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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

    2015-01-01

    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. PMID:26667690

  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. PMID:26205204

  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. PMID:22639577

  4. 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.

  5. [Immunological mechanisms involved in pregnancy].

    PubMed

    Rico-Rosillo, María Guadalupe; Vega-Robledo, Gloria Bertha

    2012-05-01

    Pregnancy progresses through mechanisms that allow the embryo implantation and its development during gestation. Those mechanisms involve the immune cells that participate in the regulation of immune tolerance and response, as well as the protection conferred by Th2 cytokines and molecules expressed on trophoblast cells. Local factors expressed in the fetal interface as HLA-G, which inhibits the cytotoxicity of uterine natural killer cells and induces apoptosis of activated CD8 cells; transforming growth factor-beta, that induces tolerance, and uterine natural killer cells that are functionally different to the peripheral, as well as circulating progesterone and the glicodeline molecules that are important regulators of the immune response, also intervene in the process. From the conventional immunological point of view, pregnancy is a unique immune condition in which the fetus, semiallogenic, avoids being rejected immunologically by the mother, apparently by inducing a tolerance more than a sensitization PMID:23301425

  6. 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

  7. The Structural Biology of Enzymes Involved in Natural Product Glycosylation

    PubMed Central

    Singh, Shanteri; Phillips, George N.

    2012-01-01

    The glycosylation of microbial natural products often dramatically influences the biological and/or pharmacological activities of the parental metabolite. Over the past decade, crystal structures of several enzymes involved in the biosynthesis and attachment of novel sugars found appended to natural products have emerged. In many cases, these studies have paved the way to a better understanding of the corresponding enzyme mechanism of action and have served as a starting point for engineering variant enzymes to facilitate to production of differentially-glycosylated natural products. This review specifically summarizes the structural studies of bacterial enzymes involved in biosynthesis of novel sugar nucleotides. PMID:22688446

  8. [Mechanism of angiogenesis. Ocular involvement].

    PubMed

    Mocanu, Carmen

    2003-01-01

    Over the past several years, there has been important progress in the field of intrinsec mechanisms of ocular neovascularization. Immunohistological studies succeeded a better systematization of the factors that stimulates and inhibits this process. Their presence in different ocular normal structures, without any angiogenic activity, suggests a physiological balance between VEGF (vascular endothelial growth factor) with stimulatory effect on angiogenesis and PEDF (pigment epithelium derived factor) with inhibitory effect. It has been discussing the possibility of modification of physiological balance between VEGF and PEDF to induce the neovascularization process. The understanding of the physiopathological mechanisms of the substances implicated in inhibition of chorioretinal neovascularization makes to be real the expectations for the development of new treatments. PMID:15083677

  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. 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.

  11. Mechanisms underlying protective effects of trimetazidine on endothelial progenitor cells biological functions against H2O2-induced injury: involvement of antioxidation and Akt/eNOS signaling pathways.

    PubMed

    Wu, Qinqin; Qi, Benling; Liu, Yun; Cheng, Bei; Liu, Lihua; Li, Yuanyuan; Wang, Qian

    2013-05-01

    Trimetazidine (TMZ) is a widely used drug exerting cardioprotective effects against ischemic heart disease through a number of mechanisms in conditions of oxidative stress. However, there are few data regarding the effects of TMZ on endothelial lineage, especially endothelial progenitor cells (EPCs). Thus, we sought to investigate whether TMZ could protect EPCs against oxidative stress injury induced by H2O2 (100 µM) and the preliminary mechanisms involved in vitro. The results showed that pretreatment of EPCs with TMZ (10 µM) protected the proliferation, adhesion, migration, and apoptosis of EPCs against H2O2, accompanied by an increase in superoxide dismutase (SOD) activity, a decrease in malonaldehyde (MDA) content, and increases in eNOS, Akt phosphorylation, and NO production. These TMZ-mediated beneficial effects on EPCs could be attenuated by pre-incubation with the Akt inhibitor triciribine. In conclusion, the present study demonstrates that TMZ ameliorated H2O2-induced impairment of biological functions in EPCs with the involvement of antioxidation and Akt/eNOS signaling pathway. These findings suggest that TMZ mediating preservation of EPCs may contribute to its cardioprotective effects on ischemic heart disease. PMID:23528356

  12. [Placebo effect: clinical, biological and therapeutical involvements in depression].

    PubMed

    Gourion, D; Mouchabac, S

    2016-02-01

    The placebo effect is an excellent model for understanding the mechanisms underlying the interaction between a subjective and complex mental activity (beliefs, expectations, hopes, learning, patient-physician relationship, socio-cultural context .) with different neural and biological systems. Initially, research on the placebo effect has focused on the mechanisms of pain and analgesia. The cognitive processes of conditioning and reward anticipation (hope of a relief) were highlighted. The involvement of different neurobiological pathways has been clearly shown: endogenous opioids, CCK, dopaminergic pathways, endocannabinoids, immunological factors… More recently, the field has open towards new perspectives: depression and anxiety, motor disorders, immune system, endocrine system. Intensive research in the field emerges because of its fundamental implications in neuroscience research but also because of the ethical, clinical and therapeutical issues. Moreover, the placebo effect is considered as a main methodological mean issue in clinical trials that allows the demonstration of the efficacy and tolerance of new drugs. In the field of psychiatry, depression is a placebo highly-sensitive disorder: placebo response rates in clinical trials are of the order of 30 % to 40 %. The identification of biological markers of placebo response, such as neuroimaging and quantitative electroencephalography may lead to develop more efficient models in clinical research. PMID:26879253

  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. 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. PMID:22326084

  15. 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

  16. [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. PMID:25275846

  17. 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

  18. Enzymatic DNA oxidation: mechanisms and biological significance

    PubMed Central

    Xu, Guo-Liang; Walsh, Colum P.

    2014-01-01

    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. [BMB Reports 2014; 47(11): 609-618] PMID:25341925

  19. Glucan: mechanisms involved in its radioprotective effect

    SciTech Connect

    Patchen, M.L.; D'Alesandro, M.M.; Brook, I.; Blakely, W.F.; MacVittie, T.J.

    1987-01-01

    It has generally been accepted that most biologically derived agents that are radioprotective in the hemopoietic-syndrome dose range (eg, endotoxin, Bacillus Calmette Guerin, Corynebacterium parvum, etc) exert their beneficial properties by enhancing hemopoietic recovery and hence, by regenerating the host's ability to resist life-threatening opportunistic infections. However, using glucan as a hemopoietic stimulant/radioprotectant, the authors demonstrated the host resistance to opportunistic infection is enhanced in mice even prior to the detection of significant hemopoietic regeneration. This early enhanced resistance microbial invasion in glucan-treated irradiated mice could be correlated with enhanced and/or prolonged macrophage (but not granulocyte) function. These results suggest that early after irradiation glucan may mediate its radioprotection by enhancing resistance to microbial invasion via mechanisms not necessarily predicated on hemopoietic recovery. In addition, preliminary evidence suggests that glucan can also function as an effective free-radical scavenger. Because macrophages have been shown to selectively phagocytize and sequester glucan, the possibility that these specific cells may be protected by virtue of glucan's scavenging ability is also suggested.

  20. Glucan: mechanisms involved in its radioprotective effect

    SciTech Connect

    Patchen, M.L.; D'Alesandro, M.M.; Brook, I.; Blakely, W.F.; MacVittie, T.J.

    1987-08-01

    It has generally been accepted that most biologically derived agents that are radioprotective in the hemopoietic-syndrome dose range (eg, endotoxin, Bacillus Calmette Guerin, Corynebacterium parvum, etc) exert their beneficial properties by enhancing hemopoietic recovery and hence, by regenerating the host's ability to resist life-threatening opportunistic infections. However, using glucan as a hemopoietic stimulant/radioprotectant, we have demonstrated that host resistance to opportunistic infection is enhanced in these mice even prior to the detection of significant hemopoietic regeneration. This early enhanced resistance to microbial invasion in glucan-treated irradiated mice could be correlated with enhanced and/or prolonged macrophage (but not granulocyte) function. These results suggest that early after irradiation glucan may mediate its radioprotection by enhancing resistance to microbial invasion via mechanisms not necessarily predicated on hemopoietic recovery. In addition, preliminary evidence suggests that glucan can also function as an effective free-radical scavenger. Because macrophages have been shown to selectively phagocytize and sequester glucan, the possibility that these specific cells may be protected by virtue of glucan's scavenging ability is also suggested.

  1. Mechanical versus biological aortic valve replacement strategies.

    PubMed

    Reineke, D; Gisler, F; Englberger, L; Carrel, T

    2016-04-01

    Aortic valve replacement (AVR) is the most frequently performed procedure in valve surgery. The controversy about the optimal choice of the prosthetic valve is as old as the technique itself. Currently there is no perfect valve substitute available. The main challenge is to choose between mechanical and biological prosthetic valves. Biological valves include pericardial (bovine, porcine or equine) and native porcine bioprostheses designed in stented, stentless and sutureless versions. Homografts and pulmonary autografts are reserved for special indications and will not be discussed in detail in this review. We will focus on the decision making between artificial biological and mechanical prostheses, respectively. The first part of this article reviews guideline recommendations concerning the choice of aortic prostheses in different clinical situations while the second part is focused on novel strategies in the treatment of patients with aortic valve pathology. PMID:26678683

  2. Physiopathologic mechanisms involved in mare endometrosis.

    PubMed

    Rebordão, M R; Galvão, A; Szóstek, A; Amaral, A; Mateus, L; Skarzynski, D J; Ferreira-Dias, G

    2014-10-01

    Endometrosis is a degenerative chronic process, characterized by paramount fibrosis development in mare endometrium. This condition is one of the major causes of subfertility/infertility in mares. As in other organs, fibrosis might be a pathologic sequel of many chronic inflammatory diseases. However, aetiology and physiopathologic mechanisms involved in endometrial fibrosis are still controversial. This review presents new hypotheses based on our newest data. As the first line of innate immune defence, systemic neutrophils arrive in the uterus at mating or in the presence of pathogens. A novel paradigm is that neutrophils cast out their DNA in response to infectious stimuli and form neutrophil extracellular traps (NETs). We have shown that bacterial strains of Streptococcus zooepidemicus, Escherichia coli or Staphylococcus capitis, known to cause endometritis in mares were able to induce NETs release in vitro by equine PMN to different extents. An intriguing dilemma is the dual action of NETs. While NETs play a desirable role fighting micro-organisms in mare uterus, they may also contribute to endometrial fibrosis. A long-term in vitro exposure of mare endometrium explants to NETs components (myeloperoxidase, elastase and cathepsin G) up-regulated fibrosis markers TGFβ and Tissue inhibitor of metalloproteinase (TIMP-1). Also, pro-fibrotic cytokines regulated collagen deposition and fibrosis. Changes in expression of connective tissue growth factor (CTGF), interleukins (IL)1-α, IL-1β, IL-6 and receptors in endometrium with different degrees of fibrosis and/or inflammation were observed. A putative role of CTGF, IL and NETs components in endometrosis development should be considered. Additionally, we speculate that in sustained endometritis in mares, prostaglandins may not only cause early luteolysis or early pregnancy loss, but may also be related to endometrial fibrosis pathogenesis by stimulating collagen deposition. PMID:25277436

  3. Changes of trabecular bone under control of biologically mechanical mechanism

    NASA Astrophysics Data System (ADS)

    Wang, C.; Zhang, C. Q.; Dong, X.; Wu, H.

    2008-10-01

    In this study, a biological process of bone remodeling was considered as a closed loop feedback control system, which enables bone to optimize and renew itself over a lifetime. A novel idea of combining strain-adaptive and damage-induced remodeling algorithms at Basic Multicellular Unit (BMU) level was introduced. In order to make the outcomes get closer to clinical observation, the stochastic occurrence of microdamage was involved and a hypothesis that remodeling activation probability is related to the value of damage rate was assumed. Integrated with Finite Element Analysis (FEA), the changes of trabecular bone in morphology and material properties were simulated in the course of five years. The results suggest that deterioration and anisotropy of trabecluar bone are inevitable with natural aging, and that compression rather than tension can be applied to strengthen the ability of resistance to fracture. This investigation helps to gain more insight the mechanism of bone loss and identify improved treatment and prevention for osteoporosis or stress fracture.

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

    PubMed

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

    2016-08-15

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

  5. Biological mechanisms, one molecule at a time

    PubMed Central

    Tinoco, Ignacio; Gonzalez, Ruben L.

    2011-01-01

    The last 15 years have witnessed the development of tools that allow the observation and manipulation of single molecules. The rapidly expanding application of these technologies for investigating biological systems of ever-increasing complexity is revolutionizing our ability to probe the mechanisms of biological reactions. Here, we compare the mechanistic information available from single-molecule experiments with the information typically obtained from ensemble studies and show how these two experimental approaches interface with each other. We next present a basic overview of the toolkit for observing and manipulating biology one molecule at a time. We close by presenting a case study demonstrating the impact that single-molecule approaches have had on our understanding of one of life's most fundamental biochemical reactions: the translation of a messenger RNA into its encoded protein by the ribosome. PMID:21685361

  6. 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

  7. 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.

  8. Mechanically driven interface propagation in biological tissues

    NASA Astrophysics Data System (ADS)

    Ranft, Jonas; Aliee, Maryam; Prost, Jacques; Jülicher, Frank; Joanny, Jean-François

    2014-03-01

    Many biological tissues consist of more than one cell type. We study the dynamics of an interface between two different cell populations as it occurs during the growth of a tumor in a healthy host tissue. Recent work suggests that the rates of cell division and cell death are under mechanical control, characterized by a homeostatic pressure. The difference in the homeostatic pressures of two cell types drives the propagation of the interface, corresponding to the invasion of one cell type into the other. We derive a front propagation equation that takes into account the coupling between cell number balance and tissue mechanics. We show that in addition to pulled fronts, pushed-front solutions occur as a result of convection driven by mechanics.

  9. 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.

  10. Identification of Inhibitors of Biological Interactions Involving Intrinsically Disordered Proteins

    PubMed Central

    Marasco, Daniela; Scognamiglio, Pasqualina Liana

    2015-01-01

    Protein–protein interactions involving disordered partners have unique features and represent prominent targets in drug discovery processes. Intrinsically Disordered Proteins (IDPs) are involved in cellular regulation, signaling and control: they bind to multiple partners and these high-specificity/low-affinity interactions play crucial roles in many human diseases. Disordered regions, terminal tails and flexible linkers are particularly abundant in DNA-binding proteins and play crucial roles in the affinity and specificity of DNA recognizing processes. Protein complexes involving IDPs are short-lived and typically involve short amino acid stretches bearing few “hot spots”, thus the identification of molecules able to modulate them can produce important lead compounds: in this scenario peptides and/or peptidomimetics, deriving from structure-based, combinatorial or protein dissection approaches, can play a key role as hit compounds. Here, we propose a panoramic review of the structural features of IDPs and how they regulate molecular recognition mechanisms focusing attention on recently reported drug-design strategies in the field of IDPs. PMID:25849651

  11. Epigenetic mechanisms involved in developmental nutritional programming

    PubMed Central

    Gabory, Anne; Attig, Linda; Junien, Claudine

    2011-01-01

    The ways in which epigenetic modifications fix the effects of early environmental events, ensuring sustained responses to transient stimuli, which result in modified gene expression patterns and phenotypes later in life, is a topic of considerable interest. This review focuses on recently discovered mechanisms and calls into question prevailing views about the dynamics, position and functions of epigenetic marks. Most epigenetic studies have addressed the long-term effects on a small number of epigenetic marks, at the global or individual gene level, of environmental stressors in humans and animal models. In parallel, increasing numbers of studies based on high-throughput technologies and focusing on humans and mice have revealed additional complexity in epigenetic processes, by highlighting the importance of crosstalk between the different epigenetic marks. A number of studies focusing on the developmental origin of health and disease and metabolic programming have identified links between early nutrition, epigenetic processes and long-term illness. The existence of a self-propagating epigenetic cycle has been demonstrated. Moreover, recent studies demonstrate an obvious sexual dimorphism both for programming trajectories and in response to the same environmental insult. Despite recent progress, we are still far from understanding how, when and where environmental stressors disturb key epigenetic mechanisms. Thus, identifying the original key marks and their changes throughout development during an individual’s lifetime or over several generations remains a challenging issue. PMID:22010058

  12. 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.

