not in saline treatment mice. Western blot results indicated that ion channel and TrpV1 expression in colorectum as well as ERK1/2 MAPK pathway activation in peripheral and central nerve system might be involved in this process. Hence, we conclude that EA is a potential therapeutic tool in the treatment and alleviation of chronic abdominal pain, and the effectiveness of acupuncture analgesia is accumulative with increased number of times of acupuncture when compared to that of a single time of acupuncture.

  16. Studies on the regulatory effect of Peony-Glycyrrhiza Decoction on prolactin hyperactivity and underlying mechanism in hyperprolactinemia rat model.

    Science.gov (United States)

    Wang, Di; Wang, Wei; Zhou, Yulin; Wang, Juan; Jia, Dongxu; Wong, Hei Kiu; Zhang, Zhang-Jin

    2015-10-08

    Clinical trials have demonstrated the beneficial effects of Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL) in schizophrenic patients. In previous experiment, PGD suppressed prolactin (PRL) level in MMQ cells, involving modulating the expression of D2 receptor (DRD2) and dopamine transporter (DAT). In the present study, hyperPRL female rat model induced by dopamine blocker metoclopramide (MCP) was applied to further confirm the anti-hyperpPRL activity of PGD and underlying mechanism. In MCP-induced hyperPRL rats, the elevated serum PRL level was significantly suppressed by either PGD (2.5-10 g/kg) or bromocriptine (BMT) (0.6 mg/kg) administration for 14 days. However, in MCP-induced rats, only PGD restored the under-expressed serum progesterone (P) to control level. Both PGD and BMT administration restore the under-expression of DRD2, DAT and TH resulted from MCP in pituitary gland and hypothalamus. Compared to untreated group, hyperPRL animals had a marked reduction on DRD2 and DAT expression in the arcuate nucleus. PGD (10 g/kg) and BMT (0.6 mg/kg) treatment significant reversed the expression of DRD2 and DAT. Collectively, the anti-hyperPRL activity of PGD associates with the modulation of dopaminergic neuronal system and the restoration of serum progesterone level. Our finding supports PGD as an effective agent against hyperPRL.

  17. Studies on gene structure, enzymatic activity and regulatory mechanism of acetohydroxy acid isomeroreductase from G2 pea

    Institute of Scientific and Technical Information of China (English)

    XU Yunjian (徐云剑); GU Xuesong (顾雪松); LI Jun (李珺); LI Qing (李 晴); Peter J. Davies; ZHU Yuxian (朱玉贤)

    2003-01-01

    The AAIR genomic DNA of G2 pea (Pisum sativum L.) was amplified by PCR method. Sequence analysis showed that it was composed of 8 introns and 9 exons with three of the introns containing specific A/T-rich endogenous promoter regions. Molecular hybridization experiments revealed that the expression of AAIR remained at a high level before and after flowering if grown in short day growth chambers. However, when grown under long day conditions, the level of AAIR expression declined very rapidly after flowering. This variation of AAIR expression is consistent with the change of enzymatic activity of acetohydroxy acid isomeroreductase. Functional complementation experiments carried out using an acetohydroxy acid isomeroreductase deficient E. coli strain showed that these cells could not grow on M9 medium without addition of branched-chain amino acids unless they were transformed with the AAIR expression vector. Further study revealed that overexpression of the pea AAIR cDNA in acetohydroxy acid isomeroreductase deficient E. coli strain enhanced significantly its branched-chain amino acid biosynthetic capacity. Results from gel shift experiments showed that fractions of pea nuclear protein extracts could bind specifically to some A/T rich regions present in introns of the AAIR gene. The A/T-rich-region-binding proteins remained at a steady level in the non-senescing apical buds of short-day grown G2 pea. In the rapid-senescing apical buds of long-day grown G2 pea, the levels of these proteins declined rapidly after flower initiation. Therefore, the nuclear protein binding capacities to endogenous promoter regions may constitute an important mechanism to regulate AAIR gene expression.

  18. A genome-wide analysis of the RNA-guided silencing pathway in coffee reveals insights into its regulatory mechanisms.

    Science.gov (United States)

    Noronha Fernandes-Brum, Christiane; Marinho Rezende, Pâmela; Cherubino Ribeiro, Thales Henrique; Ricon de Oliveira, Raphael; Cunha de Sousa Cardoso, Thaís; Rodrigues do Amaral, Laurence; de Souza Gomes, Matheus; Chalfun-Junior, Antonio

    2017-01-01

    microRNAs (miRNAs) are derived from self-complementary hairpin structures, while small-interfering RNAs (siRNAs) are derived from double-stranded RNA (dsRNA) or hairpin precursors. The core mechanism of sRNA production involves DICER-like (DCL) in processing the smallRNAs (sRNAs) and ARGONAUTE (AGO) as effectors of silencing, and siRNA biogenesis also involves action of RNA-Dependent RNA Polymerase (RDR), Pol IV and Pol V in biogenesis. Several other proteins interact with the core proteins to guide sRNA biogenesis, action, and turnover. We aimed to unravel the components and functions of the RNA-guided silencing pathway in a non-model plant species of worldwide economic relevance. The sRNA-guided silencing complex members have been identified in the Coffea canephora genome, and they have been characterized at the structural, functional, and evolutionary levels by computational analyses. Eleven AGO proteins, nine DCL proteins (which include a DCL1-like protein that was not previously annotated), and eight RDR proteins were identified. Another 48 proteins implicated in smallRNA (sRNA) pathways were also identified. Furthermore, we identified 235 miRNA precursors and 317 mature miRNAs from 113 MIR families, and we characterized ccp-MIR156, ccp-MIR172, and ccp-MIR390. Target prediction and gene ontology analyses of 2239 putative targets showed that significant pathways in coffee are targeted by miRNAs. We provide evidence of the expansion of the loci related to sRNA pathways, insights into the activities of these proteins by domain and catalytic site analyses, and gene expression analysis. The number of MIR loci and their targeted pathways highlight the importance of miRNAs in coffee. We identified several roles of sRNAs in C. canephora, which offers substantial insight into better understanding the transcriptional and post-transcriptional regulation of this major crop.

  19. Lycopene treatment against loss of bone mass, microarchitecture and strength in relation to regulatory mechanisms in a postmenopausal osteoporosis model.

    Science.gov (United States)

    Ardawi, Mohammed-Salleh M; Badawoud, Mohammed H; Hassan, Sherif M; Rouzi, Abdulrahim A; Ardawi, Jumanah M S; AlNosani, Nouf M; Qari, Mohammed H; Mousa, Shaker A

    2016-02-01

    Lycopene supplementation decreases oxidative stress and exhibits beneficial effects on bone health, but the mechanisms through which it alters bone metabolism in vivo remain unclear. The present study aims to evaluate the effects of lycopene treatment on postmenopausal osteoporosis. Six-month-old female Wistar rats (n=264) were sham-operated (SHAM) or ovariectomized (OVX). The SHAM group received oral vehicle only and the OVX rats were randomized into five groups receiving oral daily lycopene treatment (mg/kg body weight per day): 0 OVX (control), 15 OVX, 30 OVX, and 45 OVX, and one group receiving alendronate (ALN) (2μg/kg body weight per day), for 12weeks. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Micro computed tomography was also used to evaluate changes in microarchitecture. Lycopene treatment suppressed the OVX-induced increase in bone turnover, as indicated by changes in biomarkers of bone metabolism: serum osteocalcin (s-OC), serum N-terminal propeptide of type 1 collagen (s-PINP), serum crosslinked carboxyterminal telopeptides (s-CTX-1), and urinary deoxypyridinoline (u-DPD). Significant improvement in OVX-induced loss of bone mass, bone strength, and microarchitectural deterioration was observed in lycopene-treated OVX animals. These effects were observed mainly at sites rich in trabecular bone, with less effect in cortical bone. Lycopene treatment down-regulated osteoclast differentiation concurrent with up-regulating osteoblast together with glutathione peroxidase (GPx) catalase (CAT) and superoxide dismutase (SOD) activities. These findings demonstrate that lycopene treatment in OVX rats primarily suppressed bone turnover to restore bone strength and microarchitecture.

  20. A Novel Regulatory Mechanism of Type II Collagen Expression via a SOX9-dependent Enhancer in Intron 6.

    Science.gov (United States)

    Yasuda, Hideyo; Oh, Chun-do; Chen, Di; de Crombrugghe, Benoit; Kim, Jin-Hoi

    2017-01-13

    Type II collagen α1 is specific for cartilaginous tissues, and mutations in its gene are associated with skeletal diseases. Its expression has been shown to be dependent on SOX9, a master transcription factor required for chondrogenesis that binds to an enhancer region in intron 1. However, ChIP sequencing revealed that SOX9 does not strongly bind to intron 1, but rather it binds to intron 6 and a site 30 kb upstream of the transcription start site. Here, we aimed to determine the role of the novel SOX9-binding site in intron 6. We prepared reporter constructs that contain a Col2a1 promoter, intron 1 with or without intron 6, and the luciferase gene. Although the reporter constructs were not activated by SOX9 alone, the construct that contained both introns 1 and 6 was activated 5-10-fold by the SOX9/SOX5 or the SOX9/SOX6 combination in transient-transfection assays in 293T cells. This enhancement was also observed in rat chondrosarcoma cells that stably expressed the construct. CRISPR/Cas9-induced deletion of intron 6 in RCS cells revealed that a 10-bp region of intron 6 is necessary both for Col2a1 expression and SOX9 binding. Furthermore, SOX9, but not SOX5, binds to this region as demonstrated in an electrophoretic mobility shift assay, although both SOX9 and SOX5 bind to a larger 325-bp fragment of intron 6 containing this small sequence. These findings suggest a novel mechanism of action of SOX5/6; namely, the SOX9/5/6 combination enhances Col2a1 transcription through a novel enhancer in intron 6 together with the enhancer in intron 1. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Over-constraints and a unified mobility method for general spatial mechanisms Part 2: Application of the principle

    Science.gov (United States)

    Lu, Wenjuan; Zeng, Daxing; Huang, Zhen

    2016-01-01

    The pre-research on mobility analysis presented a unified-mobility formula and a methodology based on reciprocal screw theory by HUANG, which focused on classical and modern parallel mechanisms. However its range of application needs to further extend to general multi-loop spatial mechanism. This kind of mechanism is not only more complex in structure but also with strong motion coupling among loops, making the mobility analysis even more complicated, and the relevant research has long been ignored. It is focused on how to apply the new principle for general spatial mechanism to those various multi-loop spatial mechanisms, and some new meaningful knowledge is further found. Several typical examples of the general multi-loop spatial mechanisms with motion couple even strong motion couple are considered. These spatial mechanisms include different closing way: over-constraint appearing in rigid closure, in movable closure, and in dynamic closure as well; these examples also include two different new methods to solve this kind of issue: the way to recognize over-constraints by analyzing relative movement between two connected links and by constructing a virtual loop to recognize over-constraints. In addition, over-constraint determination tabulation is brought to analyze the motion couple. The researches above are all based upon the screw theory. All these multi-loop spatial mechanisms with different kinds of structures can completely be solved by following the directions and examples, and the new mobility theory based on the screw theory is also proved to be valid. This study not only enriches and develops the theory and makes the theory more universal, but also has a special meaning for innovation in mechanical engineering.

  2. 海峡两岸货币清算机制监管合作设想%On the Regulatory Mechanisms of Currency Liquidation across the Taiwan Straits

    Institute of Scientific and Technical Information of China (English)

    邱丽洪; 涂晓今; 钱远玲

    2015-01-01

    自海峡两岸货币清算机制实质运作以来,货币清算机制的监管合作显得十分必要与迫切。通过回顾和总结两岸经贸、银行业的合作历程,比较两岸银行监管的差异,从两岸银行规定的协调、货币清算机构间的协调、信息交换与共享以及风险预警与危机处理的协调,积极探索两岸对货币清算机制监管合作的拓展空间,确保两岸货币清算机制的健康运作,从而促进两岸经贸合作的进一步发展。%After the operation of the Currency Liquidation Mechanism across the Taiwan Straits in 2013, there is an urgent need for the establishment of regulatory mechanisms of currency liquidation.On review of the development of economic and trade coop-eration as well as ties-up between banks, together with the difference in banking supervision, the paper puts forward suggestions on coordination of banking laws, coordination between organizations of currency liquidation as well as coordination of information exchange, risk warning system and risk management system.It actively explores the collaboration of banking supervision across the Straits in hope of smooth functioning of currency liquidation mechanism and further development of economic and trade ex-change across the Straits.

  3. Integrative modeling of eQTLs and cis-regulatory elements suggests mechanisms underlying cell type specificity of eQTLs.

    Directory of Open Access Journals (Sweden)

    Christopher D Brown

    Full Text Available Genetic variants in cis-regulatory elements or trans-acting regulators frequently influence the quantity and spatiotemporal distribution of gene transcription. Recent interest in expression quantitative trait locus (eQTL mapping has paralleled the adoption of genome-wide association studies (GWAS for the analysis of complex traits and disease in humans. Under the hypothesis that many GWAS associations tag non-coding SNPs with small effects, and that these SNPs exert phenotypic control by modifying gene expression, it has become common to interpret GWAS associations using eQTL data. To fully exploit the mechanistic interpretability of eQTL-GWAS comparisons, an improved understanding of the genetic architecture and causal mechanisms of cell type specificity of eQTLs is required. We address this need by performing an eQTL analysis in three parts: first we identified eQTLs from eleven studies on seven cell types; then we integrated eQTL data with cis-regulatory element (CRE data from the ENCODE project; finally we built a set of classifiers to predict the cell type specificity of eQTLs. The cell type specificity of eQTLs is associated with eQTL SNP overlap with hundreds of cell type specific CRE classes, including enhancer, promoter, and repressive chromatin marks, regions of open chromatin, and many classes of DNA binding proteins. These associations provide insight into the molecular mechanisms generating the cell type specificity of eQTLs and the mode of regulation of corresponding eQTLs. Using a random forest classifier with cell specific CRE-SNP overlap as features, we demonstrate the feasibility of predicting the cell type specificity of eQTLs. We then demonstrate that CREs from a trait-associated cell type can be used to annotate GWAS associations in the absence of eQTL data for that cell type. We anticipate that such integrative, predictive modeling of cell specificity will improve our ability to understand the mechanistic basis of human

  4. Honeybee Colony Thermoregulation – Regulatory Mechanisms and Contribution of Individuals in Dependence on Age, Location and Thermal Stress

    Science.gov (United States)

    Stabentheiner, Anton; Kovac, Helmut; Brodschneider, Robert

    2010-01-01

    Honeybee larvae and pupae are extremely stenothermic, i.e. they strongly depend on accurate regulation of brood nest temperature for proper development (33–36°C). Here we study the mechanisms of social thermoregulation of honeybee colonies under changing environmental temperatures concerning the contribution of individuals to colony temperature homeostasis. Beside migration activity within the nest, the main active process is “endothermy on demand” of adults. An increase of cold stress (cooling of the colony) increases the intensity of heat production with thoracic flight muscles and the number of endothermic individuals, especially in the brood nest. As endothermy means hard work for bees, this eases much burden of nestmates which can stay ectothermic. Concerning the active reaction to cold stress by endothermy, age polyethism is reduced to only two physiologically predetermined task divisions, 0 to ∼2 days and older. Endothermic heat production is the job of bees older than about two days. They are all similarly engaged in active heat production both in intensity and frequency. Their active heat production has an important reinforcement effect on passive heat production of the many ectothermic bees and of the brood. Ectothermy is most frequent in young bees (<∼2 days) both outside and inside of brood nest cells. We suggest young bees visit warm brood nest cells not only to clean them but also to speed up flight muscle development for proper endothermy and foraging later in their life. Young bees inside brood nest cells mostly receive heat from the surrounding cell wall during cold stress, whereas older bees predominantly transfer heat from the thorax to the cell wall. Endothermic bees regulate brood comb temperature more accurately than local air temperature. They apply the heat as close to the brood as possible: workers heating cells from within have a higher probability of endothermy than those on the comb surface. The findings show that thermal

  5. Honeybee colony thermoregulation--regulatory mechanisms and contribution of individuals in dependence on age, location and thermal stress.

    Directory of Open Access Journals (Sweden)

    Anton Stabentheiner

    Full Text Available Honeybee larvae and pupae are extremely stenothermic, i.e. they strongly depend on accurate regulation of brood nest temperature for proper development (33-36 degrees C. Here we study the mechanisms of social thermoregulation of honeybee colonies under changing environmental temperatures concerning the contribution of individuals to colony temperature homeostasis. Beside migration activity within the nest, the main active process is "endothermy on demand" of adults. An increase of cold stress (cooling of the colony increases the intensity of heat production with thoracic flight muscles and the number of endothermic individuals, especially in the brood nest. As endothermy means hard work for bees, this eases much burden of nestmates which can stay ectothermic. Concerning the active reaction to cold stress by endothermy, age polyethism is reduced to only two physiologically predetermined task divisions, 0 to approximately 2 days and older. Endothermic heat production is the job of bees older than about two days. They are all similarly engaged in active heat production both in intensity and frequency. Their active heat production has an important reinforcement effect on passive heat production of the many ectothermic bees and of the brood. Ectothermy is most frequent in young bees (< approximately 2 days both outside and inside of brood nest cells. We suggest young bees visit warm brood nest cells not only to clean them but also to speed up flight muscle development for proper endothermy and foraging later in their life. Young bees inside brood nest cells mostly receive heat from the surrounding cell wall during cold stress, whereas older bees predominantly transfer heat from the thorax to the cell wall. Endothermic bees regulate brood comb temperature more accurately than local air temperature. They apply the heat as close to the brood as possible: workers heating cells from within have a higher probability of endothermy than those on the comb

  6. A Generalized Linear Model for Decomposing Cis-regulatory, Parent-of-Origin, and Maternal Effects on Allele-Specific Gene Expression

    Directory of Open Access Journals (Sweden)

    Yasuaki Takada

    2017-07-01

    Full Text Available Joint quantification of genetic and epigenetic effects on gene expression is important for understanding the establishment of complex gene regulation systems in living organisms. In particular, genomic imprinting and maternal effects play important roles in the developmental process of mammals and flowering plants. However, the influence of these effects on gene expression are difficult to quantify because they act simultaneously with cis-regulatory mutations. Here we propose a simple method to decompose cis-regulatory (i.e., allelic genotype, genomic imprinting [i.e., parent-of-origin (PO], and maternal [i.e., maternal genotype (MG] effects on allele-specific gene expression using RNA-seq data obtained from reciprocal crosses. We evaluated the efficiency of method using a simulated dataset and applied the method to whole-body Drosophila and mouse trophoblast stem cell (TSC and liver RNA-seq data. Consistent with previous studies, we found little evidence of PO and MG effects in adult Drosophila samples. In contrast, we identified dozens and hundreds of mouse genes with significant PO and MG effects, respectively. Interestingly, a similar number of genes with significant PO effect were detect in mouse TSCs and livers, whereas more genes with significant MG effect were observed in livers. Further application of this method will clarify how these three effects influence gene expression levels in different tissues and developmental stages, and provide novel insight into the evolution of gene expression regulation.

  7. Studies on gene structure, enzymatic activity and regulatory mechanism of acetohydroxy acid isomeroreductase from G2 pea

    Institute of Scientific and Technical Information of China (English)

    XU; Yunjian; (

    2003-01-01

    [1]Zhu, Y. X., Zhang, Y. F., Li, H. Y., Molecular cloning of GA suppressed G2 pea genes by cDNA RDA, Science in China, Ser. C, 1997, 40(4): 379-383.[2]Xu, H., Xu, Y., Gu, X. et al., Cloning and analysis of a cDNA encoding acetohydroxy acid isomeroreductase from G2 pea, Chinese Science Bulletin, 2001, 46(21): 1808-1811.[3]Dumas, R., Joyard, J., Douce, R., Purification and characterization of acetohydroxy acid reductoisomerase from spinach chloroplasts, Biochem. J., 1989, 262: 971-976.[4]Dumas, R., Butikofer, M. C., Job, D. et al., Evidence for two catalytically different magnesium binding sites in acetohydroxy acid isomeroreductase by site-directed mutagenesis, Biochemistry, 1995, 34: 6026-6036.[5]Singh, B. K., Biosynthesis of valine, leucine, and isoleucine, in Plant Amino Acids-Biochemistry and Biotechnology (ed. Singh, B. K.), New York: Marcel Dekker Inc., 1999, 227-247.[6]Reynolds, T. L., Effect of chlorsulfuron valine and isoleucine on division and tracheary element differentiation in cell suspension cultures of Solanum carolinense, J. Plant Physiol., 1986, 125(1-2): 179-184.[7]Spackman, V. M. T., Cobb, A. H., Cell cycle inhibition of potato root tips treated with Imazethapyr, Annals of Applied Biology, 1999, 135(3): 585-587.[8]Zelenaya-Troitskaya, O., Perlman, P. S., Butow, R. A., An enzyme in yeast mitochondria that catalyzes a step in branched-chain amino acid biosynthesis also functions in mitochondrial DNA stability, EMBO J., 1995, 14: 3268-3276.[9]MacAlpine, D. M., Perlman, P. S., Butow, R. A., The numbers of individual mitochondrial DNA molecules and mitochondrial DNA nucleoids in yeast are co-regulated by the general amino acid control pathway, EMBO J., 2000, 19(4): 767-775.[10]Kaufman, B. A., Newman, S. M., Hallberg, R. L. et al., In organello formaldehyde crosslinking of proteins to mtDNA: Identification of bifunctional proteins, Proc. Natl. Acad. Sci. USA, 2000, 97: 7772-7777.[11]Mazliak, P., Plant membrane

  8. The individual therapy process questionnaire: development and validation of a revised measure to evaluate general change mechanisms in psychotherapy.

