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Sample records for biologic mechanism involved

  1. [THE ROLE OF MATERNAL DIET IN METABOLIC AND BEHAVIOURAL PROGRAMMING: REVIEW OF BIOLOGIC MECHANISMS INVOLVED].

    PubMed

    Ramírez-López, María Teresa; Vázquez Berrios, Mariam; Arco González, Rocío; Blanco Velilla, Rosario Noemí; Decara Del Olmo, Juan; Suárez Pérez, Juan; Rodríguez de Fonseca, Fernando; Gómez de Heras, Raquel

    2015-12-01

    Over the last few years, a considerable amount of studies have focused on the effect of undernutrition and overnutrition during critical periods of offspring development and their risk of developing metabolic diseases later in life. Additionally, inadequate maternal diets have been involved in the malprogramming of brain functions and some behaviours. Several mechanisms have been associated with the process of malprogramming such as epigenetics modifications, excessive oxidative stress or hypothalamic alterations. This evidence supports the idea that nutritional prevention strategies must be considered for offspring during early development stages that include the preconceptional period. Additionally, studying involved mechanisms could be particularly useful in the search of efficient therapies against malprogramming.

  2. Is synthetic biology mechanical biology?

    PubMed

    Holm, Sune

    2015-12-01

    A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

  3. Epigenetics: Biology's Quantum Mechanics.

    PubMed

    Jorgensen, Richard A

    2011-01-01

    The perspective presented here is that modern genetics is at a similar stage of development as were early formulations of quantum mechanics theory in the 1920s and that in 2010 we are at the dawn of a new revolution in genetics that promises to enrich and deepen our understanding of the gene and the genome. The interrelationships and interdependence of two views of the gene - the molecular biological view and the epigenetic view - are explored, and it is argued that the classical molecular biological view is incomplete without incorporation of the epigenetic perspective and that in a sense the molecular biological view has been evolving to include the epigenetic view. Intriguingly, this evolution of the molecular view toward the broader and more inclusive epigenetic view of the gene has an intriguing, if not precise, parallel in the evolution of concepts of atomic physics from Newtonian mechanics to quantum mechanics that are interesting to consider.

  4. Physiological Mechanisms Only Tell Half Story: Multiple Biological Processes are involved in Regulating Freezing Tolerance of Imbibed Lactuca sativa Seeds

    PubMed Central

    Jaganathan, Ganesh K.; Han, Yingying; Li, Weijie; Song, Danping; Song, Xiaoyan; Shen, Mengqi; Zhou, Qiang; Zhang, Chenxue; Liu, Baolin

    2017-01-01

    The physiological mechanisms by which imbibed seeds survive freezing temperatures in their natural environment have been categorized as freezing avoidance by supercooling and freezing tolerance by extracellular freeze-desiccation, but the biochemical and molecular mechanisms conferring seed freezing tolerance is unexplored. In this study, using imbibed Lactuca sativa seeds we show that fast cooled seeds (60 °C h−1) suffered significantly higher membrane damage at temperature between −20 °C and −10 °C than slow cooled (3 °Ch−1) seeds (P < 0.05), presumably explaining viability loss during fast cooling when temperature approaches −20 °C. Total soluble sugars increase in low temperature environment, but did not differ significantly between two cooling rates (P > 0.05). However, both SOD activity and accumulation of free proline were induced significantly after slow cooling to −20 °C compared with fast cooling. RNA-seq demonstrated that multiple pathways were differentially regulated between slow and fast cooling. Real-time verification of some differentially expressed genes (DEGs) revealed that fast cooling caused mRNA level changes of plant hormone and ubiquitionation pathways at higher sub-zero temperature, whilst slow cooling caused mRNA level change of those pathways at lower sub-zero ttemperatures. Thus, we conclude that imbibed seed tolerate low temperature not only by physiological mechanisms but also by biochemical and molecular changes. PMID:28287125

  5. Physiological Mechanisms Only Tell Half Story: Multiple Biological Processes are involved in Regulating Freezing Tolerance of Imbibed Lactuca sativa Seeds.

    PubMed

    Jaganathan, Ganesh K; Han, Yingying; Li, Weijie; Song, Danping; Song, Xiaoyan; Shen, Mengqi; Zhou, Qiang; Zhang, Chenxue; Liu, Baolin

    2017-03-13

    The physiological mechanisms by which imbibed seeds survive freezing temperatures in their natural environment have been categorized as freezing avoidance by supercooling and freezing tolerance by extracellular freeze-desiccation, but the biochemical and molecular mechanisms conferring seed freezing tolerance is unexplored. In this study, using imbibed Lactuca sativa seeds we show that fast cooled seeds (60 °C h(-1)) suffered significantly higher membrane damage at temperature between -20 °C and -10 °C than slow cooled (3 °Ch(-1)) seeds (P < 0.05), presumably explaining viability loss during fast cooling when temperature approaches -20 °C. Total soluble sugars increase in low temperature environment, but did not differ significantly between two cooling rates (P > 0.05). However, both SOD activity and accumulation of free proline were induced significantly after slow cooling to -20 °C compared with fast cooling. RNA-seq demonstrated that multiple pathways were differentially regulated between slow and fast cooling. Real-time verification of some differentially expressed genes (DEGs) revealed that fast cooling caused mRNA level changes of plant hormone and ubiquitionation pathways at higher sub-zero temperature, whilst slow cooling caused mRNA level change of those pathways at lower sub-zero ttemperatures. Thus, we conclude that imbibed seed tolerate low temperature not only by physiological mechanisms but also by biochemical and molecular changes.

  6. Molecular Mechanism of Biological Proton Transport

    SciTech Connect

    Pomes, R.

    1998-09-01

    Proton transport across lipid membranes is a fundamental aspect of biological energy transduction (metabolism). This function is mediated by a Grotthuss mechanism involving proton hopping along hydrogen-bonded networks embedded in membrane-spanning proteins. Using molecular simulations, the authors have explored the structural, dynamic, and thermodynamic properties giving rise to long-range proton translocation in hydrogen-bonded networks involving water molecules, or water wires, which are emerging as ubiquitous H{sup +}-transport devices in biological systems.

  7. THE BIOLOGICAL ACTIONS OF DEHYDROEPIANDROSTERONE INVOLVES MULTIPLE RECEPTORS

    PubMed Central

    Webb, Stephanie J.; Geoghegan, Thomas E.; Prough, Russell A.; Miller, Kristy K. Michael

    2008-01-01

    Dehydroepiandrosterone has been thought to have physiological functions other than as an androgen precursor. The previous studies performed have demonstrated a number of biological effects in rodents, such as amelioration of disease in diabetic, chemical carcinogenesis, and obesity models. To date, activation of the peroxisome proliferators activated receptor alpha, pregnane X receptor, and estrogen receptor by DHEA and its metabolites have been demonstrated. Several membrane-associated receptors have also been elucidated leading to additional mechanisms by which DHEA may exert its biological effects. This review will provide an overview of the receptor multiplicity involved in the biological activity of this sterol. PMID:16684650

  8. Emergent mechanics of biological structures

    PubMed Central

    Dumont, Sophie; Prakash, Manu

    2014-01-01

    Mechanical force organizes life at all scales, from molecules to cells and tissues. Although we have made remarkable progress unraveling the mechanics of life's individual building blocks, our understanding of how they give rise to the mechanics of larger-scale biological structures is still poor. Unlike the engineered macroscopic structures that we commonly build, biological structures are dynamic and self-organize: they sculpt themselves and change their own architecture, and they have structural building blocks that generate force and constantly come on and off. A description of such structures defies current traditional mechanical frameworks. It requires approaches that account for active force-generating parts and for the formation of spatial and temporal patterns utilizing a diverse array of building blocks. In this Perspective, we term this framework “emergent mechanics.” Through examples at molecular, cellular, and tissue scales, we highlight challenges and opportunities in quantitatively understanding the emergent mechanics of biological structures and the need for new conceptual frameworks and experimental tools on the way ahead. PMID:25368421

  9. Mechanical Instabilities of Biological Tubes

    NASA Astrophysics Data System (ADS)

    Hannezo, Edouard; Prost, Jacques; Joanny, Jean-François

    2012-07-01

    We study theoretically the morphologies of biological tubes affected by various pathologies. When epithelial cells grow, the negative tension produced by their division provokes a buckling instability. Several shapes are investigated: varicose, dilated, sinuous, or sausagelike. They are all found in pathologies of tracheal, renal tubes, or arteries. The final shape depends crucially on the mechanical parameters of the tissues: Young’s modulus, wall-to-lumen ratio, homeostatic pressure. We argue that since tissues must be in quasistatic mechanical equilibrium, abnormal shapes convey information as to what causes the pathology. We calculate a phase diagram of tubular instabilities which could be a helpful guide for investigating the underlying genetic regulation.

  10. Theoretical Biology: Organisms and Mechanisms

    NASA Astrophysics Data System (ADS)

    Landauer, Christopher; Bellman, Kirstie L.

    2002-09-01

    The Theoretical Biology Program initiated by Robert Rosen is intended to identify the key theoretical characteristics of organisms, especially those that distinguish organisms from mechanisms, by looking for the proper abstractions and defining the appropriate relationships. There are strong claims about the distinctions in Rosen's book "Life Itself", along with some purported proofs of these assertions. Unfortunately, the Mathematics is incorrect, and the assertions remain unproven (and some of them are simply false). In this paper, we present the ideas of Rosen's approach, demonstrate that his Mathematical formulations and proofs are wrong, and then show how they might be made more successful.

  11. Mechanics of biological polymer composites

    NASA Astrophysics Data System (ADS)

    Lomakin, Joseph

    2009-12-01

    displayed a darker coloration and significantly increased n of 0.0470.004, suggesting both cuticles to be less cross-linked, a finding consistent with reduced beta-alanine metabolism. Suppression of the tanning enzyme laccase2 (TcLac2) resulted in a pale cuticle with an n of 0.043+/-0.005, implicating laccases in the formation of both pigments and cross-links during sclerotization. Cuticular cross-linking was increased and n decreased with decreased expression of structural proteins, CP10 and CP20. This work establishes n as an important novel parameter for confirming metabolic pathways within load bearing tissues and for understanding structure function relationships within biological polymer composites. Additionally, Tribolium castaneum elytral indentation modulus (800+/-200 MPa) was determined by nanoindentation and a 4nm regular hexagonal pattern on the dorsal side of elytra investigated via scanning, transmission and atomic microscopy. Based on studied biological materials, the combination of rigid macromolecules immersed in a ductile matrix was found to be significant in achieving exceptional mechanical performance. Inspired by this biological design principle, the synthesis, properties and structure of Poly(ethylene glycol) diacrylate/agarose semi-interpenetrating network hydrogels were explored. The resulting novel composite materials were 9x stiffer than agarose and 5x tougher than PEGDA alone and showed good biocompatibility, suggesting promise as a scaffold material for tissue engineering constructs for cartilage regeneration.

  12. Collaborative explanation and biological mechanisms.

    PubMed

    Fagan, Melinda Bonnie

    2015-08-01

    This paper motivates and outlines a new account of scientific explanation, which I term 'collaborative explanation.' My approach is pluralist: I do not claim that all scientific explanations are collaborative, but only that some important scientific explanations are-notably those of complex organic processes like development. Collaborative explanation is closely related to what philosophers of biology term 'mechanistic explanation' (e.g., Machamer et al., Craver, 2007). I begin with minimal conditions for mechanisms: complexity, causality, and multilevel structure. Different accounts of mechanistic explanation interpret and prioritize these conditions in different ways. This framework reveals two distinct varieties of mechanistic explanation: causal and constitutive. The two have heretofore been conflated, with philosophical discussion focusing on the former. This paper addresses the imbalance, using a case study of modeling practices in Systems Biology to reveals key features of constitutive mechanistic explanation. I then propose an analysis of this variety of mechanistic explanation, in terms of collaborative concepts, and sketch the outlines of a general theory of collaborative explanation. I conclude with some reflections on the connection between this variety of explanation and social aspects of scientific practice.

  13. The Cytoskeleton: Mechanical, Physical, and Biological Interactions

    NASA Technical Reports Server (NTRS)

    1996-01-01

    This workshop, entitled "The Cytoskeleton: Mechanical, Physical, and Biological Interactions," was sponsored by the Center for Advanced Studies in the Space Life Sciences at the Marine Biological Laboratory. This Center was established through a cooperative agreement between the MBL and the Life Sciences Division of the National Aeronautics and Space Administration. To achieve these goals, the Center sponsors a series of workshops on various topics in the life sciences. Elements of the cytoskeleton have been implicated in the effects of gravity on the growth of plants fungi. An intriguing finding in this regard is the report indicating that an integrin-like protein may be the gravireceptor in the internodal cells of Chara. Involvement of the cytoskeleton in cellular graviperception of the basidiomycete Flammulina velutipes has also been reported. Although the responses of mammalian cells to gravity are not well documented, it has been proposed that integrins can act as mechanochemical transducers in mammalian cells. Little is known about the integrated mechanical and physical properties of cytoplasm, this workshop would be the best place to begin developing interdisciplinary approaches to the effects of mechanical stresses on cells and their most likely responsive cytoplasmic elements- the fibrous proteins comprising the cytoskeleton.

  14. Mechanisms of Microwave Induced Damage in Biologic Materials

    DTIC Science & Technology

    1989-01-01

    Activities and Microwave Exposures Ornithine decarboxylase (ODC), an enzyme involved in the production of the polyamines putrescine and spermidine, has...f 0 0 Mechanisms of Microwave Induced N Damage in Biologic Materials I ,<DTIC .. E LECTEI I Annual Report S FEB08 1990 U January, 1989 m D EFFECTS OF...Clasufication) (U) Mechanisms of Microwave Induced Damage in Biologic Materials I 12. PERSONAL AUTHOR(S) .3a. TYPE OF REPORT 13b. TIME COVERED 14

  15. The concept of mechanism in biology.

    PubMed

    Nicholson, Daniel J

    2012-03-01

    The concept of mechanism in biology has three distinct meanings. It may refer to a philosophical thesis about the nature of life and biology ('mechanicism'), to the internal workings of a machine-like structure ('machine mechanism'), or to the causal explanation of a particular phenomenon ('causal mechanism'). In this paper I trace the conceptual evolution of 'mechanism' in the history of biology, and I examine how the three meanings of this term have come to be featured in the philosophy of biology, situating the new 'mechanismic program' in this context. I argue that the leading advocates of the mechanismic program (i.e., Craver, Darden, Bechtel, etc.) inadvertently conflate the different senses of 'mechanism'. Specifically, they all inappropriately endow causal mechanisms with the ontic status of machine mechanisms, and this invariably results in problematic accounts of the role played by mechanism-talk in scientific practice. I suggest that for effective analyses of the concept of mechanism, causal mechanisms need to be distinguished from machine mechanisms, and the new mechanismic program in the philosophy of biology needs to be demarcated from the traditional concerns of mechanistic biology.

  16. Involvement of Mechanical Stress in Androgenetic Alopecia

    PubMed Central

    Tellez-Segura, Rafael

    2015-01-01

    Context: Androgenetic alopecia (AGA) is a frequent disorder characterized by progressive hair miniaturization in a very similar pattern among all affected men. The pathogenesis is related to androgen-inducible overexpression of transforming growth factor β-1 from balding dermal papilla cells, which is involved in epithelial inhibition and perifollicular fibrosis. Recent research shows that hair follicle androgen sensitivity is regulated by Hic-5, an androgen receptor co-activator which may be activated by the mechanical stimulation. Moreover, the dermis of scalp susceptible to be affected by AGA is firmly bounded to the galea aponeurotica, so the physical force exerted by the occipitofrontalis muscle is transmitted to the scalp skin. Aims: To know whether mechanical stress supported by hair follicles is involved in AGA phenomenon. Materials and Methods: It is performed with a finite element analysis of a galea model and a schematic representation of AGA progression according to Hamilton–Norwood scale in order to establish the correlation between elastic deformation in scalp and clinical progression of male pattern baldness. Results: The result was a highly significant correlation (r: −0.885, P < 0.001) that clearly identifies a mechanical factor in AGA development. Conclusions: All these data suggest that mechanical stress determines AGA patterning and a stretch-induced and androgen-mediated mechanotransduction in dermal papilla cells could be the primary mechanism in AGA pathogenesis. PMID:26622151

  17. [Signaling mechanisms involved in resolution of inflammation].

    PubMed

    Cervantes-Villagrana, Rodolfo Daniel; Cervantes-Villagrana, Alberto Rafael; Presno-Bernal, José Miguel

    2014-01-01

    Inflammation is a physiological process, which eliminates pathogens and induces repair of damaged tissue. This process is controlled by negative feedback mechanisms, but if the inflammation persists, it generates a deleterious autoimmune process or can to contribute with diseases such as obesity or cancer. The inflammation resolution involves mechanisms such as decrease of proliferation and maturation of immune cells, phagocytosis and apoptosis of immune cells, and decrease of proinflammatory mediators. Therefore, is relevant to study the physiological effects of specific receptors that participate in inflammation resolution and the design of specific agonists as conventional anti-inflammatory therapeutics, without dramatic collateral effects. In this review, we study some mechanisms associated with inflammation inhibition, particularly the transduction of receptors for ligands with anti-inflammatory effects and that are relevant for their potential therapeutic.

  18. Mechanical resonant immunospecific biological detector

    NASA Astrophysics Data System (ADS)

    Ilic, B.; Czaplewski, D.; Craighead, H. G.; Neuzil, P.; Campagnolo, C.; Batt, C.

    2000-07-01

    We have demonstrated high-sensitivity detection of bacteria using an array of bulk micromachined resonant cantilevers. The biological sensor is a micromechanical oscillator that consists of an array of silicon-nitride cantilevers with an immobilized antibody layer on the surface of the resonator. Measured resonant frequency shift as a function of the additional cell loading was observed and correlated to the mass of the specifically bound Escherichia coli O157:H7 cells. Deposition and subsequent detection of E. coli cells was achieved under ambient conditions.

  19. A Review of Molecular Mechanisms Involved in Toxicity of Nanoparticles

    PubMed Central

    Khalili Fard, Javad; Jafari, Samira; Eghbal, Mohammad Ali

    2015-01-01

    In recent decades, the use of nanomaterials has received much attention in industrial and medical fields. However, some reports have mentioned adverse effects of these materials on the biological systems and cellular components. There are several major mechanisms for cytotoxicity of nanoparticles (NPs) such as physicochemical properties, contamination with toxic element, fibrous structure, high surface charge and radical species generation. In this review, a brief key mechanisms involved in toxic effect of NPs are given, followed by the in vitro toxicity assays of NPs and prooxidant effects of several NPs such as carbon nanotubes, titanium dioxide NPs, quantum dots, gold NPs and silver NPs. PMID:26819915

  20. Enzymatic DNA oxidation: mechanisms and biological significance.

    PubMed

    Xu, Guo-Liang; Walsh, Colum P

    2014-11-01

    DNA methylation at cytosines (5mC) is a major epigenetic modification involved in the regulation of multiple biological processes in mammals. How methylation is reversed was until recently poorly understood. The family of dioxygenases commonly known as Ten-eleven translocation (Tet) proteins are responsible for the oxidation of 5mC into three new forms, 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Current models link Tet-mediated 5mC oxidation with active DNA demethylation. The higher oxidation products (5fC and 5caC) are recognized and excised by the DNA glycosylase TDG via the base excision repair pathway. Like DNA methyltransferases, Tet enzymes are important for embryonic development. We will examine the mechanism and biological significance of Tet-mediated 5mC oxidation in the context of pronuclear DNA demethylation in mouse early embryos. In contrast to its role in active demethylation in the germ cells and early embryo, a number of lines of evidence suggest that the intragenic 5hmC present in brain may act as a stable mark instead. This short review explores mechanistic aspects of TET oxidation activity, the impact Tet enzymes have on epigenome organization and their contribution to the regulation of early embryonic and neuronal development.

  1. Major regulatory mechanisms involved in sperm motility.

    PubMed

    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.

  2. Major regulatory mechanisms involved in sperm motility

    PubMed Central

    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. PMID:26680031

  3. Molecular Mechanisms Involved in Schwann Cell Plasticity

    PubMed Central

    Boerboom, Angélique; Dion, Valérie; Chariot, Alain; Franzen, Rachelle

    2017-01-01

    Schwann cell incredible plasticity is a hallmark of the utmost importance following nerve damage or in demyelinating neuropathies. After injury, Schwann cells undergo dedifferentiation before redifferentiating to promote nerve regeneration and complete functional recovery. This review updates and discusses the molecular mechanisms involved in the negative regulation of myelination as well as in the reprogramming of Schwann cells taking place early following nerve lesion to support repair. Significant advance has been made on signaling pathways and molecular components that regulate SC regenerative properties. These include for instance transcriptional regulators such as c-Jun or Notch, the MAPK and the Nrg1/ErbB2/3 pathways. This comprehensive overview ends with some therapeutical applications targeting factors that control Schwann cell plasticity and highlights the need to carefully modulate and balance this capacity to drive nerve repair. PMID:28261057

  4. Brain mechanisms involved in processing unreal perceptions.

    PubMed

    Ku, Jeonghun; Kim, Jae-Jin; Jung, Young Chul; Park, Il Ho; Lee, Hyeongrae; Han, Kiwan; Yoon, Kang Jun; Kim, In Young; Kim, Sun I

    2008-12-01

    Individuals sometimes experience an illusory or hallucinatory perception. This unreal perception is usually resolved after the individual recognizes that the perception was not real. In this study, we investigated the brain mechanisms involved in the process to an illusory or hallucinatory perception through 'obtaining insight into unreality'. We used a novel and intuitive paradigm designed by combining functional magnetic resonance imaging and augmented reality technology to simulate visual illusory stimuli that mimic hallucinations during brain scanning. The results showed various brain activations, predominantly in the amygdala in the early phase, the medial frontal cortex and the occipitotemporal junction in the middle phase, and the thalamus in the late phase, which correlated with a subject's proneness to hallucinating. These activations may correspond to a 'responding stage' for a perception-based immediate emotional reaction, a 'monitoring stage' for integration and recalibration to ascertain that the perception was not real, and a 'resolving stage' for controlling the information and finally settling it, respectively. Our paradigm and findings may be useful in understanding the mechanisms for discriminating and coping with hallucinatory perceptions.

  5. Biologically Inspired Nano-Contact Mechanics

    DTIC Science & Technology

    2009-07-20

    mechanics and micro / nano - fabrication, with potentially significant benefits if we can understand and mimic some of nature’s optimized solutions for...2000) has demonstrated that the micro and nano -scale architectures of the gecko foot fibers are responsible for the animal’s excellent attachment...2. REPORT TYPE Final DATES COVERED (From - To) 01 April 2005-30 Jun 2009 4. TITLE AND SUBTITLE BIOLOGICALLY INSPIRED NANO -CONTACT MECHANICS 5a

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

    PubMed

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

    2016-08-15

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

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

    PubMed Central

    Daste, Frederic

    2016-01-01

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

  8. Interface mechanics determining biological cell shapes

    NASA Astrophysics Data System (ADS)

    Hilgenfeldt, Sascha; Carthew, Richard

    2006-11-01

    To form a functional tissue, biological cells often adhere to each other establishing connections between membranes by means of cadherin molecules. The cells achieve a well-defined relative orientation as well as a faithfully prescribed shape. An excellent example is the cell cluster making up each ommatidium element in the drosophila eye. The similarity of the shape of these cells to connected soap bubbles has been remarked upon [1]. We show that, in order to explain the observed shapes of wild-type and mutant ommatidia, the soap film model has to be expanded into a realistic description of biological membranes and their mechanical properties including changes in interfacial tension due to the presence of cadherins. Surface Evolver simulations demonstrate that realistic modeling of the shape of cell clusters can be obtained using surface energy terms only, emphasizing the importance of interfacial phenomena in cell mechanics and cell morphology. [1] T. Hayashi & R. W. Carthew, Nature 431, 647 (2004)

  9. A Systems Biology-Based Approach to Uncovering the Molecular Mechanisms Underlying the Effects of Dragon's Blood Tablet in Colitis, Involving the Integration of Chemical Analysis, ADME Prediction, and Network Pharmacology

    PubMed Central

    Gao, Xiumei; Zhai, Huaqiang; Lin, Na; Tang, Shihuan; Liang, Rixin; Ma, Yan; Li, Defeng; Zhang, Yi; Zhu, Guangrong; Yang, Hongjun; Huang, Luqi

    2014-01-01

    Traditional Chinese medicine (TCM) is one of the oldest East Asian medical systems. The present study adopted a systems biology-based approach to provide new insights relating to the active constituents and molecular mechanisms underlying the effects of dragon's blood (DB) tablets for the treatment of colitis. This study integrated chemical analysis, prediction of absorption, distribution, metabolism, and excretion (ADME), and network pharmacology. Firstly, a rapid, reliable, and accurate ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was employed to identify 48 components of DB tablets. In silico prediction of the passive absorption of these compounds, based on Caco-2 cell permeability, and their P450 metabolism enabled the identification of 22 potentially absorbed components and 8 metabolites. Finally, networks were constructed to analyze interactions between these DB components/metabolites absorbed and their putative targets, and between the putative DB targets and known therapeutic targets for colitis. This study provided a great opportunity to deepen the understanding of the complex pharmacological mechanisms underlying the effects of DB in colitis treatment. PMID:25068885

  10. Mechanisms of adverse drug reactions to biologics.

    PubMed

    Clarke, Janet B

    2010-01-01

    Biologics encompass a broad range of therapeutics that include proteins and other products derived from living systems. Although the multiplicity of target organs often seen with new chemical entities is generally not seen with biologics, they can produce significant adverse reactions. Examples include IL-12 and an anti-CD28 antibody that resulted in patient deaths and/or long stays in intensive care units. Mechanisms of toxicities can be categorized as pharmacological or nonpharmacological, with most, excepting hypersensitivity reactions, associated with the interaction of the agent with its planned target. Unexpected toxicities generally arise as a result of previously unknown biology. Manufacturing quality is a significant issue relative to the toxicity of biologics. The development of recombinant technology represented the single biggest advance leading to humanized products with minimal or no contaminants in comparison to products purified from animal tissues. Nevertheless, the type of manufacturing process including choice of cell type, culture medium, and purification method can result in changes to the protein. For example, a change to the closure system for erythropoietin led to an increase in aplastic anemia as a result of changing the immunogenicity characteristics of the protein. Monoclonal antibodies represent a major class of successful biologics. Toxicities associated with these agents include those associated with the binding of the complementary determining region (CDR) with the target. First dose reactions or infusion reactions are generally thought to be mediated via the Fc region of the antibody activating cytokine release, and have been observed with several antibodies. Usually, these effects (flu-like symptoms, etc.) are transient with subsequent dosing. Although biologics can have nonpharmacologic toxicities, these are less common than with small molecule drugs.

  11. The mechanics of soft biological composites.

    SciTech Connect

    Nguyen, Thao D.; Grazier, John Mark; Boyce, Brad Lee; Jones, Reese E.

    2007-10-01

    Biological tissues are uniquely structured materials with technologically appealing properties. Soft tissues such as skin, are constructed from a composite of strong fibrils and fluid-like matrix components. This was the first coordinated experimental/modeling project at Sandia or in the open literature to consider the mechanics of micromechanically-based anisotropy and viscoelasticity of soft biological tissues. We have exploited and applied Sandia's expertise in experimentation and mechanics modeling to better elucidate the behavior of collagen fibril-reinforced soft tissues. The purpose of this project was to provide a detailed understanding of the deformation of ocular tissues, specifically the highly structured skin-like tissue in the cornea. This discovery improved our knowledge of soft/complex materials testing and modeling. It also provided insight into the way that cornea tissue is bio-engineered such that under physiologically-relevant conditions it has a unique set of properties which enhance functionality. These results also provide insight into how non-physiologic loading conditions, such as corrective surgeries, may push the cornea outside of its natural design window, resulting in unexpected non-linear responses. Furthermore, this project created a clearer understanding of the mechanics of soft tissues that could lead to bio-inspired materials, such as highly supple and impact resistant body armor, and improve our design of human-machine interfaces, such as micro-electrical-mechanical (MEMS) based prosthetics.

  12. NASA Sponsored Research Involving Crystallization of Biological Materials

    NASA Technical Reports Server (NTRS)

    Downey, James Patton

    2000-01-01

    An overview of NASA's plans for the performing experiments involving the crystallization of biological materials on the International Space Station (ISS) is presented. In addition, a brief overview of past work is provided as background. Descriptions of flight hardware currently available for use on the ISS are given and projections of future developments are discussed. In addition, experiment selection and funding is described. As of the flight of STS-95, these crystallization projects have proven to be some of the most successful in the history of microgravity research. The NASA Microgravity Research Division alone has flown 185 different proteins, nucleic acids, viruses, and complexes on 43 different missions. 37 of the 185 have resulted, in, diffraction patterns with higher resolution than was obtained in all previous ground based experiments. This occurred despite the fact that an average of only 41 samples per protein were flown. A number of other samples have shown improved signal to noise characteristics, i.e. relative Wilson plots, when compared to the best ground experiments. In addition, a number of experiments investigating the effects of microgravity conditions on the crystallization of biological material have been conducted.

  13. Chirality, quantum mechanics, and biological determinism

    NASA Astrophysics Data System (ADS)

    Davies, P. C. W.

    2006-08-01

    life with biochemical make-up resembling that of known life. Whilst the experimental search for a second sample of life - possibly by detecting a chiral "anomaly" - continues, some theoretical investigations may be pursued to narrow down the options. Chiral determinism would be an intrinsically quantum process. There are hints that quantum mechanics plays a key role in biology, but the claim remains contentious. Here I review some of the evidence for quantum aspects of biology. I also summarize some proposals for testing biological determinism by seeking evidence for a multiple genesis events on Earth, and for identifying extant "alien microbes" - micro-organisms descended from an independent origin from familiar life.

  14. Biology beyond biochemistry: The mechanics of life

    NASA Astrophysics Data System (ADS)

    Wiggins, Paul A.

    In the last half century, biologists have made great strides towards understanding the intricate structure of the cell and the relation between this structure and cellular function. Single-molecule techniques and advances in microscopy have also significantly changed the way in which biologists ask and answer questions. As biological measurements and techniques have become increasingly quantitative, they have allowed biologists to ask ever more quantitative questions: How do the molecular machines, which comprise the cell function microscopically? Can we understand the design principles that govern the structure and function of biological systems on a microscopic scale? One outcome of this new generation of quantitative biological questions is the need to greet quantitative experiments with models at a higher level of abstraction than the traditional cartoons of molecular biology. In this thesis, I present two such quantitative models. In the first half of this thesis, I present a physical model for mechanotransduction. Mechanosensitive channels are the central agents employed by cells to transduce mechanical stimuli. Our senses of hearing and touch are both examples of this functional motif. The Mechanosensitive Channel of Large conductance (MscL) is arguably the simplest and best studied mechanosensitive channel. I present analytic estimates for the forces and free energy generated by bilayer deformation which reveal a compelling and intuitive model for the function of the MscL channel, analogous to the nucleation of a second phase. The competition between hydrophobic mismatch of the protein with the surrounding membrane and tension results in a surprisingly rich story, which can provide both a quantitative comparison to measurements of the opening tension for MscL when reconstituted in bilayers of different thickness and qualitative insights into the function of the MscL channel and other transmembrane proteins. In the second half of this thesis, I examine

  15. Mechanical properties of biological specimens explored by atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Kasas, S.; Longo, G.; Dietler, G.

    2013-04-01

    The atomic force microscope is a widely used surface scanning apparatus capable of reconstructing at a nanometric scale resolution the 3D morphology of biological samples. Due to its unique sensitivity, it is now increasingly used as a force sensor, to characterize the mechanical properties of specimens with a similar lateral resolution. This unique capability has produced, in the last years, a vast increase in the number of groups that have exploited the versatility and sensitivity of the instrument to explore the nanomechanics of various samples in the fields of biology, microbiology and medicine. In this review we outline the state of the art in this field, reporting the most interesting recent works involving the exploration of the nanomechanical properties of various biological samples.

  16. Multiscale mechanical modeling of soft biological tissues

    NASA Astrophysics Data System (ADS)

    Stylianopoulos, Triantafyllos

    2008-10-01

    Soft biological tissues include both native and artificial tissues. In the human body, tissues like the articular cartilage, arterial wall, and heart valve leaflets are examples of structures composed of an underlying network of collagen fibers, cells, proteins and molecules. Artificial tissues are less complex than native tissues and mainly consist of a fiber polymer network with the intent of replacing lost or damaged tissue. Understanding of the mechanical function of these materials is essential for many clinical treatments (e.g. arterial clamping, angioplasty), diseases (e.g. arteriosclerosis) and tissue engineering applications (e.g. engineered blood vessels or heart valves). This thesis presents the derivation and application of a multiscale methodology to describe the macroscopic mechanical function of soft biological tissues incorporating directly their structural architecture. The model, which is based on volume averaging theory, accounts for structural parameters such as the network volume fraction and orientation, the realignment of the fibers in response to strain, the interactions among the fibers and the interactions between the fibers and the interstitial fluid in order to predict the overall tissue behavior. Therefore, instead of using a constitutive equation to relate strain to stress, the tissue microstructure is modeled within a representative volume element (RVE) and the macroscopic response at any point in the tissue is determined by solving a micromechanics problem in the RVE. The model was applied successfully to acellular collagen gels, native blood vessels, and electrospun polyurethane scaffolds and provided accurate predictions for permeability calculations in isotropic and oriented fiber networks. The agreement of model predictions with experimentally determined mechanical properties provided insights into the mechanics of tissues and tissue constructs, while discrepancies revealed limitations of the model framework.

  17. Effects of distraction on muscle length: mechanisms involved in sarcomerogenesis.

    PubMed

    Caiozzo, Vincent J; Utkan, Ali; Chou, Richard; Khalafi, Afshin; Chandra, Heena; Baker, Michael; Rourke, Bryan; Adams, Greg; Baldwin, Ken; Green, Stuart

    2002-10-01

    Although a great deal of interest has been given to understanding the mechanisms involved in regulating the radial growth that occurs because of resistance training, much less has been given to studying the longitudinal growth of skeletal muscle that occurs because of passive stretch. The current authors provide a brief overview of key issues relevant to the longitudinal growth of skeletal muscle that occurs during distraction osteogenesis. Specifically, five key issues are addressed: (1) the pattern of sarcomerogenesis during distraction; (2) sarcomerogenesis and altered expression of sarcomeric and nonsarcomeric genes; (3) the satellite cell hypothesis; (4) mitogenic factors; and (5) new approaches for studying the longitudinal growth of skeletal muscle. A discussion is provided that revolves around the concept of a negative feedback loop. One of the most interesting issues to be resolved in muscle biology is the role of satellite cells in regulating the growth of skeletal muscle. Currently, it is not known whether satellite cell activation is a prerequisite for the longitudinal growth of skeletal muscle. Gene chip analyses provide a paradoxical view, showing that distraction osteogenesis results in the upregulation of a gene, GADD45, involved with growth arrest and deoxyribonucleic acid destruction.

  18. Cellular and Humoral Mechanisms Involved in the Control of Tuberculosis

    PubMed Central

    Zuñiga, Joaquin; Torres-García, Diana; Santos-Mendoza, Teresa; Rodriguez-Reyna, Tatiana S.; Granados, Julio; Yunis, Edmond J.

    2012-01-01

    Mycobacterium tuberculosis (Mtb) infection is a major international public health problem. One-third of the world's population is thought to have latent tuberculosis, a condition where individuals are infected by the intracellular bacteria without active disease but are at risk for reactivation, if their immune system fails. Here, we discuss the role of nonspecific inflammatory responses mediated by cytokines and chemokines induced by interaction of innate receptors expressed in macrophages and dendritic cells (DCs). We also review current information regarding the importance of several cytokines including IL-17/IL-23 in the development of protective cellular and antibody-mediated protective responses against Mtb and their influence in containment of the infection. Finally, in this paper, emphasis is placed on the mechanisms of failure of Mtb control, including the immune dysregulation induced by the treatment with biological drugs in different autoimmune diseases. Further functional studies, focused on the mechanisms involved in the early host-Mtb interactions and the interplay between host innate and acquired immunity against Mtb, may be helpful to improve the understanding of protective responses in the lung and in the development of novel therapeutic and prophylactic tools in TB. PMID:22666281

  19. Synthetic biology: a challenge to mechanical explanations in biology?

    PubMed

    Morange, Michel

    2012-01-01

    In their plans to modify organisms, synthetic biologists have contrasted engineering and tinkering. By drawing this contrast between their endeavors and what has happened during the evolution of organisms by natural selection, they underline the novelty of their projects and justify their ambitions. Synthetic biologists are at odds with a long tradition that has considered organisms as "perfect machines." This tradition had already been questioned by Stephen Jay Gould in the 1970s and received a major blow with the comparison made by François Jacob between organisms and the results of "bricolage" (tinkering). These contrasts between engineering and tinkering, synthetic biology and evolution, have no raison d'être. Machines built by humans are increasingly inspired by observations made on organisms. This is not a simple reversal of the previous trend-the mechanical conception of organisms-in which the characteristics of the latter were explained by comparison with human-built machines. Relations between organisms and machines have always been complex and ambiguous.

  20. Mechanical properties of nanostructure of biological materials

    NASA Astrophysics Data System (ADS)

    Ji, Baohua; Gao, Huajian

    2004-09-01

    Natural biological materials such as bone, teeth and nacre are nanocomposites of protein and mineral with superior strength. It is quite a marvel that nature produces hard and tough materials out of protein as soft as human skin and mineral as brittle as classroom chalk. What are the secrets of nature? Can we learn from this to produce bio-inspired materials in the laboratory? These questions have motivated us to investigate the mechanics of protein-mineral nanocomposite structure. Large aspect ratios and a staggered alignment of mineral platelets are found to be the key factors contributing to the large stiffness of biomaterials. A tension-shear chain (TSC) model of biological nanostructure reveals that the strength of biomaterials hinges upon optimizing the tensile strength of the mineral crystals. As the size of the mineral crystals is reduced to nanoscale, they become insensitive to flaws with strength approaching the theoretical strength of atomic bonds. The optimized tensile strength of mineral crystals thus allows a large amount of fracture energy to be dissipated in protein via shear deformation and consequently enhances the fracture toughness of biocomposites. We derive viscoelastic properties of the protein-mineral nanostructure and show that the toughness of biocomposite can be further enhanced by the viscoelastic properties of protein.

  1. [From the mechanical complexity in biology].

    PubMed

    Uribe, Libia Herrero

    2008-03-01

    From the mechanical complexity in biology. Through history, each century has brought new discoveries and beliefs that have resulted in different perspectives to study life organisms. In this essay, 1 define three periods: in the first, organisms were studied in the context of their environment, in the second, on the basis of physical and chemical laws, and on the third, systemically. My analysis starts with primitive humans, continues to Aristoteles and Newton, Lamarck and Darwin, the DNA doble helix discovery, and the beginnings of reduccionism in science. I propose that life is paradigmatical, that it obeys physical and chemical laws but cannot be explained by them I review the systemic theory, autopoiesis, discipative structures and non- linear dynamics. 1 propose that the deterministic, lineal and quantitative paradigm of nature are not the only way to study nature and invite the reader to explore the complexity paradigm.

  2. Biological Mechanism of Silver Nanoparticle Toxicity

    NASA Astrophysics Data System (ADS)

    Armstrong, Najealicka Nicole

    Silver nanoparticles (AgNPs), like almost all nanoparticles, are potentially toxic beyond a certain concentration because the survival of the organism is compromised due to scores of pathophysiological abnormalities above that concentration. However, the mechanism of AgNP toxicity remains undetermined. Instead of applying a toxic dose, these investigations were attempted to monitor the effects of AgNPs at a non-lethal concentration on wild type Drosophila melanogaster by exposing them to nanoparticles throughout their development. All adult flies raised in AgNP doped food indicated that of not more than 50 mg/L had no negative influence on median survival; however, these flies appeared uniformly lighter in body color due to the loss of melanin pigments in their cuticle. Additionally, fertility and vertical movement ability were compromised after AgNP feeding. The determination of the amount of free ionic silver (Ag+) indicated that the observed biological effects had resulted from the AgNPs and not from Ag+. Biochemical analysis suggests that the activity of copper dependent enzymes, namely tyrosinase and Cu-Zn superoxide dismutase, were decreased significantly following the consumption of AgNPs, despite the constant level of copper present in the tissue. Furthermore, copper supplementation restored the loss of AgNP induced demelanization, and the reduction of functional Ctr1 in Ctr1 heterozygous mutants caused the flies to be resistant to demelanization. Consequently, these studies proposed a mechanism whereby consumption of excess AgNPs in association with membrane bound copper transporter proteins cause sequestration of copper, thus creating a condition that resembles copper starvation. This model also explained the cuticular demelanization effect resulting from AgNP since tyrosinase activity is essential for melanin biosynthesis. Finally, these investigations demonstrated that Drosophila, an established genetic model system, can be well utilized for further

  3. Mutant p53: Multiple Mechanisms Define Biologic Activity in Cancer

    PubMed Central

    Kim, Michael Paul; Zhang, Yun; Lozano, Guillermina

    2015-01-01

    The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of alterations involve p53 missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may concomitantly gain novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant p53 gain of function in various model systems. In addition, we review mutant p53 addiction as emerging evidence suggests that tumors may depend on sustained mutant p53 activity for continued growth. We also discuss the role of p53 in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant p53 in various organ systems are reviewed and their limitations discussed. PMID:26618142

  4. Mutant p53: Multiple Mechanisms Define Biologic Activity in Cancer.

    PubMed

    Kim, Michael Paul; Zhang, Yun; Lozano, Guillermina

    2015-01-01

    The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of alterations involve p53 missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may concomitantly gain novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant p53 gain of function in various model systems. In addition, we review mutant p53 addiction as emerging evidence suggests that tumors may depend on sustained mutant p53 activity for continued growth. We also discuss the role of p53 in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant p53 in various organ systems are reviewed and their limitations discussed.

  5. Mechanisms of the formation of biological signaling profiles

    NASA Astrophysics Data System (ADS)

    Teimouri, Hamid; Kolomeisky, Anatoly B.

    2016-12-01

    The formation and growth of multi-cellular organisms and tissues from several genetically identical embryo cells is one of the most fundamental natural phenomena. These processes are stimulated and governed by multiple biological signaling molecules, which are also called morphogens. Embryo cells are able to read and pass genetic information by measuring the non-uniform concentration profiles of signaling molecules. It is widely believed that the establishment of concentration profiles of morphogens, commonly referred as morphogen gradients, is a result of complex biophysical and biochemical processes that might involve diffusion and degradation of locally produced signaling molecules. In this review, we discuss various theoretical aspects of the mechanisms for morphogen gradient formation, including stationary and transient dynamics, the effect of source delocalization, diffusion, different degradation mechanisms, and the role of spatial dimensions. Theoretical predictions are compared with experimental observations. In addition, we analyze the potential alternative mechanisms of the delivery of biological signals in embryo cells and tissues. Current challenges in understanding the mechanisms of morphogen gradients and future directions are also discussed.

  6. Why whole grains are protective: biological mechanisms.

    PubMed

    Slavin, Joanne

    2003-02-01

    Epidemiological studies find that whole-grain intake is protective against cancer, cardiovascular disease, diabetes and obesity. Potential mechanisms for this protection are diverse since whole grains are rich in nutrients and phytochemicals. First, whole grains are concentrated sources of dietary fibre, resistant starch and oligosaccharides, carbohydrates that escape digestion in the small intestine and are fermented in the gut, producing short-chain fatty acids (SCFA). SCFA lower colonic pH, serve as an energy source for the colonocytes and may alter blood lipids. These improvements in the gut environment may provide immune protection beyond the gut. Second, whole grains are rich in antioxidants, including trace minerals and phenolic compounds, and these compounds have been linked to disease prevention. Additionally, whole grains mediate insulin and glucose responses. Although lower glycaemic load and glycaemic index have been linked to diabetes and obesity, risk of cancers such as colon and breast cancer have also been linked to high intake of readily-available carbohydrate. Finally, whole grains contain many other compounds that may protect against chronic disease. These compounds include phytate, phyto-oestrogens such as lignan, plant stanols and sterols, and vitamins and minerals. As a consequence of the traditional models of conducting nutrition studies on isolated nutrients, few studies exist on the biological effects of increased whole-grain intake. The few whole-grain feeding studies that are available show improvements in biomarkers with whole-grain consumption, such as weight loss, blood lipid improvement and antioxidant protection.

  7. Combined Mechanical and Electrical Study of Polymers of Biological Origin

    NASA Astrophysics Data System (ADS)

    Zsoldos, G.; Szoda, K.; Marossy, K.

    2017-02-01

    Thermally Simulated Depolarization Current measurement is an excellent but not widely used method for identifying relaxation processes in polymers. The DMA method is used here to analyze the mechanical changes depend on temperature in biopolymers. The two techniques take advantage of the energy changes involved in the various phase transitions of certain polymer molecules. This allows for several properties of the material to be ascertained; melting points, enthalpies of melting, crystallization temperatures, glass transition temperatures and degradation temperatures. The examined biopolymer films are made from biological materials such as proteins and polysaccharides. These materials have gained wide usage in pharmaceutical, medical and food areas. The uses of biopolymer films depend on their structure and mechanical properties. This work is based on pectin and gelatin films. The films were prepared by casting. The casting technique used aqueous solutions in each case of sample preparation. The manufacturing process of the pectin and gelatin films was a single stage solving process.

  8. [Review on the main microorganisms and their metabolic mechanisms in enhanced biological phosphorus removal (EBPR) systems].

    PubMed

    Sun, Xue; Zhu, Wei-Jing; Wang, Liang; Wu, Wei-Xiang

    2014-03-01

    Enhanced biological phosphorus removal (EBPR) process is applied widely for removing phosphorus from wastewater. Studies on functional microorganisms and their metabolic mechanisms are fundamental to effective regulation for stable operation and performance improvement of EBPR process. Two main types of microorganisms in EBPR systems, polyphosphate accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs) were selected to summarize their metabolic mechanisms such as substrate uptake mechanisms, glycogen degradation pathways, extent of TCA cycle involvement and metabolic similarity between PAOs and GAOs. Application of molecular biology techniques in microbiology and metabolic mechanisms involved in the EBPR system was evaluated. Potential future research areas for the EBPR system and process optimization were also proposed.

  9. Using Spreadsheets to Teach Aspects of Biology Involving Mathematical Models

    ERIC Educational Resources Information Center

    Carlton, Kevin; Nicholls, Mike; Ponsonby, David

    2004-01-01

    Some aspects of biology, for example the Hardy-Weinberg simulation of population genetics or modelling heat flow in lizards, have an undeniable mathematical basis. Students can find the level of mathematical skill required to deal with such concepts to be an insurmountable hurdle to understanding. If not used effectively, spreadsheet models…

  10. RNA Interference: Biology, Mechanism, and Applications

    PubMed Central

    Agrawal, Neema; Dasaradhi, P. V. N.; Mohmmed, Asif; Malhotra, Pawan; Bhatnagar, Raj K.; Mukherjee, Sunil K.

    2003-01-01

    Double-stranded RNA-mediated interference (RNAi) is a simple and rapid method of silencing gene expression in a range of organisms. The silencing of a gene is a consequence of degradation of RNA into short RNAs that activate ribonucleases to target homologous mRNA. The resulting phenotypes either are identical to those of genetic null mutants or resemble an allelic series of mutants. Specific gene silencing has been shown to be related to two ancient processes, cosuppression in plants and quelling in fungi, and has also been associated with regulatory processes such as transposon silencing, antiviral defense mechanisms, gene regulation, and chromosomal modification. Extensive genetic and biochemical analysis revealed a two-step mechanism of RNAi-induced gene silencing. The first step involves degradation of dsRNA into small interfering RNAs (siRNAs), 21 to 25 nucleotides long, by an RNase III-like activity. In the second step, the siRNAs join an RNase complex, RISC (RNA-induced silencing complex), which acts on the cognate mRNA and degrades it. Several key components such as Dicer, RNA-dependent RNA polymerase, helicases, and dsRNA endonucleases have been identified in different organisms for their roles in RNAi. Some of these components also control the development of many organisms by processing many noncoding RNAs, called micro-RNAs. The biogenesis and function of micro-RNAs resemble RNAi activities to a large extent. Recent studies indicate that in the context of RNAi, the genome also undergoes alterations in the form of DNA methylation, heterochromatin formation, and programmed DNA elimination. As a result of these changes, the silencing effect of gene functions is exercised as tightly as possible. Because of its exquisite specificity and efficiency, RNAi is being considered as an important tool not only for functional genomics, but also for gene-specific therapeutic activities that target the mRNAs of disease-related genes. PMID:14665679

  11. Systems biology and mechanics of growth.

    PubMed

    Eskandari, Mona; Kuhl, Ellen

    2015-01-01

    In contrast to inert systems, living biological systems have the advantage to adapt to their environment through growth and evolution. This transfiguration is evident during embryonic development, when the predisposed need to grow allows form to follow function. Alterations in the equilibrium state of biological systems breed disease and mutation in response to environmental triggers. The need to characterize the growth of biological systems to better understand these phenomena has motivated the continuum theory of growth and stimulated the development of computational tools in systems biology. Biological growth in development and disease is increasingly studied using the framework of morphoelasticity. Here, we demonstrate the potential for morphoelastic simulations through examples of volume, area, and length growth, inspired by tumor expansion, chronic bronchitis, brain development, intestine formation, plant shape, and myopia. We review the systems biology of living systems in light of biochemical and optical stimuli and classify different types of growth to facilitate the design of growth models for various biological systems within this generic framework. Exploring the systems biology of growth introduces a new venue to control and manipulate embryonic development, disease progression, and clinical intervention.

  12. Systems biology and mechanics of growth

    PubMed Central

    Eskandari, Mona; Kuhl, Ellen

    2015-01-01

    In contrast to inert systems, living biological systems have the advantage to adapt to their environment through growth and evolution. This transfiguration is evident in embryonic development, when the predisposed need to grow allows form to follow function. Alterations in the equilibrium state of biological systems breed disease and mutation in response to environmental triggers. The need to characterize the growth of biological systems to better understand these phenomena has motivated the continuum theory of growth and stimulated the development of computational tools in systems biology. Biological growth in development and disease is increasingly studied using the framework of morphoelasticity. Here we demonstrate the potential for morphoelastic simulations through examples of volume, area, and length growth, inspired by tumor expansion, chronic bronchitis, brain development, intestine formation, plant shape, and myopia. We review the sytems biology of living systems in light of biochemical and optical stimuli and classify different types of growth to facilitate the design of growth models for various biological systems within this generic framework. Exploring the systems biology of growth introduces a new venue to control and manipulate embryonic development, disease progression, and clinical intervention. PMID:26352286

  13. Examples for biological reactivity involving free radicals followed by CIDNP

    NASA Astrophysics Data System (ADS)

    Andreu, Inmaculada; Neshchadin, Dmytro; Batchelor, Stephen N.; Miranda, Miguel A.; Gescheidt, Georg

    2013-10-01

    It is shown how chemically induced dynamic nuclear polarisation (CIDNP) spectroscopy is able to efficiently complement electron paramagnetic resonance (EPR), when molecular transformations of free radical pairs are investigated. This is demonstrated in three examples of modelling biologically relevant phenomena, particularly oxidative stress and antioxidant activity. Lipid peroxidation, topological control in the oxidation of cholesterol, and a mechanistic study of antioxidant activity of natural tea and wine polyphenols are presented.

  14. Biology: An Important Agricultural Engineering Mechanism

    ERIC Educational Resources Information Center

    Henderson, S. M.

    1974-01-01

    Describes the field of bioengineering with particular emphasis on agricultural engineering, and presents the results of a survey of schools that combine biology and engineering in their curricula. (JR)

  15. Obstructive renal injury: from fluid mechanics to molecular cell biology.

    PubMed

    Ucero, Alvaro C; Gonçalves, Sara; Benito-Martin, Alberto; Santamaría, Beatriz; Ramos, Adrian M; Berzal, Sergio; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto

    2010-04-22

    Urinary tract obstruction is a frequent cause of renal impairment. The physiopathology of obstructive nephropathy has long been viewed as a mere mechanical problem. However, recent advances in cell and systems biology have disclosed a complex physiopathology involving a high number of molecular mediators of injury that lead to cellular processes of apoptotic cell death, cell injury leading to inflammation and resultant fibrosis. Functional studies in animal models of ureteral obstruction using a variety of techniques that include genetically modified animals have disclosed an important role for the renin-angiotensin system, transforming growth factor-β1 (TGF-β1) and other mediators of inflammation in this process. In addition, high throughput techniques such as proteomics and transcriptomics have identified potential biomarkers that may guide clinical decision-making.

  16. Obstructive renal injury: from fluid mechanics to molecular cell biology

    PubMed Central

    Ucero, Alvaro C; Gonçalves, Sara; Benito-Martin, Alberto; Santamaría, Beatriz; Ramos, Adrian M; Berzal, Sergio; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto

    2010-01-01

    Urinary tract obstruction is a frequent cause of renal impairment. The physiopathology of obstructive nephropathy has long been viewed as a mere mechanical problem. However, recent advances in cell and systems biology have disclosed a complex physiopathology involving a high number of molecular mediators of injury that lead to cellular processes of apoptotic cell death, cell injury leading to inflammation and resultant fibrosis. Functional studies in animal models of ureteral obstruction using a variety of techniques that include genetically modified animals have disclosed an important role for the renin-angiotensin system, transforming growth factor-β1 (TGF-β1) and other mediators of inflammation in this process. In addition, high throughput techniques such as proteomics and transcriptomics have identified potential biomarkers that may guide clinical decision-making. PMID:24198613

  17. Biological mechanisms of bone and cartilage remodelling--genomic perspective.

    PubMed

    Borovecki, F; Pecina-Slaus, N; Vukicevic, S

    2007-12-01

    Rapid advancements in the field of genomics, enabled by the achievements of the Human Genome Project and the complete decoding of the human genome, have opened an unimaginable set of opportunities for scientists to further unveil delicate mechanisms underlying the functional homeostasis of biological systems. The trend of applying whole-genome analysis techniques has also contributed to a better understanding of physiological and pathological processes involved in homeostasis of bone and cartilage tissues. Gene expression profiling studies have yielded novel insights into the complex interplay of osteoblast and osteoclast regulation, as well as paracrine and endocrine control of bone and cartilage remodelling. Mechanisms of new bone formation responsible for fracture healing and distraction osteogenesis, as well as healing of joint cartilage defects, have also been extensively studied. Microarray experiments have been especially useful in studying pathological processes involved in diseases such as osteoporosis or bone tumours. Existing results show that microarrays hold great promise in areas such as identification of targets for novel therapies or development of new biomarkers and classifiers in skeletal diseases.

  18. Review of biological mechanisms for application to instrument design

    NASA Technical Reports Server (NTRS)

    Healer, J.

    1967-01-01

    Biological sensors are the mechanisms which enable a living organism to monitor its environment. Ways in which the functional mechanism of biosensors can be applied to develop new concepts of instrumentation, enhance and extend the human senses, and improve the sensitivity of existing instrumentation are described in a review of these mechanisms.

  19. [Molecular biology and immunopathogenetic mechanisms of sepsis].

    PubMed

    Průcha, M

    2009-01-01

    Sepsis, the systemic inflammatory response to infection, causes high mortality in patients in non-coronary units of intensive care. The most important characteristic of sepsis is the interaction between two subjects, the macro and the microorganism, associated with the dysfunction of innate and adaptive immunity. Sepsis is understood more as a dynamic syndrome characterized by many phenomenona which are often antagonistic. The inflammation, characterizing sepsis, does not act as a primary physiological compensatory mechanism and rather oscillates between the phase of hyperinflammatory response and anergy or immunoparalysis. The elucidation of the pathogenesis of sepsis is linked to the understanding of immunopathogenetic mechanisms, which characterize the interaction between the macro and microorganisms.

  20. Interfacial interactions involved in the biological assembly of Chandipura virus nucleocapsid protein.

    PubMed

    Sreejith, R; Gulati, Sahil; Gupta, Sanjay

    2013-06-01

    The biological assembly of Chandipura virus nucleocapsid (N) protein has been modeled and the amino acid residues involved in specific intermolecular interactions among N monomers during oligomerisation have been predicted.

  1. Molecular Mechanisms in Mood Regulation Involving the Circadian Clock.

    PubMed

    Albrecht, Urs

    2017-01-01

    The circadian system coordinates activities and functions in cells and tissues in order to optimize body functions in anticipation to daily changes in the environment. Disruption of the circadian system, due to irregular lifestyle such as rotating shift work, frequent travel across time-zones, or chronic stress, is correlated with several diseases such as obesity, cancer, and neurological disorders. Molecular mechanisms linking the circadian clock with neurological functions have been uncovered suggesting that disruption of the clock may be critically involved in the development of mood disorders. In this mini-review, I will summarize molecular mechanisms in which clock components play a central role for mood regulation. Such mechanisms have been identified in the monoaminergic system, the HPA axis, and neurogenesis.

  2. Molecular Mechanisms in Mood Regulation Involving the Circadian Clock

    PubMed Central

    Albrecht, Urs

    2017-01-01

    The circadian system coordinates activities and functions in cells and tissues in order to optimize body functions in anticipation to daily changes in the environment. Disruption of the circadian system, due to irregular lifestyle such as rotating shift work, frequent travel across time-zones, or chronic stress, is correlated with several diseases such as obesity, cancer, and neurological disorders. Molecular mechanisms linking the circadian clock with neurological functions have been uncovered suggesting that disruption of the clock may be critically involved in the development of mood disorders. In this mini-review, I will summarize molecular mechanisms in which clock components play a central role for mood regulation. Such mechanisms have been identified in the monoaminergic system, the HPA axis, and neurogenesis. PMID:28223962

  3. Statistical Mechanics of Confined Biological Materials

    NASA Astrophysics Data System (ADS)

    El Kinani, R.; Benhamou, M.; Kaïdi, H.

    2017-03-01

    In this work, we propose a model to study the Statistical Mechanics of a confined bilayer-membrane that fluctuates between two interactive flat substrates. From the scaling laws point of view, the bilayer-membranes and strings are very similar. Therefore, it is sufficient to consider only the problem of a string. We assume that the bilayer-membrane (or string) interact with the substrate via a Double Morse potential that reproduces well the characteristics of the real interaction. We show that the Statistical Mechanic of the string can be adequately described by the Schrödinger equation approach that we solve exactly using the Bethe method. Finally, from the exact value of the energy of the ground state, we extract the expression of the free energy density as well as the specific heat.

  4. Elastic proteins: biological roles and mechanical properties.

    PubMed Central

    Gosline, John; Lillie, Margo; Carrington, Emily; Guerette, Paul; Ortlepp, Christine; Savage, Ken

    2002-01-01

    The term 'elastic protein' applies to many structural proteins with diverse functions and mechanical properties so there is room for confusion about its meaning. Elastic implies the property of elasticity, or the ability to deform reversibly without loss of energy; so elastic proteins should have high resilience. Another meaning for elastic is 'stretchy', or the ability to be deformed to large strains with little force. Thus, elastic proteins should have low stiffness. The combination of high resilience, large strains and low stiffness is characteristic of rubber-like proteins (e.g. resilin and elastin) that function in the storage of elastic-strain energy. Other elastic proteins play very different roles and have very different properties. Collagen fibres provide exceptional energy storage capacity but are not very stretchy. Mussel byssus threads and spider dragline silks are also elastic proteins because, in spite of their considerable strength and stiffness, they are remarkably stretchy. The combination of strength and extensibility, together with low resilience, gives these materials an impressive resistance to fracture (i.e. toughness), a property that allows mussels to survive crashing waves and spiders to build exquisite aerial filters. Given this range of properties and functions, it is probable that elastic proteins will provide a wealth of chemical structures and elastic mechanisms that can be exploited in novel structural materials through biotechnology. PMID:11911769

  5. Biologic-free mechanically induced muscle regeneration

    PubMed Central

    Cezar, Christine A.; Roche, Ellen T.; Vandenburgh, Herman H.; Duda, Georg N.; Walsh, Conor J.; Mooney, David J.

    2016-01-01

    Severe skeletal muscle injuries are common and can lead to extensive fibrosis, scarring, and loss of function. Clinically, no therapeutic intervention exists that allows for a full functional restoration. As a result, both drug and cellular therapies are being widely investigated for treatment of muscle injury. Because muscle is known to respond to mechanical loading, we investigated instead whether a material system capable of massage-like compressions could promote regeneration. Magnetic actuation of biphasic ferrogel scaffolds implanted at the site of muscle injury resulted in uniform cyclic compressions that led to reduced fibrous capsule formation around the implant, as well as reduced fibrosis and inflammation in the injured muscle. In contrast, no significant effect of ferrogel actuation on muscle vascularization or perfusion was found. Strikingly, ferrogel-driven mechanical compressions led to enhanced muscle regeneration and a ∼threefold increase in maximum contractile force of the treated muscle at 2 wk compared with no-treatment controls. Although this study focuses on the repair of severely injured skeletal muscle, magnetically stimulated bioagent-free ferrogels may find broad utility in the field of regenerative medicine. PMID:26811474

  6. Mechanisms Involved in Exercise-Induced Cardioprotection: A Systematic Review

    PubMed Central

    Borges, Juliana Pereira; Lessa, Marcos Adriano

    2015-01-01

    Background Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate. Objective To perform a systematic review of the studies that have addressed the mechanisms by which aerobic exercise promotes direct cardioprotection against ischemia and reperfusion injury. Methods A search was conducted using MEDLINE, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde, and Scientific Electronic Library Online databases. Data were extracted in a standardized manner by two independent researchers, who were responsible for assessing the methodological quality of the studies. Results The search retrieved 78 studies; after evaluating the abstracts, 30 studies were excluded. The manuscripts of the remaining 48 studies were completely read and, of these, 20 were excluded. Finally, 28 studies were included in this systematic review. Conclusion On the basis of the selected studies, the following are potentially involved in the cardioprotective response to exercise: increased heat shock protein production, nitric oxide pathway involvement, increased cardiac antioxidant capacity, improvement in ATP-dependent potassium channel function, and opioid system activation. Despite all the previous investigations, further research is still necessary to obtain more consistent conclusions. PMID:25830711

  7. Mechanical and biological properties of keratose biomaterials.

    PubMed

    de Guzman, Roche C; Merrill, Michelle R; Richter, Jillian R; Hamzi, Rawad I; Greengauz-Roberts, Olga K; Van Dyke, Mark E

    2011-11-01

    The oxidized form of extractable human hair keratin proteins, commonly referred to as keratose, is gaining interest as a biomaterial for multiple tissue engineering studies including those directed toward peripheral nerve, spinal cord, skin, and bone regeneration. Unlike its disulfide cross-linked counterpart, kerateine, keratose does not possess a covalently cross-linked network structure and consequently displays substantially different characteristics. In order to understand its mode(s) of action and potential for clinical translatability, detailed characterization of the composition, physical properties, and biological responses of keratose biomaterials are needed. Keratose was obtained from end-cut human hair fibers by peracetic acid treatment, followed by base extraction, and subsequent dialysis. Analysis of lyophilized keratose powder determined that it contains 99% proteins by mass with amino acid content similar to human hair cortex. Metallic elements were also found in minute quantities. Protein oxidation led to disulfide bond cleavage and drastic reduction of free thiols due to conversion of sulfhydryl to sulfonic acid, chain fragmentation, and amino acid modifications. Mass spectrometry identified the major protein constituents as a heterogeneous mixture of 15 hair keratins (type I: K31-35 and K37-39, and type II: K81-86) with small amounts of epithelial keratins which exist in monomeric, dimeric, multimeric, and even degraded forms. Re-hydration with PBS enabled molecular assembly into an elastic solid-like hydrogel. Highly-porous scaffolds formed by lyophilization of the gel had the compression behavior of a cellular foam material and reverted back to gel upon wetting. Cytotoxicity assays showed that the EC50 for various cell lines were attained at 8-10 mg/mL keratose, indicating the non-toxic nature of the material. Implantation in mouse subcutaneous tissue pockets demonstrated that keratose resorption follows a rectangular hyperbolic regression

  8. CRISPR-Cas: biology, mechanisms and relevance

    PubMed Central

    Hille, Frank

    2016-01-01

    Prokaryotes have evolved several defence mechanisms to protect themselves from viral predators. Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas) display a prokaryotic adaptive immune system that memorizes previous infections by integrating short sequences of invading genomes—termed spacers—into the CRISPR locus. The spacers interspaced with repeats are expressed as small guide CRISPR RNAs (crRNAs) that are employed by Cas proteins to target invaders sequence-specifically upon a reoccurring infection. The ability of the minimal CRISPR-Cas9 system to target DNA sequences using programmable RNAs has opened new avenues in genome editing in a broad range of cells and organisms with high potential in therapeutical applications. While numerous scientific studies have shed light on the biochemical processes behind CRISPR-Cas systems, several aspects of the immunity steps, however, still lack sufficient understanding. This review summarizes major discoveries in the CRISPR-Cas field, discusses the role of CRISPR-Cas in prokaryotic immunity and other physiological properties, and describes applications of the system as a DNA editing technology and antimicrobial agent. This article is part of the themed issue ‘The new bacteriology’. PMID:27672148

  9. Mechanisms Involved in the Aging-Induced Vascular Dysfunction

    PubMed Central

    El Assar, Mariam; Angulo, Javier; Vallejo, Susana; Peiró, Concepción; Sánchez-Ferrer, Carlos F.; Rodríguez-Mañas, Leocadio

    2012-01-01

    Vascular aging is a key process determining health status of aged population. Aging is an independent cardiovascular risk factor associated to an impairment of endothelial function, which is a very early and important event leading to cardiovascular disease. Vascular aging, formerly being considered an immutable and inexorable risk factor, is now viewed as a target process for intervention in order to achieve a healthier old age. A further knowledge of the mechanisms underlying the age-related vascular dysfunction is required to design an adequate therapeutic strategy to prevent or restore this impairment of vascular functionality. Among the proposed mechanisms that contribute to age-dependent endothelial dysfunction, this review is focused on the following aspects occurring into the vascular wall: (1) the reduction of nitric oxide (NO) bioavailability, caused by diminished NO synthesis and/or by augmented NO scavenging due to oxidative stress, leading to peroxynitrite formation (ONOO−); (2) the possible sources involved in the enhancement of oxidative stress; (3) the increased activity of vasoconstrictor factors; and (4) the development of a low-grade pro-inflammatory environment. Synergisms and interactions between all these pathways are also analyzed. Finally, a brief summary of some cellular mechanisms related to endothelial cell senescence (including telomere and telomerase, stress-induced senescence, as well as sirtuins) are implemented, as they are likely involved in the age-dependent endothelial dysfunction, as well as in the lower vascular repairing capacity observed in the elderly. Prevention or reversion of those mechanisms leading to endothelial dysfunction through life style modifications or pharmacological interventions could markedly improve cardiovascular health in older people. PMID:22783194

  10. Mechanisms involved in the aging-induced vascular dysfunction.

    PubMed

    El Assar, Mariam; Angulo, Javier; Vallejo, Susana; Peiró, Concepción; Sánchez-Ferrer, Carlos F; Rodríguez-Mañas, Leocadio

    2012-01-01

    Vascular aging is a key process determining health status of aged population. Aging is an independent cardiovascular risk factor associated to an impairment of endothelial function, which is a very early and important event leading to cardiovascular disease. Vascular aging, formerly being considered an immutable and inexorable risk factor, is now viewed as a target process for intervention in order to achieve a healthier old age. A further knowledge of the mechanisms underlying the age-related vascular dysfunction is required to design an adequate therapeutic strategy to prevent or restore this impairment of vascular functionality. Among the proposed mechanisms that contribute to age-dependent endothelial dysfunction, this review is focused on the following aspects occurring into the vascular wall: (1) the reduction of nitric oxide (NO) bioavailability, caused by diminished NO synthesis and/or by augmented NO scavenging due to oxidative stress, leading to peroxynitrite formation (ONOO(-)); (2) the possible sources involved in the enhancement of oxidative stress; (3) the increased activity of vasoconstrictor factors; and (4) the development of a low-grade pro-inflammatory environment. Synergisms and interactions between all these pathways are also analyzed. Finally, a brief summary of some cellular mechanisms related to endothelial cell senescence (including telomere and telomerase, stress-induced senescence, as well as sirtuins) are implemented, as they are likely involved in the age-dependent endothelial dysfunction, as well as in the lower vascular repairing capacity observed in the elderly. Prevention or reversion of those mechanisms leading to endothelial dysfunction through life style modifications or pharmacological interventions could markedly improve cardiovascular health in older people.

  11. Biological control of bacterial wilt in Arabidopsis thaliana involves abscissic acid signalling.

    PubMed

    Feng, Dong Xin; Tasset, Céline; Hanemian, Mathieu; Barlet, Xavier; Hu, Jian; Trémousaygue, Dominique; Deslandes, Laurent; Marco, Yves

    2012-06-01

    Means to control bacterial wilt caused by the phytopathogenic root bacteria Ralstonia solanacearum are limited. Mutants in a large cluster of genes (hrp) involved in the pathogenicity of R. solanacearum were successfully used in a previous study as endophytic biocontrol agents in challenge inoculation experiments on tomato. However, the molecular mechanisms controlling this resistance remained unknown. We developed a protection assay using Arabidopsis thaliana as a model plant and analyzed the events underlying the biological control by genetic, transcriptomic and molecular approaches. High protection rates associated with a significant decrease in the multiplication of R. solanacearum were observed in plants pre-inoculated with a ΔhrpB mutant strain. Neither salicylic acid, nor jasmonic acid/ethylene played a role in the establishment of this resistance. Microarray analysis showed that 26% of the up-regulated genes in protected plants are involved in the biosynthesis and signalling of abscissic acid (ABA). In addition 21% of these genes are constitutively expressed in the irregular xylem cellulose synthase mutants (irx), which present a high level of resistance to R. solanacearum. We propose that inoculation with the ΔhrpB mutant strain generates a hostile environment for subsequent plant colonization by a virulent strain of R. solanacearum.

  12. Neurophysiological mechanisms involved in language learning in adults

    PubMed Central

    Rodríguez-Fornells, Antoni; Cunillera, Toni; Mestres-Missé, Anna; de Diego-Balaguer, Ruth

    2009-01-01

    Little is known about the brain mechanisms involved in word learning during infancy and in second language acquisition and about the way these new words become stable representations that sustain language processing. In several studies we have adopted the human simulation perspective, studying the effects of brain-lesions and combining different neuroimaging techniques such as event-related potentials and functional magnetic resonance imaging in order to examine the language learning (LL) process. In the present article, we review this evidence focusing on how different brain signatures relate to (i) the extraction of words from speech, (ii) the discovery of their embedded grammatical structure, and (iii) how meaning derived from verbal contexts can inform us about the cognitive mechanisms underlying the learning process. We compile these findings and frame them into an integrative neurophysiological model that tries to delineate the major neural networks that might be involved in the initial stages of LL. Finally, we propose that LL simulations can help us to understand natural language processing and how the recovery from language disorders in infants and adults can be accomplished. PMID:19933142

  13. [Ocular involvement in spondylarthritis--new mechanisms, new therapies].

    PubMed

    Itulescu, T C M; Alexandrescu, Cristina; Voinea, Liliana-Mary

    2014-01-01

    Spondyloarthrites (SPA) represent a group of heterogenous rheumatic diseases (ankylosing spondylitis/SA, psoriatic arthritis/PsA, reactive arthritis/ReA, spondyloarthritis in bowel inflammatory diseases/BID, undifferentiated spondyloarthritis/undif SpA) with distinct clinical features and common genetic predisposition (HLA-B27). SpA may also affect other organs, ocular involvement, represented by uveitis and conjunctivitis, being one of the most important extraskeletal manifestations. Pathogenic mechanisms of ocular involment in SpA are not entirely known; nevertheless, the inflammatory process which characterizes the main rheumatic diseases seems to be responsible for this extraskeletal manifestation. SpA treatment targeted at clinical remission has a favourable effect not only on articular but also on ocular involvement. The discovery of new pathogenic mechanisms of both rheumatic and eye disease in SpA have contributed to identification of new pathogenic therapies. The interdisciplinary team work of rheumatologists and ophtalmologists have prove essential for the management of SpA patients with ocular manifestations.

  14. Fluid-structure interaction involving large deformations: 3D simulations and applications to biological systems

    NASA Astrophysics Data System (ADS)

    Tian, Fang-Bao; Dai, Hu; Luo, Haoxiang; Doyle, James F.; Rousseau, Bernard

    2014-02-01

    Three-dimensional fluid-structure interaction (FSI) involving large deformations of flexible bodies is common in biological systems, but accurate and efficient numerical approaches for modeling such systems are still scarce. In this work, we report a successful case of combining an existing immersed-boundary flow solver with a nonlinear finite-element solid-mechanics solver specifically for three-dimensional FSI simulations. This method represents a significant enhancement from the similar methods that are previously available. Based on the Cartesian grid, the viscous incompressible flow solver can handle boundaries of large displacements with simple mesh generation. The solid-mechanics solver has separate subroutines for analyzing general three-dimensional bodies and thin-walled structures composed of frames, membranes, and plates. Both geometric nonlinearity associated with large displacements and material nonlinearity associated with large strains are incorporated in the solver. The FSI is achieved through a strong coupling and partitioned approach. We perform several validation cases, and the results may be used to expand the currently limited database of FSI benchmark study. Finally, we demonstrate the versatility of the present method by applying it to the aerodynamics of elastic wings of insects and the flow-induced vocal fold vibration.