  13. Systems analysis of gene ontology and biological pathways involved in post-myocardial infarction responses

    PubMed Central

    2015-01-01

    Background Pathway analysis has been widely used to gain insight into essential mechanisms of the response to myocardial infarction (MI). Currently, there exist multiple pathway databases that organize molecular datasets and manually curate pathway maps for biological interpretation at varying forms of organization. However, inconsistencies among different databases in pathway descriptions, frequently due to conflicting results in the literature, can generate incorrect interpretations. Furthermore, although pathway analysis software provides detailed images of interactions among molecules, it does not exhibit how pathways interact with one another or with other biological processes under specific conditions. Methods We propose a novel method to standardize descriptions of enriched pathways for a set of genes/proteins using Gene Ontology terms. We used this method to examine the relationships among pathways and biological processes for a set of condition-specific genes/proteins, represented as a functional biological pathway-process network. We applied this algorithm to a set of 613 MI-specific proteins we previously identified. Results A total of 96 pathways from Biocarta, KEGG, and Reactome, and 448 Gene Ontology Biological Processes were enriched with these 613 proteins. The pathways were represented as Boolean functions of biological processes, delivering an interactive scheme to organize enriched information with an emphasis on involvement of biological processes in pathways. We extracted a network focusing on MI to demonstrate that tyrosine phosphorylation of Signal Transducer and Activator of Transcription (STAT) protein, positive regulation of collagen metabolic process, coagulation, and positive/negative regulation of blood coagulation have immediate impacts on the MI response. Conclusions Our method organized biological processes and pathways in an unbiased approach to provide an intuitive way to identify biological properties of pathways under specific

  14. [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. PMID:18624253

  15. 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

  16. Biological Robustness: Paradigms, Mechanisms, and Systems Principles

    PubMed Central

    Whitacre, James Michael

    2012-01-01

    Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g., mutational, environmental) are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior. PMID:22593762

  17. Biological robustness: paradigms, mechanisms, and systems principles.

    PubMed

    Whitacre, James Michael

    2012-01-01

    Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g., mutational, environmental) are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior. PMID:22593762

  18. 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

  19. [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. PMID:24984512

  20. BIOLOGICAL ACTIVITY AND POTENTIAL REMEDIATION INVOLVING GEOTEXTILE LANDFILL LEACHATE FILTERS

    EPA Science Inventory

    This paper presents the results of a biological growth study in geotextile filters used in landfill leachate collection systems. fter reviewing the first year's activity, a completely new experimental approach has been taken. sing 100 mm diameter columns for the experimental incu...

  1. 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…

  2. Mechanical Fluidity of Fully Suspended Biological Cells

    PubMed Central

    Maloney, John M.; Lehnhardt, Eric; Long, Alexandra F.; Van Vliet, Krystyn J.

    2013-01-01

    Mechanical characteristics of single biological cells are used to identify and possibly leverage interesting differences among cells or cell populations. Fluidity—hysteresivity normalized to the extremes of an elastic solid or a viscous liquid—can be extracted from, and compared among, multiple rheological measurements of cells: creep compliance versus time, complex modulus versus frequency, and phase lag versus frequency. With multiple strategies available for acquisition of this nondimensional property, fluidity may serve as a useful and robust parameter for distinguishing cell populations, and for understanding the physical origins of deformability in soft matter. Here, for three disparate eukaryotic cell types deformed in the suspended state via optical stretching, we examine the dependence of fluidity on chemical and environmental influences at a timescale of ∼1 s. We find that fluidity estimates are consistent in the time and frequency domains under a structural damping (power-law or fractional-derivative) model, but not under an equivalent-complexity, lumped-component (spring-dashpot) model; the latter predicts spurious time constants. Although fluidity is suppressed by chemical cross-linking, we find that ATP depletion in the cell does not measurably alter the parameter, and we thus conclude that active ATP-driven events are not a crucial enabler of fluidity during linear viscoelastic deformation of a suspended cell. Finally, by using the capacity of optical stretching to produce near-instantaneous increases in cell temperature, we establish that fluidity increases with temperature—now measured in a fully suspended, sortable cell without the complicating factor of cell-substratum adhesion. PMID:24138852

  3. 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. PMID:26352286

  4. Mechanisms Involved in Nematode Control by Endophytic Fungi.

    PubMed

    Schouten, Alexander

    2016-08-01

    Colonization of plants by particular endophytic fungi can provide plants with improved defenses toward nematodes. Evidently, such endophytes can be important in developing more sustainable agricultural practices. The mechanisms playing a role in this quantitative antagonism are poorly understood but most likely multifactorial. This knowledge gap obstructs the progress regarding the development of endophytes or endophyte-derived constituents into biocontrol agents. In part, this may be caused by the fact that endophytic fungi form a rather heterogeneous group. By combining the knowledge of the currently characterized antagonistic endophytic fungi and their effects on nematode behavior and biology with the knowledge of microbial competition and induced plant defenses, the various mechanisms by which this nematode antagonism operates or may operate are discussed. Now that new technologies are becoming available and more accessible, the currently unresolved mechanisms can be studied in greater detail than ever before. PMID:27296146

  5. A theoretical study of the molecular mechanism of the GAPDH Trypanosoma cruzi enzyme involving iodoacetate inhibitor

    NASA Astrophysics Data System (ADS)

    Carneiro, Agnaldo Silva; Lameira, Jerônimo; Alves, Cláudio Nahum

    2011-10-01

    The glyceraldehyde-3-phosphate dehydrogenase enzyme (GAPDH) is an important biological target for the development of new chemotherapeutic agents against Chagas disease. In this Letter, the inhibition mechanism of GAPDH involving iodoacetate (IAA) inhibitor was studied using the hybrid quantum mechanical/molecular mechanical (QM/MM) approach and molecular dynamic simulations. Analysis of the potential energy surface and potential of mean force show that the covalent attachment of IAA inhibitor to the active site of the enzyme occurs as a concerted process. In addition, the energy terms decomposition shows that NAD+ plays an important role in stabilization of the reagents and transition state.

  6. 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.

  7. Mechanisms of and facility types involved in hazardous materials incidents.

    PubMed Central

    Kales, S N; Polyhronopoulos, G N; Castro, M J; Goldman, R H; Christiani, D C

    1997-01-01

    The purpose of this study was to systematically investigate hazardous materials (hazmat) releases and determine the mechanisms of these accidents, and the industries/activities and chemicals involved. We analyzed responses by Massachusetts' six district hazmat teams from their inception through May 1996. Information from incident reports was extracted onto standard coding sheets. The majority of hazardous materials incidents were caused by spills, leaks, or escapes of hazardous materials (76%) and occurred at fixed facilities (80%). Transportation-related accidents accounted for 20% of incidents. Eleven percent of hazardous materials incidents were at schools or health care facilities. Petroleum-derived fuels were involved in over half of transportation-related accidents, and these accounted for the majority of petroleum fuel releases. Chlorine derivatives were involved in 18% of all accidents and were associated with a wide variety of facility types and activities. In conclusion, systematic study of hazardous materials incidents allows the identification of preventable causes of these incidents. PMID:9300926

  8. Alternative splicing: An important mechanism in stem cell biology

    PubMed Central

    Chen, Kenian; Dai, Xiaojing; Wu, Jiaqian

    2015-01-01

    Alternative splicing (AS) is an essential mechanism in post-transcriptional regulation and leads to protein diversity. It has been shown that AS is prevalent in metazoan genomes, and the splicing pattern is dynamically regulated in different tissues and cell types, including embryonic stem cells. These observations suggest that AS may play critical roles in stem cell biology. Since embryonic stem cells and induced pluripotent stem cells have the ability to give rise to all types of cells and tissues, they hold the promise of future cell-based therapy. Many efforts have been devoted to understanding the mechanisms underlying stem cell self-renewal and differentiation. However, most of the studies focused on the expression of a core set of transcription factors and regulatory RNAs. The role of AS in stem cell differentiation was not clear. Recent advances in high-throughput technologies have allowed the profiling of dynamic splicing patterns and cis-motifs that are responsible for AS at a genome-wide scale, and provided novel insights in a number of studies. In this review, we discuss some recent findings involving AS and stem cells. An emerging picture from these findings is that AS is integrated in the transcriptional and post-transcriptional networks and together they control pluripotency maintenance and differentiation of stem cells. PMID:25621101

  9. 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

  10. Biologic-free mechanically induced muscle regeneration.

    PubMed

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

    2016-02-01

    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

  11. 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

  12. 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

  13. 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

  14. 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

  15. Molecular mechanisms involved in plant adaptation to low K(+) availability.

    PubMed

    Chérel, Isabelle; Lefoulon, Cécile; Boeglin, Martin; Sentenac, Hervé

    2014-03-01

    Potassium is a major inorganic constituent of the living cell and the most abundant cation in the cytosol. It plays a role in various functions at the cell level, such as electrical neutralization of anionic charges, protein synthesis, long- and short-term control of membrane polarization, and regulation of the osmotic potential. Through the latter function, K(+) is involved at the whole-plant level in osmotically driven functions such as cell movements, regulation of stomatal aperture, or phloem transport. Thus, plant growth and development require that large amounts of K(+) are taken up from the soil and translocated to the various organs. In most ecosystems, however, soil K(+) availability is low and fluctuating, so plants have developed strategies to take up K(+) more efficiently and preserve vital functions and growth when K(+) availability is becoming limited. These strategies include increased capacity for high-affinity K(+) uptake from the soil, K(+) redistribution between the cytosolic and vacuolar pools, ensuring cytosolic homeostasis, and modification of root system development and architecture. Our knowledge about the mechanisms and signalling cascades involved in these different adaptive responses has been rapidly growing during the last decade, revealing a highly complex network of interacting processes. This review is focused on the different physiological responses induced by K(+) deprivation, their underlying molecular events, and the present knowledge and hypotheses regarding the mechanisms responsible for K(+) sensing and signalling. PMID:24293613

  16. Using optics to measure biological forces and mechanics.

    PubMed

    Kuo, S C

    2001-11-01

    Spanning all size levels, regulating biological forces and transport are fundamental life processes. Used by various investigators over the last dozen years, optical techniques offer unique advantages for studying biological forces. The most mature of these techniques, optical tweezers, or the single-beam optical trap, is commercially available and is used by numerous investigators. Although technical innovations have improved the versatility of optical tweezers, simple optical tweezers continue to provide insights into cell biology. Two new, promising optical technologies, laser-tracking microrheology and the optical stretcher, allow mechanical measurements that are not possible with optical tweezers. Here, I review these various optical technologies and their roles in understanding mechanical forces in cell biology. PMID:11733041

  17. 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

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

    PubMed

    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. PMID:24415796

  19. Mechanisms of neutropenia involving myeloid maturation arrest in burn sepsis.

    PubMed Central

    Shoup, M; Weisenberger, J M; Wang, J L; Pyle, J M; Gamelli, R L; Shankar, R

    1998-01-01

    OBJECTIVE: To determine the mechanisms that lead to the decrease in bone marrow production of neutrophils during burn sepsis. SUMMARY BACKGROUND DATA: Impaired bone marrow granulopoiesis during burn sepsis often results in neutropenia despite elevated circulating levels of granulocyte colony-stimulating factor (G-CSF). To date, neither the specific stages of neutrophil maturation involved in the bone marrow suppression nor the mechanisms for the impairment have been determined. METHODS: Peripheral blood absolute neutrophil count and G-CSF levels were determined in mice 3 days after randomization to control, burn alone, or burn plus a topical inoculation of Pseudomonas aeruginosa (1000 colony-forming units). Bone marrow aspirates were analyzed for their neutrophil differentiation patterns by Gr-1 antigen expression and their G-CSF receptor status. Histologic analysis of liver, lung, spleen, and wound site was performed. RESULTS: In burn sepsis, absolute neutrophil count was reduced whereas plasma G-CSF levels were elevated, and myeloid differentiation was significantly shifted toward the immature mitotic myeloid cells. Bone marrow G-CSF receptor mRNA levels and G-CSF-stimulated proliferation were substantially decreased in burn sepsis. Histologic analysis revealed no significant neutrophil infiltration into the tissues. CONCLUSIONS: In thermal injury with superimposed sepsis, neutropenia and myeloid maturation arrest, despite the elevated levels of G-CSF, correlate with the reduction in bone marrow G-CSF receptor expression. These observations may provide a potential mechanism for neutropenia in sepsis. Images Figure 5. Figure 6. Figure 8. Figure 9. PMID:9671075

  20. Mechanisms of Physical-Biological-Biogeochemical Interaction at the Oceanic Mesoscale.

    PubMed

    McGillicuddy, Dennis J

    2016-01-01

    Mesoscale phenomena are ubiquitous and highly energetic features of ocean circulation. Their influence on biological and biogeochemical processes varies widely, stemming not only from advective transport but also from the generation of variations in the environment that affect biological and chemical rates. The ephemeral nature of mesoscale features in the ocean makes it difficult to elucidate the attendant mechanisms of physical-biological-biogeochemical interaction, necessitating the use of multidisciplinary approaches involving in situ observations, remote sensing, and modeling. All three aspects are woven through this review in an attempt to synthesize current understanding of the topic, with particular emphasis on novel developments in recent years. PMID:26359818

  1. Mechanisms of Physical-Biological-Biogeochemical Interaction at the Oceanic Mesoscale

    NASA Astrophysics Data System (ADS)

    McGillicuddy, Dennis J.

    2016-01-01

    Mesoscale phenomena are ubiquitous and highly energetic features of ocean circulation. Their influence on biological and biogeochemical processes varies widely, stemming not only from advective transport but also from the generation of variations in the environment that affect biological and chemical rates. The ephemeral nature of mesoscale features in the ocean makes it difficult to elucidate the attendant mechanisms of physical-biological-biogeochemical interaction, necessitating the use of multidisciplinary approaches involving in situ observations, remote sensing, and modeling. All three aspects are woven through this review in an attempt to synthesize current understanding of the topic, with particular emphasis on novel developments in recent years.

  2. Formation Mechanism for a Hybrid Supramolecular Network Involving Cooperative Interactions

    NASA Astrophysics Data System (ADS)

    Mura, Manuela; Silly, Fabien; Burlakov, Victor; Castell, Martin R.; Briggs, G. Andrew D.; Kantorovich, Lev N.

    2012-04-01

    A novel mechanism of hybrid assembly of molecules on surfaces is proposed stemming from interactions between molecules and on-surface metal atoms which eventually got trapped inside the network pores. Based on state-of-the-art theoretical calculations, we find that the new mechanism relies on formation of molecule-metal atom pairs which, together with molecules themselves, participate in the assembly growth. Most remarkably, the dissociation of pairs is facilitated by a cooperative interaction involving many molecules. This new mechanism is illustrated on a low coverage Melamine hexagonal network on the Au(111) surface where multiple events of gold atoms trapping via a set of so-called “gate” transitions are found by kinetic Monte Carlo simulations based on transition rates obtained using ab initio density functional theory calculations and the nudged elastic band method. Simulated STM images of gold atoms trapped in the pores of the Melamine network predict that the atoms should appear as bright spots inside Melamine hexagons. No trapping was found at large Melamine coverages, however. These predictions have been supported by preliminary STM experiments which show bright spots inside Melamine hexagons at low Melamine coverages, while empty pores are mostly observed at large coverages. Therefore, we suggest that bright spots sometimes observed in the pores of molecular assemblies on metal surfaces may be attributed to trapped substrate metal atoms. We believe that this type of mechanism could be used for delivering adatom species of desired functionality (e.g., magnetic) into the pores of hydrogen-bonded networks serving as templates for their capture.