    Science.gov (United States)

    Mander, Johannes

    2015-01-01

    There is a dearth of measures specifically designed to assess empirically validated mechanisms of therapeutic change. To fill in this research gap, the aim of the current study was to develop a measure that covers a large variety of empirically validated mechanisms of change with corresponding versions for the patient and therapist. To develop an instrument that is based on several important change process frameworks, we combined two established change mechanisms instruments: the Scale for the Multiperspective Assessment of General Change Mechanisms in Psychotherapy (SACiP) and the Scale of the Therapeutic Alliance-Revised (STA-R). In our study, 457 psychosomatic inpatients completed the SACiP and the STA-R and diverse outcome measures in early, middle and late stages of psychotherapy. Data analyses were conducted using factor analyses and multilevel modelling. The psychometric properties of the resulting Individual Therapy Process Questionnaire were generally good to excellent, as demonstrated by (a) exploratory factor analyses on both patient and therapist ratings, (b) CFA on later measuring times, (c) high internal consistencies and (d) significant outcome predictive effects. The parallel forms of the ITPQ deliver opportunities to compare the patient and therapist perspectives for a broader range of facets of change mechanisms than was hitherto possible. Consequently, the measure can be applied in future research to more specifically analyse different change mechanism profiles in session-to-session development and outcome prediction. Key Practitioner Message This article describes the development of an instrument that measures general mechanisms of change in psychotherapy from both the patient and therapist perspectives. Post-session item ratings from both the patient and therapist can be used as feedback to optimize therapeutic processes. We provide a detailed discussion of measures developed to evaluate therapeutic change mechanisms.

  9. Heart rate variability indices as bio-markers of top-down self-regulatory mechanisms: A meta-analytic review.

    Science.gov (United States)

    Holzman, Jacob B; Bridgett, David J

    2017-03-01

    Theoretical perspectives posit that heart-rate variability (HRV) reflects self-regulatory capacity and therefore can be employed as a bio-marker of top-down self-regulation (the ability to regulate behavioral, cognitive, and emotional processes). However, existing findings of relations between self-regulation and HRV indices are mixed. To clarify the nature of such relations, we conducted a meta-analysis of 123 studies (N=14,347) reporting relations between HRV indices and aspects of top-down self-regulation (e.g., executive functioning, emotion regulation, effortful control). A significant, albeit small, effect was observed (r=0.09) such that greater HRV was related to better top-down self-regulation. Differences in relations were negligible across aspects of self-regulation, self-regulation measurement methods, HRV computational techniques, at-risk compared with healthy samples, and the context of HRV measurement. Stronger relations were observed in older relative to younger samples and in published compared to unpublished studies. These findings generally support the notion that HRV indices can tentatively be employed as bio-markers of top-down self-regulation. Conceptual and theoretical implications, and critical gaps in current knowledge to be addressed by future work, are discussed.

  10. The angiosperm gibberellin-GID1-DELLA growth regulatory mechanism: how an "inhibitor of an inhibitor" enables flexible response to fluctuating environments.

    Science.gov (United States)

    Harberd, Nicholas P; Belfield, Eric; Yasumura, Yuki

    2009-05-01

    The phytohormone gibberellin (GA) has long been known to regulate the growth, development, and life cycle progression of flowering plants. However, the molecular GA-GID1-DELLA mechanism that enables plants to respond to GA has only recently been discovered. In addition, studies published in the last few years have highlighted previously unsuspected roles for the GA-GID1-DELLA mechanism in regulating growth response to environmental variables. Here, we review these advances within a general plant biology context and speculate on the answers to some remaining questions. We also discuss the hypothesis that the GA-GID1-DELLA mechanism enables flowering plants to maintain transient growth arrest, giving them the flexibility to survive periods of adversity.

  11. Microhomology-mediated mechanisms underlie non-recurrent disease-causing microdeletions of the FOXL2 gene or its regulatory domain.

    Directory of Open Access Journals (Sweden)

    Hannah Verdin

    Full Text Available Genomic disorders are often caused by recurrent copy number variations (CNVs, with nonallelic homologous recombination (NAHR as the underlying mechanism. Recently, several microhomology-mediated repair mechanisms--such as microhomology-mediated end-joining (MMEJ, fork stalling and template switching (FoSTeS, microhomology-mediated break-induced replication (MMBIR, serial replication slippage (SRS, and break-induced SRS (BISRS--were described in the etiology of non-recurrent CNVs in human disease. In addition, their formation may be stimulated by genomic architectural features. It is, however, largely unexplored to what extent these mechanisms contribute to rare, locus-specific pathogenic CNVs. Here, fine-mapping of 42 microdeletions of the FOXL2 locus, encompassing FOXL2 (32 or its regulatory domain (10, serves as a model for rare, locus-specific CNVs implicated in genetic disease. These deletions lead to blepharophimosis syndrome (BPES, a developmental condition affecting the eyelids and the ovary. For breakpoint mapping we used targeted array-based comparative genomic hybridization (aCGH, quantitative PCR (qPCR, long-range PCR, and Sanger sequencing of the junction products. Microhomology, ranging from 1 bp to 66 bp, was found in 91.7% of 24 characterized breakpoint junctions, being significantly enriched in comparison with a random control sample. Our results show that microhomology-mediated repair mechanisms underlie at least 50% of these microdeletions. Moreover, genomic architectural features, like sequence motifs, non-B DNA conformations, and repetitive elements, were found in all breakpoint regions. In conclusion, the majority of these microdeletions result from microhomology-mediated mechanisms like MMEJ, FoSTeS, MMBIR, SRS, or BISRS. Moreover, we hypothesize that the genomic architecture might drive their formation by increasing the susceptibility for DNA breakage or promote replication fork stalling. Finally, our locus-centered study

  12. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  13. "General theory of a particle mechanics" arising from a fractal surface

    CERN Document Server

    Yefremov, Alexander P

    2016-01-01

    The logical line is traced of formulation of theory of mechanics founded on the basic correlations of mathematics of hypercomplex numbers and associated geometric images. Namely, it is shown that the physical equations of quantum, classical and relativistic mechanics can be regarded as mathematical consequences of a single condition of stability of exceptional algebras of real, complex and quaternion numbers under transformations of primitive constituents of their units and elements. In the course of the study a notion of basic fractal surface underlying the physical three-dimensional space is introduces, and an original geometric treatment (admitting visualization) of some formerly considered abstract functions (mechanical action, space-time interval) are suggested.

  14. Stable Suppression of Lactate Dehydrogenase Activity during Anoxia in the Foot Muscle of Littorina littorea and the Potential Role of Acetylation as a Novel Posttranslational Regulatory Mechanism.

    Science.gov (United States)

    Shahriari, Ali; Dawson, Neal J; Bell, Ryan A V; Storey, Kenneth B

    2013-01-01

    The intertidal marine snail, Littorina littorea, has evolved to withstand extended bouts of oxygen deprivation brought about by changing tides or other potentially harmful environmental conditions. Survival is dependent on a strong suppression of its metabolic rate and a drastic reorganization of its cellular biochemistry in order to maintain energy balance under fixed fuel reserves. Lactate dehydrogenase (LDH) is a crucial enzyme of anaerobic metabolism as it is typically responsible for the regeneration of NAD(+), which allows for the continued functioning of glycolysis in the absence of oxygen. This study compared the kinetic and structural characteristics of the D-lactate specific LDH (E.C. 1.1.1.28) from foot muscle of aerobic control versus 24 h anoxia-exposed L. littorea. Anoxic LDH displayed a near 50% decrease in V max (pyruvate-reducing direction) as compared to control LDH. These kinetic differences suggest that there may be a stable modification and regulation of LDH during anoxia, and indeed, subsequent dot-blot analyses identified anoxic LDH as being significantly less acetylated than the corresponding control enzyme. Therefore, acetylation may be the regulatory mechanism that is responsible for the suppression of LDH activity during anoxia, which could allow for the production of alternative glycolytic end products that in turn would increase the ATP yield under fixed fuel reserves.

  15. Stable Suppression of Lactate Dehydrogenase Activity during Anoxia in the Foot Muscle of Littorina littorea and the Potential Role of Acetylation as a Novel Posttranslational Regulatory Mechanism

    Directory of Open Access Journals (Sweden)

    Ali Shahriari

    2013-01-01

    Full Text Available The intertidal marine snail, Littorina littorea, has evolved to withstand extended bouts of oxygen deprivation brought about by changing tides or other potentially harmful environmental conditions. Survival is dependent on a strong suppression of its metabolic rate and a drastic reorganization of its cellular biochemistry in order to maintain energy balance under fixed fuel reserves. Lactate dehydrogenase (LDH is a crucial enzyme of anaerobic metabolism as it is typically responsible for the regeneration of NAD+, which allows for the continued functioning of glycolysis in the absence of oxygen. This study compared the kinetic and structural characteristics of the D-lactate specific LDH (E.C. 1.1.1.28 from foot muscle of aerobic control versus 24 h anoxia-exposed L. littorea. Anoxic LDH displayed a near 50% decrease in Vmax (pyruvate-reducing direction as compared to control LDH. These kinetic differences suggest that there may be a stable modification and regulation of LDH during anoxia, and indeed, subsequent dot-blot analyses identified anoxic LDH as being significantly less acetylated than the corresponding control enzyme. Therefore, acetylation may be the regulatory mechanism that is responsible for the suppression of LDH activity during anoxia, which could allow for the production of alternative glycolytic end products that in turn would increase the ATP yield under fixed fuel reserves.

  16. Zymosan-induced generalized inflammation: experimental studies into mechanisms leading to multiple organ dysfunction syndrome.

    NARCIS (Netherlands)

    Volman, T.J.H.; Hendriks, T.; Goris, R.J.A.

    2005-01-01

    Patients suffering from multiple organ dysfunction syndrome (MODS) comprise a heterogeneous population, which complicates research in its pathogenesis. Elucidation of the mechanisms involved in the development of MODS will ultimately necessitate the collection of tissue samples and the performance

  17. REGULATORY MECHANISMS OF CELLULAR RESPIRATION

    Science.gov (United States)

    Barron, E. S. Guzman; Nelson, Leonard; Ardao, Maria Isabel

    1948-01-01

    Oxidizing agents of sulfhydryl groups such as iodosobenzoate, alkylating agents such as iodoacetamide, and mercaptide-forming agents such as cadmium chloride, mercuric chloride, p-chloromercuribenzoate, sodium arsenite, and p-carboxyphenylarsine oxide, added in small concentrations to a suspension of sea urchin sperm produced an increase in respiration. When the concentration was increased there was an inhibition. These effects are explained by postulating the presence in the cells of two kinds of sulfhydryl groups: soluble sulfhydryl groups, which regulate cellular respiration, and fixed sulfhydryl groups, present in the protein moiety of enzymes. Small concentrations of sulfhydryl reagents combine only with the first, thus producing an increase in respiration; when the concentration is increased, the fixed sulfhydryl groups are also attacked and inhibition of respiration is the consequence. Other inhibitors of cell respiration, such as cyanide and urethanes, which do not combine with —SH groups, did not stimulate respiration in small concentration. PMID:18891144

  18. Chunking in Soar: The Anatomy of a General Learning Mechanism. Technical Report.

    Science.gov (United States)

    Laird, John E.; And Others

    Soar, an architecture for problem solving and learning based on heuristic search and chunking, has been applied to a variety of tasks during the development of the Soar project, the goal of which is to build a system capable of general intelligent behavior. The hypothesis being tested in this aspect of Soar research is that chunking, a simple…

  19. Midlatitude Forcing Mechanisms for Glacier Mass Balance Investigated Using General Circulation Models

    NARCIS (Netherlands)

    Reichert, B.K.; Bengtsson, L.; Oerlemans, J.

    2001-01-01

    A process-oriented modeling approach is applied in order to simulate glacier mass balance for individual glaciers using statistically downscaled general circulation models (GCMs). Glacier-specific seasonal sensitivity characteristics based on a mass balance model of intermediate complexity are used

  20. The dynamics of general developmental mechanisms : From Piaget and Vygotsky to dynamic systems models

    NARCIS (Netherlands)

    van Geert, P

    2000-01-01

    Dynamic systems theory conceives of development as a self-organizational process. Both complexity and order emerge as a product of elementary principles of interaction between components involved in the developmental process. This article presents a dynamic systems model based on a general dual deve

  1. Generalization of the Activated Complex Theory of Reaction Rates. II. Classical Mechanical Treatment

    Science.gov (United States)

    Marcus, R. A.

    1964-01-01

    In its usual classical form activated complex theory assumes a particular expression for the kinetic energy of the reacting system -- one associated with a rectilinear motion along the reaction coordinate. The derivation of the rate expression given in the present paper is based on the general kinetic energy expression.

  2. A Gauge-Independent Mechanism for Confinement and Mass Gap: Part I -- The General Framework

    CERN Document Server

    Cherrington, J Wade

    2009-01-01

    We propose a gauge-independent mechanism for the area-law behavior of Wilson loop expectation values in terms of worldsheets spanning Wilson loops interacting with the spin foams that contribute to the vacuum partition function. The method uses an exact transformation of lattice-regularized Yang-Mills theory that is valid for all couplings. Within this framework, some natural conjectures can be made as to what physical mechanism enforces the confinement property in the continuum (weak coupling) limit. Details for the SU(2) case in three dimensions are provided in a companion paper.

  3. Nuclear Regulatory Commission 1989 Information Digest

    Energy Technology Data Exchange (ETDEWEB)

    None,

    1989-03-01

    The Nuclear Regulatory Commission 1989 Information Digest provides summary information regarding the US Nuclear Regulatory Commission, its regulatory responsibilities, and areas licensed by the Commission. This is the first of an annual publication for the general use of the NRC staff and is available to the public. The Digest is divided into two parts: the first presents an overview of the US Nuclear Regulatory Commission and the second provides data on NRC commercial nuclear reactor licensees and commercial nuclear power reactors worldwide.

  4. Recruitment of a hedgehog regulatory circuit in butterfly eyespot evolution.

    Science.gov (United States)

    Keys, D N; Lewis, D L; Selegue, J E; Pearson, B J; Goodrich, L V; Johnson, R L; Gates, J; Scott, M P; Carroll, S B

    1999-01-22

    The origin of new morphological characters is a long-standing problem in evolutionary biology. Novelties arise through changes in development, but the nature of these changes is largely unknown. In butterflies, eyespots have evolved as new pattern elements that develop from special organizers called foci. Formation of these foci is associated with novel expression patterns of the Hedgehog signaling protein, its receptor Patched, the transcription factor Cubitus interruptus, and the engrailed target gene that break the conserved compartmental restrictions on this regulatory circuit in insect wings. Redeployment of preexisting regulatory circuits may be a general mechanism underlying the evolution of novelties.

  5. A New Form of the General Solution of the Elastic Space Axisymmetric Problem in Pavement Mechanics

    Directory of Open Access Journals (Sweden)

    Jia Liang

    2016-01-01

    Full Text Available In order to analyze the stress and displacement of pavement, a new form of the general solution of the elastic space axisymmetric problem is proposed by the method of mathematics reasoning. Depending on the displacement function put forward by Southwell, displacement function is derived based on Hankel transform and inverse Hankel transform. A new form of the general solution of the elastic space axisymmetric problem has been set up according to a few basic equations as the geometric equations, constitutive equations, and equilibrium equations. The present solution applies to elastic half-space foundation and Winkler foundation; the stress and displacement of pavement are obtained by mathematical deduction. The example results show that the proposed method is practically feasible.

  6. Generalized One-Dimensional Point Interaction in Relativistic and Non-relativistic Quantum Mechanics

    CERN Document Server

    Shigehara, T; Mishima, T; Cheon, T; Cheon, Taksu

    1999-01-01

    We first give the solution for the local approximation of a four parameter family of generalized one-dimensional point interactions within the framework of non-relativistic model with three neighboring $\\delta$ functions. We also discuss the problem within relativistic (Dirac) framework and give the solution for a three parameter family. It gives a physical interpretation for so-called high energy substantially differ between non-relativistic and relativistic cases.

  7. Inquiry guided learning in a chemical engineering core curriculum: General instructional approach and specific application to the fluid mechanics case

    OpenAIRE

    Atilhan, Mert; Eljack, Fadwa; Alfadala, Hassan; Froyd, Jeffrey E.; El-Halwagi, Mahmoud; Mahalec, Vladimir

    2014-01-01

    This paper presents results from a preliminary study of the effectiveness of using inquiry-guided learning instructional strategies both in chemical engineering classrooms and laboratories. For readers unfamiliar with the instructional strategy, the paper describes the general approach and then reports on results of its application for the fluid mechanics course taken by undergraduate students in the Chemical Engineering Department at Qatar University. Inquiry-guided activities were developed...

  8. Regulatory role of acupuncture and moxibustion in immunosenescence and epigenetic mechanisms%针灸调节免疫衰老及其表观遗传机制

    Institute of Scientific and Technical Information of China (English)

    沈文宾; 周次利; 吴焕淦; 黄艳; 赵琛; 崔云华

    2015-01-01

    BACKGROUND:The acupuncture and moxibustion is an effective method to regulate the immunosenescence. The epigenetic modification has become a focus in the research of immunosenescence regulation. OBJECTIVE: To summarize the relationship between epigenetic regulation and the regulatory role of acupuncture and moxibustion on immunosenescence, and to explore the relevant mechanisms. METHODS: We searched CNKI, VIP, WANFANG DATA, SinoMed, Ebsco Medline, Springer, ScienceDirect and Embase by computer for relevant articles published from January 1999 to August 2014. The keywords were “acupuncture”, “moxibustion”, “aging”, “immunosenescence” and “epigenetic” in Chinese and English. Al databases were cross-searched to minimize missing data. We excluded documents based on inclusion and exclusion criteria thereby checking the title and abstract. RESULTS AND CONCLUSION:Finaly 64 articles were included, including 8 Chinese publications and 56 English publications. The innate immune system and the adaptive immune system can vary with aging, which is the most obvious feature in immunosenescence. The acupuncture and moxibustion can improve immunosenescence overal. The epigenetic modification plays an important role in immunosenescence. The acupuncture and moxibustion can affect the epigenetic modification directly. However, the epigenetic mechanism underlying the regulatory role of acupuncture and moxibustion in immunosenescence needs further studies.%背景:针灸可有效调节免疫衰老,运用表观遗传修饰手段研究免疫衰老成为了近年来国内外研究的热点之一。目的:归纳总结针灸对免疫衰老的调节作用及与表观遗传调控的关系,探讨其作用机制。方法:通过计算机检索中国知网(CNKI)、维普期刊资源整合服务平台(VIP)、万方数据知识服务平台(WANFANG DATA)、中国生物医学文献服务系统(SinoMed)、PubMed、Ebsco Medline、Springer、ScienceDirect和Embase,所有

  9. General Relationships Between the Various Systems of Reference Axes Employed in Flight Mechanics

    Science.gov (United States)

    Rautenberg, H J

    1940-01-01

    The different possibilities of orientation of the systems of axes currently employed in flight mechanics are compiled and described. Of the three possible couplings between the wind and aircraft axes, the most suitable coupling is that in which the y axis is made the principal axis of rotation for one of the two coupling angles (angles of attack). In connection with this coupling, an experimental system of axes is introduced, whose axes x(sub e) and z(sub e) are situated in the plane of symmetry of the airplane and rotate about the airplane lateral axis y = y(sub e). This system of axes enables the utilization of the coefficients obtained in the wind tunnel in the flight-mechanic equations by a simple transformation, with the aid of the angle of attack, measured in the plane of symmetry of the airplane.

  10. Redox Mechanisms in Regulation of Adipocyte Differentiation: Beyond a General Stress Response

    Directory of Open Access Journals (Sweden)

    Fan Jiang

    2012-11-01

    Full Text Available In this review, we summarize advances in our understanding of redox-sensitive mechanisms that regulate adipogenesis. Current evidence indicates that reactive oxygen species may act to promote both the initiation of adipocyte lineage commitment of precursor or stem cells, and the terminal differentiation of preadipocytes to mature adipose cells. These can involve redox regulation of pathways mediated by receptor tyrosine kinases, peroxisome proliferator-activated receptor γ (PPARγ, PPARγ coactivator 1α (PGC-1α, AMP-activated protein kinase (AMPK, and CCAAT/enhancer binding protein β (C/EBPβ. However, the precise roles of ROS in adipogenesis in vivo remain controversial. More studies are needed to delineate the roles of reactive oxygen species and redox signaling mechanisms, which could be either positive or negative, in the pathogenesis of obesity and related metabolic disorders.

  11. Water, Resilience and the Law: From General Concepts and Governance Design Principles to Actionable Mechanisms

    Science.gov (United States)

    Hill Clarvis, M.; Allan, A.; Hannah, D. M.

    2013-12-01

    Climate change has significant ramifications for water law and governance, yet, there is strong evidence that legal regulations have often failed to protect environments or promote sustainable development. Scholars have increasingly suggested that the preservation and restoration paradigms of legislation and regulation are no longer adequate for climate change related challenges in complex and cross-scale social-ecological systems. This is namely due to past assumptions of stationarity, uniformitarianism and the perception of ecosystem change as predictable and reversible. This paper reviews the literature on law and resilience and then presents and discusses a set of practical examples of legal mechanisms from the water resources management sector, identified according to a set of guiding principles from the literature on adaptive capacity, adaptive governance as well as adaptive and integrated water resources management. It then assesses the aptness of these different measures according to scientific evidence of increased uncertainty and changing ecological baselines. A review of the best practice examples demonstrates that there are a number of best practice examples attempting to integrate adaptive elements of flexibility, iterativity, connectivity and subsidiarity into a variety of legislative mechanisms, suggesting that there is not as significant a tension between resilience and the law as many scholars have suggested. However, while many of the mechanisms may indeed be suitable for addressing challenges relating to current levels of change and uncertainty, analysis across a broader range of uncertainty highlights challenges relating to more irreversible changes associated with greater levels of warming. Furthermore the paper identifies a set of pre-requisites that are fundamental to the successful implementation of such mechanisms, namely monitoring and data sharing, financial and technical capacity, particularly in nations that are most at risk with the

  12. Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms.

    Directory of Open Access Journals (Sweden)

    Alan E Bilsland

    2014-02-01

    Full Text Available Cancer cells depend on transcription of telomerase reverse transcriptase (TERT. Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3'-oxime (BIO predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several

  13. Analysis of tomato plasma membrane H(+)-ATPase gene family suggests a mycorrhiza-mediated regulatory mechanism conserved in diverse plant species.