  15. Fluid–structure interaction involving large deformations: 3D simulations and applications to biological systems

    PubMed Central

    Tian, Fang-Bao; Dai, Hu; Luo, Haoxiang; Doyle, James F.; Rousseau, Bernard

    2013-01-01

    Three-dimensional fluid–structure interaction (FSI) involving large deformations of flexible bodies is common in biological systems, but accurate and efficient numerical approaches for modeling such systems are still scarce. In this work, we report a successful case of combining an existing immersed-boundary flow solver with a nonlinear finite-element solid-mechanics solver specifically for three-dimensional FSI simulations. This method represents a significant enhancement from the similar methods that are previously available. Based on the Cartesian grid, the viscous incompressible flow solver can handle boundaries of large displacements with simple mesh generation. The solid-mechanics solver has separate subroutines for analyzing general three-dimensional bodies and thin-walled structures composed of frames, membranes, and plates. Both geometric nonlinearity associated with large displacements and material nonlinearity associated with large strains are incorporated in the solver. The FSI is achieved through a strong coupling and partitioned approach. We perform several validation cases, and the results may be used to expand the currently limited database of FSI benchmark study. Finally, we demonstrate the versatility of the present method by applying it to the aerodynamics of elastic wings of insects and the flow-induced vocal fold vibration. PMID:24415796

  16. Critical Motor Involvement in Prediction of Human and Non-biological Motion Trajectories

    PubMed Central

    de Wit, Matthieu M.; Buxbaum, Laurel J.

    2017-01-01

    Objectives Adaptive interaction with the environment requires the ability to predict both human and non-biological motion trajectories. Prior accounts of the neurocognitive basis for prediction of these two motion classes may generally be divided into those that posit that non-biological motion trajectories are predicted using the same motor planning and/or simulation mechanisms used for human actions, and those that posit distinct mechanisms for each. Using brain lesion patients and healthy controls, this study examined critical neural substrates and behavioral correlates of human and non-biological motion prediction. Methods Twenty-seven left hemisphere stroke patients and 13 neurologically intact controls performed a visual occlusion task requiring prediction of pantomimed tool use, real tool use, and non-biological motion videos. Patients were also assessed with measures of motor strength and speed, praxis, and action recognition. Results Prediction impairment for both human and non-biological motion was associated with limb apraxia and, weakly, with the severity of motor production deficits, but not with action recognition ability. Furthermore, impairment for human and non-biological motion prediction was equivalently associated with lesions in the left inferior parietal cortex, left dorsal frontal cortex, and the left insula. Conclusions These data suggest that motor planning mechanisms associated with specific loci in the sensorimotor network are critical for prediction of spatiotemporal trajectory information characteristic of both human and non-biological motions. PMID:28205497

  17. Change Is Good: Variations in Common Biological Mechanisms in the Epsilonproteobacterial Genera Campylobacter and Helicobacter

    PubMed Central

    Gilbreath, Jeremy J.; Cody, William L.; Merrell, D. Scott; Hendrixson, David R.

    2011-01-01

    Summary: Microbial evolution and subsequent species diversification enable bacterial organisms to perform common biological processes by a variety of means. The epsilonproteobacteria are a diverse class of prokaryotes that thrive in diverse habitats. Many of these environmental niches are labeled as extreme, whereas other niches include various sites within human, animal, and insect hosts. Some epsilonproteobacteria, such as Campylobacter jejuni and Helicobacter pylori, are common pathogens of humans that inhabit specific regions of the gastrointestinal tract. As such, the biological processes of pathogenic Campylobacter and Helicobacter spp. are often modeled after those of common enteric pathogens such as Salmonella spp. and Escherichia coli. While many exquisite biological mechanisms involving biochemical processes, genetic regulatory pathways, and pathogenesis of disease have been elucidated from studies of Salmonella spp. and E. coli, these paradigms often do not apply to the same processes in the epsilonproteobacteria. Instead, these bacteria often display extensive variation in common biological mechanisms relative to those of other prototypical bacteria. In this review, five biological processes of commonly studied model bacterial species are compared to those of the epsilonproteobacteria C. jejuni and H. pylori. Distinct differences in the processes of flagellar biosynthesis, DNA uptake and recombination, iron homeostasis, interaction with epithelial cells, and protein glycosylation are highlighted. Collectively, these studies support a broader view of the vast repertoire of biological mechanisms employed by bacteria and suggest that future studies of the epsilonproteobacteria will continue to provide novel and interesting information regarding prokaryotic cellular biology. PMID:21372321

  18. Early mechanisms in radiation-induced biological damage

    SciTech Connect

    Powers, E.L.

    1983-01-01

    An introduction to the mechanisms of radiation action in biological systems is presented. Several questions about the nature of the radiation damage process are discussed, including recognition of the oxygen effects, dose-response relationships, and the importance of the hydroxyl radical. (ACR)

  19. How divergence mechanisms influence disassortative mixing property in biology

    NASA Astrophysics Data System (ADS)

    Xu, Chunsui; Liu, Zengrong; Wang, Ruiqi

    2010-02-01

    The duplication-divergence mechanism of network growth has been widely investigated, especially in gene and protein networks. Both the duplication and divergence have a key role in biological network evolution. However, the relative roles of these mechanisms in the influence of disassortative property in protein interaction networks remain to be clarified. It has been shown that duplication can indeed make protein networks evolve towards disassortative networks. To make the relationship between the disassortative property and the duplication-divergence mechanism more clear, we further discuss how the divergence mechanism influences the disassortative property. We tested four different divergence mechanisms, i.e., node deletion, edge deletion, edge addition, and edge rewiring to study their effects on disassortative property. Our study highlights the crucial roles of different divergence evolution mechanisms.

  20. Swarming mechanisms in the yellow fever mosquito: aggregation pheromones involved in the mating behavior of Aedes aegypti

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mosquitoes of various species mate in swarms comprised of tens to thousands flying males. Yet little information is known about mosquito swarming mechanism. Discovering chemical cues involved in mosquito biology leads to better adaptation of disease control interventions. In this study, we aimed ...

  1. Structure and mechanics of interfaces in biological materials

    NASA Astrophysics Data System (ADS)

    Barthelat, Francois; Yin, Zhen; Buehler, Markus J.

    2016-04-01

    Hard biological materials — for example, seashells, bone or wood — fulfil critical structural functions and display unique and attractive combinations of stiffness, strength and toughness, owing to their intricate architectures, which are organized over several length scales. The size, shape and arrangement of the ‘building blocks’ of which these materials are made are essential for defining their properties and their exceptional performance, but there is growing evidence that their deformation and toughness are also largely governed by the interfaces that join these building blocks. These interfaces channel nonlinear deformations and deflect cracks into configurations in which propagation is more difficult. In this Review, we discuss comparatively the composition, structure and mechanics of a set of representative biological interfaces in nacre, bone and wood, and show that these interfaces possess unusual mechanical characteristics, which can encourage the development of advanced bioinspired composites. Finally, we highlight recent examples of synthetic materials inspired from the mechanics and architecture of natural interfaces.

  2. Mechanisms involved in BACE upregulation associated to stress.

    PubMed

    Martisova, Eva; Solas, Maite; Gerenu, Gorka; Milagro, Fermin I; Campion, Javier; Ramirez, Maria J

    2012-09-01

    The objective of the present work was to study a purported involvement of stress in amyloid pathology through the modulation of BACE expression. Early-life stressed rats (maternal separation, MS) showed significant increases in corticosterone levels, BACE expression and Aβ levels. The CpG7 site of the BACE promoter was significantly hypomethylated in MS, and corticosterone levels negatively correlated to the methylation status of CpG7. The activation of the stress-activated protein kinase JNK was also increased in MS rats. In SHSY-5Y neuroblastoma cells, corticosterone induced a rapid increase in BACE expression that was abolished by specific inhibiton of JNK activation or by spironolactone, a mineralocorticoid receptor antagonist, but not by mifepristone, a glucocorticoid receptor antagonist. Corticosterone was also able to increase pJNK expression and this effect was fully reverted by spironolactone. Mice chronically treated with corticosterone showed increased BACE and pJNK expression. These increases were reverted by treatment with spironolactone or with a JNK inhibitor. It is suggested that increased corticosterone levels associated to stress lead to increase BACE transcription both through epigenetic mechanisms and activation of JNK.

  3. On the mechanics of growing thin biological membranes

    NASA Astrophysics Data System (ADS)

    Rausch, Manuel K.; Kuhl, Ellen

    2014-02-01

    Despite their seemingly delicate appearance, thin biological membranes fulfill various crucial roles in the human body and can sustain substantial mechanical loads. Unlike engineering structures, biological membranes are able to grow and adapt to changes in their mechanical environment. Finite element modeling of biological growth holds the potential to better understand the interplay of membrane form and function and to reliably predict the effects of disease or medical intervention. However, standard continuum elements typically fail to represent thin biological membranes efficiently, accurately, and robustly. Moreover, continuum models are typically cumbersome to generate from surface-based medical imaging data. Here we propose a computational model for finite membrane growth using a classical midsurface representation compatible with standard shell elements. By assuming elastic incompressibility and membrane-only growth, the model a priori satisfies the zero-normal stress condition. To demonstrate its modular nature, we implement the membrane growth model into the general-purpose non-linear finite element package Abaqus/Standard using the concept of user subroutines. To probe efficiently and robustness, we simulate selected benchmark examples of growing biological membranes under different loading conditions. To demonstrate the clinical potential, we simulate the functional adaptation of a heart valve leaflet in ischemic cardiomyopathy. We believe that our novel approach will be widely applicable to simulate the adaptive chronic growth of thin biological structures including skin membranes, mucous membranes, fetal membranes, tympanic membranes, corneoscleral membranes, and heart valve membranes. Ultimately, our model can be used to identify diseased states, predict disease evolution, and guide the design of interventional or pharmaceutic therapies to arrest or revert disease progression.

  4. On the mechanics of growing thin biological membranes

    PubMed Central

    Rausch, Manuel K.; Kuhl, Ellen

    2013-01-01

    Despite their seemingly delicate appearance, thin biological membranes fulfill various crucial roles in the human body and can sustain substantial mechanical loads. Unlike engineering structures, biological membranes are able to grow and adapt to changes in their mechanical environment. Finite element modeling of biological growth holds the potential to better understand the interplay of membrane form and function and to reliably predict the effects of disease or medical intervention. However, standard continuum elements typically fail to represent thin biological membranes efficiently, accurately, and robustly. Moreover, continuum models are typically cumbersome to generate from surface-based medical imaging data. Here we propose a computational model for finite membrane growth using a classical midsurface representation compatible with standard shell elements. By assuming elastic incompressibility and membrane-only growth, the model a priori satisfies the zero-normal stress condition. To demonstrate its modular nature, we implement the membrane growth model into the general-purpose non-linear finite element package Abaqus/Standard using the concept of user subroutines. To probe efficiently and robustness, we simulate selected benchmark examples of growing biological membranes under different loading conditions. To demonstrate the clinical potential, we simulate the functional adaptation of a heart valve leaflet in ischemic cardiomyopathy. We believe that our novel approach will be widely applicable to simulate the adaptive chronic growth of thin biological structures including skin membranes, mucous membranes, fetal membranes, tympanic membranes, corneoscleral membranes, and heart valve membranes. Ultimately, our model can be used to identify diseased states, predict disease evolution, and guide the design of interventional or pharmaceutic therapies to arrest or revert disease progression. PMID:24563551

  5. MECHANISMS INVOLVED IN MYCORRHIZAL WHEAT PROTECTION AGAINST POWDERY MILDEW.

    PubMed

    Mustafa, G; Tisserant, B; Randoux, B; Fontaine, J; Sahraoui, A Lounes-Hadj; Reignault, Ph

    2014-01-01

    In France, the Ecophyto 2018 national action plan will set out to reduce the use of pesticides by 50% by 2018, if possible. To achieve this goal, the use of arbuscular mycorrhizal (AM) fungi could be a potential alternative method allowing the control of crop diseases. The inoculation by AM fungi has been demonstrated to protect plants against soil-borne pathogens, but little is known about their effectiveness against aerial pathogens, such as the biotrophic fungus Blumeria graminis f.sp. tritici (Bgt) causing wheat (Triticum aestivum) powdery mildew. In the present study, wheat plants were grown in pots, under controlled conditions. Using various phosphorus (P) concentrations, the effectiveness of three AM inocula (Rhizophagus irregularis (Ri), Funneliformis mosseae (Fm)) and Solrize, a mixture of Ri and Fm) in Orvantis wheat cultivar, were tested. After 42 days of culture, mycorrhizal (M) and non-mycorrhizal (NM) wheat plants were infected by Bgt. A satisfactory mycorrhizal rate was obtained with the phosphorus concentration P/5 (P corresponding to the dose used in wheat fields in = 62 mg/L). Our work shows, for the first time, (i) a protective effect of AM inoculation against wheat powdery mildew, reaching up to 73% with Fm inocula, and (ii) its ability to induce a systemic resistance in wheat. Thereafter, we investigated mechanisms involved in this protection. Control plants, M plants, infected plants by Bgt, and M-infected plants were compared at: (i) cytological level, our results revealed that papillae and whole-fluorescent cells presence was induced, conversely fungal haustorium formation in epidermal cells was reduced within M plants leaves (ii) enzymatic level-by assessing defense enzyme activities (lipoxygenase, peroxidase) known as defense markers were measured 24, 48, 72 and 96 hours after infection (hai). The importance of these activities in the defense pathways induced in wheat by AM fungi will be discussed.

  6. Biological phosphoryl-transfer reactions: understanding mechanism and catalysis.

    PubMed

    Lassila, Jonathan K; Zalatan, Jesse G; Herschlag, Daniel

    2011-01-01

    Phosphoryl-transfer reactions are central to biology. These reactions also have some of the slowest nonenzymatic rates and thus require enormous rate accelerations from biological catalysts. Despite the central importance of phosphoryl transfer and the fascinating catalytic challenges it presents, substantial confusion persists about the properties of these reactions. This confusion exists despite decades of research on the chemical mechanisms underlying these reactions. Here we review phosphoryl-transfer reactions with the goal of providing the reader with the conceptual and experimental background to understand this body of work, to evaluate new results and proposals, and to apply this understanding to enzymes. We describe likely resolutions to some controversies, while emphasizing the limits of our current approaches and understanding. We apply this understanding to enzyme-catalyzed phosphoryl transfer and provide illustrative examples of how this mechanistic background can guide and deepen our understanding of enzymes and their mechanisms of action. Finally, we present important future challenges for this field.

  7. Biological Phosphoryl-Transfer Reactions: Understanding Mechanism and Catalysis

    PubMed Central

    Lassila, Jonathan K.; Zalatan, Jesse G.; Herschlag, Daniel

    2012-01-01

    Phosphoryl-transfer reactions are central to biology. These reactions also have some of the slowest nonenzymatic rates and thus require enormous rate accelerations from biological catalysts. Despite the central importance of phosphoryl transfer and the fascinating catalytic challenges it presents, substantial confusion persists about the properties of these reactions. This confusion exists despite decades of research on the chemical mechanisms underlying these reactions. Here we review phosphoryl-transfer reactions with the goal of providing the reader with the conceptual and experimental background to understand this body of work, to evaluate new results and proposals, and to apply this understanding to enzymes. We describe likely resolutions to some controversies, while emphasizing the limits of our current approaches and understanding. We apply this understanding to enzyme-catalyzed phosphoryl transfer and provide illustrative examples of how this mechanistic background can guide and deepen our understanding of enzymes and their mechanisms of action. Finally, we present important future challenges for this field. PMID:21513457

  8. Mechanical engineering problems in preserving biological objects by temperature lowering.

    PubMed

    Dvorák, Z

    1990-01-01

    Analysis of dangers caused by mechanical refrigerating and liquid nitrogen systems used for low temperature preserving of biological material and safety measures to be adopted. Hazards are caused by moving or protruding parts of the machinery, its hot parts, noise and vibration, work in cold rooms, possible destruction of pressure vessels, refrigerant inflammation or explosion, breathing the refrigerant or its decomposition products, direct contact of the refrigerant with the skin or mucous tissues, depletion of stratospheric ozone or contamination of food-stuffs.

  9. Mechanisms for control of biological electron transfer reactions

    PubMed Central

    Williamson, Heather R.; Dow, Brian A.; Davidson, Victor L.

    2014-01-01

    Electron transfer (ET) through and between proteins is a fundamental biological process. The rates and mechanisms of these ET reactions are controlled by the proteins in which the redox centers that donate and accept electrons reside. The protein influences the magnitudes of the ET parameters, the electronic coupling and reorganization energy that are associated with the ET reaction. The protein can regulate the rates of the ET reaction by requiring reaction steps to optimize the system for ET, leading to kinetic mechanisms of gated or coupled ET. Amino acid residues in the segment of the protein through which long range ET occurs can also modulate the ET rate by serving as staging points for hopping mechanisms of ET. Specific examples are presented to illustrate these mechanisms by which proteins control rates of ET reactions. PMID:25085775

  10. Large-scale study of the interactions between proteins involved in type IV pilus biology in Neisseria meningitidis: characterization of a subcomplex involved in pilus assembly.

    PubMed

    Georgiadou, Michaella; Castagnini, Marta; Karimova, Gouzel; Ladant, Daniel; Pelicic, Vladimir

    2012-06-01

    The functionally versatile type IV pili (Tfp) are one of the most widespread virulence factors in bacteria. However, despite generating much research interest for decades, the molecular mechanisms underpinning the various aspects of Tfp biology remain poorly understood, mainly because of the complexity of the system. In the human pathogen Neisseria meningitidis for example, 23 proteins are dedicated to Tfp biology, 15 of which are essential for pilus biogenesis. One of the important gaps in our knowledge concerns the topology of this multiprotein machinery. Here we have used a bacterial two-hybrid system to identify and quantify the interactions between 11 Pil proteins from N. meningitidis. We identified 20 different binary interactions, many of which are novel. This represents the most complex interaction network between Pil proteins reported to date and indicates, among other things, that PilE, PilM, PilN and PilO, which are involved in pilus assembly, indeed interact. We focused our efforts on this subset of proteins and used a battery of assays to determine the membrane topology of PilN and PilO, map the interaction domains between PilE, PilM, PilN and PilO, and show that a widely conserved N-terminal motif in PilN is essential for both PilM-PilN interactions and pilus assembly. Finally, we show that PilP (another protein involved in pilus assembly) forms a complex with PilM, PilN and PilO. Taken together, these findings have numerous implications for understanding Tfp biology and provide a useful blueprint for future studies.

  11. Technical key and mechanism of laser-involved therapy

    NASA Astrophysics Data System (ADS)

    Tian, Zhaobing; Zhang, Dan; Gao, Feng

    1997-06-01

    The method of laser-involved therapy can be classified as the following: (1) intravascular low level He-Ne laser irradiation therapy; (2) light-oxygen-blood therapy; (3) light-oxygen-blood therapy. The key of laser-involved therapy is the proper wavelength light. The use of energy in laser-involved therapy is different from that in laser acupuncture. Of all kinds of light-involved therapy, oxygen has direct influence on the curative effect. Oxygen can be thought as the carrier of laser energy. Having absorbed the photon, the oxygen get excited and reaches every part of the organism through blood circulation, which promotes physiological and biochemistry reaction and therefore improves the metabolism.

  12. Modular elastic patches – mechanical and biological effects

    PubMed Central

    Serban, Monica A.; Kluge, Jonathan A.; Laha, Michael M.; Kaplan, David L.

    2010-01-01

    A modular approach to engineering crosslinked elastic biomaterials is presented for fine tuning of material mechanical and biological properties. The three components, soluble elastin, hyaluronic acid and silk fibroin, contribute with different features to the overall properties of the final material system. The elastic biomaterial is chemically crosslinked via interaction between primary amine groups naturally present on the two proteins, silk and elastin, or chemically introduced on hyaluronan and N-succinimide functionalities of the crosslinker. The materials obtained by crosslinking the three components in different ratios have Young’s moduli ranging from ~700 kPa to 100 kPa, strain to failure between ~ 65-15 % and ultimate tensile strengths of ~ 50 to 20 kPa. The biological effects and enzymatic degradation rates of the different composites are also different based on material composition. These findings further underline the strength of modular, multi-component systems in creating a range of biomaterials, targeted tissue engineering and regenerative medicine applications, with application-tailored mechanical and biological properties. PMID:20712340

  13. Interaction mechanisms and biological effects of static magnetic fields

    SciTech Connect

    Tenforde, T.S.

    1994-06-01

    Mechanisms through which static magnetic fields interact with living systems are described and illustrated by selected experimental observations. These mechanisms include electrodynamic interactions with moving, ionic charges (blood flow and nerve impulse conduction), magnetomechanical interactions (orientation and translation of molecules structures and magnetic particles), and interactions with electronic spin states in charge transfer reactions (photo-induced electron transfer in photosynthesis). A general summary is also presented of the biological effects of static magnetic fields. There is convincing experimental evidence for magnetoreception mechanisms in several classes of lower organisms, including bacteria and marine organisms. However, in more highly evolved species of animals, there is no evidence that the interactions of static magnetic fields with flux densities up to 2 Tesla (1 Tesla [T] = 10{sup 4} Gauss) produce either behavioral or physiolocical alterations. These results, based on controlled studies with laboratory animals, are consistent with the outcome of recent epidemiological surveys on human populations exposed occupationally to static magnetic fields.

  14. Mechanism of long-range proton translocation along biological membranes.

    PubMed

    Medvedev, Emile S; Stuchebrukhov, Alexei A

    2013-02-14

    Recent experiments suggest that protons can travel along biological membranes up to tens of micrometers, but the mechanism of transport is unknown. To explain such a long-range proton translocation we describe a model that takes into account the coupled bulk diffusion that accompanies the migration of protons on the surface. We show that protons diffusing at or near the surface before equilibrating with the bulk desorb and re-adsorb at the surface thousands of times, giving rise to a power-law desorption kinetics. As a result, the decay of the surface protons occurs very slowly, allowing for establishing local gradient and local exchange, as was envisioned in the early local models of biological energy transduction.

  15. Using Quantum Mechanical Approaches to Study Biological Systems

    PubMed Central

    2015-01-01

    Conspectus Quantum mechanics (QM) has revolutionized our understanding of the structure and reactivity of small molecular systems. Given the tremendous impact of QM in this research area, it is attractive to believe that this could also be brought into the biological realm where systems of a few thousand atoms and beyond are routine. Applying QM methods to biological problems brings an improved representation to these systems by the direct inclusion of inherently QM effects such as polarization and charge transfer. Because of the improved representation, novel insights can be gleaned from the application of QM tools to biomacromolecules in aqueous solution. To achieve this goal, the computational bottlenecks of QM methods had to be addressed. In semiempirical theory, matrix diagonalization is rate limiting, while in density functional theory or Hartree–Fock theory electron repulsion integral computation is rate-limiting. In this Account, we primarily focus on semiempirical models where the divide and conquer (D&C) approach linearizes the matrix diagonalization step with respect to the system size. Through the D&C approach, a number of applications to biological problems became tractable. Herein, we provide examples of QM studies on biological systems that focus on protein solvation as viewed by QM, QM enabled structure-based drug design, and NMR and X-ray biological structure refinement using QM derived restraints. Through the examples chosen, we show the power of QM to provide novel insights into biological systems, while also impacting practical applications such as structure refinement. While these methods can be more expensive than classical approaches, they make up for this deficiency by the more realistic modeling of the electronic nature of biological systems and in their ability to be broadly applied. Of the tools and applications discussed in this Account, X-ray structure refinement using QM models is now generally available to the community in the

  16. Homing orientation in salamanders: A mechanism involving chemical cues

    NASA Technical Reports Server (NTRS)

    Madison, D. M.

    1972-01-01

    A detailed description is given of experiments made to determine the senses and chemical cues used by salamanders for homing orientation. Sensory impairment and cue manipulative techniques were used in the investigation. All experiments were carried out at night. Results show that sense impaired animals did not home as readily as those who were blind but retained their sensory mechanism. This fact suggests that the olfactory mechanism is necessary for homing in the salamander. It was determined that after the impaired salamander regenerated its sensory mechanism it too returned home. It was concluded that homing ability in salamanders is direction independent, distant dependent, and vision independent.

  17. [Classical dengue transmission dynamics involving mechanical control and prophylaxis].

    PubMed

    Toro-Zapata, Hernán D; Restrepo, Leonardo D; Vergaño-Salazar, Juan G; Muñoz-Loaiza, Aníbal

    2010-12-01

    Dengue fever transmission dynamics were studied in an endemic region considering the use of preventative measures and mechanical control in reducing transmission of the disease. A system of ordinary differential equations was proposed, describing the dynamics and their evolution as determined by numerical simulation. Different mechanical control and prophylaxis strategies were compared to the situation without control. The basic reproduction number R₀ was determined R₀ to show that if R₀ > 1 there would be a risk of an epidemic and otherwise the disease would have low impact levels. The basic reproduction number helps determine the dynamics' future pattern and contrast the results so obtained with those obtained numerically. It was concluded that although prophylaxis and mechanical control alone provide effective results in controlling the disease, if both controls are combined then infection levels become significantly reduced. Around 60 % mechanical control and prevention levels are needed to provide suitable results in controlling dengue outbreaks.

  18. Mechanisms Involved in Virus-Induced Neural Cell Death

    DTIC Science & Technology

    2001-09-01

    We are using experimental infection with reoviruses as a model to study how viruses induce cell death (apoptosis) and cause dysregulation of the cell...and their ligand (TRAIL). Apoptosis involves both death-receptor (DR) and mitochondrial-associated cell death pathways, and leads to the early

  19. Molecular mechanism(s) involved in differential expression of vitamin C transporters along the intestinal tract.

    PubMed

    Subramanian, Veedamali S; Srinivasan, Padmanabhan; Wildman, Alexis J; Marchant, Jonathan S; Said, Hamid M

    2017-04-01

    Mammalian cells utilize two transporters for the uptake of ascorbic acid (AA), Na(+)-dependent vitamin C transporter SVCT-1 and SVCT-2. In the intestine, these transporters are involved in AA absorption and are expressed at the apical and basolateral membrane domains of the polarized epithelia, respectively. Little is known about the differential expression of these two transporters along the anterior-posterior axis of the intestinal tract and the molecular mechanism(s) that dictate this pattern of expression. We used mouse and human intestinal cDNAs to address these issues. The results showed a significantly lower rate of carrier-mediated AA uptake by mouse colon than jejunum. This was associated with a significantly lower level of expression of SVCT-1 and SVCT-2 at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels in the colon than the jejunum, implying the involvement of transcriptional mechanism(s). Similarly, expression levels of SVCT-1 and SVCT-2 mRNA and hnRNA were significantly lower in human colon. We also examined the levels of expression of hepatocyte nuclear factor 1α and specificity protein 1, which drive transcription of the Slc23a1 and Slc23a2 promoters, respectively, and found them to be markedly lower in the colon. Furthermore, significantly lower levels of the activating markers for histone (H3) modifications [H3 trimethylation of lysine 4 (H3K4me3) and H3 triacetylation of lysine 9 (H3K9ac)] were observed in the Slc23a1 and Slc23a2 promoters in the colon. These findings show, for the first time, that SVCT-1 and SVCT-2 are differentially expressed along the intestinal tract and that this pattern of expression is, at least in part, mediated via transcriptional/epigenetic mechanisms.NEW & NOTEWORTHY Our findings show, for the first time, that transporters of the water-soluble vitamin ascorbic acid (i.e., the vitamin C transporters SVCT-1 and SVCT-2) are differentially expressed along the length of the intestinal tract and that the

  20. [New mechanisms of biological effects of electromagnetic fields].

    PubMed

    Buchachenko, A L; Kuznetsov, D A; Berdinskiĭ, V L

    2006-01-01

    The production of ATP in mitochondria depends on the magnesium nuclear spin and magnetic moment of a Mg2+ ion in creatine kinase and ATPase. This suggests that enzymatic synthesis of ATP is an ion-radical process and thus depends on the external magnetic field (magnetobiology originates from this fact) and microwave fields, which control the spin states of ion-radical pairs and affect the ATP synthesis. The chemical mechanism of ATP synthesis and the origin of biological effects of electromagnetic (microwave) fields are discussed.

  1. Diurnal rhythmicity in biological processes involved in bioavailability of functional food factors.

    PubMed

    Tsurusaki, Takashi; Sakakibara, Hiroyuki; Aoshima, Yoshiki; Yamazaki, Shunsuke; Sakono, Masanobu; Shimoi, Kayoko

    2013-05-01

    In the past few decades, many types of functional factors have been identified in dietary foods; for example, flavonoids are major groups widely distributed in the plant kingdom. However, the absorption rates of the functional food factors are usually low, and many of these are difficult to be absorbed in the intact forms because of metabolization by biological processes during absorption. To gain adequate beneficial effects, it is therefore mandatory to know whether functional food factors are absorbed in sufficient quantity, and then reach target organs while maintaining beneficial effects. These are the reasons why the bioavailability of functional food factors has been well investigated using rodent models. Recently, many of the biological processes have been reported to follow diurnal rhythms recurring every 24 h. Therefore, absorption and metabolism of functional food factors influenced by the biological processes may vary with time of day. Consequently, the evaluation of the bioavailability of functional food factors using rodent models should take into consideration the timing of consumption. In this review, we provide a perspective overview of the diurnal rhythm of biological processes involved in the bioavailability of functional food factors, particularly flavonoids.

  2. Ochratoxin A carcinogenicity involves a complex network of epigenetic mechanisms.

    PubMed

    Marin-Kuan, Maricel; Cavin, Christophe; Delatour, Thierry; Schilter, Benoît

    2008-08-01

    Ochratoxin A (OTA) is a mycotoxin occurring in a wide range of food products. Because of the limitation of human epidemiological data, the safety significance of OTA in food has to rely on animal data, with renal toxicity and carcinogenicity being considered the pivotal effects. The elucidation of the mechanism of action would improve the use of experimental animal data for risk assessment. Direct genotoxicity versus epigenetic mechanisms appears to be a key question. In the present review, the increasingly documented epigenetic cellular effects of OTA and their potential toxicological relevance are discussed. The information available suggests that OTA is unlikely to act through a single, well-defined mechanism of action. Instead, it is proposed that a network of interacting epigenetic mechanisms, including protein synthesis inhibition, oxidative stress and the activation of specific cell signalling pathways, is responsible for OTA carcinogenicity. From a risk assessment perspective, it has to be noted that the mechanisms proposed above depend mainly upon gene expression and enzyme activation, and are, therefore, likely to be thresholded.

  3. Mechanisms of molecular mimicry involving the microbiota in neurodegeneration.

    PubMed

    Friedland, Robert P

    2015-01-01

    The concept of molecular mimicry was established to explain commonalities of structure which developed in response to evolutionary pressures. Most examples of molecular mimicry in medicine have involved homologies of primary protein structure which cause disease. Molecular mimicry can be expanded beyond amino acid sequence to include microRNA and proteomic effects which are either pathogenic or salutogenic (beneficial) in regard to Parkinson's disease, Alzheimer's disease, and related disorders. Viruses of animal or plant origin may mimic nucleotide sequences of microRNAs and influence protein expression. Both Parkinson's and Alzheimer's diseases involve the formation of transmissible self-propagating prion-like proteins. However, the initiating factors responsible for creation of these misfolded nucleating factors are unknown. Amyloid patterns of protein folding are highly conserved through evolution and are widely distributed in the world. Similarities of tertiary protein structure may be involved in the creation of these prion-like agents through molecular mimicry. Cross-seeding of amyloid misfolding, altered proteostasis, and oxidative stress may be induced by amyloid proteins residing in bacteria in our microbiota in the gut and in the diet. Pathways of molecular mimicry induced processes induced by bacterial amyloid in neurodegeneration may involve TLR 2/1, CD14, and NFκB, among others. Furthermore, priming of the innate immune system by the microbiota may enhance the inflammatory response to cerebral amyloids (such as amyloid-β and α-synuclein). This paper describes the specific molecular pathways of these cross-seeding and neuroinflammatory processes. Evolutionary conservation of proteins provides the opportunity for conserved sequences and structures to influence neurological disease through molecular mimicry.

  4. Ultrasound-Induced New Cellular Mechanism Involved in Drug Resistance

    PubMed Central

    Hassan, Mariame A.; Furusawa, Yukihiro; Minemura, Masami; Rapoport, Natalya; Sugiyama, Toshiro; Kondo, Takashi

    2012-01-01

    The acoustic effects in a biological milieu offer several scenarios for the reversal of multidrug resistance. In this study, we have observed higher sensitivity of doxorubicin-resistant uterine sarcoma MES-SA/DX5 cells to ultrasound exposure compared to its parent counterpart MES-SA cells; however, the results showed that the acoustic irradiation was genotoxic and could promote neotic division in exposed cells that was more pronounced in the resistant variant. The neotic progeny, imaged microscopically 24 hr post sonication, could contribute in modulating the final cell survival when an apoptotic dose of doxorubicin was combined with ultrasound applied either simultaneously or sequentially in dual-treatment protocols. Depending on the time and order of application of ultrasound and doxorubicin in combination treatments, there was either desensitization of the parent cells or sensitization of the resistant cells to doxorubicin action. PMID:23284614

  5. Quantitative nano-mechanics of biological cells with AFM

    NASA Astrophysics Data System (ADS)

    Sokolov, Igor

    2013-03-01

    The importance of study of living cells is hard to overestimate. Cell mechanics is a relatively young, yet not a well-developed area. Besides just a fundamental interest, large practical need has emerged to measure cell mechanics quantitatively. Recent studies revealed a significant correlation between stiffness of biological cells and various human diseases, such as cancer, malaria, arthritis, and even aging. However, really quantitative studies of mechanics of biological cells are virtually absent. It is not even clear if the cell, being a complex and heterogeneous object, can be described by the elastic modulus at all. Atomic force microscopy (AFM) is a natural instrument to study properties of cells in their native environments. Here we will demonstrate that quantitative measurements of elastic modulus of cells with AFM are possible. Specifically, we will show that the ``cell body'' (cell without ``brush'' surface layer, a non-elastic layer surrounding cells) typically demonstrates the response of a homogeneous elastic medium up to the deformation of 10-20%, but if and only if a) the cellular brush layer is taken into account, b) rather dull AFM probes are used. This will be justified with the help of the strong condition of elastic behavior of material: the elastic modulus is shown to be independent on the indentation depth. We will also demonstrate that an attempt either to ignore the brush layer or to use sharp AFM probes will result in the violation of the strong condition, which implies impossibility to use the concept of the elastic modulus to describe cell mechanics in such experiments. Examples of quantitative measurements of the Young's modulus of the cell body and the cell brush parameters will be given for various cells. Address when submitting: Clarkson University, Potsdam, NY 13699

  6. ALTERED IRON HOMEOSTATIS AND THE MECHANISM OF BIOLOGIC EFFECT BY PARTICLES

    EPA Science Inventory

    Several features of the clinical presentation and changes in physiology and pathology following exposure to many diverse ambient air pollution particles are comparable, suggesting a common mechanism for their biological effect. We propose that a mechanism of biological effect com...

  7. Lactose Intolerance in Adults: Biological Mechanism and Dietary Management.

    PubMed

    Deng, Yanyong; Misselwitz, Benjamin; Dai, Ning; Fox, Mark

    2015-09-18

    Lactose intolerance related to primary or secondary lactase deficiency is characterized by abdominal pain and distension, borborygmi, flatus, and diarrhea induced by lactose in dairy products. The biological mechanism and lactose malabsorption is established and several investigations are available, including genetic, endoscopic and physiological tests. Lactose intolerance depends not only on the expression of lactase but also on the dose of lactose, intestinal flora, gastrointestinal motility, small intestinal bacterial overgrowth and sensitivity of the gastrointestinal tract to the generation of gas and other fermentation products of lactose digestion. Treatment of lactose intolerance can include lactose-reduced diet and enzyme replacement. This is effective if symptoms are only related to dairy products; however, lactose intolerance can be part of a wider intolerance to variably absorbed, fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). This is present in at least half of patients with irritable bowel syndrome (IBS) and this group requires not only restriction of lactose intake but also a low FODMAP diet to improve gastrointestinal complaints. The long-term effects of a dairy-free, low FODMAPs diet on nutritional health and the fecal microbiome are not well defined. This review summarizes recent advances in our understanding of the genetic basis, biological mechanism, diagnosis and dietary management of lactose intolerance.

  8. Lactose Intolerance in Adults: Biological Mechanism and Dietary Management

    PubMed Central

    Deng, Yanyong; Misselwitz, Benjamin; Dai, Ning; Fox, Mark

    2015-01-01

    Lactose intolerance related to primary or secondary lactase deficiency is characterized by abdominal pain and distension, borborygmi, flatus, and diarrhea induced by lactose in dairy products. The biological mechanism and lactose malabsorption is established and several investigations are available, including genetic, endoscopic and physiological tests. Lactose intolerance depends not only on the expression of lactase but also on the dose of lactose, intestinal flora, gastrointestinal motility, small intestinal bacterial overgrowth and sensitivity of the gastrointestinal tract to the generation of gas and other fermentation products of lactose digestion. Treatment of lactose intolerance can include lactose-reduced diet and enzyme replacement. This is effective if symptoms are only related to dairy products; however, lactose intolerance can be part of a wider intolerance to variably absorbed, fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). This is present in at least half of patients with irritable bowel syndrome (IBS) and this group requires not only restriction of lactose intake but also a low FODMAP diet to improve gastrointestinal complaints. The long-term effects of a dairy-free, low FODMAPs diet on nutritional health and the fecal microbiome are not well defined. This review summarizes recent advances in our understanding of the genetic basis, biological mechanism, diagnosis and dietary management of lactose intolerance. PMID:26393648

  9. Biological and mechanical implications of PEGylating proteins into hydrogel biomaterials.

    PubMed

    Gonen-Wadmany, Maya; Goldshmid, Revital; Seliktar, Dror

    2011-09-01

    Protein PEGylation has been successfully applied in pharmaceuticals and more recently in biomaterials development for making bioactive and structurally versatile hydrogels. Despite many advantages in this regard, PEGylation of proteins is also known to alter biological activity and modify biophysical characteristics in ways that may be detrimental to cells. The aim of this study was to evaluate the relative loss of biological compatibility associated with PEGylating a fibrinogen precursor into a hydrogel scaffold, in comparison to thrombin cross-linked fibrin hydrogels. Specifically, we investigated the consequences of conjugating fibrinogen with linear polyethtylene glycol (PEG) polymer chains (10 kDa) on the ability to cultivate neonatal human foreskin fibroblasts (HFFs) in 3-D. For this purpose, thrombin cross-linked fibrin (TCL-Fib) and PEGylated fibrinogen (PEG-Fib) gels were prepared with HFFs and cultured for up to seven days. The benchmark biological compatibility test was based on a combined assessment of cellular morphology, proliferation, actin expression, and matrix metalloproteinase (MMP) expression in the 3-D culture systems. The results showed correlations between modulus and proteolytic biodegradation in both materials, but no correlation between the mechanical properties and the ability of HFFs to remodel the microenvironment. A slight reduction of actin, MMPs, and spindled morphology of the cells in the PEG-Fib hydrogels indicated that the PEGylation process altered the biological compatibility of the fibrin. Nevertheless, the overall benchmark performance of the two materials demonstrated that PEGylated fibrinogen hydrogels still retains much to the inherent biofunctionality of the fibrin precursor when used as a scaffold for 3-D cell cultivation.

  10. Molecular Mechanisms of Biological Aging in Intervertebral Discs

    PubMed Central

    Vo, Nam V.; Hartman, Robert A.; Patil, Prashanti R.; Risbud, Makarand V.; Kletsas, Dimitris; Iatridis, James C.; Hoyland, Judith A.; Le Maitre, Christine L.; Sowa, Gwendolyn A.; Kang, James D.

    2016-01-01

    Advanced age is the greatest risk factor for the majority of human ailments, including spine-related chronic disability and back pain, which stem from age-associated intervertebral disc degeneration (IDD). Given the rapid global rise in the aging population, understanding the biology of intervertebral disc aging in order to develop effective therapeutic interventions to combat the adverse effects of aging on disc health is now imperative. Fortunately, recent advances in aging research have begun to shed light on the basic biological process of aging. Here we review some of these insights and organize the complex process of disc aging into three different phases to guide research efforts to understand the biology of disc aging. The objective of this review is to provide an overview of the current knowledge and the recent progress made to elucidate specific molecular mechanisms underlying disc aging. In particular, studies over the last few years have uncovered cellular senescence and genomic instability as important drivers of disc aging. Supporting evidence comes from DNA repair-deficient animal models that show increased disc cellular senescence and accelerated disc aging. Additionally, stress-induced senescent cells have now been well documented to secrete catabolic factors, which can negatively impact the physiology of neighboring cells and ECM. These along with other molecular drivers of aging are reviewed in depth to shed crucial insights into the underlying mechanisms of age-related disc degeneration. We also highlight molecular targets for novel therapies and emerging candidate therapeutics that may mitigate age-associated IDD. PMID:26890203

  11. Fluctuating Nonlinear Spring Model of Mechanical Deformation of Biological Particles

    PubMed Central

    Kononova, Olga; Snijder, Joost; Kholodov, Yaroslav; Marx, Kenneth A.; Wuite, Gijs J. L.; Roos, Wouter H.; Barsegov, Valeri

    2016-01-01

    The mechanical properties of virus capsids correlate with local conformational dynamics in the capsid structure. They also reflect the required stability needed to withstand high internal pressures generated upon genome loading and contribute to the success of important events in viral infectivity, such as capsid maturation, genome uncoating and receptor binding. The mechanical properties of biological nanoparticles are often determined from monitoring their dynamic deformations in Atomic Force Microscopy nanoindentation experiments; but a comprehensive theory describing the full range of observed deformation behaviors has not previously been described. We present a new theory for modeling dynamic deformations of biological nanoparticles, which considers the non-linear Hertzian deformation, resulting from an indenter-particle physical contact, and the bending of curved elements (beams) modeling the particle structure. The beams’ deformation beyond the critical point triggers a dynamic transition of the particle to the collapsed state. This extreme event is accompanied by a catastrophic force drop as observed in the experimental or simulated force (F)-deformation (X) spectra. The theory interprets fine features of the spectra, including the nonlinear components of the FX-curves, in terms of the Young’s moduli for Hertzian and bending deformations, and the structural damage dependent beams’ survival probability, in terms of the maximum strength and the cooperativity parameter. The theory is exemplified by successfully describing the deformation dynamics of natural nanoparticles through comparing theoretical curves with experimental force-deformation spectra for several virus particles. This approach provides a comprehensive description of the dynamic structural transitions in biological and artificial nanoparticles, which is essential for their optimal use in nanotechnology and nanomedicine applications. PMID:26821264

  12. The cytotoxic mechanism of glyoxal involves oxidative stress.

    PubMed

    Shangari, Nandita; O'Brien, Peter J

    2004-10-01

    Glyoxal is a reactive alpha-oxoaldehyde that is a physiological metabolite formed by lipid peroxidation, ascorbate autoxidation, oxidative degradation of glucose and degradation of glycated proteins. Glyoxal is capable of inducing cellular damage, like methylglyoxal (MG), but may also accelerate the rate of glycation leading to the formation of advanced glycation end-products (AGEs). However, the mechanism of glyoxal cytotoxicity has not been precisely defined. In this study we have focused on the cytotoxic effects of glyoxal and its ability to overcome cellular resistance to oxidative stress. Isolated rat hepatocytes were incubated with different concentrations of glyoxal. Glyoxal by itself was cytotoxic at 5mM, depleted GSH, formed reactive oxygen species (ROS) and collapsed the mitochondrial membrane potential. Glyoxal also induced lipid peroxidation and formaldehyde formation. Glycolytic substrates, e.g. fructose, sorbitol and xylitol inhibited glyoxal-induced cytotoxicity and prevented the decrease in mitochondrial membrane potential suggesting that mitochondrial toxicity contributed to the cytotoxic mechanism. Glyoxal cytotoxicity was prevented by the glyoxal traps d-penicillamine or aminoguanidine or ROS scavengers were also cytoprotective even when added some time after glyoxal suggesting that oxidative stress contributed to the glyoxal cytotoxic mechanism.

  13. Rough fibrils provide a toughening mechanism in biological fibers.

    PubMed

    Brown, Cameron P; Harnagea, Catalin; Gill, Harinderjit S; Price, Andrew J; Traversa, Enrico; Licoccia, Silvia; Rosei, Federico

    2012-03-27

    Spider silk is a fascinating natural composite material. Its combination of strength and toughness is unrivalled in nature, and as a result, it has gained considerable interest from the medical, physics, and materials communities. Most of this attention has focused on the one to tens of nanometer scale: predominantly the primary (peptide sequences) and secondary (β sheets, helices, and amorphous domains) structure, with some insights into tertiary structure (the arrangement of these secondary structures) to describe the origins of the mechanical and biological performance. Starting with spider silk, and relating our findings to collagen fibrils, we describe toughening mechanisms at the hundreds of nanometer scale, namely, the fibril morphology and its consequences for mechanical behavior and the dissipation of energy. Under normal conditions, this morphology creates a nonslip fibril kinematics, restricting shearing between fibrils, yet allowing controlled local slipping under high shear stress, dissipating energy without bulk fracturing. This mechanism provides a relatively simple target for biomimicry and, thus, can potentially be used to increase fracture resistance in synthetic materials.

  14. Acetylome analysis reveals the involvement of lysine acetylation in diverse biological processes in Phytophthora sojae.

    PubMed

    Li, Delong; Lv, Binna; Tan, Lingling; Yang, Qianqian; Liang, Wenxing

    2016-07-14

    Lysine acetylation is a dynamic and highly conserved post-translational modification that plays an important regulatory role in almost every aspects of cell metabolism in both eukaryotes and prokaryotes. Phytophthora sojae is one of the most important plant pathogens due to its huge economic impact. However, to date, little is known about the functions of lysine acetylation in this Phytopthora. Here, we conducted a lysine acetylome in P. sojae. Overall, 2197 lysine acetylation sites in 1150 proteins were identified. The modified proteins are involved in diverse biological processes and are localized to multiple cellular compartments. Importantly, 7 proteins involved in the pathogenicity or the secretion pathway of P. sojae were found to be acetylated. These data provide the first comprehensive view of the acetylome of P. sojae and serve as an important resource for functional analysis of lysine acetylation in plant pathogens.

  15. Acetylome analysis reveals the involvement of lysine acetylation in diverse biological processes in Phytophthora sojae

    PubMed Central

    Li, Delong; Lv, Binna; Tan, Lingling; Yang, Qianqian; Liang, Wenxing

    2016-01-01

    Lysine acetylation is a dynamic and highly conserved post-translational modification that plays an important regulatory role in almost every aspects of cell metabolism in both eukaryotes and prokaryotes. Phytophthora sojae is one of the most important plant pathogens due to its huge economic impact. However, to date, little is known about the functions of lysine acetylation in this Phytopthora. Here, we conducted a lysine acetylome in P. sojae. Overall, 2197 lysine acetylation sites in 1150 proteins were identified. The modified proteins are involved in diverse biological processes and are localized to multiple cellular compartments. Importantly, 7 proteins involved in the pathogenicity or the secretion pathway of P. sojae were found to be acetylated. These data provide the first comprehensive view of the acetylome of P. sojae and serve as an important resource for functional analysis of lysine acetylation in plant pathogens. PMID:27412925

  16. Waste-Activated Sludge Fermentation for Polyacrylamide Biodegradation Improved by Anaerobic Hydrolysis and Key Microorganisms Involved in Biological Polyacrylamide Removal

    PubMed Central

    Dai, Xiaohu; Luo, Fan; Zhang, Dong; Dai, Lingling; Chen, Yinguang; Dong, Bin

    2015-01-01

    During the anaerobic digestion of dewatered sludge, polyacrylamide (PAM), a chemical conditioner, can usually be consumed as a carbon and nitrogen source along with other organic matter (e.g., proteins and carbohydrates in the sludge). However, a significant accumulation of acrylamide monomers (AMs) was observed during the PAM biodegradation process. To improve the anaerobic hydrolysis of PAM, especially the amide hydrolysis process, and to avoid the generation of the intermediate product AM, a new strategy is reported herein that uses an initial pH of 9, 200 mg COD/L of PAM and a fermentation time of 17 d. First, response surface methodology (RSM) was applied to optimize PAM removal in the anaerobic digestion of the sludge. The biological hydrolysis of PAM reached 86.64% under the optimal conditions obtained from the RSM. Then, the mechanisms for the optimized parameters that significantly improved the biological hydrolysis of PAM were investigated by the synergistic effect of the main organic compounds in the sludge, the floc size distribution, and the enzymatic activities. Finally, semi-continuous-flow experiments for a microbial community study were investigated based on the determination of key microorganisms involved in the biological hydrolysis of PAM. PMID:26144551

  17. Molecular mechanisms involved in mammalian primary sex determination.

    PubMed

    She, Zhen-Yu; Yang, Wan-Xi

    2014-08-01

    Sex determination refers to the developmental decision that directs the bipotential genital ridge to develop as a testis or an ovary. Genetic studies on mice and humans have led to crucial advances in understanding the molecular fundamentals of sex determination and the mutually antagonistic signaling pathway. In this review, we summarize the current molecular mechanisms of sex determination by focusing on the known critical sex determining genes and their related signaling pathways in mammalian vertebrates from mice to humans. We also discuss the underlying delicate balance between testis and ovary sex determination pathways, concentrating on the antagonisms between major sex determining genes.

  18. Mechanisms involved in antibody- and complement-mediated allograft rejection

    PubMed Central

    2010-01-01

    Antibody-mediated rejection has become critical clinically because this form of rejection is usually unresponsive to conventional anti-rejection therapy, and therefore, it has been recognized as a major cause of allograft loss. Our group developed experimental animal models of vascularized organ transplantation to study pathogenesis of antibody- and complement-mediated endothelial cell injury leading to graft rejection. In this review, we discuss mechanisms of antibody-mediated graft rejection resulting from activation of complement by C1q- and MBL (mannose-binding lectin)-dependent pathways and interactions with a variety of effector cells, including macrophages and monocytes through Fcγ receptors and complement receptors. PMID:20135240

  19. The radical mechanism of biological methane synthesis by methyl-coenzyme M reductase

    SciTech Connect

    Wongnate, T.; Sliwa, D.; Ginovska, B.; Smith, D.; Wolf, M. W.; Lehnert, N.; Raugei, S.; Ragsdale, S. W.

    2016-05-19

    Methyl-coenzyme M reductase (MCR), the rate-limiting enzyme in methanogenesis and anaerobic methane oxidation, is responsible for the production of over one billion tons of methane per year. The mechanism of methane synthesis is unknown, with the two leading proposals involving either a methyl-nickel(III) (Mechanism I) or methyl radical/Ni(II)-thiolate (Mechanism II) intermediate(s). When the reaction between the active Ni(I) enzyme with substrates was studied by transient kinetic, spectroscopic and computational methods, formation of an EPR-silent Ni(II)-thiolate intermediate was positively identified by magnetic circular dichroism spectroscopy. There was no evidence for an EPR-active methyl-Ni(III) species. Temperature-dependent transient kinetic studies revealed that the activation energy for the initial catalytic step closely matched the value computed by density functional theory for Mechanism II. Thus, our results demonstrate that biological methane synthesis occurs by generation of a methyl radical.

  20. Mechanisms Involved in Osteoblast Response to Implant Surface Morphology

    NASA Astrophysics Data System (ADS)

    Boyan, Barbara D.; Lohmann, Christoph H.; Dean, David D.; Sylvia, Victor L.; Cochran, David L.; Schwartz, Zvi

    2001-08-01

    Osteoblasts respond to surface topography with altered morphology, proliferation, and differentiation. The effects observed vary with cell culture model and the topographical features of the surface. In general, increased surface roughness is associated with decreased proliferation and increased differentiation. Cell responses to hormones, growth factors, and cytokines are altered as well, as is autocrine production of these factors. The cells interact with the surface via integrin receptors, and their expression is also surface roughness-dependent. Integrin binding to cell attachment proteins activates signal transduction cascades, including those mediated by protein kinase C and phospholipase A2. These signaling pathways are also used by regulatory factors, which results in synergistic responses. Prostaglandins are important mediators of the surface effects, and both constitutive and inducible cyclooxygenase are involved.

  1. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements.

    PubMed

    Liu, Pengfei; Erez, Ayelet; Nagamani, Sandesh C Sreenath; Dhar, Shweta U; Kołodziejska, Katarzyna E; Dharmadhikari, Avinash V; Cooper, M Lance; Wiszniewska, Joanna; Zhang, Feng; Withers, Marjorie A; Bacino, Carlos A; Campos-Acevedo, Luis Daniel; Delgado, Mauricio R; Freedenberg, Debra; Garnica, Adolfo; Grebe, Theresa A; Hernández-Almaguer, Dolores; Immken, LaDonna; Lalani, Seema R; McLean, Scott D; Northrup, Hope; Scaglia, Fernando; Strathearn, Lane; Trapane, Pamela; Kang, Sung-Hae L; Patel, Ankita; Cheung, Sau Wai; Hastings, P J; Stankiewicz, Paweł; Lupski, James R; Bi, Weimin

    2011-09-16

    Complex genomic rearrangements (CGRs) consisting of two or more breakpoint junctions have been observed in genomic disorders. Recently, a chromosome catastrophe phenomenon termed chromothripsis, in which numerous genomic rearrangements are apparently acquired in one single catastrophic event, was described in multiple cancers. Here, we show that constitutionally acquired CGRs share similarities with cancer chromothripsis. In the 17 CGR cases investigated, we observed localization and multiple copy number changes including deletions, duplications, and/or triplications, as well as extensive translocations and inversions. Genomic rearrangements involved varied in size and complexities; in one case, array comparative genomic hybridization revealed 18 copy number changes. Breakpoint sequencing identified characteristic features, including small templated insertions at breakpoints and microhomology at breakpoint junctions, which have been attributed to replicative processes. The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism's life cycle.

  2. Systems Biology Approaches for Identifying Adverse Drug Reactions and Elucidating Their Underlying Biological Mechanisms

    PubMed Central

    Boland, Mary Regina; Jacunski, Alexandra; Lorberbaum, Tal; Romano, Joseph; Moskovitch, Robert; Tatonetti, Nicholas P.

    2015-01-01

    Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and post-market surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, while post-market surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work. PMID:26559926

  3. Systems biology approaches for identifying adverse drug reactions and elucidating their underlying biological mechanisms.

    PubMed

    Boland, Mary Regina; Jacunski, Alexandra; Lorberbaum, Tal; Romano, Joseph D; Moskovitch, Robert; Tatonetti, Nicholas P

    2016-01-01

    Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and postmarket surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, whereas postmarket surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work.

  4. Chemical biology at the crossroads of molecular structure and mechanism.

    PubMed

    Doudna, Jennifer A

    2005-11-01

    Chemical insight into biological function is the holy grail of structural biology. Small molecules are central players as building blocks, effectors and probes of macromolecular structure and function.

  5. Mechanisms involved in the development of chemotherapy-induced neuropathy

    PubMed Central

    Boyette-Davis, Jessica A; Walters, Edgar T; Dougherty, Patrick M

    2015-01-01

    SUMMARY Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition seen in patients undergoing treatment with common agents such as vincristine, paclitaxel, oxaliplatin and bortezomib. The mechanisms of this condition are diverse, and include an array of molecular and cellular contributions. Current research implicates genetic predispositions to this condition, which then may influence cellular responses to chemotherapy. Processes found to be influenced during CIPN include increased expression of inflammatory mediators, primarily cytokines, which can create cascading effects in neurons and glia. Changes in ion channels and neurotransmission, as well as changes in intracellular signaling and structures have been implicated in CIPN. This review explores these issues and suggests considerations for future research. PMID:26087973

  6. Kinetics and mechanisms of reactions involving small aromatic reactive intermediates

    SciTech Connect

    Lin, M.C.

    1993-12-01

    Small aromatic radicals such as C{sub 6}H{sub 5}, C{sub 6}H{sub 5}O and C{sub 6}H{sub 4} are key prototype species of their homologs. C{sub 6}H{sub 5} and its oxidation product, C{sub 6}H{sub 5}O are believed to be important intermediates which play a pivotal role in hydrocarbon combustion, particularly with regard to soot formation. Despite their fundamental importance, experimental data on the reaction mechanisms and reactivities of these species are very limited. For C{sub 6}H{sub 5}, most kinetic data except its reactions with NO and NO{sub 2}, were obtained by relative rate measurements. For C{sub 6}H{sub 5}O, the authors have earlier measured its fragmentation reaction producing C{sub 5}H{sub 5} + CO in shock waves. For C{sub 6}H{sub 4}, the only rate constant measured in the gas phase is its recombination rate at room temperature. The authors have proposed to investigate systematically the kinetics and mechanisms of this important class of molecules using two parallel laser diagnostic techniques--laser resonance absorption (LRA) and resonance enhanced multiphoton ionization mass spectrometry (REMPI/MS). In the past two years, study has been focused on the development of a new multipass adsorption technique--the {open_quotes}cavity-ring-down{close_quotes} technique for kinetic applications. The preliminary results of this study appear to be quite good and the sensitivity of the technique is at least comparable to that of the laser-induced fluorescence method.

  7. The importance of mechanical loading in bone biology and medicine.

    PubMed

    Martin, R B

    2007-01-01

    This paper discusses the premise that the skeleton is primarily a mechanical organ, and reviews the reasons that mechanical factors play a major role in bone biology. It begins by considering three basic observations: (1) Galileo's observation that bone proportions become more robust as the species' overall size increases; (2) da Vinci's observation that larger structures are inherently weaker than smaller structures subjected to the same stress; and (3) the general observation that each unit of bone mass provides structural support for about 15 units of soft tissue organ mass. Together, these observations lead to the concept that it can be advantageous to minimize bone mass, consistent with constraints on other factors. This premise is discussed here in relation to the phenomenon of bone remodeling, which is seen to serve two purposes: the adjustment of bone mass and geometry to maintain peak bone strains at their maximum tolerable values, and the continual removal of fatigue damage produced at those strain levels. Finally, it is observed that bone remodeling apparently originated approximately 250 million years ago when the first vertebrates of substantial size became weight-bearing on land, suggesting that mechanical forces associated with weight-bearing were instrumental in the evolution of bone remodeling.

  8. Mechanisms and Targets Involved in Dissemination of Ovarian Cancer

    PubMed Central

    H. WEIDLE, ULRICH; BIRZELE, FABIAN; KOLLMORGEN, GWENDLYN; RUEGER, RÜDIGER

    2016-01-01

    Ovarian carcinoma is associated with the highest death rate of all gynecological tumors. On one hand, its aggressiveness is based on the rapid dissemination of ovarian cancer cells to the peritoneum, the omentum, and organs located in the peritoneal cavity, and on the other hand, on the rapid development of resistance to chemotherapeutic agents. In this review, we focus on the metastatic process of ovarian cancer, which involves dissemination of, homing to and growth of tumor cells in distant organs, and describe promising molecular targets for possible therapeutic intervention. We provide an outline of the interaction of ovarian cancer cells with the microenvironment such as mesothelial cells, adipocytes, fibroblasts, endothelial cells, and other stromal components in the context of approaches for therapeutic interference with dissemination. The targets described in this review are discussed with respect to their validity as drivers of metastasis and to the availability of suitable efficient agents for their blockage, such as small molecules, monoclonal antibodies or antibody conjugates as emerging tools to manage this disease. PMID:27807064

  9. Nutritional systems biology modeling: from molecular mechanisms to physiology.

    PubMed

    de Graaf, Albert A; Freidig, Andreas P; De Roos, Baukje; Jamshidi, Neema; Heinemann, Matthias; Rullmann, Johan A C; Hall, Kevin D; Adiels, Martin; van Ommen, Ben

    2009-11-01

    The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today's important nutritional research questions poses a challenge for modeling to become truly integrative in the consideration and interpretation of experimental data at widely differing scales of space and time. In this review, we discuss a selection of available modeling approaches and applications relevant for nutrition. We then put these models into perspective by categorizing them according to their space and time domain. Through this categorization process, we identified a dearth of models that consider processes occurring between the microscopic and macroscopic scale. We propose a "middle-out" strategy to develop the required full-scale, multilevel computational models. Exhaustive and accurate phenotyping, the use of the virtual patient concept, and the development of biomarkers from "-omics" signatures are identified as key elements of a successful systems biology modeling approach in nutrition research--one that integrates physiological mechanisms and data at multiple space and time scales.

  10. Fluid mechanics of biological surfaces and their technological application.

    PubMed

    Bechert, D W; Bruse, M; Hage, W; Meyer, R

    2000-04-01

    A survey is given on fluid-dynamic effects caused by the structure and properties of biological surfaces. It is demonstrated that the results of investigations aiming at technological applications can also provide insights into biophysical phenomena. Techniques are described both for reducing wall shear stresses and for controlling boundary-layer separation. (a) Wall shear stress reduction was investigated experimentally for various riblet surfaces including a shark skin replica. The latter consists of 800 plastic model scales with compliant anchoring. Hairy surfaces are also considered, and surfaces in which the no-slip condition is modified. Self-cleaning surfaces such as that of lotus leaves represent an interesting option to avoid fluid-dynamic deterioration by the agglomeration of dirt. An example of technological implementation is discussed for riblets in long-range commercial aircraft. (b) Separation control is also an important issue in biology. After a few brief comments on vortex generators, the mechanism of separation control by bird feathers is described in detail. Self-activated movable flaps (= artificial bird feathers) represent a high-lift system enhancing the maximum lift of airfoils by about 20%. This is achieved without perceivable deleterious effects under cruise conditions. Finally, flight experiments on an aircraft with laminar wing and movable flaps are presented.

  11. Can We Describe Biological Systems with Quantum Mechanics?

    NASA Astrophysics Data System (ADS)

    Granados-Ramírez, C. G.; Benítez-Cardoza, C. G.; Carbajal-Tinoco, M. D.

    2016-03-01

    Quantum Mechanics is the favourite theory to predict the structure of any group of atoms, including biological molecules. Due to numerous difficulties, however, it is necessary to introduce a series of approximations to overcome such impediments. We present a coarse-grained model of circular dichroism (CD) that is based on the theory of optical activity, developed by DeVoe, in order to predict CD spectra. In first stage, we determine the polarisability of individual monomers (residues, in the case of peptides) from experiments of molar absorptivity. The complex polarisabilities are used together with peptide structures obtained by density functional theory and other methods to determine their corresponding CD spectra, which are in reasonable agreement with their experimental counterparts.

  12. Quantum information and the problem of mechanisms of biological evolution.

    PubMed

    Melkikh, Alexey V

    2014-01-01

    One of the most important conditions for replication in early evolution is the de facto elimination of the conformational degrees of freedom of the replicators, the mechanisms of which remain unclear. In addition, realistic evolutionary timescales can be established based only on partially directed evolution, further complicating this issue. A division of the various evolutionary theories into two classes has been proposed based on the presence or absence of a priori information about the evolving system. A priori information plays a key role in solving problems in evolution. Here, a model of partially directed evolution, based on the learning automata theory, which includes a priori information about the fitness space, is proposed. A potential repository of such prior information is the states of biologically important molecules. Thus, the need for extended evolutionary synthesis is discussed. Experiments to test the hypothesis of partially directed evolution are proposed.

  13. Mechanical systems biology of C. elegans touch sensation

    PubMed Central

    Krieg, Michael; Dunn, Alex; Goodman, Miriam B.

    2015-01-01

    The sense of touch informs us of the physical properties of our surroundings and is a critical aspect of communication. Before touches are perceived, mechanical signals are transmitted quickly and reliably from the skin’s surface to mechano-electrical transduction channels embedded within specialized sensory neurons. We are just beginning to understand how soft tissues participate in force transmission and how they are deformed. Here, we review empirical and theoretical studies of single molecules and molecular ensembles thought to be involved in mechanotransmission and apply the concepts emerging from this work to the sense of touch. We focus on the nematode Caenorhabditis elegans as a well-studied model for touch sensation in which mechanics can be studied on the molecular, cellular, and systems level. Finally, we conclude that force transmission is an emergent property of macromolecular cellular structures that mutually stabilize one another. PMID:25597279

  14. Involvement of ASR genes in aluminium tolerance mechanisms in rice.

    PubMed

    Arenhart, Rafael Augusto; Lima, Julio César de; Pedron, Marcelo; Carvalho, Fabricio E L; Silveira, Joaquim Albenisio Gomes da; Rosa, Silvia Barcelos; Caverzan, Andreia; Andrade, Claudia M B; Schünemann, Mariana; Margis, Rogério; Margis-Pinheiro, Márcia

    2013-01-01

    Among cereal crops, rice is considered the most tolerant to aluminium (Al). However, variability among rice genotypes leads to remarkable differences in the degree of Al tolerance for distinct cultivars. A number of studies have demonstrated that rice plants achieve Al tolerance through an unknown mechanism that is independent of root tip Al exclusion. We have analysed expression changes of the rice ASR gene family as a function of Al treatment. The gene ASR5 was differentially regulated in the Al-tolerant rice ssp. Japonica cv. Nipponbare. However, ASR5 expression did not respond to Al exposure in Indica cv. Taim rice roots, which are highly Al sensitive. Transgenic plants carrying RNAi constructs that targeted the ASR genes were obtained, and increased Al susceptibility was observed in T1 plants. Embryogenic calli of transgenic rice carrying an ASR5-green fluorescent protein fusion revealed that ASR5 was localized in both the nucleus and cytoplasm. Using a proteomic approach to compare non-transformed and ASR-RNAi plants, a total of 41 proteins with contrasting expression patterns were identified. We suggest that the ASR5 protein acts as a transcription factor to regulate the expression of different genes that collectively protect rice cells from Al-induced stress responses.

  15. Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium.

    PubMed

    Mdluli, K; Swanson, J; Fischer, E; Lee, R E; Barry, C E

    1998-03-01

    Isoniazid (INH), which acts by inhibiting mycolic acid biosynthesis, is very potent against the tuberculous mycobacteria. It is about 100-fold less effective against Mycobacterium avium. This difference has often been attributed to a decreased permeability of the cell wall. We measured the rate of conversion of radiolabelled INH to 4-pyridylmethanol by whole cells and cell-free extracts and estimated the permeability barrier imposed by the cell wall to INH influx in Mycobacterium tuberculosis and M. avium. There was no significant difference in the relative permeability to INH between these two species. However, the total conversion rate in M. tuberculosis was found to be four times greater. Examination of in vitro-generated mutants revealed that the major resistance mechanism for both species is loss of the catalase-peroxidase KatG. Analysis of lipid and protein biosynthetic profiles demonstrated that the molecular target of activated INH was identical for both species. M. avium, however, formed colonies at INH concentrations inhibitory for mycolic acid biosynthesis. These mycolate-deficient M. avium exhibited altered colony morphologies, modified cell wall ultrastructure and were 10-fold more sensitive to treatment with hydrophobic antibiotics, such as rifampin. These findings may significantly impact the design of new therapeutic regimens for the treatment of infections with atypical mycobacteria.

  16. Mechanisms involved in cholesterol-induced neuronal insulin resistance.

    PubMed

    Taghibiglou, Changiz; Bradley, Clarrisa A; Gaertner, Tara; Li, Yuping; Wang, Yushan; Wang, Yu Tian

    2009-09-01

    Insulin receptors (IRs) are highly expressed in the central nervous system (CNS) and play an important role in normal brain functions, such as learning and memory. Due to the increasing rate of obesity in western societies and overall high fat diets, the incidents of neuronal insulin resistance is also on the rise, but the underlying mechanism is still poorly characterized. We found that cholesterol treatment produces robust insulin signaling resistance that is characterized by the marked reduction in insulin-stimulated tyrosine phosphorylation of the IR and its downstream targets insulin receptor substrate 1 (IRS1) and 2 (IRS2). Surface expression of IRs was also decreased and was correlated with an increase in facilitated receptor endocytosis. Membrane fractionation showed that after cholesterol treatment, the proportion of IRs localized in the lipid raft increased and correspondingly there was a reduction of IRs in the non-raft membrane. Interestingly, we found that IRs in the lipid rafts, unlike their counterparts in the non-raft membrane domain, were essentially unresponsive to insulin stimulation and that a high level of tyrosine phosphatase activity was associated with these raft fractions. Our results suggest that the lipid raft microdomain of the neuronal plasma membrane has a strong influence on IR signaling, and that incorporation of high levels of cholesterol may reduce IR signaling by increasing their representation in lipid rafts. The trapping of the IR in the lipid raft domain may result in its inactivation and promote its endocytosis: effects that could contribute to neuronal insulin resistance in obesity.

  17. Mechanisms involved in the developmental programming of adulthood disease.

    PubMed

    Warner, Matthew J; Ozanne, Susan E

    2010-04-14

    There are many instances in life when the environment plays a critical role in the health outcomes of an individual, yet none more so than those experienced in fetal and neonatal life. One of the most detrimental environmental problems encountered during this critical growth period are changes in nutrition to the growing fetus and newborn. Disturbances in the supply of nutrients and oxygen to the fetus can not only lead to adverse fetal growth patterns, but they have also been associated with the development of features of metabolic syndrome in adult life. This fetal response has been termed developmental programming or the developmental origins of health and disease. The present review focuses on the epidemiological studies that identified this association and the importance that animal models have played in studying this concept. We also address the potential mechanisms that may underpin the developmental programming of future disease. It also highlights (i) how developmental plasticity, although beneficial for short-term survival, can subsequently programme glucose intolerance and insulin resistance in adult life by eliciting changes in key organ structures and the epigenome, and (ii) how aberrant mitochondrial function can potentially lead to the development of Type 2 diabetes and other features of metabolic syndrome.

  18. Mechanism involved in enhancement of osteoblast differentiation by hyaluronic acid

    SciTech Connect

    Kawano, Michinao; Ariyoshi, Wataru; Iwanaga, Kenjiro; Okinaga, Toshinori; Habu, Manabu; Yoshioka, Izumi; Tominaga, Kazuhiro; Nishihara, Tatsuji

    2011-02-25

    Research highlights: {yields} In this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. {yields} MG63 cells were incubated with BMP-2 and HA for various time periods. {yields} Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. {yields} HA enhanced BMP-2 induces osteoblastic differentiation in MG63 cells via down-regulation of BMP-2 antagonists and ERK phosphorylation. -- Abstract: Objectives: Bone morphogenetic protein-2 (BMP-2) is expected to be utilized to fill bone defects and promote healing of fractures. However, it is unable to generate an adequate clinical response for use in bone regeneration. Recently, it was reported that glycosaminoglycans, including heparin, heparan sulfate, keratan sulfate, dermatan sulfate, chondroitin-4-sulfate, chondroitin-6-sulfate, and hyaluronic acid (HA), regulate BMP-2 activity, though the mechanism by which HA regulates osteogenic activities has not been fully elucidated. The aim of this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. Materials and methods: Monolayer cultures of osteoblastic lineage MG63 cells were incubated with BMP-2 and HA for various time periods. To determine osteoblastic differentiation, alkaline phosphatase (ALP) activity in the cell lysates was quantified. Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by Western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. To further elucidate the role of HA in enhancement of BMP-2-induced Smad signaling, mRNA expressions of the BMP-2 receptor antagonists noggin and follistatin were detected using real-time RT-PCR. Results: BMP-2-induced ALP activation, Smad 1/5/8 phosphorylation, and

  19. Influences of mechanical pretreatment on the non-biological treatment of municipal wastewater by forward osmosis.

    PubMed

    Hey, Tobias; Zarebska, Agata; Bajraktari, Niada; Vogel, Jörg; Hélix-Nielsen, Claus; la Cour Jansen, Jes; Jönsson, Karin

    2016-11-24

    Municipal wastewater treatment involves mechanical, biological and chemical treatment steps for protecting the environment from adverse effects. The biological treatment step consumes the most energy and can create greenhouse gases. This study investigates municipal wastewater treatment without the biological treatment step, including the effects of different pretreatment configurations, for example, direct membrane filtration before forward osmosis. Forward osmosis was tested using raw wastewater and wastewater subjected to different types of mechanical pretreatment, for example, microsieving and microfiltration permeation, as a potential technology for municipal wastewater treatment. Forward osmosis was performed using Aquaporin Inside™ and Hydration Technologies Inc. (HTI) membranes with NaCl as the draw solution. Both types of forward osmosis membranes were tested in parallel for the different types of pretreated feed and evaluated in terms of water flux and solute rejection, that is, biochemical oxygen demand (BOD7) and total and soluble phosphorus contents. The Aquaporin and HTI membranes achieved a stable water flux with rejection rates of more than 96% for BOD7 and total and soluble phosphorus, regardless of the type of mechanical pretreated wastewater considered. This result indicates that forward osmosis membranes can tolerate exposure to municipal waste water and that the permeate can fulfil the Swedish discharge limits.