  3. Multiple cellular mechanisms prevent chromosomal rearrangements involving repetitive DNA

    PubMed Central

    George, Carolyn M.; Alani, Eric

    2012-01-01

    Repetitive DNA is present in the eukaryotic genome in the form of segmental duplications, tandem and interspersed repeats, and satellites. Repetitive sequences can be beneficial by serving specific cellular functions (e.g. centromeric and telomeric DNA) and by providing a rapid means for adaptive evolution. However, such elements are also substrates for deleterious chromosomal rearrangements that affect fitness and promote human disease. Recent studies analyzing the role of nuclear organization in DNA repair and factors that suppress non-allelic homologous recombination have provided insights into how genome stability is maintained in eukaryotes. In this review we outline the types of repetitive sequences seen in eukaryotic genomes and how recombination mechanisms are regulated at the DNA sequence, cell organization, chromatin structure, and cell cycle control levels to prevent chromosomal rearrangements involving these sequences. PMID:22494239

  4. Complement involvement in periodontitis: molecular mechanisms and rational therapeutic approaches

    PubMed Central

    Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D.

    2015-01-01

    The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis. PMID:26306443

  5. FMR1 Premutation: Basic Mechanisms and Clinical Involvement.

    PubMed

    Milà, Montserrat; Rodriguez-Revenga, Laia; Matilla-Dueñas, Antoni

    2016-10-01

    The wide spectrum of clinical phenotypes associated with the FMR1 premutation affect more than two million people worldwide. The clinical implications have only been recognized recently despite this disorder constitutes a relevant health problem. The present issue of The Cerebellum is focused on the "2(nd) International Conference on the FMR1 Premutation: Basic Mechanisms and Clinical Involvement" held in Sitges, Barcelona (Spain), from September 30th to October 2nd, 2015. The conference was attended by professionals from different countries in Europe, the USA, Chile, Israel, Australia, and Indonesia and covered the latest clinical and molecular findings resulting from FMR1 premutation studies. Although the pathologies associated with the FMR1 premutation are considered as rare diseases, seventy abstracts were presented. This reflects the relevance of this topic in the medical community and the growing interest among professionals from other disciplines. The major topics discussed included why and how the mRNA toxicity due to a gain of function and non-canonical RAN are responsible for disorders associated with the premutation. Several presentations addressed the impact of these mechanisms in FXTAS and FXPOI, two clinical presentations caused by the FMR1 premutation. Interestingly, a deterioration of the DNA repair machinery was first proposed as the pathogenicity cause of premutation alleles. Communications related to FXTAS and FXPOI animal models were also presented. These models facilitate studies aimed to understand disease progression and early treatment interventions. Finally, there were presentations related to psychiatric, psychological, neurological, and radiological aspects. Interesting discussion on intermediate alleles and their involvement in clinical and reproductive aspects was generated. In this regards, genetic counselling is improved by taking into account the AGG interruptions and including information about the FMR1 premutation associated

  6. Neural involvement in endometriosis: Review of anatomic distribution and mechanisms.

    PubMed

    Siquara De Sousa, Ana C; Capek, Stepan; Amrami, Kimberly K; Spinner, Robert J

    2015-11-01

    Endometriosis (EM) is an infrequent cause of peripheral neuropathy, most commonly sciatic. Perineural spread has recently been introduced as an alternate explanation for cases of lumbosacral or sciatic nerve EM. We performed a literature review to collect all reported cases of peripheral and central nervous system EM in search of anatomic patterns of involvement; potentially to support the perineural spread theory. If available, intraneural invasion and presence of peritoneal EM were recorded. The search revealed 83 articles describing 365 cases of somatic peripheral nervous EM and 13 cases of central nervous EM. The most frequently involved site was the sacral plexus (57%, n = 211), followed by the sciatic nerve (39%, n = 140). Other nerves were reported in significantly smaller numbers. Ninety seven percent (97%, n = 355) of peripheral nerve cases presented with pain, 20% (n = 72) reported weakness and 31% (n = 114), numbness. Thirty four percent (34%, n = 38) had solely intraneural EM of which 89% (n = 33) had no peritoneal EM (percentage based on available information). In the central nervous system, the conus medullaris and/or cauda equina constituted the majority of cases with 54% (n = 7). Apart from perineural spread, other discussed mechanisms include retrograde menstruation with peritoneal seeding, hematogenous and lymphogenous spread, stem cell implantation either hematogenously or via retrograde menstruation with subsequent EM differentiation, and coelomic or Müllerian duct metaplasia. We believe this literature review supports perineural spread as an alternate mechanism for EM of nerve, particularly the subgroup with intraneural EM and without peritoneal disease. PMID:26296428

  7. Dynamic Compression Effects on Intervertebral Disc Mechanics and Biology

    PubMed Central

    Korecki, Casey L.; MacLean, Jeffrey J.; Iatridis, James C.

    2008-01-01

    Study Design A bovine intervertebral disc organ culture model was used to study the effect of dynamic compression magnitude on mechanical behavior and measurement of biosynthesis rate, cell viability, and mRNA expression. Objective The objective of this study was to examine the effect of loading magnitude on intervertebral disc mechanics and biology in an organ culture model. Summary of Background Data The in vivo and cell culture response of intervertebral disc cells to dynamic mechanical loading provides evidence the disc responds in a magnitude dependant manner. However, the ability to link mechanical behavior of the disc with biologic phenomena has been limited. A large animal organ culture system facilitates measurements of tissue mechanics and biologic response parameters on the same sample allowing a broader understanding of disc mechanobiology. Methods Bovine caudal intervertebral discs were placed in organ culture for 6 days and assigned to a static control or 1 of 2 dynamic compression loading protocols (0.2–1 MPa or 0.2–2.5 MPa) at 1 Hz for 1 hour for 5 days. Disc structure was assessed with measurements of dynamic modulus, creep, height loss, water content, and proteoglycan loss to the culture medium. Cellular responses were assessed through changes in cell viability, metabolism, and qRT-PCR analyses. Results Increasing magnitudes of compression increased disc modulus and creep; however, all mechanical parameters recovered each day. In the anulus, significant increases in gene expression for collagen I and a trend of increasing sulfate incorporation were observed. In the nucleus, increasing gene expression for collagen I and MMP3 was observed between magnitudes and between static controls and the lowest magnitude of loading. Conclusion Results support the hypothesis that biologic remodeling precedes damage to the intervertebral disc structure, that compression is a healthy loading condition for the disc, and further support the link between applied

  8. Introduction to Special Section: Mechanical Involvement of Fluids in Faulting

    NASA Astrophysics Data System (ADS)

    Hickman, Stephen; Sibson, Richard; Bruhn, Ronald

    1995-07-01

    A growing body of evidence suggests that fluids are intimately linked to a variety of faulting processes. These include the long term structural and compositional evolution of fault zones; fault creep; and the nucleation, propagation, arrest, and recurrence of earthquake ruptures. Besides the widely recognized physical role of fluid pressures in controlling the strength of crustal fault zones, it is also apparent that fluids can exert mechanical influence through a variety of chemical effects. The United States Geological Survey sponsored a Conference on the Mechanical Effects of Fluids in Faulting under the auspices of the National Earthquake Hazards Reduction Program at Fish Camp, California, from June 6 to 10, 1993. The purpose of the conference was to draw together and to evaluate the disparate evidence for the involvement of fluids in faulting; to establish communication on the importance of fluids in the mechanics of faulting between the different disciplines concerned with fault zone processes; and to help define future critical investigations, experiments, and observational procedures for evaluating the role of fluids in faulting. This conference drew together a diverse group of 45 scientists, with expertise in electrical and magnetic methods, geochemistry, hydrology, ore deposits, rock mechanics, seismology, and structural geology. Some of the outstanding questions addressed at this workshop included the following: 1. What are fluid pressures at different levels within seismically active fault zones? Do they remain hydrostatic throughout the full depth extent of the seismogenic regime, or are they generally superhydrostatic at depths in excess of a few kilometers? 2. Are fluid pressures at depth within fault zones constant through an earthquake cycle, or are they time-dependent? What is the spatial variability in fluid pressures? 3. What is the role of crustal fluids in the overall process of stress accumulation, release, and transfer during the earthquake

  9. A possible mechanism of biological silicification in plants

    PubMed Central

    Exley, Christopher

    2015-01-01

    Plants are significant exponents of biological silicification. While not all plants are generally considered as biosilicifiers the extent to which all plants deposit biogenic silica is largely unknown. There are plants which are known as silica accumulators though even in these plants the extent and degree to which their tissues are silicified is neither appreciated nor understood. An elucidation of the mechanism of silicification in biota is complicated by a lack of known bio-organic chemistry of silicic acid, the starting point in this process. Herein I argue the case that biological silicification is an entirely passive process. It is passive from the point of view that its underlying mechanisms and processes do not require us to invoke any as yet undiscovered silicon biochemistry. It is also passive in that although silicification confers clear biological/ecological advantages under certain conditions, it is actually non-essential in all plants and potentially, at least, toxic in some. PMID:26500676

  10. A possible mechanism of biological silicification in plants.

    PubMed

    Exley, Christopher

    2015-01-01

    Plants are significant exponents of biological silicification. While not all plants are generally considered as biosilicifiers the extent to which all plants deposit biogenic silica is largely unknown. There are plants which are known as silica accumulators though even in these plants the extent and degree to which their tissues are silicified is neither appreciated nor understood. An elucidation of the mechanism of silicification in biota is complicated by a lack of known bio-organic chemistry of silicic acid, the starting point in this process. Herein I argue the case that biological silicification is an entirely passive process. It is passive from the point of view that its underlying mechanisms and processes do not require us to invoke any as yet undiscovered silicon biochemistry. It is also passive in that although silicification confers clear biological/ecological advantages under certain conditions, it is actually non-essential in all plants and potentially, at least, toxic in some. PMID:26500676

  11. 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 ...

  12. 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.

  13. Absorption of Carotenoids and Mechanisms Involved in Their Health-Related Properties.

    PubMed

    Cervantes-Paz, Braulio; Victoria-Campos, Claudia I; Ornelas-Paz, José de Jesús

    2016-01-01

    Carotenoids participate in the normal metabolism and function of the human body. They are involved in the prevention of several diseases, especially those related to the inflammation syndrome. Their main mechanisms of action are associated to their potent antioxidant activity and capacity to regulate the expression of specific genes and proteins. Recent findings suggest that carotenoid metabolites may explain several processes where the participation of their parent carotenoids was unclear. The health benefits of carotenoids strongly depend on their absorption and transformation during gastrointestinal digestion. The estimation of the 'bioaccessibility' of carotenoids through in vitro models have made possible the evaluation of the effect of a large number of factors on key stages of carotenoid digestion and intestinal absorption. The bioaccessibility of these compounds allows us to have a clear idea of their potential bioavailability, a term that implicitly involves the biological activity of these compounds. PMID:27485232

  14. Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing.

    PubMed

    Roelands, Bart; de Koning, Jos; Foster, Carl; Hettinga, Floor; Meeusen, Romain

    2013-05-01

    improve performance. The distribution of the power output reveals that after dopamine reuptake inhibition, subjects are able to maintain a higher power output compared with placebo. Manipulations of serotonin and, especially, noradrenaline, have the opposite effect and force subjects to decrease power output early in the time trial. Interestingly, after manipulation of brain serotonin, subjects are often unable to perform an end sprint, indicating an absence of a reserve capacity or motivation to increase power output. Taken together, it appears that many factors, such as ambient conditions and manipulation of brain neurotransmitters, have the potential to influence power output during exercise, and might thus be involved as regulatory mechanisms in the complex skill of pacing. PMID:23456493

  15. 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

  16. 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.

  17. Assessment of mechanisms involved in antinociception caused by sesquiterpene polygodial.

    PubMed

    Mendes, G L; Santos, A R; Malheiros, A; Filho, V C; Yunes, R A; Calixto, J B

    2000-01-01

    Polygodial, a sesquiterpene isolated from the bark of Drymis winteri given systemically, intraplantarly, or by spinal or supraspinal sites, produced antinociception when assessed in both phases of the formalin test and against capsaicin-induced pain. Polygodial, even at high doses, had no antinociceptive or antihyperalgesic effect when assessed in hot-plate assay or in glutamate-induced hyperalgesia, nor did it significantly interfere with the motor coordination of animals when tested in the rota-rod test. The polygodial antinociception assessed in the formalin test was not affected by i.p. treatment of animals with cyprodime, yohimbine, phaclofen, bicuculine, or nitric oxide precursor or by intrathecal administration of potassium channel blockers such as apamin, charybdotoxin, glibenclamide, or tetraethylammonium. In contrast, polygodial antinociception was significantly attenuated by i.p. treatment of animals with naloxone, naltrindole, 2-(3, 4-dichlorophenyl)-n-methyl-n-[(1S)-1-(3-isothiocynatophenyl)-2-(1- pry rolidinyl)ethyl]acetamide, p-chlorophenylalanine, prazosin, or by i. c.v. treatment with pertussis toxin. In addition, polygodial antinociception was not cross-tolerant to morphine, nor was its effect affected by the adrenalectomy of animals. Together, these results show that polygodial produces pronounced systemic, spinal, and supraspinal antinociception in mice, mainly preventing the neurogenic pain produced by formalin and capsaicin. The mechanism by which polygodial produces antinociception seems likely to involve an interaction with the opioid system, mainly kappa and delta subtypes, depend on the activation of G(i/o) protein sensitive to pertussis toxin, alpha(1)-adrenoceptors, and the serotoninergic system. Collectively, these results suggest that polygodial itself or its derivatives may have potential therapeutic value for the development of new analgesic drugs. PMID:10604944

  18. 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. PMID:21513457

  19. On the mechanical theory for biological pattern formation

    NASA Astrophysics Data System (ADS)

    Bentil, D. E.; Murray, J. D.

    1993-02-01

    We investigate the pattern-forming potential of mechanical models in embryology proposed by Oster, Murray and their coworkers. We show that the presence of source terms in the tissue extracellular matrix and cell density equations give rise to spatio-temporal oscillations. An extension of one such model to include ‘biologically realistic long range effects induces the formation of stationary spatial patterns. Previous attempts to solve the full system were in one dimension only. We obtain solutions in one dimension and extend our simulations to two dimensions. We show that a single mechanical model alone is capable of generating complex but regular spatial patterns rather than the requirement of model interaction as suggested by Nagorcka et al. and Shaw and Murray. We discuss some biological applications of the models among which are would healing and formation of dermatoglyphic (fingerprint) patterns.

  20. 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

  1. 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. PMID:22486968

  2. Involvement of Nitric Oxide on Bothropoides insularis Venom Biological Effects on Murine Macrophages In Vitro

    PubMed Central

    de Menezes, Ramon R. P. P. B.; Mello, Clarissa P.; Lima, Dânya B.; Tessarolo, Louise D.; Sampaio, Tiago Lima; Paes, Lívia C. F.; Alves, Natacha T. Q.; Assis Junior, Eudmar M.; Lima Junior, Roberto C. P.; Toyama, Marcos H.; Martins, Alice M. C.

    2016-01-01

    Viperidae venom has several local and systemic effects, such as pain, edema, inflammation, kidney failure and coagulopathy. Additionally, bothropic venom and its isolated components directly interfere on cellular metabolism, causing alterations such as cell death and proliferation. Inflammatory cells are particularly involved in pathological envenomation mechanisms due to their capacity of releasing many mediators, such as nitric oxide (NO). NO has many effects on cell viability and it is associated to the development of inflammation and tissue damage caused by Bothrops and Bothropoides venom. Bothropoides insularis is a snake found only in Queimada Grande Island, which has markedly toxic venom. Thus, the aim of this work was to evaluate the biological effects of Bothropoides insularis venom (BiV) on RAW 264.7 cells and assess NO involvement. The venom was submitted to colorimetric assays to identify the presence of some enzymatic components. We observed that BiV induced H2O2 production and showed proteolytic and phospholipasic activities. RAW 264.7 murine macrophages were incubated with different concentrations of BiV and then cell viability was assessed by MTT reduction assay after 2, 6, 12 and 24 hours of incubation. A time- and concentration-dependent effect was observed, with a tendency to cell proliferation at lower BiV concentrations and cell death at higher concentrations. The cytotoxic effect was confirmed after lactate dehydrogenase (LDH) measurement in the supernatant from the experimental groups. Flow cytometry analyses revealed that necrosis is the main cell death pathway caused by BiV. Also, BiV induced NO release. The inhibition of both proliferative and cytotoxic effects with L-NAME were demonstrated, indicating that NO is important for these effects. Finally, BiV induced an increase in iNOS expression. Altogether, these results demonstrate that B. insularis venom have proliferative and cytotoxic effects on macrophages, with necrosis participation

  3. Inference on biological mechanisms using an integrated phenotype prediction model.

    PubMed

    Enomoto, Yumi; Ushijima, Masaru; Miyata, Satoshi; Matsuura, Masaaki; Ohtaki, Megu

    2008-03-01

    We propose a methodology for constructing an integrated phenotype prediction model that accounts for multiple pathways regulating a targeted phenotype. The method uses multiple prediction models, each expressing a particular pattern of gene-to-gene interrelationship, such as epistasis. We also propose a methodology using Gene Ontology annotations to infer a biological mechanism from the integrated phenotype prediction model. To construct the integrated models, we employed multiple logistic regression models using a two-step learning approach to examine a number of patterns of gene-to-gene interrelationships. We first selected individual prediction models with acceptable goodness of fit, and then combined the models. The resulting integrated model predicts phenotype as a logical sum of predicted results from the individual models. We used published microarray data on neuroblastoma from Ohira et al (2005) for illustration, constructing an integrated model to predict prognosis and infer the biological mechanisms controlling prognosis. Although the resulting integrated model comprised a small number of genes compared to a previously reported analysis of these data, the model demonstrated excellent performance, with an error rate of 0.12 in a validation analysis. Gene Ontology analysis suggested that prognosis of patients with neuroblastoma may be influenced by biological processes such as cell growth, G-protein signaling, phosphoinositide-mediated signaling, alcohol metabolism, glycolysis, neurophysiological processes, and catecholamine catabolism. PMID:18578362

  4. 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.