    Science.gov (United States)

    Liu, Junli; Liu, Jianjian; Chen, Aiqun; Ji, Minjie; Chen, Jiadong; Yang, Xiaofeng; Gu, Mian; Qu, Hongye; Xu, Guohua

    2016-10-01

    In plants, the plasma membrane H(+)-ATPase (HA) is considered to play a crucial role in regulating plant growth and respoding to environment stresses. Multiple paralogous genes encoding different isozymes of HA have been identified and characterized in several model plants, while limited information of the HA gene family is available to date for tomato. Here, we describe the molecular and expression features of eight HA-encoding genes (SlHA1-8) from tomato. All these genes are interrupted by multiple introns with conserved positions. SlHA1, 2, and 4 were widely expressed in all tissues, while SlHA5, 6, and 7 were almost only expressed in flowers. SlHA8, the transcripts of which were barely detectable under normal or nutrient-/salt-stress growth conditions, was strongly activated in arbuscular mycorrhizal (AM) fungal-colonized roots. Extreme lack of SlHA8 expression in M161, a mutant defective to AM fungal colonization, provided genetic evidence towards the dependence of its expression on AM symbiosis. A 1521-bp SlHA8 promoter could direct the GUS reporter expression specifically in colonized cells of transgenic tobacco, soybean, and rice mycorrhizal roots. Promoter deletion assay revealed a 223-bp promoter fragment of SlHA8 containing a variant of AM-specific cis-element MYCS (vMYCS) sufficient to confer the AM-induced activity. Targeted deletion of this motif in the corresponding promoter region causes complete abolishment of GUS staining in mycorrhizal roots. Together, these results lend cogent evidence towards the evolutionary conservation of a potential regulatory mechanism mediating the activation of AM-responsive HA genes in diverse mycorrhizal plant species.

  14. Progesterone stimulates adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c gene expression. potential mechanism for the lipogenic effect of progesterone in adipose tissue.

    Science.gov (United States)

    Lacasa, D; Le Liepvre, X; Ferre, P; Dugail, I

    2001-04-13

    Fatty acid synthase (FAS), a nutritionally regulated lipogenic enzyme, is transcriptionally controlled by ADD1/SREBP1c (adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c), through insulin-mediated stimulation of ADD1/SREBP1c expression. Progesterone exerts lipogenic effects on adipocytes, and FAS is highly induced in breast tumor cell lines upon progesterone treatment. We show here that progesterone up-regulates ADD1/SREBP1c expression in the MCF7 breast cancer cell line and the primary cultured preadipocyte from rat parametrial adipose tissue. In MCF7, progesterone induced ADD1/SREBP1c and Metallothionein II (a well known progesterone-regulated gene) mRNAs, with comparable potency. In preadipocytes, progesterone increased ADD1/SREBP1c mRNA dose-dependently, but not SREBP1a or SREBP2. Run-on experiments demonstrated that progesterone action on ADD1/SREBP1c was primarily at the transcriptional level. The membrane-bound and mature nuclear forms of ADD1/SREBP1 protein accumulated in preadipocytes cultured with progesterone, and FAS induction could be abolished by adenovirus-mediated overexpression of a dominant negative form of ADD1/SREBP1 in these cells. Finally, in the presence of insulin, progesterone was unable to up-regulate ADD1/SREBP1c mRNA in preadipocytes, whereas its effect was restored after 24 h of insulin deprivation. Together these results demonstrate that ADD1/SREBP1c is controlled by progesterone, which, like insulin, acts by increasing ADD1/SREBP1c gene transcription. This provides a potential mechanism for the lipogenic actions of progesterone on adipose tissue.

  15. TGF-β1 exerts opposing effects on grass carp leukocytes: implication in teleost immunity, receptor signaling and potential self-regulatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Mu Yang

    Full Text Available In fish immunity, the regulatory role of transforming growth factor-β1 (TGF-β1 has not been fully characterized. Here we examined the immunoregulatory effects of TGF-β1 in grass carp peripheral blood leukocytes (PBL and head kidney leukocytes (HKL. It is interesting that TGF-β1 consistently stimulated the cell viability and the mRNA levels of pro-inflammatory cytokines (Tnfα and Ifnγ and T/B cell markers [Cd4-like (Cd4l, Cd8α, Cd8β and Igμ] in PBL, which contrasted with its inhibitory tone in HKL. Further studies showed that grass carp TGF-β1 type I receptor, activin receptor-like kinase 5 (ALK5, was indispensable for the immunoregulatory effects of TGF-β1 in PBL and HKL. Notably, TGF-β1 persistently attenuated ALK5 expression, whereas immunoneutralization of endogenous grass carp TGF-β1 could increase ALK5 mRNA and protein levels. It is consistent with the observation that TGF-β1 decreased the number of ALK5(+ leukocytes in PBL and HKL, revealing a negative regulation of TGF-β1 signaling at the receptor level. Moreover, transient treatment with TGF-β1 for 24 h was sufficient to induce similar cellular responses compared with the continuous treatment. This indicated a possible mechanism by which TGF-β1 triggered the down-regulation of ALK5 mRNA and protein, leading to the desensitization of grass carp leukocytes toward TGF-β1. Accordingly, our data revealed a dual role of TGF-β1 in teleost immunity in which it can serve as a positive or negative control device and provided additional mechanistic insights as to how TGF-β1 controls its signaling in vertebrate leukocytes.

  16. General mechanisms of drought response and their application in drought resistance improvement in plants.

    Science.gov (United States)

    Fang, Yujie; Xiong, Lizhong

    2015-02-01

    Plants often encounter unfavorable environmental conditions because of their sessile lifestyle. These adverse factors greatly affect the geographic distribution of plants, as well as their growth and productivity. Drought stress is one of the premier limitations to global agricultural production due to the complexity of the water-limiting environment and changing climate. Plants have evolved a series of mechanisms at the morphological, physiological, biochemical, cellular, and molecular levels to overcome water deficit or drought stress conditions. The drought resistance of plants can be divided into four basic types-drought avoidance, drought tolerance, drought escape, and drought recovery. Various drought-related traits, including root traits, leaf traits, osmotic adjustment capabilities, water potential, ABA content, and stability of the cell membrane, have been used as indicators to evaluate the drought resistance of plants. In the last decade, scientists have investigated the genetic and molecular mechanisms of drought resistance to enhance the drought resistance of various crops, and significant progress has been made with regard to drought avoidance and drought tolerance. With increasing knowledge to comprehensively decipher the complicated mechanisms of drought resistance in model plants, it still remains an enormous challenge to develop water-saving and drought-resistant crops to cope with the water shortage and increasing demand for food production in the future.

  17. The gravitational analogue to the hydrogen atom (A summer study at the borders of quantum mechanics and general relativity)

    CERN Document Server

    Kober, M; Koch, B; Bleicher, Marcus; Kober, Martin; Koch, Ben

    2007-01-01

    This article reports on a student summer project performed in 2006 at the University of Frankfurt. It is addressed to undergraduate students familiar with the basic principles of relativistic quantum mechanics and general relativity. The aim of the project was to study the Dirac equation in curved space time. To obtain the general relativistic Dirac equation we use the formulation of gravity as a gauge theory in the first part. After these general considerations we restrict the further discussion to the special case of the Schwarzschild metric. This setting corresponds to the hydrogen atom, with the electromagnetic field replaced by gravity. Although there is a singularity at the event horizon it turns out that a regular solution of the time independent Dirac equation exists. Finally the Dirac equation is solved numerically using suitable boundary conditions.

  18. Equivalence of the generalized Lie-Hori method and the method of averaging. [in celestial mechanics

    Science.gov (United States)

    Ahmed, A. H.; Tapley, B. D.

    1984-01-01

    In this investigation, a comparison is made of two methods for developing perturbation theories for non-canonical dynamical systems. The methods compared are the generalized Lie-Hori method and the method of averaging. In the comparison presented here, the equivalence of the methods up to the second order in the small parameter is shown. However, the approach used can be extended to demonstrate the equivalence for higher orders. To illustrate the equivalence Duffing's equation, the van der Pol equation and the oscillator with quadratic damping problem are solved using each method.

  19. Generalized molecular chaos hypothesis and the H theorem: problem of constraints and amendment of nonextensive statistical mechanics.

    Science.gov (United States)

    Abe, Sumiyoshi

    2009-04-01

    Quite unexpectedly, kinetic theory is found to specify the correct definition of average value to be employed in nonextensive statistical mechanics. It is shown that the normal average is consistent with the generalized Stosszahlansatz (i.e., molecular chaos hypothesis) and the associated H theorem, whereas the q average widely used in the relevant literature is not. In the course of the analysis, the distributions with finite cutoff factors are rigorously treated. Accordingly, the formulation of nonextensive statistical mechanics is amended based on the normal average. In addition, the Shore-Johnson theorem, which supports the use of the q average, is carefully re-examined and it is found that one of the axioms may not be appropriate for systems to be treated within the framework of nonextensive statistical mechanics.

  20. The Concurrency Control Mechanism of SDD-1: A System for Distributed Databases (The General Case)

    Science.gov (United States)

    1977-12-15

    before the WRITE message WJ .-abe abeta ’.., and the READ message Rj is processed before the WRITE gamma message Wamma then there is no serial ordering...following properties of LOGblocked: i. b i b’ ii. Rb is not in Abeta b Abiii. Rlh is not in A .*’- - - -- " Page -148- SDD-1 Concurrency Control Mechanism... abeta alpha b the same argument as (ii). * From (iv) and part II of lemma S, we conclude that every b’ R atom in class B in between R and b in LOG

  1. [On improvement of the mechanism for establishing and changing indicators of quality and food safety in the regulatory and legal acts of the Eurasian Economical Union].

    Science.gov (United States)

    Arnautov, O V

    2016-01-01

    In accordance with the Treaty on the Eurasian Economic Union (EAEU) to ensure the sanitary and epidemiological welfare of the population within the Union, a coordinated policy in agreed policy in the sphere of application of sanitary measures is carried out. Sanitary measures are the obligatory requirements and procedures, including requirements for the final product, processing methods, production, transportation, storage and disposal, sampling procedures, methods of research (tests), risk assessment, the state registration, requirements for packaging directly aimed at ensuring the safety of products (goods) in order to protect human welfare, and they should be applied on the basis having a scientific explanation, and only to the extent that is necessary to protect human welfare. Sanitary measures applied within the Union should be based on international and regional standards, guidelines and (or) the recommendations, except when they based on appropriate scientific studies and explanations. In this case sanitary measures which could provide a higher level of sanitary protection are introduced. At present, the mechanism of the development, justification and approval of common sanitary and epidemiological requirements (ESR) and procedures of the Eurasian Economic Commission (the Commission) is not installed. The absence of a clear mechanism for the development, approval and implementation of the ESR to the products (goods) on the basis having a scientific explanation on the one hand could lead to the creation of unjustified barriers to foreign and mutual trade, on the other--to weaken the level of safety for human life and health of products (goods) placed on markets of the Union. In order to bring the regulatory legal acts of the Customs Union in accordance with the Treaty on the Eurasian Economic Union the Commission in cooperation with the competent authorities of the Member States in the field of sanitary and epidemiological welfare developed the project of

  2. Complex generalized minimal residual algorithm for iterative solution of quantum-mechanical reactive scattering equations

    Science.gov (United States)

    Chatfield, David C.; Reeves, Melissa S.; Truhlar, Donald G.; Duneczky, Csilla; Schwenke, David W.

    1992-01-01

    Complex dense matrices corresponding to the D + H2 and O + HD reactions were solved using a complex generalized minimal residual (GMRes) algorithm described by Saad and Schultz (1986) and Saad (1990). To provide a test case with a different structure, the H + H2 system was also considered. It is shown that the computational effort for solutions with the GMRes algorithm depends on the dimension of the linear system, the total energy of the scattering problem, and the accuracy criterion. In several cases with dimensions in the range 1110-5632, the GMRes algorithm outperformed the LAPACK direct solver, with speedups for the linear equation solution as large as a factor of 23.

  3. Adsorbate-induced lifting of substrate relaxation is a general mechanism governing titania surface chemistry.

    Science.gov (United States)

    Silber, David; Kowalski, Piotr M; Traeger, Franziska; Buchholz, Maria; Bebensee, Fabian; Meyer, Bernd; Wöll, Christof

    2016-09-30

    Under ambient conditions, almost all metals are coated by an oxide. These coatings, the result of a chemical reaction, are not passive. Many of them bind, activate and modify adsorbed molecules, processes that are exploited, for example, in heterogeneous catalysis and photochemistry. Here we report an effect of general importance that governs the bonding, structure formation and dissociation of molecules on oxidic substrates. For a specific example, methanol adsorbed on the rutile TiO2(110) single crystal surface, we demonstrate by using a combination of experimental and theoretical techniques that strongly bonding adsorbates can lift surface relaxations beyond their adsorption site, which leads to a significant substrate-mediated interaction between adsorbates. The result is a complex superstructure consisting of pairs of methanol molecules and unoccupied adsorption sites. Infrared spectroscopy reveals that the paired methanol molecules remain intact and do not deprotonate on the defect-free terraces of the rutile TiO2(110) surface.

  4. Steam Generator tube integrity -- US Nuclear Regulatory Commission perspective

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, E.L.; Sullivan, E.J.

    1997-02-01

    In the US, the current regulatory framework was developed in the 1970s when general wall thinning was the dominant degradation mechanism; and, as a result of changes in the forms of degradation being observed and improvements in inspection and tube repair technology, the regulatory framework needs to be updated. Operating experience indicates that the current U.S. requirements should be more stringent in some areas, while in other areas they are overly conservative. To date, this situation has been dealt with on a plant-specific basis in the US. However, the NRC staff is now developing a proposed steam generator rule as a generic framework for ensuring that the steam generator tubes are capable of performing their intended safety functions. This paper discusses the current U.S. regulatory framework for assuring steam generator (SG) tube integrity, the need to update this regulatory framework, the objectives of the new proposed rule, the US Nuclear Regulatory Commission (NRC) regulatory guide (RG) that will accompany the rule, how risk considerations affect the development of the new rule, and some outstanding issues relating to the rule that the NRC is still dealing with.

  5. Effect of initial bulk density on high-solids anaerobic digestion of MSW: General mechanism.

    Science.gov (United States)

    Caicedo, Luis M; Wang, Hongtao; Lu, Wenjing; De Clercq, Djavan; Liu, Yanjun; Xu, Sai; Ni, Zhe

    2017-06-01

    Initial bulk density (IBD) is an important variable in anaerobic digestion since it defines and optimizes the treatment capacity of a system. This study reveals the mechanism on how IBD might affect anaerobic digestion of waste. Four different IBD values: D1 (500-700kgm(-3)), D2 (900-1000kgm(-3)), D3 (1100-1200kgm(-3)) and D4 (1200-1400kgm(-3)) were set and tested over a period of 90days in simulated landfill reactors. The main variables affected by the IBD are the methane generation, saturation degree, extraction of organic matter, and the total population of methanogens. The study identified that IBD >1000kgm(-3) may have significant effect on methane generation, either prolonging the lag time or completely inhibiting the process. This study provides a new understanding of the anaerobic digestion process in saturated high-solids systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. General classical and quantum-mechanical description of magnetic resonance: an application to electric-dipole-moment experiments

    Energy Technology Data Exchange (ETDEWEB)

    Silenko, Alexander J. [Belarusian State University, Research Institute for Nuclear Problems, Minsk (Belarus); Joint Institute for Nuclear Research, Bogoliubov Laboratory of Theoretical Physics, Dubna (Russian Federation)

    2017-05-15

    A general theoretical description of a magnetic resonance is presented. This description is necessary for a detailed analysis of spin dynamics in electric-dipole-moment experiments in storage rings. General formulas describing a behavior of all components of the polarization vector at the magnetic resonance are obtained for an arbitrary initial polarization. These formulas are exact on condition that the nonresonance rotating field is neglected. The spin dynamics is also calculated at frequencies far from resonance with allowance for both rotating fields. A general quantum-mechanical analysis of the spin evolution at the magnetic resonance is fulfilled and the full agreement between the classical and quantum-mechanical approaches is shown. Quasimagnetic resonances for particles and nuclei moving in noncontinuous perturbing fields of accelerators and storage rings are considered. Distinguishing features of quasimagnetic resonances in storage ring electric-dipole-moment experiments are investigated in detail. The exact formulas for the effect caused by the electric dipole moment are derived. The difference between the resonance effects conditioned by the rf electric-field flipper and the rf Wien filter is found and is calculated for the first time. The existence of this difference is crucial for the establishment of a consent between analytical derivations and computer simulations and for checking spin tracking programs. The main systematical errors are considered. (orig.)

  7. Statistical mechanics of charged objects: General method and applications to simple systems

    Science.gov (United States)

    Rosenfeld, Y.; Blum, L.

    1986-05-01

    Real fluids are composed of molecules that are objects of complex geometries and charge distributions. By studying the asymptotic high density limit (AHDL) and the asymptotic strong coupling limit (ASCL) one is able to reduce the problem of computing the thermodynamics and correlation functions of the system to a geometrical calculation involving overlap integrals between the objects. In previous work a simple geometrical, physically intuitive meaning of the direct correlation functions (dcf) I for point charges in a background (as interactions between smeared charges) and hard sphere (as overlap volumes) within the mean spherical approximation (MSA) was given, thus also revealing its analytic structure. A general variational approach to study a system composed of complex charged molecules is discussed. In this approach the variational trial functions for the free energy functional are constructed from the asymptotic limiting (AL) forms of the direct correlation functions. A number of examples are discussed, and in each case the variational form of the direct correlation is given explicitly. The relation to Onsager's procedure of immersing the system in a infinite conducting fluid of obtaining an energy bound is discussed in detail.

  8. One-dimensional tensile constitutive equation cannot be directly generalized to deal with two-dimensional bulging mechanical problems

    Institute of Scientific and Technical Information of China (English)

    SONG; Yuquan(宋玉泉); LIU; Shumei(刘术梅)

    2002-01-01

    Superplastic forming has been extensively applied to manufacture parts and components with complex shapes or high-precisions. However, superplastic formation is in multi-stress state. In a long time, uniaxial tensile constitutive equation has been directly generalized to deal with multi-stress state. Whether so doing is feasible or not needs to be proved in theory. This paper first summarizes the establishing processes of superplastic tensile and bulging constitutive equation with variable m, and, using the analytical expressions of equivalent stress ? and equivalent strain rateof free bulge based on the fundamentals of continuum medium plastic mechanics, derives the analytical expressions of optimum loading rules for superplastic free bulge. By comparing the quantitative results on typical superplastic alloy ZnAl22, it is shown that one-dimensional tensile constitutive equations cannot be directly generalized to deal with two-dimensional bulging quantitative mechanical problems; only superplastic bulging constitutive equation based on bulging stress state can be used to treat the quantitative mechanical problems of bulge.

  9. Phosphine-gold(I) compounds as anticancer agents: general description and mechanisms of action.

    Science.gov (United States)

    Lima, João Carlos; Rodriguez, Laura

    2011-12-01

    Gold complexes have been explored as metallodrugs with great potential applications as antitumoral agents. In particular, gold-phosphine derivatives seemed quite promising since the use of the antiarthritic auranofin drug (thiolate-Au-PEt3 complex) presented also biological activity against different cancer cells. So, different auranofin analogues have been explored within this context and for this reason, the main number of phosphine-gold complexes developed with this goal contain thiolate ligands. Other complexes have been also studied such as tetrahedral bis(phosphine)gold(I) and phosphine-gold-halides. Very recently, phosphine-gold-alkynyl complexes have also shown very interesting biological activities although few reports are published related to them. Their mechanism of action seems to be clearly different that the used by platinum drugs (DNA intercalating processes) and recent studies point to be related to the inhibition of Trx reductase. Cellular uptake and biodistribution studies are well reported in the original works but the use of luminescence techniques is relatively less explored. For this, the use of these techniques is also specifically reported in this review.

  10. Generalized mechanical pain sensitivity over nerve tissues in patients with strictly unilateral migraine.

    Science.gov (United States)

    Fernández-de-las-Peñas, César; Arendt-Nielsen, Lars; Cuadrado, María Luz; Pareja, Juan A

    2009-06-01

    No study has previously analyzed pressure pain sensitivity of nerve trunks in migraine. This study aimed to examine the differences in mechanical pain sensitivity over specific nerves between patients with unilateral migraine and healthy controls. Blinded investigators assessed pressure pain thresholds (PPT) over the supra-orbital nerves (V1) and peripheral nerve trunks of both upper extremities (median, radial, and ulnar nerves) in 20 patients with strictly unilateral migraine and 20 healthy matched controls. Pain intensity after palpation over both supra-orbital nerves was also assessed. A pressure algometer was used to quantify PPT, whereas a 10-point numerical pain rate scale was used to evaluate pain to palpation over the supra-orbital nerve. The analysis of covariance revealed that pain to palpation over the supra-orbital nerve was significantly higher (P0.6). In patients with unilateral migraine, we found increased mechano-sensitivity of the supra-orbital nerve on the symptomatic side of the head. Outside the head, the same patients showed increased mechano-sensitivity of the main peripheral nerves of both upper limbs, without asymmetries. Such diffuse hypersensitivity of the peripheral nerves lends further evidence to the presence of a state of hyperexcitability of the central nervous system in patients with unilateral migraine.

  11. Generalized theory on the mechanism of site-specific DNA-protein interactions

    Science.gov (United States)

    Niranjani, G.; Murugan, R.

    2016-05-01

    We develop a generalized theoretical framework on the binding of transcription factor proteins (TFs) with specific sites on DNA that takes into account the interplay of various factors regarding overall electrostatic potential at the DNA-protein interface, occurrence of kinetic traps along the DNA sequence, presence of other roadblock protein molecules along DNA and crowded environment, conformational fluctuations in the DNA binding domains (DBDs) of TFs, and the conformational state of the DNA. Starting from a Smolochowski type theoretical framework on site-specific binding of TFs we logically build our model by adding the effects of these factors one by one. Our generalized two-step model suggests that the electrostatic attractive forces present inbetween the positively charged DBDs of TFs and the negatively charged phosphate backbone of DNA, along with the counteracting shielding effects of solvent ions, is the core factor that creates a fluidic type environment at the DNA-protein interface. This in turn facilitates various one-dimensional diffusion (1Dd) processes such as sliding, hopping and intersegmental transfers. These facilitating processes as well as flipping dynamics of conformational states of DBDs of TFs between stationary and mobile states can enhance the 1Dd coefficient on a par with three-dimensional diffusion (3Dd). The random coil conformation of DNA also plays critical roles in enhancing the site-specific association rate. The extent of enhancement over the 3Dd controlled rate seems to be directly proportional to the maximum possible 1Dd length. We show that the overall site-specific binding rate scales with the length of DNA in an asymptotic way. For relaxed DNA, the specific binding rate will be independent of the length of DNA as length increases towards infinity. For condensed DNA as in in vivo conditions, the specific binding rate depends on the length of DNA in a turnover way with a maximum. This maximum rate seems to scale with the

  12. Pregabalin reduces sleep disturbance in patients with generalized anxiety disorder via both direct and indirect mechanisms

    Directory of Open Access Journals (Sweden)

    Vamsi Bollu

    2010-03-01

    Full Text Available Background and Objectives: To characterize the impact of pregabalin on sleep in patients with generalized anxiety disorder (GAD and to determine whether the impact is a direct or an indirect effect, mediated through the reduction of anxiety symptoms. Methods: A post-hoc analysis of data from a randomized, double-blind, placebo- and active-controlled study in patients with GAD was conducted. Patients received pregabalin 300 mg/day, venlafaxine XR 75 mg/day or placebo for a week, followed by pregabalin 300-600 mg/day, venlafaxine XR 75-225 mg/day, or placebo for 7 weeks. Treatment effect on sleep was evaluated using the Medical Outcomes Study Sleep Scale. Anxiety symptoms were assessed with the Hamilton Anxiety Rating Scale. A mediation model was used to estimate separately for both treatment arms the direct and indirect treatment effects on sleep disturbance. Results: Compared with placebo (n = 128, treatment with pregabalin (n = 121 significantly reduced scores on the sleep disturbance subscale and Sleep Problems Index II at both week 4 and week 8, and the sleep adequacy subscale at week 8. Venlafaxine XR (n = 125 had no significant effect on these measures. The mediation model indicated that 53% of the total pregabalin effect on sleep disturbance was direct (p < 0.01 and 47% indirect, mediated through anxiety symptoms (p < 0.05. Conclusions: Pregabalin decreased sleep disturbance in patients with GAD both directly, and indirectly by reducing anxiety symptoms. Given the drug specificity of the results, this study provides evidence of an additional important pathway of action for pregabalin and its efficacy in GAD.