  20. Effects of Ionizing Radiation on Biological Molecules—Mechanisms of Damage and Emerging Methods of Detection

    PubMed Central

    Reisz, Julie A.; Bansal, Nidhi; Qian, Jiang; Zhao, Weiling

    2014-01-01

    Abstract Significance: The detrimental effects of ionizing radiation (IR) involve a highly orchestrated series of events that are amplified by endogenous signaling and culminating in oxidative damage to DNA, lipids, proteins, and many metabolites. Despite the global impact of IR, the molecular mechanisms underlying tissue damage reveal that many biomolecules are chemoselectively modified by IR. Recent Advances: The development of high-throughput “omics” technologies for mapping DNA and protein modifications have revolutionized the study of IR effects on biological systems. Studies in cells, tissues, and biological fluids are used to identify molecular features or biomarkers of IR exposure and response and the molecular mechanisms that regulate their expression or synthesis. Critical Issues: In this review, chemical mechanisms are described for IR-induced modifications of biomolecules along with methods for their detection. Included with the detection methods are crucial experimental considerations and caveats for their use. Additional factors critical to the cellular response to radiation, including alterations in protein expression, metabolomics, and epigenetic factors, are also discussed. Future Directions: Throughout the review, the synergy of combined “omics” technologies such as genomics and epigenomics, proteomics, and metabolomics is highlighted. These are anticipated to lead to new hypotheses to understand IR effects on biological systems and improve IR-based therapies. Antioxid. Redox Signal. 21: 260–292. PMID:24382094

  1. A mechanism for biologically induced iodine emissions from sea ice

    NASA Astrophysics Data System (ADS)

    Saiz-Lopez, A.; Blaszczak-Boxe, C. S.; Carpenter, L. J.

    2015-09-01

    Ground- and satellite-based measurements have reported high concentrations of iodine monoxide (IO) in coastal Antarctica. The sources of such a large iodine burden in the coastal Antarctic atmosphere remain unknown. We propose a mechanism for iodine release from sea ice based on the premise that micro-algae are the primary source of iodine emissions in this environment. The emissions are triggered by the biological production of iodide (I-) and hypoiodous acid (HOI) from micro-algae (contained within and underneath sea ice) and their diffusion through sea-ice brine channels, ultimately accumulating in a thin brine layer (BL) on the surface of sea ice. Prior to reaching the BL, the diffusion timescale of iodine within sea ice is depth-dependent. The BL is also a vital component of the proposed mechanism as it enhances the chemical kinetics of iodine-related reactions, which allows for the efficient release of iodine to the polar boundary layer. We suggest that iodine is released to the atmosphere via three possible pathways: (1) emitted from the BL and then transported throughout snow atop sea ice, from where it is released to the atmosphere; (2) released directly from the BL to the atmosphere in regions of sea ice that are not covered with snowpack; or (3) emitted to the atmosphere directly through fractures in the sea-ice pack. To investigate the proposed biology-ice-atmosphere coupling at coastal Antarctica we use a multiphase model that incorporates the transport of iodine species, via diffusion, at variable depths, within brine channels of sea ice. Model simulations were conducted to interpret observations of elevated springtime IO in the coastal Antarctic, around the Weddell Sea. While a lack of experimental and observational data adds uncertainty to the model predictions, the results nevertheless show that the levels of inorganic iodine (i.e. I2, IBr, ICl) released from sea ice through this mechanism could account for the observed IO concentrations during

  2. Mechanism(S) Involved in the Colon-Specific Expression of the Thiamine Pyrophosphate (Tpp) Transporter.

    PubMed

    Nabokina, Svetlana M; Ramos, Mel Brendan; Said, Hamid M

    2016-01-01

    Microbiota of the large intestine synthesizes considerable amount of vitamin B1 (thiamine) in the form of thiamine pyrophosphate (TPP). We have recently demonstrated the existence of an efficient and specific carrier-mediated uptake process for TPP in human colonocytes, identified the TPP transporter (TPPT) involved (product of the SLC44A4 gene), and shown that expression of TPPT along the gastrointestinal (GI) tract is restricted to the colon. Our aim in this study was to determine the molecular basis of the colon-specific expression of TPPT focusing on a possible epigenetic mechanism. Our results showed that the CpG island predicted in the SLC44A4 promoter is non-methylated in the human colonic epithelial NCM460 cells, but is hyper-methylated in the human duodenal epithelial HuTu80 cells (as well as in the human retinal pigment epithelial ARPE19 cells). In the mouse (where TPPT expression in the GI tract is also restricted to the colon), the CpG island predicted in the Slc44a4 promoter is non-methylated in both the jejunum and colon, thus arguing against possible contribution of DNA methylation in the colon-specific expression of TPPT. A role for histone modifications in the tissue-specific pattern of Slc44a4 expression, however, was suggested by the findings that in mouse colon, histone H3 in the 5'-regulatory region of Slc44a4 is tri-methylated at lysine 4 and acetylated at lysine 9, whereas the tri-methylation at lysine 27 modification was negligible. In contrast, in the mouse jejunum, histone H3 is hyper-trimethylated at lysine 27 (repressor mark). Similarly, possible involvement of miRNA(s) in the tissue-specific expression of TPPT was also suggested by the findings that the 3'-UTR of SLC44A4 is targeted by specific miRNAs/RNA binding proteins in non-colonic, but not in colonic, epithelial cells. These studies show, for the first time, epigenetic mechanisms (histone modifications) play a role in determining the tissue-specific pattern of expression of TPPT

  3. [Molecular Biology on the Mechanisms of Autism Spectrum Disorder for Clinical Psychiatrists].

    PubMed

    Makinodan, Manabu

    2015-01-01

    While, in general, a certain number of clinical psychiatrists might not be familiar with molecular biology, the mechanisms of mental illnesses have been uncovered by molecular biology for decades. Among mental illnesses, even biological psychiatrists and neuroscientists have paid less attention to the biological treatment of autism spectrum disorder (ASD) than Alzheimer's disease and schizophrenia since ASD has been regarded as a developmental disorder that was seemingly untreatable. However, multifaceted methods of molecular biology have revealed the mechanisms that would lead to the medication of ASD. In this article, how molecular biology dissects the pathobiology of ASD is described in order to announce the possibilities of biological treatment for clinical psychiatrists.

  4. The radical mechanism of biological methane synthesis by methyl-coenzyme M reductase.

    PubMed

    Wongnate, Thanyaporn; Sliwa, Dariusz; Ginovska, Bojana; Smith, Dayle; Wolf, Matthew W; Lehnert, Nicolai; Raugei, Simone; Ragsdale, Stephen W

    2016-05-20

    Methyl-coenzyme M reductase, the rate-limiting enzyme in methanogenesis and anaerobic methane oxidation, is responsible for the biological production of more than 1 billion tons of methane per year. The mechanism of methane synthesis is thought to involve either methyl-nickel(III) or methyl radical/Ni(II)-thiolate intermediates. We employed transient kinetic, spectroscopic, and computational approaches to study the reaction between the active Ni(I) enzyme and substrates. Consistent with the methyl radical-based mechanism, there was no evidence for a methyl-Ni(III) species; furthermore, magnetic circular dichroism spectroscopy identified the Ni(II)-thiolate intermediate. Temperature-dependent transient kinetics also closely matched density functional theory predictions of the methyl radical mechanism. Identifying the key intermediate in methanogenesis provides fundamental insights to develop better catalysts for producing and activating an important fuel and potent greenhouse gas.

  5. Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth

    PubMed Central

    Commandeur, Arno E.; Styer, Aaron K.; Teixeira, Jose M.

    2015-01-01

    BACKGROUND Uterine leiomyomas (fibroids) are highly prevalent benign smooth muscle tumors of the uterus. In the USA, the lifetime risk for women developing uterine leiomyomas is estimated as up to 75%. Except for hysterectomy, most therapies or treatments often provide only partial or temporary relief and are not successful in every patient. There is a clear racial disparity in the disease; African-American women are estimated to be three times more likely to develop uterine leiomyomas and generally develop more severe symptoms. There is also familial clustering between first-degree relatives and twins, and multiple inherited syndromes in which fibroid development occurs. Leiomyomas have been described as clonal and hormonally regulated, but despite the healthcare burden imposed by the disease, the etiology of uterine leiomyomas remains largely unknown. The mechanisms involved in their growth are also essentially unknown, which has contributed to the slow progress in development of effective treatment options. METHODS A comprehensive PubMed search for and critical assessment of articles related to the epidemiological, biological and genetic clues for uterine leiomyoma development was performed. The individual functions of some of the best candidate genes are explained to provide more insight into their biological function and to interconnect and organize genes and pathways in one overarching figure that represents the current state of knowledge about uterine leiomyoma development and growth. RESULTS In this review, the widely recognized roles of estrogen and progesterone in uterine leiomyoma pathobiology on the basis of clinical and experimental data are presented. This is followed by fundamental aspects and concepts including the possible cellular origin of uterine fibroids. The central themes in the subsequent parts are cytogenetic aberrations in leiomyomas and the racial/ethnic disparities in uterine fibroid biology. Then, the attributes of various in vitro and

  6. Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map.

    PubMed

    Collins, Sean R; Miller, Kyle M; Maas, Nancy L; Roguev, Assen; Fillingham, Jeffrey; Chu, Clement S; Schuldiner, Maya; Gebbia, Marinella; Recht, Judith; Shales, Michael; Ding, Huiming; Xu, Hong; Han, Junhong; Ingvarsdottir, Kristin; Cheng, Benjamin; Andrews, Brenda; Boone, Charles; Berger, Shelley L; Hieter, Phil; Zhang, Zhiguo; Brown, Grant W; Ingles, C James; Emili, Andrew; Allis, C David; Toczyski, David P; Weissman, Jonathan S; Greenblatt, Jack F; Krogan, Nevan J

    2007-04-12

    Defining the functional relationships between proteins is critical for understanding virtually all aspects of cell biology. Large-scale identification of protein complexes has provided one important step towards this goal; however, even knowledge of the stoichiometry, affinity and lifetime of every protein-protein interaction would not reveal the functional relationships between and within such complexes. Genetic interactions can provide functional information that is largely invisible to protein-protein interaction data sets. Here we present an epistatic miniarray profile (E-MAP) consisting of quantitative pairwise measurements of the genetic interactions between 743 Saccharomyces cerevisiae genes involved in various aspects of chromosome biology (including DNA replication/repair, chromatid segregation and transcriptional regulation). This E-MAP reveals that physical interactions fall into two well-represented classes distinguished by whether or not the individual proteins act coherently to carry out a common function. Thus, genetic interaction data make it possible to dissect functionally multi-protein complexes, including Mediator, and to organize distinct protein complexes into pathways. In one pathway defined here, we show that Rtt109 is the founding member of a novel class of histone acetyltransferases responsible for Asf1-dependent acetylation of histone H3 on lysine 56. This modification, in turn, enables a ubiquitin ligase complex containing the cullin Rtt101 to ensure genomic integrity during DNA replication.

  7. Mechanical properties of the beetle elytron, a biological composite material.

    PubMed

    Lomakin, Joseph; Huber, Patricia A; Eichler, Christian; Arakane, Yasuyuki; Kramer, Karl J; Beeman, Richard W; Kanost, Michael R; Gehrke, Stevin H

    2011-02-14

    We determined the relationship between composition and mechanical properties of elytra (modified forewings that are composed primarily of highly sclerotized dorsal and less sclerotized ventral cuticles) from the beetles Tribolium castaneum (red flour beetle) and Tenebrio molitor (yellow mealworm). Elytra of both species have similar mechanical properties at comparable stages of maturation (tanning). Shortly after adult eclosion, the elytron of Tenebrio is ductile and soft with a Young's modulus (E) of 44 ± 8 MPa, but it becomes brittle and stiff with an E of 2400 ± 1100 MPa when fully tanned. With increasing tanning, dynamic elastic moduli (E') increase nearly 20-fold, whereas the frequency dependence of E' diminishes. These results support the hypothesis that cuticle tanning involves cross-linking of components, while drying to minimize plasticization has a lesser impact on cuticular stiffening and frequency dependence. Suppression of the tanning enzymes laccase-2 (TcLac2) or aspartate 1-decarboxylase (TcADC) in Tribolium altered mechanical characteristics consistent with hypotheses that (1) ADC suppression favors formation of melanic pigment with a decrease in protein cross-linking and (2) Lac2 suppression reduces both cuticular pigmentation and protein cross-linking.

  8. Formamidopyrimidines in DNA: mechanisms of formation, repair, and biological effects.

    PubMed

    Dizdaroglu, Miral; Kirkali, Güldal; Jaruga, Pawel

    2008-12-15

    Oxidatively induced damage to DNA results in a plethora of lesions comprising modified bases and sugars, DNA-protein cross-links, tandem lesions, strand breaks, and clustered lesions. Formamidopyrimidines, 4,6-diamino-5-formamidopyrimidine (FapyAde) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua), are among the major lesions generated in DNA by hydroxyl radical attack, UV radiation, or photosensitization under numerous in vitro and in vivo conditions. They are formed by one-electron reduction of C8-OH-adduct radicals of purines and thus have a common precursor with 8-hydroxypurines generated upon one-electron oxidation. Methodologies using mass spectrometry exist to accurately measure FapyAde and FapyGua in vitro and in vivo. Formamidopyrimidines are repaired by base excision repair. Numerous prokaryotic and eukaryotic DNA glycosylases are highly specific for removal of these lesions from DNA in the first step of this repair pathway, indicating their biological importance. FapyAde and FapyGua are bypassed by DNA polymerases with the insertion of the wrong intact base opposite them, leading to mutagenesis. In mammalian cells, the mutagenicity of FapyGua exceeds that of 8-hydroxyguanine, which is thought to be the most mutagenic of the oxidatively induced lesions in DNA. The background and formation levels of the former in vitro and in vivo equal or exceed those of the latter under various conditions. FapyAde and FapyGua exist in living cells at significant background levels and are abundantly generated upon exposure to oxidative stress. Mice lacking the genes that encode specific DNA glycosylases accumulate these lesions in different organs and, in some cases, exhibit a series of pathological conditions including metabolic syndrome and cancer. Animals exposed to environmental toxins accumulate formamidopyrimidines in their organs. Here, we extensively review the mechanisms of formation, measurement, repair, and biological effects of formamidopyrimidines

  9. Molecular change signal-to-noise criteria for interpreting experiments involving exposure of biological systems to weakly interacting electromagnetic fields.

    PubMed

    Vaughan, Timothy E; Weaver, James C

    2005-05-01

    We describe an approach to aiding the design and interpretation of experiments involving biological effects of weakly interacting electromagnetic fields that range from steady (dc) to microwave frequencies. We propose that if known biophysical mechanisms cannot account for an inferred, underlying molecular change signal-to-noise ratio, (S/N)gen, of a observed result, then there are two interpretation choices: (1) there is an unknown biophysical mechanism with stronger coupling between the field exposure and the ongoing biochemical process, or (2) the experiment is responding to something other than the field exposure. Our approach is based on classical detection theory, the recognition that weakly interacting fields cannot break chemical bonds, and the consequence that such fields can only alter rates of ongoing, metabolically driven biochemical reactions, and transport processes. The approach includes both fundamental chemical noise (molecular shot noise) and other sources of competing chemical change, to be compared quantitatively to the field induced change for the basic case that the field alters a single step in a biochemical network. Consistent with pharmacology and toxicology, we estimate the molecular dose (mass associated with field induced molecular change per mass tissue) resulting from illustrative low frequency field exposures for the biophysical mechanism of voltage gated channels. For perspective, we then consider electric field-mediated delivery of small molecules across human skin and into individual cells. Specifically, we consider the examples of iontophoretic and electroporative delivery of fentanyl through skin and electroporative delivery of bleomycin into individual cells. The total delivered amount corresponds to a molecular change signal and the delivery variability corresponds to generalized chemical noise. Viewed broadly, biological effects due to nonionizing fields may include animal navigation, medical applications, and environmental

  10. Free radicals: how do we stand them? Anaerobic and aerobic free radical (chain) reactions involved in the use of fluorogenic probes and in biological systems.

    PubMed

    Liochev, Stefan I

    2014-01-01

    Biologically significant conclusions have been based on the use of fluorogenic and luminogenic probes for the detection of reactive species. The basic mechanisms of the processes involved have not been satisfactorily elucidated. In the present work, the mechanism of the enzyme and photosensitized oxidation of NAD(P)H by resorufin is analyzed and appears to involve both aerobic and anaerobic free radical chain reactions. There are two major fallouts of this analysis. Many of the conclusions about the participation of radicals based on the use of probes such as resorufin and Amplex red need reevaluation. It is also concluded that anaerobic free radical reactions may be biologically significant, and the possible existence of enzymatic systems to eliminate certain free radicals is discussed.

  11. Redox chemistry of molybdenum in natural waters and its involvement in biological evolution.

    PubMed

    Wang, Deli

    2012-01-01

    The transition element molybdenum (Mo) possesses diverse valances (+II to +VI), and is involved in forming cofactors in more than 60 enzymes in biology. Redox switching of the element in these enzymes catalyzes a series of metabolic reactions in both prokaryotes and eukaryotes, and the element therefore plays a fundamental role in the global carbon, nitrogen, and sulfur cycling. In the present oxygenated waters, oxidized Mo(VI) predominates thermodynamically, whilst reduced Mo species are mainly confined within specific niches including cytoplasm. Only recently has the reduced Mo(V) been separated from Mo(VI) in sulfidic mats and even in some reducing waters. Given the presence of reduced Mo(V) in contemporary anaerobic habitats, it seems that reduced Mo species were present in the ancient reducing ocean (probably under both ferruginous and sulfidic conditions), prompting the involvement of Mo in enzymes including nitrogenase and nitrate reductase. During the global transition to oxic conditions, reduced Mo species were constrained to specific anaerobic habitats, and efficient uptake systems of oxidized Mo(VI) became a selective advantage for current prokaryotic and eukaryotic cells. Some prokaryotes are still able to directly utilize reduced Mo if any exists in ambient environments. In total, this mini-review describes the redox chemistry and biogeochemistry of Mo over the Earth's history.

  12. Role of the Wasp Venom Peptide Mastoparan in the Study of Mechanisms Involved in Cell Death

    DTIC Science & Technology

    1989-08-23

    Involved in Cell Death 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK...study of mechanisms involved in cell death " beyond brief excerpts is with the permission of the copyright owner, and will save and hold harmless...Dissertation: Role of the wasp venom peptide mastoparan in the study of mechanisms involved in cell death . Samuel P. Eng, Master of Science, 1989

  13. Genes and mechanisms involved in beta-amyloid generation and Alzheimer's disease.

    PubMed

    Steiner, H; Capell, A; Leimer, U; Haass, C

    1999-01-01

    article, we like to give an overview on mechanisms involved in the proteolytic generation of Amyloid beta-peptide (Abeta), the major pathological player of this devastating disease. In the second part of this article recent results will be described, which demonstrate an unexpected biological and pathological function of an AD associated gene.

  14. Green house gas emissions from composting and mechanical biological treatment.

    PubMed

    Amlinger, Florian; Peyr, Stefan; Cuhls, Carsten

    2008-02-01

    In order to carry out life-cycle assessments as a basis for far-reaching decisions about environmentally sustainable waste treatment, it is important that the input data be reliable and sound. A comparison of the potential greenhouse gas (GHG) emissions associated with each solid waste treatment option is essential. This paper addresses GHG emissions from controlled composting processes. Some important methodological prerequisites for proper measurement and data interpretation are described, and a common scale and dimension of emission data are proposed so that data from different studies can be compared. A range of emission factors associated with home composting, open windrow composting, encapsulated composting systems with waste air treatment and mechanical biological waste treatment (MBT) are presented from our own investigations as well as from the literature. The composition of source materials along with process management issues such as aeration, mechanical agitation, moisture control and temperature regime are the most important factors controlling methane (CH4), nitrous oxide (N2O) and ammoniac (NH3) emissions. If ammoniac is not stripped during the initial rotting phase or eliminated by acid scrubber systems, biofiltration of waste air provides only limited GHG mitigation, since additional N2O may be synthesized during the oxidation of NH3, and only a small amount of CH4 degradation occurs in the biofilter. It is estimated that composting contributes very little to national GHG inventories generating only 0.01-0.06% of global emissions. This analysis does not include emissions from preceding or post-treatment activities (such as collection, transport, energy consumption during processing and land spreading), so that for a full emissions account, emissions from these activities would need to be added to an analysis.

  15. Biological Nanomotors with a Revolution, Linear, or Rotation Motion Mechanism

    PubMed Central

    Noji, Hiroyuki; Yengo, Christopher M.; Zhao, Zhengyi; Grainge, Ian

    2016-01-01

    SUMMARY The ubiquitous biological nanomotors were classified into two categories in the past: linear and rotation motors. In 2013, a third type of biomotor, revolution without rotation (http://rnanano.osu.edu/movie.html), was discovered and found to be widespread among bacteria, eukaryotic viruses, and double-stranded DNA (dsDNA) bacteriophages. This review focuses on recent findings about various aspects of motors, including chirality, stoichiometry, channel size, entropy, conformational change, and energy usage rate, in a variety of well-studied motors, including FoF1 ATPase, helicases, viral dsDNA-packaging motors, bacterial chromosome translocases, myosin, kinesin, and dynein. In particular, dsDNA translocases are used to illustrate how these features relate to the motion mechanism and how nature elegantly evolved a revolution mechanism to avoid coiling and tangling during lengthy dsDNA genome transportation in cell division. Motor chirality and channel size are two factors that distinguish rotation motors from revolution motors. Rotation motors use right-handed channels to drive the right-handed dsDNA, similar to the way a nut drives the bolt with threads in same orientation; revolution motors use left-handed motor channels to revolve the right-handed dsDNA. Rotation motors use small channels (<2 nm in diameter) for the close contact of the channel wall with single-stranded DNA (ssDNA) or the 2-nm dsDNA bolt; revolution motors use larger channels (>3 nm) with room for the bolt to revolve. Binding and hydrolysis of ATP are linked to different conformational entropy changes in the motor that lead to altered affinity for the substrate and allow work to be done, for example, helicase unwinding of DNA or translocase directional movement of DNA. PMID:26819321

  16. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders.

    PubMed

    Campos, Alline Cristina; Moreira, Fabricio Araújo; Gomes, Felipe Villela; Del Bel, Elaine Aparecida; Guimarães, Francisco Silveira

    2012-12-05

    Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound Δ(9)-tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamide-mediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARγ receptors agonism, intracellular (Ca(2+)) increase, etc.), on CBD behavioural effects.

  17. Physical activity and cancer prevention: etiologic evidence and biological mechanisms.

    PubMed

    Friedenreich, Christine M; Orenstein, Marla R

    2002-11-01

    Scientific evidence is accumulating on physical activity as a means for the primary prevention of cancer. Nearly 170 observational epidemiologic studies of physical activity and cancer risk at a number of specific cancer sites have been conducted. The evidence for decreased risk with increased physical activity is classified as convincing for breast and colon cancers, probable for prostate cancer, possible for lung and endometrial cancers and insufficient for cancers at all other sites. Despite the large number of studies conducted on physical activity and cancer, most have been hampered by incomplete assessment of physical activity and a lack of full examination of effect modification and confounding. Several plausible hypothesized biological mechanisms exist for the association between physical activity and cancer, including changes in endogenous sexual and metabolic hormone levels and growth factors, decreased obesity and central adiposity and possibly changes in immune function. Weight control may play a particularly important role because links between excess weight and increased cancer risk have been established for several sites, and central adiposity has been particularly implicated in promoting metabolic conditions amenable to carcinogenesis. Based on existing evidence, some public health organizations have issued physical activity guidelines for cancer prevention, generally recommending at least 30 min of moderate-to-vigorous intensity physical activity on > or =5 d/wk. Although most research has focused on the efficacy of physical activity in cancer prevention, evidence is increasing that exercise also influences other aspects of the cancer experience, including cancer detection, coping, rehabilitation and survival after diagnosis.

  18. Mechanism of biological liquid superlubricity of Brasenia schreberi mucilage.

    PubMed

    Liu, Pengxiao; Liu, Yuhong; Yang, Ye; Chen, Zhe; Li, Jinjin; Luo, Jianbin

    2014-04-08

    In the present work, an excellent biological lubricant extracted from an aquatic plant called Brasenia schreberi (B.s) is reported. With a rotary cylinder-on-ring tribometer, the lubrication properties of the B.s mucilage between quartz glass surfaces have been investigated under different rotation velocity, and an ultralow friction coefficient between 0.004 and 0.006 is obtained. It is observed that the ultralow friction coefficient is independent of the rotation speed, when it is less than 0.1 m/s. SEM images indicate that the mucilage surrounding B.s is composed of polysaccharide gels with a layered structure, which are called nanosheets in the following work. Moreover, it can be deduced that the liquid superlubricity is closely related to the B.s mucilage layer absorbed on the quartz glass surface by hydrogen bonds and the superlubricity behavior only occurs when the adsorption layer stably forms between the quartz glass surface and the B.s mucilage. It is also found that superlubricity is closely dependent upon the sheet structure of the B.s mucilage and water molecules in the mucilage. According to these results, a layered nanosheets lubrication mechanism has been revealed, i.e., the ultralow friction coefficient is due to the adsorption layer of polysaccharide on the quartz glass surface and the hydration layers of water molecules bonded on the polysaccharide nanosheets between the sliding surfaces.

  19. Mechanics of Dynamic Needle Insertion into a Biological Material

    PubMed Central

    Mahvash, Mohsen; Dupont, Pierre E.

    2010-01-01

    During needle-based procedures, transitions between tissue layers often lead to rupture events that involve large forces and tissue deformations and produce uncontrollable crack extensions. In this paper, the mechanics of these rupture events is described, and the effect of insertion velocity on needle force, tissue deformation, and needle work is analyzed. Using the J integral method from fracture mechanics, rupture events are modeled as sudden crack extensions that occur when the release rate J of strain energy concentrated at the tip of the crack exceeds the fracture toughness of the material. It is shown that increasing the velocity of needle insertion will reduce the force of the rupture event when it increases the energy release rate. A nonlinear viscoelastic Kelvin model is then used to predict the relationship between the deformation of tissue and the rupture force at different velocities. The model predicts that rupture deformation and work asymptotically approach minimum values as needle velocity increases. Consequently, most of the benefit of using a higher needle velocity can be achieved using a finite velocity that is inversely proportional to the relaxation time of the tissue. Experiments confirm the analytical predictions with multilayered porcine cardiac tissue. PMID:19932986

  20. Mechanics of dynamic needle insertion into a biological material.

    PubMed

    Mahvash, Mohsen; Dupont, Pierre E

    2010-04-01

    During needle-based procedures, transitions between tissue layers often lead to rupture events that involve large forces and tissue deformations and produce uncontrollable crack extensions. In this paper, the mechanics of these rupture events is described, and the effect of insertion velocity on needle force, tissue deformation, and needle work is analyzed. Using the J integral method from fracture mechanics, rupture events are modeled as sudden crack extensions that occur when the release rate J of strain energy concentrated at the tip of the crack exceeds the fracture toughness of the material. It is shown that increasing the velocity of needle insertion will reduce the force of the rupture event when it increases the energy release rate. A nonlinear viscoelastic Kelvin model is then used to predict the relationship between the deformation of tissue and the rupture force at different velocities. The model predicts that rupture deformation and work asymptotically approach minimum values as needle velocity increases. Consequently, most of the benefit of using a higher needle velocity can be achieved using a finite velocity that is inversely proportional to the relaxation time of the tissue. Experiments confirm the analytical predictions with multilayered porcine cardiac tissue.

  1. Modelling the molecular mechanisms of synaptic plasticity using systems biology approaches.

    PubMed

    Kotaleski, Jeanette Hellgren; Blackwell, Kim T

    2010-04-01

    Synaptic plasticity is thought to underlie learning and memory, but the complexity of the interactions between the ion channels, enzymes and genes that are involved in synaptic plasticity impedes a deep understanding of this phenomenon. Computer modelling has been used to investigate the information processing that is performed by the signalling pathways involved in synaptic plasticity in principal neurons of the hippocampus, striatum and cerebellum. In the past few years, new software developments that combine computational neuroscience techniques with systems biology techniques have allowed large-scale, kinetic models of the molecular mechanisms underlying long-term potentiation and long-term depression. We highlight important advancements produced by these quantitative modelling efforts and introduce promising approaches that use advancements in live-cell imaging.

  2. Mechanisms of interaction and biological effects of extremely-low-frequency electromagnetic fields

    SciTech Connect

    Tenforde, T.S.

    1994-07-01

    Evidence is mounting, that environmental electric and magnetic fields in the extremely-low-frequency (ELF) band below 300 Hz can influence biological functions by mechanisms that are only poorly understood at the present time. The primary objectives of this paper are to review the physical properties of ELF fields, their interactions with living systems at the tissue, cellular, and subcellular levels, and the key role of cell membranes in the transduction of signals from imposed ELF fields. Topics of discussion include signal-to-noise ratios for single cells and cell aggregates, resonance phenomena involving a combination of static and ELF magnetic fields, and the possible influence of ELF fields on molecular signaling pathways that involve membrane receptors and cytoplasmic second messengers. The implications of these findings for promotion of tumor growth by ELF fields are also reviewed.

  3. Physical and biological mechanisms of nanosecond- and microsecond-pulsed FE-DBD plasma interaction with biological objects

    NASA Astrophysics Data System (ADS)

    Dobrynin, Danil

    2013-09-01

    Mechanisms of plasma interaction with living tissues and cells can be quite complex, owing to the complexity of both the plasma and the tissue. Thus, unification of all the mechanisms under one umbrella might not be possible. Here, analysis of interaction of floating electrode dielectric barrier discharge (FE-DBD) with living tissues and cells is presented and biological and physical mechanisms are discussed. In physical mechanisms, charged species are identified as the major contributors to the desired effect and a mechanism of this interaction is proposed. Biological mechanisms are also addressed and a hypothesis of plasma selectivity and its effects is offered. Spatially uniform nanosecond and sub-nanosecond short-pulsed dielectric barrier discharge plasmas are gaining popularity in biological and medical applications due to their increased uniformity, lower plasma temperature, lower surface power density, and higher concentration of the active species produced. In this presentation we will compare microsecond pulsed plasmas with nanosecond driven systems and their applications in biology and medicine with specific focus on wound healing and tissue regeneration. Transition from negative to positive streamer will be discussed with proposed hypothesis of uniformity mechanisms of positive streamer and the reduced dependence on morphology and surface chemistry of the second electrode (human body) being treated. Uniform plasma offers a more uniform delivery of active species to the tissue/surface being treated thus leading to better control over the biological results.

  4. System biology analysis of cell cycle pathway involved in hepatocellular carcinoma.

    PubMed

    Sun, Meiqian; Mo, Wenjuan; Fu, Xuping; Wu, Gang; Huang, Yan; Tang, Rong; Guo, Yi; Qiu, Minyan; Zhao, Feng; Li, Lin; Huang, Shengdong; Mao, Yumin; Li, Yao; Xie, Yi

    2010-06-01

    To investigate genetic mechanisms of hepatocarcinogenesis and identify potential anticancer targets in hepatocellular carcinoma (HCC), we analyzed microarray gene expression profiles between 33 HCCs and their corresponding noncancerous liver tissues. Functional analysis of differentially-expressed genes in HCC indicated that cell cycle dysregulation plays an important role in hepatocarcinogenesis. Based on 14 differentially-expressed genes involved in cell cycle in HCC, we applied Structural Equation Modeling (SEM) to establish a potential genetic network which could assist understanding of HCC molecular mechanisms. siRNA-mediated knock-down of two significantly up-regulated genes, minichromosome maintenance protein 2 (MCM2) and cyclin B1 (CCNB1), in HCC cells (SMMC-7721 and QGY-7703) induced G2/M-phase arrest, apoptosis and antiproliferation in HCC. Some up-regulated cell cycle-related genes in HCC were down-regulated following specific depletion of MCM2 or/and CCNB1 in HCC cells, which might well validate and complement the reconstructed cell cycle network. This study may contribute to further disclose hepatocarcinogenesis mechanism through systematically analyzed the HCC-related-cell-cycle pathway. This study also shows that MCM2 and CCNB1 could be promising prognostic and therapeutic targets for HCC.

  5. Mechanisms involved in Escherichia coli and Serratia marcescens removal during activated sludge wastewater treatment

    PubMed Central

    Orruño, Maite; Garaizabal, Idoia; Bravo, Zaloa; Parada, Claudia; Barcina, Isabel; Arana, Inés

    2014-01-01

    Wastewater treatment reduces environmental contamination by removing gross solids and mitigating the effects of pollution. Treatment also reduces the number of indicator organisms and pathogens. In this work, the fates of two coliform bacteria, Escherichia coli and Serratia marcescens, were analyzed in an activated sludge process to determine the main mechanisms involved in the reduction of pathogenic microorganisms during wastewater treatment. These bacteria, modified to express green fluorescent protein, were inoculated in an activated sludge unit and in batch systems containing wastewater. The results suggested that, among the different biological factors implied in bacterial removal, bacterivorous protozoa play a key role. Moreover, a representative number of bacteria persisted in the system as free-living or embedded cells, but their distribution into liquid or solid fractions varied depending on the bacterium tested, questioning the real value of bacterial indicators for the control of wastewater treatment process. Additionally, viable but nonculturable cells constituted an important part of the bacterial population adhered to solid fractions, what can be derived from the competition relationships with native bacteria, present in high densities in this environment. These facts, taken together, emphasize the need for reliable quantitative and qualitative analysis tools for the evaluation of pathogenic microbial composition in sludge, which could represent an undefined risk to public health and ecosystem functions when considering its recycling. PMID:25044599

  6. Biological monitoring involving children exposed to mercury from a barometer in a private residence.

    PubMed

    Scheepers, Paul T J; van Ballegooij-Gevers, Marieke; Jans, Henk

    2014-12-15

    A small spill of approximately 3 mL of mercury from a broken barometer in a residential setting resulted in blood values of 32 μg/L in a boy of 9 months and 26 μg/L in a girl of 2.5 years in samples collected within 6h after the start of the incident. A nanny who attempted to remove the spill had a blood mercury value of 20 μg/L at the same time point. These elevated blood values were attributed to inhalation rather than dermal uptake or ingestion. Exposure was aggravated by the use of a vacuum cleaner in an early attempt to remove the spill and incomplete decontamination of involved persons, leading to a continuation of exposure. Over a period of three months general cleaning was followed by targeted cleaning of hot spots until the indoor air mercury levels reached a median value of 0.090 μg/m(3) with a range of 0.032-0.140 μg/m(3). Meanwhile the family was staying in a shelter home. Human biological monitoring (HBM) was motivated by the complex exposure situation and the involvement of young children. Initially high blood values triggered alertness for clinical signs of intoxication, that (as it turned out) were not observed in any of the exposed individuals. Despite continued exposure from hair and clothes, within six weeks after the incident, blood levels returned to a background level normally seen in children. HBM contributed to reassurance of the parents of the young children that quick elimination of the mercury did not require medical treatment.

  7. Blood Flow and the Vascular System: An Interface of Fluid Mechanics with Biology

    NASA Astrophysics Data System (ADS)

    Nerem, Robert

    1998-11-01

    The cardiovascular system has as its primary function the delivery of blood to the tissues of the body. Important in the regulation of this function is the monolayer of endothelial cells positioned as the inner lining of a blood vessel. This endothelium represents the interface with flowing blood, and over the past two decades much has been learned about the response of endothelial cells to flow and the associated shear stress. The nature of this response is dependent on the detailed characteristics of the flow, with there as an example being significant differences in the response to steady flow as compared to oscillatory flow. The response to flow also is an active process, one involving structural and shape changes as well as alterations in the cell's ability to synthesize and secrete biologically active molecules. A critical question is how does the endothelial cell sense its fluid mechanical environment? Having sensed this environment, how is this signal transduced into the types of cellular changes that have been observed? These questions are beginning to be answered, and with this knowledge one can begin to develop computational models of the response of an endothelial cell to flow. The model described here focuses on intracellular calcium, an important second messenger in the transduction of a flow signal. As mechanisms for the recognition of flow, the model includes effects due to both convection diffusion coupling of the transport of small molecules to the cell's surface and mechanically-gated ion channels in the cell's membrane. It also includes a variety of intracellular mechanisms involved in the regulation of calcium dynamics. Although the model is only an initial step in quantifying our understanding of endothelial biology, approximate agreement with experimental results has been obtained. Even so, there still is much to be done if the model is to be further improved.

  8. Microbial community analysis involved in the aerobic/extended-idle process performing biological phosphorus removal.

    PubMed

    Zeng, Tian-jing; Yang, Guo-jing; Wang, Dong-bo; Li, Xiao-ming; Zheng, Wei; Yang, Qi; Zeng, Guang-ming

    2013-01-01

    Recently, it has been found that biological phosphorus removal can be achieved in an aerobic/extended-idle (AEI) process using both glucose and acetate as the sole substrate. However, the microbial consortiums involved in glucose-fed and acetate-fed systems have not yet been characterized. Thus the aims of this paper were to investigate the diversities and dynamics of bacterial communities during the acclimation period, and to quantify polyphosphate-accumulating organisms (PAOs) and glycogen-accumulating organisms (GAOs) in the systems. The phylogenetic analysis showed that the microbial communities were mainly composed of phylum Proteobacteria, Bacteroidetes, Chlorobi and another six kinds of unclassified bacteria. Fluorescence in-situ hybridization (FISH) analysis revealed that PAOs and GAOs accounted for 43 ± 7 and 16 ± 3% of all bacteria in the glucose-fed system, and 19 ± 4 and 35 ± 5% of total bacteria in the acetate-fed system, respectively. The results showed that the conventional PAOs could thrive in the AEI process, and a defined anaerobic zone was not necessarily required for putative PAOs growth.

  9. Biological functions of glycosyltransferase genes involved in O-fucose glycan synthesis.

    PubMed

    Okajima, Tetsuya; Matsuura, Aiko; Matsuda, Tsukasa

    2008-07-01

    Rare types of glycosylation often occur in a domain-specific manner and are involved in specific biological processes. Well-known examples of such modification are O-linked fucose (O-fucose) and O-linked glucose (O-glucose) glycans on epidermal growth factor (EGF) domains. In particular, O-fucose glycans are reported to regulate the functions of EGF domain-containing proteins such as urinary-type plasminogen activator and Notch receptors. Two glycosyltransferases catalyze the initiation and elongation of O-fucose glycans. The initiation process is catalyzed by O-fucosyltransferase 1, which is essential for Notch signalling in both Drosophila and mice. O-fucosyltransferase 1 can affect the folding, ligand interaction and endocytosis of Notch receptors, and both the glycosyltransferase and non-catalytic activities of O-fucosyltransferase 1 have been reported. The elongation of O-fucose monosaccharide is catalyzed by Fringe-related genes, which differentially modulate the interaction between Notch and two classes of ligands, namely, Delta and Serrate/Jagged. In this article, we have reviewed the recent reports addressing the distinctive features of the glycosyltransferases and O-glycans present on the EGF domains.

  10. Epidemiology of fine particulate air pollution and human health: biologic mechanisms and who's at risk?

    PubMed Central

    Pope, C A

    2000-01-01

    This article briefly summarizes the epidemiology of the health effects of fine particulate air pollution, provides an early, somewhat speculative, discussion of the contribution of epidemiology to evaluating biologic mechanisms, and evaluates who's at risk or is susceptible to adverse health effects. Based on preliminary epidemiologic evidence, it is speculated that a systemic response to fine particle-induced pulmonary inflammation, including cytokine release and altered cardiac autonomic function, may be part of the pathophysiologic mechanisms or pathways linking particulate pollution with cardiopulmonary disease. The elderly, infants, and persons with chronic cardiopulmonary disease, influenza, or asthma are most susceptible to mortality and serious morbidity effects from short-term acutely elevated exposures. Others are susceptible to less serious health effects such as transient increases in respiratory symptoms, decreased lung function, or other physiologic changes. Chronic exposure studies suggest relatively broad susceptibility to cumulative effects of long-term repeated exposure to fine particulate pollution, resulting in substantive estimates of population average loss of life expectancy in highly polluted environments. Additional knowledge is needed about the specific pollutants or mix of pollutants responsible for the adverse health effects and the biologic mechanisms involved. PMID:10931790

  11. Mechanisms of Microwave Induced Damage in Biologic Materials

    DTIC Science & Technology

    1990-01-01

    246, 1978. [6] F. Oosawa, Polyelectrolytes, Marcel Dekker, New York, 88, 1971. (7] Z. Alexandrowics, A. Katchalsky, " Colligative properties of...condensation in polyelectrolyte solutions: I. Colligative properties ", The Journal of Chemical Physics, 51, 924-933, 1969. e3 CAPTER IV EXPERIMENTAL BIOLOGICAL...exogenously applied electromagnetic fields on certain measured properties of a biological system is a transient one. 1,203,4 The system’s response, determined

  12. A Comparison of Molecular Biology Mechanism of Shewanella putrefaciens between Fresh and Terrestrial Sewage Wastewater

    PubMed Central

    Xu, Jiajie; He, Weina; Wang, Zhonghua; Zhang, Dijun; Sun, Jing; Zhou, Jun; Li, Yanyan; Su, Xiurong

    2016-01-01

    Municipal and industrial wastewater is often discharged into the environment without appropriate treatment, especially in developing countries. As a result, many rivers and oceans are contaminated. It is urgent to control and administer treatments to these contaminated rivers and oceans. However, most mechanisms of bacterial colonization in contaminated rivers and oceans were unknown, especially in sewage outlets. We found Shewanella putrefaciens to be the primary bacteria in the terrestrial sewage wastewater outlets around Ningbo City, China. Therefore, in this study, we applied a combination of differential proteomics, metabolomics, and real-time fluorescent quantitative PCR techniques to identify bacteria intracellular metabolites. We found S. putrefaciens had 12 different proteins differentially expressed in freshwater culture than when grown in wastewater, referring to the formation of biological membranes (Omp35, OmpW), energy metabolism (SOD, deoxyribose-phosphate pyrophosphokinase), fatty acid metabolism (beta-ketoacyl synthase), secondary metabolism, TCA cycle, lysine degradation (2-oxoglutarate reductase), and propionic acid metabolism (succinyl coenzyme A synthetase). The sequences of these 12 differentially expressed proteins were aligned with sequences downloaded from NCBI. There are also 27 differentially concentrated metabolites detected by NMR, including alcohols (ethanol, isopropanol), amines (dimethylamine, ethanolamine), amino acids (alanine, leucine), amine compounds (bilinerurine), nucleic acid compounds (nucleosides, inosines), and organic acids (formate, acetate). Formate and ethanolamine show significant difference between the two environments and are possibly involved in energy metabolism, glycerophospholipid and ether lipids metabolism to provide energy supply, and material basis for engraftment in sewage. Because understanding S. putrefaciens’s biological mechanism of colonization (protein, gene express, and metabolites) in terrestrial

  13. Karyopherins: potential biological elements involved in the delayed graft function in renal transplant recipients

    PubMed Central

    2014-01-01

    Background Immediately after renal transplantation, patients experience rapid and significant improvement of their clinical conditions and undergo considerable systemic and cellular modifications. However, some patients present a slow recovery of the renal function commonly defined as delayed graft function (DGF). Although clinically well characterized, the molecular mechanisms underlying this condition are not totally defined, thus, we are currently missing specific clinical markers to predict and to make early diagnosis of this event. Methods We investigated, using a pathway analysis approach, the transcriptomic profile of peripheral blood mononuclear cells (PBMC) from renal transplant recipients with DGF and with early graft function (EGF), before (T0) and 24 hours (T24) after transplantation. Results Bioinformatics/statistical analysis showed that 15 pathways (8 up-regulated and 7 down-regulated) and 11 pathways (5 up-regulated and 6 down-regulated) were able to identify DGF patients at T0 and T24, respectively. Interestingly, the most up-regulated pathway at both time points was NLS-bearing substrate import into nucleus, which includes genes encoding for several subtypes of karyopherins, a group of proteins involved in nucleocytoplasmic transport. Signal transducers and activators of transcription (STAT) utilize karyopherins-alpha (KPNA) for their passage from cytoplasm into the nucleus. In vitro functional analysis demonstrated that in PBMCs of DGF patients, there was a significant KPNA-mediated nuclear translocation of the phosphorylated form of STAT3 (pSTAT3) after short-time stimulation (2 and 5 minutes) with interleukin-6. Conclusions Our study suggests the involvement, immediately before transplantation, of karyopherin-mediated nuclear transport in the onset and development of DGF. Additionally, it reveals that karyopherins could be good candidates as potential DGF predictive clinical biomarkers and targets for pharmacological interventions in renal

  14. Mechanical properties of the beetle elytron, a biological composite material

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We determined the relationship between composition and mechanical properties of elytral (modified forewing) cuticle of the beetles Tribolium castaneum and Tenebrio molitor. Elytra of both species have similar mechanical properties at comparable stages of maturation (tanning). Shortly after adult ecl...

  15. Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?

    PubMed Central

    Marini, Francesca; Cianferotti, Luisella; Brandi, Maria Luisa

    2016-01-01

    Osteoporosis is a complex multifactorial disorder of the skeleton. Genetic factors are important in determining peak bone mass and structure, as well as the predisposition to bone deterioration and fragility fractures. Nonetheless, genetic factors alone are not sufficient to explain osteoporosis development and fragility fracture occurrence. Indeed, epigenetic factors, representing a link between individual genetic aspects and environmental influences, are also strongly suspected to be involved in bone biology and osteoporosis. Recently, alterations in epigenetic mechanisms and their activity have been associated with aging. Also, bone metabolism has been demonstrated to be under the control of epigenetic mechanisms. Runt-related transcription factor 2 (RUNX2), the master transcription factor of osteoblast differentiation, has been shown to be regulated by histone deacetylases and microRNAs (miRNAs). Some miRNAs were also proven to have key roles in the regulation of Wnt signalling in osteoblastogenesis, and to be important for the positive or negative regulation of both osteoblast and osteoclast differentiation. Exogenous and environmental stimuli, influencing the functionality of epigenetic mechanisms involved in the regulation of bone metabolism, may contribute to the development of osteoporosis and other bone disorders, in synergy with genetic determinants. The progressive understanding of roles of epigenetic mechanisms in normal bone metabolism and in multifactorial bone disorders will be very helpful for a better comprehension of disease pathogenesis and translation of this information into clinical practice. A deep understanding of these mechanisms could help in the future tailoring of proper individual treatments, according to precision medicine’s principles. PMID:27529237

  16. Physical and chemical mechanisms in molecular radiation biology

    SciTech Connect

    Glass, W.A.; Varma, M.N.

    1991-01-01

    Through its Radiological and Chemical Physics Program, the Department of Energy (DOE) has been a primary source of funding for research in radiation physics and radiochemistry, supporting a wide range of explorations of the link between physical, chemical and biological events. This book is a series of articles by authors working within this field, most of whom have been central to the DOE-sponsored research. The opening papers focus on radiological physics; the second section covers radiation chemistry in a discussion that extends from the initial energy transfer to the production of intermediate chemical species and DNA damage. The third section explores the link between the physical and chemical events and the production of biological effects. Finally the book closes with a series of papers on molecular radiation biology.

  17. Biologically inspired load balancing mechanism in neocortical competitive learning

    PubMed Central

    Tal, Amir; Peled, Noam; Siegelmann, Hava T.

    2014-01-01

    A unique delayed self-inhibitory pathway mediated by layer 5 Martinotti Cells was studied in a biologically inspired neural network simulation. Inclusion of this pathway along with layer 5 basket cell lateral inhibition caused balanced competitive learning, which led to the formation of neuronal clusters as were indeed reported in the same region. Martinotti pathway proves to act as a learning “conscience,” causing overly successful regions in the network to restrict themselves and let others fire. It thus spreads connectivity more evenly throughout the net and solves the “dead unit” problem of clustering algorithms in a local and biologically plausible manner. PMID:24653679

  18. [Mechanisms of formation and biological role of protein carbamates].

    PubMed

    Mel'nichuk, D A

    1985-01-01

    Experimental data are presented evidencing for the fact that tissue proteins under conditions in vivo are subjected to enzymic carboxylation with formation of carbaminic groups. In this case a charge variation in definite sites of protein molecule is observed, which specifies variation of the protein conformation and biological properties. Basic regularities of protein carbamate formation reactions are revealed with factors affecting their intensity enumerated. The reactions are shown to be of great biological significance for the respiration processes, realization of hormonal effects of peptide and protein hormones as well as for regulation of tissue homeostasis under conditions of acidic-alkaline state variation in the organism.

  19. Fractal mechanisms of light scattering in biological tissue and cells

    NASA Astrophysics Data System (ADS)

    Xu, M.; Alfano, R. R.

    2005-11-01

    We use fractal continuous random media to model visible and near-infrared light scattering by biological tissue and cell suspensions. The power law of the reduced scattering coefficient, the anisotropy factor of scattering, and the phase function are derived with good agreement with experimental results. Implications for spectroscopic tissue diagnosis are discussed.

  20. Duplication: a Mechanism Producing Disassortative Mixing Networks in Biology

    NASA Astrophysics Data System (ADS)

    Zhao, Dan; Liu, Zeng-Rong; Wang, Jia-Zeng

    2007-10-01

    Assortative/disassortative mixing is an important topological property of a network. A network is called assortative mixing if the nodes in the network tend to connect to their connectivity peers, or disassortative mixing if nodes with low degrees are more likely to connect with high-degree nodes. We have known that biological networks such as protein-protein interaction networks (PPI), gene regulatory networks, and metabolic networks tend to be disassortative. On the other hand, in biological evolution, duplication and divergence are two fundamental processes. In order to make the relationship between the property of disassortative mixing and the two basic biological principles clear and to study the cause of the disassortative mixing property in biological networks, we present a random duplication model and an anti-preference duplication model. Our results show that disassortative mixing networks can be obtained by both kinds of models from uncorrelated initial networks. Moreover, with the growth of the network size, the disassortative mixing property becomes more obvious.

  1. Mechanism(s) involved in opioid drug abuse modulation of HAND.

    PubMed

    Dutta, Raini; Roy, Sabita

    2012-07-01

    Drug abuse and HIV infection are interlinked. From the onset of the HIV/AIDS epidemic, the impact of illicit drug use on HIV disease progression has been a focus of many investigations. Both laboratory-based and epidemiological studies strongly indicate that drug abuse may exacerbate HIV disease progression and increase mortality and morbidity in these patients. Increase susceptibility to opportunistic infection has been implicated as one of the major causes for this detriment. Furthermore, opioids are known to elicit prevalence of neurodegenerative disorders in HIV-infected patients. Numerous authors have delineated various molecular as well as cellular mechanisms associated with neurological complications in these patients. This review gives an overview of these findings. Understanding the mechanisms will allow for the development of targeted therapies aimed at reducing the progression of neurocognitive decline in the drug abusing HIV infected individuals.

  2. [Study on action mechanism of Danhong injection based on computational system biology approach].

    PubMed

    Lv, Yan-ni; Wei, Xiao-hua; Xiao, Pin

    2015-02-01

    Danhong injection is a compound preparation of traditional Chinese medicine Salvia miltiorrhiza and Carthamus tinctorius, and has been widely applied in treating coronary heart diseases and ischemic encephalopathy in clinic. Despite the complexity of its chemical compounds and the diversity of targets, especially in system biology, there have not a report for its action mechanism as a whole regulatory biological network. In this study, protein data of S. miltiorrhiza and C. tinctorius were searched in TCMGeneDIT database and agilent literature search (ALS) system to establish the multi-component protein network of S. miltiorrhiza, C. tinctorius and Danhong injection. Besides, the protein interaction network was built based on the protein-protein interaction in Genecards, BIND, BioGRID, IntAct, MINT and other databases. According to the findings, 10 compounds of S. miltiorrhiza and 14 compounds of C. tinctorius were correlated with proteins. The 24 common compounds had interactions with 81 proteins, and formed a protein interaction network with 60 none-isolated nodes. The Cluster ONE module was applied to make an enrichment analysis on the protein interaction network and extract one sub-network with significant difference P <0.05. The sub-network contains 23 key proteins, which involved five signaling pathways, namely Nod-like receptor signaling pathway, epithelial cell signaling in helicobacter pylori infection, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway and neurotrophin signaling pathway through KEGG signaling pathway mapping. In this study, the computational system biology approach was adopted to preliminarily explain the molecular mechanism of main compounds of Danhong injection in preventing and treating diseases and provide reference for systematic studies on traditional Chinese medicine compounds.

  3. Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

    SciTech Connect

    Kaneuji, Takeshi; Ariyoshi, Wataru; Okinaga, Toshinori; Toshinaga, Akihiro; Takahashi, Tetsu; Nishihara, Tatsuji

    2011-04-29

    Highlights: {yields} Effect of compressive force on osteoblasts were examined. {yields} Compressive force induced OPG expression and suppressed osteoclastogenesis. {yields} This enhancement of OPG is dependent on Wnt/Ca2+ signal pathway. -- Abstract: Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm{sup 2}) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-{kappa}B ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of I{kappa}B{alpha}, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca{sup 2+} pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-{kappa}B) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt

  4. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?

    PubMed Central

    2011-01-01

    The potential mechanisms of action of ozone therapy are reviewed in this paper. The therapeutic efficacy of ozone therapy may be partly due the controlled and moderate oxidative stress produced by the reactions of ozone with several biological components. The line between effectiveness and toxicity of ozone may be dependent on the strength of the oxidative stress. As with exercise, it is well known that moderate exercise is good for health, whereas excessive exercise is not. Severe oxidative stress activates nuclear transcriptional factor kappa B (NFκB), resulting in an inflammatory response and tissue injury via the production of COX2, PGE2, and cytokines. However, moderate oxidative stress activates another nuclear transcriptional factor, nuclear factor-erythroid 2-related factor 2 (Nrf2). Nrf2 then induces the transcription of antioxidant response elements (ARE). Transcription of ARE results in the production of numerous antioxidant enzymes, such as SOD, GPx, glutathione-s-transferase(GSTr), catalase (CAT), heme-oxygenase-1 (HO-1), NADPH-quinone-oxidoreductase (NQO-1), phase II enzymes of drug metabolism and heat shock proteins (HSP). Both free antioxidants and anti-oxidative enzymes not only protect cells from oxidation and inflammation but they may be able to reverse the chronic oxidative stress. Based on these observations, ozone therapy may also activate Nrf2 via moderate oxidative stress, and suppress NFκB and inflammatory responses. Furthermore, activation of Nrf2 results in protection against neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Mild immune responses are induced via other nuclear transcriptional factors, such as nuclear factor of activated T-cells (NFAT) and activated protein-1 (AP-1). Additionally, the effectiveness of ozone therapy in vascular diseases may also be explained by the activation of another nuclear transcriptional factor, hypoxia inducible factor-1α (HIF-1a), which is also induced via moderate

  5. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?

    PubMed

    Sagai, Masaru; Bocci, Velio

    2011-12-20

    The potential mechanisms of action of ozone therapy are reviewed in this paper. The therapeutic efficacy of ozone therapy may be partly due the controlled and moderate oxidative stress produced by the reactions of ozone with several biological components. The line between effectiveness and toxicity of ozone may be dependent on the strength of the oxidative stress. As with exercise, it is well known that moderate exercise is good for health, whereas excessive exercise is not.Severe oxidative stress activates nuclear transcriptional factor kappa B (NFκB), resulting in an inflammatory response and tissue injury via the production of COX2, PGE2, and cytokines. However, moderate oxidative stress activates another nuclear transcriptional factor, nuclear factor-erythroid 2-related factor 2 (Nrf2). Nrf2 then induces the transcription of antioxidant response elements (ARE). Transcription of ARE results in the production of numerous antioxidant enzymes, such as SOD, GPx, glutathione-s-transferase(GSTr), catalase (CAT), heme-oxygenase-1 (HO-1), NADPH-quinone-oxidoreductase (NQO-1), phase II enzymes of drug metabolism and heat shock proteins (HSP). Both free antioxidants and anti-oxidative enzymes not only protect cells from oxidation and inflammation but they may be able to reverse the chronic oxidative stress. Based on these observations, ozone therapy may also activate Nrf2 via moderate oxidative stress, and suppress NFκB and inflammatory responses. Furthermore, activation of Nrf2 results in protection against neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Mild immune responses are induced via other nuclear transcriptional factors, such as nuclear factor of activated T-cells (NFAT) and activated protein-1 (AP-1).Additionally, the effectiveness of ozone therapy in vascular diseases may also be explained by the activation of another nuclear transcriptional factor, hypoxia inducible factor-1α (HIF-1a), which is also induced via moderate oxidative

  6. Molecular Mechanisms Mediating Involvement of Glial Cells in Brain Plastic Remodeling in Epilepsy.

    PubMed

    Khaspekov, L G; Frumkina, L E

    2017-03-01

    In this review we summarize published data on the involvement of glial cells in molecular mechanisms underlying brain plastic reorganization in epilepsy. The role of astrocytes as glial elements in pathological plasticity in epilepsy is discussed. Data on the involvement of aquaporin-4 in epileptogenic plastic changes and on participation of microglia and extracellular matrix in dysregulation of synaptic transmission and plastic remodeling in epileptic brain tissue are reviewed.

  7. Inducing mechanism of biological phosphorus removal driven by the aerobic/extended-idle regime.

    PubMed

    Wang, Dongbo; Yang, Guojing; Li, Xiaoming; Zheng, Wei; Wu, Yan; Yang, Qi; Zeng, Guangming

    2012-11-01

    Recently, it was found that excess phosphorus (Pi) removal could be achieved in activated sludge with an aerobic/extended-idle (AEI) process. In this study, batch tests were performed to further reveal the inducing mechanism of Pi removal involved in the AEI process. Unlike the classical anaerobic/aerobic process where an anaerobic Pi release along with a significant polyhydroxyalkanoate (PHA) accumulation drives polyphosphate (poly-P) accumulating organisms (PAOs) to over-store Pi as poly-P, an idle Pi release accompanied by a low-idle PHA production, which is usually considered to be detrimental for biological Pi removal, was observed to induce some cells to effectively uptake Pi in excess of metabolic requirement in the AEI process. With the increase of idle Pi release, Pi removal efficiency linearly increased. The results also showed that a long idle period with a low level of intracellular glycogen could significantly increase Pi release contents, thus remarkably enhancing Pi removal performances. Fluorescence in situ hybridization analysis further revealed that activated sludge in the AEI process contained 37.6% of Accumulibacter (PAOs) and 28.2% of Competibacter and Defluviicoccus-related organisms (glycogen accumulating organisms). This study revealed an actually existent, yet previously unrecognized, inducing mechanism of poly-P accumulation, and this mechanism behind the AEI regime may provide a scientific basis for the development of an alternative strategy for Pi removal from wastewaters.

  8. Nanotwin-governed toughening mechanism in hierarchically structured biological materials

    NASA Astrophysics Data System (ADS)

    Shin, Yoon Ah; Yin, Sheng; Li, Xiaoyan; Lee, Subin; Moon, Sungmin; Jeong, Jiwon; Kwon, Minhyug; Yoo, Seung Jo; Kim, Young-Min; Zhang, Teng; Gao, Huajian; Oh, Sang Ho

    2016-02-01

    As a natural biocomposite, Strombus gigas, commonly known as the giant pink queen conch shell, exhibits outstanding mechanical properties, especially a high fracture toughness. It is known that the basic building block of conch shell contains a high density of growth twins with average thickness of several nanometres, but their effects on the mechanical properties of the shell remain mysterious. Here we reveal a toughening mechanism governed by nanoscale twins in the conch shell. A combination of in situ fracture experiments inside a transmission electron microscope, large-scale atomistic simulations and finite element modelling show that the twin boundaries can effectively block crack propagation by inducing phase transformation and delocalization of deformation around the crack tip. This mechanism leads to an increase in fracture energy of the basic building block by one order of magnitude, and contributes significantly to that of the overall structure via structural hierarchy.

  9. Nanotwin-governed toughening mechanism in hierarchically structured biological materials.

    PubMed

    Shin, Yoon Ah; Yin, Sheng; Li, Xiaoyan; Lee, Subin; Moon, Sungmin; Jeong, Jiwon; Kwon, Minhyug; Yoo, Seung Jo; Kim, Young-Min; Zhang, Teng; Gao, Huajian; Oh, Sang Ho

    2016-02-17

    As a natural biocomposite, Strombus gigas, commonly known as the giant pink queen conch shell, exhibits outstanding mechanical properties, especially a high fracture toughness. It is known that the basic building block of conch shell contains a high density of growth twins with average thickness of several nanometres, but their effects on the mechanical properties of the shell remain mysterious. Here we reveal a toughening mechanism governed by nanoscale twins in the conch shell. A combination of in situ fracture experiments inside a transmission electron microscope, large-scale atomistic simulations and finite element modelling show that the twin boundaries can effectively block crack propagation by inducing phase transformation and delocalization of deformation around the crack tip. This mechanism leads to an increase in fracture energy of the basic building block by one order of magnitude, and contributes significantly to that of the overall structure via structural hierarchy.

  10. Nanotwin-governed toughening mechanism in hierarchically structured biological materials

    PubMed Central

    Shin, Yoon Ah; Yin, Sheng; Li, Xiaoyan; Lee, Subin; Moon, Sungmin; Jeong, Jiwon; Kwon, Minhyug; Yoo, Seung Jo; Kim, Young-Min; Zhang, Teng; Gao, Huajian; Oh, Sang Ho

    2016-01-01

    As a natural biocomposite, Strombus gigas, commonly known as the giant pink queen conch shell, exhibits outstanding mechanical properties, especially a high fracture toughness. It is known that the basic building block of conch shell contains a high density of growth twins with average thickness of several nanometres, but their effects on the mechanical properties of the shell remain mysterious. Here we reveal a toughening mechanism governed by nanoscale twins in the conch shell. A combination of in situ fracture experiments inside a transmission electron microscope, large-scale atomistic simulations and finite element modelling show that the twin boundaries can effectively block crack propagation by inducing phase transformation and delocalization of deformation around the crack tip. This mechanism leads to an increase in fracture energy of the basic building block by one order of magnitude, and contributes significantly to that of the overall structure via structural hierarchy. PMID:26883846

  11. Mechanisms involved in the transport of mercuric ions in target tissues.

    PubMed

    Bridges, Christy C; Zalups, Rudolfs K

    2017-01-01

    Mercury exists in the environment in various forms, all of which pose a risk to human health. Despite guidelines regulating the industrial release of mercury into the environment, humans continue to be exposed regularly to various forms of this metal via inhalation or ingestion. Following exposure, mercuric ions are taken up by and accumulate in numerous organs, including brain, intestine, kidney, liver, and placenta. In order to understand the toxicological effects of exposure to mercury, a thorough understanding of the mechanisms that facilitate entry of mercuric ions into target cells must first be obtained. A number of mechanisms for the transport of mercuric ions into target cells and organs have been proposed in recent years. However, the ability of these mechanisms to transport mercuric ions and the regulatory features of these carriers have not been characterized completely. The purpose of this review is to summarize the current findings related to the mechanisms that may be involved in the transport of inorganic and organic forms of mercury in target tissues and organs. This review will describe mechanisms known to be involved in the transport of mercury and will also propose additional mechanisms that may potentially be involved in the transport of mercuric ions into target cells.

  12. Thermochemical Pretreatments of Organic Fraction of Municipal Solid Waste from a Mechanical-Biological Treatment Plant

    PubMed Central

    Álvarez-Gallego, Carlos José; Fdez-Güelfo, Luis Alberto; Romero Aguilar, María de los Ángeles; Romero García, Luis Isidoro

    2015-01-01

    The organic fraction of municipal solid waste (OFMSW) usually contains high lignocellulosic and fatty fractions. These fractions are well-known to be a hard biodegradable substrate for biological treatments and its presence involves limitations on the performance of anaerobic processes. To avoid this, thermochemical pretreatments have been applied on the OFMSW coming from a full-scale mechanical-biological treatment (MBT) plant, in order to pre-hydrolyze the waste and improve the organic matter solubilisation. To study the solubilisation yield, the increments of soluble organic matter have been measured in terms of dissolved organic carbon (DOC), soluble chemical oxygen demand (sCOD), total volatile fatty acids (TVFA) and acidogenic substrate as carbon (ASC). The process variables analyzed were temperature, pressure and NaOH dosage. The levels of work for each variable were three: 160–180–200 °C, 3.5–5.0–6.5 bar and 2–3–4 g NaOH/L. In addition, the pretreatment time was also modified among 15 and 120 min. The best conditions for organic matter solubilisation were 160 °C, 3 g NaOH/L, 6.5 bar and 30 min, with yields in terms of DOC, sCOD, TVFA and ASC of 176%, 123%, 119% and 178% respectively. Thus, predictably the application of this pretreatment in these optimum conditions could improve the H2 production during the subsequent Dark Fermentation process. PMID:25671816

  13. Thermochemical pretreatments of organic fraction of municipal solid waste from a mechanical-biological treatment plant.

    PubMed

    Álvarez-Gallego, Carlos José; Fdez-Güelfo, Luis Alberto; de los Ángeles Romero Aguilar, María; Romero García, Luis Isidoro

    2015-02-09

    The organic fraction of municipal solid waste (OFMSW) usually contains high lignocellulosic and fatty fractions. These fractions are well-known to be a hard biodegradable substrate for biological treatments and its presence involves limitations on the performance of anaerobic processes. To avoid this, thermochemical pretreatments have been applied on the OFMSW coming from a full-scale mechanical-biological treatment (MBT) plant, in order to pre-hydrolyze the waste and improve the organic matter solubilisation. To study the solubilisation yield, the increments of soluble organic matter have been measured in terms of dissolved organic carbon (DOC), soluble chemical oxygen demand (sCOD), total volatile fatty acids (TVFA) and acidogenic substrate as carbon (ASC). The process variables analyzed were temperature, pressure and NaOH dosage. The levels of work for each variable were three: 160-180-200 °C, 3.5-5.0-6.5 bar and 2-3-4 g NaOH/L. In addition, the pretreatment time was also modified among 15 and 120 min. The best conditions for organic matter solubilisation were 160 °C, 3 g NaOH/L, 6.5 bar and 30 min, with yields in terms of DOC, sCOD, TVFA and ASC of 176%, 123%, 119% and 178% respectively. Thus, predictably the application of this pretreatment in these optimum conditions could improve the H2 production during the subsequent Dark Fermentation process.

  14. Structural biology of disease-associated repetitive DNA sequences and protein-DNA complexes involved in DNA damage and repair

    SciTech Connect

    Gupta, G.; Santhana Mariappan, S.V.; Chen, X.; Catasti, P.; Silks, L.A. III; Moyzis, R.K.; Bradbury, E.M.; Garcia, A.E.

    1997-07-01

    This project is aimed at formulating the sequence-structure-function correlations of various microsatellites in the human (and other eukaryotic) genomes. Here the authors have been able to develop and apply structure biology tools to understand the following: the molecular mechanism of length polymorphism microsatellites; the molecular mechanism by which the microsatellites in the noncoding regions alter the regulation of the associated gene; and finally, the molecular mechanism by which the expansion of these microsatellites impairs gene expression and causes the disease. Their multidisciplinary structural biology approach is quantitative and can be applied to all coding and noncoding DNA sequences associated with any gene. Both NIH and DOE are interested in developing quantitative tools for understanding the function of various human genes for prevention against diseases caused by genetic and environmental effects.

  15. Formative Assessment and Increased Student Involvement Increase Grades in an Upper Secondary School Biology Course

    ERIC Educational Resources Information Center

    Granbom, Martin

    2016-01-01

    This study shows that formative methods and increased student participation has a positive influence on learning measured as grades. The study was conducted during the course Biology A in a Swedish Upper Secondary School. The students constructed grade criteria and defined working methods and type of examination within a given topic, Gene…

  16. On reaction mechanisms involved in the deuteron–induced surrogate reactions

    SciTech Connect

    Avrigeanu, M.; Avrigeanu, V.; Mănăilescu, C.

    2015-02-24

    An extended analysis of the nuclear reaction mechanisms involved within deuteron interaction with nuclei, namely the breakup, stripping, pick-up, pre-equilibrium emission, and evaporation from fully equilibrated compound nucleus, is presented in order to highlight the importance of the direct mechanisms still neglected in the analysis of deuteron-induced surrogate reactions. Particularly, the dominance of the breakup mechanism at low energies around the Coulomb barrier should be considered in the case of (d,x) surrogate reactions on actinide target nuclei.

  17. Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injury

    EPA Science Inventory

    Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injuryHenriquez, A.1, Snow, S.2, Miller, D1.,Schladweiler, M.2 and Kodavanti, U2.1 Curriculum in Toxicology, UNC, Chapel Hill, NC. 2 EPHD/NHEERL, US EPA, RTP, Durham, NC. ...

  18. Involvement of the Central Cognitive Mechanism in Word Production in Adults Who Stutter

    ERIC Educational Resources Information Center

    Tsai, Pei-Tzu; Bernstein Ratner, Nan

    2016-01-01

    Purpose: The study examined whether semantic and phonological encoding processes were capacity demanding, involving the central cognitive mechanism, in adults who do and do not stutter (AWS and NS) to better understand the role of cognitive demand in linguistic processing and stuttering. We asked (a) whether the two linguistic processes in AWS are…

  19. Holistic systems biology approaches to molecular mechanisms of human helper T cell differentiation to functionally distinct subsets.

    PubMed

    Chen, Z; Lönnberg, T; Lahesmaa, R

    2013-08-01

    Current knowledge of helper T cell differentiation largely relies on data generated from mouse studies. To develop therapeutical strategies combating human diseases, understanding the molecular mechanisms how human naïve T cells differentiate to functionally distinct T helper (Th) subsets as well as studies on human differentiated Th cell subsets is particularly valuable. Systems biology approaches provide a holistic view of the processes of T helper differentiation, enable discovery of new factors and pathways involved and generation of new hypotheses to be tested to improve our understanding of human Th cell differentiation and immune-mediated diseases. Here, we summarize studies where high-throughput systems biology approaches have been exploited to human primary T cells. These studies reveal new factors and signalling pathways influencing T cell differentiation towards distinct subsets, important for immune regulation. Such information provides new insights into T cell biology and into targeting immune system for therapeutic interventions.

  20. Changes of color coordinates of biological tissue with superficial skin damage due to mechanical trauma

    NASA Astrophysics Data System (ADS)

    Pteruk, Vail; Mokanyuk, Olexander; Kvaternuk, Olena; Yakenina, Lesya; Kotyra, Andrzej; Romaniuk, Ryszard S.; Dussembayeva, Shynar

    2015-12-01

    Change of color coordinates of normal and pathological biological tissues is based on calculated spectral diffuse reflection. The proposed color coordinates of normal and pathological biological tissues of skin provided using standard light sources, allowing accurately diagnose skin damage due to mechanical trauma with a blunt object for forensic problems.

  1. Static fields: biological effects and mechanisms relevant to exposure limits.

    PubMed

    van Rongen, Eric; Saunders, Richard D; van Deventer, Emilie T; Repacholi, Michael H

    2007-06-01

    Recently, the International EMF Project of the World Health Organization (WHO) published an Environmental Health Criteria monograph on static electric and magnetic fields. In the present paper a short overview is given of the biological and health effects discussed in this document. The main conclusions are that no acute effects other than transient phenomena such as vertigo and nausea have been observed with exposure to static magnetic flux densities up to 8 T. There are no reports of long term or chronic adverse effects following prolonged static magnetic field exposure, but few data are available on which to base any judgment. The guidelines on static field exposure recommended by ICNIRP in 1994 are discussed in the light of current scientific knowledge.

  2. On Mechanical Transitions in Biologically Motivated Soft Matter Systems

    NASA Astrophysics Data System (ADS)

    Fogle, Craig

    The notion of phase transitions as a characterization of a change in physical properties pervades modern physics. Such abrupt and fundamental changes in the behavior of physical systems are evident in condensed matter system and also occur in nuclear and subatomic settings. While this concept is less prevalent in the field of biology, recent advances have pointed to its relevance in a number of settings. Recent studies have modeled both the cell cycle and cancer as phase transition in physical systems. In this dissertation we construct simplified models for two biological systems. As described by those models, both systems exhibit phase transitions. The first model is inspired by the shape transition in the nuclei of neutrophils during differentiation. During differentiation the nucleus transitions from spherical to a shape often described as "beads on a string." As a simplified model of this system, we investigate the spherical-to-wrinkled transition in an elastic core bounded to a fluid shell system. We find that this model exhibits a first-order phase transition, and the shape that minimizes the energy of the system scales as (micror3/kappa). . The second system studied is motivated by the dynamics of globular proteins. These proteins may undergoes conformational changes with large displacements relative to their size. Transitions between conformational states are not possible if the dynamics are governed strictly by linear elasticity. We construct a model consisting of an predominantly elastic region near the energetic minimum of the system and a non-linear softening of the system at a critical displacement. We find that this simple model displays very rich dynamics include a sharp dynamical phase transition and driving-force-dependent symmetry breaking.

  3. Computational modeling of chemo-bio-mechanical coupling: a systems-biology approach toward wound healing.

    PubMed

    Buganza Tepole, A; Kuhl, E

    2016-01-01

    Wound healing is a synchronized cascade of chemical, biological, and mechanical phenomena, which act in concert to restore the damaged tissue. An imbalance between these events can induce painful scarring. Despite intense efforts to decipher the mechanisms of wound healing, the role of mechanics remains poorly understood. Here, we establish a computational systems biology model to identify the chemical, biological, and mechanical mechanisms of scar formation. First, we introduce the generic problem of coupled chemo-bio-mechanics. Then, we introduce the model problem of wound healing in terms of a particular chemical signal, inflammation, a particular biological cell type, fibroblasts, and a particular mechanical model, isotropic hyperelasticity. We explore the cross-talk between chemical, biological, and mechanical signals and show that all three fields have a significant impact on scar formation. Our model is the first step toward rigorous multiscale, multifield modeling in wound healing. Our formulation has the potential to improve effective wound management and optimize treatment on an individualized patient-specific basis.