  5. Molecular mechanism of biological responses to homoeopathic medicines.

    PubMed

    Matsumoto, J

    1995-09-01

    Assuming that homeopathy is effective beyond the placebo effects, its biological explanation in favour of the hypothesis of the hydrate-structure formation is presented. Since cell-surface proteins are likely to be activated by the hydration-shell structure of molecules in some cases, the interaction between cell-surface proteins and the putative clathrate-like hydrate microcrystals formed during the homoeopathic dilution process is suggested as a primary molecular mechanism of biological responses to homoeopathic medicines. This paper examines the probable protein-microcrystal interaction, forcusing on the cases in which silicon dioxide (silica) microcrystals cause inflammation and in which hydrate microcrystals may be formed during general anesthesia. PMID:8569554

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

    PubMed Central

    Medvedev, Emile S.; Stuchebrukhov, Alexei A.

    2014-01-01

    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. PMID:23268201

  7. Using quantum mechanical approaches to study biological systems.

    PubMed

    Merz, Kenneth M

    2014-09-16

    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

  8. 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.

  9. A comparison of form processing involved in the perception of biological and nonbiological movements.

    PubMed

    Thurman, Steven M; Lu, Hongjing

    2016-01-01

    Although there is evidence for specialization in the human brain for processing biological motion per se, few studies have directly examined the specialization of form processing in biological motion perception. The current study was designed to systematically compare form processing in perception of biological (human walkers) to nonbiological (rotating squares) stimuli. Dynamic form-based stimuli were constructed with conflicting form cues (position and orientation), such that the objects were perceived to be moving ambiguously in two directions at once. In Experiment 1, we used the classification image technique to examine how local form cues are integrated across space and time in a bottom-up manner. By comparing with a Bayesian observer model that embodies generic principles of form analysis (e.g., template matching) and integrates form information according to cue reliability, we found that human observers employ domain-general processes to recognize both human actions and nonbiological object movements. Experiments 2 and 3 found differential top-down effects of spatial context on perception of biological and nonbiological forms. When a background does not involve social information, observers are biased to perceive foreground object movements in the direction opposite to surrounding motion. However, when a background involves social cues, such as a crowd of similar objects, perception is biased toward the same direction as the crowd for biological walking stimuli, but not for rotating nonbiological stimuli. The model provided an accurate account of top-down modulations by adjusting the prior probabilities associated with the internal templates, demonstrating the power and flexibility of the Bayesian approach for visual form perception. PMID:26746875

  10. International cancer risk assessment: the impact of biologic mechanisms.

    PubMed

    Whysner, J; Williams, G M

    1992-02-01

    The use of risk assessment by different governments and agencies varies widely in theory and practice. One major difference is in the consideration given to the biologic mechanisms of cancer causation. U.S. government agencies consider all animal carcinogens to be presumptive human carcinogens and to act in a similar manner without regard to available knowledge on the mechanism of carcinogenicity. Accordingly, standardized models that give linear dose-response at low doses without a threshold are used for predicting human cancer risk from animal studies. Accumulated evidence on biologic mechanisms reveals that some animal carcinogens should not cause cancer in humans at low exposures; other should not at any exposure level. The Netherlands has included such considerations in their cancer classification and risk assessment process. Other governments evaluate each chemical on a case-by-case basis or do not use standardized risk assessment methods for regulatory decisions. To address these issues, the American Health Foundation has convened an International Expert Panel on Carcinogen Risk Assessment. PMID:1553411

  11. Modeling Selection and Extinction Mechanisms of Biological Systems

    NASA Astrophysics Data System (ADS)

    Amirjanov, Adil

    In this paper, the behavior of a genetic algorithm is modeled to enhance its applicability as a modeling tool of biological systems. A new description model for selection mechanism is introduced which operates on a portion of individuals of population. The extinction and recolonization mechanism is modeled, and solving the dynamics analytically shows that the genetic drift in the population with extinction/recolonization is doubled. The mathematical analysis of the interaction between selection and extinction/recolonization processes is carried out to assess the dynamics of motion of the macroscopic statistical properties of population. Computer simulations confirm that the theoretical predictions of described models are in good approximations. A mathematical model of GA dynamics was also examined, which describes the anti-predator vigilance in an animal group with respect to a known analytical solution of the problem, and showed a good agreement between them to find the evolutionarily stable strategies.

  12. Roles of Biological Mechanisms in Floodplain Construction and Dynamics

    NASA Astrophysics Data System (ADS)

    Beechie, T.; Pollock, M.

    2006-12-01

    Biological mechanisms force patchy and episodic construction of floodplain surfaces across a wide gradient of climatic environments. Common biological mechanisms include sediment trapping by beaver dams, bed load accumulation at wood jams, and settling of suspended sediments in floodplain vegetation. Each of these mechanisms is a direct control on ΔS (change in sediment storage) in the framework of reach-level sediment budgets (ΔS=Input-Output). However, floodplain construction is discontinuous in both lateral and longitudinal dimensions, which complicates estimation of rates of floodplain construction. In this paper we illustrate how biological mechanisms drive rates and dynamics of floodplain construction in rivers in semi-arid regions of the Columbia River basin, as well as in the densely forested Olympic and Cascade Mountain ranges, USA. Floodplain sedimentation rates in the semi-arid region vary depending upon sediment source and biological retention mechanism. Rivers draining fined-grained source lithologies have silt-dominated sediment loads, and floodplains aggrade primarily by settling of particles on vegetated floodplains (10^{0} cm/yr), or by infilling behind beaver dams (101 cm/yr). Typical longitudinal spacing between beaver dams is several hundred meters, and filling of beaver ponds occurs within 10^{0} to 101 years. Hence, new floodplain patches are created on roughly decadal intervals and at longitudinal spacing of ~102 meters. Abandonment and failure of old dams erodes portions of some floodplain surfaces, but significant terraces remain and new beaver dams initiate construction of additional floodplain surfaces. Where beaver dams are sparse, aggradation rates are spatially more uniform, but slower as the aggradation rate in floodplain vegetation is one order of magnitude lower than in beaver ponds. Floodplains of semi-arid rivers dominated by coarse sediment loads aggrade primarily by overbank deposition in sparsely forested riparian zones, and

  13. Mechanical and biological properties of oxidized horn keratin.

    PubMed

    Zhang, Quanbin; Shan, Guanghua; Cao, Ping; He, Jia; Lin, Zhongshi; Huang, Yaoxiong; Ao, Ningjian

    2015-02-01

    The goal of this study was to investigate the mechanical and biological properties of oxidized keratin materials, which were obtained by using buffalo horns to oxidize. It could provide a way to evaluate their potential for clinical translatability. The characterization on their composition, mechanical properties, and biological responses was performed. It is found that the oxidation process could lead the disulfide bond to break down and then to form sulfonic acid, or even make partial peptide chain to be fragment for the new modification of amino acid. Hence the oxidized horn keratins have lower thermal stability and hydrolytic stability in comparison with horn keratin, but the degradation products of oxidized horn keratins have no significant difference. In addition, the mechanical properties of oxidized horn keratins are poorer than that of horn keratin, but the oxidized horn keratins still have disulfide bonds to form a three-dimensional structure, which benefits for their mechanical properties. The fracture toughness of oxidized horn keratins increases with the increase in the degree of oxidation. After oxidation, the oxidized horn keratins have lower cytotoxicity and lower hemolysis ratio. Moreover, when the oxidized horn keratins, as well as different concentration of degradation products of oxidized horn keratins, are directly in contact with platelet-rich plasma, platelets are not activated. It suggests that the oxidized horn keratins have good hemocompatibility, without triggering blood thrombosis. The implantation experiment in vivo also demonstrates that the oxidized horn keratins are compatible with the tissue, because there are minimal fibrous capsule and less of infiltration of host cells, without causing serious inflammation. In summary, the oxidized horn keratins can act as implanted biomaterial devices that are directly in contact with blood and tissue. PMID:25492180

  14. 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

  15. 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...

  16. 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

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

    PubMed

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

    2015-09-01

    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

  18. On the mechanism of biological activation by tritium.

    PubMed

    Rozhko, T V; Badun, G A; Razzhivina, I A; Guseynov, O A; Guseynova, V E; Kudryasheva, N S

    2016-06-01

    The mechanism of biological activation by beta-emitting radionuclide tritium was studied. Luminous marine bacteria were used as a bioassay to monitor the biological effect of tritium with luminescence intensity as the physiological parameter tested. Two different types of tritium sources were used: HTO molecules distributed regularly in the surrounding aqueous medium, and a solid source with tritium atoms fixed on its surface (tritium-labeled films, 0.11, 0.28, 0.91, and 2.36 MBq/cm(2)). When using the tritium-labeled films, tritium penetration into the cells was prevented. The both types of tritium sources revealed similar changes in the bacterial luminescence kinetics: a delay period followed by bioluminescence activation. No monotonic dependences of bioluminescence activation efficiency on specific radioactivities of the films were found. A 15-day exposure to tritiated water (100 MBq/L) did not reveal mutations in bacterial DNA. The results obtained give preference to a "non-genomic" mechanism of bioluminescence activation by tritium. An activation of the intracellular bioluminescence process develops without penetration of tritium atoms into the cells and can be caused by intensification of trans-membrane cellular processes stimulated by ionization and radiolysis of aqueous media. PMID:27035890

  19. Investigation into the non-biological outputs of mechanical-biological treatment facilities.

    PubMed

    Cook, Ed; Wagland, Stuart; Coulon, Frédéric

    2015-12-01

    Mechanical-biological and biological-mechanical treatment (MBT/BMT) are effective methods for reducing biogenic additions to landfill, producing fuel products and recovering recyclate from residual waste. However, large amounts of contamination in the non-biological outputs reduce their market value. The aim of this study was therefore to identify the principal drivers and barriers to the marketability of ferrous metals (MBTFe) and heavy inert rejects (MBTr) recovered from four UK MBT/BMT plants. The plants were either using biodrying or anaerobic digestion (AD-MBT) for biological processing. Samples were collected at the different recovery stage processes and characterised for elemental composition and particle size distribution. Results showed that processes at the two biodrying plants produced MBTFe with 10% less contamination by non-target materials than the two AD-MBT plants. Further to this, approximately 10% of the MBTFe fraction sampled at all four facilities comprised non-target material which had become entrapped in the folds of metal food containers. A possible cause is waste comminution in the cutting gap of the low-speed high-torque cutting mills. Upgrading MBTFe outputs could save the UK MBT/BMT industry up to £ 4.4 million per annum which equates to £ 230,000 per annum for an average sized facility (i.e. capacity 108,000 tpa). Glass content in the MBTr samples ranged between 44% and 62%, however all plants showed approximately 85% combined content of glass, bricks, stones and ceramics. The biodegradable content in the MBTr samples indicated that only minimal upgrade would be required to achieve the Landfill Directive requirements for inert waste. Again valorisation of MBTr could save the UK MBT/BMT industry up to £ 1.9 million pa which equates to £ 160,000 per annum for an average sized facility. PMID:26394679

  20. 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

  1. Molecular mechanisms of biological aging in intervertebral discs.

    PubMed

    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

    2016-08-01

    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. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1289-1306, 2016. PMID:26890203

  2. 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

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

    PubMed

    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

  4. Probing mechanical properties of fully hydrated gels and biological tissues.

    PubMed

    Constantinides, Georgios; Kalcioglu, Z Ilke; McFarland, Meredith; Smith, James F; Van Vliet, Krystyn J

    2008-11-14

    A longstanding challenge in accurate mechanical characterization of engineered and biological tissues is maintenance of both stable sample hydration and high instrument signal resolution. Here, we describe the modification of an instrumented indenter to accommodate nanomechanical characterization of biological and synthetic tissues in liquid media, and demonstrate accurate acquisition of force-displacement data that can be used to extract viscoelastoplastic properties of hydrated gels and tissues. We demonstrate the validity of this approach via elastoplastic analysis of relatively stiff, water-insensitive materials of elastic moduli E>1000 kPa (borosilicate glass and polypropylene), and then consider the viscoelastic response and representative mechanical properties of compliant, synthetic polymer hydrogels (polyacrylamide-based hydrogels of varying mol%-bis crosslinker) and biological tissues (porcine skin and liver) of E<500 kPa. Indentation responses obtained via loading/unloading hystereses and contact creep loading were highly repeatable, and the inferred E were in good agreement with available macroscopic data for all samples. As expected, increased chemical crosslinking of polyacrylamide increased stiffness (E40 kPa) and decreased creep compliance. E of porcine liver (760 kPa) and skin (222 kPa) were also within the range of macroscopic measurements reported for a limited subset of species and disease states. These data show that instrumented indentation of fully immersed samples can be reliably applied for materials spanning several orders of magnitude in stiffness (E=kPa-GPa). These capabilities are particularly important to materials design and characterization of macromolecules, cells, explanted tissues, and synthetic extracellular matrices as a function of spatial position, degree of hydration, or hydrolytic/enzymatic/corrosion reaction times. PMID:18922534

  5. Conference explores mechanical involvement of fluids in faulting

    NASA Astrophysics Data System (ADS)

    Hickman, Stephen; Sibson, Richard; Bruhn, Ronald

    A growing body of evidence suggests that fluids are intimately linked to a variety of faulting processes. These include the long-term structural and compositional evolution of fault zones; fault creep; and the nucleation, propagation, arrest, and recurrence of earthquake ruptures. Besides the widely recognized physical role of fluid pressures in controlling the strength of crustal fault zones, it is also apparent that fluids can exert mechanical influence through a variety of chemical effects.To address these issues, a “Red-Book” Conference on the Mechanical Effects of Fluids in Faulting was sponsored by the U.S. Geological Survey under the auspices of the National Earthquake Hazards Reduction Program at Fish Camp, Calif., from June 6-10, 1993. The coconvenors were Steve Hickman, Rick Sibson, and Ron Bruhn.