  13. Electrophilic assistance to the cleavage of an RNA model phopshodiester via specific and general base-catalyzed mechanisms.

    Science.gov (United States)

    Corona-Martínez, David Octavio; Gomez-Tagle, Paola; Yatsimirsky, Anatoly K

    2012-10-19

    Kinetics of transesterification of the RNA model substrate 2-hydroxypropyl 4-nitrophenyl phosphate promoted by Mg(2+) and Ca(2+), the most common biological metals acting as cofactors for nuclease enzymes and ribozymes, as well as by Co(NH(3))(6)(3+), Co(en)(3)(3+), Li(+), and Na(+) cations, often employed as mechanistic probes, was studied in 80% v/v (50 mol %) aqueous DMSO, a medium that allows one to discriminate easily specific base (OH(-)-catalyzed) and general base (buffer-catalyzed) reaction paths. All cations assist the specific base reaction, but only Mg(2+) and Na(+) assist the general base reaction. For Mg(2+)-assisted reactions, the solvent deuterium isotope effects are 1.23 and 0.25 for general base and specific base mechanisms, respectively. Rate constants for Mg(2+)-assisted general base reactions measured with different bases fit the Brønsted correlation with a slope of 0.38, significantly lower than the slope for the unassisted general base reaction (0.77). Transition state binding constants for catalysts in the specific base reaction (K(‡)(OH)) both in aqueous DMSO and pure water correlate with their binding constants to 4-nitrophenyl phosphate dianion (K(NPP)) used as a minimalist transition state model. It was found that K(‡)(OH) ≈ K(NPP) for "protic" catalysts (Co(NH(3))(6)(3+), Co(en)(3)(3+), guanidinium), but K(‡)(OH) ≫ K(NPP) for Mg(2+) and Ca(2+) acting as Lewis acids. It appears from results of this study that Mg(2+) is unique in its ability to assist efficiently the general base-catalyzed transesterification often occurring in active sites of nuclease enzymes and ribozymes.

  14. Generalized Toda Mechanics Associated with Loop Algebras (L)(Cr) and (L)(Dr) and Their Reductions

    Institute of Scientific and Technical Information of China (English)

    YANG Zhan-Ying; ZHAO Liu; YLIU Wang-Yun; SHI Kang-Jie

    2005-01-01

    We construct a class of integrable generalization of Toda mechanics with long-range interactions. These systems are associated with the loop algebras L(Cr) and L(Dr) in the sense that their Lax matrices can be realized in terms of the c = 0 representations of the affine Lie algebras Cr(1) and Dr(1) and the interactions pattern involved bears the typical characters of the corresponding root systems. We present the equations of motion and the Hamiltonian structure.These generalized systems can be identified unambiguously by specifying the underlying loop algebra together with an ordered pair of integers (n, m). It turns out that different systems associated with the same underlying loop algebra but with different pairs of integers (n1, m1 ) and (n2, m2) with n2 < n1 and m2 < m1 can be related by a nested Hamiltonian reduction procedure. For all nontrivial generalizations, the extra coordinates besides the standard Toda variables are Poisson non-commute, and when either n or m ≥ 3, the Poisson structure for the extra coordinate variables becomes some Lie algebra (i.e. the extra variables appear linearly on the right-hand side of the Poisson brackets). In the quantum case, such generalizations will become systems with noncommutative variables without spoiling the integrability.

  15. The limit passage of space curvature in problems of celestial mechanics with the generalized Kepler and Hooke potentials

    Science.gov (United States)

    Vozmishcheva, Tatiana

    2016-09-01

    The connection between the problems of celestial mechanics: the Kepler problem, the two-center problem and the two body problem in spaces of constant curvature with the generalized Kepler and Hooke potentials is investigated. The limit passage in the two-center and two body problems in the Lobachevsky space and on a sphere is carried out as λto0 (λ is the curvature of the corresponding space) for the two potentials. The potentials and metrics in spaces under study are written in the gnomonic coordinates. It is shown that as the curvature radius tends to infinity, the generalized gravitational and elastic potentials transform to the Kepler and Hooke forms in the Euclidean space.

  16. Dose response relationship in anti-stress gene regulatory networks.

    OpenAIRE

    Qiang Zhang; Andersen, Melvin E.

    2007-01-01

    To maintain a stable intracellular environment, cells utilize complex and specialized defense systems against a variety of external perturbations, such as electrophilic stress, heat shock, and hypoxia, etc. Irrespective of the type of stress, many adaptive mechanisms contributing to cellular homeostasis appear to operate through gene regulatory networks that are organized into negative feedback loops. In general, the degree of deviation of the controlled variables, such as electrophiles, misf...

  17. An integrative view of mechanisms underlying generalized spike-and-wave epileptic seizures and its implication on optimal therapeutic treatments.

    Directory of Open Access Journals (Sweden)

    Boyuan Yan

    Full Text Available Many types of epileptic seizures are characterized by generalized spike-and-wave discharges. In the past, notable effort has been devoted to understanding seizure dynamics and various hypotheses have been proposed to explain the underlying mechanisms. In this paper, by taking an integrative view of the underlying mechanisms, we demonstrate that epileptic seizures can be generated by many different combinations of synaptic strengths and intrinsic membrane properties. This integrative view has important medical implications: the specific state of a patient characterized by a set of biophysical characteristics ultimately determines the optimal therapeutic treatment. Through the same view, we further demonstrate the potentiation effect of rational polypharmacy in the treatment of epilepsy and provide a new angle to resolve the debate on polypharmacy. Our results underscore the need for personalized medicine and demonstrate that computer modeling and simulation may play an important role in assisting the clinicians in selecting the optimal treatment on an individual basis.

  18. Eflfux seems to be a general mechanism to resist tetracycline in the yeasts and possibly the moulds

    Institute of Scientific and Technical Information of China (English)

    Sanjay Sahay

    2016-01-01

    Objective:To isolate yeasts and moulds from selected natural systems and study the effect of tetracycline (Tet) on them so as to generate comprehensive data for further elucidation of transfer or evolutionary development of Tet resistance in general and in these lower eukaryotes in particular. Methods: A total of 139 natural yeasts have been isolated from various ecosystems on potato dextrose agar medium. These along with model yeasts and selected natural and model moulds have been tested for their responses to Tet at various concentrations added to the growth media. The effluxed materials were obtained by vortexing and centrifugation of cells and tested against sensitive bacterium. Results: It was found that Tet efflux was a general feature of natural yeasts and filamentous fungi (moulds) could resist Tet upto a concentration of 5 mg/mL. However, at a very high concentration (10 mg/mL) neither the yeasts nor the moulds could grow indicating that Tet is toxic for these eukaryotes at very high concentrations. The presence of Tet in the medium exaggerates filamentation in all the hyphal forming yeasts. Conclusions:The results suggest efflux as the general mechanism of Tet-resistance in yeasts and moulds possibly acquired from bacteria via horizontal transfer.

  19. 全身麻醉药在脊髓内的作用机制%Subcortical mechanisms of general anesthetics

    Institute of Scientific and Technical Information of China (English)

    杨静; 张宏

    2008-01-01

    The spinal cord plays an important role in two general anesthetic end-points: analgesia and immobility in response to a noxious stimulus. The spinal components that may contribute to anesthetic actions include the central termination of sensory primary afferent neurons, interneurones and the cell bodies and initial axon segments of motor neurons, which are contained in dorsal horn and ventral horn respectively. Different general anesthetics have both presynaptic and postsynaptic effects to produce analgesia and immobility via multitude of cellular and subcellular sites identified as potential targets of anaesthetic action, such as diverse ligand-gated ion channels etc. This review will focus on anesthetic targets and molecular mechanisms mediated analgesia and immobility of general anesthetics in spinal cord.%脊髓是全身麻醉药抑制伤害性刺激体动反应和抗伤害效应的重要作用部位,含有不同配体门控离子受体等多个可能介导麻醉效应的靶点.不同药物在脊髓内经各自特异靶点通过多种分子机制发挥作用.现就全身麻醉药制动和镇痛效应在脊髓内的作用位点和分子机制作一综述.

  20. Stigma, medication adherence and coping mechanism among people living with HIV attending General Hospital, Lagos Island, Nigeria

    Directory of Open Access Journals (Sweden)

    Adekemi O. Sekoni

    2012-02-01

    Full Text Available Background: People living with HIV and AIDS (PLWHA experience some form of stigma which could lead to poor medication adherence.Objectives: This study assessed the various domains of stigma experienced by PLWHAs attending an HIV clinic at General Hospital, Lagos Island, their medication adherence patterns and their coping mechanisms for ensuring adherence to antiretroviral therapy.Method: A cross-sectional study design with a sample size of 200 was used. Respondents were selected using systematic random sampling. Interviewers administered structured questionnaires were used to collect information on the domains of stigma. Data was analysed using EPI info©. This was followed by a focus group discussion (FGD with seven participants at the clinic using an interview guide with open-ended questions.Results: Overall, stigma was experienced by 35% of the respondents. Within this group, 6.6%, 37.1%, 43.1% and 98.0% of the respondents reported experiencing negative self image stigma, personalised stigma, disclosure stigma and public attitude stigma respectively. Almost 90% of the respondents were adherent. The FGD revealed that disclosure was usually confined to family members and the coping mechanism for achieving adherence was to put antiretroviral (ARVs in unlabelled pill boxes.Conclusion: This study found that stigma was low and that the most common domain of stigma experienced was public attitude stigma. Medication adherence of respondents was good as a result of the coping mechanism, which involves putting ARVs in unlabelled pill boxes.

  1. 77 FR 29718 - Self-Regulatory Organizations; BOX Options Exchange LLC; Notice of Filing and Immediate...

    Science.gov (United States)

    2012-05-18

    ... exchange, be operated by BOX Market LLC as a facility of the Exchange. As such, the operation and... determinations will be made pursuant to procedures of BOX Market Operations Center with regulatory oversight... perfect the mechanism for a free and open market and a national market system, and, in general, to...

  2. Steady-State Response of a Micropolar Generalized Thermoelastic Half-Space to the Moving Mechanical/Thermal Loads

    Indian Academy of Sciences (India)

    Rajneesh Kumar; Sunita Deswal

    2000-11-01

    Microrotation effect of a load applied normal to the boundary and moving at a constant velocity along one of the co-ordinate axis in a generalized thermoelastic half-space is studied. The analytical expressions of the displacement component, force stress, couple stress and temperature field for two different theories i.e. Lord-Shulman (L-S) and Green-Lindsay (G-L) for supersonic, subsonic and transonic velocities in case of mechanical and thermal sources applied, are obtained by the use of Fourier transform technique. The integral transforms have been inverted by using a numerical technique and the numerical results are illustrated graphically for magnesium crystal-like material.

  3. Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

    Directory of Open Access Journals (Sweden)

    Joana P Gonçalves

    Full Text Available Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1 apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2 ignore local patterns, abundant in most interesting cases of transcriptional activity; (3 neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4 limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots. Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in

  4. Response Theory for Equilibrium and Non-Equilibrium Statistical Mechanics: Causality and Generalized Kramers-Kronig Relations

    Science.gov (United States)

    Lucarini, Valerio

    2008-05-01

    We consider the general response theory recently proposed by Ruelle for describing the impact of small perturbations to the non-equilibrium steady states resulting from Axiom A dynamical systems. We show that the causality of the response functions entails the possibility of writing a set of Kramers-Kronig (K-K) relations for the corresponding susceptibilities at all orders of nonlinearity. Nonetheless, only a special class of directly observable susceptibilities obey K-K relations. Specific results are provided for the case of arbitrary order harmonic response, which allows for a very comprehensive K-K analysis and the establishment of sum rules connecting the asymptotic behavior of the harmonic generation susceptibility to the short-time response of the perturbed system. These results set in a more general theoretical framework previous findings obtained for optical systems and simple mechanical models, and shed light on the very general impact of considering the principle of causality for testing self-consistency: the described dispersion relations constitute unavoidable benchmarks that any experimental and model generated dataset must obey. The theory exposed in the present paper is dual to the time-dependent theory of perturbations to equilibrium states and to non-equilibrium steady states, and has in principle similar range of applicability and limitations. In order to connect the equilibrium and the non equilibrium steady state case, we show how to rewrite the classical response theory by Kubo so that response functions formally identical to those proposed by Ruelle, apart from the measure involved in the phase space integration, are obtained. These results, taking into account the chaotic hypothesis by Gallavotti and Cohen, might be relevant in several fields, including climate research. In particular, whereas the fluctuation-dissipation theorem does not work for non-equilibrium systems, because of the non-equivalence between internal and external

  5. Fine-tuning the extent and dynamics of binding cleft opening as a potential general regulatory mechanism in parvulin-type peptidyl prolyl isomerases

    Science.gov (United States)

    Czajlik, András; Kovács, Bertalan; Permi, Perttu; Gáspári, Zoltán

    2017-03-01

    Parvulins or rotamases form a distinct group within peptidyl prolyl cis-trans isomerases. Their exact mode of action as well as the role of conserved residues in the family are still not unambiguously resolved. Using backbone S2 order parameters and NOEs as restraints, we have generated dynamic structural ensembles of three distinct parvulins, SaPrsA, TbPin1 and CsPinA. The resulting ensembles are in good agreement with the experimental data but reveal important differences between the three enzymes. The largest difference can be attributed to the extent of the opening of the substrate binding cleft, along which motional mode the three molecules occupy distinct regions. Comparison with a wide range of other available parvulin structures highlights structural divergence along the bottom of the binding cleft acting as a hinge during the opening-closing motion. In the prototype WW-domain containing parvulin, Pin1, this region is also important in forming contacts with the WW domain known to modulate enzymatic activity of the catalytic domain. We hypothesize that modulation of the extent and dynamics of the identified ‘breathing motion’ might be one of the factors responsible for functional differences in the distinct parvulin subfamilies.

  6. Review of the toxicity of chemical mixtures: Theory, policy, and regulatory practice.

    Science.gov (United States)

    McCarty, L S; Borgert, C J

    2006-07-01

    An analysis of current mixture theory, policy, and practice was conducted by examining standard reference texts, regulatory guidance documents, and journal articles. Although this literature contains useful theoretical concepts, clear definitions of most terminology, and well developed protocols for study design and statistical analysis, no general theoretical basis for the mechanisms and interactions of mixture toxicity could be discerned. There is also a poor understanding of the relationship between exposure-based and internal received dose metrics. This confounds data interpretation and limits reliable determinations of the nature and extent of additivity. The absence of any generally accepted classification scheme for either modes/mechanisms of toxic action or of mechanisms of toxicity interactions is problematic as it produces a cycle in which research and policy are interdependent and mutually limiting. Current regulatory guidance depends heavily on determination of toxicological similarity concluded from the presence of a few prominent constituents, assumed from a common toxicological effect, or presumed from an alleged similar toxic mode/mechanism. Additivity, or the lack of it, is largely based on extrapolation of existing knowledge for single chemicals in this context. Thus, regulatory risk assessment protocols lack authoritative theoretical underpinnings, creating substantial uncertainty. Development of comprehensive classification schemes for modes/mechanisms of toxic action and mechanisms of interaction is needed to ensure a sound theoretical foundation for mixture-related regulatory activity and provide a firm basis for iterative hypothesis development and experimental testing.

  7. Speckle-Tracking Strain Imaging Identifies Alterations in Left Atrial Mechanics With General Anesthesia and Positive-Pressure Ventilation.

    Science.gov (United States)

    Howard-Quijano, Kimberly; Anderson-Dam, John; McCabe, Melissa; Hall, Michael; Mazor, Einat; Mahajan, Aman

    2015-08-01

    The primary aim of this study was to use speckle-tracking strain imaging to evaluate the effect of general anesthesia (GA) and positive-pressure ventilation (PPV) on left atrial (LA) mechanics. The authors hypothesized that GA and PPV would be associated with a decrease in LA strain. The secondary aims were to investigate the effects of GA and PPV on traditional Doppler-derived measures of LA function and Doppler echocardiographic grade of diastolic function. A prospective observational study. A university hospital. Adult patients undergoing cardiac surgery. Transthoracic echocardiography was performed at baseline and under GA with PPV. Changes in LA function associated with GA and PPV were assessed using LA speckle-tracking strain imaging. A reduction was observed in LA peak longitudinal strain (24% v 18%, pSpeckle-tracking strain imaging of the left atrium demonstrated that GA and PPV had a significant impact on LA mechanics by decreasing strain measures of LA preload, with a lesser effect on LA contractility. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Arterial to end-tidal carbon dioxide difference in children undergoing mechanical ventilation of the lungs during general anaesthesia.

    Science.gov (United States)

    Onodi, C; Bühler, P K; Thomas, J; Schmitz, A; Weiss, M

    2017-07-11

    Capnography (ETCO2 ) is routinely used as a non-invasive estimate of arterial carbon dioxide (PaCO2 ) levels in order to modify ventilatory settings, whereby it is assumed that there is a positive gap between PaCO2 and ETCO2 of approximately 0.5 kPa. However, negative values (ETCO2 > PaCO2 ) can be observed. We retrospectively analysed arterial to end-tidal carbon dioxide differences in 799 children undergoing general anaesthesia with mechanical ventilation of the lungs in order to elucidate predictors for a negative gap. A total of 2452 blood gas analysis readings with complete vital sign monitoring, anaesthesia gas analysis and spirometry data were analysed. Mean arterial to end-tidal carbon dioxide difference was -0.18 kPa (limits of 95% agreement -1.10 to 0.74) and 71.2% of samples demonstrated negative values. The intercept model revealed PaCO2 to be the strongest predictor for a negative PaCO2 -ETCO2 difference. A decrease in PaCO2 by 1 kPa resulted in a decrease in the PaCO2 -ETCO2 difference by 0.23 kPa. This study demonstrates that ETCO2 monitoring in children whose lungs are mechanically ventilated may paradoxically lead to overestimation of ETCO2 (ETCO2 > PaCO2 ) with a subsequent risk of unrecognised hypocarbia. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

  9. No evidence of general CO2 insensitivity in ferns: one stomatal control mechanism for all land plants?

    Science.gov (United States)

    Franks, Peter J; Britton-Harper, Zoe J

    2016-08-01

    Stomatal regulation of plant carbon uptake and water loss under changing environmental conditions was a crucial evolutionary step in the colonization of land by plants. There are currently two conflicting models describing the nature of stomatal regulation across terrestrial vascular plants: the first is characterized by a fundamental mechanistic similarity across all lineages, and the second is characterized by the evolution of major differences in angiosperms compared with more ancient lineages. Specifically, the second model posits that stomata of ferns lack a response to elevated atmospheric CO2 concentration (ca ) and therefore cannot regulate leaf intercellular CO2 concentration (ci ). We compared stomatal sensitivity to changes in ca in three distantly related fern species and a representative angiosperm species. Fern and angiosperm stomata responded strongly and similarly to changes in ca . As a result, ci /ca was maintained within narrow limits during ca changes. Our results challenge the model in which stomata of ferns generally lack a response to elevated ca and that angiosperms evolved new dynamic mechanisms for regulating leaf gas exchange that differ fundamentally from ferns. Instead, the results are consistent with a universal stomatal control mechanism that is fundamentally conserved across ferns and angiosperms, and therefore likely all vascular plant divisions.

  10. Mechanisms of chemical vapor generation by aqueous tetrahydridoborate. Recent developments toward the definition of a more general reaction model

    Science.gov (United States)

    D'Ulivo, Alessandro

    2016-05-01

    A reaction model describing the reactivity of metal and semimetal species with aqueous tetrahydridoborate (THB) has been drawn taking into account the mechanism of chemical vapor generation (CVG) of hydrides, recent evidences on the mechanism of interference and formation of byproducts in arsane generation, and other evidences in the field of the synthesis of nanoparticles and catalytic hydrolysis of THB by metal nanoparticles. The new "non-analytical" reaction model is of more general validity than the previously described "analytical" reaction model for CVG. The non-analytical model is valid for reaction of a single analyte with THB and for conditions approaching those typically encountered in the synthesis of nanoparticles and macroprecipitates. It reduces to the previously proposed analytical model under conditions typically employed in CVG for trace analysis (analyte below the μM level, borane/analyte ≫ 103 mol/mol, no interference). The non-analytical reaction model is not able to explain all the interference effects observed in CVG, which can be achieved only by assuming the interaction among the species of reaction pathways of different analytical substrates. The reunification of CVG, the synthesis of nanoparticles by aqueous THB and the catalytic hydrolysis of THB inside a common frame contribute to rationalization of the complex reactivity of aqueous THB with metal and semimetal species.