  4. Mechanization and Control Concepts for Biologically Inspired Micro Aerial Vehicles

    NASA Technical Reports Server (NTRS)

    Raney, David L.; Slominski, Eric C.

    2003-01-01

    It is possible that MAV designs of the future will exploit flapping flight in order to perform missions that require extreme agility, such as rapid flight beneath a forest canopy or within the confines of a building. Many of nature's most agile flyers generate flapping motions through resonant excitation of an aeroelastically tailored structure: muscle tissue is used to excite a vibratory mode of their flexible wing structure that creates propulsion and lift. A number of MAV concepts have been proposed that would operate in a similar fashion. This paper describes an ongoing research activity in which mechanization and control concepts with application to resonant flapping MAVs are being explored. Structural approaches, mechanical design, sensing and wingbeat control concepts inspired by hummingbirds, bats and insects are examined. Experimental results from a testbed capable of generating vibratory wingbeat patterns that approximately match those exhibited by hummingbirds in hover, cruise, and reverse flight are presented.

  5. Glucosinolate Breakdown in Arabidopsis: Mechanism, Regulation and Biological Significance

    PubMed Central

    Wittstock, Ute; Burow, Meike

    2010-01-01

    Glucosinolates are a group of thioglucosides in plants of the Brassicales order. Together with their hydrolytic enzymes, the myrosinases, they constitute the ‘mustard oil bomb’ involved in plant defense. Here we summarize recent studies in Arabidopsis that have provided molecular evidence that the glucosinolate-myrosinase system is much more than a ‘two-component defense system,’ and started to unravel the roles of different glucosinolate breakdown pathways in the context of plant responses to biotic and abiotic stresses. PMID:22303260

  6. Mechanically switchable polymer fibers for sensing in biological conditions

    NASA Astrophysics Data System (ADS)

    McMillan, Sean; Rader, Chris; Jorfi, Mehdi; Pickrell, Gary; Foster, E. Johan

    2017-02-01

    The area of in vivo sensing using optical fibers commonly uses materials such as silica and polymethyl methacrylate, both of which possess much higher modulus than human tissue. The mechanical mismatch between materials and living tissue has been seen to cause higher levels of glial encapsulation, scarring, and inflammation, leading to failure of the implanted medical device. We present the use of a fiber made from polyvinyl alcohol (PVA) for use as an implantable sensor as it is an easy to work with functionalized polymer that undergoes a transition from rigid to soft when introduced to water. This ability to switch from stiff to soft reduces the severity of the immune response. The fabricated PVA fibers labeled with fluorescein for sensing applications showed excellent response to various stimuli while exhibiting mechanical switchability. For the dry fibers, a tensile storage modulus of 4700 MPa was measured, which fell sharply to 145 MPa upon wetting. The fibers showed excellent response to changing pH levels, producing values that were detectable in a range consistent with those seen in the literature and in proposed applications. The results show that these mechanically switchable fibers are a viable option for future sensing applications.

  7. Sensitizing Curium Luminescence through an Antenna Protein to Investigate Biological Actinide Transport Mechanisms

    PubMed Central

    Sturzbecher-Hoehne, Manuel; Goujon, Christophe; Deblonde, Gauthier J.-P.; Mason, Anne B.; Abergel, Rebecca J.

    2013-01-01

    Worldwide stocks of actinides and lanthanide fission products produced through conventional nuclear spent fuel are increasing continuously, resulting in a growing risk of environmental and human exposure to these toxic radioactive metal ions. Understanding the bio-molecular pathways involved in mammalian uptake, transport and storage of these f-elements is crucial to the development of new decontamination strategies and could also be beneficial to the design of new containment and separation processes. To start unraveling these pathways, our approach takes advantage of the unique spectroscopic properties of trivalent curium. We clearly show that the human iron transporter transferrin acts as an antenna that sensitizes curium luminescence through intramolecular energy transfer. This behavior has been used to describe the coordination of curium within the two binding sites of the protein and to investigate the recognition of curium-transferrin complexes by the cognate transferrin receptor. In addition to providing the first protein-curium spectroscopic characterization, these studies prove that transferrin receptor-mediated endocytosis is a viable mechanism of intracellular entry for trivalent actinides such as curium and provide a new tool utilizing the specific luminescence of curium for the determination of other biological actinide transport mechanisms. PMID:23363005

  8. Sensitizing curium luminescence through an antenna protein to investigate biological actinide transport mechanisms.

    PubMed

    Sturzbecher-Hoehne, Manuel; Goujon, Christophe; Deblonde, Gauthier J-P; Mason, Anne B; Abergel, Rebecca J

    2013-02-20

    Worldwide stocks of actinides and lanthanide fission products produced through conventional nuclear spent fuel are increasing continuously, resulting in a growing risk of environmental and human exposure to these toxic radioactive metal ions. Understanding the biomolecular pathways involved in mammalian uptake, transport and storage of these f-elements is crucial to the development of new decontamination strategies and could also be beneficial to the design of new containment and separation processes. To start unraveling these pathways, our approach takes advantage of the unique spectroscopic properties of trivalent curium. We clearly show that the human iron transporter transferrin acts as an antenna that sensitizes curium luminescence through intramolecular energy transfer. This behavior has been used to describe the coordination of curium within the two binding sites of the protein and to investigate the recognition of curium-transferrin complexes by the cognate transferrin receptor. In addition to providing the first protein-curium spectroscopic characterization, these studies prove that transferrin receptor-mediated endocytosis is a viable mechanism of intracellular entry for trivalent actinides such as curium and provide a new tool utilizing the specific luminescence of curium for the determination of other biological actinide transport mechanisms.

  9. Bleomycin in the setting of lung fibrosis induction: From biological mechanisms to counteractions.

    PubMed

    Della Latta, Veronica; Cecchettini, A; Del Ry, S; Morales, M A

    2015-07-01

    Bleomycin (BLM) is a drug used to treat different types of neoplasms. BLM's most severe adverse effect is lung toxicity, which induces remodeling of lung architecture and loss of pulmonary function, rapidly leading to death. While its clinical role as an anticancer agent is limited, its use in experimental settings is widespread since BLM is one of the most widely used drugs for inducing lung fibrosis in animals, due to its ability to provoke a histologic lung pattern similar to that described in patients undergoing chemotherapy. This pattern is characterized by patchy parenchymal inflammation, epithelial cell injury with reactive hyperplasia, epithelial-mesenchymal transition, activation and differentiation of fibroblasts to myofibroblasts, basement membrane and alveolar epithelium injuries. Several studies have demonstrated that BLM damage is mediated by DNA strand scission producing single- or double-strand breaks that lead to increased production of free radicals. Up to now, the mechanisms involved in the development of pulmonary fibrosis have not been fully understood; several studies have analyzed various potential biological molecular factors, such as transforming growth factor beta 1, tumor necrosis factor alpha, components of the extracellular matrix, chaperones, interleukins and chemokines. The aim of this paper is to review the specific characteristics of BLM-induced lung fibrosis in different animal models and to summarize modalities and timing of in vivo drug administration. Understanding the mechanisms of BLM-induced lung fibrosis and of commonly used therapies for counteracting fibrosis provides an opportunity for translating potential molecular targets from animal models to the clinical arena.

  10. Cell resistance to the Cytolethal Distending Toxin involves an association of DNA repair mechanisms

    PubMed Central

    Bezine, Elisabeth; Malaisé, Yann; Loeuillet, Aurore; Chevalier, Marianne; Boutet-Robinet, Elisa; Salles, Bernard; Mirey, Gladys; Vignard, Julien

    2016-01-01

    The Cytolethal Distending Toxin (CDT), produced by many bacteria, has been associated with various diseases including cancer. CDT induces DNA double-strand breaks (DSBs), leading to cell death or mutagenesis if misrepaired. At low doses of CDT, other DNA lesions precede replication-dependent DSB formation, implying that non-DSB repair mechanisms may contribute to CDT cell resistance. To address this question, we developed a proliferation assay using human cell lines specifically depleted in each of the main DNA repair pathways. Here, we validate the involvement of the two major DSB repair mechanisms, Homologous Recombination and Non Homologous End Joining, in the management of CDT-induced lesions. We show that impairment of single-strand break repair (SSBR), but not nucleotide excision repair, sensitizes cells to CDT, and we explore the interplay of SSBR with the DSB repair mechanisms. Finally, we document the role of the replicative stress response and demonstrate the involvement of the Fanconi Anemia repair pathway in response to CDT. In conclusion, our work indicates that cellular survival to CDT-induced DNA damage involves different repair pathways, in particular SSBR. This reinforces a model where CDT-related genotoxicity primarily involves SSBs rather than DSBs, underlining the importance of cell proliferation during CDT intoxication and pathogenicity. PMID:27775089

  11. Uncovering the underlying physical mechanisms of biological systems via quantification of landscape and flux

    NASA Astrophysics Data System (ADS)

    Li, Xu; Xiakun, Chu; Zhiqiang, Yan; Xiliang, Zheng; Kun, Zhang; Feng, Zhang; Han, Yan; Wei, Wu; Jin, Wang

    2016-01-01

    In this review, we explore the physical mechanisms of biological processes such as protein folding and recognition, ligand binding, and systems biology, including cell cycle, stem cell, cancer, evolution, ecology, and neural networks. Our approach is based on the landscape and flux theory for nonequilibrium dynamical systems. This theory provides a unifying principle and foundation for investigating the underlying mechanisms and physical quantification of biological systems. Project supported by the Natural Science Foundation of China (Grant Nos. 21190040, 11174105, 91225114, 91430217, and 11305176) and Jilin Province Youth Foundation, China (Grant No. 20150520082JH).

  12. The role of mechanics in biological and bio-inspired systems.

    PubMed

    Egan, Paul; Sinko, Robert; LeDuc, Philip R; Keten, Sinan

    2015-07-06

    Natural systems frequently exploit intricate multiscale and multiphasic structures to achieve functionalities beyond those of man-made systems. Although understanding the chemical make-up of these systems is essential, the passive and active mechanics within biological systems are crucial when considering the many natural systems that achieve advanced properties, such as high strength-to-weight ratios and stimuli-responsive adaptability. Discovering how and why biological systems attain these desirable mechanical functionalities often reveals principles that inform new synthetic designs based on biological systems. Such approaches have traditionally found success in medical applications, and are now informing breakthroughs in diverse frontiers of science and engineering.

  13. The role of mechanics in biological and bio-inspired systems

    NASA Astrophysics Data System (ADS)

    Egan, Paul; Sinko, Robert; Leduc, Philip R.; Keten, Sinan

    2015-07-01

    Natural systems frequently exploit intricate multiscale and multiphasic structures to achieve functionalities beyond those of man-made systems. Although understanding the chemical make-up of these systems is essential, the passive and active mechanics within biological systems are crucial when considering the many natural systems that achieve advanced properties, such as high strength-to-weight ratios and stimuli-responsive adaptability. Discovering how and why biological systems attain these desirable mechanical functionalities often reveals principles that inform new synthetic designs based on biological systems. Such approaches have traditionally found success in medical applications, and are now informing breakthroughs in diverse frontiers of science and engineering.

  14. Bacterial endotoxins: biological properties and mechanisms of action

    PubMed Central

    Freudenberg, M. A.

    1993-01-01

    Endotoxins (lipopolysaccharides, LPS) are agents of pathogenicity of Gram-negative bacteria, implicated in the development of Gram-negative shock. Endotoxin reacts with lipopolysaccharide-sensitive cells producing endogenous mediators such as tumour necrosis factor alpha (TNFα). Macrophages are cells mediating the toxic activities of LPS and TNFα is the primary mediator of the lethal action of endotoxin. This review article discusses the various mechanisms by which endotoxin hypersensitivity in bacteria-sensitized animals develops. The paper concludes with a discussion on the possible protective effect of carnitine congeners against the lethal action of LPS. PMID:18475562

  15. Mapping Transcriptional Networks in Plants: Data-Driven Discovery of Novel Biological Mechanisms.

    PubMed

    Gaudinier, Allison; Brady, Siobhan M

    2016-04-29

    In plants, systems biology approaches have led to the generation of a variety of large data sets. Many of these data are created to elucidate gene expression profiles and their corresponding transcriptional regulatory mechanisms across a range of tissue types, organs, and environmental conditions. In an effort to map the complexity of this transcriptional regulatory control, several types of experimental assays have been used to map transcriptional regulatory networks. In this review, we discuss how these methods can be best used to identify novel biological mechanisms by focusing on the appropriate biological context. Translating network biology back to gene function in the plant, however, remains a challenge. We emphasize the need for validation and insight into the underlying biological processes to successfully exploit systems approaches in an effort to determine the emergent properties revealed by network analyses.

  16. Cissus sicyoides: Pharmacological Mechanisms Involved in the Anti-Inflammatory and Antidiarrheal Activities

    PubMed Central

    Beserra, Fernando Pereira; de Cássia Santos, Raquel; Périco, Larissa Lucena; Rodrigues, Vinicius Peixoto; de Almeida Kiguti, Luiz Ricardo; Saldanha, Luiz Leonardo; Pupo, André Sampaio; da Rocha, Lúcia Regina Machado; Dokkedal, Anne Lígia; Vilegas, Wagner; Hiruma-Lima, Clélia Akiko

    2016-01-01

    The objective of this study was to evaluate the pharmacological mechanisms involved in anti-inflammatory and antidiarrheal actions of hydroalcoholic extract obtained from the leaves of Cissus sicyoides (HECS). The anti-inflammatory effect was evaluated by oral administration of HECS against acute model of edema induced by xylene, and the mechanisms of action were analysed by involvement of arachidonic acid (AA) and prostaglandin E2 (PGE2). The antidiarrheal effect of HECS was observed and we analyzed the motility and accumulation of intestinal fluid. We also analyzed the antidiarrheal mechanisms of action of HECS by evaluating the role of the opioid receptor, α2 adrenergic receptor, muscarinic receptor, nitric oxide (NO) and PGE2. The oral administration of HECS inhibited the edema induced by xylene and AA and was also able to significantly decrease the levels of PGE2. The extract also exhibited significant anti-diarrheal activity by reducing motility and intestinal fluid accumulation. This extract significantly reduced intestinal transit stimulated by muscarinic agonist and intestinal secretion induced by PGE2. Our data demonstrate that the mechanism of action involved in the anti-inflammatory effect of HECS is related to PGE2. The antidiarrheal effect of this extract may be mediated by inhibition of contraction by acting on the intestinal smooth muscle and/or intestinal transit. PMID:26805827

  17. Energy implications of mechanical and mechanical-biological treatment compared to direct waste-to-energy.

    PubMed

    Cimpan, Ciprian; Wenzel, Henrik

    2013-07-01

    Primary energy savings potential is used to compare five residual municipal solid waste treatment systems, including configurations with mechanical (MT) and mechanical-biological (MBT) pre-treatment, which produce waste-derived fuels (RDF and SRF), biogas and/or recover additional materials for recycling, alongside a system based on conventional mass burn waste-to-energy and ash treatment. To examine the magnitude of potential savings we consider two energy efficiency levels (state-of-the-art and best available technology), the inclusion/exclusion of heat recovery (CHP vs. PP) and three different background end-use energy production systems (coal condensing electricity and natural gas heat, Nordic electricity mix and natural gas heat, and coal CHP energy quality allocation). The systems achieved net primary energy savings in a range between 34 and 140 MJprimary/100 MJinput waste, in the different scenario settings. The energy footprint of transportation needs, pre-treatment and reprocessing of recyclable materials was 3-9.5%, 1-18% and 1-8% respectively, relative to total energy savings. Mass combustion WtE achieved the highest savings in scenarios with CHP production, nonetheless, MBT-based systems had similarly high performance if SRF streams were co-combusted with coal. When RDF and SRF was only used in dedicated WtE plants, MBT-based systems totalled lower savings due to inherent system losses and additional energy costs. In scenarios without heat recovery, the biodrying MBS-based system achieved the highest savings, on the condition of SRF co-combustion. As a sensitivity scenario, alternative utilisation of SRF in cement kilns was modelled. It supported similar or higher net savings for all pre-treatment systems compared to mass combustion WtE, except when WtE CHP was possible in the first two background energy scenarios. Recovery of plastics for recycling before energy recovery increased net energy savings in most scenario variations, over those of full

  18. Tissue transglutaminase is involved in mechanical load-induced osteogenic differentiation of human ligamentum flavum cells.

    PubMed

    Chao, Yuan-Hung; Huang, Shih-Yung; Yang, Ruei-Cheng; Sun, Jui-Sheng

    2016-07-01

    Mechanical load-induced osteogenic differentiation might be the key cellular event in the calcification and ossification of ligamentum flavum. The aim of this study was to investigate the influence of tissue transglutaminase (TGM2) on mechanical load-induced osteogenesis of ligamentum flavum cells. Human ligamentum flavum cells were obtained from 12 patients undergoing lumbar spine surgery. Osteogenic phenotypes of ligamentum flavum cells, such as alkaline phosphatase (ALP), Alizarin red-S stain, and gene expression of osteogenic makers were evaluated following the administration of mechanical load and BMP-2 treatment. The expression of TGM2 was evaluated by real-time PCR, Western blotting, and enzyme-linked immunosorbent assay (ELISA) analysis. Our results showed that mechanical load in combination with BMP-2 enhanced calcium deposition and ALP activity. Mechanical load significantly increased ALP and OC gene expression on day 3, whereas BMP-2 significantly increased ALP, OPN, and Runx2 on day 7. Mechanical load significantly induced TGM2 gene expression and enzyme activity in human ligamentum flavum cells. Exogenous TGM2 increased ALP and OC gene expression; while, inhibited TG activity significantly attenuated mechanical load-induced and TGM2-induced ALP activity. In summary, mechanical load-induced TGM2 expression and enzyme activity is involved in the progression of the calcification of ligamentum flavum.

  19. Biological mechanisms determining the success of RNA interference in insects.

    PubMed

    Wynant, Niels; Santos, Dulce; Vanden Broeck, Jozef

    2014-01-01

    Insects constitute the largest group of animals on this planet, having a huge impact on our environment, as well as on our quality of life. RNA interference (RNAi) is a posttranscriptional gene silencing mechanism triggered by double-stranded (ds)RNA fragments. This process not only forms the basis of a widely used reverse genetics research method in many different eukaryotes but also holds great promise to contribute to the species-specific control of agricultural pests and to combat viral infections in beneficial and disease vectoring insects. However, in many economically important insect species, such as flies, mosquitoes, and caterpillars, systemic delivery of naked dsRNA does not trigger effective gene silencing. Although many components of the RNAi pathway have initially been deciphered in the fruit fly, Drosophila melanogaster, it will be of major importance to investigate this process in a wider variety of species, including dsRNA-sensitive insects such as locusts and beetles, to elucidate the factors responsible for the remarkable variability in RNAi efficiency, as observed in different insects. In this chapter, we review the current knowledge on the RNAi pathway, as well as the most recent insights into the mechanisms that might determine successful RNAi in insects.

  20. Regenerative biology of tendon: mechanisms for renewal and repair

    PubMed Central

    Dyment, Nathaniel A.; Galloway, Jenna L.

    2015-01-01

    Understanding the molecular and cellular mechanisms underlying tissue turnover and repair are essential towards addressing pathologies in aging, injury and disease. Each tissue has distinct means of maintaining homeostasis and healing after injury. For some, resident stem cell populations mediate both of these processes. These stem cells, by definition, are self renewing and give rise to all the differentiated cells of that tissue. However, not all organs fit with this traditional stem cell model of regeneration, and some do not appear to harbor somatic stem or progenitor cells capable of multilineage in vivo reconstitution. Despite recent progress in tendon progenitor cell research, our current knowledge of the mechanisms regulating tendon cell homeostasis and injury response is limited. Understanding the role of resident tendon cell populations is of great importance for regenerative medicine based approaches to tendon injuries and disease. The goal of this review is to bring to light our current knowledge regarding tendon progenitor cells and their role in tissue maintenance and repair. We will focus on pressing questions in the field and the new tools, including model systems, available to address them. PMID:26389023

  1. Bioactive glass/hydroxyapatite composites: mechanical properties and biological evaluation.

    PubMed

    Bellucci, Devis; Sola, Antonella; Anesi, Alexandre; Salvatori, Roberta; Chiarini, Luigi; Cannillo, Valeria

    2015-06-01

    Bioactive glass/hydroxyapatite composites for bone tissue repair and regeneration have been produced and discussed. The use of a recently developed glass, namely BG_Ca/Mix, with its low tendency to crystallize, allowed one to sinter the samples at a relatively low temperature thus avoiding several adverse effects usually reported in the literature, such as extensive crystallization of the glassy phase, hydroxyapatite (HA) decomposition and reaction between HA and glass. The mechanical properties of the composites with 80wt.% BG_Ca/Mix and 20wt.% HA are sensibly higher than those of Bioglass® 45S5 reference samples due to the presence of HA (mechanically stronger than the 45S5 glass) and to the thermal behaviour of the BG_Ca/Mix, which is able to favour the sintering process of the composites. Biocompatibility tests, performed with murine fibroblasts BALB/3T3 and osteocites MLO-Y4 throughout a multi-parametrical approach, allow one to look with optimism to the produced composites, since both the samples themselves and their extracts do not induce negative effects in cell viability and do not cause inhibition in cell growth.

  2. Sequential mechanisms underlying concentration invariance in biological olfaction

    PubMed Central

    Cleland, Thomas A.; Chen, Szu-Yu T.; Hozer, Katarzyna W.; Ukatu, Hope N.; Wong, Kevin J.; Zheng, Fangfei

    2011-01-01

    Concentration invariance—the capacity to recognize a given odorant (analyte) across a range of concentrations—is an unusually difficult problem in the olfactory modality. Nevertheless, humans and other animals are able to recognize known odors across substantial concentration ranges, and this concentration invariance is a highly desirable property for artificial systems as well. Several properties of olfactory systems have been proposed to contribute to concentration invariance, but none of these alone can plausibly achieve full concentration invariance. We here propose that the mammalian olfactory system uses at least six computational mechanisms in series to reduce the concentration-dependent variance in odor representations to a level at which different concentrations of odors evoke reasonably similar representations, while preserving variance arising from differences in odor quality. We suggest that the residual variance then is treated like any other source of stimulus variance, and categorized appropriately into “odors” via perceptual learning. We further show that naïve mice respond to different concentrations of an odorant just as if they were differences in quality, suggesting that, prior to odor categorization, the learning-independent compensatory mechanisms are limited in their capacity to achieve concentration invariance. PMID:22287949

  3. Sirolimus: its discovery, biological properties, and mechanism of action.

    PubMed

    Sehgal, S N

    2003-05-01

    Sirolimus is the USAN-assigned generic name for the natural product rapamycin. Sirolimus is produced by a strain of Streptomyces hygroscopicus, isolated from a soil sample collected from Rapa Nui commonly known as Easter Island. Although sirolimus was isolated as an antifungal agent with potent anticandida activity, subsequent studies revealed impressive antitumor and immunosuppressive activities. Sirolimus demonstrates activity against several murine tumors, such as B16 43 melanocarcinoma, Colon 26 tumor, EM ependymoblastoma, and mammary and colon 38 solid tumors. Sirolimus is a potent inhibitor of antigen-induced proliferation of T cells, B cells, and antibody production. Demonstration of the potent immunosuppressive activity of sirolimus in animal models of organ transplantation led to clinical trials and subsequent approval by regulatory authorities for prophylaxis of renal graft rejection. Interest in sirolimus as an immunosuppressive therapy in organ transplantation derives from its unique mechanism of action, its unique side-effect profile, and its ability to synergize with other immunosuppressive agents. The molecular mechanism underlying the antifungal, antiproliferative, and immunosuppressive activities of sirolimus is the same. Sirolimus forms an immunosuppressive complex with intracellular protein, FKBP12. This complex blocks the activation of the cell-cycle-specific kinase, TOR. The downstream events that follow the inactivation of TOR result in the blockage of cell-cycle progression at the juncture of G1 and S phase.

  4. Biological mechanisms supporting adaptation to ocean acidification in coastal ecosystems

    NASA Astrophysics Data System (ADS)

    Hendriks, Iris E.; Duarte, Carlos M.; Olsen, Ylva S.; Steckbauer, Alexandra; Ramajo, Laura; Moore, Tommy S.; Trotter, Julie A.; McCulloch, Malcolm

    2015-01-01

    The direct influence of anthropogenic CO2 might play a limited role in pH regulation in coastal ecosystems as pH regulation in these areas can be complex. They experience large variability across a broad range of spatial and temporal scales, with complex external and internal drivers. Organisms influence pH at a patch scale, where community metabolic effects and hydrodynamic processes interact to produce broad ranges in pH, (∼0.3-0.5 pH units) over daily cycles and spatial scales (mm to m) particularly in shallow vegetated habitats and coral reefs where both respiration and photosynthetic activity are intense. Biological interactions at the ecosystem scale, linked to patchiness in habitat landscapes and seasonal changes in metabolic processes and temperature lead to changes of about 0.3-0.5 pH units throughout a year. Furthermore, on the scale of individual organisms, small-scale processes including changes at the Diffusive Boundary Layer (DBL), interactions with symbionts, and changes to the specific calcification environment, induce additional changes in excess of 0.5 pH units. In these highly variable pH environments calcifying organisms have developed the capacity to alter the pH of their calcifying environment, or specifically within critical tissues where calcification occurs, thus achieving a homeostasis. This capacity to control the conditions for calcification at the organism scale may therefore buffer the full impacts of ocean acidification on an organism scale, although this might be at a cost to the individual. Furthermore, in some areas, calcifiers may potentially benefit from changes to ambient seawater pH, where photosynthetic organisms drawdown CO2.

  5. Noise in biological systems: pros, cons, and mechanisms of control.

    PubMed

    Pilpel, Yitzhak

    2011-01-01

    Genetic regulatory circuits are often regarded as precise machines that accurately determine the level of expression of each protein. Most experimental technologies used to measure gene expression levels are incapable of testing and challenging this notion, as they often measure levels averaged over entire populations of cells. Yet, when expression levels are measured at the single cell level of even genetically identical cells, substantial cell-to-cell variation (or "noise") may be observed. Sometimes different genes in a given genome may display different levels of noise; even the same gene, expressed under different environmental conditions, may display greater cell-to-cell variability in specific conditions and more tight control in other situations. While at first glance noise may seem to be an undesired property of biological networks, it might be beneficial in some cases. For instance, noise will increase functional heterogeneity in a population of microorganisms facing variable, often unpredictable, environmental changes, increasing the probability that some cells may survive the stress. In that respect, we can speculate that the population is implementing a risk distribution strategy, long before genetic heterogeneity could be acquired. Organisms may have evolved to regulate not only the averaged gene expression levels but also the extent of allowed deviations from such an average, setting it at the desired level for every gene under each specific condition. Here we review the evolving understanding of noise, its molecular underpinnings, and its effect on phenotype and fitness--when it can be detrimental, beneficial, or neutral and which regulatory tools eukaryotic cells may use to optimally control it.

  6. Viral evasion mechanisms of early antiviral responses involving regulation of ubiquitin pathways.

    PubMed

    Rajsbaum, Ricardo; García-Sastre, Adolfo

    2013-08-01

    Early innate and cell-intrinsic responses are essential to protect host cells against pathogens. In turn, viruses have developed sophisticated mechanisms to establish productive infections by counteracting host innate immune responses. Increasing evidence indicates that these antiviral factors may have a dual role by directly inhibiting viral replication as well as by sensing and transmitting signals to induce antiviral cytokines. Recent studies have pointed at new, unappreciated mechanisms of viral evasion of host innate protective responses including manipulating the host ubiquitin (Ub) system. Virus-mediated inhibition of antiviral factors by Ub-dependent degradation is emerging as a crucial mechanism for evading the antiviral response. In addition, recent studies have uncovered new mechanisms by which virus-encoded proteins inhibit Ub and Ub-like (Ubl) modification of host proteins involved in innate immune signaling pathways. Here we discuss recent findings and novel strategies that viruses have developed to counteract these early innate antiviral defenses.

  7. Mechanisms of bacterial morphogenesis: evolutionary cell biology approaches provide new insights.

    PubMed

    Jiang, Chao; Caccamo, Paul D; Brun, Yves V

    2015-04-01

    How Darwin's "endless forms most beautiful" have evolved remains one of the most exciting questions in biology. The significant variety of bacterial shapes is most likely due to the specific advantages they confer with respect to the diverse environments they occupy. While our understanding of the mechanisms generating relatively simple shapes has improved tremendously in the last few years, the molecular mechanisms underlying the generation of complex shapes and the evolution of shape diversity are largely unknown. The emerging field of bacterial evolutionary cell biology provides a novel strategy to answer this question in a comparative phylogenetic framework. This relatively novel approach provides hypotheses and insights into cell biological mechanisms, such as morphogenesis, and their evolution that would have been difficult to obtain by studying only model organisms. We discuss the necessary steps, challenges, and impact of integrating "evolutionary thinking" into bacterial cell biology in the genomic era.

  8. Mechanisms of bacterial morphogenesis: Evolutionary cell biology approaches provide new insights

    PubMed Central

    Jiang, Chao; Caccamo, Paul D.; Brun, Yves V.

    2015-01-01

    How Darwin’s “endless forms most beautiful” have evolved remains one of the most exciting questions in biology. The significant variety of bacterial shapes is most likely due to the specific advantages they confer with respect to the diverse environments they occupy. While our understanding of the mechanisms generating relatively simple shapes has improved tremendously in the last few years, the molecular mechanisms underlying the generation of complex shapes and the evolution of shape diversity are largely unknown. The emerging field of bacterial evolutionary cell biology provides a novel strategy to answer this question in a comparative phylogenetic framework. This relatively novel approach provides hypotheses and insights into cell biological mechanisms, such as morphogenesis, and their evolution that would have been difficult to obtain by studying only model organisms. We discuss the necessary steps, challenges, and impact of integrating “evolutionary thinking” into bacterial cell biology in the genomic era. PMID:25664446

  9. Large deformation mechanical testing of biological membranes using speckle interferometry in transmission. I: Experimental apparatus.

    PubMed

    Charette, P G; Hunter, I W; Hunter, P J

    1997-04-01

    This paper describes an apparatus designed to study large mechanical deformations in biological membranes. The task of mechanically characterizing biological membranes is challenging because of the anisotropic and nonlinear nature of their material properties. The apparatus described here is well suited to the task because it uses speckle interferometry to measure in-plane displacements in a distributed fashion and has multiple degrees of freedom in the applied stress mechanism. In this way few a priori assumptions or restrictions are imposed on the applied stress and strain fields. The interferometer operates in transmission mode to increase the light efficiency of the system since the sample biological membranes are translucent and reflect little light. The experimental results confirm that the strain fields in the biological membranes that are generated in the experiments are highly nonuniform and cannot be properly estimated from a small number of point measurements.

  10. Reductive activation of mitomycin C by thiols: kinetics, mechanism, and biological implications.

    PubMed

    Paz, Manuel M

    2009-10-01

    The clinically used antitumor antibiotic mitomycin C requires a reductive activation to be converted to a bis-electrophile that forms several covalent adducts with DNA, including an interstrand cross-link which is considered to be the lesion responsible for the cytotoxic effects of the drug. Enzymes such as cytochrome P450 reductase and DT-diaphorase have traditionally been implicated in the bioreduction of mitomycin C, but recent reports indicate that enzymes containing a dithiol active site are also involved in the metabolism of mitomycin C. The reductive activation can also be effected in vitro with chemical reductants, but until now, mitomycin C was considered to be inert to thiols. We report here that mitomycin C can, in fact, be reductively activated by thiols. We show that the reaction is autocatalytic and that the end product is a relatively stable aziridinomitosene that can be trapped by adding several nucleophiles after the activation reaction. Kinetic studies show that the reaction is highly sensitive to pH and does not proceed or proceeds very slowly at neutral pH, an observation that explains the unsuccessful results on previous attempts to activate mitomycin C with thiols. The optimum pH for the reactions is around the pK(a) values of the thiols used in the activation. A mechanism for the reaction is hypothesized, involving the initial formation of a thiolate-mitomycin adduct, that then evolves to give the hydroquinone of mitomycin C and disulfide. The results presented here provide a chemical mechanism to explain how some biological dithiols containing an unusually acidic thiol group (deprotonated at physiological pH) participate in the modulation of mitomycin C cytotoxicity.

  11. An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields

    PubMed Central

    Tuszynski, Jack A.; Wenger, Cornelia; Friesen, Douglas E.; Preto, Jordane

    2016-01-01

    Long-standing research on electric and electromagnetic field interactions with biological cells and their subcellular structures has mainly focused on the low- and high-frequency regimes. Biological effects at intermediate frequencies between 100 and 300 kHz have been recently discovered and applied to cancer cells as a therapeutic modality called Tumor Treating Fields (TTFields). TTFields are clinically applied to disrupt cell division, primarily for the treatment of glioblastoma multiforme (GBM). In this review, we provide an assessment of possible physical interactions between 100 kHz range alternating electric fields and biological cells in general and their nano-scale subcellular structures in particular. This is intended to mechanistically elucidate the observed strong disruptive effects in cancer cells. Computational models of isolated cells subject to TTFields predict that for intermediate frequencies the intracellular electric field strength significantly increases and that peak dielectrophoretic forces develop in dividing cells. These findings are in agreement with in vitro observations of TTFields’ disruptive effects on cellular function. We conclude that the most likely candidates to provide a quantitative explanation of these effects are ionic condensation waves around microtubules as well as dielectrophoretic effects on the dipole moments of microtubules. A less likely possibility is the involvement of actin filaments or ion channels. PMID:27845746

  12. Approaching magnetic field effects in biology using the radical pair mechanism

    NASA Astrophysics Data System (ADS)

    Canfield, Jeffrey Michael

    1997-11-01

    The overall goal of this thesis has been to explain any of the reported magnetic field effects in biology (magnetic orientation of many species and/or health effects, such as cancer, due to man-made electromagnetic fields) using the radical pair mechanism, a quantum mechanical mechanism known for over 20 years that lets singlet-to-triplet yields (which can be related to reaction rates) of radical pair reactions depend on applied magnetic fields. This goal seems reasonable considering the known roles of many biological free radicals in cancer, disease, aging, development, and cellular signaling, the constant reminders in the media to take anti-oxidant vitamins to protect against certain deleterious free radicals, and the success of the radical pair mechanism in explaining magnetic field effects in photosynthetic reaction centers. To approach the above goal, this thesis develops several methods (using perturbation theory and other techniques in the Schrodinger and Liouville formalisms) for calculating singlet-to-triplet yields in combinations of steady and oscillating fields (some of these algorithms are more versatile or efficient while others give more insight, and all serve as cross-checks on each other) and uses these tools to explore and explain a number of interesting phenomena such as yields sensitive to the magnitude and orientation of earth-strength (0.5 G) steady fields as well as the magnitude, orientation, and frequency of very weak (7 mG or less) oscillating fields. In particular, this thesis examines such effects in several coenzyme B12 systems, systems long studied by EPR (Electron Paramagnetic Resonance, the chief method for determining the spin Hamiltonians, spin relaxation rates, and other parameters needed for calculations) in which organometallic cobalt-carbon bonds are often cleaved homolytically to form radical pairs. Among the B12-dependent enzymes are ribonucleotide reductase (which converts RNA to DNA nucleotides), methyl malonyl CoA mutase

  13. Application of bacteria involved in the biological sulfur cycle for paper mill effluent purification.

    PubMed

    Janssen, Albert J H; Lens, Piet N L; Stams, Alfons J M; Plugge, Caroline M; Sorokin, Dimitri Y; Muyzer, Gerard; Dijkman, Henk; Van Zessen, Erik; Luimes, Peter; Buisman, Cees J N

    2009-02-01

    In anaerobic wastewater treatment, the occurrence of biological sulfate reduction results in the formation of unwanted hydrogen sulfide, which is odorous, corrosive and toxic. In this paper, the role and application of bacteria in anaerobic and aerobic sulfur transformations are described and exemplified for the treatment of a paper mill wastewater. The sulfate containing wastewater first passes an anaerobic UASB reactor for bulk COD removal which is accompanied by the formation of biogas and hydrogen sulfide. In an aeration pond, the residual CODorganic and the formed dissolved hydrogen sulfide are removed. The biogas, consisting of CH4 (80-90 vol.%), CO2 (10-20 vol.%) and H2S (0.8-1.2 vol.%), is desulfurised prior to its combustion in a power generator thereby using a new biological process for H2S removal. This process will be described in more detail in this paper. Biomass from the anaerobic bioreactor has a compact granular structure and contains a diverse microbial community. Therefore, other anaerobic bioreactors throughout the world are inoculated with biomass from this UASB reactor. The sludge was also successfully used in investigation on sulfate reduction with carbon monoxide as the electron donor and the conversion of methanethiol. This shows the biotechnological potential of this complex reactor biomass.

  14. Elucidating the coordination chemistry and mechanism of biological nitrogen fixation.

    PubMed

    Dance, Ian

    2007-08-03

    How does the enzyme nitrogenase reduce the inert molecule N2 to NH3 under ambient conditions that are so different from the energy-expensive conditions of the best industrial practices? This review focuses on recent theoretical investigations of the catalytic site, the iron-molybdenum cofactor FeMo-co, and the way in which it is hydrogenated by protons and electrons and then binds N2. Density functional calculations provide reaction profiles and activation energies for possible mechanistic steps. This establishes a conceptual framework and the principles for the coordination chemistry of FeMo-co that are essential to the chemical mechanism of catalysis. The model advanced herein explains relevant experimental data.

  15. The CRISPR-Cas immune system: biology, mechanisms and applications.

    PubMed

    Rath, Devashish; Amlinger, Lina; Rath, Archana; Lundgren, Magnus

    2015-10-01

    Viruses are a common threat to cellular life, not the least to bacteria and archaea who constitute the majority of life on Earth. Consequently, a variety of mechanisms to resist virus infection has evolved. A recent discovery is the adaptive immune system in prokaryotes, a type of system previously thought to be present only in vertebrates. The system, called CRISPR-Cas, provide sequence-specific adaptive immunity and fundamentally affect our understanding of virus-host interaction. CRISPR-based immunity acts by integrating short virus sequences in the cell's CRISPR locus, allowing the cell to remember, recognize and clear infections. There has been rapid advancement in our understanding of this immune system and its applications, but there are many aspects that await elucidation making the field an exciting area of research. This review provides an overview of the field and highlights unresolved issues.

  16. Cell biological mechanisms of multidrug resistance in tumors.

    PubMed Central

    Simon, S M; Schindler, M

    1994-01-01

    Multidrug resistance (MDR) is a generic term for the variety of strategies tumor cells use to evade the cytotoxic effects of anticancer drugs. MDR is characterized by a decreased sensitivity of tumor cells not only to the drug employed for chemotherapy but also to a broad spectrum of drugs with neither obvious structural homology nor common targets. This pleiotropic resistance is one of the major obstacles to the successful treatment of tumors. MDR may result from structural or functional changes at the plasma membrane or within the cytoplasm, cellular compartments, or nucleus. Molecular mechanisms of MDR are discussed in terms of modifications in detoxification and DNA repair pathways, changes in cellular sites of drug sequestration, decreases in drug-target affinity, synthesis of specific drug inhibitors within cells, altered or inappropriate targeting of proteins, and accelerated removal or secretion of drugs. PMID:7909602

  17. [Involvement of adrenergic mechanisms in developing the nervous syndrome of high pressure and nitrogen narcosis].

    PubMed

    Sledkov, A I; Bernarskii, K V; Shilina, M N

    1996-01-01

    Involvement of the adrenergic mediator system in central mechanisms of hyperbaric nitrogen narcosis or the high pressure nervous syndrome (NSHP) produced by nitrogen or heliox gas mixtures under increased pressure was studied in mice and rabbit experiments with the use of pharmacological substances-analyzers. Accumulated data are indicative of lack of a significant role of the adrenergic system in the NSHP genesis and a protective effect of activation of the central but not peripheric adrenergic mediation in development of the behavioural and electrophysiological symptomatics of nitrogen narcosis. Mechanisms of NSHP and nitrogen narcosis and possible principles of pharmacological correction are under discussion.

  18. Neural Mechanisms Involved in Hypersensitive Hearing: Helping Children with ASD Who Are Overly Sensitive to Sounds

    PubMed Central

    Lucker, Jay R.; Doman, Alex

    2015-01-01

    Professionals working with children diagnosed with autism spectrum disorder (ASD) may find that these children are overly sensitive to sounds. These professionals are often concerned as to why children may have auditory hypersensitivities. This review article discusses the neural mechanisms identified underlying hypersensitive hearing in people. The authors focus on brain research to support the idea of the nonclassical auditory pathways being involved in connecting the auditory system with the emotional system of the brain. The authors also discuss brain mechanisms felt to be involved in auditory hypersensitivity. The authors conclude with a discussion of some treatments for hypersensitive hearing. These treatments include desensitization training and the use of listening therapies such as The Listening Program. PMID:26823983

  19. A Model of How Different Biology Experts Explain Molecular and Cellular Mechanisms

    ERIC Educational Resources Information Center

    Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

    2015-01-01

    Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do…

  20. Ionic mechanisms involved in the nodal swelling of myelinated axons caused by marine toxins.

    PubMed

    Benoit, Evelyne; Mattei, Cesar; Ouanounou, Gilles; Meunier, Frederic A; Suput, Dusan; Le Gall, Frederic; Marquais, Michel; Dechraoui, Marie Y; Molgo, Jordi

    2002-01-01

    This review describes the ionic mechanisms involved in the nodal swelling of frog myelinated axons caused by specific marine neurotoxins (ciguatoxins, brevetoxins, Conus consors toxin and equinatoxin-II), analysed using confocal laser scanning microscopy. We have focussed on toxins that either target neuronal voltage-dependent Na+ channels, or that form cation-selective pores and indirectly affect the functioning of the Na(+)-Ca(++)exchanger.

  1. Stimulating immune responses to fight cancer: Basic biology and mechanisms.

    PubMed

    O'Byrne, Kenneth

    2015-04-01

    Chronic inflammation is now recognized as a major cause of malignant disease. In concert with various mechanisms (including DNA instability), hypoxia and activation of inflammatory bioactive lipid pathways and pro-inflammatory cytokines open the doorway to malignant transformation and proliferation, angiogenesis, and metastasis in many cancers. A balance between stimulatory and inhibitory signals regulates the immune response to cancer. These include inhibitory checkpoints that modulate the extent and duration of the immune response and may be activated by tumor cells. This contributes to immune resistance, especially against tumor antigen-specific T-cells. Targeting these checkpoints is an evolving approach to cancer immunotherapy, designed to foster an immune response. The current focus of these trials is on the programmed cell death protein 1 (PD-1) receptor and its ligands (PD-L1, PD-L2) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Researchers have developed anti-PD-1 and anti-PDL-1 antibodies that interfere with the ligands and receptor and allow the tumor cell to be recognized and attacked by tumor-infiltrating T-cells. These are currently being studied in lung cancer. Likewise, CTLA-4 inhibitors, which have had success treating advanced melanoma, are being studied in lung cancer with encouraging results.

  2. Triage, monitoring, and treatment of mass casualty events involving chemical, biological, radiological, or nuclear agents

    PubMed Central

    Ramesh, Aruna C.; Kumar, S.

    2010-01-01

    In a mass casualty situation due to chemical, biological, radiological, or nuclear (CBRN) event, triage is absolutely required for categorizing the casualties in accordance with medical care priorities. Dealing with a CBRN event always starts at the local level. Even before the detection and analysis of agents can be undertaken, zoning, triage, decontamination, and treatment should be initiated promptly. While applying the triage system, the available medical resources and maximal utilization of medical assets should be taken into consideration by experienced triage officers who are most familiar with the natural course of the injury presented and have detailed information on medical assets. There are several triage systems that can be applied to CBRN casualties. With no one standardized system globally or nationally available, it is important for deploying a triage and decontamination system which is easy to follow and flexible to the available medical resources, casualty number, and severity of injury. PMID:21829319

  3. Microbial communities involved in biological ammonium removal from coal combustion wastewaters.

    PubMed

    Vishnivetskaya, Tatiana A; Fisher, L Suzanne; Brodie, Greg A; Phelps, Tommy J

    2013-07-01

    The efficiency of a novel integrated treatment system for biological removal of ammonium, nitrite, nitrate, and heavy metals from fossil power plant effluent was evaluated. Microbial communities were analyzed using bacterial and archaeal 16S rRNA gene clone libraries (Sanger sequences) and 454 pyrosequencing technology. While seasonal changes in microbial community composition were observed, the significant (P = 0.001) changes in bacterial and archaeal communities were consistent with variations in ammonium concentration. Phylogenetic analysis of 16S rRNA gene sequences revealed an increase of potential ammonium-oxidizing bacteria (AOB), Nitrosomonas, Nitrosococcus, Planctomycetes, and OD1, in samples with elevated ammonium concentration. Other bacteria, such as Nitrospira, Nitrococcus, Nitrobacter, Thiobacillus, ε-Proteobacteria, Firmicutes, and Acidobacteria, which play roles in nitrification and denitrification, were also detected. The AOB oxidized 56 % of the ammonium with the concomitant increase in nitrite and ultimately nitrate in the trickling filters at the beginning of the treatment system. Thermoprotei within the phylum Crenarchaeota thrived in the splitter box and especially in zero-valent iron extraction trenches, where an additional 25 % of the ammonium was removed. The potential ammonium-oxidizing Archaea (AOA) (Candidatus Nitrosocaldus) were detected towards the downstream end of the treatment system. The design of an integrated treatment system consisting of trickling filters, zero-valent iron reaction cells, settling pond, and anaerobic wetlands was efficient for the biological removal of ammonium and several other contaminants from wastewater generated at a coal burning power plant equipped with selective catalytic reducers for nitrogen oxide removal.

  4. Unravelling novel synergies between organometallic and biological partners: a quantum mechanics/molecular mechanics study of an artificial metalloenzyme

    PubMed Central

    Ortega-Carrasco, Elisabeth; Lledós, Agustí; Maréchal, Jean-Didier

    2014-01-01

    In recent years, the design of artificial metalloenzymes obtained by the insertion of homogeneous catalysts into biological macromolecules has become a major field of research. These hybrids, and the corresponding X-ray structures of several of them, are offering opportunities to better understand the synergy between organometallic and biological subsystems. In this work, we investigate the resting state and activation process of a hybrid inspired by an oxidative haemoenzyme but presenting an unexpected reactivity and structural features. An extensive series of quantum mechanics/molecular mechanics calculations show that the resting state and the activation processes of the novel enzyme differ from naturally occurring haemoenzymes in terms of the electronic state of the metal, participation of the first coordination sphere of the metal and the dynamic process. This study presents novel insights into the sensitivity of the association between organometallic and biological partners and illustrates the molecular challenge that represents the design of efficient enzymes based on this strategy. PMID:24829279

  5. Unravelling novel synergies between organometallic and biological partners: a quantum mechanics/molecular mechanics study of an artificial metalloenzyme.

    PubMed

    Ortega-Carrasco, Elisabeth; Lledós, Agustí; Maréchal, Jean-Didier

    2014-07-06

    In recent years, the design of artificial metalloenzymes obtained by the insertion of homogeneous catalysts into biological macromolecules has become a major field of research. These hybrids, and the corresponding X-ray structures of several of them, are offering opportunities to better understand the synergy between organometallic and biological subsystems. In this work, we investigate the resting state and activation process of a hybrid inspired by an oxidative haemoenzyme but presenting an unexpected reactivity and structural features. An extensive series of quantum mechanics/molecular mechanics calculations show that the resting state and the activation processes of the novel enzyme differ from naturally occurring haemoenzymes in terms of the electronic state of the metal, participation of the first coordination sphere of the metal and the dynamic process. This study presents novel insights into the sensitivity of the association between organometallic and biological partners and illustrates the molecular challenge that represents the design of efficient enzymes based on this strategy.

  6. Motivational concordance: an important mechanism in self-help therapeutic rituals involving inert (placebo) substances.

    PubMed

    Hyland, Michael E; Whalley, Ben

    2008-11-01

    We tested the contribution of two mechanisms, response expectancy and motivational concordance, to reported psychological benefit from a popular, biologically inactive, self-help, complementary therapy (a placebo). Flower essences were taken by 251 people for self-selected symptoms and were randomized to receive three different kinds of information. When the flower essence was presented as a spiritual therapy, then baseline spirituality (beta=.35, P=.01) and expectancy (beta=.25, P=.03) independently predicted outcome. When flower essences were presented as an affirmation (i.e., nonspiritual) therapy, then spirituality negatively (beta=-.27, P=.03) and expectancy (beta=.33, P=.01) predicted outcome. For both groups, expectancy predicted outcome after controlling for spirituality and compliance, but did not after controlling for ease of task completion. Expectancy failed to predict outcome in the nonenhanced ritual group. The results suggest that motivational concordance is an important therapeutic mechanism for real-life placebos.

  7. Structure and mechanical properties of Saxidomus purpuratus biological shells.

    PubMed

    Yang, W; Zhang, G P; Zhu, X F; Li, X W; Meyers, M A

    2011-10-01

    The strength and fracture behavior of Saxidomus purpuratus shells were investigated and correlated with the structure. The shells show a crossed lamellar structure in the inner and middle layers and a fibrous/blocky and porous structure composed of nanoscaled particulates (~100 nm diameter) in the outer layer. It was found that the flexure strength and fracture mode are a function of lamellar organization and orientation. The crossed lamellar structure of this shell is composed of domains of parallel lamellae with approximate thickness of 200-600 nm. These domains have approximate lateral dimensions of 10-70 μm with a minimum of two orientations of lamellae in the inner and middle layers. Neighboring domains are oriented at specific angles and thus the structure forms a crossed lamellar pattern. The microhardness across the thickness was lower in the outer layer because of the porosity and the absence of lamellae. The tensile (from flexure tests) and compressive strengths were analyzed by means of Weibull statistics. The mean tensile (flexure) strength at probability of 50%, 80-105 MPa, is on the same order as the compressive strength (~50-150 MPa) and the Weibull moduli vary from 3.0 to 7.6. These values are significantly lower than abalone nacre, in spite of having the same aragonite structure. The lower strength can be attributed to a smaller fraction of the organic interlayer. The fracture path in the specimens is dominated by the orientation of the domains and proceeds preferentially along lamella boundaries. It also correlates with the color changes in the cross section of the shell. The cracks tend to undergo a considerable change in orientation when the color changes abruptly. The distributions of strengths, cracking paths, and fracture surfaces indicate that the mechanical properties of the shell are anisotropic with a hierarchical nature.

  8. Investigation on thiosulfate-involved organics and nitrogen removal by a sulfur cycle-based biological wastewater treatment process.

    PubMed

    Qian, Jin; Lu, Hui; Cui, Yanxiang; Wei, Li; Liu, Rulong; Chen, Guang-Hao

    2015-02-01

    Thiosulfate, as an intermediate of biological sulfate/sulfite reduction, can significantly improve nitrogen removal potential in a biological sulfur cycle-based process, namely the Sulfate reduction-Autotrophic denitrification-Nitrification Integrated (SANI(®)) process. However, the related thiosulfate bio-activities coupled with organics and nitrogen removal in wastewater treatment lacked detailed examinations and reports. In this study, S2O3(2-) transformation during biological SO4(2-)/SO3(2-) co-reduction coupled with organics removal as well as S2O3(2-) oxidation coupled with chemolithotrophic denitrification were extensively evaluated under different experimental conditions. Thiosulfate is produced from the co-reduction of sulfate and sulfite through biological pathway at an optimum pH of 7.5 for organics removal. And the produced S2O3(2-) may disproportionate to sulfide and sulfate during both biological S2O3(2-) reduction and oxidation most possibly carried out by Desulfovibrio-like species. Dosing the same amount of nitrate, pH was found to be the more direct factor influencing the denitritation activity than free nitrous acid (FNA) and the optimal pH for denitratation (7.0) and denitritation (8.0) activities were different. Spiking organics significantly improved both denitratation and denitritation activities while minimizing sulfide inhibition of NO3(-) reduction during thiosulfate-based denitrification. These findings in this study can improve the understanding of mechanisms of thiosulfate on organics and nitrogen removal in biological sulfur cycle-based wastewater treatment.

  9. Ideas and perspectives: climate-relevant marine biologically driven mechanisms in Earth system models

    NASA Astrophysics Data System (ADS)

    Hense, Inga; Stemmler, Irene; Sonntag, Sebastian

    2017-01-01

    The current generation of marine biogeochemical modules in Earth system models (ESMs) considers mainly the effect of marine biota on the carbon cycle. We propose to also implement other biologically driven mechanisms in ESMs so that more climate-relevant feedbacks are captured. We classify these mechanisms in three categories according to their functional role in the Earth system: (1) biogeochemical pumps, which affect the carbon cycling; (2) biological gas and particle shuttles, which affect the atmospheric composition; and (3) biogeophysical mechanisms, which affect the thermal, optical, and mechanical properties of the ocean. To resolve mechanisms from all three classes, we find it sufficient to include five functional groups: bulk phyto- and zooplankton, calcifiers, and coastal gas and surface mat producers. We strongly suggest to account for a larger mechanism diversity in ESMs in the future to improve the quality of climate projections.

  10. Quantum Information Biology: From Information Interpretation of Quantum Mechanics to Applications in Molecular Biology and Cognitive Psychology

    NASA Astrophysics Data System (ADS)

    Asano, Masanari; Basieva, Irina; Khrennikov, Andrei; Ohya, Masanori; Tanaka, Yoshiharu; Yamato, Ichiro

    2015-10-01

    We discuss foundational issues of quantum information biology (QIB)—one of the most successful applications of the quantum formalism outside of physics. QIB provides a multi-scale model of information processing in bio-systems: from proteins and cells to cognitive and social systems. This theory has to be sharply distinguished from "traditional quantum biophysics". The latter is about quantum bio-physical processes, e.g., in cells or brains. QIB models the dynamics of information states of bio-systems. We argue that the information interpretation of quantum mechanics (its various forms were elaborated by Zeilinger and Brukner, Fuchs and Mermin, and D' Ariano) is the most natural interpretation of QIB. Biologically QIB is based on two principles: (a) adaptivity; (b) openness (bio-systems are fundamentally open). These principles are mathematically represented in the framework of a novel formalism— quantum adaptive dynamics which, in particular, contains the standard theory of open quantum systems.

  11. A metabolic model for members of the genus Tetrasphaera involved in enhanced biological phosphorus removal

    PubMed Central

    Kristiansen, Rikke; Nguyen, Hien Thi Thu; Saunders, Aaron Marc; Nielsen, Jeppe Lund; Wimmer, Reinhard; Le, Vang Quy; McIlroy, Simon Jon; Petrovski, Steve; Seviour, Robert J; Calteau, Alexandra; Nielsen, Kåre Lehmann; Nielsen, Per Halkjær

    2013-01-01

    Members of the genus Tetrasphaera are considered to be putative polyphosphate accumulating organisms (PAOs) in enhanced biological phosphorus removal (EBPR) from wastewater. Although abundant in Danish full-scale wastewater EBPR plants, how similar their ecophysiology is to ‘Candidatus Accumulibacter phosphatis' is unclear, although they may occupy different ecological niches in EBPR communities. The genomes of four Tetrasphaera isolates (T. australiensis, T. japonica, T. elongata and T. jenkinsii) were sequenced and annotated, and the data used to construct metabolic models. These models incorporate central aspects of carbon and phosphorus metabolism critical to understanding their behavior under the alternating anaerobic/aerobic conditions encountered in EBPR systems. Key features of these metabolic pathways were investigated in pure cultures, although poor growth limited their analyses to T. japonica and T. elongata. Based on the models, we propose that under anaerobic conditions the Tetrasphaera-related PAOs take up glucose and ferment this to succinate and other components. They also synthesize glycogen as a storage polymer, using energy generated from the degradation of stored polyphosphate and substrate fermentation. During the aerobic phase, the stored glycogen is catabolized to provide energy for growth and to replenish the intracellular polyphosphate reserves needed for subsequent anaerobic metabolism. They are also able to denitrify. This physiology is markedly different to that displayed by ‘Candidatus Accumulibacter phosphatis', and reveals Tetrasphaera populations to be unusual and physiologically versatile PAOs carrying out denitrification, fermentation and polyphosphate accumulation. PMID:23178666

  12. Population dynamics of bacteria involved in enhanced biological phosphorus removal in Danish wastewater treatment plants.

    PubMed

    Mielczarek, Artur Tomasz; Nguyen, Hien Thi Thu; Nielsen, Jeppe Lund; Nielsen, Per Halkjær

    2013-03-15

    The enhanced biological phosphorus removal (EBPR) process is increasingly popular as a sustainable method for removal of phosphorus (P) from wastewater. This study consisted of a comprehensive three-year investigation of the identity and population dynamics of polyphosphate-accumulating organisms (PAOs) and glycogen-accumulating organisms (GAOs) in 28 Danish municipal wastewater treatment plants with nutrient removal. Fluorescence in situ hybridization was applied to quantify ten probe-defined populations of PAO and GAO that in total constituted a large fraction (30% on average) of the entire microbial community targeted by the EUBmix probes. Two PAO genera, Accumulibacter and Tetrasphaera, were very abundant in all EBPR plants (average of 3.7% and 27% of all bacteria, respectively), and their abundance was relatively stable in the Danish full-scale plants without clear temporal variations. GAOs were occasionally present in some plants (Competibacter in 11 plants, Defluviicoccus in 6 plants) and were consistent in only a few plants. This shows that these were not core species in the EBPR communities. The total GAO abundance was always lower than that of Accumulibacter. In plants without EBPR design, the abundance of PAO and GAO was significantly lower. Competibacter correlated in general with high fraction of industrial wastewater. In specific plants Accumulibacter correlated with high C/P ratio of the wastewater and Tetrasphaera with high organic loading. Interestingly, the relative microbial composition of the PAO/GAO species was unique to each plant over time, which gives a characteristic plant-specific "fingerprint".

  13. A metabolic model for members of the genus Tetrasphaera involved in enhanced biological phosphorus removal.

    PubMed

    Kristiansen, Rikke; Nguyen, Hien Thi Thu; Saunders, Aaron Marc; Nielsen, Jeppe Lund; Wimmer, Reinhard; Le, Vang Quy; McIlroy, Simon Jon; Petrovski, Steve; Seviour, Robert J; Calteau, Alexandra; Nielsen, Kåre Lehmann; Nielsen, Per Halkjær

    2013-03-01

    Members of the genus Tetrasphaera are considered to be putative polyphosphate accumulating organisms (PAOs) in enhanced biological phosphorus removal (EBPR) from wastewater. Although abundant in Danish full-scale wastewater EBPR plants, how similar their ecophysiology is to 'Candidatus Accumulibacter phosphatis' is unclear, although they may occupy different ecological niches in EBPR communities. The genomes of four Tetrasphaera isolates (T. australiensis, T. japonica, T. elongata and T. jenkinsii) were sequenced and annotated, and the data used to construct metabolic models. These models incorporate central aspects of carbon and phosphorus metabolism critical to understanding their behavior under the alternating anaerobic/aerobic conditions encountered in EBPR systems. Key features of these metabolic pathways were investigated in pure cultures, although poor growth limited their analyses to T. japonica and T. elongata. Based on the models, we propose that under anaerobic conditions the Tetrasphaera-related PAOs take up glucose and ferment this to succinate and other components. They also synthesize glycogen as a storage polymer, using energy generated from the degradation of stored polyphosphate and substrate fermentation. During the aerobic phase, the stored glycogen is catabolized to provide energy for growth and to replenish the intracellular polyphosphate reserves needed for subsequent anaerobic metabolism. They are also able to denitrify. This physiology is markedly different to that displayed by 'Candidatus Accumulibacter phosphatis', and reveals Tetrasphaera populations to be unusual and physiologically versatile PAOs carrying out denitrification, fermentation and polyphosphate accumulation.

  14. Involvement of TBL/DUF231 proteins into cell wall biology

    PubMed Central

    Selbig, Joachim; Scheible, Wolf-Rüdiger

    2010-01-01

    Through map-based cloning we determined TRICHOME BIREFRINGENCE (TBR) belongs to a plant-specific, yet anonymous gene family with 46 members in Arabidopsis thaliana. These genes all encode the domain of unknown function 231 (DUF231). TBR and its homolog TRICHOME BIREFRINGENCE-LIKE3 (TBL3) are transcriptionally coordinated with CELLULOSE SYNTHASE (CESA) genes, and loss of TBR or TBL3 results in decreased levels of crystalline secondary wall cellulose in trichomes and stems, respectively. Loss of TBR or TBL3 further results in increased pectin methylesterase (PME) activity and reduced pectin esterification in etiolated Arabidopsis hypocotyls. Together, the results suggest that DUF231 proteins might function in the maintenance of pectin- and probably homogalacturonan esterification, and that this is a requirement for normal secondary wall cellulose synthesis, at least in some tissues and organs. Here we expand the discussion about the role of TBL/DUF231 proteins in cell wall biology based on sequence and structure analyses. Our analysis revealed structural similarities of TBR with a rhamnogalacturonan acetylesterase (RGAE) of Aspergillus aculeatus and the protein LUSTRIN A-LIKE (Oryza sativa). The implications of these findings in regard to TBL functions are discussed. PMID:20657172

  15. Involvement of TBL/DUF231 proteins into cell wall biology.

    PubMed

    Bischoff, Volker; Selbig, Joachim; Scheible, Wolf-Rüdiger

    2010-08-01

    Through map-based cloning we determined TRICHOME BIREFRINGENCE (TBR) to belong to a plant-specific, yet anonymous gene family with 46 members in Arabidopsis thaliana. These genes all encode the domain of unknown function 231 (DUF231). TBR and its homolog TRICHOME BIREFRINGENCE-LIKE3 (TBL3) are transcriptionally coordinated with CELLULOSE SYNTHASE (CESA) genes, and loss of TBR or TBL3 results in decreased levels of crystalline secondary wall cellulose in trichomes and stems, respectively. Loss of TBR or TBL3 further results in increased pectin methylesterase (PME) activity and reduced pectin esterification in etiolated Arabidopsis hypocotyls. Together, the results suggest that DUF231 proteins might function in the maintenance of pectin- and probably homogalacturonan esterification, and that this is a requirement for normal secondary wall cellulose synthesis, at least in some tissues and organs. Here we expand the discussion about the role of TBL/DUF231 proteins in cell wall biology based on sequence and structure analyses. Our analysis revealed structural similarities of TBR with a rhamnogalacturonan acetylesterase (RGAE) of Aspergillus aculeatus and the protein LUSTRIN A-LIKE (Oryza sativa). The implications of these findings in regard to TBL functions are discussed.

  16. Peripheral and Central Mechanisms Involved in the Hormonal Control of Male and Female Reproduction

    PubMed Central

    Rudolph, L. M.; Bentley, G. E.; Calandra, R. S.; Paredes, A. H.; Tesone, M.; Wu, T. J.; Micevych, P. E.

    2016-01-01

    Reproduction involves the integration of hormonal signals acting across multiple systems to generate a synchronised physiological output. A critical component of reproduction is the luteinising hormone (LH) surge, which is mediated by oestradiol (E2) and neuroprogesterone interacting to stimulate kisspeptin release in the rostral periventricular nucleus of the third ventricle in rats. Recent evidence indicates the involvement of both classical and membrane E2 and progesterone signalling in this pathway. A metabolite of gonadotrophin-releasing hormone (GnRH), GnRH-(1-5), has been shown to stimulate GnRH expression and secretion, and has a role in the regulation of lordosis. Additionally, gonadotrophin release-inhibitory hormone (GnIH) projects to and influences the activity of GnRH neurones in birds. Stress-induced changes in GnIH have been shown to alter breeding behaviour in birds, demonstrating another mechanism for the molecular control of reproduction. Peripherally, paracrine and autocrine actions within the gonad have been suggested as therapeutic targets for infertility in both males and females. Dysfunction of testicular prostaglandin synthesis is a possible cause of idiopathic male infertility. Indeed, local production of melatonin and corticotrophin-releasing hormone could influence spermatogenesis via immune pathways in the gonad. In females, vascular endothelial growth factor A has been implicated in an angiogenic process that mediates development of the corpus luteum and thus fertility via the Notch signalling pathway. Age-induced decreases in fertility involve ovarian kisspeptin and its regulation of ovarian sympathetic innervation. Finally, morphological changes in the arcuate nucleus of the hypothalamus influence female sexual receptivity in rats. The processes mediating these morphological changes have been shown to involve the rapid effects of E2 controlling synaptogenesis in this hypothalamic nucleus. In summary, this review highlights new

  17. Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster

    NASA Astrophysics Data System (ADS)

    Jeibmann, Astrid; Eikmeier, Kristin; Linge, Anna; Kool, Marcel; Koos, Björn; Schulz, Jacqueline; Albrecht, Stefanie; Bartelheim, Kerstin; Frühwald, Michael C.; Pfister, Stefan M.; Paulus, Werner; Hasselblatt, Martin

    2014-06-01

    Atypical teratoid/rhabdoid tumours (AT/RT) are malignant brain tumours. Unlike most other human brain tumours, AT/RT are characterized by inactivation of one single gene, SMARCB1. SMARCB1 is a member of the evolutionarily conserved SWI/SNF chromatin remodelling complex, which has an important role in the control of cell differentiation and proliferation. Little is known, however, about the pathways involved in the oncogenic effects of SMARCB1 inactivation, which might also represent targets for treatment. Here we report a comprehensive genetic screen in the fruit fly that revealed several genes not yet associated with loss of snr1, the Drosophila homologue of SMARCB1. We confirm the functional role of identified genes (including merlin, kibra and expanded, known to regulate hippo signalling pathway activity) in human rhabdoid tumour cell lines and AT/RT tumour samples. These results demonstrate that fly models can be employed for the identification of clinically relevant pathways in human cancer.

  18. Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression.

    PubMed

    Verduijn, J; Milaneschi, Y; Schoevers, R A; van Hemert, A M; Beekman, A T F; Penninx, B W J H

    2015-09-29

    Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18-65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are

  19. Octamer-binding protein 4 affects the cell biology and phenotypic transition of lung cancer cells involving β-catenin/E-cadherin complex degradation.

    PubMed

    Chen, Zhong-Shu; Ling, Dong-Jin; Zhang, Yang-De; Feng, Jian-Xiong; Zhang, Xue-Yu; Shi, Tian-Sheng

    2015-03-01

    Clinical studies have reported evidence for the involvement of octamer‑binding protein 4 (Oct4) in the tumorigenicity and progression of lung cancer; however, the role of Oct4 in lung cancer cell biology in vitro and its mechanism of action remain to be elucidated. Mortality among lung cancer patients is more frequently due to metastasis rather than their primary tumors. Epithelial‑mesenchymal transition (EMT) is a prominent biological event for the induction of epithelial cancer metastasis. The aim of the present study was to investigate whether Oct4 had the capacity to induce lung cancer cell metastasis via the promoting the EMT in vitro. Moreover, the effect of Oct4 on the β‑catenin/E‑cadherin complex, associated with EMT, was examined using immunofluorescence and immunoprecipitation assays as well as western blot analysis. The results demonstrated that Oct4 enhanced cell invasion and adhesion accompanied by the downregulation of epithelial marker cytokeratin, and upregulation of the mesenchymal markers vimentin and N‑cadherin. Furthermore, Oct4 induced EMT of lung cancer cells by promoting β‑catenin/E‑cadherin complex degradation and regulating nuclear localization of β‑catenin. In conclusion, the present study indicated that Oct4 affected the cell biology of lung cancer cells in vitro through promoting lung cancer cell metastasis via EMT; in addition, the results suggested that the association and degradation of the β‑catenin/E‑cadherin complex was regulated by Oct4 during the process of EMT.

  20. Neuroimaging mechanisms of change in psychotherapy for addictive behaviors: emerging translational approaches that bridge biology and behavior.

    PubMed

    Feldstein Ewing, Sarah W; Chung, Tammy

    2013-06-01

    Research on mechanisms of behavior change provides an innovative method to improve treatment for addictive behaviors. An important extension of mechanisms of change research involves the use of translational approaches, which examine how basic biological (i.e., brain-based mechanisms) and behavioral factors interact in initiating and sustaining positive behavior change as a result of psychotherapy. Articles in this special issue include integrative conceptual reviews and innovative empirical research on brain-based mechanisms that may underlie risk for addictive behaviors and response to psychotherapy from adolescence through adulthood. Review articles discuss hypothesized mechanisms of change for cognitive and behavioral therapies, mindfulness-based interventions, and neuroeconomic approaches. Empirical articles cover a range of addictive behaviors, including use of alcohol, cigarettes, marijuana, cocaine, and pathological gambling and represent a variety of imaging approaches including fMRI, magneto-encephalography, real-time fMRI, and diffusion tensor imaging. Additionally, a few empirical studies directly examine brain-based mechanisms of change, whereas others examine brain-based indicators as predictors of treatment outcome. Finally, two commentaries discuss craving as a core feature of addiction, and the importance of a developmental approach to examining mechanisms of change. Ultimately, translational research on mechanisms of behavior change holds promise for increasing understanding of how psychotherapy may modify brain structure and functioning and facilitate the initiation and maintenance of positive treatment outcomes for addictive behaviors.

  1. Neuroimaging mechanisms of change in psychotherapy for addictive behaviors: Emerging translational approaches that bridge biology and behavior

    PubMed Central

    Feldstein Ewing, Sarah W.; Chung, Tammy

    2013-01-01

    Research on mechanisms of behavior change provides an innovative method to improve treatment for addictive behaviors. An important extension of mechanisms of change research involves the use of translational approaches, which examine how basic biological (i.e., brain-based mechanisms) and behavioral factors interact in initiating and sustaining positive behavior change as a result of psychotherapy. Articles in this special issue include integrative conceptual reviews and innovative empirical research on brain-based mechanisms that may underlie risk for addictive behaviors and response to psychotherapy from adolescence through adulthood. Review articles discuss hypothesized mechanisms of change for cognitive and behavioral therapies, mindfulness-based interventions, and neuroeconomic approaches. Empirical articles cover a range of addictive behaviors, including use of alcohol, cigarettes, marijuana, cocaine, and pathological gambling and represent a variety of imaging approaches including fMRI, magneto-encephalography, real time fMRI, and diffusion tensor imaging. Additionally, a few empirical studies directly examined brain-based mechanisms of change, whereas others examined brain-based indicators as predictors of treatment outcome. Finally, two commentaries discuss craving as a core feature of addiction, and the importance of a developmental approach to examining mechanisms of change. Ultimately, translational research on mechanisms of behavior change holds promise for increasing understanding of how psychotherapy may modify brain structure and functioning and facilitate the initiation and maintenance of positive treatment outcomes for addictive behaviors. PMID:23815447

  2. Mechanism and stereoselectivity of biologically important oxygenation reactions of the 7-dehydrocholesterol radical.

    PubMed

    Rajeev, Ramanan; Sunoj, Raghavan B

    2013-07-19

    The mechanism of free radical oxygenation of 7-dehydrocholesterol (7-DHC), one of the biologically important sterols, is investigated by using density functional theory. The energetic origin of the product distribution and the stereoelectronic factors involved in various mechanistic pathways are delineated. The addition of triplet molecular oxygen to two types of conjugatively stabilized radicals, generated by the removal of the reactive allylic hydrogens from C9 or C14 positions, respectively denoted as H9 and H14 pathways, is studied. The distortion-interaction analysis of the C-O bond formation transition states suggests that the energetic preference toward the α prochiral face stems from reduced skeletal distortions of the cholesterol backbone as compared to that in the corresponding β prochiral face. This insight derived through a detailed quantitative analysis of the stereocontrolling transition states suggests that the commonly found interpretations solely based on steric interactions between the incoming oxygen and the protruding angular methyl groups (C10, C13 methyls) in the β face calls for adequate refinement. The relative energies of the transition states for molecular oxygen addition to C9, C5, and C14 (where spin densities are higher) and the ensuing products thereof are in agreement with the experimentally reported distribution of oxygenated 7-DHCs.

  3. Formation of ring-opened and rearranged products of guanine: mechanisms and biological significance.

    PubMed

    Jena, N R; Mishra, P C

    2012-07-01

    DNA damage by endogenous and exogenous agents is a serious concern, as the damaged products can affect genome integrity severely. Damage to DNA may arise from various factors such as DNA base modifications, strand break, inter- and intrastrand crosslinks, and DNA-protein crosslinks. Among these factors, DNA base modification is a common and important form of DNA damage that has been implicated in mutagenesis, carcinogenesis, and many other pathological conditions. Among the four DNA bases, guanine (G) has the smallest oxidation potential, because of which it is frequently modified by reactive species, giving rise to a plethora of lethal lesions. Similarly, 8-oxo-7,8-dihydroguanine (8-oxoG), an oxidatively damaged guanine lesion, also undergoes various degradation reactions giving rise to several mutagenic species. The various products formed from reactions of G or 8-oxoG with different reactive species are mainly 2,6-diamino-4-oxo-5-formamidopyrimidine, 2,5-diamino-4H-imidazolone, 2,2,4-triamino-5-(2H)-oxazolone, 5-guanidino-4-nitroimidazole, guanidinohydantoin, spiroiminodihydantoin, cyanuric acid, parabanic acid, oxaluric acid, and urea, among others. These products are formed from either ring opening or ring opening and subsequent rearrangement. The main aim of this review is to provide a comprehensive overview of various possible reactions and the mechanisms involved, after which these ring-opened and rearranged products of guanine would be formed in DNA. The biological significance of oxidatively damaged products of G is also discussed.