  6. Identification of genes involved in regulatory mechanism of pigments in broiler chickens.

    PubMed

    Tarique, T M; Yang, S; Mohsina, Z; Qiu, J; Yan, Z; Chen, G; Chen, A

    2014-01-01

    Chicken is an important model organism that unites the evolutionary gap between mammals and other vertebrates and provide major source of protein from meat and eggs for all over the world population. However, specific genes underlying the regulatory mechanism of broiler pigmentation have not yet been determined. In order to better understand the genes involved in the mechanism of pigmentation in the muscle tissues of broilers, the Affymetrix microarray hybridization experiment platform was used to identify gene expression profiles at 7 weeks of age. Broilers fed canthaxanthin, natural lutein, and orangeII pigments (100 mg/kg) were used to explore gene expression profiles). Our data showed that the 7th week of age was a very important phase with regard to gene expression profiles. We identified a number of differentially expressed genes; in canthaxanthin, natural lutein, and orangeII, there were 54 (32 upregulated and 22 downregulated), 23 (15 upregulated and 8 downregulated), and 7 (5 upregulated and 2 downregulated) known genes, respectively. Our data indicate that the numbers of differentially expressed genes were more upregulated than downregulated, and several genes showed conserved signaling to previously known functions. Thus, functional characterization of differentially expressed genes revealed several categories that are involved in important biological processes, including pigmentation, growth, molecular mechanisms, fat metabolism, cell proliferation, immune response, lipid metabolism, and protein synthesis and degradation. The results of the present study demonstrate that the genes associated with canthaxanthin, natural lutein, and orangeII are key regulatory genes that control the regulatory mechanisms of pigmentation. PMID:25222226

  7. Orosensory self-stimulation by sucrose involves brain dopaminergic mechanisms.

    PubMed

    Schneider, L H

    1989-01-01

    The most convincing body of evidence supporting a role for brain dopaminergic mechanisms in sweet taste reward has been obtained using the sham-feeding rat. In rats prepared with a chronic gastric fistula and tested with the cannula open, intake is a direct function of the palatability of the solution offered as well as of the state of food deprivation. Because essentially none of the ingested fluid passes on to the intestine, negative postingestive feedback is eliminated. Thus, the relative orosensory/hedonic potency of the food determines and sustains the rate of sham intake; long periods of food deprivation are not required. In this way, the sham feeding of sweet solutions may be considered a form of oral self-stimulation behavior and afford a preparation through which the neurochemical and neuranatomical substrates of sweet taste reward may be identified. The results obtained in the series of experiments summarized in this paper clearly indicate that central D-1 and D-2 receptor mechanisms are critical for the orosensory self-stimulation by sucrose in the rat. In conclusion, I suggest that such investigations of the roles of brain dopaminergic mechanisms in the sucrose sham-feeding rat preparation may further our understanding of normal and aberrant attractions to sweet fluids in humans (see Cabanac, Drewnowski, and Halmi, this volume), as an innate, positive affective response of human neonates to sucrose and the sustained positive hedonic ratings for glucose when tasted but not when consumed have demonstrated. PMID:2699194

  8. Molecular mechanisms involved in Bacillus subtilis biofilm formation

    PubMed Central

    Mielich-Süss, Benjamin; Lopez, Daniel

    2014-01-01

    Summary Biofilms are the predominant lifestyle of bacteria in natural environments, and they severely impact our societies in many different fashions. Therefore, biofilm formation is a topic of growing interest in microbiology, and different bacterial models are currently studied to better understand the molecular strategies that bacteria undergo to build biofilms. Among those, biofilms of the soil-dwelling bacterium Bacillus subtilis are commonly used for this purpose. Bacillus subtilis biofilms show remarkable architectural features that are a consequence of sophisticated programs of cellular specialization and cell-cell communication within the community. Many laboratories are trying to unravel the biological role of the morphological features of biofilms, as well as exploring the molecular basis underlying cellular differentiation. In this review, we present a general perspective of the current state of knowledge of biofilm formation in B. subtilis. In particular, a special emphasis is placed on summarizing the most recent discoveries in the field and integrating them into the general view of these truly sophisticated microbial communities. PMID:24909922

  9. 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

  10. 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

    2016-01-01

    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

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

    PubMed

    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

  12. 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

  13. Mechanisms involved in quinolone resistance in Mycoplasma mycoides subsp. capri.

    PubMed

    Antunes, Nuno T; Assunção, Patrícia; Poveda, José B; Tavío, María M

    2015-06-01

    Mycoplasma mycoides subsp. capri is a causative agent of contagious agalactia in goats. In this study, M. mycoides subsp. capri mutants were selected for resistance to fluoroquinolones (norfloxacin, enrofloxacin and ciprofloxacin) by serial passes in broth with increasing concentrations of antibiotic. Mutations conferring cross-resistance to the three fluoroquinolones were found in the quinolone resistance determining regions of the four genes encoding DNA gyrase and topoisomerase IV. Different mutations in the DNA gyrase GyrA subunit suggest a different mechanism of inhibition between norfloxacin and the other tested fluoroquinolones. The presence of an adenosine triphosphate-dependent efflux system was suggested through the use of the inhibitor orthovanadate. PMID:25951987

  14. Molecular and cellular mechanisms involved in leg joint morphogenesis.

    PubMed

    Suzanne, Magali

    2016-07-01

    In summary, the patterning of the presumptive leg depends on gradients of Dpp and Wg morphogens, which lead to the establishment of the proximo-distal axis marked by the expression of Hth, Dac and Dll in broad domains along the leg. Then, EGFR signaling specifies the tarsal region by regulating the expression of tarsal gap genes in different tarsal segments. This patterning is closely linked to the formation of rings of Notch activation in the distal part of each leg segment. These rings of Notch activation are further regulated by different mechanisms: (1) the maintenance of a sharp border of Dl expression, (2) the inhibition of N activation in cells located proximally to the ligands, thus restricting N activity specifically to the distal part of cells. This localised activation of Notch induces the expression of Dysfusion which controls the expression of both pro-apoptotic genes and RhoGTPase regulators. Finally, apoptotic cells appear within the pro-apoptotic domain, and while dying, generate a transient pulling force. This force constitutes a mechanical signal that propagates to the rest of the tissue and triggers cytoskeleton reorganisation specifically in the presumptive fold, where RhoGTPase regulators are expressed. Altogether, this complex array of patterning and signaling leads to precise cellular mapping of the developing leg to correctly position local cell shape modifications, inducing tissue folding. PMID:26845195

  15. Genetic mechanisms involved in the phenotype of Down syndrome.

    PubMed

    Patterson, David

    2007-01-01

    Down syndrome (DS) is the most common genetic cause of significant intellectual disability in the human population, occurring in roughly 1 in 700 live births. The ultimate cause of DS is trisomy of all or part of the set of genes located on chromosome 21. How this trisomy leads to the phenotype of DS is unclear. The completion of the DNA sequencing and annotation of the long arm of chromosome 21 was a critical step towards understanding the genetics of the phenotype. However, annotation of the chromosome continues and the functions of many genes on chromosome 21 remain uncertain. Recent findings about the structure of the human genome and of chromosome 21, in particular, and studies on mechanisms of gene regulation indicate that various genetic mechanisms may be contributors to the phenotype of DS and to the variability of the phenotype. These include variability of gene expression, the activity of transcription factors both encoded on chromosome 21 and encoded elsewhere in the genome, copy number polymorphisms, the function of conserved nongenic regions, microRNA activities, RNA editing, and perhaps DNA methylation. In this manuscript, we describe current knowledge about these genetic complexities and their likely importance in the context of DS. We identify gaps in current knowledge and suggest priorities to fill these gaps. PMID:17910086

  16. 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. PMID:26559926

  17. 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

  18. 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.

  19. A Model to Study Articular Cartilage Mechanical and Biological Responses to Sliding Loads.

    PubMed

    Schätti, Oliver R; Gallo, Luigi M; Torzilli, Peter A

    2016-08-01

    In physiological conditions, joint function involves continuously moving contact areas over the tissue surface. Such moving contacts play an important role for the durability of the tissue. It is known that in pathological joints these motion paths and contact mechanics change. Nevertheless, limited information exists on the impact of such physiological and pathophysiological dynamic loads on cartilage mechanics and its subsequent biological response. We designed and validated a mechanical device capable of applying simultaneous compression and sliding forces onto cartilage explants to simulate moving joint contact. Tests with varying axial loads (1-4 kg) and sliding speeds (1-20 mm/s) were performed on mature viable bovine femoral condyles to investigate cartilage mechanobiological responses. High loads and slow sliding speeds resulted in highest cartilage deformations. Contact stress and effective cartilage moduli increased with increasing load and increasing speed. In a pilot study, changes in gene expression of extracellular matrix proteins were correlated with strain, contact stress and dynamic effective modulus. This study describes a mechanical test system to study the cartilage response to reciprocating sliding motion and will be helpful in identifying mechanical and biological mechanisms leading to the initiation and development of cartilage degeneration. PMID:26698580

  20. Biologically Inspired Object Tracking Using Center-Surround Saliency Mechanisms.

    PubMed

    Mahadevan, Vijay; Vasconcelos, Nuno

    2013-03-01

    A biologically inspired discriminant object tracker is proposed. It is argued that discriminant tracking is a consequence of top-down tuning of the saliency mechanisms that guide the deployment of visual attention. The principle of discriminant saliency is then used to derive a tracker that implements a combination of center-surround saliency, a spatial spotlight of attention, and feature-based attention. In this framework, the tracking problem is formulated as one of continuous target-background classification, implemented in two stages. The first, or learning stage, combines a focus of attention (FoA) mechanism, and bottom-up saliency to identify a maximally discriminant set of features for target detection. The second, or detection stage, uses a feature-based attention mechanism and a target-tuned top-down discriminant saliency detector to detect the target. Overall, the tracker iterates between learning discriminant features from the target location in a video frame and detecting the location of the target in the next. The statistics of natural images are exploited to derive an implementation which is conceptually simple and computationally efficient. The saliency formulation is also shown to establish a unified framework for classifier design, target detection, automatic tracker initialization, and scale adaptation. Experimental results show that the proposed discriminant saliency tracker outperforms a number of state-of-the-art trackers in the literature. PMID:22529325

  1. A mechanism of paraquat toxicity involving nitric oxide synthase

    PubMed Central

    Day, Brian J.; Patel, Manisha; Calavetta, Lisa; Chang, Ling-Yi; Stamler, Jonathan S.

    1999-01-01

    Paraquat (PQ) is a well described pneumotoxicant that produces toxicity by redox cycling with cellular diaphorases, thereby elevating intracellular levels of superoxide (O2⨪). NO synthase (NOS) has been shown to participate in PQ-induced lung injury. Current theory holds that NO reacts with O2⨪ generated by PQ to produce the toxin peroxynitrite. We asked whether NOS might alternatively function as a PQ diaphorase and reexamined the question of whether NO/O2⨪ reactions were toxic or protective. Here, we show that: (i) neuronal NOS has PQ diaphorase activity that inversely correlates with NO formation; (ii) PQ-induced endothelial cell toxicity is attenuated by inhibitors of NOS that prevent NADPH oxidation, but is not attenuated by those that do not; (iii) PQ inhibits endothelium-derived, but not NO-induced, relaxations of aortic rings; and (iv) PQ-induced cytotoxicity is potentiated in cytokine-activated macrophages in a manner that correlates with its ability to block NO formation. These data indicate that NOS is a PQ diaphorase and that toxicity of such redox-active compounds involves a loss of NO-related activity. PMID:10535996

  2. Distinctive pathological mechanisms involved in primary progressive aphasias.

    PubMed

    Leyton, Cristian E; Britton, Anna K; Hodges, John R; Halliday, Glenda M; Kril, Jillian J

    2016-02-01

    Primary progressive aphasia (PPA) comprises a heterogeneous group of neurodegenerative conditions that can be classified in three cliniconeuroanatomic syndromes. Limited information exists, however, about patterns of neuropathologic spreading and microscopic changes underpinning each syndrome. We performed an analysis of a longitudinal in vivo cohort and a postmortem PPA cohort to investigate neurodegeneration over time and to quantify microscopic changes in key language brain areas. The longitudinal analyses demonstrated distinctive patterns of topological extension of brain atrophy. Although semantic variant (sv-PPA) showed an eccentric pattern, nonfluent and/or agrammatic (nfv-PPA) and logopenic (lv-PPA) variants showed additional multifocal extension. The quantitative pathology showed that sv-PPA had neuronal loss and thinning in BA 38, whereas nfv-PPA showed thinning in BA 44/45 and evidence of microscopic involvement in BA 40/22. Although lv-PPA showed neuronal loss focused on BA 40/22, imaging results demonstrated widespread left-sided brain atrophy. These analyses provide an account of the pathologic process whereby each variant has stereotypical patterns of brain atrophy extension, which is largely determined by the specific pathologic type. PMID:26827646

  3. 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. PMID:10840802

  4. Fluid Mechanics of Biological Surfaces and their Technological Application

    NASA Astrophysics Data System (ADS)

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

    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.

  5. Nutritional Systems Biology Modeling: From Molecular Mechanisms to Physiology

    PubMed Central

    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

    2009-01-01

    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. PMID:19956660

  6. Drug interactions involving cimetidine--mechanisms, documentation, implications.

    PubMed

    Greene, W

    1984-01-01

    In summary, cimetidine is a potent inhibitor of liver microsomal activity, which may also decrease hepatic blood flow. Other effects of the drug include inhibition of gastric secretion and intrinsic toxic properties. These effects, combined with the common use of cimetidine in clinical practice, make the risk of adverse drug interactions a relatively frequent risk in the clinical setting. Although a multitude of interactions with cimetidine has been evaluated, many of these are incompletely described or understood. At the present time, a potentially significant alteration of absorption appears to exist with only ketoconazole, elemental iron, vitamin B12 (long-term therapy), and pancreatic enzyme supplements (increased activity). Significant metabolic inhibition or decreased excretion appears to exist with warfarin, propranolol, theophylline, phenytoin, quinidine, possibly lidocaine and procainamide, and certain benzodiazepines. Other potential, but less well ascertained interactions may involve the narcotic analgesics, caffeine, ethanol, pentobarbital, imipramine, chlormethiazole, and metronidazole. In these settings, the clinician must be aware of interaction potential, and astutely monitor the patient during combination therapy. Other data indicate that concomitant administration of antacids may reduce the absorption of cimetidine, that the drug may protect against the toxic effects of acetaminophen overdose, and that combination with certain other myelosuppressants may carry a significant risk. Thus, in regard to these reports, cimetidine is a drug with complex effects on the absorption, elimination, and toxicity of other drugs. When used in the setting of multiple drug therapy, the clinician must be alert to potentially increased or decreased effects of the drugs mentioned in this review. In addition, one must be aware that other hepatically metabolised agents not mentioned here may be affected by the addition of cimetidine therapy. Because of the therapeutic

  7. Damage and failure mechanisms associated with photoablation of biological tissues

    SciTech Connect

    Antoun, T.; Seaman, L.; Curran, D.; Glinsky, M.

    1996-05-01

    This paper aims to examine the processes associated with failure of the cornea and other collagenous tissues during photoablation. Two different constitutive models are applied to simulate a series of laser deposition experiments into porcine reticular dermis (1), a biological tissue similar to the cornea in composition and photoablation characteristics. The first of our constitutive models, DFRACT, is a physically motivated, micromechanical model based on the nucleation and growth of spherical voids (2). The second is a relatively simple model that allows the material to vaporize and thermally soften. The simulation results reproduce the prominent features observed experimentally thereby shedding a new light on the operative mechanisms during photoablation. The good qualitative agreement between the simulated stress histories and the stress histories measured during the experiments also demonstrates the effectiveness of micromechanical damage and failure modeling as a viable tool for optimizing existing laser surgery procedures and designing new ones. {copyright} {ital 1996 American Institute of Physics.}

  8. 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.