  11. 硼胁迫下植物生理调控机制的研究进展%The Advances of Physiological Regulatory Mechanism of Plants under Boron Stress

    Institute of Scientific and Technical Information of China (English)

    王瑞东; 姜存仓; 刘桂东; 张祥; 王运华; 彭抒昂

    2011-01-01

    硼是植物的必需营养元素,它对植物的许多生理过程有着重要的作用,特别是在低硼或高硼胁迫情况时会影响植物正常的生理代谢.本文将对最近几年有关硼胁迫下植物生理调节机制的研究成果进行综述,着重阐述低硼胁迫下诱发植物产生硼高效吸收、转运、分配和再利用的机理,以及在高硼胁迫下植物自身可能存在的调控机制.%Boron is an essential nutrient element for plant. It plays an important role in variety of biological processes of plants and may affect the normal physiological metabolism especially in the low B or high boron stress situations. This review is related on recent research about the regulatory mechanisms of plant in boron stress, focusing on the mechanism of B-efficient absorption, transport, distribution and reuse in low B stress and the possible regulatory mechanisms in high B stress in plant.

  12. Preliminary Analysis of the General Performance and Mechanical Behavior of Irradiated FeCrAl Base Alloys and Weldments

    Energy Technology Data Exchange (ETDEWEB)

    Gussev, Maxim N. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Briggs, Samuel A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Yamamoto, Yukinori [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-09-30

    The iron-based, iron-chromium-aluminum (FeCrAl) alloys are promising, robust materials for deployment in current and future nuclear power plants. This class of alloys demonstrates excellent performance in a range of environments and conditions, including high-temperature steam (>1000°C). Furthermore, these alloys have the potential to have prolonged survival under loss-of-coolant accident (LOCA) conditions compared to the more traditional cladding materials that are either Zr-based alloys or austenitic steels. However, one of the issues associated with FeCrAl alloys is cracking during welding. The present project investigates the possibility of mitigating welding-induced cracking via alloying and precise structure control of the weldments; in the frame work of the project, several advanced alloys were developed and are being investigated prior to and after neutron irradiation to provide insight into the radiation tolerance and mechanical performance of the weldments. The present report provides preliminary results on the post-irradiation characterization and mechanical tests performed during United States Fiscal Year (FY) 2016. Chapter 1 provides a general introduction, and Chapter 2 describes the alloy compositions, welding procedure, specimen geometry and manufacturing parameters. Also, a brief discussion of the irradiation at the High Flux Isotope Reactor (HFIR) is provided. Chapter 3 is devoted to the analysis of mechanical tests performed at the hot cell facility; tensile curves and mechanical properties are discussed in detail focusing on the irradiation temperature. Limited fractography results are also presented and analyzed. The discussion highlights the limitations of the testing within a hot cell. Chapter 4 underlines the advantages of in-situ testing and discusses the preliminary results obtained with newly developed miniature specimens. Specimens were moved to the Low Activation Materials Development and Analysis (LAMDA) laboratory and prepared for

  13. Preliminary Analysis of the General Performance and Mechanical Behavior of Irradiated FeCrAl Base Alloys and Weldments

    Energy Technology Data Exchange (ETDEWEB)

    Gussev, Maxim N [ORNL; Field, Kevin G [ORNL; Yamamoto, Yukinori [ORNL

    2016-09-01

    The iron-based, iron-chromium-aluminum (FeCrAl) alloys are promising, robust materials for deployment in current and future nuclear power plants. This class of alloys demonstrates excellent performance in a range of environments and conditions, including high-temperature steam (>1000 C). Furthermore, these alloys have the potential to survive greater durations under lost-of-coolant incident (LOCA) conditions compared to the more traditional cladding materials that are Zr-based or austenitic steels. However, one of the issues associated with FeCrAl alloys is cracking during welding. The present project investigates the possibility to mitigate welding-induced cracking via alloying and precise structure control of the weldments; in the frame work of the project, several advanced alloys were developed and are being investigated prior to and after neutron irradiation to provide insight into the radiation tolerance and mechanical performance of the weldments. The present report provides preliminary, working results on the post-irradiation characterization and mechanical tests performed during United States Fiscal Year (FY) 2016. Chapter 1 provides a general introduction, and Chapter 2 describes the alloy compositions, welding procedure, specimen geometry and manufacturing. Also, a brief discussion of the irradiation at the High-Flux Isotope Reactor (HFIR) is provided. Chapter 3 is devoted to the analysis of mechanical tests performed at the hot cell facility; tensile curves and mechanical properties are discussed in details focusing on the irradiation temperature role. Limited fractography results are also given and analyzed. The discussion highlights the limitations of the testing at the hot cell. Chapter 4 underlines the advantages of in-situ testing and discusses the preliminary results obtained with newly developed miniature specimens. Specimens were moved to the Low Activation Materials Development Laboratory (LAMDA) and prepared for mechanical tests. Follow-on SEM

  14. 21 CFR 26.18 - Regulatory collaboration.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Regulatory collaboration. 26.18 Section 26.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL... Specific Sector Provisions for Pharmaceutical Good Manufacturing Practices § 26.18 Regulatory...

  15. 5 CFR 847.102 - Regulatory structure.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Regulatory structure. 847.102 Section 847.102 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS... INSTRUMENTALITIES General Provisions § 847.102 Regulatory structure. (a)(1) Subpart A of this part...

  16. The SUMOylation of Kif18A and its regulatory mechanism%Kif18A 的 SUMO 化修饰及其调控机制

    Institute of Scientific and Technical Information of China (English)

    李艳; 夏南松; 左勇

    2015-01-01

    Objective To investigate the SUMOylation of Kif18A and its regulatory mechanism.Methods Plas-mids Flag -Kif18A and HA -SUMO1 or His -SUMO1 were co -transfected into HEK293T cells.Flag -Kif18A proteins were pulled down by Flag M2 beads and its SUMOylation was detected by immunoblotting with anti -HA.His -SUMO1 conjugated proteins were also precipitated by TALON Resin and the level of SUMOylated Kif18A was detected by immno-blotting with Flag antibody.The potential sites of Kif18A SUMOlation were predicted by SUMOsp 2.0 software and its coding sequences were mutated from lysine to arginine on the Flag -Kif18A plasmid.Kif18A wide and mutant types were separately expressed in HEK293T cells.The change in the quantity of SUMOylated Kif18A was adopted to determine the site of SUMOylation in Flag -Kif18A.Furthermore, plasmids Flag -Kif18A, HA -SUMO1 and SENP1 WT or mutant were co -transfected into HEK293T cells.Then the amount of SUMOylated Kif18A was detected by immunoprecipitation to determine whether Kif18A can be de -SUMOylated by SENP1.Finally, HeLa cells were synchronized in G2 /M phase by Nocodazole treatment.The SUMOylation of Kif18A in HeLa cells in G2 /M phase were detected by immunoprecipitati-on and immunobloting.Results Kif18A could be SUMOylated by SUMO1 or SUMO2.K47 and K148 were two impor-tant sites for Kif18A SUMOylation.Besides, Kif18A could be de -SUMOylated by SENP1.The SUMOylation of Kif18A was decreased in HeLa cells arrested in G2 /M phase.Conclusion Kif18A can be SUMOylated and its SUMOylation is regulated by mitosis progression.%目的:探讨 Kif18A 的 SUMO 化修饰及其调控机制。方法在 HEK293T 细胞中共转染 Flag -Kif18A、HA -SUMO1或 His -SUMO1质粒,免疫沉淀富集 Flag -Kif18A,免疫印迹检测 HA -SUMO;用 TALON 树脂富集His -SUMO1蛋白,免疫印迹检测 Flag -Kif18A 考察 Kif18A 的 SUMO 化水平。利用 SUMOsp 2.0软件预测Kif18A 可能发生 SUMO 化的潜在位点,将 Flag -Kif18A

  17. Desenho e funcionamento dos mecanismos de controle e accountability das agências reguladoras brasileiras: semelhanças e diferenças Design and operation of the Brazilian regulatory agencies' control and accountability mechanisms: similarities and differences

    Directory of Open Access Journals (Sweden)

    Marcos Vinicius Pó

    2006-08-01

    Full Text Available Este artigo estuda o formato e o funcionamento dos mecanismos de controle e accountability das agências reguladoras, ressaltando suas similaridades e distinções. Suas observações permitem abrir novas frentes de investigação para explicar as diferenças e semelhanças encontradas, tais como a influência da burocracia no processo e os contextos histórico e político de cada setor. O artigo analisa a formatação prevista legalmente para os dispositivos que proporcionam maior accountability às agências reguladoras, como a ouvidoria, as consultas públicas e os conselhos, e verifica indicadores de seu funcionamento efetivo, de forma a avaliar se a aparente uniformidade institucional dos órgãos reflete-se em uniformidade de procedimentos e de resultados. Por fim, aponta alguns impactos que o modelo institucional das agências reguladoras provoca na accountability do Estado brasileiro.This article studies the design and operation of the regulatory agencies' control and accountability mechanisms, underlining their similarities and differences. Its observations open new investigation fronts for the explanation of the differences and similarities found, such as the influence of bureaucracy on the process and each sector's historical and political context. The article analyzes the design determined by legislation for mechanisms that provide the regulatory agencies with more accountability, such as the ombudsman department, public consultations and councils, and assesses the indicators of their effectiveness, in order to verify if the apparent institutional uniformity of the agencies corresponds to the uniformity of procedures and results. Finally, it points out some of the impacts of the regulatory agencies' institutional model on the accountability of the Brazilian state.

  18. Robust and general method for determining surface fluid flow boundary conditions in articular cartilage contact mechanics modeling.

    Science.gov (United States)

    Pawaskar, Sainath Shrikant; Fisher, John; Jin, Zhongmin

    2010-03-01

    Contact detection in cartilage contact mechanics is an important feature of any analytical or computational modeling investigation when the biphasic nature of cartilage and the corresponding tribology are taken into account. The fluid flow boundary conditions will change based on whether the surface is in contact or not, which will affect the interstitial fluid pressurization. This in turn will increase or decrease the load sustained by the fluid phase, with a direct effect on friction, wear, and lubrication. In laboratory experiments or clinical hemiarthroplasty, when a rigid indenter or metallic prosthesis is used to apply load to the cartilage, there will not be any fluid flow normal to the surface in the contact region due to the impermeable nature of the indenter/prosthesis. In the natural joint, on the other hand, where two cartilage surfaces interact, flow will depend on the pressure difference across the interface. Furthermore, in both these cases, the fluid would flow freely in non-contacting regions. However, it should be pointed out that the contact area is generally unknown in advance in both cases and can only be determined as part of the solution. In the present finite element study, a general and robust algorithm was proposed to decide nodes in contact on the cartilage surface and, accordingly, impose the fluid flow boundary conditions. The algorithm was first tested for a rigid indenter against cartilage model. The algorithm worked well for two-dimensional four-noded and eight-noded axisymmetric element models as well as three-dimensional models. It was then extended to include two cartilages in contact. The results were in excellent agreement with the previous studies reported in the literature.

  19. The Analysis of the General Performance and Mechanical Behavior of Unirradiated FeCrAl Alloys Before and After Welding

    Energy Technology Data Exchange (ETDEWEB)

    Gussev, Maxim N. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Yamamoto, Yukinori [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-06-03

    The present report summarizes and discusses the preliminary results for the in-depth characterization of the modern, nuclear-grade FeCrAl alloys currently under development. The alloys were designed for enhanced radiation tolerance and weldability, and the research is currently being pursued by the Department of Energy (DOE) Nuclear Energy Enabling Technologies (NEET) program. Last year, seven candidate FeCrAl alloys with well-controlled chemistry and microstructures were designed and produced; welding was performed under well-controlled conditions. The structure and general performance of unirradiated alloys were assessed using standardized and advanced microstructural characterization techniques and mechanical testing. The primary objective is to identify the best candidate alloy, or at a minimum to identify the contributing factors that increase the weldability and radiation tolerance of FeCrAl alloys, therefore enabling future generations of FeCrAl alloys to deliver better performance parameters. This report is structured so as to describe these critical assessments of the weldability; radiation tolerance will be reported on in later reports from this program.

  20. Biomolecular Cell-Signaling Mechanisms and Dental Implants: A Review on the Regulatory Molecular Biologic Patterns Under Functional and Immediate Loading.

    Science.gov (United States)

    Romanos, Georgios E

    2016-01-01

    Bone tissue adapts its structure and mass to the stresses of mechanical loading. The purpose of this review article was to summarize recent advances on cell signaling relating to the phenomenon of bone remodeling, focused on bone ossification and healing at the interface of dental implants and bone under loading conditions. When a dental implant is placed within an osteotomy, osteocytes, osteoblasts, and osteoclasts are all present. As functional loads are imposed, the remodeling processes adapt the peri-implant bony tissues to mechanical stimuli over time and reestablish a steady state. Based on the current literature, this article demonstrates fundamental information to these remodeling processes, such as the conversion of mechanical cues to electrical or biochemical signals. Multiple intracellular signals are involved in cellular mechanotransduction; the two Wnt signaling pathways (the canonical, β-catenin-dependent and the noncanonical, β-catenin-independent Wnt pathway) are particularly significant. Knowledge of how these molecular signaling pathways are translated into intracellular signals that regulate cell behavior may provide new therapeutic approaches to enhancing osteogenesis, especially around implants with immediate function or placed in areas of poor bone quality. New knowledge about the primary cilia as an organelle and bone cellular mechanosensor is critical for endochondral ossification and proper signal transduction. Other mechanisms, such as the expression of sclerostin as a negative regulator of bone formation (due to deactivation of the Wnt receptor) and downregulation of sclerostin under loading conditions, also present new understanding of the cellular and pericellular mechanics of bone. The complexity of the cell signaling pathways and the mechanisms involved in the mechanoregulation of the bone formation provide new technologies and perspectives for mechanically induced cellular response. Future novel therapeutic approaches based on the

  1. Mechanism for transcriptional synergy between interferon regulatory factor (IRF)-3 and IRF-7 in activation of the interferon-beta gene promoter.

    Science.gov (United States)

    Yang, Hongmei; Ma, Gang; Lin, Charles H; Orr, Melissa; Wathelet, Marc G

    2004-09-01

    The interferon-beta promoter has been studied extensively as a model system for combinatorial transcriptional regulation. In virus-infected cells the transcription factors ATF-2, c-Jun, interferon regulatory factor (IRF)-3, IRF-7 and NF-kappaB, and the coactivators p300/CBP play critical roles in the activation of this and other promoters. It remains unclear, however, why most other combinations of AP-1, IRF and Rel proteins fail to activate the interferon-beta gene. Here we have explored how different IRFs may cooperate with other factors to activate transcription. First we showed in undifferentiated embryonic carcinoma cells that ectopic expression of either IRF-3 or IRF-7, but not IRF-1, was sufficient to allow virus-dependent activation of the interferon-beta promoter. Moreover, the activity of IRF-3 and IRF-7 was strongly affected by promoter context, with IRF-7 preferentially being recruited to the natural interferon-beta promoter. We fully reconstituted activation of this promoter in insect cells. Maximal synergy required IRF-3 and IRF-7 but not IRF-1, and was strongly dependent on the presence of p300/CBP, even when these coactivators only modestly affected the activity of each factor by itself. These results suggest that specificity in activation of the interferon-beta gene depends on a unique promoter context and on the role played by coactivators as architectural factors. Copyright 2004 FEBS

  2. Fine-mapping analysis revealed complex pleiotropic effect and tissue-specific regulatory mechanism of TNFSF15 in primary biliary cholangitis, Crohn's disease and leprosy.

    Science.gov (United States)

    Sun, Yonghu; Irwanto, Astrid; Toyo-Oka, Licht; Hong, Myunghee; Liu, Hong; Andiappan, Anand Kumar; Choi, Hyunchul; Hitomi, Yuki; Yu, Gongqi; Yu, Yongxiang; Bao, Fangfang; Wang, Chuan; Fu, Xian; Yue, Zhenhua; Wang, Honglei; Zhang, Huimin; Kawashima, Minae; Kojima, Kaname; Nagasaki, Masao; Nakamura, Minoru; Yang, Suk-Kyun; Ye, Byong Duk; Denise, Yosua; Rotzschke, Olaf; Song, Kyuyoung; Tokunaga, Katsushi; Zhang, Furen; Liu, Jianjun

    2016-08-10

    Genetic polymorphism within the 9q32 locus is linked with increased risk of several diseases, including Crohn's disease (CD), primary biliary cholangitis (PBC) and leprosy. The most likely disease-causing gene within 9q32 is TNFSF15, which encodes the pro-inflammatory cytokine TNF super-family member 15, but it was unknown whether these disparate diseases were associated with the same genetic variance in 9q32, and how variance within this locus might contribute to pathology. Using genetic data from published studies on CD, PBC and leprosy we revealed that bearing a T allele at rs6478108/rs6478109 (r(2) = 1) or rs4979462 was significantly associated with increased risk of CD and decreased risk of leprosy, while the T allele at rs4979462 was associated with significantly increased risk of PBC. In vitro analyses showed that the rs6478109 genotype significantly affected TNFSF15 expression in cells from whole blood of controls, while functional annotation using publicly-available data revealed the broad cell type/tissue-specific regulatory potential of variance at rs6478109 or rs4979462. In summary, we provide evidence that variance within TNFSF15 has the potential to affect cytokine expression across a range of tissues and thereby contribute to protection from infectious diseases such as leprosy, while increasing the risk of immune-mediated diseases including CD and PBC.

  3. A systematic computational analysis of the rRNA–3′ UTR sequence complementarity suggests a regulatory mechanism influencing post-termination events in metazoan translation

    Science.gov (United States)

    Pánek, Josef; Kolář, Michal; Herrmannová, Anna; Valášek, Leoš Shivaya

    2016-01-01

    Nucleic acid sequence complementarity underlies many fundamental biological processes. Although first noticed a long time ago, sequence complementarity between mRNAs and ribosomal RNAs still lacks a meaningful biological interpretation. Here we used statistical analysis of large-scale sequence data sets and high-throughput computing to explore complementarity between 18S and 28S rRNAs and mRNA 3′ UTR sequences. By the analysis of 27,646 full-length 3′ UTR sequences from 14 species covering both protozoans and metazoans, we show that the computed 18S rRNA complementarity creates an evolutionarily conserved localization pattern centered around the ribosomal mRNA entry channel, suggesting its biological relevance and functionality. Based on this specific pattern and earlier data showing that post-termination 80S ribosomes are not stably anchored at the stop codon and can migrate in both directions to codons that are cognate to the P-site deacylated tRNA, we propose that the 18S rRNA–mRNA complementarity selectively stabilizes post-termination ribosomal complexes to facilitate ribosome recycling. We thus demonstrate that the complementarity between 18S rRNA and 3′ UTRs has a non-random nature and very likely carries information with a regulatory potential for translational control. PMID:27190231

  4. Combinatorial readout of unmodified H3R2 and acetylated H3K14 by the tandem PHD finger of MOZ reveals a regulatory mechanism for HOXA9 transcription.

    Science.gov (United States)

    Qiu, Yu; Liu, Lei; Zhao, Chen; Han, Chuanchun; Li, Fudong; Zhang, Jiahai; Wang, Yan; Li, Guohong; Mei, Yide; Wu, Mian; Wu, Jihui; Shi, Yunyu

    2012-06-15

    Histone acetylation is a hallmark for gene transcription. As a histone acetyltransferase, MOZ (monocytic leukemia zinc finger protein) is important for HOX gene expression as well as embryo and postnatal development. In vivo, MOZ forms a tetrameric complex with other subunits, including several chromatin-binding modules with regulatory functions. Here we report the solution structure of the tandem PHD (plant homeodomain) finger (PHD12) of human MOZ in a free state and the 1.47 Å crystal structure in complex with H3K14ac peptide, which reveals the structural basis for the recognition of unmodified R2 and acetylated K14 on histone H3. Moreover, the results of chromatin immunoprecipitation (ChIP) and RT-PCR assays indicate that PHD12 facilitates the localization of MOZ onto the promoter locus of the HOXA9 gene, thereby promoting the H3 acetylation around the promoter region and further up-regulating the HOXA9 mRNA level. Taken together, our findings suggest that the combinatorial readout of the H3R2/K14ac by PHD12 might represent an important epigenetic regulatory mechanism that governs transcription and also provide a clue of cross-talk between the MOZ complex and histone H3 modifications.

  5. 77 FR 43618 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

    Science.gov (United States)

    2012-07-25

    ... COMMISSION Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule Change... Stock Market LLC (``Nasdaq'' or ``Exchange'') filed with the Securities and Exchange Commission... perfect the mechanism of a free and open market and a national market system and, in general, to protect...

  6. 75 FR 43591 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

    Science.gov (United States)

    2010-07-26

    ... COMMISSION Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate... is hereby given that on June 30, 2010, The NASDAQ Stock Market LLC (``Nasdaq'' or the ``Exchange... mechanism of a free and open market and a national market system, and, in general, to protect investors and...

  7. Mechanisms of action of hormone-sensitive lipase in mouse Leydig cells: its role in the regulation of the steroidogenic acute regulatory protein.

    Science.gov (United States)

    Manna, Pulak R; Cohen-Tannoudji, Joëlle; Counis, Raymond; Garner, Charles W; Huhtaniemi, Ilpo; Kraemer, Fredric B; Stocco, Douglas M

    2013-03-22

    Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of cholesteryl esters in steroidogenic tissues and, thus, facilitates cholesterol availability for steroidogenesis. The steroidogenic acute regulatory protein (StAR) controls the rate-limiting step in steroid biosynthesis. However, the modes of action of HSL in the regulation of StAR expression remain obscure. We demonstrate in MA-10 mouse Leydig cells that activation of the protein kinase A (PKA) pathway, by a cAMP analog Bt2cAMP, enhanced expression of HSL and its phosphorylation (P) at Ser-660 and Ser-563, but not at Ser-565, concomitant with increased HSL activity. Phosphorylation and activation of HSL coincided with increases in StAR, P-StAR (Ser-194), and progesterone levels. Inhibition of HSL activity by CAY10499 effectively suppressed Bt2cAMP-induced StAR expression and progesterone synthesis. Targeted silencing of endogenous HSL, with siRNAs, resulted in increased cholesteryl ester levels and decreased cholesterol content in MA-10 cells. Depletion of HSL affected lipoprotein-derived cellular cholesterol influx, diminished the supply of cholesterol to the mitochondria, and resulted in the repression of StAR and P-StAR levels. Cells overexpressing HSL increased the efficacy of liver X receptor (LXR) ligands on StAR expression and steroid synthesis, suggesting HSL-mediated steroidogenesis entails enhanced oxysterol production. Conversely, cells deficient in LXRs exhibited decreased HSL responsiveness. Furthermore, an increase in HSL was correlated with the LXR target genes, steroid receptor element-binding protein 1c and ATP binding cassette transporter A1, demonstrating HSL-dependent regulation of steroidogenesis predominantly involves LXR signaling. LXRs interact/cooperate with RXRs and result in the activation of StAR gene transcription. These findings provide novel insight and demonstrate the molecular events by which HSL acts to drive cAMP/PKA-mediated regulation of StAR expression and

  8. Characterization of regulatory mechanism of Poncirus trifoliata microRNAs on their target genes with an integrated strategy of newly developed PPM-RACE and RLM-RACE.