  4. Reactivity of inorganic nanoparticles in biological environments: insights into nanotoxicity mechanisms

    NASA Astrophysics Data System (ADS)

    Casals, E.; Gonzalez, E.; Puntes, V. F.

    2012-11-01

    A deeper understanding of the behaviour of inorganic nanoparticles in biological media is needed not only to fully control and develop the potential of these materials but also to increase knowledge of the physical chemistry of inorganic materials when their morphology approaches that of molecular entities. Although this knowledge and control is not yet entirely acquired, industry and society are already using nanomaterials in greater quantities and in consumer products. As normally happens when something new arrives in society, the interest in the broader implications of this emerging technology has grown together with unfounded ‘nanoeuphoria’ and ‘nanoscares’. In this context, only by understanding the mechanisms of the nano-bio interaction will it be possible to safely develop nanotechnology. In this review, we discuss on how nanoparticles behave once they are naturally or intentionally produced and are exposed to humans and the environment. The response of nanoparticles inside organisms or released to the environment is complex and diverse, and depends on a variety of parameters involved. Mainly, they may (i) be aggregated into microscopic particles or embedded in exposed materials; (ii) the surfaces of the nanoparticles, which determine their bioactivity, experience constant modifications; and (iii) nanoparticles may corrode and dissolve or they can suffer morphological modifications.

  5. Modelling and pathway identification involving the transport mechanism of a complex metabolic system in batch culture

    NASA Astrophysics Data System (ADS)

    Yuan, Jinlong; Zhang, Xu; Zhu, Xi; Feng, Enmin; Yin, Hongchao; Xiu, Zhilong

    2014-06-01

    The bio-dissimilation of glycerol to 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae (K. pneumoniae) can be characterized by a complex metabolic system of interactions among biochemical fluxes, metabolic compounds, key enzymes and genetic regulation. In this paper, in consideration of the fact that the transport ways of 1,3-PD and glycerol with different weights across cell membrane are still unclear in batch culture, we consider 121 possible metabolic pathways and establish a novel mathematical model which is represented by a complex metabolic system. Taking into account the difficulty in accurately measuring the concentration of intracellular substances and the absence of equilibrium point for the metabolic system of batch culture, the novel approach used here is to define quantitatively biological robustness of the intracellular substance concentrations for the overall process of batch culture. To determine the most possible metabolic pathway, we take the defined biological robustness as cost function and establish an identification model, in which 1452 system parameters and 484 pathway parameters are involved. Simultaneously, the identification model is subject to the metabolic system, continuous state constraints and parameter constraints. As such, solving the identification model by a serial program is a very complicated task. We propose a parallel migration particle swarm optimization algorithm (MPSO) capable of solving the identification model in conjunction with the constraint transcription and smoothing approximation techniques. Numerical results show that the most possible metabolic pathway and the corresponding metabolic system can reasonably describe the process of batch culture.

  6. Transcriptomics and systems biology analysis in identification of specific pathways involved in cacao resistance and susceptibility to witches' broom disease.

    PubMed

    da Hora Junior, Braz Tavares; Poloni, Joice de Faria; Lopes, Maíza Alves; Dias, Cristiano Villela; Gramacho, Karina Peres; Schuster, Ivan; Sabau, Xavier; Cascardo, Júlio Cézar De Mattos; Mauro, Sônia Marli Zingaretti Di; Gesteira, Abelmon da Silva; Bonatto, Diego; Micheli, Fabienne

    2012-04-01

    This study reports on expression analysis associated with molecular systems biology of cacao-Moniliophthora perniciosa interaction. Gene expression data were obtained for two cacao genotypes (TSH1188, resistant; Catongo, susceptible) challenged or not with the fungus M. perniciosa and collected at three time points through disease. Using expression analysis, we identified 154 and 227 genes that are differentially expressed in TSH1188 and Catongo, respectively. The expression of some of these genes was confirmed by RT-qPCR. Physical protein-protein interaction (PPPI) networks of Arabidopsis thaliana orthologous proteins corresponding to resistant and susceptible interactions were obtained followed by cluster and gene ontology analyses. The integrated analysis of gene expression and systems biology allowed designing a general scheme of major mechanisms associated with witches' broom disease resistance/susceptibility. In this sense, the TSH1188 cultivar shows strong production of ROS and elicitors at the beginning of the interaction with M. perniciosa followed by resistance signal propagation and ROS detoxification. On the other hand, the Catongo genotype displays defense mechanisms that include the synthesis of some defense molecules but without success in regards to elimination of the fungus. This phase is followed by the activation of protein metabolism which is achieved with the production of proteasome associated with autophagy as a precursor mechanism of PCD. This work also identifies candidate genes for further functional studies and for genetic mapping and marker assisted selection.

  7. GABA(B) receptors and opioid mechanisms involved in homotaurine-induced analgesia.

    PubMed

    Serrano, M I; Serrano, J S; Fernández, A; Asadi, I; Serrano-Martino, M C

    1998-03-01

    1. The involvement of GABA(B) receptors and opioid mechanisms in homotaurine-induced analgesia has been investigated in current models of nociception by using a GABA(B) receptor antagonist, morphine, and naloxone. CGP 35348 (50-200 mg/kg IP), a highly selective GABA(B) antagonist, was administered prior to carrying out a dose-response curve of homotaurine (22.6-445 mg/kg IP) antinociceptive effect in the abdominal constriction (mice) and tail flick (rats) tests. 2. The tail flick test was performed in animals pretreated with morphine (0.5 mg/kg SC) and naloxone (1 mg/kg), 15 min before amino acid. Animals treated with saline 10 ml/kg (mice) or 1.25 ml/kg (rats) were included as control for the vehicle used. 3. CGP 35348 antagonized the antinociceptive effect of homotaurine in both tests. The range of doses affected by the interaction depended on the test assayed, but it was coincident for the main part of the dose-response curve. 4. A subanalgesic dose of morphine potentiated the antinociceptive effect of lower doses of homotaurine in the tail flick test. Naloxone pretreatment inhibited the antinociceptive effect of homotaurine. 5. These data imply that GABA(B) receptor subpopulations and opiate mechanisms are involved in the antinociceptive effect of homotaurine. Because functional relationships have been found between GABAergic and opiate systems in analgesic effects, an interaction of the two mechanisms may be operating in the effects described for homotaurine.

  8. Differential gene expression in seasonal sympatry: mechanisms involved in diverging life histories

    PubMed Central

    Peterson, Mark P.; Greives, Timothy J.; Atwell, Jonathan W.; Bridge, Eli S.; Ketterson, Ellen D.

    2016-01-01

    In an era of climate change, understanding the genetic and physiological mechanisms underlying flexibility in phenology and life history has gained greater importance. These mechanisms can be elucidated by comparing closely related populations that differ in key behavioural and physiological traits such as migration and timing of reproduction. We compared gene expression in two recently diverged dark-eyed Junco ( Junco hyemalis) subspecies that live in seasonal sympatry during winter and early spring, but that differ in behaviour and physiology, despite exposure to identical environmental cues. We identified 547 genes differentially expressed in blood and pectoral muscle. Genes involved in lipid transport and metabolism were highly expressed in migrant juncos, while genes involved in reproductive processes were highly expressed in resident breeders. Seasonal differences in gene expression in closely related populations residing in the same environment provide significant insights into mechanisms underlying variation in phenology and life history, and have potential implications for the role of seasonal timing differences in gene flow and reproductive isolation. PMID:26979563

  9. Deciphering complex mechanisms in neurodegenerative diseases: the advent of systems biology.

    PubMed

    Noorbakhsh, Farshid; Overall, Christopher M; Power, Christopher

    2009-02-01

    Classical biological methods involving analyses of one or several genes have been the mainstay for studying the pathogenesis of neurodegenerative disorders. However, it has become clear that these diseases exhibit complex molecular interactions involving both host genomes and environmental determinants. Systems biology represents an integrated and deeper investigation of interacting biomolecules within cells or organisms. This approach has only recently become feasible as high-throughput technologies including cDNA microarrays, mass spectrometric analyses of proteins and lipids together with rigorous bioinformatics have evolved. Herein, we review recent developments from studies of systems biology applied to multiple sclerosis, Alzheimer's disease and HIV-associated dementia as three prototypic neurodegenerative disorders. Existing high-content data derived from clinically and experimentally derived neural tissues point to convergent pathways among these neurodegenerative disorders, which transcend descriptive studies to reach a more integrated understanding of disease pathogenesis and, in some instances, highlighting 'druggable' network nodes.

  10. Mechanisms Involved in the Pro-Apoptotic Effect of Melatonin in Cancer Cells

    PubMed Central

    Rodriguez, Carmen; Martín, Vanesa; Herrera, Federico; García-Santos, Guillermo; Rodriguez-Blanco, Jezabel; Casado-Zapico, Sara; Sánchez-Sánchez, Ana María; Suárez, Santos; Puente-Moncada, Noelia; Anítua, María José; Antolín, Isaac

    2013-01-01

    It is well established that melatonin exerts antitumoral effects in many cancer types, mostly decreasing cell proliferation at low concentrations. On the other hand, induction of apoptosis by melatonin has been described in the last few years in some particular cancer types. The cytotoxic effect occurs after its administration at high concentrations, and the molecular pathways involved have been only partially determined. Moreover, a synergistic effect has been found in several cancer types when it is administered in combination with chemotherapeutic agents. In the present review, we will summarize published work on the pro-apoptotic effect of melatonin in cancer cells and the reported mechanisms involved in such action. We will also construct a hypothesis on how different cell signaling pathways may relate each other on account for such effect. PMID:23528889

  11. Scientific Basis for a Coupled Thermal-Hydrological-Mechanical-Chemical-Biological Experimental Facility at DUSEL Homestake

    NASA Astrophysics Data System (ADS)

    Sonnenthal, E. L.; Elsworth, D.; Lowell, R. P.; Maher, K.; Mailloux, B. J.; Uzunlar, N.; Freifeld, B. M.; Keimowitz, A. R.; Wang, J. S.

    2009-12-01

    Most natural and engineered earth system processes involve strong coupling of thermal, mechanical, chemical, and sometimes biological processes in rocks that are heterogeneous at a wide range of spatial scales. One of the most pervasive processes in the Earth’s crust is that of fluids (primarily water, but also CO2, hydrocarbons, volcanic gases, etc.) flowing through fractured heated rock under stress. A preliminary design is being formulated for a large-scale subsurface experimental facility to investigate coupled Thermal-Hydrological-Mechanical-Chemical-Biological (THMCB) processes in fractured rock at depth. The experiment would be part of the proposed Deep Underground Science and Engineering Laboratory (DUSEL) in the Homestake Mine, South Dakota. Fundamental geochemical, isotopic, microbiological, laboratory THMC experiments, and numerical modeling will be used to guide the experimental design and evaluation of the time and spatial scales of the coupled THMCB processes. Although we sometimes analyze rocks and fluids for physical and chemical properties, it is difficult to create quantitative numerical models based on fundamental physics and chemistry that can capture the dynamic changes that have occurred or may yet take place. Initial conditions and history are only known roughly at best, and the boundary conditions have likely varied over time as well. Processes such as multicomponent chemical and thermal diffusion, multiphase flow, advection, and thermal expansion/contraction, are taking place simultaneously in rocks that are structurally and chemically complex—heterogeneous assemblages of mineral grains, pores, and fractures—and visually opaque. The only way to fully understand such processes is to carry out well-controlled experiments at a range of scales (grain/pore-scale to decimeter-scale) that can be interrogated and modeled. The THMCB experimental facility is also intended to be a unique laboratory for testing hypotheses regarding effects of

  12. Pathogenic mechanisms involved in the hematological alterations of arenavirus-induced hemorrhagic fevers.

    PubMed

    Schattner, Mirta; Rivadeneyra, Leonardo; Pozner, Roberto G; Gómez, Ricardo M

    2013-01-21

    Viral hemorrhagic fevers (VHFs) caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.

  13. Pathogenic Mechanisms Involved in the Hematological Alterations of Arenavirus-induced Hemorrhagic Fevers

    PubMed Central

    Schattner, Mirta; Rivadeneyra, Leonardo; Pozner, Roberto G.; Gómez, Ricardo M.

    2013-01-01

    Viral hemorrhagic fevers (VHFs) caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms. PMID:23337384

  14. Mechanisms regulating proteostasis are involved in sympatric speciation of the blind mole rat, Spalax galili.

    PubMed

    Rodriguez, Karl A; Li, Kexin; Nevo, Eviatar; Buffenstein, Rochelle

    2016-01-01

    Genome-wide analysis demonstrates extensive genomic adaptive complexes involved in sympatric speciation between blind mole rats (Spalax galili) in abutting populations living in basalt and chalk soils. Among the gene ontology (GO) enrichment, musculature and metabolism stood out in basalt dwellers while nutrition and neurogenetics were highlighted in chalk residents. Measurements of mechanisms regulating protein homeostasis inspired by these GO terms suggest that at the proteomic level there is also a habitat/soil-type driven divergence with the basalt residents exhibiting higher proteasome activity whereas elevated levels of markers of autophagy are evident in the chalk inhabitants.

  15. Mechanisms regulating proteostasis are involved in sympatric speciation of the blind mole rat, Spalax galili

    PubMed Central

    Rodriguez, Karl A.; Li, Kexin; Nevo, Eviatar; Buffenstein, Rochelle

    2016-01-01

    ABSTRACT Genome-wide analysis demonstrates extensive genomic adaptive complexes involved in sympatric speciation between blind mole rats (Spalax galili) in abutting populations living in basalt and chalk soils. Among the gene ontology (GO) enrichment, musculature and metabolism stood out in basalt dwellers while nutrition and neurogenetics were highlighted in chalk residents. Measurements of mechanisms regulating protein homeostasis inspired by these GO terms suggest that at the proteomic level there is also a habitat/soil-type driven divergence with the basalt residents exhibiting higher proteasome activity whereas elevated levels of markers of autophagy are evident in the chalk inhabitants. PMID:27050459

  16. Myco-Biocontrol of Insect Pests: Factors Involved, Mechanism, and Regulation

    PubMed Central

    Sandhu, Sardul Singh; Sharma, Anil K.; Beniwal, Vikas; Goel, Gunjan; Batra, Priya; Kumar, Anil; Jaglan, Sundeep; Sharma, A. K.; Malhotra, Sonal

    2012-01-01

    The growing demand for reducing chemical inputs in agriculture and increased resistance to insecticides have provided great impetus to the development of alternative forms of insect-pest control. Myco-biocontrol offers an attractive alternative to the use of chemical pesticides. Myco-biocontrol agents are naturally occurring organisms which are perceived as less damaging to the environment. Their mode of action appears little complex which makes it highly unlikely that resistance could be developed to a biopesticide. Past research has shown some promise of the use of fungi as a selective pesticide. The current paper updates us about the recent progress in the field of myco-biocontrol of insect pests and their possible mechanism of action to further enhance our understanding about the biological control of insect pests. PMID:22567344

  17. Mechanisms involved in biological behavior changes associated with Angptl4 expression in colon cancer cell lines.

    PubMed

    Huang, Xue-Feng; Han, Jie; Hu, Xiao-Tong; He, Chao

    2012-05-01

    Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths throughout the world. Angiopoietin-like-4 (Angptl4), a member of the angiopoietin family of secreted proteins, is frequently expressed in the perinecrotic areas of different human tumors, yet its role is still unclear in colorectal cancer. Angptl4 mRNA expression in primary colorectal cancer tissue and seven colon cancer cell lines was measured by semi-quantitative RT-PCR; the influence of Angptl4 expression on the colon cancer cell lines was investigated by either overexpression or knockdown of Angptl4 in colon cancer cell lines HCT116 and HT29, respectively. The results showed that Angptl4 mRNA is frequently expressed in human colorectal cancer tissues and cell lines. Overexpression of Angptl4 promoted cell migration, F-actin reorganization and formation of pseudopodia. Further investigation showed that high Angptl4 expression was associated with an increase in ezrin/radixin/moesin and vasodilator-stimulated phosphoprotein expression and a decrease in E-cadherin expression. These results indicate that overexpression of Angptl4 may promote invasion and metastasis in CRC.

  18. A review on the molecular mechanisms involved in insulin resistance induced by organophosphorus pesticides.

    PubMed

    Lasram, Mohamed Montassar; Dhouib, Ines Bini; Annabi, Alya; El Fazaa, Saloua; Gharbi, Najoua

    2014-08-01

    There is increasing evidence reporting that organophosphorus pesticides (OPs) impair glucose homeostasis and cause insulin resistance and type 2 diabetes. Insulin resistance is a complex metabolic disorder that defies explanation by a single etiological pathway. Formation of advanced glycation end products, accumulation of lipid metabolites, activation of inflammatory pathways and oxidative stress have all been implicated in the pathogenesis of insulin resistance. Ultimately, these molecular processes activate a series of stress pathways involving a family of serine kinases, which in turn have a negative effect on insulin signaling. Experimental and clinical data suggest an association between these molecular mechanisms and OPs compounds. It was first reported that OPs induce hyperglycemia. Then a concomitant increase of blood glucose and insulin was pointed out. For some years only, we have begun to understand that OPs promote insulin resistance and increase the risk of type 2 diabetes. Overall, this review outlines various mechanisms that lead to the development of insulin resistance by OPs exposure.

  19. Reaction mechanisms involved in reduction of halogenated hydrocarbons using sulfated iron

    SciTech Connect

    Hassan, S.M.; Cipollone, M.G.; Wolfe, N.L.

    1995-12-01

    Experiments were carried out to investigate the mechanisms and pathways involved in the reduction of halogenated hydrocarbons represented by trichloroethylene (TCE) and tetrachloroethylene (PCE) with sulfated iron aqueous media. Results suggested that iron sulfide acted as the dehalogenation center. Zero-valent iron acted as a generator for molecular hydrogen through its reaction with water. Results of experiments in which iron sulfide was replaced by other transition metal sulfides and experiments in which zero-valent iron was replaced by other sources of molecular hydrogen will be reported. The main reduction product of chloroethylene derivatives was ethyne which under the catalytic reaction of zero-valent iron was reduced further to ethene and finally to ethane. Intermediate products were identified using GC-MS. Mechanisms and pathways will be presented.

  20. Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

    PubMed Central

    Wang, Juan; Zhang, Hai-yan; Tang, Xi-can

    2009-01-01

    Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. Moreover, cholinergic therapies have shown promising effects on cognitive improvement in VaD patients. The precise mechanisms of these cholinergic agents are currently not fully understood; however, accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway, in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation, although regulation of oxidative stress and energy metabolism, alleviation of apoptosis may also be involved. In this paper, we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation. PMID:19574993

  1. Luminal and basolateral mechanisms involved in the renal tubular uptake of inorganic mercury

    SciTech Connect

    Zalups, R.K.; Minor, K.H.

    1995-09-01

    The present study provides evidence for the existence of both a luminal and a basolateral mechanism involved in the renal tubular uptake of inorganic mercury. The researchers compared the disposition of inorganic mercury in groups of surgical control rats, rats that underwent a unilateral ureteral ligation, and rats that underwent a bilateral ureteral ligation that were pretreated with either normal saline or a 7.5 mmol/kg intravenous dose of PAH 5 min prior to receiving a nontoxic 0.5-{mu}mol/kg intravenous dose of mercuric chloride. The {open_quotes}stop-flow{close_quotes} conditions induced by either unilateral or bilateral ureteral ligation caused a significant reduction in the uptake and content of mercury in the kidneys (whose ureter was ligated) both at 1 h and 24 h after the intravenous injection of the nontoxic dose of mercuric chloride. This decreased renal uptake of mercury was due specifically to decreased uptake of mercury in the renal cortex and outer stripe of the outer medulla. The amount of mercury has not taken up during ureteral ligation represents the portion of mercury that is presumably taken up by a luminal mechanism. Pretreatment with PAH also caused a significant reduction in the renal uptake of mercury in the cortex and outer stripe of the outer medulla. When either unilateral or bilateral ureteral ligation was combined with PAH pretreatment, an additive inhibitory effect occurred with respect to the renal uptake of mercury. In fact, the renal uptake of mercury was reduced by approximately 85% at 1 h after the injection of mercuric chloride. Since the luminal uptake of mercury was blocked by ureteral ligation, the effect of PAH on the renal uptake of mercury must have occurred at the basolateral membrane. Two distinct mechanisms are involved in mercury uptake, with one mechanism located on the luminal membrane and another located on the basolateral membrane. 22 refs., 11 figs., 2 tabs.

  2. Global Analysis of Lysine Acetylation Suggests the Involvement of Protein Acetylation in Diverse Biological Processes in Rice (Oryza sativa)

    PubMed Central

    Zhong, Xiaoxian; Tan, Feng; Mujahid, Hana; Zhang, Jian; Nanduri, Bindu; Peng, Zhaohua

    2014-01-01

    Lysine acetylation is a reversible, dynamic protein modification regulated by lysine acetyltransferases and deacetylases. Recent advances in high-throughput proteomics have greatly contributed to the success of global analysis of lysine acetylation. A large number of proteins of diverse biological functions have been shown to be acetylated in several reports in human cells, E.coli, and dicot plants. However, the extent of lysine acetylation in non-histone proteins remains largely unknown in monocots, particularly in the cereal crops. Here we report the mass spectrometric examination of lysine acetylation in rice (Oryza sativa). We identified 60 lysine acetylated sites on 44 proteins of diverse biological functions. Immunoblot studies further validated the presence of a large number of acetylated non-histone proteins. Examination of the amino acid composition revealed substantial amino acid bias around the acetylation sites and the amino acid preference is conserved among different organisms. Gene ontology analysis demonstrates that lysine acetylation occurs in diverse cytoplasmic, chloroplast and mitochondrial proteins in addition to the histone modifications. Our results suggest that lysine acetylation might constitute a regulatory mechanism for many proteins, including both histones and non-histone proteins of diverse biological functions. PMID:24586658

  3. Resistance to spiramycin in Streptomyces ambofaciens, the producer organism, involves at least two different mechanisms.

    PubMed

    Pernodet, J L; Alegre, M T; Blondelet-Rouault, M H; Guérineau, M

    1993-05-01

    During its stationary phase, Streptomyces ambofaciens produces the macrolide antibiotic spiramycin, and has to protect itself against this antibiotic. Young mycelia, not yet producing spiramycin, are sensitive to it, but they become fully resistant when production begins. In a sensitive mycelium, resistance could be induced by exposure to sub-inhibitory concentrations of spiramycin, and these induced mycelia, like producing mycelia were resistant not only to spiramycin but also to several other macrolide antibiotics. Ribosomes extracted from these resistant mycelia were shown in vitro to be more resistant to spiramycin than ribosomes extracted from sensitive mycelium, indicating that S. ambofaciens possesses a spiramycin-inducible ribosomal resistance to spiramycin and to macrolide antibiotics. Studies with spiramycin non-producing mutants showed that, in these mutants, resistance to spiramycin also varies during cultivation, in that an old culture was much more resistant than a young one. But with these non-producing mutants, the spectrum of resistance was narrower, and in vitro data showed that resistance was not due to ribosomal modification. These results suggest that S. ambofaciens presents at least two distinct mechanisms for spiramycin resistance; a spiramycin-inducible ribosomal resistance, and a second resistance mechanism which might be temporally regulated and which could involve decreased permeability to, or export of, the antibiotic. The two mechanisms are probably at work simultaneously in the producing mycelium, the spiramycin-inducible resistance being induced by endogenous spiramycin. In non-producing mutants, in the absence of self-induction by spiramycin, only the second mechanism is observed.

  4. The mechanism of sperm-egg interaction and the involvement of IZUMO1 in fusion.

    PubMed

    Inoue, Naokazu; Ikawa, Masahito; Okabe, Masaru

    2011-01-01

    An average human ejaculate contains over 100 million sperm, but only a few succeed in accomplishing the journey to an egg by migration through the female reproductive tract. Among these few sperm, only one participates in fertilization. There might be an ingenious molecular mechanism to ensure that the very best sperm fertilize an egg. However, recent gene disruption experiments in mice have revealed that many factors previously described as important for fertilization are largely dispensable. One could argue that the fertilization mechanism is made robust against gene disruptions. However, this is not likely, as there are already six different gene-disrupted mouse lines (Calmegin, Adam1a, Adam2, Adam3, Ace and Pgap1), all of which result in male sterility. The sperm from these animals are known to have defective zona-binding ability and at the same time lose oviduct-migrating ability. Concerning sperm-zona binding, the widely accepted involvement of sugar moiety on zona pellucida 3 (ZP3) is indicated to be dispensable by gene disruption experiments. Thus, the landscape of the mechanism of fertilization is revolving considerably. In the sperm-egg fusion process, CD9 on egg and IZUMO1 on sperm have emerged as essential factors. This review focuses on the mechanism of fertilization elucidated by gene-manipulated animals.

  5. The Potential of Systems Biology to Discover Antibacterial Mechanisms of Plant Phenolics

    PubMed Central

    Rempe, Caroline S.; Burris, Kellie P.; Lenaghan, Scott C.; Stewart, C. Neal

    2017-01-01

    Drug resistance of bacterial pathogens is a growing problem that can be addressed through the discovery of compounds with novel mechanisms of antibacterial activity. Natural products, including plant phenolic compounds, are one source of diverse chemical structures that could inhibit bacteria through novel mechanisms. However, evaluating novel antibacterial mechanisms of action can be difficult and is uncommon in assessments of plant phenolic compounds. With systems biology approaches, though, antibacterial mechanisms can be assessed without the bias of target-directed bioassays to enable the discovery of novel mechanism(s) of action against drug resistant microorganisms. This review article summarizes the current knowledge of antibacterial mechanisms of action of plant phenolic compounds and discusses relevant methodology. PMID:28360902

  6. The Potential of Systems Biology to Discover Antibacterial Mechanisms of Plant Phenolics.

    PubMed

    Rempe, Caroline S; Burris, Kellie P; Lenaghan, Scott C; Stewart, C Neal

    2017-01-01

    Drug resistance of bacterial pathogens is a growing problem that can be addressed through the discovery of compounds with novel mechanisms of antibacterial activity. Natural products, including plant phenolic compounds, are one source of diverse chemical structures that could inhibit bacteria through novel mechanisms. However, evaluating novel antibacterial mechanisms of action can be difficult and is uncommon in assessments of plant phenolic compounds. With systems biology approaches, though, antibacterial mechanisms can be assessed without the bias of target-directed bioassays to enable the discovery of novel mechanism(s) of action against drug resistant microorganisms. This review article summarizes the current knowledge of antibacterial mechanisms of action of plant phenolic compounds and discusses relevant methodology.

  7. The Possible Mechanisms Involved in Degradation of Patulin by Pichia caribbica

    PubMed Central

    Zheng, Xiangfeng; Yang, Qiya; Zhang, Hongyin; Cao, Jing; Zhang, Xiaoyun; Apaliya, Maurice Tibiru

    2016-01-01

    In this work, we examined the mechanisms involved in the degradation of patulin by Pichia caribbica. Our results indicate that cell-free filtrate of P. caribbica reduced patutlin content. The heat-killed cells could not degrade patulin. However, the live cells significantly reduced the concentration of the patulin. In furtherance to this, it was observed that patulin was not detected in the broken yeast cells and cell wall. The addition of cycloheximide to the P. caribbica cells decreased the capacity of degradation of patulin. Proteomics analyses revealed that patulin treatment resulted in an upregulated protein which was involved in metabolism and stress response processes. Our results suggested that the mechanism of degradation of patulin by P. caribbica was not absorption; the presence of patulin can induce P. caribbica to produce associated intracellular and extracellular enzymes, both of which have the ability to degrade patulin. The result provides a new possible method that used the enzymes produced by yeast to detoxify patulin in food and feed. PMID:27735830

  8. Mechanism involved in phagocytosis and killing of Listeria monocytogenes by Acanthamoeba polyphaga.

    PubMed

    Akya, Alisha; Pointon, Andrew; Thomas, Connor

    2009-10-01

    Intra-cellular pathogen, Listeria monocytogenes, is capable of invasion and survival within mammalian cells. However, Acanthamoeba polyphaga trophozoites phagocytose and rapidly degrade Listeria cells. In order to provide more information on amoeba phagocytosis and killing mechanisms, this study used several inhibitor agents known to affect the phagocytosis and killing of bacteria by eukaryotes. Amoebae were pre-treated with mannose, cytochalasin D, wortmannin, suramin, ammonium chloride, bafilomycin A and monensin followed by co-culture with bacteria. Phagocytosis and killing of bacterial cells by amoeba trophozoites was assessed using plate counting methods and microscopy. The data presented indicates that actin polymerisation and cytoskeletal rearrangement are involved in phagocytosis of L. monocytogenes cells by A. polyphaga trophozoites. Further, both phagosomal acidification and phagosome-lysosome fusion are involved in killing and degradation of L. monocytogenes cells by A. polyphaga. However, the mannose-binding protein receptor does not play an important role in uptake of bacteria by amoeba trophozoites. In conclusion, this data reveals the similar principles of molecular mechanisms used by different types of eukaryotes in uptake and killing of bacteria.

  9. Antinociceptive Activity of Methanol Extract of Muntingia calabura Leaves and the Mechanisms of Action Involved

    PubMed Central

    Sani, M. H. Mohd.; Zakaria, Z. A.; Balan, T.; Teh, L. K.; Salleh, M. Z.

    2012-01-01

    Muntingia calabura L. (family Elaeocarpaceae) has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract of M. calabura leaves (MEMC) and to elucidate the possible mechanism of antinociception involved. The in vivo chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test) and thermal (hot plate test) models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg) was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P < 0.05) antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO) donor), NG-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS)), methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP) pathway), or their combination also caused significant (P < 0.05) change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway. PMID:22611437

  10. Soil biochar amendment as a climate change mitigation tool: Key parameters and mechanisms involved.

    PubMed

    Brassard, Patrick; Godbout, Stéphane; Raghavan, Vijaya

    2016-10-01

    Biochar, a solid porous material obtained from the carbonization of biomass under low or no oxygen conditions, has been proposed as a climate change mitigation tool because it is expected to sequester carbon (C) for centuries and to reduce greenhouse gas (GHG) emissions from soils. This review aimed to identify key biochar properties and production parameters that have an effect on these specific applications of the biochar. Moreover, mechanisms involved in interactions between biochar and soils were highlighted. Following a compilation and comparison of the characteristics of 76 biochars from 40 research studies, biochars with a lower N content, and consequently a higher C/N ratio (>30), were found to be more suitable for mitigation of N2O emissions from soils. Moreover, biochars produced at a higher pyrolysis temperature, and with O/C ratio <0.2, H/Corg ratio <0.4 and volatile matter below 80% may have high C sequestration potential. Based on these observations, biochar production and application to the field can be used as a tool to mitigate climate change. However, it is important to determine the pyrolysis conditions and feedstock needed to produce a biochar with the desired properties for a specific application. More research studies are needed to identify the exact mechanisms involved following biochar amendment to soil.

  11. Mechanisms and neuronal networks involved in reactive and proactive cognitive control of interference in working memory.

    PubMed

    Irlbacher, Kerstin; Kraft, Antje; Kehrer, Stefanie; Brandt, Stephan A

    2014-10-01

    Cognitive control can be reactive or proactive in nature. Reactive control mechanisms, which support the resolution of interference, start after its onset. Conversely, proactive control involves the anticipation and prevention of interference prior to its occurrence. The interrelation of both types of cognitive control is currently under debate: Are they mediated by different neuronal networks? Or are there neuronal structures that have the potential to act in a proactive as well as in a reactive manner? This review illustrates the way in which integrating knowledge gathered from behavioral studies, functional imaging, and human electroencephalography proves useful in answering these questions. We focus on studies that investigate interference resolution at the level of working memory representations. In summary, different mechanisms are instrumental in supporting reactive and proactive control. Distinct neuronal networks are involved, though some brain regions, especially pre-SMA, possess functions that are relevant to both control modes. Therefore, activation of these brain areas could be observed in reactive, as well as proactive control, but at different times during information processing.

  12. Integrated Innate Mechanisms Involved in Airway Allergic Inflammation to the Serine Protease Subtilisin

    PubMed Central

    Florsheim, Esther; Yu, Shuang; Bragatto, Ivan; Faustino, Lucas; Gomes, Eliane; Ramos, Rodrigo N.; Barbuto, José Alexandre M.; Medzhitov, Ruslan; Russo, Momtchilo

    2015-01-01

    Proteases are recognized environmental allergens, but little is known about the mechanisms responsible for sensing enzyme activity and initiating the development of allergic inflammation. Because usage of the serine protease subtilisin in the detergent industry resulted in an outbreak of occupational asthma in workers, we sought to develop an experimental model of allergic lung inflammation to subtilisin and to determine the immunological mechanisms involved in type 2 responses. By using a mouse model of allergic airway disease, we have defined here that subcutaneous or intranasal sensitization followed by airway challenge to subtilisin induces prototypic allergic lung inflammation, characterized by airway eosinophilia, type 2 cytokines release, mucus production, high levels of serum IgE, and airway reactivity. These allergic responses were dependent on subtilisin protease activity, protease-activated receptor (PAR)-2, IL-33 receptor ST2, and MyD88 signaling. Also, subtilisin stimulated the expression of the pro-allergic cytokines IL-1α, IL-33, TSLP, and the growth factor amphiregulin in a human bronchial epithelial cell line. Notably, acute administration of subtilisin into the airways increased lung IL-5-producing type 2 innate lymphoid cells, which required PAR-2 expression. Finally, subtilisin activity acted as a Th2 adjuvant to an unrelated airborne antigen promoting allergic inflammation to inhaled OVA. Therefore, we established a murine model of occupational asthma to a serine protease and characterized the main molecular pathways involved in allergic sensitization to subtilisin that potentially contribute to initiate allergic airway disease. PMID:25876764

  13. Dietary restriction involves NAD⁺ -dependent mechanisms and a shift toward oxidative metabolism.

    PubMed

    Moroz, Natalie; Carmona, Juan J; Anderson, Edward; Hart, Anne C; Sinclair, David A; Blackwell, T Keith

    2014-12-01

    Interventions that slow aging and prevent chronic disease may come from an understanding of how dietary restriction (DR) increases lifespan. Mechanisms proposed to mediate DR longevity include reduced mTOR signaling, activation of the NAD⁺ -dependent deacylases known as sirtuins, and increases in NAD⁺ that derive from higher levels of respiration. Here, we explored these hypotheses in Caenorhabditis elegans using a new liquid feeding protocol. DR lifespan extension depended upon a group of regulators that are involved in stress responses and mTOR signaling, and have been implicated in DR by some other regimens [DAF-16 (FOXO), SKN-1 (Nrf1/2/3), PHA-4 (FOXA), AAK-2 (AMPK)]. Complete DR lifespan extension required the sirtuin SIR-2.1 (SIRT1), the involvement of which in DR has been debated. The nicotinamidase PNC-1, a key NAD⁺ salvage pathway component, was largely required for DR to increase lifespan but not two healthspan indicators: movement and stress resistance. Independently of pnc-1, DR increased the proportion of respiration that is coupled to ATP production but, surprisingly, reduced overall oxygen consumption. We conclude that stress response and NAD⁺ -dependent mechanisms are each critical for DR lifespan extension, although some healthspan benefits do not require NAD⁺ salvage. Under DR conditions, NAD⁺ -dependent processes may be supported by a DR-induced shift toward oxidative metabolism rather than an increase in total respiration.

  14. A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

    PubMed

    Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

    2015-02-01

    The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI.

  15. An experimental study of double-peeling mechanism inspired by biological adhesive systems

    NASA Astrophysics Data System (ADS)

    Heepe, Lars; Raguseo, Saverio; Gorb, Stanislav N.

    2017-02-01

    Double- (or multiple-) peeling systems consist of two (or numerous) tapes adhering to a substrate and having a common hinge, where the pulling force is applied. Biological systems, consisting of tape-like (or spatula-like) contact elements, are widely observed in adhesive pads of flies, beetles, spiders, and geckos. It was previously hypothesized and analytically modeled that the simultaneous use of two or more such tape-like contacts in the opposite movement of contralateral legs during ceiling locomotion leads to enhanced, robust, and stable overall attachment, if compared to independently working contact points. In this paper, this biological solution for smart adhesion is demonstrated in an experiment using elastic adhesive tapes. The obtained results not only aided in explaining the functional mechanism of biological adhesive systems, but also in providing an experimental proof for biological observations and previous theoretical models.

  16. Estradiol decreases cortical reactive astrogliosis after brain injury by a mechanism involving cannabinoid receptors.

    PubMed

    López Rodríguez, Ana Belén; Mateos Vicente, Beatriz; Romero-Zerbo, Silvana Y; Rodriguez-Rodriguez, Noé; Bellini, María José; Rodriguez de Fonseca, Fernando; Bermudez-Silva, Francisco Javier; Azcoitia, Iñigo; Garcia-Segura, Luis M; Viveros, María-Paz

    2011-09-01

    The neuroactive steroid estradiol reduces reactive astroglia after brain injury by mechanisms similar to those involved in the regulation of reactive gliosis by endocannabinoids. In this study, we have explored whether cannabinoid receptors are involved in the effects of estradiol on reactive astroglia. To test this hypothesis, the effects of estradiol, the cannabinoid CB1 antagonist/inverse agonist AM251, and the cannabinoid CB2 antagonist/inverse agonist AM630 were assessed in the cerebral cortex of male rats after a stab wound brain injury. Estradiol reduced the number of vimentin immunoreactive astrocytes and the number of glial fibrillary acidic protein immunoreactive astrocytes in the proximity of the wound. The effect of estradiol was significantly inhibited by the administration of either CB1 or CB2 receptor antagonists. The effect of estradiol may be in part mediated by alterations in endocannabinoid signaling because the hormone increased in the injured cerebral cortex the messenger RNA levels of CB2 receptors and of some of the enzymes involved in the synthesis and metabolism of endocannabinoids. These findings suggest that estradiol may decrease reactive astroglia in the injured brain by regulating the activity of the endocannabinoid system.

  17. Versatile and inexpensive Hall-Effect force sensor for mechanical characterization of soft biological materials.

    PubMed

    Backman, Daniel E; LeSavage, Bauer L; Wong, Joyce Y

    2017-01-25

    Mismatch of hierarchical structure and mechanical properties between tissue-engineered implants and native tissue may result in signal cues that negatively impact repair and remodeling. With bottom-up tissue engineering approaches, designing tissue components with proper microscale mechanical properties is crucial to achieve necessary macroscale properties in the final implant. However, characterizing microscale mechanical properties is challenging, and current methods do not provide the versatility and sensitivity required to measure these fragile, soft biological materials. Here, we developed a novel, highly sensitive Hall-Effect based force sensor that is capable of measuring mechanical properties of biological materials over wide force ranges (μN to N), allowing its use at all steps in layer-by-layer fabrication of engineered tissues. The force sensor design can be easily customized to measure specific force ranges, while remaining easy to fabricate using inexpensive, commercial materials. Although we used the force sensor to characterize mechanics of single-layer cell sheets and silk fibers, the design can be easily adapted for different applications spanning larger force ranges (>N). This platform is thus a novel, versatile, and practical tool for mechanically characterizing biological and biomimetic materials.

  18. A Review of Biological Communication Mechanisms Applicable to Small Autonomous Systems

    DTIC Science & Technology

    2010-09-01

    Characteristics of different biological channels of communication (Wyatt, 2003). .........1 Table 2. Insect sound- production methods (Alexander, 1957...different types of sound-producing mechanisms. Table 2. Insect sound- production methods (Alexander, 1957). Method Examples Stridulation Crickets...of creating sound by rubbing two rough surfaces together. This method is the most common method of insect sound production . Many insects use

  19. The Perception of Biological and Mechanical Motion in Female Fragile X Premutation Carriers

    ERIC Educational Resources Information Center

    Keri, Szabolcs; Benedek, Gyorgy

    2010-01-01

    Previous studies reported impaired visual information processing in patients with fragile x syndrome and in premutation carriers. In this study, we assessed the perception of biological motion (a walking point-light character) and mechanical motion (a rotating shape) in 25 female fragile x premutation carriers and in 20 healthy non-carrier…

  20. Features of Knowledge Building in Biology: Understanding Undergraduate Students' Ideas about Molecular Mechanisms

    ERIC Educational Resources Information Center

    Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S.

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections…

  1. On the mechanisms of interaction of low-intensity millimeter waves with biological objects

    NASA Astrophysics Data System (ADS)

    Betskii, O. V.

    1994-01-01

    The interaction of low-intensity millimeter-band electromagnetic waves with biological objects is examined. These waves are widely used in medical practice as a means of physiotherapy for the treatment of various human disorders. Principal attention is given to the mechanisms through which millimeter waves act on the human organism.

  2. On the mechanisms of interaction of low-intensity millimeter waves with biological objects

    SciTech Connect

    Betskii, O.V.

    1994-07-01

    The interaction of low-intensity millimeter-band electromagnetic waves with biological objects is examined. These waves are widely used in medical practice as a means of physiotherapy for the treatment of various human disorders. Principal attention is given to the mechanisms through which millimeter waves act on the human organism.

  3. The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation

    PubMed Central

    2016-01-01

    Over the past decade, numerous advances have been made in the role and regulation of inflammasomes during pathogenic and sterile insults. An inflammasome complex comprises a sensor, an adaptor, and a zymogen procaspase-1. The functional output of inflammasome activation includes secretion of cytokines, IL-1β and IL-18, and induction of an inflammatory form of cell death called pyroptosis. Recent studies have highlighted the intersection of this inflammatory response with fundamental cellular processes. Novel modulators and functions of inflammasome activation conventionally associated with the maintenance of homeostatic biological functions have been uncovered. In this review, we discuss the biological processes involved in the activation and regulation of the inflammasome. PMID:27325789

  4. Glyoxalase I inhibition induces apoptosis in irradiated MCF-7 cells via a novel mechanism involving Hsp27, p53 and NF-κB

    PubMed Central

    Antognelli, C; Palumbo, I; Aristei, C; Talesa, V N

    2014-01-01

    Background: Glyoxalase I (GI) is a cellular defence enzyme involved in the detoxification of methylglyoxal (MG), a cytotoxic byproduct of glycolysis, and MG-derived advanced glycation end products (AGEs). Argpyrimidine (AP), one of the major AGEs coming from MG modifications of proteins arginines, is a pro-apoptotic agent. Radiotherapy is an important modality widely used in cancer treatment. Exposure of cells to ionising radiation (IR) results in a number of complex biological responses, including apoptosis. The present study was aimed at investigating whether, and through which mechanism, GI was involved in IR-induced apoptosis. Methods: Apoptosis, by TUNEL assay, transcript and protein levels or enzymatic activity, by RT–PCR, western blot and spectrophotometric methods, respectively, were evaluated in irradiated MCF-7 breast cancer cells, also in experiments with appropriate inhibitors or using small interfering RNA. Results: Ionising radiation induced a dramatic reactive oxygen species (ROS)-mediated inhibition of GI, leading to AP-modified Hsp27 protein accumulation that, in a mechanism involving p53 and NF-κB, triggered an apoptotic mitochondrial pathway. Inhibition of GI occurred at both functional and transcriptional levels, the latter occurring via ERK1/2 MAPK and ERα modulation. Conclusions: Glyoxalase I is involved in the IR-induced MCF-7 cell mitochondrial apoptotic pathway via a novel mechanism involving Hsp27, p53 and NF-κB. PMID:24918814

  5. Mitochondrial DNA replication proceeds via a ‘bootlace’ mechanism involving the incorporation of processed transcripts

    PubMed Central

    Reyes, Aurelio; Kazak, Lawrence; Wood, Stuart R.; Yasukawa, Takehiro; Jacobs, Howard T.; Holt, Ian J.

    2013-01-01

    The observation that long tracts of RNA are associated with replicating molecules of mitochondrial DNA (mtDNA) suggests that the mitochondrial genome of mammals is copied by an unorthodox mechanism. Here we show that these RNA-containing species are present in living cells and tissue, based on interstrand cross-linking. Using DNA synthesis in organello, we demonstrate that isolated mitochondria incorporate radiolabeled RNA precursors, as well as DNA precursors, into replicating DNA molecules. RNA-containing replication intermediates are chased into mature mtDNA, to which they are thus in precursor–product relationship. While a DNA chain terminator rapidly blocks the labeling of mitochondrial replication intermediates, an RNA chain terminator does not. Furthermore, processed L-strand transcripts can be recovered from gel-extracted mtDNA replication intermediates. Therefore, instead of concurrent DNA and RNA synthesis, respectively, on the leading and lagging strands, preformed processed RNA is incorporated as a provisional lagging strand during mtDNA replication. These findings indicate that RITOLS is a physiological mechanism of mtDNA replication, and that it involves a ‘bootlace' mechanism, in which processed transcripts are successively hybridized to the lagging-strand template, as the replication fork advances. PMID:23595151

  6. Mechanisms Involved in the Nociception Triggered by the Venom of the Armed Spider Phoneutria nigriventer

    PubMed Central

    Gewehr, Camila; Oliveira, Sara Marchesan; Rossato, Mateus Fortes; Trevisan, Gabriela; Dalmolin, Gerusa Duarte; Rigo, Flávia Karine; de Castro Júnior, Célio José; Cordeiro, Marta Nascimento; Ferreira, Juliano; Gomez, Marcus V.

    2013-01-01

    Background The frequency of accidental spider bites in Brazil is growing, and poisoning due to bites from the spider genus Phoneutria nigriventer is the second most frequent source of such accidents. Intense local pain is the major symptom reported after bites of P. nigriventer, although the mechanisms involved are still poorly understood. Therefore, the aim of this study was to identify the mechanisms involved in nociception triggered by the venom of Phoneutria nigriventer (PNV). Methodology/Principal Findings Twenty microliters of PNV or PBS was injected into the mouse paw (intraplantar, i.pl.). The time spent licking the injected paw was considered indicative of the level of nociception. I.pl. injection of PNV produced spontaneous nociception, which was reduced by arachnid antivenin (ArAv), local anaesthetics, opioids, acetaminophen and dipyrone, but not indomethacin. Boiling or dialysing the venom reduced the nociception induced by the venom. PNV-induced nociception is not dependent on glutamate or histamine receptors or on mast cell degranulation, but it is mediated by the stimulation of sensory fibres that contain serotonin 4 (5-HT4) and vanilloid receptors (TRPV1). We detected a kallikrein-like kinin-generating enzyme activity in tissue treated with PNV, which also contributes to nociception. Inhibition of enzymatic activity or administration of a receptor antagonist for kinin B2 was able to inhibit the nociception induced by PNV. PNV nociception was also reduced by the blockade of tetrodotoxin-sensitive Na+ channels, acid-sensitive ion channels (ASIC) and TRPV1 receptors. Conclusion/Significance Results suggest that both low- and high-molecular-weight toxins of PNV produce spontaneous nociception through direct or indirect action of kinin B2, TRPV1, 5-HT4 or ASIC receptors and voltage-dependent sodium channels present in sensory neurons but not in mast cells. Understanding the mechanisms involved in nociception caused by PNV are of interest not only for

  7. Water transport mechanism through open capillaries analyzed by direct surface modifications on biological surfaces

    NASA Astrophysics Data System (ADS)

    Ishii, Daisuke; Horiguchi, Hiroko; Hirai, Yuji; Yabu, Hiroshi; Matsuo, Yasutaka; Ijiro, Kuniharu; Tsujii, Kaoru; Shimozawa, Tateo; Hariyama, Takahiko; Shimomura, Masatsugu

    2013-10-01

    Some small animals only use water transport mechanisms passively driven by surface energies. However, little is known about passive water transport mechanisms because it is difficult to measure the wettability of microstructures in small areas and determine the chemistry of biological surfaces. Herein, we developed to directly analyse the structural effects of wettability of chemically modified biological surfaces by using a nanoliter volume water droplet and a hi-speed video system. The wharf roach Ligia exotica transports water only by using open capillaries in its legs containing hair- and paddle-like microstructures. The structural effects of legs chemically modified with a self-assembled monolayer were analysed, so that the wharf roach has a smart water transport system passively driven by differences of wettability between the microstructures. We anticipate that this passive water transport mechanism may inspire novel biomimetic fluid manipulations with or without a gravitational field.

  8. Water transport mechanism through open capillaries analyzed by direct surface modifications on biological surfaces.

    PubMed

    Ishii, Daisuke; Horiguchi, Hiroko; Hirai, Yuji; Yabu, Hiroshi; Matsuo, Yasutaka; Ijiro, Kuniharu; Tsujii, Kaoru; Shimozawa, Tateo; Hariyama, Takahiko; Shimomura, Masatsugu

    2013-10-23

    Some small animals only use water transport mechanisms passively driven by surface energies. However, little is known about passive water transport mechanisms because it is difficult to measure the wettability of microstructures in small areas and determine the chemistry of biological surfaces. Herein, we developed to directly analyse the structural effects of wettability of chemically modified biological surfaces by using a nanoliter volume water droplet and a hi-speed video system. The wharf roach Ligia exotica transports water only by using open capillaries in its legs containing hair- and paddle-like microstructures. The structural effects of legs chemically modified with a self-assembled monolayer were analysed, so that the wharf roach has a smart water transport system passively driven by differences of wettability between the microstructures. We anticipate that this passive water transport mechanism may inspire novel biomimetic fluid manipulations with or without a gravitational field.

  9. Peptide Bond Synthesis by a Mechanism Involving an Enzymatic Reaction and a Subsequent Chemical Reaction.

    PubMed

    Abe, Tomoko; Hashimoto, Yoshiteru; Zhuang, Ye; Ge, Yin; Kumano, Takuto; Kobayashi, Michihiko

    2016-01-22

    We recently reported that an amide bond is unexpectedly formed by an acyl-CoA synthetase (which catalyzes the formation of a carbon-sulfur bond) when a suitable acid and l-cysteine are used as substrates. DltA, which is homologous to the adenylation domain of nonribosomal peptide synthetase, belongs to the same superfamily of adenylate-forming enzymes, which includes many kinds of enzymes, including the acyl-CoA synthetases. Here, we demonstrate that DltA synthesizes not only N-(d-alanyl)-l-cysteine (a dipeptide) but also various oligopeptides. We propose that this enzyme catalyzes peptide synthesis by the following unprecedented mechanism: (i) the formation of S-acyl-l-cysteine as an intermediate via its "enzymatic activity" and (ii) subsequent "chemical" S → N acyl transfer in the intermediate, resulting in peptide formation. Step ii is identical to the corresponding reaction in native chemical ligation, a method of chemical peptide synthesis, whereas step i is not. To the best of our knowledge, our discovery of this peptide synthesis mechanism involving an enzymatic reaction and a subsequent chemical reaction is the first such one to be reported. This new process yields peptides without the use of a thioesterified fragment, which is required in native chemical ligation. Together with these findings, the same mechanism-dependent formation of N-acyl compounds by other members of the above-mentioned superfamily demonstrated that all members most likely form peptide/amide compounds by using this novel mechanism. Each member enzyme acts on a specific substrate; thus, not only the corresponding peptides but also new types of amide compounds can be formed.

  10. Coral bleaching under thermal stress: putative involvement of host/symbiont recognition mechanisms

    PubMed Central

    Vidal-Dupiol, Jeremie; Adjeroud, Mehdi; Roger, Emmanuel; Foure, Laurent; Duval, David; Mone, Yves; Ferrier-Pages, Christine; Tambutte, Eric; Tambutte, Sylvie; Zoccola, Didier; Allemand, Denis; Mitta, Guillaume

    2009-01-01

    Background Coral bleaching can be defined as the loss of symbiotic zooxanthellae and/or their photosynthetic pigments from their cnidarian host. This major disturbance of reef ecosystems is principally induced by increases in water temperature. Since the beginning of the 1980s and the onset of global climate change, this phenomenon has been occurring at increasing rates and scales, and with increasing severity. Several studies have been undertaken in the last few years to better understand the cellular and molecular mechanisms of coral bleaching but the jigsaw puzzle is far from being complete, especially concerning the early events leading to symbiosis breakdown. The aim of the present study was to find molecular actors involved early in the mechanism leading to symbiosis collapse. Results In our experimental procedure, one set of Pocillopora damicornis nubbins was subjected to a gradual increase of water temperature from 28°C to 32°C over 15 days. A second control set kept at constant temperature (28°C). The differentially expressed mRNA between the stressed states (sampled just before the onset of bleaching) and the non stressed states (control) were isolated by Suppression Subtractive Hybridization. Transcription rates of the most interesting genes (considering their putative function) were quantified by Q-RT-PCR, which revealed a significant decrease in transcription of two candidates six days before bleaching. RACE-PCR experiments showed that one of them (PdC-Lectin) contained a C-Type-Lectin domain specific for mannose. Immunolocalisation demonstrated that this host gene mediates molecular interactions between the host and the symbionts suggesting a putative role in zooxanthellae acquisition and/or sequestration. The second gene corresponds to a gene putatively involved in calcification processes (Pdcyst-rich). Its down-regulation could reflect a trade-off mechanism leading to the arrest of the mineralization process under stress. Conclusion Under thermal

  11. Involvement of endothelium-dependent and -independent mechanisms in midazolam-induced vasodilation.

    PubMed

    Colussi, Gian Luca; Di Fabio, Alessandro; Catena, Cristiana; Chiuch, Alessandra; Sechi, Leonardo A

    2011-08-01

    Benzodiazepine (BDZ) infusion has been shown to reduce blood pressure in both humans and animals. Although the inhibitory effects of BDZ on the central nervous system have been well documented, less is known about the direct effects of BDZ on the vascular bed. The aims of this study were to assess the effects of the BDZ midazolam on the vascular system in C57/BL6 mouse aortic rings and to investigate the mechanisms of its direct vascular action. We found that midazolam induced reversible, dose-dependent vasodilation in potassium- and phenylephrine-precontracted rings. In rings that were precontracted with potassium or phenylephrine, treatment with 10 μmol l(-1) midazolam increased vasodilation by 15 and 60%, respectively, compared with baseline. Vasodilation increased by 80 and 87%, respectively, after treatment with 50 μmol l(-1) midazolam. Only the low concentration of midazolam (10 μmol l(-1)) induced endothelium-dependent vasodilation in phenylephrine-precontracted rings. Vasodilation increased by 60% in rings with endothelium and by 20% in rings without endothelium. Conversely, only the high concentration of midazolam (50 μmol l(-1)) reduced the CaCl(2)-induced vasoconstriction of aortic rings with EC(50) (the concentration giving 50% of the maximal effect) values of 1 and 6 mmol l(-1) for vehicle- and midazolam-treated rings, respectively. Furthermore, the incubation of phenylephrine-precontracted rings with an inhibitor of the nitric oxide synthase (NOS) NG-nitro-L-arginine methyl ester or the inhibitors of central or peripheral type BDZ receptors (flumazenil or PK 11195, respectively) produced no change in midazolam-induced vasodilation. Thus, low concentrations of midazolam induce vasodilation via an endothelium-dependent mechanism that does not involve NO production. In contrast, high concentrations of midazolam induce vasodilation via an endothelium-independent mechanism that implies reduced sensitivity of aortic rings to calcium ions. Additionally

  12. One mechanism of glucocorticoid action in asthma may involve the inhibition of IL-25 expression

    PubMed Central

    Lu, Wei; Lu, Chao; Zhang, Chengming; Zhang, Chenghao

    2017-01-01

    While the mechanism of action of classic cytokines in asthma has received increased attention from researchers, certain non-classical cytokines, such as IL-25, also participate in this mechanism. The present study was performed to investigate the changes in IL-25 (IL-17E) mRNA and protein in bronchial asthma and to further characterize the mechanism underlying the action of glucocorticoids in asthma. A total of 96 specific pathogen-free BALB/c male mice were randomly divided into three normal groups (after the first allergization, after the second allergization and after excitation), three asthma groups (with the same three subgroups), a dexamethasone group and a budesonide group (n=12/group). An asthma model was established via the ovalbumin-sensitized excitation method. Mice in the dexamethasone group received intraperitoneal injections of dexamethasone 1 h prior to each excitation, the budesonide group received a budesonide suspension via inhalation 2 h before and after each provocation, and the normal group was sensitized and challenged with isotonic saline. IL-25 protein expression levels in the bronchoalveolar lavage fluid were measured by ELISA, and the relative IL-25 mRNA content in lung tissue was determined by reverse transcription-quantitative polymerase chain reaction. Compared with the normal groups, both the protein and mRNA levels of IL-25 were significantly increased (P<0.05) in the asthma groups. Dexamethasone and budesonide groups exhibited significant protein and mRNA reductions in IL-25, as compared with the asthma group after excitation (P<0.05), whereas these two groups significantly increased levels compared with the normal group after excitation (P<0.05). No significant differences in IL-25 mRNA expression levels were detected in the dexamethasone and budesonide groups when compared with the normal group after excitation. Therefore, we conclude that IL-25 is involved throughout the process of inflammation and inflammatory immune pathogenesis

  13. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    PubMed Central

    Massi, Paola; Valenti, Marta; Solinas, Marta; Parolaro, Daniela

    2010-01-01

    Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells. PMID:24281104

  14. Afferent control mechanisms involved in the development of soleus fiber alterations in simulated hypogravity

    NASA Astrophysics Data System (ADS)

    Shenkman, B. S.; Nemirovskaya, T. L.; Shapovalova, K. B.; Podlubnaya, Z. A.; Vikhliantsev, I. M.; Moukhina, A. M.; Kozlovskaya, I. B.

    2007-02-01

    It was recently established that support withdrawal (withdrawal of support reaction force) in microgravity provokes a sequence of functional shifts in the activity of motor units (inactivation of slow ones) and peripheral muscle apparatus which lead to the decline of postural muscle contractility and alterations in fiber characteristics. However, mechanisms involved in inactivation of the slow motor units and appropriate slow-twitch muscle fiber disuse under the supportless conditions remained unknown. We show here that artificial inactivation of muscles-antagonists (which are known to be hyperactive during unloading) counteracts some of the unloading-induced events in the rat soleus (fiber size reduction, slow-to-fast fiber-type transition and decline of titin and nebulin content). It was also demonstrated that direct activation of the muscarinic receptors of the neostriatum neurons prevented slow-to-fast fiber-type transformation in soleus of hindlimb suspended rats.

  15. Cardioproteomics: advancing the discovery of signaling mechanisms involved in cardiovascular diseases

    PubMed Central

    Cui, Ziyou; Dewey, Shannamar; Gomes, Aldrin V

    2011-01-01

    Cardioproteomics (Cardiovascular proteomics) is fast becoming an indispensible technique in deciphering changes in signaling pathways that occur in cardiovascular diseases (CVDs). The quality and availability of the instruments and bioinformatics software used for cardioproteomics continues to improve, and these techniques are now available to most cardiovascular researchers either directly or indirectly via university core centers. The heart and aorta are specialized tissues which present unique challenges to investigate. Currently, the diverse range of proteomic techniques available for cardiovascular research makes the choice of the best method or best combination of methods for the disease parameter(s) being investigated as important as the equipment used. This review focuses on proteomic techniques and their applications which have advanced our understanding of the signaling mechanisms involved in CVDs at the levels of protein complex/protein-protein interaction, post-translational modifications and signaling induced protein changes. PMID:22254205

  16. Myeloma cells resistance to NK cell lysis mainly involves an HLA class I-dependent mechanism.

    PubMed

    Gao, Minjie; Gao, Lu; Yang, Guang; Tao, Yi; Hou, Jun; Xu, Hongwei; Hu, Xiaojing; Han, Ying; Zhang, Qianqiao; Zhan, Fenghuang; Wu, Xiaosong; Shi, Jumei

    2014-07-01

    The anti-multiple myeloma (MM) potential of natural killer (NK) cells has been of rising interest in recent years. However, the molecular mechanism of NK cell cytotoxicity to myeloma cells remains unclear. In the present study, we investigated the expressions of human leukocyte antigen (HLA) class I and HLA-G in patient myeloma cells, and determined their relevance in patient tumor-cell susceptibility to NK cell cytotoxicity. Our results showed that patient myeloma cells (n = 12) were relatively resistant to NK-92 cell lysis, compared with myeloma cell lines (n = 7, P < 0.01). Gene expression profiling and flow cytometry analysis showed that both mRNA and protein of HLA class I were highly expressed in 12 patient myeloma cells. Interestingly, no or low HLA-G surface expression was detected, although multiple HLA-G transcripts were detected in these myeloma cells. NK cell function assay showed that down-regulating HLA class I expression on patient cells by acid treatment significantly increased the susceptibility of MM cells to NK-mediated lysis. Furthermore, we found that the blocking of membrane-bound HLA class I rather than HLA-G using antibodies on myeloma samples markedly increased their susceptibility to NK-mediated killing. These results demonstrated that the resistance of patient MM cells to NK lysis mainly involves an HLA class I-dependent mechanism, suggesting that HLA class I may be involved in protecting MM cells from NK-mediated attack and contribute to their immune escape in vivo.

  17. GABAB receptors modulate catecholamine secretion in chromaffin cells by a mechanism involving cyclic AMP formation.

    PubMed Central

    Oset-Gasque, M. J.; Parramón, M.; González, M. P.

    1993-01-01

    1. The function of gamma-aminobutyric acidB (GABAB) receptors in modulation of catecholamine secretion by chromaffin cells and the possible mechanism involved in this action have been examined. 2. The GABAB agonists (-)-baclofen and 3-aminopropylphosphinic acid (3-APPA) were found to induce a dose-dependent increase of basal catecholamine secretion. The EC50s were 151 +/- 35 microM and 225 +/- 58 microM for baclofen and 3-APPA, respectively. This stimulatory effect was specific since it could be blocked by 0.5 mM of the specific GABAB antagonist CGP-35348. 3. In contrast, preincubation of chromaffin cells with the GABAB agonists was found to inhibit, in a dose-dependent manner, the catecholamine secretion evoked by 10 microM nicotine and 200 microM muscimol. 4. The effects of GABAB agonists on both basal and evoked catecholamine secretion were found to be accompanied by parallel changes in intracellular calcium concentration ([Ca2+]i). GABAB agonists produced a dose-dependent increase in [Ca2+]i which was partially blocked by CGP 35348, but they produced a strong inhibition of the [Ca2+]i increase induced by nicotine and muscimol. 5. The GABAB agonists also produced a dose-dependent increase in intracellular cyclic AMP levels, there being a direct correlation between both increase in catecholamine secretion and in intracellular cyclic AMP levels. 6. The pretreatment of chromaffin cells with pertussis toxin doubled the catecholamine secretion and increased by four times the intracellular cyclic AMP levels evoked by GABAB agonists. 7. The possible involvement of adenylate cyclase in the mechanism of GABAA receptor modulation of catecholamine secretion is discussed. PMID:8306105

  18. GABAB receptors modulate catecholamine secretion in chromaffin cells by a mechanism involving cyclic AMP formation.

    PubMed

    Oset-Gasque, M J; Parramón, M; González, M P

    1993-12-01

    1. The function of gamma-aminobutyric acidB (GABAB) receptors in modulation of catecholamine secretion by chromaffin cells and the possible mechanism involved in this action have been examined. 2. The GABAB agonists (-)-baclofen and 3-aminopropylphosphinic acid (3-APPA) were found to induce a dose-dependent increase of basal catecholamine secretion. The EC50s were 151 +/- 35 microM and 225 +/- 58 microM for baclofen and 3-APPA, respectively. This stimulatory effect was specific since it could be blocked by 0.5 mM of the specific GABAB antagonist CGP-35348. 3. In contrast, preincubation of chromaffin cells with the GABAB agonists was found to inhibit, in a dose-dependent manner, the catecholamine secretion evoked by 10 microM nicotine and 200 microM muscimol. 4. The effects of GABAB agonists on both basal and evoked catecholamine secretion were found to be accompanied by parallel changes in intracellular calcium concentration ([Ca2+]i). GABAB agonists produced a dose-dependent increase in [Ca2+]i which was partially blocked by CGP 35348, but they produced a strong inhibition of the [Ca2+]i increase induced by nicotine and muscimol. 5. The GABAB agonists also produced a dose-dependent increase in intracellular cyclic AMP levels, there being a direct correlation between both increase in catecholamine secretion and in intracellular cyclic AMP levels. 6. The pretreatment of chromaffin cells with pertussis toxin doubled the catecholamine secretion and increased by four times the intracellular cyclic AMP levels evoked by GABAB agonists. 7. The possible involvement of adenylate cyclase in the mechanism of GABAA receptor modulation of catecholamine secretion is discussed.

  19. Mechanisms Involved in Glucocorticoid Induction of Pituitary GH Expression During Embryonic Development

    PubMed Central

    Ellestad, Laura E.; Puckett, Stefanie A.

    2015-01-01

    Glucocorticoid hormones are involved in functional differentiation of GH-producing somatotrophs. Glucocorticoid treatment prematurely induces GH expression in mammals and birds in a process requiring protein synthesis and Rat sarcoma (Ras) signaling. The objective of this study was to investigate mechanisms through which glucocorticoids initiate GH expression during embryogenesis, taking advantage of the unique properties of chicken embryos as a developmental model. We determined that stimulation of GH expression occurred through transcriptional activation of GH, rather than enhancement of mRNA stability, and this process requires histone deacetylase activity. Through pharmacological inhibition, we identified the ERK1/2 pathway as a likely downstream Ras effector necessary for glucocorticoid stimulation of GH. However, we also found that chronic activation of ERK1/2 activity with a constitutively active mutant or stimulatory ligand reduced initiation of GH expression by glucocorticoid treatment. Corticosterone treatment of cultured embryonic pituitary cells increased ERK1/2 activity in an apparent cyclical manner, with a rapid increase within 5 minutes, followed by a reduction to near-basal levels at 3 hours, and a subsequent increase again at 6 hours. Therefore, we conclude that ERK1/2 signaling must be strictly controlled for maximal glucocorticoid induction of GH to occur. These results are the first in any species to demonstrate that Ras- and ERK1/2-mediated transcriptional events requiring histone deacetylase activity are involved in glucocorticoid induction of pituitary GH during embryonic development. This report increases our understanding of the molecular mechanisms underlying glucocorticoid recruitment of somatotrophs during embryogenesis and should provide insight into glucocorticoid-induced developmental changes in other tissues and cell types. PMID:25560830

  20. Key diffusion mechanisms involved in regulating bidirectional water permeation across E. coli outer membrane lectin

    PubMed Central

    Sachdeva, Shivangi; Kolimi, Narendar; Nair, Sanjana Anilkumar; Rathinavelan, Thenmalarchelvi

    2016-01-01

    Capsular polysaccharides (CPSs) are major bacterial virulent determinants that facilitate host immune evasion. E. coli group1 K30CPS is noncovalently attached to bacterial surface by Wzi, a lectin. Intriguingly, structure based phylogenetic analysis indicates that Wzi falls into porin superfamily. Molecular dynamics (MD) simulations further shed light on dual role of Wzi as it also functions as a bidirectional passive water specific porin. Such a functional role of Wzi was not realized earlier, due to the occluded pore. While five water specific entry points distributed across extracellular & periplasmic faces regulate the water diffusion involving different mechanisms, a luminal hydrophobic plug governs water permeation across the channel. Coincidently, MD observed open state structure of “YQF” triad is seen in sugar-binding site of sodium-galactose cotransporters, implicating its involvement in K30CPS surface anchorage. Importance of Loop 5 (L5) in membrane insertion is yet another highlight. Change in water diffusion pattern of periplasmic substitution mutants suggests Wzi’s role in osmoregulation by aiding in K30CPS hydration, corroborating earlier functional studies. Water molecules located inside β-barrel of Wzi crystal structure further strengthens the role of Wzi in osmoregulation. Thus, interrupting water diffusion or L5 insertion may reduce bacterial virulence. PMID:27320406

  1. Post-ictal analgesia: involvement of opioid, serotoninergic and cholinergic mechanisms.

    PubMed

    Coimbra, N C; Castro-Souza, C; Segato, E N; Nora, J E; Herrero, C F; Tedeschi-Filho, W; Garcia-Cairasco, N

    2001-01-12

    The neural mechanisms involved in post-ictal analgesia remain to be elucidated. Pentylenetetrazol (PTZ) is used experimentally to induce seizure in animal subjects. This non-competitive antagonist blocks GABA-mediated Cl(-) flux. The aim of this work is to study the neurochemical basis of the antinociception induced by convulsions elicited by peripheral administration of PTZ (64 mg/kg). The analgesia was measured by the tail-flick test, in eight rats per group. Convulsions were followed by significant increase in the tail-flick latencies (TFL), at least for 30 min of the post-ictal period. Peripheral administration of naloxone (5 mg/kg and 10 mg/kg), atropine (1 mg/kg and 5 mg/kg), methysergide (1 mg/kg and 5 mg/kg) and ketanserine (1 mg/kg and 2 mg/kg) caused a significant decrease in the TFL in seizing animals, as compared to controls. However, while naloxone antagonized analgesia 15 and 25 min post convulsions, the other drugs caused a blockade of the post-ictal analgesia in a relatively greater period of time. These results indicate that endogenous opioids, serotonin and acetylcholine may be involved in post-ictal analgesia.

  2. Enhancement mechanisms of graphene in nano-58S bioactive glass scaffold: mechanical and biological performance

    PubMed Central

    Gao, Chengde; Liu, Tingting; Shuai, Cijun; Peng, Shuping

    2014-01-01

    Graphene is a novel material and currently popular as an enabler for the next-generation nanocomposites. Here, we report the use of graphene to improve the mechanical properties of nano-58S bioactive glass for bone repair and regeneration. And the composite scaffolds were fabricated by a homemade selective laser sintering system. Qualitative and quantitative analysis demonstrated the successful incorporation of graphene into the scaffold without obvious structural damage and weight loss. The optimum compressive strength and fracture toughness reached 48.65 ± 3.19 MPa and 1.94 ± 0.10 MPa·m1/2 with graphene content of 0.5 wt%, indicating significant improvements by 105% and 38% respectively. The mechanisms of pull-out, crack bridging, crack deflection and crack tip shielding were found to be responsible for the mechanical enhancement. Simulated body fluid and cell culture tests indicated favorable bioactivity and biocompatibility of the composite scaffold. The results suggest a great potential of graphene/nano-58S composite scaffold for bone tissue engineering applications. PMID:24736662

  3. Surface mechanics of biological tissues using low-frequency rayleigh waves detected by laser speckle

    NASA Astrophysics Data System (ADS)

    Kirkpatrick, Sean J.; Duncan, Donald D.; Baker, Deborah A.; Adams, Jon

    2002-07-01

    An acousto-optical method for the determination of the mechanical loss factor in biological tissues is presented. Measurements of the loss factor were made on a polyvinyl chloride (PVC) phantom, elastin derived from a bovine nuchal ligament, and porcine skin. The acousto-optical values of the loss factor were compared with those measured with a more conventional mechanical testing system. The values for the mechanical loss factor for PVC and nuchal elastin as calculated from the acousto-optical method agreed with those determined using the mechanical testing system. However, there was a significant difference between the two methods for the porcine skin. We hypothesize that the acousto- optical method measures only the stratum corneum of the skin while the mechanical method evaluates the bulk properties of the skin. The rigid, keratinous fibers of the stratum corneum are believed to be responsible for the lower loss factor measured with the acousto-optical method.

  4. How do bifidobacteria counteract environmental challenges? Mechanisms involved and physiological consequences.

    PubMed

    Ruiz, Lorena; Ruas-Madiedo, Patricia; Gueimonde, Miguel; de Los Reyes-Gavilán, Clara G; Margolles, Abelardo; Sánchez, Borja

    2011-08-01

    An effective response to stress is of paramount importance for probiotic bifidobacteria administered in foods, since it determines their performance as beneficial microorganisms. Firstly, bifidobacteria have to be resistant to the stress sources typical in manufacturing, including heating, exposure to low water activities, osmotic shock and presence of oxygen. Secondly, and once they are orally ingested, bifidobacteria have to overcome physiological barriers in order to arrive in the large intestine biologically active. These barriers are mainly the acid pH in the stomach and the presence of high bile salt concentrations in the small intestine. In addition, the large intestine is, in terms of microbial amounts, a densely populated environment in which there is an extreme variability in carbon source availability. For this reason, bifidobacteria harbours a wide molecular machinery allowing the degradation of a wide variety of otherwise non-digestible sugars. In this review, the molecular mechanisms allowing this bacterial group to favourably react to the presence of different stress sources are presented and discussed.