  9. The prion hypothesis: from biological anomaly to basic regulatory mechanism

    PubMed Central

    Tuite, Mick F; Serio, Tricia R

    2010-01-01

    Preface Prions are unusual proteinaceous infectious agents that are typically associated with a class of fatal degenerative diseases of the mammalian brain. However, the discovery of fungal prions, which are not associated with disease, suggests that we must now consider the impact of these factors on basic cellular physiology in a different light. Fungal prions are epigenetic determinants that can alter a range of cellular processes, including metabolism and gene expression pathways, and these changes can lead to a range of prion-associated phenotypes. The mechanistic similarities between prion propagation in mammals and fungi suggest that prions are not a biological anomaly but instead are a new appreciated and perhaps ubiquitous regulatory mechanism. PMID:21081963

  10. Physical basis and biological mechanisms of gold nanoparticle radiosensitization.

    PubMed

    Butterworth, Karl T; McMahon, Stephen J; Currell, Fred J; Prise, Kevin M

    2012-08-21

    The unique properties of nanomaterials, in particular gold nanoparticles (GNPs) have applications for a wide range of biomedical applications. GNPs have been proposed as novel radiosensitizing agents due to their strong photoelectric absorption coefficient. Experimental evidence supporting the application of GNPs as radiosensitizing agents has been provided from extensive in vitro investigation and a relatively limited number of in vivo studies. Whilst these studies provide experimental evidence for the use of GNPs in combination with ionising radiation, there is an apparent disparity between the observed experimental findings and the level of radiosensitization predicted by mass energy absorption and GNP concentration. This review summarises experimental findings and attempts to highlight potential underlying biological mechanisms of response in GNP radiosensitization. PMID:22767423

  11. 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

  12. Central mechanisms involved in pilocarpine-induced pressor response.

    PubMed

    Takakura, Ana C; Moreira, Thiago S; Borella, Thais L; Paulin, Renata F; Colombari, Débora S A; De Luca, Laurival A; Colombari, Eduardo; Menani, José V

    2011-10-28

    Pilocarpine (cholinergic muscarinic agonist) injected peripherally may act centrally to produce pressor responses; in the present study, using c-fos immunoreactive expression, we investigated the forebrain and brainstem areas activated by pressor doses of intravenous (i.v.) pilocarpine. In addition, the importance of vasopressin secretion and/or sympathetic activation and the effects of lesions in the anteroventral third ventricle (AV3V) region in awake rats were also investigated. In male Holtzman rats, pilocarpine (0.04 to 4μmol/kg b.w.) i.v. induced transitory hypotension followed by long lasting hypertension. Sympathetic blockade with prazosin (1mg/kg b.w.) i.v. or AV3V lesions (1 day) almost abolished the pressor response to i.v. pilocarpine (2μmol/kg b.w.), whereas the vasopressin antagonist (10μg/kg b.w.) i.v. reduced the response to pilocarpine. Pilocarpine (2 and 4μmol/kg b.w.) i.v. increased the number of c-fos immunoreactive cells in the subfornical organ, paraventricular and supraoptic nuclei of the hypothalamus, organ vasculosum of the lamina terminalis, median preoptic nucleus, nucleus of the solitary tract and caudal and rostral ventrolateral medulla. These data suggest that i.v. pilocarpine activates specific forebrain and brainstem mechanisms increasing sympathetic activity and vasopressin secretion to induce pressor response. PMID:21689994

  13. Computation of the effective mechanical response of biological networks accounting for large configuration changes.

    PubMed

    El Nady, K; Ganghoffer, J F

    2016-05-01

    The asymptotic homogenization technique is involved to derive the effective elastic response of biological membranes viewed as repetitive beam networks. Thereby, a systematic methodology is established, allowing the prediction of the overall mechanical properties of biological membranes in the nonlinear regime, reflecting the influence of the geometrical and mechanical micro-parameters of the network structure on the overall response of the equivalent continuum. Biomembranes networks are classified based on nodal connectivity, so that we analyze in this work 3, 4 and 6-connectivity networks, which are representative of most biological networks. The individual filaments of the network are described as undulated beams prone to entropic elasticity, with tensile moduli determined from their persistence length. The effective micropolar continuum evaluated as a continuum substitute of the biological network has a kinematics reflecting the discrete network deformation modes, involving a nodal displacement and a microrotation. The statics involves the classical Cauchy stress and internal moments encapsulated into couple stresses, which develop internal work in duality to microcurvatures reflecting local network undulations. The relative ratio of the characteristic bending length of the effective micropolar continuum to the unit cell size determines the relevant choice of the equivalent medium. In most cases, the Cauchy continuum is sufficient to model biomembranes. The peptidoglycan network may exhibit a re-entrant hexagonal configuration due to thermal or pressure fluctuations, for which micropolar effects become important. The homogenized responses are in good agreement with FE simulations performed over the whole network. The predictive nature of the employed homogenization technique allows the identification of a strain energy density of a hyperelastic model, for the purpose of performing structural calculations of the shape evolutions of biomembranes. PMID:26541071

  14. 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

  15. 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

  16. Mechanisms of biological effects of radiofrequency electromagnetic fields: an overview

    SciTech Connect

    Erwin, D.N.

    1988-11-01

    Manmade sources of electromagnetic (EM) fields, and therefore human exposures to them, continue to increase. Public concerns stem from the effects reported in the literature, the visibility of the sources, and somewhat from confusion between EM fields and ionizing radiation. Protecting humans from the real hazards and allaying groundless fears requires a self-consistent body of scientific data concerning effects of the fields, levels of exposures which cause those effects, and which effects are deleterious (or beneficial or neutral). With that knowledge, appropriate guidelines for safety can be devised, while preserving the beneficial uses of radiofrequency radiation (RFR) energy for military or civilian purposes. The task is monumental because of the large and growing number of biological endpoints and the infinite array of RFR exposure conditions under which those endpoints might be examined. The only way to reach this goal is to understand the mechanisms by which EM fields interact with tissues. As in other fields of science, a mechanistic understanding of RFR effects will enable scientists to generalize from a selected few experiments to derive the laws of RFR bioeffects. This article gives an overview of present knowledge of those mechanisms and the part that the USAF School of Aerospace Medicine has played in expanding that knowledge. 91 references.

  17. Biological effects of menadione photochemistry: effects of menadione on biological systems may not involve classical oxidant production.

    PubMed

    McCormick, M L; Denning, G M; Reszka, K J; Bilski, P; Buettner, G R; Rasmussen, G T; Railsback, M A; Britigan, B E

    2000-09-15

    Because cell-mediated reduction of menadione leads to the generation of reactive oxygen species (ROS), this quinone is widely used to investigate the effects of ROS on cellular functions. We report that A549 human lung epithelial cells exposed to menadione demonstrate a dose-dependent increase in both intracellular calcium ([Ca(2+)](i)) and ROS formation. The concentrations of menadione required to initiate these two events are markedly different, with ROS detection requiring higher levels of menadione. Modulators of antioxidant defences (e.g. buthionine sulphoximine, 3-amino-1,2,4-triazole) have little effect on the [Ca(2+)](i) response to menadione, suggesting that ROS formation does not account for menadione-dependent alterations in [Ca(2+)](i). Additional evidence suggests that menadione photochemistry may be responsible for the observed [Ca(2+)](i) effects. Specifically: (a) EPR studies with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) show that light exposure (maximum effect at 340 nm) stimulates menadione-dependent formation of the DMPO/(.)OH spin adduct that was not sensitive to antioxidant interventions; (b) DMPO inhibits menadione and light-dependent increases in [Ca(2+)](i); and (c) light (maximum effect at 340 nm) augments the deleterious effects of menadione on cell viability as determined by (51)Cr release. These photo effects do not appear to involve formation of singlet oxygen by menadione, but rather are the result of the oxidizing chemistry initiated by menadione in the triplet state. This work demonstrates that menadione species generated by photo-irradiation can exert biological effects on cellular functions and points to the potential importance of photochemistry in studies of menadione-mediated cell damage. PMID:10970795

  18. Biological effects of menadione photochemistry: effects of menadione on biological systems may not involve classical oxidant production.

    PubMed Central

    McCormick, M L; Denning, G M; Reszka, K J; Bilski, P; Buettner, G R; Rasmussen, G T; Railsback, M A; Britigan, B E

    2000-01-01

    Because cell-mediated reduction of menadione leads to the generation of reactive oxygen species (ROS), this quinone is widely used to investigate the effects of ROS on cellular functions. We report that A549 human lung epithelial cells exposed to menadione demonstrate a dose-dependent increase in both intracellular calcium ([Ca(2+)](i)) and ROS formation. The concentrations of menadione required to initiate these two events are markedly different, with ROS detection requiring higher levels of menadione. Modulators of antioxidant defences (e.g. buthionine sulphoximine, 3-amino-1,2,4-triazole) have little effect on the [Ca(2+)](i) response to menadione, suggesting that ROS formation does not account for menadione-dependent alterations in [Ca(2+)](i). Additional evidence suggests that menadione photochemistry may be responsible for the observed [Ca(2+)](i) effects. Specifically: (a) EPR studies with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) show that light exposure (maximum effect at 340 nm) stimulates menadione-dependent formation of the DMPO/(.)OH spin adduct that was not sensitive to antioxidant interventions; (b) DMPO inhibits menadione and light-dependent increases in [Ca(2+)](i); and (c) light (maximum effect at 340 nm) augments the deleterious effects of menadione on cell viability as determined by (51)Cr release. These photo effects do not appear to involve formation of singlet oxygen by menadione, but rather are the result of the oxidizing chemistry initiated by menadione in the triplet state. This work demonstrates that menadione species generated by photo-irradiation can exert biological effects on cellular functions and points to the potential importance of photochemistry in studies of menadione-mediated cell damage. PMID:10970795

  19. 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

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

    PubMed Central

    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

  1. 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

  2. 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. PMID:27199421

  3. Alaska Native people's perceptions, understandings, and expectations for research involving biological specimens

    PubMed Central

    Hiratsuka, Vanessa Y.; Brown, Jennifer K.; Hoeft, Theresa J.; Dillard, Denise A.

    2012-01-01

    Objectives Members of racially and ethnically diverse groups have been persistently underrepresented in biomedical research in general, possibly due to mistrust with the medical and research community. This article describes the perceptions, understandings, and expectations of Alaska Native people about research involving the collection and storage of biological specimens. Study design Stratified focus groups. Methods Twenty-nine focus groups with Alaska Native people (n = 178) were held in 14 locations using a semi-structured moderator guide. ATLAS.ti was used for thematic analysis through iterative readings and coding. Alaska Native peoples’ perceptions, understandings, and expectations of researcher beneficence, informed consent processes, and provision of research findings were elicited. Results and conclusions Alaska Native people desired extensive disclosure of information beyond that typically provided in consent and results dissemination processes. Information germane to the motivation and intent of researchers and specifics of specimen storage and destruction were specifically requested. A clear and extensive process of informed consent and continued improvements in sharing results may enhance the transparency of research intent, conduct, and use of obtained results among Alaska Native people. Meeting expectations may improve relationships between researchers and the Alaska Native population which could result in increased research participation. Our findings offer a guide for researchers and communities when planning and implementing research with biological specimens. PMID:22663942

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

    PubMed

    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

  5. 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. PMID:24356000

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

    PubMed Central

    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. PMID:23267355

  7. Fundamental Mechanisms of Pulsed Laser Ablation of Biological Tissue

    NASA Astrophysics Data System (ADS)

    Albagli, Douglas

    The ability to cut and remove biological tissue with short pulsed laser light, a process called laser ablation, has the potential to revolutionize many surgical procedures. Ablation procedures using short pulsed lasers are currently being developed or used in many fields of medicine, including cardiology, ophthalmology, dermatology, dentistry, orthopedics, and urology. Despite this, the underlying physics of the ablation process is not well understood. In fact, there is wide disagreement over whether the fundamental mechanism is primarily photothermal, photomechanical, or photochemical. In this thesis, both experimental and theoretical techniques are developed to explore this issue. The photothermal model postulates that ablation proceeds through vaporization of the target material. The photomechanical model asserts that ablation is initiated when the laser-induced tensile stress exceeds the ultimate tensile strength of the target. I have developed a three dimensional model of the thermoelastic response of tissue to short pulsed laser irradiation which allows the time dependent stress distribution to be calculated given the optical, thermal and mechanical properties of the target. A complimentary experimental technique has been developed to verify this model, measure the needed physical properties of the tissue, and record the thermoelastic response of the tissue at the onset of ablation. The results of this work have been widely disseminated to the international research community and have led to significant findings which support the photomechanical model of ablation of tissue. First, the energy deposited in tissue is an order of magnitude less than that required for vaporization. Second, unlike the one-dimensional thermoelastic model of laser-induced stress generation that has appeared in the literature, the full three-dimensional model predicts the development of significant tensile stresses on the surface of the target, precisely where ablation is observed to

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

    PubMed

    Guo, Peixuan; Noji, Hiroyuki; Yengo, Christopher M; Zhao, Zhengyi; Grainge, Ian

    2016-03-01

    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

  9. 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. PMID:18338701

  10. 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

    2012-12-01

    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. PMID:23108553

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

    PubMed Central

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

    2012-01-01

    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 Δ9-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 (Ca2+) increase, etc.), on CBD behavioural effects. PMID:23108553

  12. 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. PMID:19932986

  13. 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.

  14. 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

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

    PubMed

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

    2014-10-01

    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

  16. Mechanism of aerobic biological destabilisation of wool scour effluent emulsions.

    PubMed

    Poole, Andrew J; Cord-Ruwisch, Ralf; William Jones, F

    2005-07-01

    Wool scouring effluent is a highly polluted industrial wastewater in which the main pollutant, wool wax, is held in a stable oil-in-water emulsion by non-ionic detergent. The use of microbial action to cause emulsion destabilisation has been proposed as a new treatment strategy for this effluent stream. This strategy aims at improving aerobic treatment performance by physically removing the high-COD, slowly bio-degradable wool wax from the system without bio-degradation. The mechanism by which an aerobic-mixed culture destabilises the wool scouring effluent emulsion was investigated. Our results show that destabilisation is due to partial bio-degradation of both the scouring detergent and the wool wax. Cleavage of the wool wax esters was the first stage in wax degradation, when 40-50% of wax was de-emulsified. Over the same period, detergent degradation was low, at 7-21%. With further incubation, detergent degradation increased, aiding further breakdown of the emulsion. The degradation of the detergent, a nonylphenol ethoxylate, resulted in both a reduction in molar concentration (of up to 82%) and a shortening of the ethoxylate chain length. The latter reduced the hydrophile-lipophile balance (HLB) from 12 to approximately 7, thereby reducing the ability of the residual detergent to stabilise the emulsion. Analysis of the emulsified and de-emulsified wax fractions could not identify a group of compounds that were preferentially de-emulsified based on molecular weight or polarity. These findings will assist in using a de-emulsification strategy in both existing and new treatment systems in order to save on aeration costs and treatment times for biological treatment of this highly polluted wastewater. PMID:15979119

  17. Biological pattern formation: from basic mechanisms to complex structures

    SciTech Connect

    Koch, A.J.; Meinhardt, H. )

    1994-10-01

    The reliable development of highly complex organisms is an intriguing and fascinating problem. The genetic material is, as a rule, the same in each cell of an organism. How then do cells, under the influence of their common genes, produce spatial patterns Simple models are discussed that describe the generation of patterns out of an initially nearly homogeneous state. They are based on nonlinear interactions of at least two chemicals and on their diffusion. The concepts of local autocatalysis and of long-range inhibition play a fundamental role. Numerical simulations show that the models account for many basic biological observations such as the regeneration of a pattern after excision of tissue or the production of regular (or nearly regular) arrays of organs during (or after) completion of growth. Very complex patterns can be generated in a reproducible way by hierarchical coupling of several such elementary reactions. Applications to animal coats and to the generation of polygonally shaped patterns are provided. It is further shown how to generate a strictly periodic pattern of units that themselves exhibit a complex and polar fine structure. This is illustrated by two examples: the assembly of photoreceptor cells in the eye of [ital Drosophila] and the positioning of leaves and axillary buds in a growing shoot. In both cases, the substructures have to achieve an internal polarity under the influence of some primary pattern-forming system existing in the fly's eye or in the plant. The fact that similar models can describe essential steps in organisms as distantly related as animals and plants suggests that they reveal some universal mechanisms.