    Science.gov (United States)

    Shangguan, Lingfei; Song, Changnian; Han, Jian; Leng, Xiangpeng; Kibet, Korir Nicholas; Mu, Qian; Kayesh, Emrul; Fang, Jinggui

    2014-02-01

    MicroRNAs (miRNAs) play an important role in post-transcriptional gene regulation that involved various biological and metabolic processes. Many extensive studies have been done in model plant species, to discover miRNAs' regulating expression of their target genes and analyze their functions. But, the function of Poncirus trifoliata miRNAs has not been properly investigated. In this study, we employed the RNA ligase-mediated 5' rapid amplification of cDNA ends (RLM-RACE) and the newly developed method called poly (A) polymerase-mediated 3' rapid amplification of cDNA ends (PPM-RACE), which mapped the cleavage site of target mRNAs and detected expression patterns of cleaved fragments that could in turn indicate the regulatory functions of the miRNAs on their target genes. Furthermore, the spatiotemporal expression levels of target genes were analyzed by qRT-PCR, with exhibiting different expression trends from their corresponding miRNAs, thus indicating the cleavage mode of miRNAs on their target genes. The expression patterns of miRNAs, their target mRNAs and cleaved target mRNAs in different organs of juvenile and adult trifoliate orange were studied. The results showed that the expression of miRNAs and their target mRNAs was in a trade-off trend. When the miRNA expression was high, its corresponding target mRNA expression was low, while the cleaved target mRNA expression was high; when the miRNA expression was low, its target mRNA expression was high, while the expression of cleaved target mRNAs follows that of the miRNA. The validation of the cleavage site of target mRNAs and the detection of expression patterns of cleaved fragments can further broaden the knowledge of small RNA-mediated regulation in P. trifoliate.

  9. RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle

    DEFF Research Database (Denmark)

    Salleh, M. S.; Mazzoni, G.; Höglund, J. K.

    2017-01-01

    genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency...

  10. Mechanisms for water allocation and water rights in Europe and the Netherlands : lessons from a general public law perspective

    NARCIS (Netherlands)

    van Rijswick, Marleen

    2015-01-01

    This article focuses on the allocation and regulation of water rights. Although there is a general concern about the allocation and restriction of the right to use scarce water resources, there is also a debate regarding the implementation of a public right to water in general and, in particular, th

  11. General load function in geo-mechanics: application to underground works; Fonction de charge generale en geomecanique: application aux travaux souterrains

    Energy Technology Data Exchange (ETDEWEB)

    Maiolino, S

    2006-04-15

    This work deals both with the behavioral and numerical aspects of the mechanical response of a rock massif to the digging out of a tunnel. The comparison between existing criteria has permitted to stress on some key points, like the dependence of the criterion to the average stress and the extension ratio. A load function, easily identifiable with tests, with regular and convex properties, has been proposed which allows to take into account the shape of the Mohr envelope of the criterion and the extension ratio. Regularized forms of Mohr-Coulomb and Hoek-Brown criteria can thus be achieved. The development of this new criterion has been completed by the proposal of a numerical charts method which greatly speeds up the resolution. For the proposed criterion, the physical problem is equivalent to a purely geometrical problem in polar coordinates in the plan. Numerical charts can thus be built which allow to find immediately the value of plastic deformations and to greatly reduce the processing time. Tunnel calculation methods have been the object of a bibliographic synthesis, specifying the domains and limitations of use of tunnel dimensioning methods used by engineers. The modeling of tunnels excavation has been performed with the stationary algorithm designed for the calculation of systems submitted to mobile loads. This algorithm has been adapted to integrate the new criterion and the numerical charts system. These tools have been validated using a real case study and data supplied by the French national agency of radioactive waste management (ANDRA) in the framework of the MODEX-REP European project (5. Euratom plan). The study of these data has permitted to define a rock wear variable, easily identifiable and allowing to parameterize the damaged rock criterion. (J.S.)

  12. Inferring the Impact of Regulatory Mechanisms that Underpin CD8+ T Cell Control of B16 Tumor Growth In vivo Using Mechanistic Models and Simulation

    Science.gov (United States)

    Klinke, David J.; Wang, Qing

    2017-01-01

    A major barrier for broadening the efficacy of immunotherapies for cancer is identifying key mechanisms that limit the efficacy of tumor infiltrating lymphocytes. Yet, identifying these mechanisms using human samples and mouse models for cancer remains a challenge. While interactions between cancer and the immune system are dynamic and non-linear, identifying the relative roles that biological components play in regulating anti-tumor immunity commonly relies on human intuition alone, which can be limited by cognitive biases. To assist natural intuition, modeling and simulation play an emerging role in identifying therapeutic mechanisms. To illustrate the approach, we developed a multi-scale mechanistic model to describe the control of tumor growth by a primary response of CD8+ T cells against defined tumor antigens using the B16 C57Bl/6 mouse model for malignant melanoma. The mechanistic model was calibrated to data obtained following adenovirus-based immunization and validated to data obtained following adoptive transfer of transgenic CD8+ T cells. More importantly, we use simulation to test whether the postulated network topology, that is the modeled biological components and their associated interactions, is sufficient to capture the observed anti-tumor immune response. Given the available data, the simulation results also provided a statistical basis for quantifying the relative importance of different mechanisms that underpin CD8+ T cell control of B16F10 growth. By identifying conditions where the postulated network topology is incomplete, we illustrate how this approach can be used as part of an iterative design-build-test cycle to expand the predictive power of the model. PMID:28101055

  13. Insights into the mechanism of FTY720 and compatibility with regulatory T cells for the inhibition of graft-versus-host disease (GVHD)

    OpenAIRE

    Taylor, Patricia A.; Ehrhardt, Michael J.; Lees, Christopher J.; Tolar, Jakub; Weigel, Brenda J; Panoskaltsis-Mortari, Angela; Serody, Jonathan S.; Brinkmann, Volker; Blazar, Bruce R.

    2007-01-01

    The immunomodulator FTY720 (FTY) has been shown to be beneficial in experimental models of organ transplantation and autoimmunity. We show that FTY significantly inhibited but did not prevent graft-versus-host disease (GVHD) in lethally irradiated or nonirradiated allogeneic recipients. Although most studies implicate prevention of lymphocyte egress from lymphoid organs as the primary mechanism of action, our data indicate that FTY effects on the host are more likely to be responsible for GVH...

  14. Potential Nociceptive Regulatory Effect of Probiotic Lactobacillus rhamnosus PB01 (DSM 14870) on Mechanical Sensitivity in Diet-Induced Obesity Model

    Science.gov (United States)

    Brandsborg, Erik

    2016-01-01

    Treatments for obesity have been shown to reduce pain secondary to weight loss. Intestinal microbiota, as an endogenous factor, influences obesity and pain sensitivity but the effect of oral probiotic supplementation on musculoskeletal pain perception has not been studied systematically. The present study examined the effect of a single daily oral dose (1 × 109 CFU) of probiotics (Lactobacillus rhamnosus PB01, DSM14870) supplement on mechanical pain thresholds in behaving diet-induced obese (DIO) mice and their normal weight (NW) controls. The mice (N = 24, 6-week-old male) were randomly divided into four groups on either standard or high fat diet with and without probiotic supplementation. Both DIO and NW groups with probiotic supplementation maintained an insignificant weight gain while the control groups gained significant weight (P < 0.05). Similarly, both DIO and NW probiotics supplemented groups demonstrated a significantly (P < 0.05) lower sensitivity to mechanical stimulation compared to their corresponding control. The results of this study suggest a protective effect of probiotics on nociception circuits, which propose a direct result of the weight reduction or an indirect result of anti-inflammatory properties of the probiotics. Deciphering the exact underlying mechanism of the weight loss and lowering nociception effect of the probiotic applied in this study require further investigation. PMID:27647980

  15. Potential Nociceptive Regulatory Effect of Probiotic Lactobacillus rhamnosus PB01 (DSM 14870 on Mechanical Sensitivity in Diet-Induced Obesity Model

    Directory of Open Access Journals (Sweden)

    Fereshteh Dardmeh

    2016-01-01

    Full Text Available Treatments for obesity have been shown to reduce pain secondary to weight loss. Intestinal microbiota, as an endogenous factor, influences obesity and pain sensitivity but the effect of oral probiotic supplementation on musculoskeletal pain perception has not been studied systematically. The present study examined the effect of a single daily oral dose (1 × 109 CFU of probiotics (Lactobacillus rhamnosus PB01, DSM14870 supplement on mechanical pain thresholds in behaving diet-induced obese (DIO mice and their normal weight (NW controls. The mice (N=24, 6-week-old male were randomly divided into four groups on either standard or high fat diet with and without probiotic supplementation. Both DIO and NW groups with probiotic supplementation maintained an insignificant weight gain while the control groups gained significant weight (P<0.05. Similarly, both DIO and NW probiotics supplemented groups demonstrated a significantly (P<0.05 lower sensitivity to mechanical stimulation compared to their corresponding control. The results of this study suggest a protective effect of probiotics on nociception circuits, which propose a direct result of the weight reduction or an indirect result of anti-inflammatory properties of the probiotics. Deciphering the exact underlying mechanism of the weight loss and lowering nociception effect of the probiotic applied in this study require further investigation.

  16. Mechanics

    CERN Document Server

    Hartog, J P Den

    1961-01-01

    First published over 40 years ago, this work has achieved the status of a classic among introductory texts on mechanics. Den Hartog is known for his lively, discursive and often witty presentations of all the fundamental material of both statics and dynamics (and considerable more advanced material) in new, original ways that provide students with insights into mechanical relationships that other books do not always succeed in conveying. On the other hand, the work is so replete with engineering applications and actual design problems that it is as valuable as a reference to the practicing e

  17. Genome-Wide Mapping of Targets of Maize Histone Deacetylase HDA101 Reveals Its Function and Regulatory Mechanism during Seed Development[OPEN

    Science.gov (United States)

    Yang, Hua; Liu, Xinye; Xin, Mingming; Du, Jinkun; Hu, Zhaorong; Peng, HuiRu; Sun, Qixin; Ni, Zhongfu; Yao, Yingyin

    2016-01-01

    Histone deacetylases (HDACs) regulate histone acetylation levels by removing the acetyl group from lysine residues. The maize (Zea mays) HDAC HDA101 influences several aspects of development, including kernel size; however, the molecular mechanism by which HDA101 affects kernel development remains unknown. In this study, we find that HDA101 regulates the expression of transfer cell-specific genes, suggesting that their misregulation may be associated with the defects in differentiation of endosperm transfer cells and smaller kernels observed in hda101 mutants. To investigate HDA101 function during the early stages of seed development, we performed genome-wide mapping of HDA101 binding sites. We observed that, like mammalian HDACs, HDA101 mainly targets highly and intermediately expressed genes. Although loss of HDA101 can induce histone hyperacetylation of its direct targets, this often does not involve variation in transcript levels. A small subset of inactive genes that must be negatively regulated during kernel development is also targeted by HDA101 and its loss leads to hyperacetylation and increased expression of these inactive genes. Finally, we report that HDA101 interacts with members of different chromatin remodeling complexes, such as NFC103/MSI1 and SNL1/SIN3-like protein corepressors. Taken together, our results reveal a complex genetic network regulated by HDA101 during seed development and provide insight into the different mechanisms of HDA101-mediated regulation of transcriptionally active and inactive genes. PMID:26908760

  18. Deep Sequencing-Based Transcriptome Analysis Reveals the Regulatory Mechanism of Bemisia tabaci (Hemiptera: Aleyrodidae Nymph Parasitized by Encarsia sophia (Hymenoptera: Aphelinidae.

    Directory of Open Access Journals (Sweden)

    Yingying Wang

    Full Text Available The whitefly Bemisia tabaci is a genetically diverse complex with multiple cryptic species, and some are the most destructive invasive pests of many ornamentals and crops worldwide. Encarsia sophia is an autoparasitoid wasp that demonstrated high efficiency as bio-control agent of whiteflies. However, the immune mechanism of B. tabaci parasitization by E. sophia is unknown. In order to investigate immune response of B. tabaci to E. Sophia parasitization, the transcriptome of E. sophia parasitized B. tabaci nymph was sequenced by Illumina sequencing. De novo assembly generated 393,063 unigenes with average length of 616 bp, in which 46,406 unigenes (15.8% of all unigenes were successfully mapped. Parasitization by E. sophia had significant effects on the transcriptome profile of B. tabaci nymph. A total of 1482 genes were significantly differentially expressed, of which 852 genes were up-regulated and 630 genes were down-regulated. These genes were mainly involved in immune response, development, metabolism and host signaling pathways. At least 52 genes were found to be involved in the host immune response, 33 genes were involved in the development process, and 29 genes were involved in host metabolism. Taken together, the assembled and annotated transcriptome sequences provided a valuable genomic resource for further understanding the molecular mechanism of immune response of B. tabaci parasitization by E. sophia.

  19. A Negative Regulatory Mechanism Involving 14-3-3ζ Limits Signaling Downstream of ROCK to Regulate Tissue Stiffness in Epidermal Homeostasis.

    Science.gov (United States)

    Kular, Jasreen; Scheer, Kaitlin G; Pyne, Natasha T; Allam, Amr H; Pollard, Anthony N; Magenau, Astrid; Wright, Rebecca L; Kolesnikoff, Natasha; Moretti, Paul A; Wullkopf, Lena; Stomski, Frank C; Cowin, Allison J; Woodcock, Joanna M; Grimbaldeston, Michele A; Pitson, Stuart M; Timpson, Paul; Ramshaw, Hayley S; Lopez, Angel F; Samuel, Michael S

    2015-12-21

    ROCK signaling causes epidermal hyper-proliferation by increasing ECM production, elevating dermal stiffness, and enhancing Fak-mediated mechano-transduction signaling. Elevated dermal stiffness in turn causes ROCK activation, establishing mechano-reciprocity, a positive feedback loop that can promote tumors. We have identified a negative feedback mechanism that limits excessive ROCK signaling during wound healing and is lost in squamous cell carcinomas (SCCs). Signal flux through ROCK was selectively tuned down by increased levels of 14-3-3ζ, which interacted with Mypt1, a ROCK signaling antagonist. In 14-3-3ζ(-/-) mice, unrestrained ROCK signaling at wound margins elevated ECM production and reduced ECM remodeling, increasing dermal stiffness and causing rapid wound healing. Conversely, 14-3-3ζ deficiency enhanced cutaneous SCC size. Significantly, inhibiting 14-3-3ζ with a novel pharmacological agent accelerated wound healing 2-fold. Patient samples of chronic non-healing wounds overexpressed 14-3-3ζ, while cutaneous SCCs had reduced 14-3-3ζ. These results reveal a novel 14-3-3ζ-dependent mechanism that negatively regulates mechano-reciprocity, suggesting new therapeutic opportunities.

  20. IPTV Market Development and Regulatory Aspects

    DEFF Research Database (Denmark)

    Tadayoni, Reza; Sigurdsson, Halldór Matthias

    2006-01-01

    The aim of this paper is to analyse the development of IPTV technology / market and to discuss major regulatory parameters. A general overview of architectures and the technologies deployed for establishing IPTV services is given and the main stake holder identified, along with, the current service...... architecture, the available content in IPTV platforms, and the current business models. Furthermore the regulatory framework of the TV broadcast and IPTV in Europe is analysed....

  1. Genomics in the land of regulatory science.

    Science.gov (United States)

    Tong, Weida; Ostroff, Stephen; Blais, Burton; Silva, Primal; Dubuc, Martine; Healy, Marion; Slikker, William

    2015-06-01

    Genomics science has played a major role in the generation of new knowledge in the basic research arena, and currently question arises as to its potential to support regulatory processes. However, the integration of genomics in the regulatory decision-making process requires rigorous assessment and would benefit from consensus amongst international partners and research communities. To that end, the Global Coalition for Regulatory Science Research (GCRSR) hosted the fourth Global Summit on Regulatory Science (GSRS2014) to discuss the role of genomics in regulatory decision making, with a specific emphasis on applications in food safety and medical product development. Challenges and issues were discussed in the context of developing an international consensus for objective criteria in the analysis, interpretation and reporting of genomics data with an emphasis on transparency, traceability and "fitness for purpose" for the intended application. It was recognized that there is a need for a global path in the establishment of a regulatory bioinformatics framework for the development of transparent, reliable, reproducible and auditable processes in the management of food and medical product safety risks. It was also recognized that training is an important mechanism in achieving internationally consistent outcomes. GSRS2014 provided an effective venue for regulators andresearchers to meet, discuss common issues, and develop collaborations to address the challenges posed by the application of genomics to regulatory science, with the ultimate goal of wisely integrating novel technical innovations into regulatory decision-making.

  2. Improving the Regulatory Framework for the Legal Status of Applicants for International Protection in the Context of the implementation of Relocation Mechanisms

    Directory of Open Access Journals (Sweden)

    Tache Bocaneala

    2016-05-01

    Full Text Available The unprecedented refugee crisis facing the European Union, the impossibility of some Member States unable to cope and to process the massive flow of people on their borders and blocking the “Balkan Route” that moved towards the states where they wanted to reach, led the pressing need for putting in place new instruments to manage the situation. The mechanisms of relocating refugees, the principle of solidarity through quotas imposed on member states put to the authorities in these countries, implicitly in Romania, a number of issues with great difficulty in solving them. By the present study we have highlighted some of these issues in connection with the specific legal status of refugees resettled in other countries in Romania and any possible solutions to solve them.

  3. A Negative Regulatory Mechanism Involving 14-3-3ζ Limits Signaling Downstream of ROCK to Regulate Tissue Stiffness in Epidermal Homeostasis

    DEFF Research Database (Denmark)

    Kular, Jasreen; Scheer, Kaitlin G; Pyne, Natasha T

    2015-01-01

    ROCK signaling causes epidermal hyper-proliferation by increasing ECM production, elevating dermal stiffness, and enhancing Fak-mediated mechano-transduction signaling. Elevated dermal stiffness in turn causes ROCK activation, establishing mechano-reciprocity, a positive feedback loop that can...... promote tumors. We have identified a negative feedback mechanism that limits excessive ROCK signaling during wound healing and is lost in squamous cell carcinomas (SCCs). Signal flux through ROCK was selectively tuned down by increased levels of 14-3-3ζ, which interacted with Mypt1, a ROCK signaling...... antagonist. In 14-3-3ζ(-/-) mice, unrestrained ROCK signaling at wound margins elevated ECM production and reduced ECM remodeling, increasing dermal stiffness and causing rapid wound healing. Conversely, 14-3-3ζ deficiency enhanced cutaneous SCC size. Significantly, inhibiting 14-3-3ζ with a novel...

  4. RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle.

    Science.gov (United States)

    Salleh, M S; Mazzoni, G; Höglund, J K; Olijhoek, D W; Lund, P; Løvendahl, P; Kadarmideen, H N

    2017-03-24

    The selective breeding of cattle with high-feed efficiencies (FE) is an important goal of beef and dairy cattle producers. Global gene expression patterns in relevant tissues can be used to study the functions of genes that are potentially involved in regulating FE. In the present study, high-throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency. On average, 57 million reads (short reads or short mRNA sequences genes showed interaction effects in the Jersey cows. The analyses showed that DEGs act through certain pathways to affect or regulate FE, including steroid hormone biosynthesis, retinol metabolism, starch and sucrose metabolism, ether lipid metabolism, arachidonic acid metabolism and drug metabolism cytochrome P450. We used RNA-Seq-based liver transcriptomic profiling of high- and low-RFI dairy cows in two breeds and identified significantly DEGs, their molecular mechanisms, their interactions with other genes and functional enrichments of different molecular pathways. The DEGs that were identified were the CYP's and GIMAP genes for the Holstein and Jersey cows, respectively, which are related to the primary immunodeficiency pathway and play a major role in feed utilization and the metabolism of lipids, sugars and proteins.

  5. RhoA S-nitrosylation as a regulatory mechanism influencing endothelial barrier function in response to G(+)-bacterial toxins.

    Science.gov (United States)

    Chen, F; Wang, Y; Rafikov, R; Haigh, S; Zhi, W B; Kumar, S; Doulias, P T; Rafikova, O; Pillich, H; Chakraborty, T; Lucas, R; Verin, A D; Catravas, J D; She, J X; Black, S M; Fulton, D J R

    2017-03-01

    Disruption of the endothelial barrier in response to Gram positive (G(+)) bacterial toxins is a major complication of acute lung injury (ALI) and can be further aggravated by antibiotics which stimulate toxin release. The integrity of the pulmonary endothelial barrier is mediated by the balance of disruptive forces such as the small GTPase RhoA, and protective forces including endothelium-derived nitric oxide (NO). How NO protects against the barrier dysfunction is incompletely understood and our goal was to determine whether NO and S-nitrosylation can modulate RhoA activity and whether this mechanism is important for G(+) toxin-induced microvascular permeability. We found that the G(+) toxin listeriolysin-O (LLO) increased RhoA activity and that NO and S-NO donors inhibit RhoA activity. RhoA was robustly S-nitrosylated as determined by biotin-switch and mercury column analysis. MS revealed that three primary cysteine residues are S-nitrosylated including cys16, cys20 and cys159. Mutation of these residues to serine diminished S-nitrosylation to endogenous NO and mutant RhoA was less sensitive to inhibition by S-NO. G(+)-toxins stimulated the denitrosylation of RhoA which was not mediated by S-nitrosoglutathione reductase (GSNOR), thioredoxin (TRX) or thiol-dependent enzyme activity but was instead stimulated directly by elevated calcium levels. Calcium-promoted the direct denitrosylation of WT but not mutant RhoA and mutant RhoA adenovirus was more effective than WT in disrupting the barrier integrity of human lung microvascular endothelial cells. In conclusion, we reveal a novel mechanism by which NO and S-nitrosylation reduces RhoA activity which may be of significance in the management of pulmonary endothelial permeability induced by G(+)-toxins.