  5. Anti-inflammatory effect of certain dihydroxy flavones and the mechanisms involved.

    PubMed

    Vidyalakshmi, K; Kamalakannan, P; Viswanathan, S; Ramaswamy, S

    2012-01-01

    This study was designed to evaluate the anti-inflammatory action of four dihydroxy flavone derivatives; 3,3'- dihydroxy flavone, 5,6-dihydroxy flavone, 3,7-dihydroxy flavone and 6,3'-dihydroxy flavone and to further investigate the multiple cellular mechanisms underlying the anti-inflammatory effect of these compounds. The effect of dihydroxy flavones on acute inflammation was studied in rats employing carrageenan induced hind paw edema method. Further, the role of proinflammatory cytokines like TNF-α and IL-1β, cyclooxygenases (COX-1 and COX-2), and free radicals in the action of flavone derivatives was investigated using in vitro assays. All the four dihydroxy flavone derivatives exhibited time and dose dependent inhibition of carrageenan induced paw edema. In addition, the investigated compounds inhibited both the isoforms of cyclooxygenase and cytokines in a concentration dependent manner and also suppressed the release of reactive oxygen species. The anti-inflammatory effect of dihydroxy flavones may be through mechanisms that involve an interaction with cyclooxygenases, cytokines and reactive oxygen species.

  6. Exploring the temporal mechanism involved in the pitch of unresolved harmonics.

    PubMed

    Kaernbach, C; Bering, C

    2001-08-01

    This paper continues a line of research initiated by Kaernbach and Demany [J. Acoust. Soc. Am. 104, 2298-2306 (1998)], who employed filtered click sequences to explore the temporal mechanism involved in the pitch of unresolved harmonics. In a first experiment, the just noticeable difference (jnd) for the fundamental frequency (F0) of high-pass filtered and low-pass masked click trains was measured, with F0 (100 to 250 Hz) and the cut frequency (0.5 to 6 kHz) being varied orthogonally. The data confirm the result of Houtsma and Smurzynski [J. Acoust. Soc. Am. 87, 304-310 (1990)] that a pitch mechanism working on the temporal structure of the signal is responsible for analyzing frequencies higher than ten times the fundamental. Using high-pass filtered click trains, however, the jnd for the temporal analysis is at 1.2% as compared to 2%-3% found in studies using band-pass filtered stimuli. Two further experiments provide evidence that the pitch of this stimulus can convey musical information. A fourth experiment replicates the finding of Kaernbach and Demany on first- and second-order regularities with a cut frequency of 2 kHz and extends the paradigm to binaural aperiodic click sequences. The result suggests that listeners can detect first-order temporal regularities in monaural click streams as well as in binaurally fused click streams.

  7. Depletion of bovine pituitary prolactin by cysteamine involves a thiol:disulfide mechanism

    SciTech Connect

    Lorenson, M.Y.; Jacobs, L.S.

    1984-10-01

    Cysteamine (2-aminoethanethiol (CySH)) reduces measurable PRL concentrations in vivo and in vitro. Since secretion is also inhibited, CySH may block conversion from a poorly assayable hormone storage form(s) to readily assayable, releasable PRL. This would represent a previously unrecognized mechanism for secretory regulation. We undertook the present study to identify the sites involved in the loss of measurable PRL (depletion) induced by cysteamine. The disulfide cystamine was ineffective on secretory granules unless combined with reduced glutathione, indicating the generation of the active CySH-thiol form. Pretreatment of granules with thiol-blocking agents resulted in dose-dependent enhancement of CySH inhibition, achieving nearly complete inhibition with 5 mM iodoacetamide. In contrast, pretreatment with reduced glutathione or dithiothreitol, respectively, impaired or abolished the CySH effect. These data suggest that the mechanism by which CySH causes PRL depletion is mediated by granule disulfides and the -SH of CySH. The regulation of thiol:disulfide equilibria appears to be an important determinant of the detectability of PRL storage forms and of their secretion.

  8. 3D deformation field in growing plant roots reveals both mechanical and biological responses to axial mechanical forces.

    PubMed

    Bizet, François; Bengough, A Glyn; Hummel, Irène; Bogeat-Triboulot, Marie-Béatrice; Dupuy, Lionel X

    2016-10-01

    Strong regions and physical barriers in soils may slow root elongation, leading to reduced water and nutrient uptake and decreased yield. In this study, the biomechanical responses of roots to axial mechanical forces were assessed by combining 3D live imaging, kinematics and a novel mechanical sensor. This system quantified Young's elastic modulus of intact poplar roots (32MPa), a rapid <0.2 mN touch-elongation sensitivity, and the critical elongation force applied by growing roots that resulted in bending. Kinematic analysis revealed a multiphase bio-mechanical response of elongation rate and curvature in 3D. Measured critical elongation force was accurately predicted from an Euler buckling model, indicating that no biologically mediated accommodation to mechanical forces influenced bending during this short period of time. Force applied by growing roots increased more than 15-fold when buckling was prevented by lateral bracing of the root. The junction between the growing and the mature zones was identified as a zone of mechanical weakness that seemed critical to the bending process. This work identified key limiting factors for root growth and buckling under mechanical constraints. The findings are relevant to crop and soil sciences, and advance our understanding of root growth in heterogeneous structured soils.

  9. 3D deformation field in growing plant roots reveals both mechanical and biological responses to axial mechanical forces

    PubMed Central

    Bizet, François; Bengough, A. Glyn; Hummel, Irène; Bogeat-Triboulot, Marie-Béatrice; Dupuy, Lionel X.

    2016-01-01

    Strong regions and physical barriers in soils may slow root elongation, leading to reduced water and nutrient uptake and decreased yield. In this study, the biomechanical responses of roots to axial mechanical forces were assessed by combining 3D live imaging, kinematics and a novel mechanical sensor. This system quantified Young’s elastic modulus of intact poplar roots (32MPa), a rapid <0.2 mN touch-elongation sensitivity, and the critical elongation force applied by growing roots that resulted in bending. Kinematic analysis revealed a multiphase bio-mechanical response of elongation rate and curvature in 3D. Measured critical elongation force was accurately predicted from an Euler buckling model, indicating that no biologically mediated accommodation to mechanical forces influenced bending during this short period of time. Force applied by growing roots increased more than 15-fold when buckling was prevented by lateral bracing of the root. The junction between the growing and the mature zones was identified as a zone of mechanical weakness that seemed critical to the bending process. This work identified key limiting factors for root growth and buckling under mechanical constraints. The findings are relevant to crop and soil sciences, and advance our understanding of root growth in heterogeneous structured soils. PMID:27664958

  10. A Concert between Biology and Biomechanics: The Influence of the Mechanical Environment on Bone Healing

    PubMed Central

    Glatt, Vaida; Evans, Christopher H.; Tetsworth, Kevin

    2017-01-01

    In order to achieve consistent and predictable fracture healing, a broad spectrum of growth factors are required to interact with one another in a highly organized response. Critically important, the mechanical environment around the fracture site will significantly influence the way bone heals, or if it heals at all. The role of the various biological factors, the timing, and spatial relationship of their introduction, and how the mechanical environment orchestrates this activity, are all crucial aspects to consider. This review will synthesize decades of work and the acquired knowledge that has been used to develop new treatments and technologies for the regeneration and healing of bone. Moreover, it will discuss the current state of the art in experimental and clinical studies concerning the application of these mechano-biological principles to enhance bone healing, by controlling the mechanical environment under which bone regeneration takes place. This includes everything from the basic principles of fracture healing, to the influence of mechanical forces on bone regeneration, and how this knowledge has influenced current clinical practice. Finally, it will examine the efforts now being made for the integration of this research together with the findings of complementary studies in biology, tissue engineering, and regenerative medicine. By bringing together these diverse disciplines in a cohesive manner, the potential exists to enhance fracture healing and ultimately improve clinical outcomes. PMID:28174539

  11. Ritualized fighting and biological armor: the impact mechanics of the mantis shrimp's telson.

    PubMed

    Taylor, J R A; Patek, S N

    2010-10-15

    Resisting impact and avoiding injury are central to survival in situations ranging from the abiotic forces of crashing waves to biotic collisions with aggressive conspecifics. Although impacts and collisions in biology are ubiquitous, most studies focus on the material properties of biological structures under static loading. Here, we examine the mechanical impact properties of the mantis shrimp's telson, a piece of abdominal armor that withstands repeated, intense impacts from the potent hammer-like appendages used by conspecifics during ritualized fighting. We measured the coefficient of restitution, an index of elasticity, of the telson and compared it with that of an adjacent abdominal segment that is not impacted. We found that the telson behaves more like an inelastic punching bag than an elastic trampoline, dissipating 69% of the impact energy. Furthermore, although the abdominal segment provides no mechanical correlates with size, the telson's coefficient of restitution, displacement and impact duration all correlate with body size. The telson's mineralization patterns were determined through micro-CT (Computed Tomography) and correspond to the mechanical behavior of the telson during impact. The mineralized central region of the telson 'punched' inward during an impact whereas the surrounding areas provided elasticity owing to their reduced mineralization. Thus, the telson effectively dissipates impact energy while potentially providing the size-related information crucial to its role in conspecific assessment. This study reveals the mechanical infrastructure of impact resistance in biological armor and opens a new window to the biomechanical underpinnings of animal behavior and assessment.

  12. Biological and mechanical evaluation of a Bio-Hybrid scaffold for autologous valve tissue engineering.

    PubMed

    Jahnavi, S; Saravanan, U; Arthi, N; Bhuvaneshwar, G S; Kumary, T V; Rajan, S; Verma, R S

    2017-04-01

    Major challenge in heart valve tissue engineering for paediatric patients is the development of an autologous valve with regenerative capacity. Hybrid tissue engineering approach is recently gaining popularity to design scaffolds with desired biological and mechanical properties that can remodel post implantation. In this study, we fabricated aligned nanofibrous Bio-Hybrid scaffold made of decellularized bovine pericardium: polycaprolactone-chitosan with optimized polymer thickness to yield the desired biological and mechanical properties. CD44(+), αSMA(+), Vimentin(+) and CD105(-) human valve interstitial cells were isolated and seeded on these Bio-Hybrid scaffolds. Subsequent biological evaluation revealed interstitial cell proliferation with dense extra cellular matrix deposition that indicated the viability for growth and proliferation of seeded cells on the scaffolds. Uniaxial mechanical tests along axial direction showed that the Bio-Hybrid scaffolds has at least 20 times the strength of the native valves and its stiffness is nearly 3 times more than that of native valves. Biaxial and uniaxial mechanical studies on valve interstitial cells cultured Bio-Hybrid scaffolds revealed that the response along the axial and circumferential direction was different, similar to native valves. Overall, our findings suggest that Bio-Hybrid scaffold is a promising material for future development of regenerative heart valve constructs in children.

  13. A Model of How Different Biology Experts Explain Molecular and Cellular Mechanisms

    PubMed Central

    Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

    2015-01-01

    Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do explanations made by experts from different biology subdisciplines at a university support the validity of this model? Guided by the modeling framework of R. S. Justi and J. K. Gilbert, the validity of an initial model was tested by asking seven biologists to explain a molecular mechanism of their choice. Data were collected from interviews, artifacts, and drawings, and then subjected to thematic analysis. We found that biologists explained the specific activities and organization of entities of the mechanism. In addition, they contextualized explanations according to their biological and social significance; integrated explanations with methods, instruments, and measurements; and used analogies and narrated stories. The derived methods, analogies, context, and how themes informed the development of our final MACH model of mechanistic explanations. Future research will test the potential of the MACH model as a guiding framework for instruction to enhance the quality of student explanations. PMID:25999313

  14. A model of how different biology experts explain molecular and cellular mechanisms.

    PubMed

    Trujillo, Caleb M; Anderson, Trevor R; Pelaez, Nancy J

    2015-01-01

    Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do explanations made by experts from different biology subdisciplines at a university support the validity of this model? Guided by the modeling framework of R. S. Justi and J. K. Gilbert, the validity of an initial model was tested by asking seven biologists to explain a molecular mechanism of their choice. Data were collected from interviews, artifacts, and drawings, and then subjected to thematic analysis. We found that biologists explained the specific activities and organization of entities of the mechanism. In addition, they contextualized explanations according to their biological and social significance; integrated explanations with methods, instruments, and measurements; and used analogies and narrated stories. The derived methods, analogies, context, and how themes informed the development of our final MACH model of mechanistic explanations. Future research will test the potential of the MACH model as a guiding framework for instruction to enhance the quality of student explanations.

  15. Bovine glycomacropeptide ameliorates experimental rat ileitis by mechanisms involving downregulation of interleukin 17

    PubMed Central

    Requena, P; Daddaoua, A; Martínez-Plata, E; González, M; Zarzuelo, A; Suárez, M D; Sánchez de Medina, F; Martínez-Augustin, O

    2008-01-01

    Background and purpose: Bovine glycomacropeptide (BGMP) is an inexpensive, non-toxic milk peptide with anti-inflammatory effects in rat experimental colitis but its mechanism of action is unclear. It is also unknown whether BGMP can ameliorate inflammation in proximal regions of the intestine. Our aim was therefore two-fold: first, to determine the anti-inflammatory activity of BGMP in the ileum; second, to characterise its mechanism of action. Experimental approach: We used a model of ileitis induced by trinitrobenzenesulphonic acid in rats. Rats were treated orally with BGMP and its efficacy compared with that of oral 5-aminosalicylic acid or vehicle, starting 2 days before ileitis induction. Key results: BGMP pretreatment (500 mg kg−1 day−1) resulted in marked reduction of inflammatory injury, as assessed by lower extension of necrosis and damage score, myeloperoxidase, alkaline phosphatase, inducible nitric oxide synthase, interleukin 1β, tumour necrosis factor and interleukin 17. These effects were generally comparable to those of 5-aminosalicylic acid (200 mg kg−1 day−1). Neither compound affected the production of interferon γ, tumour necrosis factor and interleukin 2 by mesenteric lymph node cells isolated from animals with ileitis. The expression of Foxp3 was increased in ileitis and not reduced significantly by BGMP or aminosalicylate treatment. Conclusions and implications: These results demonstrate that BGMP has anti-inflammatory activity in the ileum with similar efficacy to 5-aminosalicylic acid. The mechanism of action may involve Th17 and regulatory T cells and perhaps macrophages but probably not Th1 lymphocytes. Patients with Crohn's ileitis may benefit from treatment with BGMP. PMID:18536735

  16. Crosstalk of Signaling Mechanisms Involved in Host Defense and Symbiosis Against Microorganisms in Rice

    PubMed Central

    Akamatsu, Akira; Shimamoto, Ko; Kawano, Yoji

    2016-01-01

    Rice is one of the most important food crops, feeding about half population in the world. Rice pathogens cause enormous damage to rice production worldwide. In plant immunity research, considerable progress has recently been made in our understanding of the molecular mechanisms underlying microbe-associated molecular pattern (MAMP)-triggered immunity. Using genome sequencing and molecular techniques, a number of new MAMPs and their receptors have been identified in the past two decades. Notably, the mechanisms for chitin perception via the lysine motif (LysM) domain-containing receptor OsCERK1, as well as the mechanisms for bacterial MAMP (e.g. flg22, elf18) perception via the leucine-rich repeat (LRR) domain-containing receptors FLS2 and EFR, have been clarified in rice and Arabidopsis, respectively. In chitin signaling in rice, two direct substrates of OsCERK1, Rac/ROP GTPase guanine nucleotide exchange factor OsRacGEF1 and receptor-like cytoplasmic kinase OsRLCK185, have been identified as components of the OsCERK1 complex and are rapidly phosphorylated by OsCERK1 in response to chitin. Interestingly, OsCERK1 also participates in symbiosis with arbuscular mycorrhizal fungi (AMF) in rice and plays a role in the recognition of short-chitin molecules (CO4/5), which are symbiotic signatures included in AMF germinated spore exudates and induced by synthetic strigolactone. Thus, OsCERK1 contributes to both immunity and symbiotic responses. In this review, we describe recent studies on pathways involved in rice immunity and symbiotic signaling triggered by interactions with microorganisms. In addition, we describe recent advances in genetic engineering by using plant immune receptors and symbiotic microorganisms to enhance disease resistance of rice. PMID:27499679

  17. Mechanism of PP2A-mediated IKKβ dephosphorylation: a systems biological approach

    PubMed Central

    Witt, Johannes; Barisic, Sandra; Schumann, Eva; Allgöwer, Frank; Sawodny, Oliver; Sauter, Thomas; Kulms, Dagmar

    2009-01-01

    Background Biological effects of nuclear factor-κB (NFκB) can differ tremendously depending on the cellular context. For example, NFκB induced by interleukin-1 (IL-1) is converted from an inhibitor of death receptor induced apoptosis into a promoter of ultraviolet-B radiation (UVB)-induced apoptosis. This conversion requires prolonged NFκB activation and is facilitated by IL-1 + UVB-induced abrogation of the negative feedback loop for NFκB, involving a lack of inhibitor of κB (IκBα) protein reappearance. Permanent activation of the upstream kinase IKKβ results from UVB-induced inhibition of the catalytic subunit of Ser-Thr phosphatase PP2A (PP2Ac), leading to immediate phosphorylation and degradation of newly synthesized IκBα. Results To investigate the mechanism underlying the general PP2A-mediated tuning of IKKβ phosphorylation upon IL-1 stimulation, we have developed a strictly reduced mathematical model based on ordinary differential equations which includes the essential processes concerning the IL-1 receptor, IKKβ and PP2A. Combining experimental and modelling approaches we demonstrate that constitutively active, but not post-stimulation activated PP2A, tunes out IKKβ phosphorylation thus allowing for IκBα resynthesis in response to IL-1. Identifiability analysis and determination of confidence intervals reveal that the model allows reliable predictions regarding the dynamics of PP2A deactivation and IKKβ phosphorylation. Additionally, scenario analysis is used to scrutinize several hypotheses regarding the mode of UVB-induced PP2Ac inhibition. The model suggests that down regulation of PP2Ac activity, which results in prevention of IκBα reappearance, is not a direct UVB action but requires instrumentality. Conclusion The model developed here can be used as a reliable building block of larger NFκB models and offers comprehensive simplification potential for future modeling of NFκB signaling. It gives more insight into the newly discovered

  18. Energy saving mechanisms, collective behavior and the variation range hypothesis in biological systems: A review.

    PubMed

    Trenchard, Hugh; Perc, Matjaž

    2016-09-01

    Energy saving mechanisms are ubiquitous in nature. Aerodynamic and hydrodynamic drafting, vortice uplift, Bernoulli suction, thermoregulatory coupling, path following, physical hooks, synchronization, and cooperation are only some of the better-known examples. While drafting mechanisms also appear in non-biological systems such as sedimentation and particle vortices, the broad spectrum of these mechanisms appears more diversely in biological systems that include bacteria, spermatozoa, various aquatic species, birds, land animals, semi-fluid dwellers like turtle hatchlings, as well as human systems. We present the thermodynamic framework for energy saving mechanisms, and we review evidence in favor of the variation range hypothesis. This hypothesis posits that, as an evolutionary process, the variation range between strongest and weakest group members converges on the equivalent energy saving quantity that is generated by the energy saving mechanism. We also review self-organized structures that emerge due to energy saving mechanisms, including convective processes that can be observed in many systems over both short and long time scales, as well as high collective output processes in which a form of collective position locking occurs.

  19. [Modern evolutional developmental biology: mechanical and molecular genetic or phenotypic approaches?].

    PubMed

    Vorob'eva, É I

    2010-01-01

    Heightened interest in the evolutionary problems of developmental biology in the 1980s was due to the success of molecular genetics and disappointment in the synthetic theory of evolution, where the chapters of embryology and developmental biology seem to have been left out. Modern evo-devo, which turned out to be antipodean to the methodology of the synthetic theory of evolution, propagandized in the development of evolutionary problems only the mechanical and molecular genetic approach to the evolution of ontogenesis, based on cellular and intercellular interactions. The phonotypical approach to the evaluation of evolutionary occurrences in ontogenesis, which aids in the joining of the genetic and epigenetic levels of research, the theory of natural selection, the nomogenetic conception, and the problem of the wholeness of the organism in onto- and phylogenesis may be against this. The phenotypic approach to ontogenesis is methodologically the most perspective for evolutionary developmental biology.

  20. Systems Cancer Biology and the Controlling Mechanisms for the J-Shaped Cancer Dose Response: Towards Relaxing the LNT Hypothesis.

    PubMed

    Lou, In Chio; Zhao, Yuchao; Wu, Yingjie; Ricci, Paolo F

    2012-01-01

    The hormesis phenomena or J-shaped dose response have been accepted as a common phenomenon regardless of the involved biological model, endpoint measured and chemical class/physical stressor. This paper first introduced a mathematical dose response model based on systems biology approach. It links molecular-level cell cycle checkpoint control information to clonal growth cancer model to predict the possible shapes of the dose response curves of Ionizing Radiation (IR) induced tumor transformation frequency. J-shaped dose response curves have been captured with consideration of cell cycle checkpoint control mechanisms. The simulation results indicate the shape of the dose response curve relates to the behavior of the saddle-node points of the model in the bifurcation diagram. A simplified version of the model in previous work of the authors was used mathematically to analyze behaviors relating to the saddle-node points for the J-shaped dose response curve. It indicates that low-linear energy transfer (LET) is more likely to have a J-shaped dose response curve. This result emphasizes the significance of systems biology approach, which encourages collaboration of multidiscipline of biologists, toxicologists and mathematicians, to illustrate complex cancer-related events, and confirm the biphasic dose-response at low doses.

  1. Association of environmental enrichment and locomotor stimulation in a rodent model of cerebral palsy: Insights of biological mechanisms.

    PubMed

    Meireles, André L F; Marques, Marília R; Segabinazi, Ethiane; Spindler, Christiano; Piazza, Francele V; Salvalaggio, Gabriela S; Augustin, Otávio A; Achaval, Matilde; Marcuzzo, Simone

    2017-01-01

    Several physiotherapy approaches are used with different aims in the treatment of cerebral palsy (CP), such as the early stimulation and the locomotor training, but their biological effects, isolated or combined, are not completely known. In animals models, these strategies can be compared, with due translational restrictions, to the environmental enrichment (EE), that involves the enhancement of animal's physical and social environment, and locomotor stimulation (LS), that can be performed using the treadmill adapted for rats. This study was designed to describe which biological and functional mechanisms underlying rehabilitative process in clinical practice. Male rat pups were initially divided in two groups: control (healthy) and submitted to a CP model. Then, pups were divided in eight groups: CP, CPEE, CPLS, CPEELS and its respectively control groups. Functional outcomes were assessed at the postnatal day (P) 31 and P52. The tibialis anterior and soleus muscles, tibia bone parameters, the expression of synaptophysin in the primary motor cortex (M1) and ventral horn (VH) of the spinal cord, were evaluated. The association of therapies was able to improve the functional assessments and musculoskeletal parameters. Isolated therapies presented complementary benefits in CP, but the association of therapies proved to be a fundamental and effective strategy to functional recovery, besides alter positively all biological tissues evaluated in this study.

  2. Exploring the MACH Model's Potential as a Metacognitive Tool to Help Undergraduate Students Monitor Their Explanations of Biological Mechanisms

    ERIC Educational Resources Information Center

    Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

    2016-01-01

    When undergraduate biology students learn to explain biological mechanisms, they face many challenges and may overestimate their understanding of living systems. Previously, we developed the MACH model of four components used by expert biologists to explain mechanisms: Methods, Analogies, Context, and How. This study explores the implementation of…

  3. The radical-pair mechanism as a paradigm for the emerging science of quantum biology

    NASA Astrophysics Data System (ADS)

    Kominis, Iannis K.

    2015-12-01

    The radical-pair mechanism (RPM) was introduced in the 1960s to explain anomalously large EPR and NMR signals in chemical reactions of organic molecules. It has evolved to the cornerstone of spin chemistry, the study of the effect electron and nuclear spins have on chemical reactions, with the avian magnetic compass mechanism and the photosynthetic reaction center dynamics being prominent biophysical manifestations of such effects. In recent years the RPM was shown to be an ideal biological system where the conceptual tools of quantum-information science can be fruitfully applied. We will here review recent work making the case that RPM is indeed a major driving force of the emerging field of quantum biology.

  4. Insights into reference point indentation involving human cortical bone: sensitivity to tissue anisotropy and mechanical behavior.

    PubMed

    Granke, Mathilde; Coulmier, Aurélie; Uppuganti, Sasidhar; Gaddy, Jennifer A; Does, Mark D; Nyman, Jeffry S

    2014-09-01

    Reference point indentation (RPI) is a microindentation technique involving 20 cycles of loading in "force-control" that can directly assess a patient׳s bone tissue properties. Even though preliminary clinical studies indicate a capability for fracture discrimination, little is known about what mechanical behavior the various RPI properties characterize and how these properties relate to traditional mechanical properties of bone. To address this, the present study investigated the sensitivity of RPI properties to anatomical location and tissue organization as well as examined to what extent RPI measurements explain the intrinsic mechanical properties of human cortical bone. Multiple indents with a target force of 10N were done in 2 orthogonal directions (longitudinal and transverse) per quadrant (anterior, medial, posterior, and lateral) of the femoral mid-shaft acquired from 26 donors (25-101 years old). Additional RPI measurements were acquired for 3 orthogonal directions (medial only). Independent of age, most RPI properties did not vary among these locations, but they did exhibit transverse isotropy such that resistance to indentation is greater in the longitudinal (axial) direction than in the transverse direction (radial or circumferential). Next, beam specimens (~2mm×5mm×40mm) were extracted from the medial cortex of femoral mid-shafts, acquired from 34 donors (21-99 years old). After monotonically loading the specimens in three-point bending to failure, RPI properties were acquired from an adjacent region outside the span. Indent direction was orthogonal to the bending axis. A significant inverse relationship was found between resistance to indentation and the apparent-level mechanical properties. Indentation distance increase (IDI) and a linear combination of IDI and the loading slope, averaged over cycles 3 through 20, provided the best explanation of the variance in ultimate stress (r(2)=0.25, p=0.003) and toughness (r(2)=0.35, p=0.004), respectively

  5. A biological mechanism for Bayesian feature selection: Weight decay and raising the LASSO.

    PubMed

    Connor, Patrick; Hollensen, Paul; Krigolson, Olav; Trappenberg, Thomas

    2015-07-01

    Biological systems are capable of learning that certain stimuli are valuable while ignoring the many that are not, and thus perform feature selection. In machine learning, one effective feature selection approach is the least absolute shrinkage and selection operator (LASSO) form of regularization, which is equivalent to assuming a Laplacian prior distribution on the parameters. We review how such Bayesian priors can be implemented in gradient descent as a form of weight decay, which is a biologically plausible mechanism for Bayesian feature selection. In particular, we describe a new prior that offsets or "raises" the Laplacian prior distribution. We evaluate this alongside the Gaussian and Cauchy priors in gradient descent using a generic regression task where there are few relevant and many irrelevant features. We find that raising the Laplacian leads to less prediction error because it is a better model of the underlying distribution. We also consider two biologically relevant online learning tasks, one synthetic and one modeled after the perceptual expertise task of Krigolson et al. (2009). Here, raising the Laplacian prior avoids the fast erosion of relevant parameters over the period following training because it only allows small weights to decay. This better matches the limited loss of association seen between days in the human data of the perceptual expertise task. Raising the Laplacian prior thus results in a biologically plausible form of Bayesian feature selection that is effective in biologically relevant contexts.

  6. Determining chemical reactivity driving biological activity from SMILES transformations: the bonding mechanism of anti-HIV pyrimidines.

    PubMed

    Putz, Mihai V; Dudaş, Nicoleta A

    2013-07-30

    Assessing the molecular mechanism of a chemical-biological interaction and bonding stands as the ultimate goal of any modern quantitative structure-activity relationship (QSAR) study. To this end the present work employs the main chemical reactivity structural descriptors (electronegativity, chemical hardness, chemical power, electrophilicity) to unfold the variational QSAR though their min-max correspondence principles as applied to the Simplified Molecular Input Line Entry System (SMILES) transformation of selected uracil derivatives with anti-HIV potential with the aim of establishing the main stages whereby the given compounds may inhibit HIV infection. The bonding can be completely described by explicitly considering by means of basic indices and chemical reactivity principles two forms of SMILES structures of the pyrimidines, the Longest SMILES Molecular Chain (LoSMoC) and the Branching SMILES (BraS), respectively, as the effective forms involved in the anti-HIV activity mechanism and according to the present work, also necessary intermediates in molecular pathways targeting/docking biological sites of interest.

  7. Lysine 2,3-aminomutase. Support for a mechanism of hydrogen transfer involving S-adenosylmethionine.

    PubMed

    Baraniak, J; Moss, M L; Frey, P A

    1989-01-25

    The conversion of L-lysine to L-beta-lysine is catalyzed by lysine 2,3-aminomutase. The reaction involves the interchange of the 2-amino group of lysine with a hydrogen at carbon 3. As such the reaction is formally analogous to adenosylcobalamin-dependent rearrangements. However, the enzyme does not contain and is not activated by this coenzyme. Instead it contains iron and pyridoxal phosphate and is activated by S-adenosylmethionine. Earlier experiments implicated adenosyl-C-5' of S-adenosylmethionine in the hydrogen transfer mechanism, apparently in a role similar or analogous to that of adenosyl moiety of adenosylcobalamin in the B12-dependent rearrangements. The question of whether both hydrogens or only one hydrogen at adenosyl-C-5' participate in the hydrogen-transfer process has been addressed by carrying out the lysine 2,3-aminomutase reaction with S-[5'-3H] adenosylmethionine in the presence of 10 times its molar concentration of enzyme. Under these conditions all of the tritium appeared in lysine and beta-lysine, showing that C-5'-hydrogens participate. To determine whether hydrogen transfer is compulsorily intermolecular and intramolecular, various molar ratios of [3,3-2H2]lysine and unlabeled lysine were submitted to the action of lysine 2,3-aminomutase under conditions in which 10-15% conversion to beta-lysine occurred. Mass spectral analysis of the beta-lysine for monodeutero and dideutero species showed conclusively that hydrogen transfer is both intramolecular and intermolecular. The results quantitatively support our postulate that activation of the enzyme involves a transformation of S-adenosylmethionine into a form that promotes the generation of an adenosyl-5' free radical, which abstracts hydrogen from lysine to form 5'-deoxyadenosine as an intermediate.

  8. Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms.

    PubMed

    Srinivasan, Padmanabhan; Kapadia, Rubina; Biswas, Arundhati; Said, Hamid M

    2014-11-01

    Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5'-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na(+) dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.

  9. Toxic effects of expanded ataxin-1 involve mechanical instability of the nuclear membrane.

    PubMed

    Mapelli, Lisa; Canale, Claudio; Pesci, Daniela; Averaimo, Stefania; Guizzardi, Fabiana; Fortunati, Valentina; Falasca, Laura; Piacentini, Mauro; Gliozzi, Alessandra; Relini, Annalisa; Mazzanti, Michele; Jodice, Carla

    2012-06-01

    Ataxin 1 (ATXN1) is the protein involved in spinocerebellar ataxia type 1, one of nine dominantly inherited neurodegenerative diseases triggered by polyglutamine expansion. One of the isolated polyglutamine tracts properties is to interact with lipid bilayers. Here we used a multidisciplinary approach to test whether one of the mechanisms responsible for neuronal degeneration involves the destabilization of the nuclear membrane. We thus analyzed the interaction between ATXN1 and lipid membranes, both on cellular models and on artificial lipid bilayers, comparing pathological expanded polyglutamine and histidine interrupted non-harmful polyglutamine tracts of the same length. The toxicity of the different constructs was tested in transiently transfected COS1 cells. Cells expressing pathological ATXN1 presented a significantly higher frequency of anomalous nuclei with respect to those expressing non-harmful ATXN1. Immunofluorescence and electron microscopy showed severe damage in the nuclear membrane of cells expressing the pathological protein. Atomic force microscopy on artificial membranes containing interrupted and non-interrupted partial ATXN1 peptides revealed a different arrangement of the peptides within the lipid bilayer. Force-distance measurements indicated that membrane fragility increases with the lengthening of the uninterrupted glutamine. Transmembrane electrical measurements were performed on artificial bilayers and on the inner nuclear membrane of ATXN1 full length transfected cells. Both artificial lipid bilayers and cellular models demonstrated the dynamic appearance of ionic pathways. Uninterrupted polyglutamines showed not only a larger ionic flow, but also an increase in the single event conductance. Collectively, our results suggest that expanded ATXN1 may induce unregulated ionic pathways in the nuclear membrane, causing severe damage to the cell.

  10. Development of neurodevelopmental disorders: a regulatory mechanism involving bromodomain-containing proteins.

    PubMed

    Li, Junlin; Zhao, Guifang; Gao, Xiaocai

    2013-02-20

    Neurodevelopmental disorders are classified as diseases that cause abnormal functions of the brain or central nervous system. Children with neurodevelopmental disorders show impaired language and speech abilities, learning and memory damage, and poor motor skills. However, we still know very little about the molecular etiology of these disorders. Recent evidence implicates the bromodomain-containing proteins (BCPs) in the initiation and development of neurodevelopmental disorders. BCPs have a particular domain, the bromodomain (Brd), which was originally identified as specifically binding acetyl-lysine residues at the N-terminus of histone proteins in vitro and in vivo. Other domains of BCPs are responsible for binding partner proteins to form regulatory complexes. Once these complexes are assembled, BCPs alter chromosomal states and regulate gene expression. Some BCP complexes bind nucleosomes, are involved in basal transcription regulation, and influence the transcription of many genes. However, most BCPs are involved in targeting. For example, some BCPs function as a recruitment platform or scaffold through their Brds-binding targeting sites. Others are recruited to form a complex to bind the targeting sites of their partners. The regulation mediated by these proteins is especially critical during normal and abnormal development. Mutant BCPs or dysfunctional BCP-containing complexes are implicated in the initiation and development of neurodevelopmental disorders. However, the pathogenic molecular mechanisms are not fully understood. In this review, we focus on the roles of regulatory BCPs associated with neurodevelopmental disorders, including mental retardation, Fragile X syndrome (FRX), Williams syndrome (WS), Rett syndrome and Rubinstein-Taybi syndrome (RTS). A better understanding of the molecular pathogenesis, based upon the roles of BCPs, will lead to screening of targets for the treatment of neurodevelopmental disorders.

  11. Molecular Mechanisms Involved in the Interaction Effects of Alcohol and Hepatitis C Virus in Liver Cirrhosis

    PubMed Central

    Mas, Valeria R; Fassnacht, Ryan; Archer, Kellie J; Maluf, Daniel

    2010-01-01

    The mechanisms by which alcohol consumption accelerates liver disease in patients with chronic hepatitis C virus (HCV) are not well understood. To identify the characteristics of molecular pathways affected by alcohol in HCV patients, we fit probe-set level linear models that included the additive effects as well as the interaction between alcohol and HCV. The study included liver tissue samples from 78 patients, 23 (29.5%) with HCV-cirrhosis, 13 (16.7%) with alcohol-cirrhosis, 23 (29.5%) with HCV/alcohol cirrhosis and 19 (24.4%) with no liver disease (no HCV/no alcohol group). We performed gene-expression profiling by using microarrays. Probe-set expression summaries were calculated by using the robust multiarray average. Probe-set level linear models were fit where probe-set expression was modeled by HCV status, alcohol status, and the interaction between HCV and alcohol. We found that 2172 probe sets (1895 genes) were differentially expressed between HCV cirrhosis versus alcoholic cirrhosis groups. Genes involved in the virus response and the immune response were the more important upregulated genes in HCV cirrhosis. Genes involved in apoptosis regulation were also overexpressed in HCV cirrhosis. Genes of the cytochrome P450 superfamily of enzymes were upregulated in alcoholic cirrhosis, and 1230 probe sets (1051 genes) had a significant interaction estimate. Cell death and cellular growth and proliferation were affected by the interaction between HCV and alcohol. Immune response and response to the virus genes were downregulated in HCV-alcohol interaction (interaction term alcohol*HCV). Alcohol*HCV in the cirrhotic tissues resulted in a strong negative regulation of the apoptosis pattern with concomitant positive regulation of cellular division and proliferation. PMID:20386865

  12. Zuclopenthixol facilitates memory retrieval in rats: possible involvement of noradrenergic and serotonergic mechanisms.

    PubMed

    Khalifa, Amani E

    2003-07-01

    Although disturbed memory function often coexists with psychosis, the cognitive effects of antipsychotic medications with diverse pharmacodynamic properties are rarely investigated. The neurocognitive profile of zuclopenthixol, a thioxanthene dopaminergic antagonist and a conventional neuroleptic agent, has yet to be investigated despite the effect of the drug on a variety of neurotransmitter systems involved in mediation of learning and memory processes. In this study, the effect of zuclopenthixol was tested on memory retrieval 24 h after training using an inhibitory avoidance task in rats. Acute administration of zuclopenthixol (0.7 and 1.4 mg/kg i.p.) before retrieval testing increased step-through latency during the test session. The same doses of zuclopenthixol did not affect the ambulatory activity of rats in the openfield test and therefore the facilitatory effect of the drug on memory function could not be confounded with any motoric properties. This study also investigated the effect of zuclopenthixol on cortical and hippocampal monoaminergic neurotransmitters' levels together with acetylcholinesterase enzyme (AChE) activity, both of which are known to be important in control of cognitive function. Administration of zuclopenthixol (0.7 and 1.4 mg/kg i.p.) neither affected dopamine (DA) level nor AChE activity in rat cortex and hippocampus. On the other hand, the lower dose of zuclopenthixol elevated cortical norepinephrine (NE) level, while the higher dose elevated both cortical and hippocampal NE level together with hippocampal serotonin (5-HT) level. These results may suggest the involvement of adrenergic and serotonergic mechanisms in the facilitatory effect of zuclopenthixol on retrieval memory. Zuclopenthixol may therefore be a better alternative than other commonly used antipsychotic medications reported to impair cognitive function of schizophrenic patients.

  13. An Integrated Review of Psychological Stress in Parkinson's Disease: Biological Mechanisms and Symptom and Health Outcomes.

    PubMed

    Austin, Kim Wieczorek; Ameringer, Suzanne Weil; Cloud, Leslie Jameleh

    2016-01-01

    Parkinson's disease (PD) is characterized by complex symptoms and medication-induced motor complications that fluctuate in onset, severity, responsiveness to treatment, and disability. The unpredictable and debilitating nature of PD and the inability to halt or slow disease progression may result in psychological stress. Psychological stress may exacerbate biological mechanisms believed to contribute to neuronal loss in PD and lead to poorer symptom and health outcomes. The purpose of this integrated review is to summarize and appraise animal and human research studies focused on biological mechanisms, symptom, and health outcomes of psychological stress in PD. A search of the electronic databases PubMed/Medline and CINAHL from 1980 to the present using the key words Parkinson's disease and stress, psychological stress, mental stress, and chronic stress resulted in 11 articles that met inclusion criteria. The results revealed significant associations between psychological stress and increased motor symptom severity and loss of dopamine-producing neurons in animal models of PD and between psychological stress and increased symptom severity and poorer health outcomes in human subjects with PD. Further research is needed to fully elucidate the underlying biological mechanisms responsible for these relationships, for the ultimate purpose of designing targeted interventions that may modify the disease trajectory.

  14. An Integrated Review of Psychological Stress in Parkinson's Disease: Biological Mechanisms and Symptom and Health Outcomes

    PubMed Central

    2016-01-01

    Parkinson's disease (PD) is characterized by complex symptoms and medication-induced motor complications that fluctuate in onset, severity, responsiveness to treatment, and disability. The unpredictable and debilitating nature of PD and the inability to halt or slow disease progression may result in psychological stress. Psychological stress may exacerbate biological mechanisms believed to contribute to neuronal loss in PD and lead to poorer symptom and health outcomes. The purpose of this integrated review is to summarize and appraise animal and human research studies focused on biological mechanisms, symptom, and health outcomes of psychological stress in PD. A search of the electronic databases PubMed/Medline and CINAHL from 1980 to the present using the key words Parkinson's disease and stress, psychological stress, mental stress, and chronic stress resulted in 11 articles that met inclusion criteria. The results revealed significant associations between psychological stress and increased motor symptom severity and loss of dopamine-producing neurons in animal models of PD and between psychological stress and increased symptom severity and poorer health outcomes in human subjects with PD. Further research is needed to fully elucidate the underlying biological mechanisms responsible for these relationships, for the ultimate purpose of designing targeted interventions that may modify the disease trajectory. PMID:28058129

  15. A Stable Biologically Motivated Learning Mechanism for Visual Feature Extraction to Handle Facial Categorization

    PubMed Central

    Rajaei, Karim; Khaligh-Razavi, Seyed-Mahdi; Ghodrati, Masoud; Ebrahimpour, Reza; Shiri Ahmad Abadi, Mohammad Ebrahim

    2012-01-01

    The brain mechanism of extracting visual features for recognizing various objects has consistently been a controversial issue in computational models of object recognition. To extract visual features, we introduce a new, biologically motivated model for facial categorization, which is an extension of the Hubel and Wiesel simple-to-complex cell hierarchy. To address the synaptic stability versus plasticity dilemma, we apply the Adaptive Resonance Theory (ART) for extracting informative intermediate level visual features during the learning process, which also makes this model stable against the destruction of previously learned information while learning new information. Such a mechanism has been suggested to be embedded within known laminar microcircuits of the cerebral cortex. To reveal the strength of the proposed visual feature learning mechanism, we show that when we use this mechanism in the training process of a well-known biologically motivated object recognition model (the HMAX model), it performs better than the HMAX model in face/non-face classification tasks. Furthermore, we demonstrate that our proposed mechanism is capable of following similar trends in performance as humans in a psychophysical experiment using a face versus non-face rapid categorization task. PMID:22719892

  16. Structure and Mechanism of Enzymes Involved in Biosynthesis and Breakdown of the Phosphonates Fosfomycin, Dehydrophos, and Phosphinothricin

    PubMed Central

    Nair, Satish K.; van der Donk, Wilfred A.

    2011-01-01

    Recent years have seen a rapid increase in the mechanistic and structural information on enzymes that are involved in the biosynthesis and breakdown of naturally occurring phosphonates. This review focuses on these recent developments with an emphasis on those enzymes that have been characterized crystallographically in the past five years, including proteins involved in the biosynthesis of phosphinothricin, fosfomycin, and dehydrophos and proteins involved in resistance mechanisms. PMID:20854789

  17. Semiquinone Intermediates are involved in the Energy Coupling Mechanism of E. coli Complex I

    PubMed Central

    Narayanan, Madhavan; Leung, Steven A.; Inaba, Yuta; Elguindy, Mahmoud M.; Nakamaru-Ogiso, Eiko

    2015-01-01

    Complex I (NADH:quinone oxidoreductase) is central to cellular aerobic energy metabolism, and its deficiency is involved in many human mitochondrial diseases. Complex I translocates protons across the membrane using electron transfer energy. Semiquinone (SQ) intermediates appearing during catalysis are suggested to be key for the coupling mechanism in complex I. However, the existence of SQ has remained controversial due to the extreme difficulty in detecting unstable and low intensity SQ signals. Here, for the first time with E. coli complex I reconstituted in proteoliposomes, we successfully resolved and characterized three distinct SQ species by EPR. These species include: fast-relaxing SQ (SQNf) with P1/2 (half-saturation power level) > 50 mW and a wider linewidth (12.8 G); slow-relaxing SQ (SQNs) with P1/2 = 2–3 mW and a 10 G linewidth; and very slow-relaxing SQ (SQNvs) with P1/2 = ~ 0.1 mW and a 7.5 G linewidth. The SQNf signals completely disappeared in the presence of the uncoupler gramicidin D or squamotacin, a potent E. coli complex I inhibitor. The pH dependency of the SQNf signals correlated with the proton-pumping activities of complex I. The SQNs signals were insensitive to gramicidin D, but sensitive to squamotacin. The SQNvs signals were insensitive to both gramicidin D and squamotacin. Our deuterium exchange experiments suggested that SQNf is neutral, while SQNs and SQNvs are anion radicals. The SQNs signals were lost in the ΔNuoL mutant missing transporter module subunits NuoL and NuoM. The roles and relationships of the SQ intermediates in the coupling mechanism are discussed. PMID:25868873

  18. Distinct molecular mechanisms involved in carbon catabolite repression of the arabinose regulon in Bacillus subtilis.

    PubMed

    Inácio, José Manuel; Costa, Carla; de Sá-Nogueira, Isabel

    2003-09-01

    The Bacillus subtilis proteins involved in the utilization of L-arabinose are encoded by the araABDLMNPQ-abfA metabolic operon and by the araE/araR divergent unit. Transcription from the ara operon, araE transport gene and araR regulatory gene is induced by L-arabinose and negatively controlled by AraR. Additionally, expression of both the ara operon and the araE gene is regulated at the transcriptional level by glucose repression. Here, by transcriptional fusion analysis in different mutant backgrounds, it is shown that CcpA most probably complexed with HPr-Ser46-P plays the major role in carbon catabolite repression of the ara regulon by glucose and glycerol. Site-directed mutagenesis and deletion analysis indicate that two catabolite responsive elements (cres) present in the ara operon (cre araA and cre araB) and one cre in the araE gene (cre araE) are implicated in this mechanism. Furthermore, cre araA located between the promoter region of the ara operon and the araA gene, and cre araB placed 2 kb downstream within the araB gene are independently functional and both contribute to glucose repression. In Northern blot analysis, in the presence of glucose, a CcpA-dependent transcript consistent with a message stopping at cre araB was detected, suggesting that transcription 'roadblocking' of RNA polymerase elongation is the most likely mechanism operating in this system. Glucose exerts an additional repression of the ara regulon, which requires a functional araR.

  19. Neural Correlates of Successful and Unsuccessful Strategical Mechanisms Involved in Uncertain Decision-Making.

    PubMed

    Giustiniani, Julie; Gabriel, Damien; Nicolier, Magali; Monnin, Julie; Haffen, Emmanuel

    2015-01-01

    The ability to develop successful long-term strategies in uncertain situations relies on complex neural mechanisms. Although lesion studies have shown some of the mechanisms involved, it is still unknown why some healthy subjects are able to make the right decision whereas others are not. The aim of our study was to investigate neurophysiological differences underlying this ability to develop a successful strategy in a group of healthy subjects playing a monetary card game called the Iowa Gambling Task (IGT). In this task, subjects have to win and earn money by choosing between four decks of cards, two were advantageous in the long term and two disadvantageous. Twenty healthy right-handed subjects performed the IGT while their cerebral activity was recorded by electroencephalography. Based on their behavioral performances, two groups of subjects could clearly be distinguished: one who selected the good decks and thus succeeded in developing a Favorable strategy (9 subjects) and one who remained Undecided (11 subjects). No neural difference was found between each group before the selection of a deck, but in both groups a greater negativity was found emerging from the right superior frontal gyrus 600 ms before a disadvantageous selection. During the processing of the feedback, an attenuation of the P200 and P300 waveforms was found for the Undecided group, and a P300 originating from the medial frontal gyrus was found in response to a loss only in the Favorable group. Our results suggest that undecided subjects are hyposensitive to the valence of the cards during gambling, which affects the feedback processing.

  20. Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both transcription and DNA licensing

    PubMed Central

    Zhang, Ruowen; Wu, Jiahui; Ferrandon, Sylvain; Glowacki, Katie J.; Houghton, Janet A.

    2016-01-01

    The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter. Pretreatment of HT29 cells with α-amanitin reduced GANT61-induced γH2AX foci. Co-localization of GLI1 and BrdU foci, inhibited by GANT61, indicated GLI1 and DNA replication to be linked. By co-immunoprecipitation and confocal microscopy, GLI1 co-localized with the DNA licensing factors ORC4, CDT1, and MCM2. Significant co-localization of GLI1 and ORC4 was inhibited by GANT61, and enrichment of ORC4 occurred at the GLI binding site in the FOXM1 promoter. CDT1 was found to be a transcription target of GLI1. Overexpression of CDT1 in HT29 and SW480 cells reduced GANT61-induced cell death, gH2AX foci, and cleavage of caspase-3. Data demonstrate involvement of transcription and of DNA replication licensing factors by non-transcriptional and transcriptional mechanisms in the GLI-dependent mechanism of action of GANT61. PMID:27863397

  1. Neural Correlates of Successful and Unsuccessful Strategical Mechanisms Involved in Uncertain Decision-Making

    PubMed Central

    Giustiniani, Julie; Gabriel, Damien; Nicolier, Magali; Monnin, Julie; Haffen, Emmanuel

    2015-01-01

    The ability to develop successful long-term strategies in uncertain situations relies on complex neural mechanisms. Although lesion studies have shown some of the mechanisms involved, it is still unknown why some healthy subjects are able to make the right decision whereas others are not. The aim of our study was to investigate neurophysiological differences underlying this ability to develop a successful strategy in a group of healthy subjects playing a monetary card game called the Iowa Gambling Task (IGT). In this task, subjects have to win and earn money by choosing between four decks of cards, two were advantageous in the long term and two disadvantageous. Twenty healthy right-handed subjects performed the IGT while their cerebral activity was recorded by electroencephalography. Based on their behavioral performances, two groups of subjects could clearly be distinguished: one who selected the good decks and thus succeeded in developing a Favorable strategy (9 subjects) and one who remained Undecided (11 subjects). No neural difference was found between each group before the selection of a deck, but in both groups a greater negativity was found emerging from the right superior frontal gyrus 600 ms before a disadvantageous selection. During the processing of the feedback, an attenuation of the P200 and P300 waveforms was found for the Undecided group, and a P300 originating from the medial frontal gyrus was found in response to a loss only in the Favorable group. Our results suggest that undecided subjects are hyposensitive to the valence of the cards during gambling, which affects the feedback processing. PMID:26086196

  2. Involvement of metabolites in early defense mechanism of oil palm (Elaeis guineensis Jacq.) against Ganoderma disease.

    PubMed

    Nusaibah, S A; Siti Nor Akmar, A; Idris, A S; Sariah, M; Mohamad Pauzi, Z

    2016-12-01

    Understanding the mechanism of interaction between the oil palm and its key pathogen, Ganoderma spp. is crucial as the disease caused by this fungal pathogen leads to a major loss of revenue in leading palm oil producing countries in Southeast Asia. Here in this study, we assess the morphological and biochemical changes in Ganoderma disease infected oil palm seedling roots in both resistant and susceptible progenies. Rubber woodblocks fully colonized by G. boninense were applied as a source of inoculum to artificially infect the roots of resistant and susceptible oil palm progenies. Gas chromatography-mass spectrometry was used to measure an array of plant metabolites in 100 resistant and susceptible oil palm seedling roots treated with pathogenic Ganoderma boninense fungus. Statistical effects, univariate and multivariate analyses were used to identify key-Ganoderma disease associated metabolic agitations in both resistant and susceptible oil palm root tissues. Ganoderma disease related defense shifts were characterized based on (i) increased antifungal activity in crude extracts, (ii) increased lipid levels, beta- and gamma-sitosterol particularly in the resistant progeny, (iii) detection of heterocyclic aromatic organic compounds, benzo [h] quinoline, pyridine, pyrimidine (iv) elevation in antioxidants, alpha- and beta-tocopherol (iv) degraded cortical cell wall layers, possibly resulting from fungal hydrolytic enzyme activity needed for initial penetration. The present study suggested that plant metabolites mainly lipids and heterocyclic aromatic organic metabolites could be potentially involved in early oil palm defense mechanism against G. boninense infection, which may also highlight biomarkers for disease detection, treatment, development of resistant variety and monitoring.

  3. Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

    SciTech Connect

    Wang, Jun; Cao, Hui; Wang, Hongjie; Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli; Xiang, Ming

    2015-06-15

    Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation.

  4. The involvement and possible mechanism of NR4A1 in chondrocyte apoptosis during osteoarthritis

    PubMed Central

    Shi, Xinge; Ye, Hui; Yao, Xuedong; Gao, Yanzheng

    2017-01-01

    Osteoarthritis (OA) is a joint disease caused by the breakdown of joint cartilage and underlying bone, and places great burdens to daily life of patients. Nuclear orphan receptor nuclear receptor subfamily 4, group A, member 1 (NR4A1) is vital for cell apoptosis, but little is known about its role in OA. This study aims to reveal the expression and function of NR4A1 during OA chondrocyte apoptosis. NR4A1 expression by qRT-PCR and western blot, and chondrocyte apoptosis by TUNEL assay were detected in normal and OA joint cartilage. NR4A1 was located in cartilage sections by immunohistofluorescence. Chondrocytes from normal joint cartilage were cultured in vitro for interleukin 6 (IL6) or tumor necrosis factor (TNF) treatment and si-NR4A1 transfection, after which the possible mechanism involving NR4A1 was analyzed. Results showed that NR4A1 expression and chondrocyte apoptosis were significantly elevated in OA cartilage (P < 0.05 and P < 0.01). NR4A1 was located in nuclei of normal cartilage chondrocytes, but was translocated to mitochondria and co-located with B-cell lymphoma 2 in OA chondrocytes. NR4A1 expression in cultured chondrocytes could be promoted by both IL6 and TNF treatment. si-NR4A1 partly reduced TNF-induced cell apoptosis. Inhibiting p38 by SB203580 could decrease TNF-induced NR4A1 to some extent, while inhibiting JNK could not. So NR4A1 is likely to facilitate OA chondrocyte apoptosis, which is associated with p38 MAPK and mitochondrial apoptosis pathway. This study provides a potential therapeutic target for OA treatment and offers information for regulatory mechanisms in OA. PMID:28337303

  5. The central anorexigenic mechanism of adrenocorticotropic hormone involves the caudal hypothalamus in chicks.

    PubMed

    Shipp, Steven L; Yi, Jiaqing; Dridi, Sami; Gilbert, Elizabeth R; Cline, Mark A

    2015-10-01

    Adrenocorticotropic hormone (ACTH), consisting of 39 amino acids, is most well-known for its involvement in an organism's response to stress. It also participates in satiety, as exogenous ACTH causes decreased food intake in rats. However, its anorexigenic mechanism is not well understood in any species and its effect on appetite is not reported in the avian class. Thus, the present study was designed to evaluate central ACTH's effect on food intake and to elucidate the mechanism mediating this response using broiler chicks. Chicks that received intracerebroventricular (ICV) injection of 1, 2, or 4 nmol of ACTH reduced food intake, under both ad libitum and 180 min fasted conditions. Water intake was also reduced in ACTH-injected chicks under both feeding conditions, but when measured without access to feed it was not affected. Blood glucose was not affected in either feeding condition. Following ACTH injection, c-Fos immunoreactivity was quantified in key appetite-associated hypothalamic nuclei including the ventromedial hypothalamus (VMH), dorsomedial hypothalamus, lateral hypothalamus (LH), arcuate nucleus (ARC) and the parvo- and magno-cellular portions of the paraventricular nucleus. ACTH-injected chicks had increased c-Fos immunoreactivity in the VMH, LH, and ARC. Hypothalamus was collected at 1h post-injection, and real-time PCR performed to measure mRNA abundance of some appetite-associated factors. Neuropeptide Y, pro-opiomelanocortin, glutamate decarboxylase 1, melanocortin receptors 2-5, and urocortin 3 mRNA abundance was not affected by ACTH treatment. However, expression of corticotropin releasing factor (CRF), urotensin 2 (UT), agouti-related peptide (AgRP), and orexin (ORX), and melanocortin receptor 1 (MC1R) mRNA decreased in the hypothalamus of ACTH-injected chicks. In conclusion, ICV ACTH causes decreased food intake in chicks, and is associated with VMH, LH, and ARC activation, and a decrease in hypothalamic mRNA abundance of CRF, UT, AgRP, ORX

  6. Noradrenergic mechanism involved in the nociceptive modulation of hippocampal CA3 region of normal rats.

    PubMed

    Jin, Hua; Teng, Yueqiu; Zhang, Xuexin; Yang, Chunxiao; Xu, Manying; Yang, Lizhuang

    2014-06-27

    Norepinephrine (NE) is an important neurotransmitter in the brain, and regulates antinociception. However, the mechanism of action of NE on pain-related neurons in the hippocampal CA3 region is not clear. This study examines the effects of NE, phentolamine on the electrical activities of pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the hippocampal CA3 region of rats. Trains of electric impulses applied to the right sciatic nerve were used as noxious stimulation. The electrical activities of PENs or PINs in the hippocampal CA3 region were recorded by using a glass microelectrode. Our results revealed that, in the hippocampal CA3 region, the intra-CA3 region microinjection of NE decreased the pain-evoked discharged frequency and prolonged the discharged latency of PEN, and increased the pain-evoked discharged frequency and shortened discharged inhibitory duration (ID) of PIN, exhibiting the specific analgesic effect of NE. While intra-CA3 region microinjection of phentolamine produced the opposite response. It implies that phentolamine can block the effect of endogenous NE to cause the enhanced response of PEN and PIN to noxious stimulation. On the basis of above findings we can deduce that NE, phentolamine and alpha-adrenoceptor are involved in the modulation of nociceptive information transmission in the hippocampal CA3 region.

  7. Strict control of auricin production in Streptomyces aureofaciens CCM 3239 involves a feedback mechanism.

    PubMed

    Kutas, Peter; Feckova, Lubomira; Rehakova, Alena; Novakova, Renata; Homerova, Dagmar; Mingyar, Erik; Rezuchova, Bronislava; Sevcikova, Beatrica; Kormanec, Jan

    2013-03-01

    The polyketide gene cluster aur1 is responsible for the production of the angucycline antibiotic auricin in Streptomyces aureofaciens CCM 3239. Auricin production is regulated in a complex manner involving several regulators, including a key pathway-specific positive regulator Aur1P that belongs to the family of 'atypical' response regulators. Production of auricin is induced after entry into stationary phase. However, auricin was produced in only a short time interval of several hours. We found that the decrease of auricin production was due to a strict regulation of auricin biosynthetic genes at the transcriptional level by a feedback mechanism; auricin and/or its intermediate(s) inhibited binding of Aur1P to its cognate biosynthetic promoter aur1Ap and consequently stopped its activation. In addition, we also determined that synthesised auricin is unstable during growth of S. aureofaciens CCM3239 in the production medium even though purified auricin is stable for days in various organic solvents. The critical parameter affecting its stability was pH. Auricin is stable at acid pH and unstable at neutral and alkaline pH. The drop in auricin concentration was due to an increase of pH shortly after induction of auricin production during cultivation of S. aureofaciens CCM3239.

  8. Molecular mechanisms involved in the pathogenesis of alphavirus-induced arthritis.

    PubMed

    Assunção-Miranda, Iranaia; Cruz-Oliveira, Christine; Da Poian, Andrea T

    2013-01-01

    Arthritogenic alphaviruses, including Ross River virus (RRV), Chikungunya virus (CHIKV), Sindbis virus (SINV), Mayaro virus (MAYV), O'nyong-nyong virus (ONNV), and Barmah Forest virus (BFV), cause incapacitating and long lasting articular disease/myalgia. Outbreaks of viral arthritis and the global distribution of these diseases point to the emergence of arthritogenic alphaviruses as an important public health problem. This review discusses the molecular mechanisms involved in alphavirus-induced arthritis, exploring the recent data obtained with in vitro systems and in vivo studies using animal models and samples from patients. The factors associated to the extension and persistence of symptoms are highlighted, focusing on (a) virus replication in target cells, and tissues, including macrophages and muscle cells; (b) the inflammatory and immune responses with recruitment and activation of macrophage, NK cells and T lymphocytes to the lesion focus and the increase of inflammatory mediators levels; and (c) the persistence of virus or viral products in joint and muscle tissues. We also discuss the importance of the establishment of novel animal models to test new molecular targets and to develop more efficient and selective drugs to treat these diseases.

  9. Evidence for the involvement of central serotonin in mechanism of domestication of silver foxes.

    PubMed

    Popova, N K; Voitenko, N N; Kulikov, A V; Avgustinovich, D F

    1991-12-01

    Silver foxes selected for more than 30 years for tame behavior and displaying no defensive reaction to human contact were shown to have a higher serotonin level in midbrain and hypothalamus, and a higher 5-hydroxyindole acetic acid (5-HIAA) content in midbrain, hypothalamus and hippocampus in comparison to nonselected wild silver foxes bred in captivity over the same time span. Tryptophan hydroxylase (TPH) activity in midbrain and hypothalamus in domesticated foxes was increased as compared with their aggressive/defensive counterparts. Monoamine oxidase type A (MAO A) activity was was decreased with an increased Km and unchanged Vmax in domesticated foxes. No changes in specific [3H]ketanserin or [3H]8-OH-DPAT binding in frontal cortex was revealed. A reduced density (Bmax) of 5HT1A receptors in hypothalamic membranes in domesticated foxes was shown. It is suggested that the brain serotonergic system is involved in the mechanism of domestication converting wild aggressive/defensive animals into tame ones.

  10. Molecular mechanisms of tolerance in tardigrades: new perspectives for preservation and stabilization of biological material.

    PubMed

    Schill, Ralph O; Mali, Brahim; Dandekar, Thomas; Schnölzer, Martina; Reuter, Dirk; Frohme, Marcus

    2009-01-01

    Certain organisms found across a range of taxa, including bacteria, yeasts, plants and many invertebrates such as nematodes and tardigrades are able to survive almost complete loss of body water. The dry organisms may remain in this state, which is known as anhydrobiosis, for decades without apparent damage. When water again becomes available, they rapidly rehydrate and resume active life. Research in anhydrobiosis has focused mainly on sugar metabolism and stress proteins. Despite the discovery of various molecules which are involved in desiccation and water stress, knowledge of the regulatory network governing the stability of the cellular architecture and the metabolic machinery during dehydration is still fragmentary and not well understood. A combination of transcriptional, proteomic and metabolic approaches with bioinformatics tools can provide a better understanding of gene regulation that underlie the biological functions and physiology related to anhydrobiosis. The development of this concept will raise exciting possibilities and techniques for the preservation and stabilization of biological materials in the dry state.

  11. Biological Mechanisms that Promote Weight Regain Following Weight Loss in Obese Humans

    PubMed Central

    Ochner, Christopher N.; Barrios, Dulce M.; Lee, Clement D.; Pi-Sunyer, F. Xavier

    2013-01-01

    Weight loss dieting remains the treatment of choice for the vast majority of obese individuals, despite the limited long-term success of behavioral weight loss interventions. The reasons for the near universal unsustainability of behavioral weight loss in [formerly] obese individuals have not been fully elucidated, relegating researchers to making educated guesses about how to improve obesity treatment, as opposed to developing interventions targeting the causes of weight regain. This article discusses research on several factors that may contribute to weight regain following weight loss achieved through behavioral interventions, including adipose cellularity, endocrine function, energy metabolism, neural responsivity, and addiction-like neural mechanisms. All of these mechanisms are engaged prior to weight loss, suggesting that so called “anti-starvation” mechanisms are activated via reductions in energy intake, rather than depletion of energy stores. Evidence suggests that these mechanisms are not necessarily part of a homeostatic feedback system designed to regulate body weight or even anti-starvation mechanisms per se. Though they may have evolved to prevent starvation, they appear to be more accurately described as anti-weight loss mechanisms, engaged with caloric restriction irrespective of the adequacy of energy stores. It is hypothesized that these factors may combine to create a biological disposition that fosters the maintenance of an elevated body weight and work to restore the highest sustained body weight, thus precluding the long-term success of behavioral weight loss. It may be necessary to develop interventions that attenuate these biological mechanisms in order to achieve long-term weight reduction in obese individuals. PMID:23911805

  12. Mass balance to assess the efficiency of a mechanical-biological treatment

    SciTech Connect

    Araujo Morais, J. de; Ducom, G. Achour, F.; Rouez, M.; Bayard, R.

    2008-07-01

    Using mechanical-biological treatment of residual municipal solid waste, it is possible to significantly lower landfill volume and gas and leachate emissions. Moreover, the landfill characteristics are improved. The performance of the Mende (France) mechanical-biological treatment plant is assessed via mass balances coupled with manual sorting according to the MODECOM{sup TM} methodology and biochemical methane potential after 90 days of incubation. The site includes mechanical sorting operations, a rotary sequential bioreactor, controlled aerobic stabilisation corridors, maturation platforms, and a sanitary landfill site for waste disposal in separated cells. Results showed that several steps could be improved: after a first sieving step, about 12% of the potentially biodegradable matter is landfilled directly without any treatment; mechanical disintegration of papers and cardboards in the rotary sequential bioreactor is insufficient and leads to a high proportion of papers and cardboards being landfilled without further treatment. Two fine fractions go through stabilisation and maturation steps. At the end of the maturation step, about 54% of the potentially biodegradable matter is degraded. The biochemical methane potential after 90 days of incubation is reduced by 81% for one of the two fine fractions and reduced by 88% for the other one. Considering the whole plant, there is a reduction of nearly 20% DM of the entering residual municipal solid waste.

  13. Physical mechanisms and biological significance of supramolecular protein self-assembly.

    PubMed

    Kentsis, Alex; Borden, Katherine L B

    2004-04-01

    In living cells, chemical reactions of metabolism, information processing, growth and development are organized in a complex network of interactions. At least in part, the organization of this network is accomplished as a result of physical assembly by supramolecular scaffolds. Indeed, most proteins function in cells within the context of multimeric or supramolecular assemblies. With the increasing availability of atomic structures and molecular thermodynamics, it is possible to recast the problem of non-covalent molecular self-assembly from a unified perspective of structural thermodynamics and kinetics. Here, we present a generalized theory of self-assembly based on Wegner's kinetic model and use it to delineate three physical mechanisms of self-assembly: as limited by association of assembly units (nucleation), by association of monomers (isodesmic), and by conformational reorganization of monomers that is coupled to assembly (conformational). Thus, we discuss actin, tubulin, clathrin, and the capsid of icosahedral cowpea chlorotic mottle virus with respect to assembly of architectural scaffolds that perform largely mechanical functions, and pyruvate dehydrogenase, and RING domain proteins PML, arenaviral Z, and BRCA1:BARD1 with regard to assembly of supramolecular enzymes with metabolic and chemically directive functions. In addition to the biological functions made possible by supramolecular self-assembly, such as mesoscale mechanics of architectural scaffolds and metabolic coupling of supramolecular enzymes, we show that the physical mechanisms of self-assembly and their structural bases are biologically significant as well, having regulatory roles in both formation and function of the assembled structures in health and disease.

  14. Methods for using 3-D ultrasound speckle tracking in biaxial mechanical testing of biological tissue samples.

    PubMed

    Yap, Choon Hwai; Park, Dae Woo; Dutta, Debaditya; Simon, Marc; Kim, Kang

    2015-04-01

    Being multilayered and anisotropic, biological tissues such as cardiac and arterial walls are structurally complex, making the full assessment and understanding of their mechanical behavior challenging. Current standard mechanical testing uses surface markers to track tissue deformations and does not provide deformation data below the surface. In the study described here, we found that combining mechanical testing with 3-D ultrasound speckle tracking could overcome this limitation. Rat myocardium was tested with a biaxial tester and was concurrently scanned with high-frequency ultrasound in three dimensions. The strain energy function was computed from stresses and strains using an iterative non-linear curve-fitting algorithm. Because the strain energy function consists of terms for the base matrix and for embedded fibers, spatially varying fiber orientation was also computed by curve fitting. Using finite-element simulations, we first validated the accuracy of the non-linear curve-fitting algorithm. Next, we compared experimentally measured rat myocardium strain energy function values with those in the literature and found a matching order of magnitude. Finally, we retained samples after the experiments for fiber orientation quantification using histology and found that the results satisfactorily matched those computed in the experiments. We conclude that 3-D ultrasound speckle tracking can be a useful addition to traditional mechanical testing of biological tissues and may provide the benefit of enabling fiber orientation computation.

  15. Chitosan fibers with improved biological and mechanical properties for tissue engineering applications.

    PubMed

    Albanna, Mohammad Z; Bou-Akl, Therese H; Blowytsky, Oksana; Walters, Henry L; Matthew, Howard W T

    2013-04-01

    The low mechanical properties of hydrogel materials such as chitosan hinder their broad utility for tissue engineering applications. Previous research efforts improved the mechanical properties of chitosan fiber through chemical and physical modifications; however, unfavorable toxicity effects on cells were reported. In this paper, we report the preparation of chitosan fibers with improved mechanical and biocompatibility properties. The structure-property relationships of extruded chitosan fibers were explored by varying acetic acid (AA) concentration, ammonia concentration, annealing temperature and degree of heparin crosslinking. Results showed that optimizing AA concentration to 2vol% improved fiber strength and stiffness by 2-fold. Extruding chitosan solution into 25wt% of ammonia solution reduced fiber diameters and improved fiber strength by 2-fold and stiffness by 3-fold, due to an increase in crystallinity as confirmed by XRD. Fiber annealing further reduced fiber diameter and improved fiber strength and stiffness as temperature increased. Chitosan fibers crosslinked with heparin had increased diameter but lower strength and stiffness properties and higher breaking strain values. When individual parameters were combined, further improvement in fiber mechanical properties was achieved. All mechanically improved fibers and heparin crosslinked fibers promoted valvular interstitial cells (VIC) attachment and growth over 10 day cultures. Our results demonstrate the ability to substantially improve the mechanical properties of chitosan fibers without adversely affecting their biological properties. The investigated treatments offer numerous advantages over previous physical/chemical modifications and thus are expected to expand the utility of chitosan fibers with tunable mechanical properties in various tissue engineering applications.

  16. [Annexins--proteins involved in organization and function of biological membranes--from Arabidopsis thaliana to Homo sapiens].

    PubMed

    Bandorowicz-Pikuła, Joanna

    2007-01-01

    The mini-review series presented in this issue of Postepy Biochemii is focussed on some aspects of biology of calcium- and membrane-binding proteins, annexins, ubiquitous in all eucaryotic organisms (excluding yeasts), from Arabidopsis thaliana to Homo sapiens. Annexins are encoded by twelve genes in verterbrates and by eight in higher plants. Their physiological significance is underlined by two facts: the numer of the annexin genes seems to grow during evolution and in some cell types they comprise up to 2% of total protein. In the present review the hypothesis is discussed suggesting that multiplication of annexin genes in evolution represents mechanism of organism adaptation to changes in environment. In addition, the experimental data are presented suggestive of annexins playing a crucial role in functioning of plasma membrane, such as signal transduction, ion and vesicular transport and membrane repair. The review is then followed by articlesdealing in details with participation of annexins in plant response to abiotic stress (Arabidopsis thaliana), in tissue mineralization (Gallus gallus), in exocytosis of catecholamines by PC12 cells (mammals) and in Niemann-Pick type C disease related to abnormal transport and intracellular storage of cholesterol (Homo sapiens).

  17. Particle Disease: A Current Review of the Biological Mechanisms in Periprosthetic Osteolysis After Hip Arthroplasty

    PubMed Central

    Sukur, Erhan; Akman, Yunus Emre; Ozturkmen, Yusuf; Kucukdurmaz, Fatih

    2016-01-01

    Background: Inflammatory responses to wear debris cause osteolysis that leads to aseptic prosthesis loosening and hip arthroplasty failure. Although osteolysis is usually associated with aseptic loosening, it is rarely seen around stable implants. Aseptic implant loosening is a simple radiologic phenomenon, but a complex immunological process. Particulate debris produced by implants most commonly causes osteolysis, and this is called particle-associated periprosthetic osteolysis (PPO). Objective: The objective of this review is to outline the features of particle-associated periprosthetic osteolysis to allow the physician to recognise this condition and commence early treatment, thereby optimizing patient outcome. Methods: A thorough literature search was performed using available databases, including Pubmed, to cover important research published covering particle-associated PPO. Results: Although osteolysis causes bone resorption, clinical, animal, and in vitro studies of particle bioreactivity suggest that particle-associated PPO represents the culmination of several biological reactions of many cell types, rather than being caused solely by the osteoclasts. The biological activity is highly dependent on the characteristics and quantity of the wear particles. Conclusion: Despite advances in total hip arthroplasty (THA), particle-associated PPO and aseptic loosening continue to be major factors that affect prosthetic joint longevity. Biomarkers could be exploited as easy and objective diagnostic and prognostic targets that would enable testing for osteolysis after THA. Further research is needed to identify new biomarkers in PPO. A comprehensive understanding of the underlying biological mechanisms is crucial for developing new therapeutic interventions to reverse or suppress biological responses to wear particles. PMID:27499822

  18. Mammary blood flow and metabolic activity are linked by a feedback mechanism involving nitric oxide synthesis.

    PubMed

    Cieslar, S R L; Madsen, T G; Purdie, N G; Trout, D R; Osborne, V R; Cant, J P

    2014-01-01

    To test which, if any, of the major milk precursors can elicit a rapid change in the rate of mammary blood flow (MBF) and to define the time course and magnitude of such changes, 4 lactating cows were infused with glucose, amino acids, or triacylglycerol into the external iliac artery feeding one udder half while iliac plasma flow (IPF) was monitored continuously by dye dilution. Adenosine and saline were infused as positive and negative controls, respectively, and insulin was infused to characterize the response to a centrally produced anabolic hormone. To test the roles of cyclooxygenase, NO synthase and ATP-sensitive K (KATP) channels in nutrient-mediated changes in blood flow, their respective inhibitors-indomethacin, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), and glibenclamide-were infused simultaneously with glucose. Each day, 1 infusate was given twice to each cow, over a 20-min period each time, separated by a 20-min washout period. In addition, each treatment protocol was administered on 2 separate days. A 73% increase in IPF during adenosine infusion showed that the mammary vasodilatory response was quadratic in time, with most changes occurring in the first 5min. Glucose infusion decreased IPF by 9% in a quadratic manner, most rapidly in the first 5min, indicating that a feedback mechanism of local blood flow control, likely through adenosine release, was operative in the mammary vasculature. Amino acid infusion increased IPF 9% in a linear manner, suggesting that mammary ATP utilization was stimulated more than ATP production. This could reflect a stimulation of protein synthesis. Triacylglycerol only tended to decrease IPF and insulin did not affect IPF. A lack of IPF response to glibenclamide indicates that KATP channels are not involved in MBF regulation. Indomethacin and L-NAME both depressed IPF. In the presence of indomethacin, glucose infusion caused a quadratic 9% increase in IPF. Indomethacin is an inhibitor of mitochondrial

  19. Study of the Genes and Mechanism Involved in the Radioadaptive Response

    NASA Technical Reports Server (NTRS)

    Dasgupta, Pushan R.