  18. 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

  19. Mechanics of elastin: molecular mechanism of biological elasticity and its relationship to contraction.

    PubMed

    Urry, D W; Parker, T M

    2002-01-01

    Description of the mechanics of elastin requires the understanding of two interlinked but distinct physical processes; the development of entropic elastic force and the occurrence of hydrophobic association. Elementary statistical-mechanical analysis of AFM single-chain force-extension data of elastin model molecules identifies damping of internal chain dynamics on extension as a fundamental source of entropic elastic force and eliminates the requirement of random chain networks. For elastin and its models, this simple analysis is substantiated experimentally by the observation of mechanical resonances in the dielectric relaxation and acoustic absorption spectra, and theoretically by the dependence of entropy on frequency of torsion-angle oscillations, and by classical molecular-mechanics and dynamics calculations of relaxed and extended states of the beta-spiral description of the elastin repeat, (GVGVP)n. The role of hydrophobic hydration in the mechanics of elastin becomes apparent under conditions of isometric contraction. During force development at constant length, increase in entropic elastic force resulting from decrease in elastomer entropy occurs under conditions of increase in solvent entropy. This eliminates the solvent entropy change as the entropy change that gives rise to entropic elastic force and couples association of hydrophobic domains to the process. Therefore, association of hydrophobic domains within the elastomer at fixed length stretches interconnecting dynamic chain segments and causes an increase in the entropic elastic force due to the resulting damping of internal chain dynamics. Fundamental to the mechanics of elastin is the inverse temperature transition of hydrophobic association that occurs with development of mechanical resonances within fibrous elastin and polymers of repeat elastin sequences, which, with design of truly minimal changes in sequence, demonstrate energy conversions extant in biology and demonstrate the special

  20. Oxidative mechanisms of biological activity of low-intensity radiofrequency radiation.

    PubMed

    Yakymenko, Igor; Tsybulin, Olexandr; Sidorik, Evgeniy; Henshel, Diane; Kyrylenko, Olga; Kyrylenko, Sergiy

    2016-01-01

    This review aims to cover experimental data on oxidative effects of low-intensity radiofrequency radiation (RFR) in living cells. Analysis of the currently available peer-reviewed scientific literature reveals molecular effects induced by low-intensity RFR in living cells; this includes significant activation of key pathways generating reactive oxygen species (ROS), activation of peroxidation, oxidative damage of DNA and changes in the activity of antioxidant enzymes. It indicates that among 100 currently available peer-reviewed studies dealing with oxidative effects of low-intensity RFR, in general, 93 confirmed that RFR induces oxidative effects in biological systems. A wide pathogenic potential of the induced ROS and their involvement in cell signaling pathways explains a range of biological/health effects of low-intensity RFR, which include both cancer and non-cancer pathologies. In conclusion, our analysis demonstrates that low-intensity RFR is an expressive oxidative agent for living cells with a high pathogenic potential and that the oxidative stress induced by RFR exposure should be recognized as one of the primary mechanisms of the biological activity of this kind of radiation. PMID:26151230

  1. FROM THE CURRENT LITERATURE: Mechanisms and models of the dehydration self-organization in biological fluids

    NASA Astrophysics Data System (ADS)

    Tarasevich, Yurii Yu

    2004-07-01

    The dehydration self-organization phenomenon in biological fluids attracted the attention of researchers slightly more than a decade ago. While seemingly simple (the structure formation is possible to observe even in domestic conditions), the effect turned out to be extremely complicated and to involve a number of interrelated processes of a different physical nature. The dehydration self-organization effect in biological fluids underlies a medical diagnostic technique patented in 40 countries of the world, while the mechanisms that underlie the technique still remain largely obscure. This review is an attempt to draw an integrated picture of the current state of the problem: to emphasize reliably established facts and the problems that remain to be solved, to put an end to speculation, and to characterize the available theories and models. An analysis of the literature sources allows us to draw the conclusion that the effects observed in the dehydration of biological fluids are typical for colloidal solutions in general and can be described in the framework of conventional physical approaches.

  2. 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

  3. 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

  4. Systems biology approaches to understanding mycobacterial survival mechanisms

    PubMed Central

    Boshoff, Helena I.M.; Lun, Desmond S.

    2010-01-01

    The advent of high-throughput platforms for the interrogation of biological systems at the cellular and molecular level have allowed living cells to be observed and understood at a hitherto unprecedented level of detail and have enabled the construction of comprehensive, predictive in silico models. Here, we review the application of such high-throughput, systems-biological techniques to mycobacteria—specifically to the pernicious human pathogen Mycobacterium tuberculosis (MTb) and its ability to survive in human hosts. We discuss the development and application of transcriptomic, proteomic, regulomic, and metabolomic techniques for MTb as well as the development and application of genome-scale in silico models. Thus far, systems-biological approaches have largely focused on in vitro models of MTb growth; reliably extending these approaches to in vivo conditions relevant to infection is a significant challenge for the future that holds the ultimate promise of novel chemotherapeutic interventions. PMID:21072257

  5. 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.

  6. Effects of mechanical ventilation on diaphragm function and biology.

    PubMed

    Gayan-Ramirez, G; Decramer, M

    2002-12-01

    The pathophysiological mechanisms of weaning from mechanical ventilation are not fully known, but there is accumulating evidence that mechanical ventilation induces inspiratory muscle dysfunction. Recently, several animal models have provided potential mechanisms for mechanical ventilation-induced effects on muscle function. In patients, weaning difficulties are associated with inspiratory muscle weakness and reduced endurance capacity. Animal studies demonstrated that diaphragm force was already decreased after 12 h of controlled mechanical ventilation and this worsened with time spent on the ventilator. Diaphragmatic myofibril damage observed after 3-days controlled mechanical ventilation was inversely correlated with maximal diaphragmatic force. Downregulation of the diaphragm insulin-like growth factor-I and MyoD/myogenin messenger ribonucleic acid occurred after 24 h and diaphragmatic oxidative stress and increased protease activity after 18 h. In keeping with these findings, diaphragm fibre atrophy was shown after 12 h and reduced diaphragm mass was reported after 48 h of controlled mechanical ventilation. These animal studies show that early alterations in diaphragm function develop after short-term mechanical ventilation. These alterations may contribute to the difficulties in weaning from mechanical ventilation seen in patients. Strategies to preserve respiratory muscle mass and function during mechanical ventilation should be developed. These may include: adaptation of medication, training of the diaphragm, stabilisation of the catabolic state and pharmacotherapy. PMID:12503720

  7. Teaching the basics of redox biology to medical and graduate students: Oxidants, antioxidants and disease mechanisms.

    PubMed

    Kalyanaraman, Balaraman

    2013-01-01

    This article provides a succinct but limited overview of the protective and deleterious effects of reactive oxygen and nitrogen species in a clinical context. Reactive oxygen species include superoxide, hydrogen peroxide, single oxygen and lipid peroxides. Reactive nitrogen species include species derived from nitric oxide. This review gives a brief overview of the reaction chemistry of these species, the role of various enzymes involved in the generation and detoxification of these species in disease mechanisms and drug toxicity and the protective role of dietary antioxidants. I hope that the graphical review will be helpful for teaching both the first year medical and graduate students in the U.S. and abroad the fundamentals of reactive oxygen and nitrogen species in redox biology and clinical medicine. PMID:24024158

  8. [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. PMID:26084184

  9. 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

  10. 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

  11. Nanomechanical strength mechanisms of hierarchical biological materials and tissues.

    PubMed

    Buehler, Markus J; Ackbarow, Theodor

    2008-12-01

    Biological protein materials (BPMs), intriguing hierarchical structures formed by assembly of chemical building blocks, are crucial for critical functions of life. The structural details of BPMs are fascinating: They represent a combination of universally found motifs such as alpha-helices or beta-sheets with highly adapted protein structures such as cytoskeletal networks or spider silk nanocomposites. BPMs combine properties like strength and robustness, self-healing ability, adaptability, changeability, evolvability and others into multi-functional materials at a level unmatched in synthetic materials. The ability to achieve these properties depends critically on the particular traits of these materials, first and foremost their hierarchical architecture and seamless integration of material and structure, from nano to macro. Here, we provide a brief review of this field and outline new research directions, along with a review of recent research results in the development of structure-property relationships of biological protein materials exemplified in a study of vimentin intermediate filaments. PMID:18803059

  12. On the mechanism of adhesion in biological systems

    NASA Astrophysics Data System (ADS)

    Persson, B. N. J.

    2003-04-01

    I study adhesion relevant to biological systems, e.g., flies, crickets and lizards, where the adhesive microstructures consist of arrays of thin fibers. The effective elastic modulus of the fiber arrays can be very small which is of fundamental importance for adhesion on smooth and rough substrates. I study how the adhesion depend on the substrate roughness amplitude and apply the theoretical results to lizards.

  13. 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

    2016-01-01

    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

  14. 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.

  15. 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

  16. 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

    2015-01-01

    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

  17. 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

  18. 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.

  19. 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.

  20. On reaction mechanisms involved in the deuteron-induced surrogate reactions

    NASA Astrophysics Data System (ADS)

    Avrigeanu, M.; Avrigeanu, V.; Mǎnǎilescu, C.

    2015-02-01

    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.

  1. Mechanisms involved in calcium deficiency development in tomato fruit in response to gibberellins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although gibberellins (GAs) have been shown to induce the calcium deficiency disorder, blossom-end rot (BER), development in tomato fruit (Solanum lycopersicum), the mechanisms involved remain largely unexplored. Our objectives were to better understand how GAs and a GA biosynthesis inhibitor affect...

  2. Sound and Faulty Arguments Generated by Preservice Biology Teachers When Testing Hypotheses Involving Unobservable Entities.

    ERIC Educational Resources Information Center

    Lawson, Anton E.

    2002-01-01

    Investigates the responses of a sample of preservice biology teachers enrolled in a teaching methods course to a casual question about why water rose in a jar inverted over a burning candle placed in a pan of water by formulating and testing six hypotheses. (Contains 43 references.) (Author/YDS)

  3. 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…

  4. 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.

  5. Some Electrical and Mechanical Devices to Illustrate Biological Principles

    ERIC Educational Resources Information Center

    Kramer, L. M. J.

    1971-01-01

    Describes the use of metal construction toys (erector sets) to build laboratory equipment (to compare rates of decay, record small mammal activity, stir solutions, and function as a kymograph) and to build analogue models of skeletal joints, and feedback mechanisms responding to external stimuli. (AL)

  6. "Coding" and "Decoding": hypothesis for the regulatory mechanism involved in heparan sulfate biosynthesis.

    PubMed

    Zhang, Xu; Wang, Fengshan; Sheng, Juzheng

    2016-06-16

    Heparan sulfate (HS) is widely distributed in mammalian tissues in the form of HS proteoglycans, which play essential roles in various physiological and pathological processes. In contrast to the template-guided processes involved in the synthesis of DNA and proteins, HS biosynthesis is not believed to involve a template. However, it appears that the final structure of HS chains was strictly regulated. Herein, we report research based hypothesis that two major steps, namely "coding" and "decoding" steps, are involved in the biosynthesis of HS, which strictly regulate its chemical structure and biological activity. The "coding" process in this context is based on the distribution of sulfate moieties on the amino groups of the glucosamine residues in the HS chains. The sulfation of these amine groups is catalyzed by N-deacetylase/N-sulfotransferase, which has four isozymes. The composition and distribution of sulfate groups and iduronic acid residues on the glycan chains of HS are determined by several other modification enzymes, which can recognize these coding sequences (i.e., the "decoding" process). The degree and pattern of the sulfation and epimerization in the HS chains determines the extent of their interactions with several different protein factors, which further influences their biological activity. PMID:27088396

  7. 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.

  8. 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. PMID:25421487

  9. Multiple mechanisms for critical behavior in the biologically relevant phase of lecithin bilayers

    NASA Astrophysics Data System (ADS)

    Nagle, John F.; Petrache, Horia I.; Gouliaev, Nikolai; Tristram-Nagle, Stephanie; Liu, Yufeng; Suter, Robert M.; Gawrisch, Klaus

    1998-12-01

    Lipid bilayer membranes manifest critical behavior in the lamellar D spacing observed by x-ray and neutron diffraction as the main phase transition is approached from the biologically relevant high temperature phase. The freezing out of conformational disorder of the hydrocarbon chains drives the main transition, but how this causes critical behavior of D(T) has been an interesting puzzle and various models are under investigation. This paper presents x-ray scattering and NMR data to test the various models. One model involves the straightforward lengthening of hydrocarbon chains as TM is approached, but it is shown that this accounts only for about half the anomalous increase in D. Another model of fluctuation induced expansion of the water region is shown to be inconsistent with two kinds of data. The first inconsistency is the lack of an increase in the Caillé fluctuation parameter η1. The second inconsistency is with D(T) data taken under osmotic pressure. Accurate simulations are employed to predict the theoretical values. A third model considers that the water spacing could expand because other interactions between bilayers may change as TM is approached, but there is no quantitative support for this model at present. A fourth model involving expansion of the headgroup region is tested with NMR data; results are qualitatively consistent but quantitatively inconclusive. While the precise mixture of models is still unresolved, it is concluded that multiple mechanisms must be operating in this critical regime.

  10. 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.

  11. 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

  12. 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

  13. 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. PMID:23363005

  14. 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.

  15. 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).

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

    PubMed

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

    2015-01-01

    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. PMID:26145480

  17. Von Neumann's growth model: Statistical mechanics and biological applications

    NASA Astrophysics Data System (ADS)

    De Martino, A.; Marinari, E.; Romualdi, A.

    2012-09-01

    We review recent work on the statistical mechanics of Von Neumann's growth model and discuss its application to cellular metabolic networks. In this context, we present a detailed analysis of the physiological scenario underlying optimality à la Von Neumann in the metabolism of the bacterium E. coli, showing that optimal solutions are characterized by a considerable microscopic flexibility accompanied by a robust emergent picture for the key physiological functions. This suggests that the ideas behind optimal economic growth in Von Neumann's model can be helpful in uncovering functional organization principles of cell energetics.

  18. Chemical and Biological Mechanisms of Pathogen Reduction Technologies

    PubMed Central

    Mundt, Janna M; Rouse, Lindsay; Van den Bossche, Jeroen; Goodrich, Raymond P

    2014-01-01

    Within the last decade new technologies have been developed and implemented which employ light, often in the presence of a photosensitizer, to inactivate pathogens that reside in human blood products for the purpose of transfusion. These pathogen reduction technologies attempt to find the proper balance between pathogen kill and cell quality. Each system utilizes various chemistries that not only impact which pathogens they can inactivate and how, but also how the treatments affect the plasma and cellular proteins and to what degree. This paper aims to present the various chemical mechanisms for pathogen reduction in transfusion medicine that are currently practiced or in development. PMID:25041351

  19. 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

  20. 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

  1. 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. PMID:27115725

  2. 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. PMID:25842126

  3. 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. PMID:21863500

  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. 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

  6. 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

  7. Cell Biological Mechanisms of Multidrug Resistance in Tumors

    NASA Astrophysics Data System (ADS)

    Simon, Sanford M.; Schindler, Melvin

    1994-04-01

    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 pleotropic 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.