  6. Regulatory mechanisms controlling expression of the DAN/TIR mannoprotein genes during anaerobic remodeling of the cell wall in Saccharomyces cerevisiae.

    Science.gov (United States)

    Abramova, N E; Cohen, B D; Sertil, O; Kapoor, R; Davies, K J; Lowry, C V

    2001-03-01

    The DAN/TIR genes of Saccharomyces cerevisiae encode homologous mannoproteins, some of which are essential for anaerobic growth. Expression of these genes is induced during anaerobiosis and in some cases during cold shock. We show that several heme-responsive mechanisms combine to regulate DAN/TIR gene expression. The first mechanism employs two repression factors, Mox1 and Mox2, and an activation factor, Mox4 (for mannoprotein regulation by oxygen). The genes encoding these proteins were identified by selecting for recessive mutants with altered regulation of a dan1::ura3 fusion. MOX4 is identical to UPC2, encoding a binucleate zinc cluster protein controlling expression of an anaerobic sterol transport system. Mox4/Upc2 is required for expression of all the DAN/TIR genes. It appears to act through a consensus sequence termed the AR1 site, as does Mox2. The noninducible mox4Delta allele was epistatic to the constitutive mox1 and mox2 mutations, suggesting that Mox1 and Mox2 modulate activation by Mox4 in a heme-dependent fashion. Mutations in a putative repression domain in Mox4 caused constitutive expression of the DAN/TIR genes, indicating a role for this domain in heme repression. MOX4 expression is induced both in anaerobic and cold-shocked cells, so heme may also regulate DAN/TIR expression through inhibition of expression of MOX4. Indeed, ectopic expression of MOX4 in aerobic cells resulted in partially constitutive expression of DAN1. Heme also regulates expression of some of the DAN/TIR genes through the Rox7 repressor, which also controls expression of the hypoxic gene ANB1. In addition Rox1, another heme-responsive repressor, and the global repressors Tup1 and Ssn6 are also required for full aerobic repression of these genes.

  7. 肥胖状态下L细胞功能状态及调控机制%L-cell function and regulatory mechanism in obesity

    Institute of Scientific and Technical Information of China (English)

    苏静; 李晓华

    2012-01-01

    Obesity is a high risk factor of diabetes.Several studies indicate that plasma glucagon like peptide(GLP) -1 and peptide YY (PYY) levels are decreased because of L-cell dysfunction in non-diabetic obese subjects.However,the mechanism of L-cell dysfunction in obesity is unclear.Abnormal concentrations and composition of plasma free fatty acids ( FFAs),leptin resistance,high level of plasma interleukin-6 (IL-6),aberrant composition and amount of gut microbiota may contribute to L-cell dysfunction.Exploring the mechanism of L-cell dysfunction is helpful to find new therapeutic targets for preventing the progression of obesity to diabetes.%肥胖是2型糖尿病的高危因素.多项研究表明非2型糖尿病肥胖者即出现L细胞功能紊乱,表现为胰高血糖素样肽-1(GLP-1)及肽YY( PYY)水平下降.然而肥胖状态下L细胞功能紊乱的发生机制并不明确,血浆游离脂肪酸( FFAs)浓度及组分异常、瘦素抵抗、白细胞介素-6(IL-6)水平升高以及肠道菌群结构异常以各自不同的方式影响L细胞功能.探索肥胖状态下L细胞功能紊乱的发生机制,有助于寻找新的治疗靶点,控制肥胖向2型糖尿病发展.

  8. Regulatory mechanism of length-dependent activation in skinned porcine ventricular muscle: role of thin filament cooperative activation in the Frank-Starling relation.

    Science.gov (United States)

    Terui, Takako; Shimamoto, Yuta; Yamane, Mitsunori; Kobirumaki, Fuyu; Ohtsuki, Iwao; Ishiwata, Shin'ichi; Kurihara, Satoshi; Fukuda, Norio

    2010-10-01

    Cardiac sarcomeres produce greater active force in response to stretch, forming the basis of the Frank-Starling mechanism of the heart. The purpose of this study was to provide the systematic understanding of length-dependent activation by investigating experimentally and mathematically how the thin filament "on-off" switching mechanism is involved in its regulation. Porcine left ventricular muscles were skinned, and force measurements were performed at short (1.9 µm) and long (2.3 µm) sarcomere lengths. We found that 3 mM MgADP increased Ca(2+) sensitivity of force and the rate of rise of active force, consistent with the increase in thin filament cooperative activation. MgADP attenuated length-dependent activation with and without thin filament reconstitution with the fast skeletal troponin complex (sTn). Conversely, 20 mM of inorganic phosphate (Pi) decreased Ca(2+) sensitivity of force and the rate of rise of active force, consistent with the decrease in thin filament cooperative activation. Pi enhanced length-dependent activation with and without sTn reconstitution. Linear regression analysis revealed that the magnitude of length-dependent activation was inversely correlated with the rate of rise of active force. These results were quantitatively simulated by a model that incorporates the Ca(2+)-dependent on-off switching of the thin filament state and interfilament lattice spacing modulation. Our model analysis revealed that the cooperativity of the thin filament on-off switching, but not the Ca(2+)-binding ability, determines the magnitude of the Frank-Starling effect. These findings demonstrate that the Frank-Starling relation is strongly influenced by thin filament cooperative activation.

  9. The Regulatory Mechanism of Hepcidin Expression by Interleukin 6(IL-6) in Exercise%运动引起的白细胞介素6的改变与铁调素的调控

    Institute of Scientific and Technical Information of China (English)

    闫芬; 李颖; 刘树欣; 刘玉倩

    2011-01-01

    运动可改变机体铁状态,过度运动会引起机体铁缺乏,甚至导致机体出现运动性贫血,影响运动员成绩.近几年研究表明铁调素(Hepcidin)是调控机体铁代谢的关键因素,而运动中产生的白细胞介素6(IL-6)是影响Hepcidin表达变化的重要原因之一.介绍了IL-6对Hepcidin表达的影响、运动对IL-6表达调控的研究进展,综合分析了运动引起的IL-6的改变及其对Hepcidin的调控机制.%The iron status can be changed during exercise. Excessive exercise can lead to iron deficiency, even sports anemia. Accordingly athletes performance is greatly affected by iron status. The researches on the regulatory mechanism of iron metabolism show that hepcidin plays an important role in iron metabolism,and IL -6 is one of the important reasons for the expression of hepcidin in exercise. This review reveals the regulaory mechanism of IL-6 on hepcidin expression in exercise.

  10. A blueprint for a simultaneous test of quantum mechanics and general relativity in a space-based quantum optics experiment

    CERN Document Server

    Pallister, Sam; Formichella, Valerio; Gampierakis, Nicolas; Notaro, Virginia; Knott, Paul; Azevedo, Rui; Buchheim, Nikolaus; de Carvalho, Silvio; Jarvela, Emilia; Laporte, Matthieu; Kaikkonen, Jukka-Pekka; Meshksar, Neda; Nikkanen, Timo; Yttergren, Madeleine

    2016-01-01

    In this paper we propose an experiment designed to observe a general-relativistic effect on single photon interference. The experiment consists of a folded Mach-Zehnder interferometer, with the arms distributed between a single Earth orbiter and a ground station. By compensating for other degrees of freedom and the motion of the orbiter, this setup aims to detect the influence of general relativistic time dilation on a spatially superposed single photon. The proposal details a payload to measure the required effect, along with an extensive feasibility analysis given current technological capabilities.

  11. A blueprint for a simultaneous test of quantum mechanics and general relativity in a space-based quantum optics experiment

    Energy Technology Data Exchange (ETDEWEB)

    Pallister, Sam [University of Bristol, School of Mathematics, Bristol (United Kingdom); Coop, Simon [The Barcelona Institute of Science and Technology, ICFO-Institut de Ciencies Fotoniques, Barcelona (Spain); Formichella, Valerio [Politecnico di Torino, Torino (Italy); Istituto Nazionale di Ricerca Metrologica (INRiM), Torino (Italy); Gampierakis, Nicolas [University of East Anglia, School of Natural Sciences, Norwich (United Kingdom); Notaro, Virginia [Sapienza University of Rome, Department of Mechanical and Aerospace Engineering, Rome (Italy); Knott, Paul [University of Sussex, Department of Physics and Astronomy, Brighton (United Kingdom); Azevedo, Rui [Faculdade de Ciencias da Universidade do Porto, Porto (Portugal); Buchheim, Nikolaus [Max Planck Institute of Quantum Optics, Garching (Germany); De Carvalho, Silvio [University of Applied Sciences Wiener Neustadt, Aerospace Engineering Department, Wiener Neustadt (Austria); Jaervelae, Emilia [Aalto University Metsaehovi Radio Observatory, Kylmaelae (Finland); Aalto University Department of Radio Science and Engineering, Aalto (Finland); Laporte, Matthieu [Universite Paris Diderot, APC (AstroParticule et Cosmologie), Paris (France); Kaikkonen, Jukka-Pekka [Aalto University, Low Temperature Laboratory, Department of Applied Physics, Aalto (Finland); Meshksar, Neda [Leibniz University Hanover, Albert Einstein Institute, Hanover (Germany); Nikkanen, Timo [Aalto University Department of Radio Science and Engineering, Aalto (Finland); Finnish Meteorological Institute, Radar and Space Technology Research Group, Helsinki (Finland); Yttergren, Madeleine [Chalmers University of Technology, Physics and Astronomy, Goeteborg (Sweden)

    2017-12-15

    In this paper we propose an experiment designed to observe a general-relativistic effect on single photon interference. The experiment consists of a folded Mach-Zehnder interferometer, with the arms distributed between a single Earth orbiter and a ground station. By compensating for other degrees of freedom and the motion of the orbiter, this setup aims to detect the influence of general relativistic time dilation on a spatially superposed single photon. The proposal details a payload to measure the required effect, along with an extensive feasibility analysis given current technological capabilities. (orig.)

  12. Regulatory network operations in the Pathway Tools software

    Directory of Open Access Journals (Sweden)

    Paley Suzanne M

    2012-09-01

    Full Text Available Abstract Background Biologists are elucidating complex collections of genetic regulatory data for multiple organisms. Software is needed for such regulatory network data. Results The Pathway Tools software supports storage and manipulation of regulatory information through a variety of strategies. The Pathway Tools regulation ontology captures transcriptional and translational regulation, substrate-level regulation of enzyme activity, post-translational modifications, and regulatory pathways. Regulatory visualizations include a novel diagram that summarizes all regulatory influences on a gene; a transcription-unit diagram, and an interactive visualization of a full transcriptional regulatory network that can be painted with gene expression data to probe correlations between gene expression and regulatory mechanisms. We introduce a novel type of enrichment analysis that asks whether a gene-expression dataset is over-represented for known regulators. We present algorithms for ranking the degree of regulatory influence of genes, and for computing the net positive and negative regulatory influences on a gene. Conclusions Pathway Tools provides a comprehensive environment for manipulating molecular regulatory interactions that integrates regulatory data with an organism’s genome and metabolic network. Curated collections of regulatory data authored using Pathway Tools are available for Escherichia coli, Bacillus subtilis, and Shewanella oneidensis.

  13. Preliminary research on regulatory effect of estrogen on malignant biological behaviors of triple-negative breast cancer cells and its molecular mechanisms

    Institute of Scientific and Technical Information of China (English)

    Tian-Fang Zhou

    2016-01-01

    Objective:To study the regulating effect of estrogen on malignant biological behaviors of triple-negative breast cancer cells and its molecular mechanisms. Methods:Triple-negative breast cancer cell lines MDA-MB-468 were cultured and treated with different doses of estrogen and 10-6 mol/L estrogen combined with GPR30 antagonist G15 for 12 h, 24 h and 48 h, and then cell viability, migration as well as mRNA expression levels of ITGβ1, Sema 4D, MK, c-Met and AEG-1 were detected. Results:Estradiol could increase cell viability, reduce scratch area and increase mRNA expression levels of ITGβ1, Sema 4D, MK, c-Met and AEG-1 in dose-dependent and time-dependent manner;after estradiol combined with G15 treatment, cell viability was significantly lower than that of estradiol treatment alone, scratch area was significantly larger than that of estradiol treatment alone, and mRNA contents of ITGβ1, Sema 4D, MK, c-Met and AEG-1 were significantly lower than those of estradiol treatment alone. Conclusion:Estrogen can regulate the malignant biological behaviors of triple-negative breast cancer cells, promote cell proliferation and migration, and increase the expression of related genes through GPR30.

  14. Bound State Solution of Dirac Equation for Generalized Pöschl-Teller plus Trigomometric Pöschl-Teller Non- Central Potential Using SUSY Quantum Mechanics

    Directory of Open Access Journals (Sweden)

    Suparmi

    2014-12-01

    Full Text Available The bound state solution of the Dirac equation for generalized PöschlTeller and trigonometric Pöschl-Teller non-central potentials was obtained using SUSY quantum mechanics and the idea of shape invariance potential. The approximate relativistic energy spectrum was expressed in the closed form. The radial and polar wave functions were obtained using raising and lowering of radial and polar operators. The orbital quantum numbers were found from the polar Dirac equation, which was solved using SUSY quantum mechanics and the idea of shape invariance.

  15. Advance in vitamin D metabolism and its regulatory mechanism%维生素D的代谢及调控研究新进展

    Institute of Scientific and Technical Information of China (English)

    祁珊珊; 王永吉

    2015-01-01

    Discovery and clinical application of vitamin D, a prohormone, result in successful treatment for rickets and osteomalacia. The major biological function of vitamin D is to regulate the metabolism of calcium and phosphate and bone formation. Vitamin D inhibits cell proliferation and regulates immune system, and it is effective in the prevention and treatment of many diseases, such as osteoporosis, hyperparathyroidism, psoriasis, autoimmune disease, and cancer. Therefore, there is a great expectation on gaining healthy benefits from vitamin D supplements. However, overdosing vitamin D may cause severe side effects. This review discusses the effect of the vitamin D hormone system and its self protection function from aspects of metabolism and regulation mechanism of vitamin D.%维生素D是前激素( prohormone),它的发现及其在临床上的成功应用,为治愈佝偻病和成人软骨症开辟了有效途径。维生素D的主要作用是参与调节人体内钙、磷代谢及骨的形成,并有抑制细胞生长、调节免疫作用的功能,尤其对骨质疏松症、自身免疫疾病、肿瘤等多种疾病有防治的功效。正因如此,人们对维生素D的健康效能有着广泛的期待,可是摄入维生素D的同时又担心因过量而引起毒副作用。本文从维生素D的代谢和调控两方面来讨论维生素D激素系统的作用及自我保护功能。

  16. Genome-wide comparative analysis of type-A Arabidopsis response regulator genes by overexpression studies re-veals their diverse roles and regulatory mechanisms in cytokinin signaling

    Institute of Scientific and Technical Information of China (English)

    Bo Ren; Yan Liang; Yan Deng; Qingguo Chen; Jian Zhang; Xiaohui Yang; Jianru Zuo

    2009-01-01

    Cytokinin is a critical growth regulator for various aspects of plant growth and development. In Arabidopsis, cyto-kinin signaling is mediated by a two-component system-based phosphorelay that transmits a signal from the recep-tors, through histidine phosphotransfer proteins, to the downstream response regulators (ARRs). Of these ARRs, type-A ARR genes, whose transcription can be rapidly induced by cytokinin, act as negative regulators of cytokinin signaling. However, because of functional redundancy, the function of type-A ARR genes in plant growth and de-velopment is not well understood by analyzing loss-of-function mutants. In this study, we performed a comparative functional study on all ten type-A ARR genes by analyzing transgenic plants overexpressing these ARR genes fused to a MYC epitope tag. Overexpression of ARR genes results in a variety of cytokinin-associated phenotypes. Notably, overexpression of different ARR transgenes causes diverse phenotypes, even between phylogenetically closely-related gene pairs, such as within the ARR3-ARR4 and ARRS-ARR6 pairs. We found that the accumulation of a subset of ARR proteins (ARR3, ARR5, ARR7, ARR16 and ARR17; possibly ARR8 and ARR15) is increased by MGI32, a spe-cific proteasomal inhibitor, indicating that stability of these proteins is regulated by proteasomal degradation. More-over, similar to that of previously characterized ARR5, ARR6 and ARR7, stability of ARR16 and ARR17, possibly including ARR8 and ARRI5, is regulated by cytokinin. These results suggest that type-A ARR proteins are regulated by a combinatorial mechanism involving both the cytokinin and proteasome pathways, thereby executing distinctive functions in plant growth and development.

  17. Evolutionary dynamics and functional roles of regulatory systems in plants

    NARCIS (Netherlands)

    Berke, L.

    2015-01-01

    Transcription, the process of generating RNA copies of the genetic information stored in the DNA, is crucial for every organism. As with other essential processes in life, correct activation and repression of transcription is governed by complex regulatory mechanisms. These regulatory mechanisms ope

  18. A general mixed mode fracture mechanics test specimen: The DCB-specimen loaded with uneven bending moments

    DEFF Research Database (Denmark)

    Sørensen, Bent F.; Jørgensen, K.; Jacobsen, T.K.;

    2004-01-01

    A mixed mode specimen is proposed for fracture mechanics characterisation of adhesive joints, laminates and multilayers. The specimen is a double cantilever beam specimen loaded with uneven bending moments at the two free beams. By varying the ratiobetween the two applied moments, the full mode...

  19. Regulatory T Cells and Parasites

    Directory of Open Access Journals (Sweden)

    TP. Velavan

    2011-01-01

    Full Text Available Human host encounters a wide array of parasites; however, the crucial aspect is the failure of the host immune system to clear these parasites despite antigen recognition. In the recent past, a new immunological concept has emerged, which provides a framework to better understand several aspects of host susceptibility to parasitic infection. It is widely believed that parasites are able to modulate the magnitude of effector responses by inducing regulatory T cell (Tregs population and several studies have investigated whether this cell population plays a role in balancing protective immunity and pathogenesis during parasite infection. This review discusses the several mechanism of Treg-mediated immunosuppression in the human host and focuses on the functional role of Tregs and regulatory gene polymorphisms in infectious diseases.

  20. Reduction by symmetries in singular quantum-mechanical problems: General scheme and application to Aharonov-Bohm model

    Energy Technology Data Exchange (ETDEWEB)

    Smirnov, A. G., E-mail: smirnov@lpi.ru [I. E. Tamm Theory Department, P. N. Lebedev Physical Institute, Leninsky Prospect 53, Moscow 119991 (Russian Federation)

    2015-12-15

    We develop a general technique for finding self-adjoint extensions of a symmetric operator that respects a given set of its symmetries. Problems of this type naturally arise when considering two- and three-dimensional Schrödinger operators with singular potentials. The approach is based on constructing a unitary transformation diagonalizing the symmetries and reducing the initial operator to the direct integral of a suitable family of partial operators. We prove that symmetry preserving self-adjoint extensions of the initial operator are in a one-to-one correspondence with measurable families of self-adjoint extensions of partial operators obtained by reduction. The general scheme is applied to the three-dimensional Aharonov-Bohm Hamiltonian describing the electron in the magnetic field of an infinitely thin solenoid. We construct all self-adjoint extensions of this Hamiltonian, invariant under translations along the solenoid and rotations around it, and explicitly find their eigenfunction expansions.

  1. Evolutionary dynamics of prokaryotic transcriptional regulatory networks.

    Science.gov (United States)

    Madan Babu, M; Teichmann, Sarah A; Aravind, L

    2006-04-28

    The structure of complex transcriptional regulatory networks has been studied extensively in certain model organisms. However, the evolutionary dynamics of these networks across organisms, which would reveal important principles of adaptive regulatory changes, are poorly understood. We use the known transcriptional regulatory network of Escherichia coli to analyse the conservation patterns of this network across 175 prokaryotic genomes, and predict components of the regulatory networks for these organisms. We observe that transcription factors are typically less conserved than their target genes and evolve independently of them, with different organisms evolving distinct repertoires of transcription factors responding to specific signals. We show that prokaryotic transcriptional regulatory networks have evolved principally through widespread tinkering of transcriptional interactions at the local level by embedding orthologous genes in different types of regulatory motifs. Different transcription factors have emerged independently as dominant regulatory hubs in various organisms, suggesting that they have convergently acquired similar network structures approximating a scale-free topology. We note that organisms with similar lifestyles across a wide phylogenetic range tend to conserve equivalent interactions and network motifs. Thus, organism-specific optimal network designs appear to have evolved due to selection for specific transcription factors and transcriptional interactions, allowing responses to prevalent environmental stimuli. The methods for biological network analysis introduced here can be applied generally to study other networks, and these predictions can be used to guide specific experiments.

  2. Type D personality in the general population: a systematic review of health status, mechanisms of disease, and work-related problems.

    Science.gov (United States)

    Mols, Floortje; Denollet, Johan

    2010-01-23

    The objective was to review all available literature concerning Type D (distressed) personality among the general population and to discuss its implications for research on health status, disease-promoting mechanisms and work-related problems in non-clinical populations. A computerized search of the literature was performed independently and in duplicate by both investigators on December 21st, 2009. Published research reports were included if they studied Type D personality among the general population. Nineteen articles were selected and they were subjected to an 11-item standardised quality checklist by both investigators. The methodological quality of the selected studies was adequate to high. The studies included in this review showed that the presence of Type D characteristics had a negative impact on mental health status (more symptoms of depression, anxiety, post-traumatic stress disorder, mental distress, passive coping, and less social support) and physical health status (more somatic complaints, lower health status, more influenza-like illness reporting). Other studies reported on behavioral and biological mechanisms of disease in apparently healthy individuals with a Type D personality. Finally, some studies also showed a negative effect of Type D personality on work-related problems (higher absence-leave, higher levels of vital exhaustion and burnout, and more work-related stress). Type D personality is a vulnerability factor for general psychological distress that affects mental and physical health status and is associated with disease-promoting mechanisms and work-related problems in apparently healthy individuals.

  3. The cytoplasmic poly(A) polymerases GLD-2 and GLD-4 promote general gene expression via distinct mechanisms

    OpenAIRE

    Nousch, M.; Yeroslaviz, A.; Habermann, B; Eckmann, C

    2014-01-01

    Post-transcriptional gene regulation mechanisms decide on cellular mRNA activities. Essential gatekeepers of post-transcriptional mRNA regulation are broadly conserved mRNA-modifying enzymes, such as cytoplasmic poly(A) polymerases (cytoPAPs). Although these non-canonical nucleotidyltransferases efficiently elongate mRNA poly(A) tails in artificial tethering assays, we still know little about their global impact on poly(A) metabolism and their individual molecular roles in promoting protein p...