    2009-01-01

    The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor

  20. Pathophysiological mechanisms involved in non-alcoholic steatohepatitis and novel potential therapeutic targets

    PubMed Central

    Higuera-de la Tijera, Fátima; Servín-Caamaño, Alfredo I

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a major health care problem and represents the hepatic expression of the metabolic syndrome. NAFLD is classified as non-alcoholic fatty liver (NAFL) or simple steatosis, and non-alcoholic steatohepatitis (NASH). NASH is characterized by the presence of steatosis and inflammation with or without fibrosis. The physiopathology of NAFL and NASH and their progression to cirrhosis involve several parallel and interrelated mechanisms, such as, insulin resistance (IR), lipotoxicity, inflammation, oxidative stress, and recently the gut-liver axis interaction has been described. Incretin-based therapies could play a role in the treatment of NAFLD. Glucagon-like peptide-1 (GLP-1) is an intestinal mucosa-derived hormone which is secreted into the bloodstream in response to nutrient ingestion; it favors glucose-stimulated insulin secretion, inhibition of postprandial glucagon secretion and delayed gastric emptying. It also promotes weight loss and is involved in lipid metabolism. Once secreted, GLP-1 is quickly degraded by dipeptidyl peptidase-4 (DPP-4). Therefore, DPP-4 inhibitors are able to extend the activity of GLP-1. Currently, GLP-1 agonists and DPP-4 inhibitors represent attractive options for the treatment of NAFLD and NASH. The modulation of lipid and glucose metabolism through nuclear receptors, such as the farsenoid X receptor, also constitutes an attractive therapeutic target. Obeticholic acid is a potent activator of the farnesoid X nuclear receptor and reduces liver fat content and fibrosis in animal models. Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid with immunomodulatory, anti-inflammatory, antiapoptotic, antioxidant and anti-fibrotic properties. UDCA can improve IR and modulate lipid metabolism through its interaction with nuclear receptors such as, TGR5, farnesoid X receptor-α, or the small heterodimeric partner. Finally, pharmacologic modulation of the gut microbiota could have a role in the therapy of

  1. A Fast Response Mechanism for Insulin Storage in Crystals May Involve a Novel Mode of Kink Generation

    NASA Astrophysics Data System (ADS)

    Vekilov, Peter

    2010-03-01

    Crystals, likely rhombohedral, of Zn-insulin hexamers form in the islets of Langerhans in the pancreases of many mammals. The suggested function of crystal formation is to protect the insulin from proteases and increase the degree of conversion of soluble proinsulin. To accomplish this, crystal growth should be fast and adaptable to rate fluctuations in the conversion reaction. Zn-insulin crystals grow layer-by-layer. Each layer spreads by the attachment of molecules to kinks located at the layers' edges, also called steps. The kinks are thought to be generated either by thermal fluctuations, as postulated by Gibbs, or by one-dimensional nucleation of new crystalline rows. The kink density determines the rate at which steps advance, and these two kink-generation mechanisms lead to weak near-linear responses of the growth rate to concentration variations. We demonstrate for the crystallization of Zn-insulin a novel mechanism of kink generation, whereby 2D clusters of several insulin molecules pre-formed on the terraces between steps associate to the steps. This mechanism results in several-fold higher kink density, faster rate of crystallization, and a high sensitivity of the kinetics to small increases of the solute concentration. If the found mechanism operates during insulin crystallization in vivo, it could be a part of the biological regulation of insulin production and function. For other crystallizing materials in biological and non-biological systems, this mechanism provides an understanding of the often seen non-linear acceleration of the kinetics.

  2. One- and two-electron oxidation of thiols: mechanisms, kinetics and biological fates.

    PubMed

    Trujillo, Madia; Alvarez, Beatriz; Radi, Rafael

    2016-01-01

    The oxidation of biothiols participates not only in the defense against oxidative damage but also in enzymatic catalytic mechanisms and signal transduction processes. Thiols are versatile reductants that react with oxidizing species by one- and two-electron mechanisms, leading to thiyl radicals and sulfenic acids, respectively. These intermediates, depending on the conditions, participate in further reactions that converge on different stable products. Through this review, we will describe the biologically relevant species that are able to perform these oxidations and we will analyze the mechanisms and kinetics of the one- and two-electron reactions. The processes undergone by typical low-molecular-weight thiols as well as the particularities of specific thiol proteins will be described, including the molecular determinants proposed to account for the extraordinary reactivities of peroxidatic thiols. Finally, the main fates of the thiyl radical and sulfenic acid intermediates will be summarized.

  3. Molecular mechanisms involved in the hormonal prevention of aging in the rat.

    PubMed

    Tresguerres, Jesús A F; Kireev, Roman; Tresguerres, Ana F; Borras, Consuelo; Vara, Elena; Ariznavarreta, Carmen

    2008-02-01

    Previous data from our group have provided support for the role of GH, melatonin and estrogens in the prevention of aging of several physiological parameters from bone, liver metabolism, vascular activity, the central nervous system (CNS), the immune system and the skin. In the present work data on the molecular mechanisms involved are presented. A total of 140 male and female rats have been submitted to different treatments over 10 weeks, between 22 and 24 months of age. Males have been treated with GH and melatonin. Females were divided in two groups: intact and castrated at 12 months of age. The first group was treated with GH and melatonin and the second with the two latter compounds and additionally with estradiol and Phytosoya. Aging was associated with a reduction in the number of neurons of the hylus of the dentate gyrus of the hippocampus and with a reduction of neurogenesis. GH treatment increased the number of neurons but did not increase neurogenesis thus suggesting a reduction of apoptosis. This was supported by the reduction in nucleosomes and the increase in Bcl2 observed in cerebral homogenates together with an increase in sirtuin2 and a reduction of caspases 9 and 3. Melatonin, estrogen and Phytosoya treatments increased neurogenesis but did not enhance the total number of neurons. Aging induced a significant increase in mitochondrial nitric oxide in the hepatocytes, together with a reduction in the mitochondrial fraction content in cytochrome C and an increase of this compound in the cytosolic fraction. Reductions of glutathione peroxidase and glutathione S-transferase were also detected, thus indicating oxidative stress and possibly apoptosis. Treatment for 2.5 months of old rats with GH and melatonin were able to significantly and favourably affect age-induced deteriorations, thus reducing oxidative damage. Keratinocytes obtained from old rats in primary culture showed an increase in lipoperoxides, caspases 8 and 3 as well as a reduction in Bcl2

  4. A computational functional genomics based self-limiting self-concentration mechanism of cell specialization as a biological role of jumping genes.

    PubMed

    Lötsch, Jörn; Ultsch, Alfred

    2016-01-01

    Specialization is ubiquitous in biological systems and its manifold mechanisms are active research topics. Although clearly adaptive, the way in which specialization of cells is realized remains incompletely understood as it requires the reshaping of a cell's genome to favor particular biological processes in the competition on a cell's functional capacity. Here, a self-specialization mechanism is identified as a possible biological role of jumping genes, in particular LINE-1 retrotransposition. The mechanism is self-limiting and consistent with its evolutionary preservation despite its likely gene-breaking effects. The scenario we studied was the need for a cell to process a longer exposition to an extraordinary situation, for example continuous exposure to the nociceptive input or the intake of addictive drugs. Both situations may evolve toward chronification. The mechanism involves competition within a gene set in which a subset of genes cooperating in particular biological processes. The subset carries a piece of information, consisting of the LINE-1 sequence, about the destruction of their functional competitor genes which are not involved in that process. During gene transcription, an active copy of LINE-1 is co-transcribed. At a certain low probability, a subsequently transcribed and thus actually exposed gene can be rendered nonfunctional by LINE-1 retrotransposition in a relevant gene part. As retrotransposition needs time it is unlikely that LINE-1 retrotranspose into its own carrier gene. This reshapes the cell genome toward self-specializing of those biological processes that are carried out with a high number of LINE-1 containing genes. Self-termination of the mechanism is achieved by allowing LINE-1 to also occasionally jump into the coding region of itself, thus destroying the information about competitor destruction by successively decreasing the number of LINE-1 until the mechanism ceases. Employing a computational functional genomics approach, we

  5. Flexible mechanisms: the diverse roles of biological springs in vertebrate movement

    PubMed Central

    Roberts, Thomas J.; Azizi, Emanuel

    2011-01-01

    The muscles that power vertebrate locomotion are associated with springy tissues, both within muscle and in connective tissue elements such as tendons. These springs share in common the same simple action: they stretch and store elastic strain energy when force is applied to them and recoil to release energy when force decays. Although this elastic action is simple, it serves a diverse set of functions, including metabolic energy conservation, amplification of muscle power output, attenuation of muscle power input, and rapid mechanical feedback that may aid in stability. In recent years, our understanding of the mechanisms and importance of biological springs in locomotion has advanced significantly, and it has been demonstrated that elastic mechanisms are essential for the effective function of the muscle motors that power movement. Here, we review some recent advances in our understanding of elastic mechanisms, with an emphasis on two proposed organizing principles. First, we review the evidence that the various functions of biological springs allow the locomotor system to operate beyond the bounds of intrinsic muscle properties, including metabolic and mechanical characteristics, as well as motor control processes. Second, we propose that an energy-based framework is useful for interpreting the diverse functions of series-elastic springs. In this framework, the direction and timing of the flow of energy between the body, the elastic element and the contracting muscle determine the function served by the elastic mechanism (e.g. energy conservation vs power amplification). We also review recent work demonstrating that structures such as tendons remodel more actively and behave more dynamically than previously assumed. PMID:21228194

  6. Achyranthes aspera Attenuates epilepsy in experimental animals: possible involvement of GABAergic mechanism.

    PubMed

    Viswanatha, Gollapalle Lakshminarayanashastry; Venkataranganna, Marikunte V; Prasad, Nunna Bheema Lingeswara; Godavarthi, Ashok

    2017-03-06

    The present study was aimed to examine the possible anticonvulsant property of aerial parts of Achyranthes aspera using various experimental models of epilepsy in mice. Petroleum ether extract of aerial parts of A. aspera (PeAA), methanolic eAA (MeAA) and aqueous eAA (AeAA) was initially evaluated against six-hertz seizure model in mice, based on the outcomes the effective extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ) models in mice. In addition, the potent extract was evaluated against the PTZ model by co-administering with flumazenil (FMZ), and also evaluated for its effect on GABA levels in brain and NMDA-induced lethality in mice. Furthermore, the probable locomotor deficit-inducing property of the extract was evaluated by actophotometer test in mice. In results, only MeAA showed protection against six-hertz-induced seizures in mice, based on these outcomes only MeAA was evaluated in MES and PTZ models. Notably, the MeAA (200, 400 and 800 mg/kg) has offered mild and dose dependent protection against MES and PTZ-induced seizures in mice. Alongside, the MeAA (400 mg/kg) showed a significant increase in GABA levels in the brain compared to control, and in line with these findings the anti-PTZ effect of MeAA (400 mg/kg, p.o.) was blocked when co-administered with flumazenil (5 mg/kg, i.p.). However, the MeAA has not shown significant protection against NMDA-induced mortality and also did not cause significant change in locomotor activity compared to before treatment. These findings suggest that MeAA possess mild anticonvulsant activity and the outcomes further confirmed the involvement of GABAergic mechanism behind the anticonvulsant activity of MeAA.

  7. Ghrelin prevents tumour- and cisplatin-induced muscle wasting: characterization of multiple mechanisms involved

    PubMed Central

    Chen, Ji-an; Splenser, Andres; Guillory, Bobby; Luo, Jiaohua; Mendiratta, Meenal; Belinova, Blaga; Halder, Tripti; Zhang, Guohua; Li, Yi-Ping; Garcia, Jose M

    2015-01-01

    Background Cachexia and muscle atrophy are common consequences of cancer and chemotherapy administration. The novel hormone ghrelin has been proposed as a treatment for this condition. Increases in food intake and direct effects on muscle proteolysis and protein synthesis are likely to mediate these effects, but the pathways leading to these events are not well understood. Methods We characterized molecular pathways involved in muscle atrophy induced by Lewis lung carcinoma (LLC) tumour implantation in c57/bl6 adult male mice and by administration of the chemotherapeutic agent cisplatin in mice and in C2C12 myotubes. The effects of exogenous ghrelin administration and its mechanisms of action were examined in these settings. Results Tumour implantation and cisplatin induced muscle atrophy by activating pro-inflammatory cytokines, p38-C/EBP-β, and myostatin, and by down-regulating Akt, myoD, and myogenin, leading to activation of ubiquitin-proteasome-mediated proteolysis and muscle weakness. Tumour implantation also increased mortality. In vitro, cisplatin up-regulated myostatin and atrogin-1 by activating C/EBP-β and FoxO1/3. Ghrelin prevented these changes in vivo and in vitro, significantly increasing muscle mass (P < 0.05 for LLC and P < 0.01 for cisplatin models) and grip strength (P = 0.038 for LLC and P = 0.001 for cisplatin models) and improving survival (P = 0.021 for LLC model). Conclusion Ghrelin prevents muscle atrophy by down-regulating inflammation, p38/C/EBP-β/myostatin, and activating Akt, myogenin, and myoD. These changes appear, at least in part, to target muscle cells directly. Ghrelin administration in this setting is associated with improved muscle strength and survival. PMID:26136189

  8. Large-Scale Predictive Drug Safety: From Structural Alerts to Biological Mechanisms.

    PubMed

    Garcia-Serna, Ricard; Vidal, David; Remez, Nikita; Mestres, Jordi

    2015-10-19

    The recent explosion of data linking drugs, proteins, and pathways with safety events has promoted the development of integrative systems approaches to large-scale predictive drug safety. The added value of such approaches is that, beyond the traditional identification of potentially labile chemical fragments for selected toxicity end points, they have the potential to provide mechanistic insights for a much larger and diverse set of safety events in a statistically sound nonsupervised manner, based on the similarity to drug classes, the interaction with secondary targets, and the interference with biological pathways. The combined identification of chemical and biological hazards enhances our ability to assess the safety risk of bioactive small molecules with higher confidence than that using structural alerts only. We are still a very long way from reliably predicting drug safety, but advances toward gaining a better understanding of the mechanisms leading to adverse outcomes represent a step forward in this direction.

  9. Mechanisms of cell protection by adaptation to chronic and acute hypoxia: molecular biology and clinical practice.

    PubMed

    Corbucci, G G; Marchi, A; Lettieri, B; Luongo, C

    2005-11-01

    Several experimental and clinical studies have shown that specific biochemical and molecular pathways are involved in the myocardial and skeletal muscle cell tolerance to acute and/or chronic hypoxic injury. A number of different factors were proposed to play a role in the preservation of tissue viability, but to a few of them a pivotal role in the adaptive mechanisms to hypoxic stimuli could be ascribed. Starting from the observation that mitochondrial electron transport chain (ETC) enzymic complexes are the targets of oxygen reduced availability, most of data are compatible with a mechanism of enzymic adaptation in which the nitric oxide (NO) generation plays the major role. If the partial and reversible NO-induced inhibition of ETC enzymic complexes represents the most rapid and prominent adaptive mechanism in counteracting the damaging effects of hypoxia, the sarcolemmal and mitochondrial K+(ATP) channels activation results to be closely involved in cytoprotection. This process is depending on protein kinase C (PKC) isoform activation triggered by reactive oxygen species (ROS) generation, adenosine triphosphate (ATP) depletion and Ca++ overload. It is well known that all these factors are present in hypoxia-induced oxidative damage and mitochondrial Ca++ altered pools represent powerful stimuli in the damaging processes. The activation of mitochondrial K+(ATP) channels leads to a significant reduction of Ca++ influx and attenuation of mitochondrial Ca++ overload. Closely linked to these adaptive changes signal transduction pathways are involved in the nuclear DNA damage and repair mechanisms. On this context, an essential role is played by the hypoxia-induced factor-1alpha (HIF-1alpha) in terms of key transcription factor involved in oxygen-dependent gene regulation. The knowledge of the biochemical and molecular sequences involved in these adaptive processes call for a re-evaluation of the therapeutic approach to hypoxia-induced pathologies. On this light

  10. A common biological mechanism in cancer and Alzheimer’s disease?

    PubMed Central

    Behrens, Maria I; Lendon, Corinne; Roe, Catherine M.

    2009-01-01

    Cancer and Alzheimer’s disease (AD) are two common disorders for which the final pathophysiological mechanism is not yet clearly defined. In a prospective longitudinal study we have previously shown an inverse association between AD and cancer, such that the rate of developing cancer in general with time was significantly slower in participants with AD, while participants with a history of cancer had a slower rate of developing AD. In cancer, cell regulation mechanisms are disrupted with augmentation of cell survival and/or proliferation, whereas conversely, AD is associated with increased neuronal death, either caused by, or concomitant with, beta amyloid (Aβ) and tau deposition. The possibility that perturbations of mechanisms involved in cell survival/death regulation could be involved in both disorders is discussed. Genetic polymorphisms, DNA methylation or other mechanisms that induce changes in activity of molecules with key roles in determining the decision to “repair and live”- or “die” could be involved in the pathogenesis of the two disorders. As examples, the role of p53, Pin1 and the Wnt signaling pathway are discussed as potential candidates that, speculatively, may explain inverse associations between AD and cancer. PMID:19519301

  11. Features of Knowledge Building in Biology: Understanding Undergraduate Students’ Ideas about Molecular Mechanisms

    PubMed Central

    Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S.

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. PMID:26931398

  12. Mechanical and Biological Interactions of Implants with the Brain and Their Impact on Implant Design.

    PubMed

    Prodanov, Dimiter; Delbeke, Jean

    2016-01-01

    Neural prostheses have already a long history and yet the cochlear implant remains the only success story about a longterm sensory function restoration. On the other hand, neural implants for deep brain stimulation are gaining acceptance for variety of disorders including Parkinsons disease and obsessive-compulsive disorder. It is anticipated that the progress in the field has been hampered by a combination of technological and biological factors, such as the limited understanding of the longterm behavior of implants, unreliability of devices, biocompatibility of the implants among others. While the field's understanding of the cell biology of interactions at the biotic-abiotic interface has improved, relatively little attention has been paid on the mechanical factors (stress, strain), and hence on the geometry that can modulate it. This focused review summarizes the recent progress in the understanding of the mechanisms of mechanical interaction between the implants and the brain. The review gives an overview of the factors by which the implants interact acutely and chronically with the tissue: blood-brain barrier (BBB) breach, vascular damage, micromotions, diffusion etc. We propose some design constraints to be considered in future studies. Aspects of the chronic cell-implant interaction will be discussed in view of the chronic local inflammation and the ways of modulating it.

  13. Mechanical and Biological Interactions of Implants with the Brain and Their Impact on Implant Design

    PubMed Central

    Prodanov, Dimiter; Delbeke, Jean

    2016-01-01

    Neural prostheses have already a long history and yet the cochlear implant remains the only success story about a longterm sensory function restoration. On the other hand, neural implants for deep brain stimulation are gaining acceptance for variety of disorders including Parkinsons disease and obsessive-compulsive disorder. It is anticipated that the progress in the field has been hampered by a combination of technological and biological factors, such as the limited understanding of the longterm behavior of implants, unreliability of devices, biocompatibility of the implants among others. While the field's understanding of the cell biology of interactions at the biotic-abiotic interface has improved, relatively little attention has been paid on the mechanical factors (stress, strain), and hence on the geometry that can modulate it. This focused review summarizes the recent progress in the understanding of the mechanisms of mechanical interaction between the implants and the brain. The review gives an overview of the factors by which the implants interact acutely and chronically with the tissue: blood-brain barrier (BBB) breach, vascular damage, micromotions, diffusion etc. We propose some design constraints to be considered in future studies. Aspects of the chronic cell-implant interaction will be discussed in view of the chronic local inflammation and the ways of modulating it. PMID:26903786

  14. Features of Knowledge Building in Biology: Understanding Undergraduate Students' Ideas about Molecular Mechanisms.

    PubMed

    Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning.

  15. The impact of environmental stress on male reproductive development in plants: biological processes and molecular mechanisms

    PubMed Central

    de Storme, Nico; Geelen, Danny

    2014-01-01

    In plants, male reproductive development is extremely sensitive to adverse climatic environments and (a)biotic stress. Upon exposure to stress, male gametophytic organs often show morphological, structural and metabolic alterations that typically lead to meiotic defects or premature spore abortion and male reproductive sterility. Depending on the type of stress involved (e.g. heat, cold, drought) and the duration of stress exposure, the underlying cellular defect is highly variable and either involves cytoskeletal alterations, tapetal irregularities, altered sugar utilization, aberrations in auxin metabolism, accumulation of reactive oxygen species (ROS; oxidative stress) or the ectopic induction of programmed cell death (PCD). In this review, we present the critically stress-sensitive stages of male sporogenesis (meiosis) and male gametogenesis (microspore development), and discuss the corresponding biological processes involved and the resulting alterations in male reproduction. In addition, this review also provides insights into the molecular and/or hormonal regulation of the environmental stress sensitivity of male reproduction and outlines putative interaction(s) between the different processes involved. PMID:23731015

  16. The use of global transcriptional analysis to reveal the biological and cellular events involved in distinct development phases of Trichophyton rubrum conidial germination

    PubMed Central

    Liu, Tao; Zhang, Qian; Wang, Lingling; Yu, Lu; Leng, Wenchuan; Yang, Jian; Chen, Lihong; Peng, Junping; Ma, Li; Dong, Jie; Xu, Xingye; Xue, Ying; Zhu, Yafang; Zhang, Wenliang; Yang, Li; Li, Weijun; Sun, Lilian; Wan, Zhe; Ding, Guohui; Yu, Fudong; Tu, Kang; Qian, Ziliang; Li, Ruoyu; Shen, Yan; Li, Yixue; Jin, Qi

    2007-01-01

    Background Conidia are considered to be the primary cause of infections by Trichophyton rubrum. Results We have developed a cDNA microarray containing 10250 ESTs to monitor the transcriptional strategy of conidial germination. A total of 1561 genes that had their expression levels specially altered in the process were obtained and hierarchically clustered with respect to their expression profiles. By functional analysis, we provided a global view of an important biological system related to conidial germination, including characterization of the pattern of gene expression at sequential developmental phases, and changes of gene expression profiles corresponding to morphological transitions. We matched the EST sequences to GO terms in the Saccharomyces Genome Database (SGD). A number of homologues of Saccharomyces cerevisiae genes related to signalling pathways and some important cellular processes were found to be involved in T. rubrum germination. These genes and signalling pathways may play roles in distinct steps, such as activating conidial germination, maintenance of isotropic growth, establishment of cell polarity and morphological transitions. Conclusion Our results may provide insights into molecular mechanisms of conidial germination at the cell level, and may enhance our understanding of regulation of gene expression related to the morphological construction of T. rubrum. PMID:17428342

  17. Biological processes, quantum mechanics and electromagnetic fields: the possibility of device-encapsulated human intention in medical therapies.

    PubMed

    Kohane, M J; Tiller, W A

    2001-06-01

    The general hypothesis that quantum mechanics (QM) and thermodynamic concepts relate to biological systems is discussed and applied to the biological influence of: (1) electromagnetic fields (EMFs); and (2) EMFs that have been exposed to human intention. We illustrate our hypothesis with experiments involving four simultaneous treatments: exposure to ambient EMFs in the laboratory environment (C), exposure in a Faraday cage (F) and exposure in a Faraday cage with either: (i) an electronic device (IIED) which had been exposed to a specific human intention (d,j); or (ii) a non-exposed, physically identical, device (d,o). Experimental systems were fitness and energy metabolism in Drosophila melanogaster, in vitro enzyme activity and molecular concentration variability over time. Results indicated that shielding from ambient EMFs via a Faraday cage (F) made a significant difference relative to the unshielded control (C). Further, (d,o) had a significant lowering effect in the shielded environment. Finally, there was a strong 'intention' effect with the IIED (d,j) producing significant and positive effects in comparison to (d,o) in each experimental system.

  18. Behind the smile: cell biology and disease mechanisms of Giardia species.

    PubMed

    Ankarklev, Johan; Jerlström-Hultqvist, Jon; Ringqvist, Emma; Troell, Karin; Svärd, Staffan G

    2010-06-01

    The eukaryotic intestinal parasite Giardia intestinalis was first described in 1681, when Antonie van Leeuwenhoek undertook a microscopic examination of his own diarrhoeal stool. Nowadays, although G. intestinalis is recognized as a major worldwide contributor to diarrhoeal disease in humans and other mammals, the disease mechanisms are still poorly understood. Owing to its reduced complexity and proposed early evolutionary divergence, G. intestinalis is used as a model eukaryotic system for studying many basic cellular processes. In this Review we discuss recent discoveries in the molecular cell biology and pathogenesis of G. intestinalis.

  19. Biological-mechanical waste treatment tests at a landfill in East Germany

    SciTech Connect

    Wotte, J.; Brummack, J.; Paar, S.; Gemende, B.

    1996-11-01

    The paper begins by describing the present situation in East Germany with regard to sanitary landfills, that is, there is very limited space for new landfills. The paper discusses the new German waste act amendments, special waste management problems in East Germany, and the combination biological and mechanical waste treatment (BMT) method proposed to help solve these problems. In general terms the BMT method would use a combination of composting, fermentation, separation, mixing, and crushing processes to minimize the waste to be disposed of and to render it harmless to further degradation which leads to emission of methane and contaminated leachates from the landfills.

  20. Input of DNA microarrays to identify novel mechanisms in multiple myeloma biology and therapeutic applications

    PubMed Central

    Mahtouk, Karène; Hose, Dirk; De Vos, John; Moreaux, Jérôme; Jourdan, Michel; Rossi, Jean François; Rème, Thierry; Goldschmidt, Harmut; Klein, Bernard

    2007-01-01

    Multiple myeloma (MM) is a B cell neoplasia characterized by the proliferation of a clone of malignant plasma cells in the bone marrow. We review here the input of gene expression profiling (GEP) of myeloma cells and of their tumor microenvironment to develop new tumor classifiers, to better understand the biology of myeloma cells, to identify some mechanisms of drug sensitivity and resistance, to identify new myeloma growth factors, and to depict the complex interactions between tumor cells and their microenvironment. We discuss how these findings may improve the clinical outcome of this still incurable disease. PMID:18094409

  1. Closing the Loop: Involving Faculty in the Assessment of Scientific and Quantitative Reasoning Skills of Biology Majors

    ERIC Educational Resources Information Center

    Hurney, Carol A.; Brown, Justin; Griscom, Heather Peckham; Kancler, Erika; Wigtil, Clifton J.; Sundre, Donna

    2011-01-01

    The development of scientific and quantitative reasoning skills in undergraduates majoring in science, technology, engineering, and mathematics (STEM) is an objective of many courses and curricula. The Biology Department at James Madison University (JMU) assesses these essential skills in graduating biology majors by using a multiple-choice exam…

  2. Newt tail regeneration: a model for gravity-dependent morphogenesis and clues to the molecular mechanisms involved.

    NASA Astrophysics Data System (ADS)

    Radugina, Elena A.; Almeida, Eduardo; Grigoryan, Eleonora

    factors and are expressed during development, we hypothesized they may play a role newt tail regenerative morphogenesis under altered g-levels. Specifically there is increasing evidence for HSPs expression changes as a result of hyper-and microgravity. HSPs are also expressed throughout regeneration, rather than just after surgery. To test this hypothesis we performed heat shock on intact and regenerating newts and collected tail tissues. In these experiments we observed that some tails had uplifted tips while others mimicked hook-like regenerates at 1g or 2g. These findings suggest that heat shock, and HSPs induction, may be involved in the mechanism responsible for gravity effects on morphogenesis, or at least interact with them. Current work underway is focused on analyzing the expression of mRNA and localization of proteins for two members of the group, Hsp70 and Hsp90. In summary, we developed and characterized a new practical animal model in which gravity mechanostimulation at 1g, versus unloading in aquaria, causes prominent effects on newt tail regenerative morphogenesis. This model can be achieved without the use of a centrifuge, significantly simplifying its research applications. Initial results using this model suggest that induction of HSPs may be involved in gravity regulation of newt tail regenerative morphogenesis. Further research based on this simple model may help to unravel mechanisms of gravity influence relevant not only to newt tail regeneration, but also to a broad range of other biological processes in amphibian models.

  3. Adult criminal involvement: A cross-sectional inquiry into correlates and mechanisms over the life course

    PubMed Central

    DePadilla, Lara; Perkins, Molly M.; Elifson, Kirk W.; Sterk, Claire E.

    2013-01-01

    In this paper, we examine the relative contribution of four domains of predictors that have been linked to adult criminal involvement: (1) socio-demographic characteristics, (2) family-of-origin factors, (3) proximal processes developed during adolescence, and (4) current lifestyle and situational factors. Cross-sectional data were collected through face-to-face interviews with 242 community-recruited adults. Data analysis involved negative binomial regression. Being male, family size, juvenile delinquency, aggression, living with someone involved in illegal activity and recent violent victimization were independently associated with non-violent criminal involvement. Aggression, association with deviant peers, and recent violent victimization were independently associated with violent criminal involvement. Juvenile delinquency and aggression mediated the affect of multiple family-of-origin characteristics on non-violent criminal involvement and aggression mediated the effect of childhood physical abuse on violent criminal involvement. The results emphasize the importance of investigating both antecedents and proximal risk factors predictive of different types of criminal involvement, which, in turn, will assist in developing risk-focused prevention and intervention programs. PMID:24307752

  4. Extruded collagen fibres for tissue engineering applications: effect of crosslinking method on mechanical and biological properties.

    PubMed

    Enea, Davide; Henson, Frances; Kew, Simon; Wardale, John; Getgood, Alan; Brooks, Roger; Rushton, Neil

    2011-06-01

    Reconstituted collagen fibres are promising candidates for tendon and ligament tissue regeneration. The crosslinking procedure determines the fibres' mechanical properties, degradation rate, and cell-fibre interactions. We aimed to compare mechanical and biological properties of collagen fibres resulting from two different types of crosslinking chemistry based on 1-ethyl-3-(3-dimethyllaminopropyl)carbodiimide (EDC). Fibres were crosslinked with either EDC or with EDC and ethylene-glycol-diglycidyl-ether (EDC/EGDE). Single fibres were mechanically tested to failure and bundles of fibres were seeded with tendon fibroblasts (TFs) and cell attachment and proliferation were determined over 14 days in culture. Collagen type I and tenascin-C production were assessed by immunohistochemistry and dot-blotting. EDC chemistry resulted in fibres with average mechanical properties but the highest cell proliferation rate and matrix protein production. EDC/EGDE chemistry resulted in fibres with improved mechanical properties but with a lower biocompatibility profile. Both chemistries may provide useful structures for scaffolding regeneration of tendon and ligament tissue and will be evaluated for in vivo tendon regeneration in future experiments.

  5. Improving mechanical and biological properties of macroporous HA scaffolds through composite coatings.

    PubMed

    Zhao, J; Lu, X; Duan, K; Guo, L Y; Zhou, S B; Weng, J

    2009-11-01

    Interconnected porous hydroxyapatite (HA) scaffolds are widely used for bone repair and replacement, owing to their ability to support the adhesion, transfer, proliferation and differentiation of cells. In the present study, the polymer impregnation approach was adopted to produce porous HA scaffolds with three-dimensional (3D) porous structures. These scaffolds have an advantage of highly interconnected porosity (approximately 85%) but a drawback of poor mechanical strength. Therefore, the as-prepared HA scaffolds were lined with composite polymer coatings in order to improve the mechanical properties and retain its good bioactivity and biocompatibility at the same time. The composite coatings were based on poly(D,L-lactide) (PDLLA) polymer solutions, and contained single component or combination of HA, calcium sulfate (CS) and chondroitin sulfate (ChS) powders. The effects of composite coatings on scaffold porosity, microstructure, mechanical property, in vitro mineralizing behavior, and cell attachment of the resultant scaffolds were investigated. The results showed that the scaffolds with composite coatings resulted in significant improvement in both mechanical and biological properties while retaining the 3D interconnected porous structure. The in vitro mineralizing behaviors were mainly related to the compositions of CS and ChS powders in the composite coatings. Excellent cell attachments were observed on the pure HA scaffold as well as the three types of composite scaffolds. These composite scaffolds with improved mechanical properties and bioactivities are promising bone substitutes in tissue engineering fields.

  6. The mechanism of binding staphylococcal protein A to immunoglobin G does not involve helix unwinding.

    PubMed

    Jendeberg, L; Tashiro, M; Tejero, R; Lyons, B A; Uhlén, M; Montelione, G T; Nilsson, B

    1996-01-09

    maintains its three-helical bundle structure in the Z-Fc complex, though there may be a small structural change involved in the binding mechanism.

  7. Mechanisms involved in the psychological distress of Black Caribbeans in the United States

    NASA Astrophysics Data System (ADS)

    Govia, Ishtar O.

    The mental health of ethnic minorities in the United States is of urgent concern. The accelerated growth of groups of ethnic minorities and immigrants in the United States and the stressors to which they are exposed, implores academic researchers to investigate more deeply health disparities and the factors that exacerbate or minimize such inequalities. This dissertation attended to that concern. It used data from the National Survey of American Life (NSAL), the first survey with a national representative sample of Black Caribbeans, to explore mechanisms that involved in the psychological distress of Black Caribbeans in the United States. In a series of three studies, the dissertation investigated the role and consequence of (1) chronic discrimination, immigration factors, and closeness to ethnic and racial groups; (2) personal control and social support; and (3) family relations and social roles in the psychological distress of Black Caribbeans. Study 1 examined how the associations between discrimination and psychological distress were buffered or exacerbated by closeness to ethnic group and closeness to racial group. It also examined how these associations differed depending on immigration factors. Results indicated that the buffering or exacerbating effect of ethnic and racial group closeness varied according to the type of discrimination (subtle or severe) and were more pronounced among those born in the United States. Using the stress process framework, Study 2 tested moderation and mediation models of the effects of social support and personal control in the association between discrimination and distress. Results from a series of analyses on 579 respondents suggested that personal control served as a mediator in this relationship and that emotional support exerted a direct distress deterring function. Study 3 investigated sex differences in the associations between social roles, intergenerational family relationship perceptions and distress. Results

  8. Mangiferin, a natural xanthone, accelerates gastrointestinal transit in mice involving cholinergic mechanism

    PubMed Central

    Morais, Talita Cavalcante; Lopes, Synara Cavalcante; Carvalho, Karine Maria Martins Bezerra; Arruda, Bruno Rodrigues; de Souza, Francisco Thiago Correia; Trevisan, Maria Teresa Salles; Rao, Vietla Satyanarayana; Santos, Flávia Almeida

    2012-01-01

    AIM: To investigate the effects of mangiferin on gastrointestinal transit (GIT) in normal and constipated mice, together with the possible mechanism. METHODS: Intragastrically-administered charcoal meal was used to measure GIT in overnight starved Swiss mice. In the first experiments, mangiferin (3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg, po) or tegaserod (1 mg/kg, ip) were administered 30 min before the charcoal meal to study their effects on normal transit. In the second series, mangiferin (30 mg/kg) was tested on delayed GIT induced by several different pharmacological agonists (morphine, clonidine, capsaicin) or antagonists (ondansetron, verapamil, and atropine) whereas in the third series, mangiferin (30 mg/kg, 100 mg/kg and 300 mg/kg) or tegaserod (1 mg/kg) were tested on 6 h fecal pellets outputted by freely fed mice. The ratio of wet to dry weight was calculated and used as a marker of fecal water content. RESULTS: Mangiferin administered orally significantly (P < 0.05) accelerated GIT at 30 mg/kg and 100 mg/kg (89% and 93%, respectively), similarly to 5-hydroxytryptamine4 (5-HT4) agonist tegaserod (81%) when compared to vehicle-treated control (63%). Co-administered mangiferin (30 mg/kg) totally reversed the inhibitory effect of opioid agonist morphine, 5-HT3-receptor antagonist ondansetron and transient receptor potential vanilloid-1 receptor agonist capsaicin on GIT, but only to a partial extent with the GIT-delay induced by α2-adrenoceptor agonist clonidine, and calcium antagonist verapamil. However, co-administered atropine completely blocked the stimulant effect of mangiferin on GIT, suggesting the involvement of muscarinic acetylcholine receptor activation. Although mangiferin significantly enhanced the 6 h fecal output at higher doses (245.5 ± 10.43 mg vs 161.9 ± 10.82 mg and 227.1 ± 20.11 mg vs 161.9 ± 10.82 mg of vehicle-treated control, at 30 and 100 mg/kg, P < 0.05, respectively), the effect of tegaserod was more potent (297.4 ± 7.42 mg

  9. Correlates of Parents' Involvement with Their Adolescent Children in Restructured and Biological Two-Parent Families: The Role of Child Characteristics

    ERIC Educational Resources Information Center

    Flouri, Eirini

    2004-01-01

    This study used data from both 225 fathers and mothers as well as their secondary school age children to explore the role of child characteristics (sex, age, self-esteem, and emotional and behavioural well-being) in mother's and father's involvement in biological and restructured (stepfather) two-parent families after controlling for known…

  10. Biological network inferences for a protection mechanism against familial Creutzfeldt-Jakob disease with E200K pathogenic mutation

    PubMed Central

    2014-01-01

    Background Human prion diseases are caused by abnormal accumulation of misfolded prion protein in the brain tissue. Inherited prion diseases, including familial Creutzfeldt-Jakob disease (fCJD), are associated with mutations of the prion protein gene (PRNP). The glutamate (E)-to-lysine (K) substitution at codon 200 (E200K) in PRNP is the most common pathogenic mutation causing fCJD, but the E200K pathogenic mutation alone is regarded insufficient to cause prion diseases; thus, additional unidentified factors are proposed to explain the penetrance of E200K-dependent fCJD. Here, exome differences and biological network analysis between fCJD patients with E200K and healthy individuals, including a non-CJD individual with E200K, were analysed to gain new insights into possible mechanisms for CJD in individuals carrying E200K. Methods Exome sequencing of the three CJD patients with E200K and 11 of the family of one patient (case1) were performed using the Illumina HiSeq 2000. The exome sequences of 24 Healthy Koreans were used as control. The bioinformatic analysis of the exome sequences was performed using the CLC Genomics Workbench v5.5. Sanger sequencing for variants validation was processed using a BigDye Terminator Cycle Sequencing Kit and an ABI 3730xl automated sequencer. Biological networks were created using Cytoscape (v2.8.3 and v3.0.2) and Pathway Studio 9.0 software. Results Nineteen sites were only observed in healthy individuals. Four proteins (NRXN2, KLKB1, KARS, and LAMA3) that harbour rarely observed single-nucleotide variants showed biological interactions that are associated with prion diseases and/or prion protein in our biological network analysis. Conclusion Through this study, we confirmed that individuals can have a CJD-free life, even if they carry a pathogenic E200K mutation. Our research provides a possible mechanism that involves a candidate protective factor; this could be exploited to prevent fCJD onset in individuals carrying E200K. PMID

  11. Investigations on mechanical biological treatment of waste in South America: Towards more sustainable MSW management strategies

    SciTech Connect

    Bezama, Alberto . E-mail: alberto.bezama@stud.unileoben.ac.at; Aguayo, Pablo; Konrad, Odorico; Navia, Rodrigo; Lorber, Karl E.

    2007-07-01

    This work presents an analysis on the suitability of mechanical biological treatment of municipal solid waste in South America, based on two previous experimental investigations carried out in two different countries. The first experiment was performed for determining the mass and volume reduction of MSW in the province of Concepcion (Chile). The implemented bench-scale process consisted of a manual classification and separation stage, followed by an in-vessel biological degradation process. The second experiment consisted of a full-scale experiment performed in the city of Estrela (Brazil), where the existing municipal waste management facility was adapted to enhance the materials sorting and separation. Expressed in wet weight composition, 85.5% of the material input in the first experiment was separated for biological degradation. After 27 days of processing, 60% of the initial mass was reduced through degradation and water evaporation. The final fraction destined for landfilling equals 59% of the total input mass, corresponding to about 50% of the initial volume. In the second experiment, the fraction destined to landfill reaches 46.6% of the total input waste mass, whilst also significantly reducing the total volume to be disposed. These results, and the possible recovery of material streams suitable for recycling or for preparing solid recovered fuels, are the main advantages of the studied process.

  12. Biological roles and functional mechanisms of arenavirus Z protein in viral replication.

    PubMed

    Wang, Jialong; Danzy, Shamika; Kumar, Naveen; Ly, Hinh; Liang, Yuying

    2012-09-01

    Arenaviruses can cause severe hemorrhagic fever diseases in humans, with limited prophylactic or therapeutic measures. A small RING-domain viral protein Z has been shown to mediate the formation of virus-like particles and to inhibit viral RNA synthesis, although its biological roles in an infectious viral life cycle have not been directly addressed. By taking advantage of the available reverse genetics system for a model arenavirus, Pichinde virus (PICV), we provide the direct evidence for the essential biological roles of the Z protein's conserved residues, including the G2 myristylation site, the conserved C and H residues of RING domain, and the poorly characterized C-terminal L79 and P80 residues. Dicodon substitutions within the late (L) domain (PSAPPYEP) of the PICV Z protein, although producing viable mutant viruses, have significantly reduced virus growth, a finding suggestive of an important role for the intact L domain in viral replication. Further structure-function analyses of both PICV and Lassa fever virus Z proteins suggest that arenavirus Z proteins have similar molecular mechanisms in mediating their multiple functions, with some interesting variations, such as the role of the G2 residue in blocking viral RNA synthesis. In summary, our studies have characterized the biological roles of the Z protein in an infectious arenavirus system and have shed important light on the distinct functions of its domains in virus budding and viral RNA regulation, the knowledge of which may lead to the development of novel antiviral drugs.

  13. [Mechanism of nitrogen removal by partial nitrification-denitrification biological filter].

    PubMed

    Sun, Ying-Xue; Xu, Dong; Tian, Yuan; Li, Yan-Fei

    2012-10-01

    The controlling factors for nitrite accumulation in partial nitrification and mechanism of nitrogen removal from the secondary effluent of wastewater treatment plant by partial nitrification-denitrification biological filter were investigated. The results showed that nitrite accumulated with increasing of pH value in the influent under the condition of temperature was (30 +/- 1) degrees C. The nitrite accumulation achieved to the highest at a pH value of 8.5 in this batch experiments. In addition, the nitrite accumulation presented increasing tendency through the up-flow nitrifying biological filter, which can be adjusted by the changes of pH and DO through the filter. The removal efficiency of NH4+ -N was over 90% by the partial nitrification-denitrification biological filter. Meanwhile, carbon sources were supplied for the denitrifying bacteria to accomplish denitrification process. Under the condition of COD/TN at a value of 3.0, the concentration of TN in the effluent of denitrifying biofilter was 8-9 mg x L(-1) and the removal efficiency achieved 79% - 81%, stably.

  14. 2-Deoxy Glucose Modulates Expression and Biological Activity of VEGF in a SIRT-1 Dependent Mechanism.

    PubMed

    Kunhiraman, Haritha; Edatt, Lincy; Thekkeveedu, Sruthi; Poyyakkara, Aswini; Raveendran, Viji; Kiran, Manikantan Syamala; Sudhakaran, Perumana; Kumar, Sameer V B

    2017-02-01

    Reprogramming of energy metabolism particularly switching over of cells to aerobic glycolysis leading to accumulation of lactate is a hallmark of cancer. Lactate can induce angiogenesis, an important process underlying tumor growth and metastasis. VEGF is one of the most important cytokines which regulate this process and the present study was designed to examine if blocking glycolytic pathway in tumor cells can affect its angiogenic potency with respect to VEGF. For this, the expression and biological activity of VEGF synthesized and secreted by tumor derived cell lines in the presence or absence of 2-deoxy glucose (2-DG), an inhibitor of glycolysis was determined. The results suggested that inhibition of glycolysis using sub-lethal doses of 2-DG down-regulated the expression of VEGF and also significantly reduced its biological activity. Further mechanistic studies revealed that the down regulation of VEGF gene expression by 2-DG was due to an increase in SIRT-1 activity and the reduced biological activity was found to be due to an increase in the PAR modification of VEGF. Activity of SIRT-1 and PAR modification of VEGF in turn, was found to be correlated to the cellular NAD(+) levels. The results presented here therefore suggest that treatment of cancer cells with 2-DG can significantly reduce its overall angiogenic potency through transcriptional and post-translational mechanisms. J. Cell. Biochem. 118: 252-262, 2017. © 2016 Wiley Periodicals, Inc.

  15. Biological Targets and Mechanisms of Action of Natural Products from Marine Cyanobacteria

    PubMed Central

    Salvador-Reyes, Lilibeth A.

    2015-01-01

    Marine cyanobacteria are an ancient group of organisms and prolific producers of bioactive secondary metabolites. These compounds are presumably optimized by evolution over billions of years to exert high affinity for their intended biological target in the ecologically relevant organism but likely also possess activity in different biological contexts such as human cells. Screening of marine cyanobacterial extracts for bioactive natural products has largely focused on cancer cell viability; however, diversification of the screening platform led to the characterization of many new bioactive compounds. Targets of compounds have oftentimes been elusive if the compounds were discovered through phenotypic assays. Over the past few years, technology has advanced to determine mechanism of action (MOA) and targets through reverse chemical genetic and proteomic approaches, which has been applied to certain cyanobacterial compounds and will be discussed in this review. Some cyanobacterial molecules are the most-potent-in-class inhibitors and therefore may become valuable tools for chemical biology to probe protein function but also be templates for novel drugs, assuming in vitro potency translates into cellular and in vivo activity. Our review will focus on compounds for which the direct targets have been deciphered or which were found to target a novel pathway, and link them to disease states where target modulation may be beneficial. PMID:25571978

  16. Comparative developmental biology of the uterus: insights into mechanisms and developmental disruption.

    PubMed

    Spencer, Thomas E; Dunlap, Kathrin A; Filant, Justyna

    2012-05-06

    The uterus is an essential organ for reproduction in mammals that derives from the Müllerian duct. Despite the importance of the uterus for the fertility and health of women and their offspring, relatively little is known about the hormonal, cellular and molecular mechanisms that regulate development of the Müllerian duct and uterus. This review aims to summarize the hormonal, cellular and molecular mechanisms and pathways governing development of the Müllerian duct and uterus as well as highlight developmental programming effects of endocrine disruptor compounds. Organogenesis, morphogenesis, and functional differentiation of the uterus are complex, multifactorial processes. Disruption of uterine development in the fetus and neonate by genetic defects and exposure to endocrine disruptor compounds can cause infertility and cancer in the adult and their offspring via developmental programming. Clear conservation of some factors and pathways are observed between species; therefore, comparative biology is useful to identify candidate genes and pathways underlying congenital abnormalities in humans.

  17. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research

    PubMed Central

    Leon, Benjamin M; Maddox, Thomas M

    2015-01-01

    The incidence of diabetes mellitus (DM) continues to rise and has quickly become one of the most prevalent and costly chronic diseases worldwide. A close link exists between DM and cardiovascular disease (CVD), which is the most prevalent cause of morbidity and mortality in diabetic patients. Cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia are common in patients with DM, placing them at increased risk for cardiac events. In addition, many studies have found biological mechanisms associated with DM that independently increase the risk of CVD in diabetic patients. Therefore, targeting CV risk factors in patients with DM is critical to minimize the long-term CV complications of the disease. This paper summarizes the relationship between diabetes and CVD, examines possible mechanisms of disease progression, discusses current treatment recommendations, and outlines future research directions. PMID:26468341

  18. Mineral proximity influences mechanical response of proteins in biological mineral-protein hybrid systems.

    PubMed

    Ghosh, Pijush; Katti, Dinesh R; Katti, Kalpana S

    2007-03-01

    The organic phase of nacre, which is composed primarily of proteins, has an extremely high elastic modulus as compared to that of bulk proteins, and also undergoes large deformation before failure. One reason for this unusually high modulus could be the mineral-organic interactions. In this work, we elucidate the specific role of mineral proximity on the structural response of proteins in biological structural composites such as nacre through molecular modeling. The "glycine-serine" domain of a nacre protein Lustrin A has been used as a model system. It is found that the amount of work needed to unfold is significantly higher when the GS domain is pulled in the proximity of aragonite. These results indicate that the proximity of aragonite has a significant effect on the unfolding mechanisms of proteins when pulled. These results will provide very useful information in designing synthetic biocomposites, as well as further our understanding of mechanical response in structural composites in nature.

  19. Another look at the mechanism involving trimeric dUTPases in Staphylococcus aureus pathogenicity island induction involves novel players in the party

    PubMed Central

    Maiques, Elisa; Quiles-Puchalt, Nuria; Donderis, Jorge; Ciges-Tomas, J. Rafael; Alite, Christian; Bowring, Janine Z.; Humphrey, Suzanne; Penadés, José R.; Marina, Alberto

    2016-01-01

    We have recently proposed that the trimeric staphylococcal phage encoded dUTPases (Duts) are signaling molecules that act analogously to eukaryotic G-proteins, using dUTP as a second messenger. To perform this regulatory role, the Duts require their characteristic extra motif VI, present in all the staphylococcal phage coded trimeric Duts, as well as the strongly conserved Dut motif V. Recently, however, an alternative model involving Duts in the transfer of the staphylococcal islands (SaPIs) has been suggested, questioning the implication of motifs V and VI. Here, using state-of the-art techniques, we have revisited the proposed models. Our results confirm that the mechanism by which the Duts derepress the SaPI cycle depends on dUTP and involves both motifs V and VI, as we have previously proposed. Surprisingly, the conserved Dut motif IV is also implicated in SaPI derepression. However, and in agreement with the proposed alternative model, the dUTP inhibits rather than inducing the process, as we had initially proposed. In summary, our results clarify, validate and establish the mechanism by which the Duts perform regulatory functions. PMID:27112567

  20. Another look at the mechanism involving trimeric dUTPases in Staphylococcus aureus pathogenicity island induction involves novel players in the party.

    PubMed

    Maiques, Elisa; Quiles-Puchalt, Nuria; Donderis, Jorge; Ciges-Tomas, J Rafael; Alite, Christian; Bowring, Janine Z; Humphrey, Suzanne; Penadés, José R; Marina, Alberto

    2016-06-20

    We have recently proposed that the trimeric staphylococcal phage encoded dUTPases (Duts) are signaling molecules that act analogously to eukaryotic G-proteins, using dUTP as a second messenger. To perform this regulatory role, the Duts require their characteristic extra motif VI, present in all the staphylococcal phage coded trimeric Duts, as well as the strongly conserved Dut motif V. Recently, however, an alternative model involving Duts in the transfer of the staphylococcal islands (SaPIs) has been suggested, questioning the implication of motifs V and VI. Here, using state-of the-art techniques, we have revisited the proposed models. Our results confirm that the mechanism by which the Duts derepress the SaPI cycle depends on dUTP and involves both motifs V and VI, as we have previously proposed. Surprisingly, the conserved Dut motif IV is also implicated in SaPI derepression. However, and in agreement with the proposed alternative model, the dUTP inhibits rather than inducing the process, as we had initially proposed. In summary, our results clarify, validate and establish the mechanism by which the Duts perform regulatory functions.

  1. A few nascent methods for measuring mechanical properties of the biological cell.

    SciTech Connect

    Thayer, Gayle Echo; de Boer, Maarten Pieter; Corvalan, Carlos; Corwin, Alex David; Campanella, Osvaldo H. (Purdue University, West Lafayette, IN); Nivens, David (Purdue University, West Lafayette, IN); Werely, Steven (Purdue University, West Lafayette, IN); Sumali, Anton Hartono; Koch, Steven John

    2006-01-01

    This report summarizes a survey of several new methods for obtaining mechanical and rheological properties of single biological cells, in particular: (1) The use of laser Doppler vibrometry (LDV) to measure the natural vibrations of certain cells. (2) The development of a novel micro-electro-mechanical system (MEMS) for obtaining high-resolution force-displacement curves. (3) The use of the atomic force microscope (AFM) for cell imaging. (4) The adaptation of a novel squeezing-flow technique to micro-scale measurement. The LDV technique was used to investigate the recent finding reported by others that the membranes of certain biological cells vibrate naturally, and that the vibration can be detected clearly with recent instrumentation. The LDV has been reported to detect motions of certain biological cells indirectly through the motion of a probe. In this project, trials on Saccharomyces cerevisiae tested and rejected the hypothesis that the LDV could measure vibrations of the cell membranes directly. The MEMS investigated in the second technique is a polysilicon surface-micromachined force sensor that is able to measure forces to a few pN in both air and water. The simple device consists of compliant springs with force constants as low as 0.3 milliN/m and Moire patterns for nanometer-scale optical displacement measurement. Fields from an electromagnet created forces on magnetic micro beads glued to the force sensors. These forces were measured and agreed well with finite element prediction. It was demonstrated that the force sensor was fully functional when immersed in aqueous buffer. These results show the force sensors can be useful for calibrating magnetic forces on magnetic beads and also for direct measurement of biophysical forces on-chip. The use of atomic force microscopy (AFM) for profiling the geometry of red blood cells was the third technique investigated here. An important finding was that the method commonly used for attaching the cells to a

  2. Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

    PubMed Central

    Sart, Sébastien; Tsai, Ang-Chen; Li, Yan

    2014-01-01

    Mesenchymal stem cells (MSCs) are primary candidates in cell therapy and tissue engineering and are being tested in clinical trials for a wide range of diseases. Originally isolated and expanded as plastic adherent cells, MSCs have intriguing properties of in vitro self-assembly into three-dimensional (3D) aggregates reminiscent of skeletal condensation in vivo. Recent studies have shown that MSC 3D aggregation improved a range of biological properties, including multilineage potential, secretion of therapeutic factors, and resistance against ischemic condition. Hence, the formation of 3D MSC aggregates has been explored as a novel strategy to improve cell delivery, functional activation, and in vivo retention to enhance therapeutic outcomes. This article summarizes recent reports of MSC aggregate self-assembly, characterization of biological properties, and their applications in preclinical models. The cellular and molecular mechanisms underlying MSC aggregate formation and functional activation are discussed, and the areas that warrant further investigation are highlighted. These analyses are combined to provide perspectives for identifying the controlling mechanisms and refining the methods of aggregate fabrication and expansion for clinical applications. PMID:24168395

  3. A new approach to mechanical testing and modeling of biological tissues, with application to blood vessels.

    PubMed

    Brossollet, L J; Vito, R P

    1996-11-01

    The collection and processing of data from mechanical tests of biological tissues usually follow classical principles appropriate for studying engineering materials. However, difficulties specific to biological tissues have generally kept such methods from producing quantitative results for statistically-oriented studies. This paper demonstrates a different approach linking testing and data reduction with modern statistical tools. Experimental design theory is used to minimize the detrimental effects of collinearity on the stability of the parameters in constitutive equations. The numerical effects of time-dependent biasing factors such as viscoelasticity are reduced by randomizing the order of collection of data points. Some of the parameters of the model are allowed to vary from specimen to specimen while the others are computed once from a database of designed experiments on several specimens. Finally, a new self-modeling algorithm based on principal component analysis is used to generate uncorrelated parameters for a model that is linear in its specimen-dependent parameters. The method, associated with a recently published complementary energy formulation for vascular mechanics, is illustrated with biaxial canine saphenous vein data. Results show that three specimen-dependent linear parameters are enough to characterize the experimental data and that they can be repeatedly estimated from different data sets. Independently collected biaxial inflation data can also be predicted reasonably well with this model.

  4. Organic fraction of municipal solid waste from mechanical selection: biological stabilization and recovery options.

    PubMed

    Cesaro, Alessandra; Russo, Lara; Farina, Anna; Belgiorno, Vincenzo

    2016-01-01

    Although current trends address towards prevention strategies, the organic fraction of municipal solid waste is greatly produced, especially in high-income contexts. Its recovery-oriented collection is a common practice, but a relevant portion of the biodegradable waste is not source selected. Mechanical and biological treatments (MBT) are the most common option to sort and stabilize the biodegradable matter ending in residual waste stream. Following the changes of the framework around waste management, this paper aimed at analyzing the quality of the mechanically selected organic waste produced in MBT plants, in order to discuss its recovery options. The material performance was obtained by its composition as well as by its main chemical and physical parameters; biological stability was also assessed by both aerobic and anaerobic methods. On this basis, the effectiveness of an aerobic biostabilization process was assessed at pilot scale. After 21 days of treatment, results proved that the biomass had reached an acceptable biostabilization level, with a potential Dynamic Respirometric Index (DRIP) value lower than the limit required for its use as daily or final landfill cover material. However, the final stabilization level was seen to be influenced by scaling factors and the 21 days of treatment turned to be not so adequate when applied in the existing full-scale facility.

  5. Mechanism of action of moderate-intensity static magnetic fields on biological systems.

    PubMed

    Rosen, Arthur D

    2003-01-01

    There is substantial evidence indicating that moderate-intensity static magnetic fields (SMF) are capable of influencing a number of biological systems, particularly those whose function is closely linked to the properties of membrane channels. Most of the reported moderate SMF effects may be explained on the basis of alterations in membrane calcium ion flux. The mechanism suggested to explain these effects is based on the diamagnetic anisitropic properties of membrane phospholipids. It is proposed that reorientation of these molecules during moderate SMF exposure will result in the deformation of imbedded ion channels, thereby altering their activation kinetics. Channel inactivation would not be expected to be influenced by these fields because this mechanism is not located within the intramembraneous portion of the channel. Patch-clamp studies of calcium channels have provided support for this hypothesis, as well as demonstrating a temperature dependency that is understandable on the basis of the membrane thermotropic phase transition. Additional studies have demonstrated that sodium channels are similarly affected by SMFs, although to a lesser degree. These findings support the view that moderate SMF effects on biological membranes represent a general phenomenon, with some channels being more susceptible than others to membrane deformation.

  6. Involvement of mast cells and proteinase-activated receptor 2 in oxaliplatin-induced mechanical allodynia in mice.

    PubMed

    Sakamoto, Ayumi; Andoh, Tsugunobu; Kuraishi, Yasushi

    2016-03-01

    The chemotherapeutic agent oxaliplatin induces neuropathic pain, a dose-limiting side effect, but the underlying mechanisms are not fully understood. Here, we show the potential involvement of cutaneous mast cells in oxaliplatin-induced mechanical allodynia in mice. A single intraperitoneal injection of oxaliplatin induced mechanical allodynia, which peaked on day 10 after injection. Oxaliplatin-induced mechanical allodynia was almost completely prevented by congenital mast cell deficiency. The numbers of total and degranulated mast cells was significantly increased in the skin after oxaliplatin administration. Repetitive topical application of the mast cell stabilizer azelastine hydrochloride inhibited mechanical allodynia and the degranulation of mast cells without affecting the number of mast cells in oxaliplatin-treated mice. The serine protease inhibitor camostat mesilate and the proteinase-activated receptor 2 (PAR2) antagonist FSLLRY-NH2 significantly inhibited oxaliplatin-induced mechanical allodynia. However, it was not inhibited by the H1 histamine receptor antagonist terfenadine. Single oxaliplatin administration increased the activity of cutaneous serine proteases, which was attenuated by camostat and mast cell deficiency. Depletion of the capsaicin-sensitive primary afferents by neonatal capsaicin treatment almost completely prevented oxaliplatin-induced mechanical allodynia, the increase in the number of mast cells, and the activity of cutaneous serine proteases. These results suggest that serine protease(s) released from mast cells and PAR2 are involved in oxaliplatin-induced mechanical allodynia. Therefore, oxaliplatin may indirectly affect the functions of mast cells through its action on capsaicin-sensitive primary afferents.

  7. Diverse Mechanisms of Sp1-Dependent Transcriptional Regulation Potentially Involved in the Adaptive Response of Cancer Cells to Oxygen-Deficient Conditions

    PubMed Central

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    The inside of a tumor often contains a hypoxic area caused by a limited supply of molecular oxygen due to aberrant vasculature. Hypoxia-inducible factors (HIFs) are major transcription factors that are required for cancer cells to adapt to such stress conditions. HIFs, complexed with the aryl hydrocarbon receptor nuclear translocator, bind to and activate target genes as enhancers of transcription. In addition to this common mechanism, the induction of the unfolded protein response and mTOR signaling in response to endoplasmic reticulum stress is also known to be involved in the adaptation to hypoxia conditions. Sp1 is a ubiquitously-expressed transcription factor that plays a vital role in the regulation of numerous genes required for normal cell function. In addition to the well-characterized stress response mechanisms described above, increasing experimental evidence suggests that Sp1 and HIFs collaborate to drive gene expression in cancer cells in response to hypoxia, thereby regulating additional adaptive responses to cellular oxygen deficiency. However, these characteristics of Sp1 and their biological merits have not been summarized. In this review, we will discuss the diverse mechanisms of transcriptional regulation by Sp1 and their potential involvement in the adaptive response of cancer cells to hypoxic tumor microenvironments. PMID:26703734

  8. Involvement of a glibenclamide-sensitive mechanism in the nitrergic neurotransmission of the pig intravesical ureter

    PubMed Central

    Hernández, Medardo; Prieto, Dolores; Orensanz, Luis M; Barahona, María Victoria; Jiménez-Cidre, Miguel; Rivera, Luis; García-Sacristán, Albino; Simonsen, Ulf

    1997-01-01

    The present study was designed to investigate whether potassium (K+) channels are involved in the relaxations to nitric oxide (NO) of pig intravesical ureteral preparations suspended in organ baths for isometric tension recordings. In ureteral strips treated with guanethidine (10−5 M) and atropine (10−7 M) to block adrenergic neurotransmission and muscarinic receptors, respectively, NO was either released from nitrergic nerves by electrical field stimulation (EFS, 0.5–10 Hz, 1 ms duration, 20 s trains), or exogenously-applied as an acidified solution of sodium nitrite (NaNO2, 10−6–10−3 M).Incubation with an inhibitor of guanylate cyclase activation by NO, methylene blue (10−5 M) did not change the basal tension of intravesical ureteral strips but inhibited the relaxation induced by EFS or exogenous NO on ureteral preparations contracted with the thromboxane analogue U46619 (10−7 M).Incubation with charybdotoxin (3×10−8 M) and apamin (5×10−7 M), which are inhibitors of large and small conductance calcium (Ca2+)-activated K+ channels, respectively, did not modify basal tension or the relaxations induced by EFS and exogenous NO. Treatment with charybdotoxin or apamin plus methylene blue (10−5 M) significantly reduced the relaxations to EFS and exogenous NO. However, in both cases the reductions were similar to the inhibition evoked by methylene blue alone. The combined addition of charybdotoxin plus apamin did not change the relaxations to EFS or exogenously added NO of the porcine intravesical ureter.Cromakalim (10−8–3×10−6 M), an opener of ATP-sensitive K+ channels, evoked a dose-dependent relaxation with a pD2 of 7.3±0.2 and maximum relaxant effect of a 71.8±4.2% of the contraction induced by U46619 in the pig intravesical ureter. The blocker of ATP-sensitive K+ channels, glibenclamide (10−6 M), inhibited markedly the relaxations to cromakalim.Glibenclamide (10−6 M) had no effect on the basal tone of

  9. Elucidation of the binding mechanism of renin using a wide array of computational techniques and biological assays.

    PubMed

    Tzoupis, Haralambos; Leonis, Georgios; Avramopoulos, Aggelos; Reis, Heribert; Czyżnikowska, Żaneta; Zerva, Sofia; Vergadou, Niki; Peristeras, Loukas D; Papavasileiou, Konstantinos D; Alexis, Michael N; Mavromoustakos, Thomas; Papadopoulos, Manthos G

    2015-11-01

    We investigate the binding mechanism in renin complexes, involving three drugs (remikiren, zankiren and enalkiren) and one lead compound, which was selected after screening the ZINC database. For this purpose, we used ab initio methods (the effective fragment potential, the variational perturbation theory, the energy decomposition analysis, the atoms-in-molecules), docking, molecular dynamics, and the MM-PBSA method. A biological assay for the lead compound has been performed to validate the theoretical findings. Importantly, binding free energy calculations for the three drug complexes are within 3 kcal/mol of the experimental values, thus further justifying our computational protocol, which has been validated through previous studies on 11 drug-protein systems. The main elements of the discovered mechanism are: (i) minor changes are induced to renin upon drug binding, (ii) the three drugs form an extensive network of hydrogen bonds with renin, whilst the lead compound presented diminished interactions, (iii) ligand binding in all complexes is driven by favorable van der Waals interactions and the nonpolar contribution to solvation, while the lead compound is associated with diminished van der Waals interactions compared to the drug-bound forms of renin, and (iv) the environment (H2O/Na(+)) has a small effect on the renin-remikiren interaction.

  10. Toward modular biological models: defining analog modules based on referent physiological mechanisms

    PubMed Central

    2014-01-01

    Background Currently, most biomedical models exist in isolation. It is often difficult to reuse or integrate models or their components, in part because they are not modular. Modular components allow the modeler to think more deeply about the role of the model and to more completely address a modeling project’s requirements. In particular, modularity facilitates component reuse and model integration for models with different use cases, including the ability to exchange modules during or between simulations. The heterogeneous nature of biology and vast range of wet-lab experimental platforms call for modular models designed to satisfy a variety of use cases. We argue that software analogs of biological mechanisms are reasonable candidates for modularization. Biomimetic software mechanisms comprised of physiomimetic mechanism modules offer benefits that are unique or especially important to multi-scale, biomedical modeling and simulation. Results We present a general, scientific method of modularizing mechanisms into reusable software components that we call physiomimetic mechanism modules (PMMs). PMMs utilize parametric containers that partition and expose state information into physiologically meaningful groupings. To demonstrate, we modularize four pharmacodynamic response mechanisms adapted from an in silico liver (ISL). We verified the modularization process by showing that drug clearance results from in silico experiments are identical before and after modularization. The modularized ISL achieves validation targets drawn from propranolol outflow profile data. In addition, an in silico hepatocyte culture (ISHC) is created. The ISHC uses the same PMMs and required no refactoring. The ISHC achieves validation targets drawn from propranolol intrinsic clearance data exhibiting considerable between-lab variability. The data used as validation targets for PMMs originate from both in vitro to in vivo experiments exhibiting large fold differences in time scale

  11. Combined Quantum Mechanical and Molecular Mechanics Studies of the Electron-Transfer Reactions Involving Carbon Tetrachloride in Solution

    SciTech Connect

    Valiev, Marat; Bylaska, Eric J.; Dupuis, Michel; Tratnyek, Paul G.

    2008-03-27

    The reductive dechlorination of carbon tetrachloride, CC₄, was investigated using combined high level quantum mechanical and molecular mechanics (QM/MM) approach. The first electron transfer process was assumed to proceed by a concerted electron transfer-bond breaking mechanism, and reaction barriers for the first electron reduction were estimated by using the crossing point of the free energy profiles of CCl₃-Cl and CCl₃-Cl•- as a function of the CCl₃-Cl distance. The results of these calculations showed that the activation barriers for this reaction are reachable under a wide range of reduction potentials. In the gas-phase, the barrier to reduction varied from 0.8 kcal/mol for reducing agent with a -5 kcal/mol work function to 24.7 kcal/mol for a reducing agent with a 40 kcal/mol work function at the CCSD(T)/aug-cc-pVDZ level. In the aqueous phase, QM/MM calculations at the CCSD(T)/aug-cc-pVDZ level predicted that the barrier to reduction varied from 0.7 kcal/mol to 35.2 kcal/mol for -2.32 V and 0.93 V reduction potentials respectively. COSMO continuum solvation calculations were also performed for comparison. For strong reducing agents (EH < -1.5V) very little difference was seen between the QM/MM and COSMO activation barriers. For weak reducing agents (EH > 0V) the activation barriers differed by as much as 6 kcal/mol between the QM/MM and COSMO calculations. These results demonstrate that ab initio electronic structure methods coupled with explicit molecular mechanics representation of the aqueous environment offer an efficient and accurate way to calculate the free energy reaction barriers for dissociative electron transfer reactions of organochlorine compounds to identify the potentially important environmental degradation processes.

  12. Sodium tungstate activates glycogen synthesis through a non-canonical mechanism involving G-proteins.

    PubMed

    Zafra, Delia; Nocito, Laura; Domínguez, Jorge; Guinovart, Joan J

    2013-01-31

    Tungstate treatment ameliorates experimental diabetes by increasing liver glycogen deposition through an as yet unidentified mechanism. The signalling mechanism of tungstate was studied in CHOIR cells and primary cultured hepatocytes. This compound exerted its pro-glycogenic effects through a new G-protein-dependent and Tyr-Kinase Receptor-independent mechanism. Chemical or genetic disruption of G-protein signalling prevented the activation of the Ras/ERK cascade and the downstream induction of glycogen synthesis caused by tungstate. Thus, these findings unveil a novel non-canonical signalling pathway that leads to the activation of glycogen synthesis and that could be exploited as an approach to treat diabetes.

  13. A Journey with Elie Metchnikoff: From Innate Cell Mechanisms in Infectious Diseases to Quantum Biology

    PubMed Central

    Merien, Fabrice

    2016-01-01

    Many reviews of Elie Metchnikoff’s work have been published, all unanimously acknowledging the significant contributions of his cellular theory to the fields of immunology and infectious diseases. In 1883, he published a key paper describing phagocytic cells in frogs. His descriptions were not just about phagocytes involved in host defense, he also described how these specialized cells eliminated degenerating or dying cells of the host. This perspective focuses on key concepts developed by Metchnikoff by presenting relevant excerpts of his 1883 paper and matching these concepts with challenges of modern immunology. A new approach to macrophage polarization is included to introduce some creative thinking about the exciting emerging area of quantum biology. PMID:27379227

  14. A Mechanism for Land-Atmosphere Feedback Involving Planetary Wave Structures

    NASA Technical Reports Server (NTRS)

    Koster, Randal D.; Chang, Yehui; Schubert, Siegfried D.

    2014-01-01

    While the ability of land surface conditions to influence the atmosphere has been demonstrated in various modeling and observational studies, the precise mechanisms by which land-atmosphere feedback occurs are still largely unknown particularly the mechanisms that allow land moisture state in one region to affect atmospheric conditions in another. Such remote impacts are examined here in the context of atmospheric general circulation model (AGCM) simulations, leading to the identification of one potential mechanism: the phase-locking and amplification of a planetary wave through the imposition of a spatial pattern of soil moisture at the land surface. This mechanism, shown here to be relevant in the AGCM, apparently also operates in nature, as suggested by supporting evidence found in reanalysis data.

  15. Molecules and mechanisms involved in the generation and migration of cortical interneurons

    PubMed Central

    Hernández-Miranda, Luis R; Parnavelas, John G; Chiara, Francesca

    2010-01-01

    The GABA (γ-aminobutyric acid)-containing interneurons of the neocortex are largely derived from the ganglionic eminences in the subpallium. Numerous studies have previously defined the migratory paths travelled by these neurons from their origins to their destinations in the cortex. We review here results of studies that have identified many of the genes expressed in the subpallium that are involved in the specification of the subtypes of cortical interneurons, and the numerous transcription factors, motogenic factors and guidance molecules that are involved in their migration. PMID:20360946

  16. Molecules and mechanisms involved in the generation and migration of cortical interneurons.

    PubMed

    Hernández-Miranda, Luis R; Parnavelas, John G; Chiara, Francesca

    2010-03-31

    The GABA (γ-aminobutyric acid)-containing interneurons of the neocortex are largely derived from the ganglionic eminences in the subpallium. Numerous studies have previously defined the migratory paths travelled by these neurons from their origins to their destinations in the cortex. We review here results of studies that have identified many of the genes expressed in the subpallium that are involved in the specification of the subtypes of cortical interneurons, and the numerous transcription factors, motogenic factors and guidance molecules that are involved in their migration.

  17. In vitro reassortment between Infectious Pancreatic Necrosis Virus (IPNV) strains: The mechanisms involved and its effect on virulence.

    PubMed

    Lago, María; Bandín, Isabel; Olveira, José G; Dopazo, Carlos P

    2017-01-15

    Reassortment is one of the main mechanisms of evolution in dsRNA viruses with segmented genomes. It contributes to generate genetic diversity and plays an important role in the emergence and spread of new strains with altered virulence. Natural reassorment has been demonstrated among infectious pancreatic necrosis-like viruses (genus Aquabirnavirus, Birnaviridae). In the present study, coinfections between different viral strains, and genome sequencing by the Sanger and Illumina methods were applied to analyze the frequency of reassortment of this virus in vitro, the possible mechanisms involved, and its effect on virulence. Results have demonstrated that reassortment is a cell-dependent and non-random process, probably through differential expression of the different mRNA classes in the ribosomes of a specific cell, and by specific associations between the components to construct the ribonucleoprotein (RNP) complexes and/or RNP cross-inhibition. However, the precise mechanisms involved, known in other viruses, still remain to be demonstrated in birnaviruses.