  4. Effects of Sodium Butyrate Treatment on Histone Modifications and the Expression of Genes Related to Epigenetic Regulatory Mechanisms and Immune Response in European Sea Bass (Dicentrarchus Labrax) Fed a Plant-Based Diet

    Science.gov (United States)

    Díaz, Noelia; Rimoldi, Simona; Ceccotti, Chiara; Gliozheni, Emi; Piferrer, Francesc

    2016-01-01

    Bacteria that inhabit the epithelium of the animals’ digestive tract provide the essential biochemical pathways for fermenting otherwise indigestible dietary fibers, leading to the production of short-chain fatty acids (SCFAs). Of the major SCFAs, butyrate has received particular attention due to its numerous positive effects on the health of the intestinal tract and peripheral tissues. The mechanisms of action of this four-carbon chain organic acid are different; many of these are related to its potent regulatory effect on gene expression since butyrate is a histone deacetylase inhibitor that play a predominant role in the epigenetic regulation of gene expression and cell function. In the present work, we investigated in the European sea bass (Dicentrarchus labrax) the effects of butyrate used as a feed additive on fish epigenetics as well as its regulatory role in mucosal protection and immune homeostasis through impact on gene expression. Seven target genes related to inflammatory response and reinforcement of the epithelial defense barrier [tnfα (tumor necrosis factor alpha) il1β, (interleukin 1beta), il-6, il-8, il-10, and muc2 (mucin 2)] and five target genes related to epigenetic modifications [dicer1(double-stranded RNA-specific endoribonuclease), ehmt2 (euchromatic histone-lysine-N-methyltransferase 2), pcgf2 (polycomb group ring finger 2), hdac11 (histone deacetylase-11), and jarid2a (jumonji)] were analyzed in fish intestine and liver. We also investigated the effect of dietary butyrate supplementation on histone acetylation, by performing an immunoblotting analysis on liver core histone extracts. Results of the eight-week-long feeding trial showed no significant differences in weight gain or SGR (specific growth rate) of sea bass that received 0.2% sodium butyrate supplementation in the diet in comparison to control fish that received a diet without Na-butyrate. Dietary butyrate led to a twofold increase in the acetylation level of histone H4 at

  5. The formulation of dynamical contact problems with friction in the case of systems of rigid bodies and general discrete mechanical systems—Painlevé and Kane paradoxes revisited

    Science.gov (United States)

    Charles, Alexandre; Ballard, Patrick

    2016-08-01

    The dynamics of mechanical systems with a finite number of degrees of freedom (discrete mechanical systems) is governed by the Lagrange equation which is a second-order differential equation on a Riemannian manifold (the configuration manifold). The handling of perfect (frictionless) unilateral constraints in this framework (that of Lagrange's analytical dynamics) was undertaken by Schatzman and Moreau at the beginning of the 1980s. A mathematically sound and consistent evolution problem was obtained, paving the road for many subsequent theoretical investigations. In this general evolution problem, the only reaction force which is involved is a generalized reaction force, consistently with the virtual power philosophy of Lagrange. Surprisingly, such a general formulation was never derived in the case of frictional unilateral multibody dynamics. Instead, the paradigm of the Coulomb law applying to reaction forces in the real world is generally invoked. So far, this paradigm has only enabled to obtain a consistent evolution problem in only some very few specific examples and to suggest numerical algorithms to produce computational examples (numerical modeling). In particular, it is not clear what is the evolution problem underlying the computational examples. Moreover, some of the few specific cases in which this paradigm enables to write down a precise evolution problem are known to show paradoxes: the Painlevé paradox (indeterminacy) and the Kane paradox (increase in kinetic energy due to friction). In this paper, we follow Lagrange's philosophy and formulate the frictional unilateral multibody dynamics in terms of the generalized reaction force and not in terms of the real-world reaction force. A general evolution problem that governs the dynamics is obtained for the first time. We prove that all the solutions are dissipative; that is, this new formulation is free of Kane paradox. We also prove that some indeterminacy of the Painlevé paradox is fixed in this

  6. Aortic endothelial cells regulate proliferation of human monocytes in vitro via a mechanism synergistic with macrophage colony-stimulating factor. Convergence at the cyclin E/p27(Kip1) regulatory checkpoint.

    Science.gov (United States)

    Antonov, A S; Munn, D H; Kolodgie, F D; Virmani, R; Gerrity, R G

    1997-06-15

    Monocyte-derived macrophages (Mphis) are pivotal participants in the pathogenesis of atherosclerosis. Evidence from both animal and human plaques indicates that local proliferation may contribute to accumulation of lesion Mphis, and the major Mphi growth factor, macrophage colony stimulating factor (MCSF), is present in atherosclerotic plaques. However, most in vitro studies have failed to demonstrate that human monocytes/Mphis possess significant proliferative capacity. We now report that, although human monocytes cultured in isolation showed only limited MCSF-induced proliferation, monocytes cocultured with aortic endothelial cells at identical MCSF concentrations underwent enhanced (up to 40-fold) and prolonged (21 d) proliferation. In contrast with monocytes in isolation, this was optimal at low seeding densities, required endothelial cell contact, and could not be reproduced by coculture with smooth muscle cells. Intimal Mphi isolated from human aortas likewise showed endothelial cell contact-dependent, MCSF-induced proliferation. Consistent with a two-signal mechanism governing Mphi proliferation, the cell cycle regulatory protein, cyclin E, was rapidly upregulated by endothelial cell contact in an MCSFindependent fashion, but MCSF was required for successful downregulation of the cell cycle inhibitory protein p27(Kip1) before cell cycling. Thus endothelial cells and MCSF differentially and synergistically regulate two Mphi genes critical for progression through the cell cycle.

  7. Mechanics

    CERN Document Server

    Chester, W

    1979-01-01

    When I began to write this book, I originally had in mind the needs of university students in their first year. May aim was to keep the mathematics simple. No advanced techniques are used and there are no complicated applications. The emphasis is on an understanding of the basic ideas and problems which require expertise but do not contribute to this understanding are not discussed. How­ ever, the presentation is more sophisticated than might be considered appropri­ ate for someone with no previous knowledge of the subject so that, although it is developed from the beginning, some previous acquaintance with the elements of the subject would be an advantage. In addition, some familiarity with element­ ary calculus is assumed but not with the elementary theory of differential equations, although knowledge of the latter would again be an advantage. It is my opinion that mechanics is best introduced through the motion of a particle, with rigid body problems left until the subject is more fully developed. Howev...

  8. 通用机械设备维护的必要性和重要性%The Necessity and Importance of General Mechanical Equipment Maintenance

    Institute of Scientific and Technical Information of China (English)

    宁龙举; 徐凯

    2015-01-01

    随着我国经济的快速发展,我国作为工业化的生产大国,国内企业的数量正在逐步的增多,企业的发展和稳定的运行离不开机械设备的支持,通用机械设备等的好坏直接影响到企业生产线的运行质量和运行速度,机械设备也成为了企业的实习的象征,在企业机械化程度发展如此快的今天,通用技术的维护就变得尤为重要,文章分析了企业通用机械设备维护的方法,探讨企业通用机械设备维护的必要性和重要性。%With the rapid development of China's economy, China as a big country of industrial production, the number of domestic enterprises is gradually increasing. The development of enterprises and the stable operation are inseparable from the support of mechanical equipment, and general machinery equipment matches a direct impact on the operational quality and speed of the production line. Mechanical equipment has also become a symbol of corporate practice, and the degree of mechanization in the enterprise is growing so fast today. The general maintenance becomes particularly important. The article analyzes the corporate general machinery equipment maintenance methods to explore the necessity and importance of general machinery equipment maintenance.

  9. A General Simulator Using State Estimation for a Space Tug Navigation System. [computerized simulation, orbital position estimation and flight mechanics

    Science.gov (United States)

    Boland, J. S., III

    1975-01-01

    A general simulation program is presented (GSP) involving nonlinear state estimation for space vehicle flight navigation systems. A complete explanation of the iterative guidance mode guidance law, derivation of the dynamics, coordinate frames, and state estimation routines are given so as to fully clarify the assumptions and approximations involved so that simulation results can be placed in their proper perspective. A complete set of computer acronyms and their definitions as well as explanations of the subroutines used in the GSP simulator are included. To facilitate input/output, a complete set of compatable numbers, with units, are included to aid in data development. Format specifications, output data phrase meanings and purposes, and computer card data input are clearly spelled out. A large number of simulation and analytical studies were used to determine the validity of the simulator itself as well as various data runs.

  10. Generalized quantitative approach to nanoscale Raman spectroscopy: Scaled quantum-mechanical treatment of three-dimensional phonon confinement

    CERN Document Server

    Korepanov, Vitaly I

    2016-01-01

    Raman spectroscopy provides a well-established tool for studying crystalline/molecular systems with well-defined selection rules based on crystalline/molecular symmetries. However, its application to nanoscale matter is hindered by the lack of such well-defined selection rules. Here, we couple the phonon confinement model with a scaled quantum-chemical calculation to construct a universal and physically consistent basis for nanoscale Raman spectroscopy. Unlike the commonly used one-dimensional dispersion approach, we take into account the confinement along all three dimensions of the k-space. We apply it to diamond nanoparticles of sub-50nm size, a system with pronounced anisotropy of dispersion for which three-dimensional dispersion approach is requisite. The approach excellently reproduces size-sensitive spectral features, including the peak position, bandwidth and asymmetry of the sp3 C-C Raman band. This fundamental approach can be easily generalized to other nanocrystalline solids to hopefully contribute...

  11. Regulatory bioinformatics for food and drug safety.

    Science.gov (United States)

    Healy, Marion J; Tong, Weida; Ostroff, Stephen; Eichler, Hans-Georg; Patak, Alex; Neuspiel, Margaret; Deluyker, Hubert; Slikker, William

    2016-10-01

    "Regulatory Bioinformatics" strives to develop and implement a standardized and transparent bioinformatic framework to support the implementation of existing and emerging technologies in regulatory decision-making. It has great potential to improve public health through the development and use of clinically important medical products and tools to manage the safety of the food supply. However, the application of regulatory bioinformatics also poses new challenges and requires new knowledge and skill sets. In the latest Global Coalition on Regulatory Science Research (GCRSR) governed conference, Global Summit on Regulatory Science (GSRS2015), regulatory bioinformatics principles were presented with respect to global trends, initiatives and case studies. The discussion revealed that datasets, analytical tools, skills and expertise are rapidly developing, in many cases via large international collaborative consortia. It also revealed that significant research is still required to realize the potential applications of regulatory bioinformatics. While there is significant excitement in the possibilities offered by precision medicine to enhance treatments of serious and/or complex diseases, there is a clear need for further development of mechanisms to securely store, curate and share data, integrate databases, and standardized quality control and data analysis procedures. A greater understanding of the biological significance of the data is also required to fully exploit vast datasets that are becoming available. The application of bioinformatics in the microbiological risk analysis paradigm is delivering clear benefits both for the investigation of food borne pathogens and for decision making on clinically important treatments. It is recognized that regulatory bioinformatics will have many beneficial applications by ensuring high quality data, validated tools and standardized processes, which will help inform the regulatory science community of the requirements

  12. Self-Regulatory Mechanisms Governing Gender Development.

    Science.gov (United States)

    Bussey, Kay; Bandura, Albert

    1992-01-01

    Groups of younger and older children in a sample of two to five year olds were assessed for gender knowledge, gender standards, and gender-linked behavior. All children exhibited more same- than cross-sex typed behavior. Older children expressed self-approval for same-sex behavior and self-criticism for cross-sex behavior. (BC)

  13. Gene regulatory mechanisms in infected fish

    DEFF Research Database (Denmark)

    Schyth, Brian Dall; Hajiabadi, Seyed Amir Hossein Jalali; Kristensen, Lasse Bøgelund Juel;

    2011-01-01

    miRNAs) are one class of such small RNAs which are expressed from the genome. The RISC system allows for non-perfect base pairing of miRNAs to their target genes why one small RNA can in theory silence large groups of genes at the same time. It is therefore anticipated that they are able to depress...... seem to show that these microRNAs are only expressed above a certain stage in the development of the fish....

  14. Regulatory mechanisms link phenotypic plasticity to evolvability

    NARCIS (Netherlands)

    van Gestel, Jordi; Weissing, Franz J

    2016-01-01

    Organisms have a remarkable capacity to respond to environmental change. They can either respond directly, by means of phenotypic plasticity, or they can slowly adapt through evolution. Yet, how phenotypic plasticity links to evolutionary adaptability is largely unknown. Current studies of plasticit

  15. Investigation of Autophagy Induced by Amino Acid Deprivation and the Regulatory Mechanisms of miRNA in Autophagy%氨基酸缺乏诱导细胞自噬及 miRNA 调控机制

    Institute of Scientific and Technical Information of China (English)

    王琪; 齐仁立; 王敬; 黄金秀

    2016-01-01

    氨基酸是生物体内不可缺少的营养成分和生命活动最基本的物质之一,并对动物体的新陈代谢起到至关重要的作用。自噬是细胞内通过降解和回收细胞内生物大分子和受损细胞器,以完成本身代谢和某些细胞器更新的过程。研究证实氨基酸缺乏能诱导细胞自噬,而这种反应大部分是依赖于 mTORC1信号通路的方式实现的,但总氨基酸或单体氨基酸调节细胞自噬的分子作用机制和自噬水平有很大差别,且相关方面的分子调节机制尚未完全清楚,需要进一步阐明。miRNA 是一类长度为18-24 nt 的非编码核苷酸,参与细胞增殖、分化、自噬与凋亡等多种生命活动。研究表明 miRNA 在氨基酸缺乏诱导细胞自噬过程中的也发挥重要调控机制。就不同氨基酸缺乏调控自噬相关机制加以综述,并探讨 miRNA 在其中起到的关键作用。旨在为治疗自噬相关代谢提供思路。%Amino acid is a kind of indispensable nutriment and basic material for life activities,and it is critical for animal to maintain physiological function. Autophagy is a pathway to accomplish metabolism and regenerate some organelles by the turnover and recycling of intracellular macromolecules and damaged organelles. The studies confirmed that amino acid deprivation induced the cell autophagy through the mTORC1 signal pathway. However,the molecular mechanism and level of autophagy differ significantly between total and individual amino acid,moreover,the molecular regulatory mechanism is still unclear,and further revealing is necessary. miRNA is non-coding nucleotide with 18-24 nt involving in cell proliferation,differentiation,autophagy,and apoptosis. Recent researches show that miRNA plays an important role in regulating autophagy induced by amino acid deprivation. This paper reviewed the regulatory mechanisms of autophagy by different amino acid deprivation and the key effects of miRNA on

  16. EGFR相关的DNA修复及放射抗拒机制研究现状%Relativity of EGFR signal as a regulatory mechanism to DNA repair and radiation resistance

    Institute of Scientific and Technical Information of China (English)

    白静; 白晓平; 赵巧艳

    2012-01-01

    目的:总结国外关于表皮生长因子受体(EGFR)通过各种信号通路调节DNA修复导致辐射抗拒相关机制的研究进展.方法:应用PubMed数据库系统,以“表皮生长因子受体、信号通路、DNA损伤修复、放射抗拒”为关键词检索2005-01-2011-12的相关文献,共检索到英文文献198篇.纳入标准:1)EGFR的表达;2)辐射抗拒和DNA损伤修复机制;3)EGFR和辐射诱导的DNA损伤修复;4)EGFR信号通路调控DNA损伤修复导致放射抗拒的可能机制.根据纳入标准,纳入分析22篇文献.结果:EGFR过表达与放化疗抗拒相关.它可以通过联接DNA蛋白激酶催化亚单位(DNA-PKcs)来调节放疗诱导的DNA损伤的修复.EGFR及其对DNA修复能力之间的分子连接可能通过该受体的一个或多个下游信号通路介导.结论:EGFR作为调节DNA损伤修复机制的信号通路与放射抗拒之间存在相关性,靶向于其中激活的信号通路可以为改善放射抗拒提供新的治疗思路.%OBJECTIVE:To sum up the articles related to improvement that epidermal growth factor receptor (EGFR) modulate DNA repair after radiation-induced damage through many signal pathways. METHODS: Epidermal growth factor receptor,signal pathway ,DNA-damage repair and radiation resistance were searched as key words by Pubmed database system from 2005-01 to 2011-12, Altogether 198 English literatures were obtained. Enrolled criteria: 1, EGFR expression; 2. mechanism of DNA repair and radiation resistances 3, EGFR and radiation resistances 4, EGFR signal as a regulatory mechanism to DNA repair and radiation resistance. By extraction according to enrolled criteria, among roughing hundreds of relative articles,46 papers were selected, and 22 papers were finally analyzed. RESULTS: EGFR Overexpres-sion is associated with resistance to chemotherapy and radiotherapy. It modulates DNA repair after radiation-induced damage through association with the catalytic subunit of DNA protein

  17. Mechanisms of change during group metacognitive therapy for repetitive negative thinking in primary and non-primary generalized anxiety disorder.

    Science.gov (United States)

    McEvoy, Peter M; Erceg-Hurn, David M; Anderson, Rebecca A; Campbell, Bruce N C; Nathan, Paula R

    2015-10-01

    Repetitive negative thinking (RNT) is a transdiagnostic process that serves to maintain emotional disorders. Metacognitive theory suggests that positive and negative metacognitive beliefs guide the selection of RNT as a coping strategy which, in turn, increases psychological distress. The aim of this study was to test the indirect effect of metacognitive beliefs on psychological distress via RNT. Patients (N=52) with primary and non-primary generalized anxiety disorder attended a brief, six-week group metacognitive therapy program and completed measures of metacognitive beliefs, RNT, and symptoms at the first and final treatment sessions, and at a one-month follow-up. Prospective indirect effects models found that negative metacognitive beliefs (but not positive metacognitive beliefs) had a significant indirect effect on psychological distress via RNT. As predicted by metacognitive theory, targeting negative metacognitions in treatment appears to reduce RNT and, in turn, emotional distress. Further research using alternative measures at multiple time points during therapy is required to determine whether the absence of a relationship with positive metacognitive beliefs in this study was a consequence of (a) psychometric issues, (b) these beliefs only being relevant to a subgroup of patients, or (c) a lack of awareness early in treatment.

  18. 广义质量替代的曲柄群机构动平衡%Dynamic balancing of crank group mechanism based on generalized mass substitution

    Institute of Scientific and Technical Information of China (English)

    刘言松; 曹巨江

    2016-01-01

    根据曲柄群机构中连杆桁架的质心分布特点,利用广义质量替代法将连杆桁架质量向曲柄与连杆桁架的3个铰接点替代,从而将曲柄群机构分解为若干个I类和II类曲柄单元,把曲柄群机构的动平衡问题转化为I类曲柄单元的动平衡问题。计算表明。当 I 类曲柄单元实现动平衡时,曲柄群机构也实现了动平衡。结论对简化曲柄群机构的结构,减少该机构的基础振动具有较好的指导意义。%According to the distribution characteristics of center of mass of the crank group mechanism,the mechanism is broken into some crank units named class I crank unit or class II crank unit,by generalized mass substitution in which the mass of the connecting rod truss is substituted on the 3 hinged points,and the dynamic balancing of the crank group mecha-nism is converted to the dynamic balance of class I crank unit.The calculation example shows that the crank group mechanism is a dynamic balancing mechanism when each class I crank unit is a dynamic balancing rotor.The conclusions may be helpful for reducing the foundation vibration of the mechanism and simplifying the structure in the design of the crank group mechanism.

  19. High-level resistance to class IIa bacteriocins is associated with one general mechanism in Listeria monocytogenes.

    Science.gov (United States)

    Gravesen, Anne; Ramnath, Manilduth; Rechinger, K Björn; Andersen, Natalie; Jänsch, Lothar; Héchard, Yann; Hastings, John W; Knøchel, Susanne

    2002-08-01

    Class IIa bacteriocins may be used as natural food preservatives, yet resistance development in the target organisms is still poorly understood. In this study, the understanding of class IIa resistance development in Listeria monocytogenes is extended, linking the seemingly diverging results previously reported. Eight resistant mutants having a high resistance level (at least a 10(3)-fold increase in MIC), originating from five wild-type listerial strains, were independently isolated following exposure to four different class IIa bacteriocin-producing lactic acid bacteria (including pediocin PA-1 and leucocin A producers). Two of the mutants were isolated from food model systems (a saveloy-type sausage at 10 degrees C, and salmon juice at 5 degrees C). Northern blot analysis showed that the eight mutants all had increased expression of EII(Bgl) and a phospho-beta-glucosidase homologue, both originating from putative beta-glucoside-specific phosphoenolpyruvate-dependent phosphotransferase systems (PTSs). However, disruption of these genes in a resistant mutant did not confer pediocin sensitivity. Comparative two-dimensional gel analysis of proteins isolated from mutant and wild-type strains showed that one spot was consistently missing in the gels from mutant strains. This spot corresponded to the MptA subunit of the mannose-specific PTS, found only in the gels of wild-type strains. The mptACD operon was recently shown to be regulated by the sigma(54) transcription factor in conjunction with the activator ManR. Class IIa bacteriocin-resistant mutants having defined mutations in mpt or manR also exhibited the two diverging PTS expression changes. It is suggested here that high-level class IIa resistance in L. monocytogenes and at least some other Gram-positive bacteria is developed by one prevalent mechanism, irrespective of wild-type strain, class IIa bacteriocin, or the tested environmental conditions. The changes in expression of the beta-glucoside-specific and

  20. Regulatory T cell memory

    Science.gov (United States)

    Rosenblum, Michael D.; Way, Sing Sing; Abbas, Abul K.

    2016-01-01

    Memory for antigen is a defining feature of adaptive immunity. Antigen-specific lymphocyte populations show an increase in number and function after antigen encounter and more rapidly re-expand upon subsequent antigen exposure. Studies of immune memory have primarily focused on effector B cells and T cells with microbial specificity, using prime challenge models of infection. However, recent work has also identified persistently expanded populations of antigen-specific regulatory T cells that protect against aberrant immune responses. In this Review, we consider the parallels between memory effector T cells and memory regulatory T cells, along with the functional implications of regulatory memory in autoimmunity, antimicrobial host defence and maternal fetal tolerance. In addition, we discuss emerging evidence for regulatory T cell memory in humans and key unanswered questions in this rapidly evolving field. PMID:26688349