  18. Sensitizing Children to the Social and Emotional Mechanisms Involved in Racism: A Program Evaluation

    ERIC Educational Resources Information Center

    Triliva, Sofia; Anagnostopoulou, Tanya; Vleioras, Georgios

    2014-01-01

    This paper describes and discusses the results of an intervention aiming to sensitize children to the social and emotional processes involved in racism. The intervention was applied and evaluated in 10 Greek elementary schools. The goals and the intervention methods of the program modules are briefly outlined and the results of the program…

  19. Dysregulation of apoptosis is a major mechanism in the lymph node involvement in colorectal carcinoma.

    PubMed

    Bandres, Eva; Catalan, Victoria; Sola, Iosu; Honorato, Beatriz; Cubedo, Elena; Cordeu, Lucia; Andion, Esther; Escalada, Alvaro; Zarate, Ruth; Salgado, Esteban; Zabalegui, Natalia; García, Fermin; Garcia-Foncillas, Jesus

    2004-08-01

    The purpose of this study was to define gene expression profile changes in colorectal tumors in order to identify target genes involved in neoplastic progression. cDNA microarray analysis was used to detect differences in gene expression profiles between colon tumor samples obtained from 20 patients in different tumor stages. Genes included in the cDNA microarray were selected according to their role in the cell cycle, apoptosis process, drug resistance and transcription factor regulation. Cluster analysis showed 2 well differentiated gene expression profiles between colorectal tumors with or without lymph node involvement. Some of these genes are important regulators of apoptotic pathways (DAD1, APO3, DRAK1 or BIK), suggesting that this process could be associated with node involvement. Subsequent analysis of certain genes identified in the microarray analysis were confirmed by quantitative real-time PCR. Our data suggest that microarray technology could discriminate between the involvement of regional lymph node in colon cancer where apoptosis-related genes would be implied. This preliminary analysis also suggests that the gene expression profile may be useful in improving risk-group stratification.

  20. Cumulative asbestos exposure for US automobile mechanics involved in brake repair (circa 1950s-2000).

    PubMed

    Finley, Brent L; Richter, Richard O; Mowat, Fionna S; Mlynarek, Steve; Paustenbach, Dennis J; Warmerdam, John M; Sheehan, Patrick J

    2007-11-01

    We analyzed cumulative lifetime exposure to chrysotile asbestos experienced by brake mechanics in the US during the period 1950-2000. Using Monte Carlo methods, cumulative exposures were calculated using the distribution of 8-h time-weighted average exposure concentrations for brake mechanics and the distribution of job tenure data for automobile mechanics. The median estimated cumulative exposures for these mechanics, as predicted by three probabilistic models, ranged from 0.16 to 0.41 fibers per cubic centimeter (f/cm(3)) year for facilities with no dust-control procedures (1970s), and from 0.010 to 0.012 f/cm(3) year for those employing engineering controls (1980s). Upper-bound (95%) estimates for the 1970s and 1980s were 1.96 to 2.79 and 0.07-0.10 f/cm(3) year, respectively. These estimates for US brake mechanics are consistent with, but generally slightly lower than, those reported for European mechanics. The values are all substantially lower than the cumulative exposure of 4.5 f/cm(3) year associated with occupational exposure to 0.1 f/cm(3) of asbestos for 45 years that is currently permitted under the current occupational exposure limits in the US. Cumulative exposures were usually about 100- to 1,000-fold less than those of other occupational groups with asbestos exposure for similar time periods. The cumulative lifetime exposure estimates presented here, combined with the negative epidemiology data for brake mechanics, could be used to refine the risk assessments for chrysotile-exposed populations.

  1. Evolution in biological and nonbiological systems under different mechanisms of generation and inheritance.

    PubMed

    Salazar-Ciudad, Isaac

    2008-11-01

    The majority of definitions of life and evolution include the notion that part of an organism has to be copied to its offspring and that this includes some form of coded information. This article presents the thesis that this conception is too restrictive and that evolution can occur in systems in which there is no copy of information between generations. For that purpose, this article introduces a new set of concepts and a theoretical framework that is designed to be equally applicable to the study of the evolution of biological and nonbiological systems. In contrast to some theoretical approaches in evolution, like neo-Darwinism, the approach presented here is not focused on the transmission and change of hereditary information that can be copied (like in the case of DNA). Instead, multiple mechanisms by which a system can generate offspring (with and without copying) and by which information in it affects the structure and evolution of its offspring are considered. The first part of this article describes in detail these new concepts. The second part of this article discusses how these concepts are directly applicable to the diversity of systems that can evolve. The third part introduces hypotheses concerning (1) how different mechanisms of generation and inheritance can arise from each other during evolution, and (2) how the existence of several inheritance mechanisms in an organism can affect its evolution.

  2. [Action mechanism of drugs for preventing and treating coronary heart disease based on biological networks].

    PubMed

    Zhang, Yan-Ling; Huang, Ming-Feng; Qiao, Yan-Jiang

    2013-08-01

    Coronary heart disease (CHD) related genes and targets, as well as drug targets for preventing and treating CHD were taken as the study objects to build a CHD disease network and a drug action network preventing and treating CHD. Such topological characteristic parameters of the networks as degree distribution, characteristic path length, connectivity and heterogeneity were analyzed to verify the reliability of the networks. On that basis, the intersection calculation was conducted for both networks to analyze the drug action mechanism of their sub-networks. The disease network are composed of 15,221 nodes and 31,177 sides, while the drug action network preventing and treating CHD has 15,073 nodes and 32,376 sides. Both of their topological characteristic parameters showed scale-free small world structural characteristics. Two reaction pathways in the sub-networks-calcitonin gene-related peptide and IL-6 activated JAK/STAT were taken as examples to discuss the indirect action mechanism for preventing and treating CHD. The results showed that the biological network analysis method combining the disease network and the drug action network is helpful to further studies on the action mechanism of the drugs, and significant to the prevention and treatment of diseases.

  3. Mechanical and biological properties of chitosan/carbon nanotube nanocomposite films.

    PubMed

    Aryaei, Ashkan; Jayatissa, Ahalapitiya H; Jayasuriya, Ambalangodage C

    2014-08-01

    In this article, different concentrations of multiwalled carbon nanotube (MWCNT) were homogeneously dispersed throughout the chitosan (CS) matrix. A simple solvent-cast method was used to fabricate chitosan films with 0.1, 0.5, and 1% of MWCNT with the average diameter around 30 nm. The CS/MWCNT films were characterized for structural, viscous and mechanical properties with optical microscopy, wide-angle X-ray diffraction, Raman spectroscopy, tensile test machine, and microindentation testing machine. Murine osteoblasts were used to examine the cell viability and attachment of the nanocomposite films at two time points. In comparison to the pure chitosan film, the mechanical properties, including the tensile modulus and strength of the films, were greatly improved by increasing the percentage of MWCNT. Furthermore, adding MWCNT up to 1% increased the viscosity of the chitosan solution by 15%. However, adding MWCNT decreased the samples ductility and transparency. In biological point of view, no toxic effect on osteoblasts was observed in the presence of different percentages of MWCNT at day 3 and day 7. This investigation suggested MWCNT could be a promising candidate for improving chitosan mechanical properties without inducing remarkable cytotoxicity on bone cells.

  4. Population synchronies within and between ocean basins: Apparent teleconnections and implications as to physical-biological linkage mechanisms

    NASA Astrophysics Data System (ADS)

    Alheit, Jürgen; Bakun, Andrew

    2010-02-01

    Major fish populations in large marine ecosystems separated by thousands of kilometres often seem to fluctuate in decadal-scale synchrony indicating strong forcing of ecosystem processes and population dynamics by regional and global climatic variability. The climate signals propagating through the atmosphere appear to act as synchronizing agents leading to teleconnection patterns between distant marine ecosystems and populations. This review is an attempt (i) to summarize these apparent within and between ocean basin teleconnection patterns in a comparative framework using particularly suggestive examples and (ii) to unravel physical-biological linkage mechanisms between a climate signal and fish populations. Synchronies in the timing of physical and biological processes between the Kuroshio and the Humboldt Current ecosystems are particularly striking. The collapse of the Peruvian anchovy in 1971 and the rapid decrease of the Japanese anchovy seem not to be directly associated with climate indices such as the Southern Oscillation Index (SOI) and the Pacific Decadal Oscillation (PDO). The "climate regime shift" in the mid-1970s in the North Pacific indicated by the PDO is not reflected in the dynamics of anchovies and sardines and other main components in both ecosystems, whereas the Asian Winter Monsoon Index (MOI) and the Arctic Oscillation (AO) seem to correlate with these events, at least in the Northwest Pacific. We speculate that the synchrony between processes in the Kuroshio and Humboldt systems is brought about by changes in the basin-scale coupled ocean-atmosphere circulation in North and South Pacific basins. The example of European aquatic systems describes physical-biological synchronies for which the NAO appears to be the synchronizing agent. When the NAO index changed in the late 1980s from a negative to a positive phase, a coherent increase in water temperature was observed in the Central Baltic, the North Sea, the NW Mediterranean and north and

  5. Designing Laboratory Exercises for the Undergraduate Molecular Biology/Biochemistry Student: Techniques and Ethical Implications Involved in Personalized Medicine

    ERIC Educational Resources Information Center

    Weinlander, Kenneth M.; Hall, David J.

    2010-01-01

    Personalized medicine refers to medical care that involves genetically screening patients for their likelihood to develop various disorders. Commercial genome screening only involves identifying a consumer's genotype for a few single nucleotide polymorphisms. A phenotype (such as an illness) is greatly influenced by three factors: genes, gene…

  6. Mechanical homeostasis of a DOPA-enriched biological coating from mussels in response to metal variation

    PubMed Central

    Schmitt, Clemens N. Z.; Winter, Alette; Bertinetti, Luca; Masic, Admir; Strauch, Peter; Harrington, Matthew J.

    2015-01-01

    Protein–metal coordination interactions were recently found to function as crucial mechanical cross-links in certain biological materials. Mussels, for example, use Fe ions from the local environment coordinated to DOPA-rich proteins to stiffen the protective cuticle of their anchoring byssal attachment threads. Bioavailability of metal ions in ocean habitats varies significantly owing to natural and anthropogenic inputs on both short and geological spatio-temporal scales leading to large variations in byssal thread metal composition; however, it is not clear how or if this affects thread performance. Here, we demonstrate that in natural environments mussels can opportunistically replace Fe ions in the DOPA coordination complex with V and Al. In vitro removal of the native DOPA–metal complexes with ethylenediaminetetraacetic acid and replacement with either Fe or V does not lead to statistically significant changes in cuticle performance, indicating that each metal ion is equally sufficient as a DOPA cross-linking agent, able to account for nearly 85% of the stiffness and hardness of the material. Notably, replacement with Al ions also leads to full recovery of stiffness, but only 82% recovery of hardness. These findings have important implications for the adaptability of this biological material in a dynamically changing and unpredictable habitat. PMID:26311314

  7. Mechanical homeostasis of a DOPA-enriched biological coating from mussels in response to metal variation.

    PubMed

    Schmitt, Clemens N Z; Winter, Alette; Bertinetti, Luca; Masic, Admir; Strauch, Peter; Harrington, Matthew J

    2015-09-06

    Protein-metal coordination interactions were recently found to function as crucial mechanical cross-links in certain biological materials. Mussels, for example, use Fe ions from the local environment coordinated to DOPA-rich proteins to stiffen the protective cuticle of their anchoring byssal attachment threads. Bioavailability of metal ions in ocean habitats varies significantly owing to natural and anthropogenic inputs on both short and geological spatio-temporal scales leading to large variations in byssal thread metal composition; however, it is not clear how or if this affects thread performance. Here, we demonstrate that in natural environments mussels can opportunistically replace Fe ions in the DOPA coordination complex with V and Al. In vitro removal of the native DOPA-metal complexes with ethylenediaminetetraacetic acid and replacement with either Fe or V does not lead to statistically significant changes in cuticle performance, indicating that each metal ion is equally sufficient as a DOPA cross-linking agent, able to account for nearly 85% of the stiffness and hardness of the material. Notably, replacement with Al ions also leads to full recovery of stiffness, but only 82% recovery of hardness. These findings have important implications for the adaptability of this biological material in a dynamically changing and unpredictable habitat.

  8. Ultra-weak photon emission from biological samples: definition, mechanisms, properties, detection and applications.

    PubMed

    Cifra, Michal; Pospíšil, Pavel

    2014-10-05

    This review attempts to summarize molecular mechanisms, spectral and intensity properties, detection techniques and applications of ultra-weak photon emission. Ultra-weak photon emission is the chemiluminescence from biological systems where electronically excited species are formed during oxidative metabolic or oxidative stress processes. It is generally accepted that photons are emitted (1) at near UVA, visible, and near IR spectral ranges from 350 to 1300nm and (2) at the intensity of photon emission in the range of several units to several hundreds (oxidative metabolic process) and several hundreds to several thousands (oxidative stress process) photons s(-1)cm(-2). Current development in detection using low-noise photomultiplier tubes and imaging using highly sensitive charge coupled device cameras allows temporal and spatial visualization of oxidative metabolic or oxidative stress processes, respectively. As the phenomenon of ultra-weak photon emission reflects oxidative metabolic or oxidative stress processes, it can be widely used as a non-invasive tool for monitoring of the physiological state of biological systems.

  9. An updated kernel-based Turing model for studying the mechanisms of biological pattern formation.

    PubMed

    Kondo, Shigeru

    2017-02-07

    The reaction-diffusion model presented by Alan Turing has recently been supported by experimental data and accepted by most biologists. However, scientists have recognized shortcomings when the model is used as the working hypothesis in biological experiments, particularly in studies in which the underlying molecular network is not fully understood. To address some such problems, this report proposes a new version of the Turing model. This alternative model is not represented by partial differential equations, but rather by the shape of an activation-inhibition kernel. Therefore, it is named the kernel-based Turing model (KT model). Simulation of the KT model with kernels of various shapes showed that it can generate all standard variations of the stable 2D patterns (spot, stripes and network), as well as some complex patterns that are difficult to generate with conventional mathematical models. The KT model can be used even when the detailed mechanism is poorly known, as the interaction kernel can often be detected by a simple experiment and the KT model simulation can be performed based on that experimental data. These properties of the KT model complement the shortcomings of conventional models and will contribute to the understanding of biological pattern formation.

  10. Heavy-ion radiobiology: new approaches to delineate mechanisms underlying enhanced biological effectiveness

    NASA Technical Reports Server (NTRS)

    Blakely, E. A.; Kronenberg, A.; Chatterjee, A. (Principal Investigator)

    1998-01-01

    Shortly after the discovery of polonium and radium by Marie Curie and her husband and colleague, Pierre Curie, it was learned that exposure to these alpha-particle emitters produced deleterious biological effects. The mechanisms underlying the increased biological effectiveness of densely ionizing radiations, including alpha particles, neutrons and highly energetic heavy charged particles, remain an active area of investigation. In this paper, we review recent advances in several areas of the radiobiology of these densely ionizing radiations, also known as heavy ions. Advances are described in the areas of DNA damage and repair, chromosome aberrations, mutagenesis, neoplastic transformation in vitro, genomic instability, normal tissue radiobiology and carcinogenesis in vivo. We focus on technical innovations, including novel applications of pulsed-field gel electrophoresis, fluorescence in situ hybridization (FISH), linkage analysis, and studies of gene expression and protein expression. We also highlight the use of new cellular and animal systems, including those with defined DNA repair deficiencies, as well as epithelial cell model systems to assess neoplastic transformation both in vitro and in vivo. The studies reviewed herein have had a substantial impact on our understanding of the genotoxic effects of heavy ions as well as their distinct effects on tissue homeostasis. The use of these radiations in cancer therapy is also discussed. The use of both heavy-ion and proton therapy is on the upswing in several centers around the world, due to their unique energy deposition characteristics that enhance the therapeutic effect and help reduce damage to normal tissue.

  11. Biological, mechanical, and technological considerations affecting the longevity of intracortical electrode recordings.

    PubMed

    Harris, James P; Tyler, Dustin J

    2013-01-01

    Intracortical electrodes are important tools, with applications ranging from fundamental laboratory studies to potential solutions to intractable clinical applications. However, the longevity and reliability of the interfaces remain their major limitation to the wider implementation and adoption of this technology, especially in broader translational work. Accordingly, this review summarizes the most significant biological and technical factors influencing the long-term performance of intracortical electrodes. In a laboratory setting, intracortical electrodes have been used to study the normal and abnormal function of the brain. This improved understanding has led to valuable insights regarding many neurological conditions. Likewise, clinical applications of intracortical brain-machine interfaces offer the ability to improve the quality of life of many patients afflicted with high-level paralysis from spinal cord injury, brain stem stroke, amyotrophic lateral sclerosis, or other conditions. It is widely hypothesized that the tissue response to the electrodes, including inflammation, limits their longevity. Many studies have examined and modified the tissue response to intracortical electrodes to improve future intracortical electrode technologies. Overall, the relationship between biological, mechanical, and technological considerations are crucial for the fidelity of chronic electrode recordings and represent a presently active area of investigation in the field of neural engineering.

  12. Mechanism and biological role of profilin-Srv2/CAP interaction.

    PubMed

    Bertling, Enni; Quintero-Monzon, Omar; Mattila, Pieta K; Goode, Bruce L; Lappalainen, Pekka

    2007-04-01

    Profilin and cyclase-associated protein (CAP, known in yeast as Srv2) are ubiquitous and abundant actin monomer-binding proteins. Profilin catalyses the nucleotide exchange on actin monomers and promotes their addition to filament barbed ends. Srv2/CAP recycles newly depolymerized actin monomers from ADF/cofilin for subsequent rounds of polymerization. Srv2/CAP also harbors two proline-rich motifs and has been suggested to interact with profilin. However, the mechanism and biological role of the possible profilin-Srv2/CAP interaction has not been investigated. Here, we show that Saccharomyces cerevisiae Srv2 and profilin interact directly (K(D) approximately 1.3 microM) and demonstrate that a specific proline-rich motif in Srv2 mediates this interaction in vitro and in vivo. ADP-actin monomers and profilin do not interfere with each other's binding to Srv2, suggesting that these three proteins can form a ternary complex. Genetic and cell biological analyses on an Srv2 allele (srv2-201) defective in binding profilin reveals that a direct interaction with profilin is not essential for Srv2 cellular function. However, srv2-201 causes a moderate increase in cell size and partially suppresses the cell growth and actin organization defects of an actin binding mutant profilin (pfy1-4). Together these data suggest that Srv2 is an important physiological interaction partner of profilin.

  13. Statistical mechanics in biology: how ubiquitous are long-range correlations?

    NASA Technical Reports Server (NTRS)

    Stanley, H. E.; Buldyrev, S. V.; Goldberger, A. L.; Goldberger, Z. D.; Havlin, S.; Mantegna, R. N.; Ossadnik, S. M.; Peng, C. K.; Simons, M.

    1994-01-01

    The purpose of this opening talk is to describe examples of recent progress in applying statistical mechanics to biological systems. We first briefly review several biological systems, and then focus on the fractal features characterized by the long-range correlations found recently in DNA sequences containing non-coding material. We discuss the evidence supporting the finding that for sequences containing only coding regions, there are no long-range correlations. We also discuss the recent finding that the exponent alpha characterizing the long-range correlations increases with evolution, and we discuss two related models, the insertion model and the insertion-deletion model, that may account for the presence of long-range correlations. Finally, we summarize the analysis of long-term data on human heartbeats (up to 10(4) heart beats) that supports the possibility that the successive increments in the cardiac beat-to-beat intervals of healthy subjects display scale-invariant, long-range "anti-correlations" (a tendency to beat faster is balanced by a tendency to beat slower later on). In contrast, for a group of subjects with severe heart disease, long-range correlations vanish. This finding suggests that the classical theory of homeostasis, according to which stable physiological processes seek to maintain "constancy," should be extended to account for this type of dynamical, far from equilibrium, behavior.

  14. Enhancing combined biological nitrogen and phosphorus removal from wastewater by applying mechanically disintegrated excess sludge.

    PubMed

    Zubrowska-Sudol, Monika; Walczak, Justyna

    2015-06-01

    The goal of the study was to evaluate the possibility of applying disintegrated excess sludge as a source of organic carbon to enhance biological nitrogen and phosphorus removal. The experiment, performed in a sequencing batch reactor, consisted of two two-month series, without and with applying mechanically disintegrated excess sludge, respectively. The effects on carbon, nitrogen and phosphorus removal were observed. It was shown that the method allows enhancement of combined nitrogen and phosphorus removal. After using disintegrated sludge, denitrification effectiveness increased from 49.2 ± 6.8% to 76.2 ± 2.3%, which resulted in a decline in the NOx-N concentration in the effluent from the SBR by an average of 21.4 mg NOx-N/L. Effectiveness of biological phosphorus removal increased from 28.1 ± 11.3% to 96.2 ± 2.5%, thus resulting in a drop in the [Formula: see text] concentration in the effluent by, on average, 6.05 mg PO4(3-)-P/L. The application of disintegrated sludge did not deteriorate effluent quality in terms of COD and NH4(+)-N. The concentration of NH4(+)-N in both series averaged 0.16 ± 0.11 mg NH4(+)-N/L, and the concentration of COD was 15.36 ± 3.54 mg O2/L.

  15. Mechanical-biological treatment: performance and potentials. An LCA of 8 MBT plants including waste characterization.

    PubMed

    Montejo, Cristina; Tonini, Davide; Márquez, María del Carmen; Astrup, Thomas Fruergaard

    2013-10-15

    In the endeavour of avoiding presence of biodegradable waste in landfills and increasing recycling, mechanical-biological treatment (MBT) plants have seen a significant increase in number and capacity in the last two decades. The aim of these plants is separating and stabilizing the quickly biodegradable fraction of the waste as well as recovering recyclables from mixed waste streams. In this study the environmental performance of eight MBT-based waste management scenarios in Spain was assessed by means of life cycle assessment. The focus was on the technical and environmental performance of the MBT plants. These widely differed in type of biological treatment and recovery efficiencies. The results indicated that the performance is strongly connected with energy and materials recovery efficiency. The recommendation for upgrading and/or commissioning of future plants is to optimize materials recovery through increased automation of the selection and to prioritize biogas-electricity production from the organic fraction over direct composting. The optimal strategy for refuse derived fuel (RDF) management depends upon the environmental compartment to be prioritized and the type of marginal electricity source in the system. It was estimated that, overall, up to ca. 180-190 kt CO2-eq. y(-1) may be saved by optimizing the MBT plants under assessment.

  16. Heavy-ion radiobiology: new approaches to delineate mechanisms underlying enhanced biological effectiveness.

    PubMed

    Blakely, E A; Kronenberg, A

    1998-11-01

    Shortly after the discovery of polonium and radium by Marie Curie and her husband and colleague, Pierre Curie, it was learned that exposure to these alpha-particle emitters produced deleterious biological effects. The mechanisms underlying the increased biological effectiveness of densely ionizing radiations, including alpha particles, neutrons and highly energetic heavy charged particles, remain an active area of investigation. In this paper, we review recent advances in several areas of the radiobiology of these densely ionizing radiations, also known as heavy ions. Advances are described in the areas of DNA damage and repair, chromosome aberrations, mutagenesis, neoplastic transformation in vitro, genomic instability, normal tissue radiobiology and carcinogenesis in vivo. We focus on technical innovations, including novel applications of pulsed-field gel electrophoresis, fluorescence in situ hybridization (FISH), linkage analysis, and studies of gene expression and protein expression. We also highlight the use of new cellular and animal systems, including those with defined DNA repair deficiencies, as well as epithelial cell model systems to assess neoplastic transformation both in vitro and in vivo. The studies reviewed herein have had a substantial impact on our understanding of the genotoxic effects of heavy ions as well as their distinct effects on tissue homeostasis. The use of these radiations in cancer therapy is also discussed. The use of both heavy-ion and proton therapy is on the upswing in several centers around the world, due to their unique energy deposition characteristics that enhance the therapeutic effect and help reduce damage to normal tissue.

  17. A systems biology approach to defining regulatory mechanisms for cartilage and tendon cell phenotypes

    PubMed Central

    Mueller, A. J.; Tew, S. R.; Vasieva, O.; Clegg, P. D.; Canty-Laird, E. G.

    2016-01-01

    Phenotypic plasticity of adult somatic cells has provided emerging avenues for the development of regenerative therapeutics. In musculoskeletal biology the mechanistic regulatory networks of genes governing the phenotypic plasticity of cartilage and tendon cells has not been considered systematically. Additionally, a lack of strategies to effectively reproduce in vitro functional models of cartilage and tendon is retarding progress in this field. De- and redifferentiation represent phenotypic transitions that may contribute to loss of function in ageing musculoskeletal tissues. Applying a systems biology network analysis approach to global gene expression profiles derived from common in vitro culture systems (monolayer and three-dimensional cultures) this study demonstrates common regulatory mechanisms governing de- and redifferentiation transitions in cartilage and tendon cells. Furthermore, evidence of convergence of gene expression profiles during monolayer expansion of cartilage and tendon cells, and the expression of key developmental markers, challenges the physiological relevance of this culture system. The study also suggests that oxidative stress and PI3K signalling pathways are key modulators of in vitro phenotypes for cells of musculoskeletal origin. PMID:27670352

  18. Green tea catechins: biologic properties, proposed mechanisms of action, and clinical implications.

    PubMed

    Rosen, Ted

    2012-11-01

    Botanical products, including and especially green tea leaves, have a wide range of both reputed and demonstrated health benefits and have been used medicinally for thousands of years. This paper focuses on green tea catechins, principally reviewing their known biologic properties and potential mechanisms of action (MOAs). The primary objective is to discuss the proposed antiviral, antiproliferative, and immunostimulatory activity of catechins based on strong evidence from in vitro and in vivo studies conducted to date, including two preclinical in vitro studies with sinecatechins, a proprietary mixture of catechins. This review also discusses the clinical implications of catechins for the treatment of external genital and perianal warts (EGWs) and other conditions caused by human papillomavirus (HPV). While the MOA of catechins in the treatment of EGWs and other HPV-related conditions may be related to or associated with postulated or proven antiviral and immunostimulatory activity, the precise clinical significance of the various in vitro findings remains largely unknown.

  19. Microwave absorption by magnetite: a possible mechanism for coupling nonthermal levels of radiation to biological systems.

    PubMed

    Kirschvink, J L

    1996-01-01

    The presence of trace amounts of biogenic magnetite (Fe3O4) in animal and human tissues and the observation that ferromagnetic particles are ubiquitous in laboratory materials (including tissue culture media) provide a physical mechanism through which microwave radiation might produce or appear to produce biological effects. Magnetite is an excellent absorber of microwave radiation at frequencies between 0.5 and 10.0 GHz through the process of ferromagnetic resonance, where the magnetic vector of the incident field causes precession of Bohr magnetons around the internal demagnetizing field of the crystal. Energy absorbed by this process is first transduced into acoustic vibrations at the microwave carrier frequency within the crystal lattice via the magnetoacoustic effect; then, the energy should be dissipated in cellular structures in close proximity to the magnetite crystals. Several possible methods for testing this hypothesis experimentally are discussed. Studies of microwave dosimetry at the cellular level should consider effects of biogenic magnetite.

  20. [Liver regeneration after its mechanical injury in rats receiving biologically active substances "Trepel" and "Suvar"].

    PubMed

    Romanova, L P; Malysheva, I I

    2011-01-01

    The effect of biologically active substances (BAS) "Trepel" and "Suvar" on liver regeneration 1-30 days after its mechanical injury was studied using histological and morphometric methods in 110 rat pups aged 18 days. The control group comprised 90 animals that received no treatment following liver injury. It was shown that both BAS studied inhibited the inflammatory reaction around the injury focus, suppressed collagenogenesis and activated hepatocyte proliferation.This resulted in the significant substitution of the damaged area by the hepatocytes, that was absent in the control animals. In animals treated with BAS, the numbers of binucleated and mitotically dividing hepatocytes was increased, while the amount of hepatocytes with dystrophic changes was reduced. Authors associate the positive effect of BAS on liver structure regeneration with their growth-promoting activity, resulting in the hypertrophy of different organs, including the thyroid and the adrenal glands, that is accompanied by an excessive production of the respective hormones displaying their physiological actions.

  1. Biologic Mechanisms of Oral Cancer Pain and Implications for Clinical Therapy

    PubMed Central

    Viet, C.T.; Schmidt, B.L.

    2012-01-01

    Cancer pain is an ever-present public health concern. With innovations in treatment, cancer patients are surviving longer, but uncontrollable pain creates a poor quality of life for these patients. Oral cancer is unique in that it causes intense pain at the primary site and significantly impairs speech, swallowing, and masticatory functions. We propose that oral cancer pain has underlying biologic mechanisms that are generated within the cancer microenvironment. A comprehensive understanding of key mediators that control cross-talk between the cancer and peripheral nervous system, and possible interventions, underlies effective cancer pain management. The purpose of this review is to explore the current studies on oral cancer pain and their implications in clinical management for cancer pain in general. Furthermore, we will explore the endogenous opioid systems and novel cancer pain therapeutics that target these systems, which could solve the issue of opiate tolerance and improve quality of life in oral cancer patients. PMID:21972258

  2. Biological mechanism for the toxicity of haloacetic acid drinking water disinfection byproducts.

    PubMed

    Pals, Justin A; Ang, Justin K; Wagner, Elizabeth D; Plewa, Michael J

    2011-07-01

    The halogenated acetic acids are a major class of drinking water disinfection byproducts (DBPs) with five haloacetic acids regulated by the U.S. EPA. These agents are cytotoxic, genotoxic, mutagenic, and teratogenic. The decreasing toxicity rank order of the monohalogenated acetic acids (monoHAAs) is iodo- > bromo- > chloroacetic acid. We present data that the monoHAAs inhibit glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity in a concentration-dependent manner with the same rank order as above. The rate of inhibition of GAPDH and the toxic potency of the monoHAAs are highly correlated with their alkylating potential and the propensity of the halogen leaving group. This strong association between GAPDH inhibition and the monoHAA toxic potency supports a comprehensive mechanism for the adverse biological effects by this widely occurring class of regulated DBPs.

  3. Noise-Induced Mechanism for Biological Homochirality of Early Life Self-Replicators

    NASA Astrophysics Data System (ADS)

    Jafarpour, Farshid; Biancalani, Tommaso; Goldenfeld, Nigel

    2015-10-01

    The observed single-handedness of biological amino acids and sugars has long been attributed to autocatalysis. However, the stability of homochiral states in deterministic autocatalytic systems relies on cross inhibition of the two chiral states, an unlikely scenario for early life self-replicators. Here, we present a theory for a stochastic individual-level model of autocatalysis due to early life self-replicators. Without chiral inhibition, the racemic state is the global attractor of the deterministic dynamics, but intrinsic multiplicative noise stabilizes the homochiral states, in both well-mixed and spatially extended systems. We conclude that autocatalysis is a viable mechanism for homochirality, without imposing additional nonlinearities such as chiral inhibition.

  4. Parameter domains for spots and stripes in mechanical models for biological pattern formation

    NASA Astrophysics Data System (ADS)

    Zhu, M.; Murray, J. D.

    1995-07-01

    Mechanochemical models for biological pattern formation have been applied to the development of a variety of patterning problems, such as feather germ primordia and cartilage formation in the vertebrate limb. Linear analysis has been the main technique for assessing the pattern formation potential of these models to date. In this paper we carry out a nonlinear analysis and numerical simulations of a generic model in two spatial dimensions. With these methods, we obtain conditions for generating specific spatial patterns such as stripes and spots, and divide the parameter space into domains giving rise to distinct types of pattern. We accomplish our goal through a study of model parameter domains by showing how different mechanical forces affect spatial patterning.

  5. Biological effects and mechanisms of action of mesenchymal stem cell therapy in chronic obstructive pulmonary disease.

    PubMed

    Jin, Zhixian; Pan, Xinghua; Zhou, Kaihua; Bi, Hong; Wang, Liyan; Yu, Lu; Wang, Qing

    2015-06-01

    Chronic obstructive pulmonary disease (COPD) is the most frequent chronic respiratory disease and a leading cause of morbidity and mortality, worldwide. Given that the foremost risk factor leading to the development of COPD is cigarette smoke, the initial treatment for COPD is smoking cessation. Even after smoking cessation, inflammation, apoptosis and oxidative stress can persist and continue to contribute to COPD. Although current therapies for COPD (which are primarily based on anti-inflammatory drugs such as corticosteroids, theophylline and bronchodilators) reduce airway obstruction, limit COPD exacerbation and improve the patient's health-related quality-of-life, none can prevent disease progression or reduce mortality. Recent advances in stem cell research have provided novel insight into the potential of bone marrow mesenchymal stem cells (MSCs) in the treatment of several pulmonary diseases. This review article discusses the biological effects and mechanisms of action of MSC transplantation in COPD, and highlights the foundation that MSCs provide for novel therapeutic approaches in COPD.

  6. Untangling nociceptive, neuropathic and neuroplastic mechanisms underlying the biological domain of back pain.

    PubMed

    Hush, Julia M; Stanton, Tasha R; Siddall, Philip; Marcuzzi, Anna; Attal, Nadine

    2013-05-01

    SUMMARY Current clinical practice guidelines advocate a model of diagnostic triage for back pain, underpinned by the biopsychosocial paradigm. However, limitations of this clinical model have become apparent: it can be difficult to classify patients into the diagnostic triage categories; patients with 'nonspecific back pain' are clearly not a homogenous group; and mean effects of treatments based on this approach are small. In this article, it is proposed that the biological domain of the biopsychosocial model needs to be reconceptualized using a neurobiological mechanism-based approach. Recent evidence about nociceptive and neuropathic contributors to back pain is outlined in the context of maladaptive neuroplastic changes of the somatosensory system. Implications for clinical practice and research are discussed.

  7. Studying chemical reactions in biological systems with MBN Explorer: implementation of molecular mechanics with dynamical topology

    NASA Astrophysics Data System (ADS)

    Sushko, Gennady B.; Solov'yov, Ilia A.; Verkhovtsev, Alexey V.; Volkov, Sergey N.; Solov'yov, Andrey V.

    2016-01-01

    The concept of molecular mechanics force field has been widely accepted nowadays for studying various processes in biomolecular systems. In this paper, we suggest a modification for the standard CHARMM force field that permits simulations of systems with dynamically changing molecular topologies. The implementation of the modified force field was carried out in the popular program MBN Explorer, and, to support the development, we provide several illustrative case studies where dynamical topology is necessary. In particular, it is shown that the modified molecular mechanics force field can be applied for studying processes where rupture of chemical bonds plays an essential role, e.g., in irradiation- or collision-induced damage, and also in transformation and fragmentation processes involving biomolecular systems. Contribution to the Topical Issue "COST Action Nano-IBCT: Nano-scale Processes Behind Ion-Beam Cancer Therapy", edited by Andrey V. Solov'yov, Nigel Mason, Gustavo Garcia and Eugene Surdutovich.

  8. Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches.

    PubMed

    Denning, Denise; Roos, Wouter H

    2016-09-02

    The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a defined microenvironment has also garnered deep insight into the engineering mechanisms existing within the cell. This review presents recent experimental findings on the influence of several parameters of the extracellular environment on cell behavior and fate, such as substrate topography, stiffness, chemistry and charge. In addition, the use of synthetic environments to measure physical properties of the reconstituted cytoskeleton and their interaction with intracellular proteins such as molecular motors is discussed, which is relevant for understanding cell migration, division and structural integrity, as well as intracellular transport. Insight is provided regarding the next steps to be taken in this interdisciplinary field, in order to achieve the global aim of artificially directing cellular response.

  9. Shear strength characteristics of mechanically biologically treated municipal solid waste (MBT-MSW) from Bangalore

    SciTech Connect

    Sivakumar Babu, G.L.; Lakshmikanthan, P.; Santhosh, L.G.

    2015-05-15

    Highlights: • Shear strength properties of mechanically biologically treated municipal solid waste. • Effect of unit weight and particle size on the shear strength of waste. • Effect of particle size on the strength properties. • Stiffness ratio and the strength ratio of MSW. - Abstract: Strength and stiffness properties of municipal solid waste (MSW) are important in landfill design. This paper presents the results of comprehensive testing of shear strength properties of mechanically biologically treated municipal solid waste (MBT-MSW) in laboratory. Changes in shear strength of MSW as a function of unit weight and particle size were investigated by performing laboratory studies on the MSW collected from Mavallipura landfill site in Bangalore. Direct shear tests, small scale and large scale consolidated undrained and drained triaxial tests were conducted on reconstituted compost reject MSW samples. The triaxial test results showed that the MSW samples exhibited a strain-hardening behaviour and the strength of MSW increased with increase in unit weight. Consolidated drained tests showed that the mobilized shear strength of the MSW increased by 40% for a unit weight increase from 7.3 kN/m{sup 3} to 10.3 kN/m{sup 3} at 20% strain levels. The mobilized cohesion and friction angle ranged from 5 to 9 kPa and 8° to 33° corresponding to a strain level of 20%. The consolidated undrained tests exhibited reduced friction angle values compared to the consolidated drained tests. The friction angle increased with increase in the unit weight from 8° to 55° in the consolidated undrained tests. Minor variations were found in the cohesion values. Relationships for strength and stiffness of MSW in terms of strength and stiffness ratios are developed and discussed. The stiffness ratio and the strength ratio of MSW were found to be 10 and 0.43.

  10. Physical activity and postmenopausal breast cancer: proposed biologic mechanisms and areas for future research.

    PubMed

    Neilson, Heather K; Friedenreich, Christine M; Brockton, Nigel T; Millikan, Robert C

    2009-01-01

    Convincing evidence now supports a probable preventive role for physical activity in postmenopausal breast cancer. The mechanisms by which long-term physical activity affect risk, however, remain unclear. The aims of this review were to propose a biological model whereby long-term physical activity lowers postmenopausal breast cancer risk and to highlight gaps in the epidemiologic literature. To address the second aim, we summarized epidemiologic literature on 10 proposed biomarkers, namely, body mass index (BMI), estrogens, androgens, sex hormone binding globulin, leptin, adiponectin, markers of insulin resistance, tumor necrosis factor-alpha, interleukin-6, and C-reactive protein, in relation to postmenopausal breast cancer risk and physical activity, respectively. Associations were deemed "convincing," "probable," "possible," or "hypothesized" using set criteria. Our proposed biological model illustrated the co-occurrence of overweight/obesity, insulin resistance, and chronic inflammation influencing cancer risk through interrelated mechanisms. The most convincing epidemiologic evidence supported associations between postmenopausal breast cancer risk and BMI, estrogens, and androgens, respectively. In relation to physical activity, associations were most convincing for BMI, estrone, insulin resistance, and C-reactive protein. Only BMI and estrone were convincingly (or probably) associated with both postmenopausal breast cancer risk and physical activity. There is a need for prospective cohort studies relating the proposed biomarkers to cancer risk and for long-term exercise randomized controlled trials comparing biomarker changes over time, specifically in postmenopausal women. Future etiologic studies should consider interactions among biomarkers, whereas exercise trials should explore exercise effects independently of weight loss, different exercise prescriptions, and effects on central adiposity.

  11. A mechanism for biologically-induced iodine emissions from sea-ice

    NASA Astrophysics Data System (ADS)

    Saiz-Lopez, A.; Blaszczak-Boxe, C. S.; Carpenter, L. J.

    2015-04-01

    Ground- and satellite-based measurements have reported high concentrations of iodine monoxide (IO) in coastal Antarctica. The sources of such a large iodine burden in the coastal Antarctic atmosphere remain unknown. We propose a mechanism for iodine release from sea-ice based on the premise that micro-algae are the primary source of iodine emissions in this environment. The emissions are triggered by the biological production of iodide (I-) and hypoiodous acid (HOI) from micro-algae (contained within and underneath sea-ice) and their diffusion through sea-ice brine channels, to accumulate in the quasi-liquid layer (QLL) on the surface of sea-ice. Prior to reaching the QLL, the diffusion timescale of iodine within sea-ice is depth-dependent. The QLL is also a vital component of the proposed mechanism as it enhances the chemical kinetics of iodine-related reactions, which allows for the efficient release of iodine to the polar boundary layer. We suggest iodine is released to the atmosphere via 3 possible pathways: (1) emitted from the QLL and then transported throughout snow atop sea-ice, to be released to the atmosphere, (2) released directly from the QLL to the atmosphere in regions of sea-ice that are not covered with snowpack; or (3) emitted to the atmosphere directly through fractures in the sea-ice pack. To investigate the proposed biology-ice-atmosphere coupling at coastal Antarctica we use a multiphase model that incorporates the transport of iodine species, via diffusion, at variable depths, within brine channels of sea-ice. Model simulations were conducted to interpret observations of elevated springtime IO in the coastal Antarctic, around the Weddell Sea. The results show that the levels of inorganic iodine (i.e., I2, IBr, ICl) released from sea-ice through this mechanism could account for the observed IO concentrations during this timeframe. The model results also indicate that iodine may trigger the catalytic release of bromine from sea-ice through phase

  12. Genetic, molecular and physiological mechanisms involved in human obesity: Society for Endocrinology Medal Lecture 2012.

    PubMed

    Farooqi, Sadaf I

    2015-01-01

    The health consequences of obesity represent one of the major public health challenges of our time. Whilst the role of environmental drivers such as reduced physical activity and increased food intake is widely acknowledged, the importance of biological factors which influence individual variation in weight is less readily recognised. Considerable evidence suggests that genetic factors influence a person's weight in a given environment and that these genetic influences are more potent at the extremes of the body mass index (BMI) distribution. The discovery that genetic disruption of certain pathways can lead to severe obesity has informed our current understanding of how body weight is regulated by brain circuits that regulate appetite and energy expenditure. These studies provide a framework for investigating patients and ultimately may guide the development of more rational-targeted therapies for genetically susceptible individuals with severe obesity.

  13. Rapid and reversible responses to IVIG in autoimmune neuromuscular diseases suggest mechanisms of action involving competition with functionally important autoantibodies

    PubMed Central

    Berger, Melvin; McCallus, Daniel E; Lin, Cindy Shin-Yi

    2013-01-01

    Intravenous immunoglobulin (IVIG) is widely used in autoimmune neuromuscular diseases whose pathogenesis is undefined. Many different effects of IVIG have been demonstrated in vitro, but few studies actually identify the mechanism(s) most important in vivo. Doses and treatment intervals are generally chosen empirically. Recent studies in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy show that some effects of IVIG are readily reversible and highly dependent on the serum IgG level. This suggests that in some autoantibody-mediated neuromuscular diseases, IVIG directly competes with autoantibodies that reversibly interfere with nerve conduction. Mechanisms of action of IVIG which most likely involve direct competition with autoantibodies include: neutralization of autoantibodies by anti-idiotypes, inhibition of complement deposition, and increasing catabolism of pathologic antibodies by saturating FcRn. Indirect immunomodulatory effects are not as likely to involve competition and may not have the same reversibility and dose-dependency. Pharmacodynamic analyses should be informative regarding most relevant mechanism(s) of action of IVIG as well as the role of autoantibodies in the immunopathogenesis of each disease. Better understanding of the role of autoantibodies and of the target(s) of IVIG could lead to more efficient use of this therapy and better patient outcomes. PMID:24200120

  14. Are immunological mechanisms involved in colon cancer and are they possible markers for biotherapy improvement?

    PubMed

    Berghella, Anna Maria; Contasta, Ida; Pellegrini, Patrizia; Del Beato, Tiziana; Adorno, Domenico

    2006-10-01

    This paper focuses on our data on colon cancer patients. Our overall results lead us to believe that the suppressive effect of specific cytokines in colon cancer patients alters the functionality of TH1 and TH2 subsets of CD4+ T-cells, with an expansion of TH2 cells and a malfunctioning of TH1 cells. This immunological disregulation appears to increase with stage progression, suggesting a direct role in the mechanisms that allow the tumour to locate and expand within the host. It is also clear that in order to identify disease markers and generate an in vivo immune response that corrects the imbalance between TH1 and TH2 cells, we need to understand how tumour mechanisms cause this imbalance to begin with.

  15. Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

    PubMed Central

    Berrendero, Fernando; Robledo, Patricia; Trigo, José Manuel; Martín-García, Elena; Maldonado, Rafael

    2010-01-01

    Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

  16. Discovery of a Biological Mechanism of Active Transport through the Tympanic Membrane to the Middle Ear

    PubMed Central

    Kurabi, Arwa; Pak, Kwang K.; Bernhardt, Marlen; Baird, Andrew; Ryan, Allen F.

    2016-01-01

    Otitis media (OM) is a common pediatric disease for which systemic antibiotics are often prescribed. While local treatment would avoid the systemic treatment side-effects, the tympanic membrane (TM) represents an impenetrable barrier unless surgically breached. We hypothesized that the TM might harbor innate biological mechanisms that could mediate trans-TM transport. We used two M13-bacteriophage display biopanning strategies to search for mediators of trans-TM transport. First, aliquots of linear phage library displaying 1010th 12mer peptides were applied on the TM of rats with active bacterial OM. The middle ear (ME) contents were then harvested, amplified and the preparation re-applied for additional rounds. Second, the same naïve library was sequentially screened for phage exhibiting TM binding, internalization and then transit. Results revealed a novel set of peptides that transit across the TM to the ME in a time and temperature dependent manner. The peptides with highest transport capacities shared sequence similarities. Historically, the TM was viewed as an impermeable barrier. However, our studies reveal that it is possible to translocate peptide-linked small particles across the TM. This is the first comprehensive biopanning for the isolation of TM transiting peptidic ligands. The identified mechanism offers a new drug delivery platform into the ME. PMID:26946957

  17. An optofluidic mechanical system for elasticity measurement of thin biological tissues.

    PubMed

    Cha, Chaenyung; Oh, Jonghyun

    2013-05-01

    As dura mater has an anisotropic fibrous structure and exists under wet and dynamic stretching conditions in the brain, its mechanical properties have not yet been properly investigated. Here we developed a fluid-assisted mechanical system integrated with a photonic sensor and a pressure sensor in order to measure the elasticity of the dura mater. Porcine dura mater sample was loaded as a stretched diaphragm into a liquid chamber to mimic the in vivo condition. Increasing the flow rate of saline solution into the chamber swelled and deformed the dura mater. The micron-scale deflection of the dura mater was optically detected by the photonic sensor. Fluid pressure and deflection values were then used to calculate the elastic modulus. The average elastic modulus of the porcine dura mater was 31.14 MPa. We further measured the elasticity of a well-known material to further validate the system. We expect that this optofluidic system developed in this study will be useful to measure the elasticity of a variety of thin biological tissues.

  18. Elucidating the mechanisms of cooperative calcium-calmodulin interactions: a structural systems biology approach

    PubMed Central

    Valeyev, Najl V; Bates, Declan G; Heslop-Harrison, Pat; Postlethwaite, Ian; Kotov, Nikolay V

    2008-01-01

    Background Calmodulin is an important multifunctional molecule that regulates the activities of a large number of proteins in the cell. Calcium binding induces conformational transitions in calmodulin that make it specifically active to particular target proteins. The precise mechanisms underlying calcium binding to calmodulin are still, however, quite poorly understood. Results In this study, we adopt a structural systems biology approach and develop a mathematical model to investigate various types of cooperative calcium-calmodulin interactions. We compare the predictions of our analysis with physiological dose-response curves taken from the literature, in order to provide a quantitative comparison of the effects of different mechanisms of cooperativity on calcium-calmodulin interactions. The results of our analysis reduce the gap between current understanding of intracellular calmodulin function at the structural level and physiological calcium-dependent calmodulin target activation experiments. Conclusion Our model predicts that the specificity and selectivity of CaM target regulation is likely to be due to the following factors: variations in the target-specific Ca2+ dissociation and cooperatively effected dissociation constants, and variations in the number of Ca2+ ions required to bind CaM for target activation. PMID:18518982

  19. Mechanically robust, rapidly actuating, and biologically functionalized macroporous poly(N-isopropylacrylamide)/silk hybrid hydrogels.

    PubMed

    Gil, Eun Seok; Park, Sang-Hyug; Tien, Lee W; Trimmer, Barry; Hudson, Samuel M; Kaplan, David L

    2010-10-05

    A route toward mechanically robust, rapidly actuating, and biologically functionalized polymeric actuators using macroporous soft materials is described. The materials were prepared by combining silk protein and a synthetic polymer (poly(N-isopropylacrylamide) (PNIAPPm)) to form interpenetrating network materials and macroporous structures by freeze-drying, with hundreds of micrometer diameter pores and exploiting the features of both polymers related to dynamic materials and structures. The chemically cross-linked PNIPAAm networks provided stimuli-responsive features, while the silk interpenetrating network formed by inducing protein β-sheet crystallinity in situ for physical cross-links provided material robustness, improved expansion force, and enzymatic degradability. The macroporous hybrid hydrogels showed enhanced thermal-responsive properties in comparison to pure PNIPAAm hydrogels, nonporous silk/PNIPAAm hybrid hydrogels, and previously reported macroporous PNIPAAm hydrogels. These new systems reach near equilibrium sizes in shrunken/swollen states in less than 1 min, with the structural features providing improved actuation rates and stable oscillatory properties due to the macroporous transport and the mechanically robust silk network. Confocal images of the hydrated hydrogels around the lower critical solution temperature (LCST) revealed macropores that could be used to track changes in the real time morphology upon thermal stimulus. The material system transformed from a macroporous to a nonporous structure upon enzymatic degradation. To extend the utility of the system, an affinity platform for a switchable or tunable system was developed by immobilizing biotin and avidin on the macropore surfaces.

  20. A mechanism for biologically-induced iodine emissions from sea-ice

    NASA Astrophysics Data System (ADS)

    Boxe, C.

    2015-12-01

    Ground- and satellite-based measurements reported high concentrations of iodine monoxide (IO) in coastal Antarctica. The sources of such a large iodine burden in the coastal Antarctic atmosphere remain unknown. We propose a mechanism for iodine release from sea-ice based on the premise that micro-algae are the primary source of iodine emissions in this environment. The emissions are triggered by the biological production of iodide (I-) and hypoiodous acid (HOI) from micro-algae (contained within and underneath sea-ice) and their diffusion through sea-ice brine channels, to accumulate in a thin brine layer (BL) on the surface of sea-ice. Prior to reaching the BL, the diffusion timescale of iodine within sea-ice is depth-dependent. The BL is also a vital component of the proposed mechanism as it enhances the chemical kinetics of iodine-related reactions, which allows for the efficient release of iodine to the polar boundary layer. We suggest iodine is released to the atmosphere via 3 possible pathways: (1) emitted from the BL and then transported throughout snow atop sea-ice, to be released to the atmosphere; (2) released directly from the BL to the atmosphere in regions of sea-ice that are not covered with snowpack; or (3) emitted to the atmosphere directly through fractures in the sea-ice pack. To investigate the proposed biology-ice-atmosphere coupling at coastal Antarctica we use a multiphase model that incorporates the transport of iodine species, via diffusion, at variable depths, within brine channels of sea-ice. Model simulations were conducted to interpret observations of elevated springtime IO in the coastal Antarctic, around the Weddell Sea. While a lack of experimental and observational data adds uncertainty to the model predictions, nevertheless the results show that the levels of inorganic iodine (i.e., I2, IBr, ICl) released from sea-ice through this mechanism could account for the observed IO concentrations during this timeframe. The model results

  1. On a Class of Laplace Inverses Involving Doubly-Nested Square Roots and their Applications in Continuum Mechanics

    DTIC Science & Technology

    2010-01-01

    Micropolar fluids Dipolar fluids a b s t r a c t The exact inverses of a class of Laplace transforms involving doubly-nested square roots and two branch...mechanics, for a micropolar fluid is determined. Published by Elsevier Ltd. 1. Introduction and problem formulation Using the Laplace transform, we...to the case of micropolar fluids, the theory of which was formulated by Eringen (1966). In doing so, we also extend the re- sults of Jordan et al

  2. Involvement of three mechanisms in the alteration of cytokine responses by sodium methyldithiocarbamate

    SciTech Connect

    Pruett, Stephen B. . E-mail: spruet@LSUHSC.edu; Fan, Ruping; Zheng, Qiang

    2006-06-01

    Sodium methyldithiocarbamate (SMD) is the third most abundantly used conventional pesticide in the U.S. We recently reported that it alters the induction of cytokine production mediated though Toll-like receptor (TLR) 4 at relevant dosages in mice. Its chemical properties and evidence from the literature suggest thee potential mechanisms of action for this compound. It could either act as a free radical scavenger (by means of its free S{sup -}group) or promote oxidation by breaking down to form methylisothiocyanate, which can deplete glutathione. It is a potent copper chelator and may affect the availability of copper to a number of copper-dependent enzymes (including some signaling molecules). SMD induces a classical neuroendocrine stress response characterized by elevated serum corticosterone concentrations, which could affect cytokine production. Although each of these mechanisms could potentially contribute to altered cytokine responses, direct evidence is lacking. The present study was conducted to obtain such evidence. The role of redox balance was investigated by pretreating mice with N-acetyl cysteine (NAC), which increases cellular glutathione concentrations, before administration of SMD. NAC exacerbated the SMD-induced suppression of IL-12 and the SMD-induced enhancement of IL-10 in the serum. The role of copper chelation was investigated by comparing the effects of SMD with an equimolar dose to SMD that was administered in the form of a copper chelation complex. Addition of copper significantly decreased the action of SMD on IL-12 production but not on IL-10 production. The role of the stress response was investigated by pretreating mice with antagonists of corticosterone and catecholamines. This treatment partially prevented the action of SMD on IL-10 and IL-12 in the peritoneal fluid. The results suggest that all of the proposed mechanisms have some role in the alteration of cytokine production by SMD.

  3. The principal motions involved in the coupling mechanism of the recovery stroke of the myosin motor.

    SciTech Connect

    Mesentean, Sidonia; Koppole, Sampath; Smith, Jeremy C; Fischer, S.

    2007-03-01

    Muscle contraction is driven by a cycle of conformational changes in the myosin II head. After myosin binds ATP and releases from the actin fibril, myosin prepares for the next power stroke by rotating back the converter domain that carries the lever arm by 60{sup o}. This recovery stroke is coupled to the activation of myosin ATPase by a mechanism that is essential for an efficient motor cycle. The mechanics of this coupling have been proposed to occur via two distinct and successive motions of the two helices that hold the converter domain: in a first phase a seesaw motion of the relay helix, followed by a piston-like motion of the SH1 helix in a second phase. To test this model, we have determined the principal motions of these structural elements during equilibrium molecular dynamics simulations of the crystallographic end states of the recovery-stroke by using principal component analysis. This reveals that the only principal motions of these two helices that make a large-amplitude contribution towards the conformational change of the recovery stroke are indeed the predicted seesaw and piston motions. Moreover, the results demonstrate that the seesaw motion of the relay helix dominates in the dynamics of the pre-recovery stroke structure, but not in the dynamics of the post-recovery stroke structure, and vice versa for the piston motion of the SH1 helix. This is consistent with the order of the proposed two-phase model for the coupling mechanism of the recovery stroke. Molecular movies of these principal motions are available at http://www.iwr.uni-heidelberg.de/groups/biocomp/fischer.

  4. GR-127935-sensitive mechanism mediating hypotension in anesthetized rats: are 5-HT5B receptors involved?

    PubMed

    Sánchez-Maldonado, Carolina; López-Sánchez, Pedro; Anguiano-Robledo, Liliana; Leopoldo, Marcello; Lacivita, Enza; Terrón, José A

    2015-04-01

    The 5-HT1B/1D receptor antagonist, GR-127935, inhibits hypotensive responses produced by the 5-HT1A, 5-HT1B/1D and 5-HT7 receptor agonist, and 5-HT5A/5B receptor ligand, 5-carboxamidotryptamine (5-CT), in rats. This work further characterized the above mechanism using more selective 5-HT1B and 5-HT1D receptor antagonists. Also, expression of 5-HT5A and 5-HT5B receptor mRNAs in blood vessels was searched by reverse transcription polymerase chain reaction. Decreases in diastolic blood pressure induced by 5-CT (0.001-10 μg/kg, intravenously) were analyzed in anesthetized rats that had received intravenous vehicle (1 mL/kg), SB-224289 (5-HT1B antagonist; 0.3 and 1.0 mg/kg), BRL15572 (5-HT1D antagonist; 0.3 and 1.0 mg/kg), SB-224289 + BRL15572 (0.3 mg/kg, each), or SB-224289 + BRL15572 (0.3 mg/kg, each) + GR-127935 (1 mg/kg). Because only the latter treatment inhibited 5-CT-induced hypotension, suggestive of a mechanism unrelated to 5-HT1B/1D receptors, the effects of antagonists/ligands at 5-HT5A (SB-699551, 1 mg/kg), 5-HT6 (SB-399885, 1 mg/kg), and 5-HT1B/1D/5A/5B/7 receptors (ergotamine, 0.1 mg/kg) on 5-CT-induced hypotension were tested. Interestingly, only ergotamine blocked 5-CT-induced responses; this effect closely paralleled that of SB-224289 + BRL-15572 + GR-127935. Neither did ergotamine nor GR-127935 inhibit hypotensive responses induced by the 5-HT7 receptor agonist, LP-44. Faint but clear bands corresponding to 5-HT5A and 5-HT5B receptor mRNAs in aorta and mesenteric arteries were detected. Results suggest that the GR-127935-sensitive mechanism mediating hypotension in rats is unrelated to 5-HT1B, 5-HT1D, 5-HT5A, 5-HT6, and 5-HT7 receptors. This mechanism, however, resembles putative 5-HT5B receptors.

  5. A novel mechanism involved in the coupling of mitochondrial biogenesis to oxidative phosphorylation

    PubMed Central

    Ostojić, Jelena; Rago, Jean-Paul; Dujardin, Geneviève

    2014-01-01

    Mitochondria are essential organelles that are central to a multitude of cellular processes, including oxidative phosphorylation (OXPHOS), which produces most of the ATP in animal cells. Thus it is important to understand not only the mechanisms and biogenesis of this energy production machinery but also how it is regulated in both physiological and pathological contexts. A recent study by Ostojić et al. [Cell Metabolism (2013) 18, 567-577] has uncovered a regulatory loop by which the biogenesis of a major enzyme of the OXPHOS pathway, the respiratory complex III, is coupled to the energy producing activity of the mitochondria. PMID:28357209

  6. Mechanism of silver staining of histones: evidence for involvement of clustered lysine residues.

    PubMed

    Kurosaki, T; Tsutsui, K; Tsutsui, K; Aoyama, K; Oda, T

    1984-09-17

    Pretreatment of histones with formaldehyde markedly enhances the formation of metalic silver from ammoniacal silver ion. The rate of silver reduction was determined with different histones by spectrophotometric measurement of colloidal silver stabilized in solution, and the apparent reactivity thus determined was found to be in the decreasing order of H1 greater than H2B greater than H2A greater than H3 greater than H4. Involvement of lysine residues was suggested since this order coincides with that of lysine content of these histones. However, the exceptionally high reactivity of histone H1 can be explained only when greater contribution of clustered lysine residues is assumed. Amino group modification and tryptic digestion studies of H1 corroborated this assumption.

  7. Involvement of TACE in colon inflammation: a novel mechanism of regulation via SIRT-1 activation.

    PubMed

    Sharma, Manoranjan; Mohapatra, Jogeswar; Wagh, Akshaya; Patel, Hiren M; Pandey, Dheerendra; Kadam, Shekhar; Argade, Anil; Deshpande, Shrikalp S; Shah, Gourang B; Chatterjee, Abhijit; Jain, Mukul R

    2014-03-01

    TNF-α converting enzyme (TACE) processes the membrane TNF-α to release the bioactive soluble TNF-α. Several evidences suggest the involvement of TNF-α and TACE in inflammatory bowel disease (IBD). Tissue inhibitor of metalloproteinase (TIMP)-3, an endogenous inhibitor of TACE, is positively associated with silent information regulator (SIRT)-1. We aimed to study the expression of TACE, TIMP-3 and SIRT-1 at different stages of colitis and how TACE is regulated in response to SIRT-1 activation. Acute colitis was induced by 3.5% dextran sulfate sodium (DSS) in drinking water for 5days and levels of cytokines and mRNA expression of TACE, TIMP-3 and SIRT-1 were measured in colon at different time intervals. Next, the effect of SIRT-1 activator (resveratrol) or a selective TACE inhibitor (compound 11p) treatment was evaluated. Elevated levels of TNF-α, interleukin (IL)-6, IL-1β, interferon (IFN)-γ and IL-17 were observed during DSS exposure phase which restored to the normal level after DSS removal. A significant increase in TACE and suppression in TIMP-3 and SIRT-1 mRNA level was observed during DSS exposure phase which reverts back to normal towards the remission phase. Treatment with resveratrol significantly elevated SIRT-1 and TIMP-3 and suppressed TACE mRNA expression and was associated with amelioration of disease. Furthermore, treatment with selective TACE inhibitor significantly suppressed body weight loss, disease activity index, colonic myeloperoxidase activity and the elevated levels of cytokines after DSS challenge. These results strongly emphasize the involvement of TACE in colon inflammation and inhibition of TACE directly or indirectly via SIRT-1 activation ameliorates colitis.

  8. Mechanisms of Prescription Drug Diversion Among Drug-Involved Club- and Street-Based Populations

    PubMed Central

    Inciardi, James A.; Surratt, Hilary L.; Kurtz, Steven P.; Cicero, Theodore J.

    2010-01-01

    Objective Prescription drug diversion involves the unlawful channeling of regulated pharmaceuticals from legal sources to the illicit marketplace, and can occur along all points in the drug delivery process, from the original manufacturing site to the wholesale distributor, the physician's office, the retail pharmacy, or the patient. However, empirical data on diversion are limited. Method In an attempt to develop a better understanding of how specific drug-using populations are diverting prescription opioids and other medications, or obtaining controlled drugs that have already been diverted, qualitative interviews and focus group data were collected on four separate populations of prescription drug abusers in Miami, Florida—club drug users, street-based illicit drug users, methadone maintenance patients, and HIV positive individuals who abuse and/or divert drugs. Results Sources of abused prescription drugs cited by focus group participants were extremely diverse, including their physicians and pharmacists; parents and relatives; “doctor shopping”; leftover supplies following an illness or injury; personal visits to Mexico, South America and the Caribbean; prescriptions intended for the treatment of mental illness; direct sales on the street and in nightclubs; pharmacy and hospital theft; through friends or acquaintances; under-the-door apartment flyers advertising telephone numbers to call; and “stealing from grandma's medicine cabinet.” Conclusion While doctor shoppers, physicians and the Internet receive much of the attention regarding diversion, the data reported in this paper suggest that there are numerous active street markets involving patients, Medicaid recipients and pharmacies as well. In addition, there are other data which suggest that the contributions of residential burglaries, pharmacy robberies and thefts, and “sneak thefts” to the diversion problem may be understated. PMID:17305688

  9. Modulation of a voltage-gated Na+ channel by sevoflurane involves multiple sites and distinct mechanisms.

    PubMed

    Barber, Annika F; Carnevale, Vincenzo; Klein, Michael L; Eckenhoff, Roderic G; Covarrubias, Manuel

    2014-05-06

    Halogenated inhaled general anesthetic agents modulate voltage-gated ion channels, but the underlying molecular mechanisms are not understood. Many general anesthetic agents regulate voltage-gated Na(+) (NaV) channels, including the commonly used drug sevoflurane. Here, we investigated the putative binding sites and molecular mechanisms of sevoflurane action on the bacterial NaV channel NaChBac by using a combination of molecular dynamics simulation, electrophysiology, and kinetic analysis. Structural modeling revealed multiple sevoflurane interaction sites possibly associated with NaChBac modulation. Electrophysiologically, sevoflurane favors activation and inactivation at low concentrations (0.2 mM), and additionally accelerates current decay at high concentrations (2 mM). Explaining these observations, kinetic modeling suggests concurrent destabilization of closed states and low-affinity open channel block. We propose that the multiple effects of sevoflurane on NaChBac result from simultaneous interactions at multiple sites with distinct affinities. This multiple-site, multiple-mode hypothesis offers a framework to study the structural basis of general anesthetic action.

  10. Microglial cell migration stimulated by ATP and C5a involve distinct molecular mechanisms

    PubMed Central

    Miller, Aaron M.; Stella, Nephi

    2009-01-01

    Microglial cells, the macrophages of the brain, play an essential role in the propagation of neuroinflammation. Increased microglial cell migration in response to specific chemoattractants has been documented, but less is known about the differences between these stimuli and the signal transduction pathways that mediate their effects. Current methods to measure cell migration are often labor-intensive and rely on the manual counting of cell number, so more efficient and objective methods are needed. Here we present an improved and higher-throughput Boyden Chamber technique that measures microglial cell migration by using DRAQ5, a nuclear dye that emits in the near-infrared. Out of a panel of chemoattractants tested, we found that ATP and C5a potently stimulate the migration of mouse primary microglial cells. The stimulatory effects of ATP and C5a displayed significant additivity, suggesting that each chemoattractant stimulated migration through independent molecular mechanisms. Accordingly, we found key differences in these responses: ATP stimulated a combination of both chemokinesis and chemotaxis, and this response was mediated by the ROCK signaling pathway; whereas C5a stimulated only chemotaxis and this response was mediated by the Rac1 signaling pathway. Finally, we found that functional PI3-kinase is only required for random basal microglial cell migration. Thus, our results show that distinct non-overlapping signal transduction pathways control different modes of microglial cell migration and suggest that the targeting of these distinct molecular mechanisms should modulate different aspects of neuroinflammation propagation. PMID:19053059

  11. Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving CCK.

    PubMed

    Jeon, Tae-Il; Seo, Young-Kyo; Osborne, Timothy F

    2011-08-15

    T2Rs (bitter taste-sensing type 2 receptors) are expressed in the oral cavity to prevent ingestion of dietary toxins through taste avoidance. They are also expressed in other cell types, including gut enteroendocrine cells, where their physiological role is enigmatic. Previously, we proposed that T2R-dependent CCK (cholecystokinin) secretion from enteroendocrine cells limits absorption of dietary toxins, but an active mechanism was lacking. In the present study we show that T2R signalling activates ABCB1 (ATP-binding cassette B1) in intestinal cells through a CCK signalling mechanism. PTC (phenylthiocarbamide), an agonist for the T2R38 bitter receptor, increased ABCB1 expression in both intestinal cells and mouse intestine. PTC induction of ABCB1 was decreased by either T2R38 siRNA (small interfering RNA) or treatment with YM022, a gastrin receptor antagonist. Thus gut ABCB1 is regulated through signalling by CCK/gastrin released in response to PTC stimulation of T2R38 on enteroendocrine cells. We also show that PTC increases the efflux activity of ABCB1, suggesting that T2R signalling limits the absorption of bitter tasting/toxic substances through modulation of gut efflux membrane transporters.

  12. Mechanical Properties Involved in the Micro-forming of Ultra-thin Stainless Steel Sheets

    NASA Astrophysics Data System (ADS)

    Pham, Cong-Hanh; Thuillier, Sandrine; Manach, Pierre-Yves

    2015-08-01

    The objective of this paper is to characterize the mechanical behavior of an ultra-thin stainless steel, of 0.15-mm thickness, that is commonly used in the manufacturing of miniature connectors. The main focus is the relationship between some microstructural features, like grain size and surface roughness, and the macroscopic mechanical behavior investigated in uniaxial tension and simple shear. In tension, adaptations to the very small sheet thickness, in order to hold the specimen under the grips, are presented. Yield stress, initial elastic modulus, and evolution of the loading-unloading slope with plastic deformation were evaluated. Moreover, the kinematic contribution to the hardening was characterized by monotonic and cyclic simple shear test and reproduced by a mixed hardening law implemented in Abaqus finite element code. Then, the evolution of surface roughness with plastic strain, both in tension and simple shear, was analyzed. It was shown that in the case of an ultra-thin sheet, the stress levels, calculated either from an average thickness or when considering the effect of the surface roughness, exhibit a significant difference. Finally, the influence of surface roughness on the fracture of a tensile specimen was also investigated.

  13. The principal motions involved in the coupling mechanism of the recovery stroke of the myosin motor

    SciTech Connect

    Mesentean, Sidonia; Koppole, Sampath; Smith, Jeremy C; Fischer, S.

    2006-12-01

    Muscle contraction is driven by a cycle of conformational changes in the myosin II head. After myosin binds ATP and releases from the actin fibril, myosin prepares for the next power stroke by rotating back the converter domain that carries the lever arm by {approx}60 degrees. This recovery stroke is coupled to the activation of myosin's ATPase by a mechanism that is essential for an efficient motor cycle. The mechanics of this coupling have been proposed to occur via two distinct and successive motions of the two helices that hold the converter domain: in a first phase a see-saw motion of the relay helix, followed by a piston/seesaw motion of the SH1 helix in a second phase. To test this model, we have determined the principal motions of these structural elements during equilibrium molecular dynamics simulations of the crystallographic end states of the recovery stroke by using Principal Component Analysis. This reveals that the only principal motions of these two helices that make a large amplitude contribution towards the conformational change of the recovery stroke are indeed the predicted seesaw and piston motions.

  14. Modulation of a voltage-gated Na+ channel by sevoflurane involves multiple sites and distinct mechanisms

    PubMed Central

    Barber, Annika F.; Carnevale, Vincenzo; Klein, Michael L.; Eckenhoff, Roderic G.; Covarrubias, Manuel

    2014-01-01

    Halogenated inhaled general anesthetic agents modulate voltage-gated ion channels, but the underlying molecular mechanisms are not understood. Many general anesthetic agents regulate voltage-gated Na+ (NaV) channels, including the commonly used drug sevoflurane. Here, we investigated the putative binding sites and molecular mechanisms of sevoflurane action on the bacterial NaV channel NaChBac by using a combination of molecular dynamics simulation, electrophysiology, and kinetic analysis. Structural modeling revealed multiple sevoflurane interaction sites possibly associated with NaChBac modulation. Electrophysiologically, sevoflurane favors activation and inactivation at low concentrations (0.2 mM), and additionally accelerates current decay at high concentrations (2 mM). Explaining these observations, kinetic modeling suggests concurrent destabilization of closed states and low-affinity open channel block. We propose that the multiple effects of sevoflurane on NaChBac result from simultaneous interactions at multiple sites with distinct affinities. This multiple-site, multiple-mode hypothesis offers a framework to study the structural basis of general anesthetic action. PMID:24753583

  15. Mechanisms involved in the antinociception induced by spinal administration of inosine or guanine in mice.

    PubMed

    de Oliveira, Enderson D; Schallenberger, Cristhine; Böhmer, Ana Elisa; Hansel, Gisele; Fagundes, Aécio C; Milman, Michael; Silva, Marcos D P; Oses, Jean P; Porciúncula, Lisiane O; Portela, Luís V; Elisabetsky, Elaine; Souza, Diogo O; Schmidt, André P

    2016-02-05

    It is well known that adenine-based purines exert multiple effects on pain transmission. Recently, we have demonstrated that guanine-based purines may produce some antinociceptive effects against chemical and thermal pain in mice. The present study was designed to investigate the antinociceptive effects of intrathecal (i.t.) administration of inosine or guanine in mice. Additionally, investigation into the mechanisms of action of these purines, their general toxicity and measurements of CSF purine levels were performed. Animals received an i.t. injection of vehicle (30mN NaOH), inosine or guanine (up to 600nmol) and submitted to several pain models and behavioural paradigms. Guanine and inosine produced dose-dependent antinociceptive effects in the tail-flick, hot-plate, intraplantar (i.pl.) glutamate, i.pl. capsaicin and acetic acid pain models. Additionally, i.t. inosine inhibited the biting behaviour induced by spinal injection of capsaicin and i.t. guanine reduced the biting behaviour induced by spinal injection of glutamate or AMPA. Intrathecal administration of inosine (200nmol) induced an approximately 115-fold increase on CSF inosine levels. This study provides new evidence on the mechanism of action of extracellular guanine and inosine presenting antinociceptive effects following spinal administration. These effects seem to be related, at least partially, to the modulation of A1 adenosine receptors.

  16. Inhibition of adrenomedullary catecholamine release by propranolol isomers and clonidine involving mechanisms unrelated to adrenoceptors.

    PubMed Central

    Orts, A.; Orellana, C.; Cantó, T.; Ceña, V.; González-García, C.; García, A. G.

    1987-01-01

    1 Transmural electrical stimulation (10 Hz, 40 V, 1 ms for 60s) increased total catecholamine secretion from perfused cat adrenal glands; this response was enhanced by neostigmine and inhibited by mecamylamine, suggesting that release of acetylcholine from splanchnic nerve terminals was stimulating nicotinic receptors and enhancing catecholamine secretion. 2 Isoprenaline, (-)-propranolol and (+)-propranolol (10(-7)-10(-5)M) inhibited the electrically-evoked secretory response by 40-70%; similar reductions were obtained with clonidine and yohimbine. Neither, (+)-propranolol nor (-)-propranolol inhibited K-evoked secretion from cat adrenals; in contrast, nimodipine potently inhibited it (IC50 = 24 nM). 3 Either, racemic propranolol or the (+)- or (-)-isomers (1-10 microM) equally inhibited [3H]-noradrenaline release evoked by nicotine or acetylcholine from cultured bovine adrenal chromaffin cells; clonidine (10 microM) inhibited secretion by 50% and yohimbine or isoprenaline did not affect it. 4 The results indicate that adrenomedullary catecholamine release evoked by splanchnic nerve stimulation is not modulated by alpha- or beta-adrenoceptors and suggest that propranolol may inhibit secretion by blocking ion fluxes through the acetylcholine receptor ionophore. Clonidine may inhibit secretion by this same mechanism, and/or by interfering with some intracellular event in the secretory mechanism. PMID:2827826