  8. 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

  9. Systems Biology - A Pivotal Research Methodology for Understanding the Mechanisms of Traditional Medicine

    PubMed Central

    Lee, Soojin

    2015-01-01

    Objectives: Systems biology is a novel subject in the field of life science that aims at a systems’ level understanding of biological systems. Because of the significant progress in high-throughput technologies and molecular biology, systems biology occupies an important place in research during the post-genome era. Methods: The characteristics of systems biology and its applicability to traditional medicine research have been discussed from three points of view: data and databases, network analysis and inference, and modeling and systems prediction. Results: The existing databases are mostly associated with medicinal herbs and their activities, but new databases reflecting clinical situations and platforms to extract, visualize and analyze data easily need to be constructed. Network pharmacology is a key element of systems biology, so addressing the multi-component, multi-target aspect of pharmacology is important. Studies of network pharmacology highlight the drug target network and network target. Mathematical modeling and simulation are just in their infancy, but mathematical modeling of dynamic biological processes is a central aspect of systems biology. Computational simulations allow structured systems and their functional properties to be understood and the effects of herbal medicines in clinical situations to be predicted. Conclusion: Systems biology based on a holistic approach is a pivotal research methodology for understanding the mechanisms of traditional medicine. If systems biology is to be incorporated into traditional medicine, computational technologies and holistic insights need to be integrated. PMID:26388998

  10. Mechanisms involved in the chemoprotective effects of rosemary extract studied in human liver and bronchial cells.

    PubMed

    Offord, E A; Macé, K; Avanti, O; Pfeifer, A M

    1997-03-19

    Natural polyphenols found in rosemary have not only potent antioxidant activities but also anticarcinogenic properties. We have studied some of the molecular mechanisms involved in their chemopreventive action using in vitro human liver and bronchial cell models. Rosemary extract, or its active components, carnosol or carnosic acid are potent inhibitors of DNA adduct formation induced by benzo(a)pyrene or aflatoxin B1. At least two mechanisms are involved in the anticarcinogenic action of rosemary extract: (i) inhibition of the metabolic activation of procarcinogens catalysed by the phase I cytochrome P450 enzymes; (ii) induction of the detoxification pathway catalysed by the phase II enzymes such as glutathione S-transferase. PMID:9103309

  11. 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

  12. 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…

  13. A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size.

    PubMed

    Bond, Jacquelyn; Roberts, Emma; Springell, Kelly; Lizarraga, Sofia B; Lizarraga, Sophia; Scott, Sheila; Higgins, Julie; Hampshire, Daniel J; Morrison, Ewan E; Leal, Gabriella F; Silva, Elias O; Costa, Suzana M R; Baralle, Diana; Raponi, Michela; Karbani, Gulshan; Rashid, Yasmin; Jafri, Hussain; Bennett, Christopher; Corry, Peter; Walsh, Christopher A; Woods, C Geoffrey

    2005-04-01

    Autosomal recessive primary microcephaly is a potential model in which to research genes involved in human brain growth. We show that two forms of the disorder result from homozygous mutations in the genes CDK5RAP2 and CENPJ. We found neuroepithelial expression of the genes during prenatal neurogenesis and protein localization to the spindle poles of mitotic cells, suggesting that a centrosomal mechanism controls neuron number in the developing mammalian brain. PMID:15793586

  14. Hair follicle biology and topical minoxidil: possible mechanisms of action.

    PubMed

    Headington, J T

    1987-01-01

    The mechanism by which minoxidil, whether given orally or applied topically, stimulates hair growth remains undetermined. Possible indirect drug action, such as vasodilatation and increased blood flow to the dermal papilla, or possible local irritation related to minoxidil or to one or more components of the vehicle used for topical application has been suggested. Possible sites of direct drug action include either the dermal papilla of the follicle or hair matrix cells or possibly both. Morphometric studies of control scalp biopsies taken from young male patients with androgenetic alopecia reveal that the primary morphologic event in androgenetic alopecia is miniaturization of terminal hair follicles. Shortening and diminution of follicle size is undoubtedly accompanied by shortening of the hair growth cycle (decreased anagen time). Morphometric evaluation of scalp biopsies of patients receiving topical minoxidil in a vehicle composed of propylene glycol, water and ethanol has revealed growth of larger normally formed follicles when compared with pretreatment biopsies from the same individual. There has been no suggestion in any morphologic studies of minoxidil-treated patients for development of new follicles (follicular neogenesis). Because the dermal papilla of the hair follicle apparently controls both growth and differentiation of hair matrix cells and because there are no observable dysplastic or atypical changes in follicular germinal epithelium during or after application of topical minoxidil, it is concluded that the most probable site for the action of minoxidil is on the specialized mesenchymal cells of the follicular dermal papilla. PMID:3319729

  15. 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

  16. Identification of up-regulated proteins potentially involved in the antagonism mechanism of Bacillus amyloliquefaciens G1.

    PubMed

    Cao, Haipeng; Zheng, Weidong; He, Shan; Wang, Hao; Wang, Tu; Lu, Liqun

    2013-06-01

    The use of Bacillus probiotics has been demonstrated as a promising method in the biocontrol of bacterial diseases in aquaculture. However, the molecular antibacterial mechanism of Bacillus still remains unclear. In order to explore the antibacterial mechanism of the potential antagonistic Bacillus amyloliquefaciens strain G1, comparative proteomics between B. amyloliquefaciens strain G1 and its non-antagonistic mutant strain was investigated. The 2-dimensional electrophoresis gel maps of their total extracted proteins were described and 42 different proteins were found to be highly expressed in strain G1 in comparison with those in the mutant strain. 35 of these up-regulated proteins were successfully identified using MALDI-TOF-TOF MS and databank analysis, and their biological functions were analyzed through the KEGG database. The increased expression of these proteins suggested that high levels of energy metabolism, biosynthesis and stress resistance could play important roles in strain G1's antagonism. To our knowledge, this is the first report on the proteins involved in the antagonism mechanism of B. amyloliquefaciens using a proteomic approach and the proteomic data also contribute to a better understanding of the molecular basis for the antagonism of B. amyloliquefaciens. PMID:23483288

  17. Involvement of Intermediate Sulfur Species in Biological Reduction of Elemental Sulfur under Acidic, Hydrothermal Conditions

    PubMed Central

    Druschel, Gregory K.

    2013-01-01

    The thermoacidophile and obligate elemental sulfur (S80)-reducing anaerobe Acidilobus sulfurireducens 18D70 does not associate with bulk solid-phase sulfur during S80-dependent batch culture growth. Cyclic voltammetry indicated the production of hydrogen sulfide (H2S) as well as polysulfides after 1 day of batch growth of the organism at pH 3.0 and 81°C. The production of polysulfide is likely due to the abiotic reaction between S80 and the biologically produced H2S, as evinced by a rapid cessation of polysulfide formation when the growth temperature was decreased, inhibiting the biological production of sulfide. After an additional 5 days of growth, nanoparticulate S80 was detected in the cultivation medium, a result of the hydrolysis of polysulfides in acidic medium. To examine whether soluble polysulfides and/or nanoparticulate S80 can serve as terminal electron acceptors (TEA) supporting the growth of A. sulfurireducens, total sulfide concentration and cell density were monitored in batch cultures with S80 provided as a solid phase in the medium or with S80 sequestered in dialysis tubing. The rates of sulfide production in 7-day-old cultures with S80 sequestered in dialysis tubing with pore sizes of 12 to 14 kDa and 6 to 8 kDa were 55% and 22%, respectively, of that of cultures with S80 provided as a solid phase in the medium. These results indicate that the TEA existed in a range of particle sizes that affected its ability to diffuse through dialysis tubing of different pore sizes. Dynamic light scattering revealed that S80 particles generated through polysulfide rapidly grew in size, a rate which was influenced by the pH of the medium and the presence of organic carbon. Thus, S80 particles formed through abiological hydrolysis of polysulfide under acidic conditions appeared to serve as a growth-promoting TEA for A. sulfurireducens. PMID:23335768

  18. 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. PMID:23314095

  19. Thromboembolic diseases: biochemical mechanisms and new possibilities of biological diagnosis.

    PubMed

    Amiral, J; Fareed, J

    1996-01-01

    clinically. New investigations are initiated to find analytes reflecting endothelial damage, an early platelet activation, or the involvement of blood cells (mainly monocytes and neutrophils) in abnormal processes. It also becomes possible to evaluate directly pathological causes inducing blood activation, such as the presence of antiphospholipid antibodies or other autoimmune antibodies. PMID:8807728

  20. 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. PMID:21783161

  1. NOX signaling in molecular cardiovascular mechanisms involved in the blood pressure homeostasis

    PubMed Central

    Santillo, Mariarosaria; Colantuoni, Antonio; Mondola, Paolo; Guida, Bruna; Damiano, Simona

    2015-01-01

    Blood pressure homeostasis is maintained by several mechanisms regulating cardiac output, vascular resistances, and blood volume. At cellular levels, reactive oxygen species (ROS) signaling is involved in multiple molecular mechanisms controlling blood pressure. Among ROS producing systems, NADPH oxidases (NOXs), expressed in different cells of the cardiovascular system, are the most important enzymes clearly linked to the development of hypertension. NOXs exert a central role in cardiac mechanosensing, endothelium-dependent relaxation, and Angiotensin-II (Ang-II) redox signaling regulating vascular tone. The central role of NOXs in redox-dependent cardiovascular cell functions renders these enzymes a promising pharmacological target for the treatment of cardiovascular diseases, including hypertension. The aim of the present review is to focus on the physiological role of the cardiovascular NOX-generating ROS in the molecular and cellular mechanisms affecting blood pressure. PMID:26217233

  2. 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.

  3. A novel mechanism for the inhibition of type 2 iodothyronine deiodinase by tumor necrosis factor α: involvement of proteasomal degradation.

    PubMed

    Ogiwara, Takayuki; Araki, Osamu; Morimura, Tadashi; Tsunekawa, Katsuhiko; Mori, Masatomo; Murakami, Masami

    2013-01-01

    Thyroxine (T₄) needs to be converted to 3,5,3'-triiodothyronine (T₃) by iodothyronine deiodinase to exert its biological activity. Recent studies revealed the presence of type 2 iodothyronine deiodinase (D2) in human thyroid tissue, human skeletal muscle and other tissues, suggesting that D2 is involved in maintaining plasma T₃ level in human. Tumor necrosis factor α (TNFα) is an inflammatory cytokine of which production is elevated in patients with nonthyroidal illness. Although several lines of evidence suggest the causal role of TNFα in nonthyroidal illness, detailed nature of the effect of TNFα on D2 remains unclear. In the present study, we identified D2 activity and D2 mRNA in TCO-1 cells, which were derived from human anaplastic thyroid carcinoma, and studied the mechanisms involved in the regulation of D2 expression by TNFα. The characteristics of the deiodinating activity in TCO-1 cells were compatible with those of D2 and Northern analysis demonstrated that D2 mRNA was expressed in TCO-1cells. D2 activity and D2 mRNA expression were rapidly increased by dibutyryl cAMP ((Bu)₂cAMP). TNFα showed an inhibitory effect on (Bu)₂cAMP-stimulated D2 activity in spite of little effect on (Bu)₂cAMP-stimulated D2 mRNA expression. MG132, a proteasome inhibitor abolished TNFα suppression of D2 activity whereas BAY11-7082 or 6-amino-4-(4-phenoxyphenylethylamino) quinazoline, inhibitors of nuclear factor-κB (NF-κB) failed to attenuate the effect of TNFα on D2 activity. These data suggest that a posttranslational mechanism through proteasomal degradation but not NF-κB activation is involved in the suppression of D2 by TNFα. PMID:23719846

  4. 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". PMID:23317522

  5. Melanopsin: a novel photopigment involved in the photoentrainment of the brain's biological clock?

    PubMed

    Hannibal, Jens; Fahrenkrug, Jan

    2002-01-01

    The brain's biological clock located in the suprachiasmatic nucleus (SCN) generates circadian rhythms of physiology and behaviour of approximately 24 hours. The clock needs, however, like a watch that runs too fast or too slow, daily adjustment and the most important stimulus for this adjustment is the environmental light/dark cycle, a process know as photoentrainment. It is well established that the eye contains a separate anatomical and functional system mediating light information to the clock. Until recently, the photopigment responsible for light entrainment of the circadian system has been elusive but recent studies have provided evidence that melanopsin, a recently identified opsin, could be the circadian photopigment. This conclusion is based on the observation that melanopsin is expressed exclusively in retinal ganglion cells projecting to the SCN, a projection known as the retinohypothalamic tract (RHT) and that these ganglion cells are intrinsically photosensitive. Melanopsin is present in the plasma membrane of soma, dendrites and axons forming an extensive photoreceptive network in the entire retina. Although these findings make melanopsin a strong candidate as a circadian photopigment, a number of functional experiments are needed before the role of melanopsin is finally proven. PMID:12452484

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

    PubMed

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

    2016-07-01

    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

  7. 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.

  8. 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.

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

    PubMed

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

    2016-03-01

    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

  10. Review of endocrine disorders associated with environmental toxicants and possible involved mechanisms.

    PubMed

    Maqbool, Faheem; Mostafalou, Sara; Bahadar, Haji; Abdollahi, Mohammad

    2016-01-15

    Endocrine disrupting chemicals (EDC) are released into environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDC have major risks for human by targeting different organs and systems in the body. Multiple mechanisms are involved in targeting the normal system, through estrogen receptors, nuclear receptors and steroidal receptors activation. In this review, different methods by which xenobiotics stimulate signaling pathways and genetic mutation or DNA methylation have been discussed. These methods help to understand the results of xenobiotic action on the endocrine system. Endocrine disturbances in the human body result in breast cancer, ovarian problems, thyroid eruptions, testicular carcinoma, Alzheimer disease, schizophrenia, nerve damage and obesity. EDC characterize a wide class of compounds such as organochlorinated pesticides, industrial wastes, plastics and plasticizers, fuels and numerous other elements that exist in the environment or are in high use during daily life. The interactions and mechanism of toxicity in relation to human general health problems, especially endocrine disturbances with particular reference to reproductive problems, diabetes, and breast, testicular and ovarian cancers should be deeply investigated. There should also be a focus on public awareness of these EDC risks and their use in routine life. Therefore, the aim of this review is to summarize all evidence regarding different physiological disruptions in the body and possible involved mechanisms, to prove the association between endocrine disruptions and human diseases. PMID:26497928

  11. Thymus involvement in myasthenia gravis: Epidemiological and clinical impacts of different self-tolerance breakdown mechanisms.

    PubMed

    Karni, Arnon; Asmail, Ali; Drory, Vivian E; Kolb, Hadar; Kesler, Anat

    2016-09-15

    The reasons for the abrogation of self-immunological tolerance in patients with myasthenia gravis (MG) may be different between those with concomitant thymic hyperplasia or thymoma, and those with no evidence of thymic involvement. We conducted a retrospective observational case series study to investigate the epidemiology as well as the clinical, serologic, and electromyographic (EMG) characteristics of individuals diagnosed as having MG. We found that the average age at MG onset of patients with either thymic hyperplasia or thymoma was much younger (by ~20years) than that of MG patients without thymic involvement. Thymic hyperplasia was more common in females than males. There were no differences in the rates of ocular MG vs. generalized MG among those three study groups. There were also no group differences in the rates of neuromuscular junction disfunction, as observed on EMG or by the results of serology tests for acetyl choline receptor antibody. Interestingly, only patients without thymic involvement had other autoimmune diseases, and most of them were females. The patients with other coexisting autoimmune disease had a similar age at MG onset as the other patients with no thymic involvement. These results shed light on the impact of epidemiological and clinical factors that result from different mechanisms of self-immunological tolerance breakdown that occurs in MG. PMID:27609276

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

    PubMed

    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

    2014-01-01

    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. PMID:24892285

  13. Mechanisms involved in Korean mistletoe lectin-induced apoptosis of cancer cells

    PubMed Central

    Khil, Lee-Yong; Kim, Wi; Lyu, Suyun; Park, Won Bong; Yoon, Ji-Won; Jun, Hee-Sook

    2007-01-01

    AIM: To investigate the anti-cancer mechanisms of Korean mistletoe lectin (Viscum album coloratum agglutinin, VCA) using a human colon cancer cell line (COLO). METHODS: Cytotoxic effects of VCA on COLO cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro and tumor-killing effects in vivo. To study the mechanisms involved, the expression of various pro-caspases, anti-apoptotic proteins, and death receptors was determined by western blot. To determine which death receptor is involved in VCA-induced apoptosis of COLO cells, cytotoxicity was examined by MTT assay after treatment with agonists or antagonists of death receptors. RESULTS: VCA killed COLO cells in a time- and dose-dependent manner and induced complete regression of tumors in nude mice transplanted with COLO cells. Treatment of COLO cells with VCA activated caspase-2, -3, -8, and -9 and decreased expression of anti-apoptotic molecules including receptor interacting protein, nuclear factor-κB, X-linked inhibitor of apoptosis protein, and Akt/protein kinase B. We then examined the involvement of death receptors in VCA-induced apoptosis. Only tumor necrosis factor receptor 1, among the death receptors examined, was involved in apoptosis of COLO cells, evidenced by inhibition of VCA-induced apoptosis and decreased activation of caspases, particularly caspase-8, by tumor necrosis factor receptor 1 antagonizing antibody. CONCLUSION: VCA-induced apoptotic COLO cell death is due to the activation of caspases and inhibition of anti-apoptotic proteins, in part through the tumor necrosis factor receptor 1 signaling pathway. PMID:17569116

  14. 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

  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. 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. PMID:27050459

  17. 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

  18. 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.

  19. 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 was introduced in the 1960's 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 radical-pair mechanism 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 the radical-pair mechanism is indeed a major driving force of the emerging field of quantum biology.

  20. Characterization of compost-like outputs from mechanical biological treatment of municipal solid waste.

    PubMed

    Donovan, Sally M; Bateson, Thomas; Gronow, Jan R; Voulvoulis, Nikolaos

    2010-06-01

    Throughout the world, most municipal solid waste consists of biodegradable components. The most abundant biological component is cellulose, followed by hemicellulose and lignin. Recycling of these components is important for the carbon cycle. In an attempt to reduce the environmental impacts of biodegradable wastes, mechanical biological treatments (MBTs) are being used as a waste management process in many countries. MBT plants attempt to mechanically separate the biodegradable and nonbiodegradable components. The nonbiodegradable components are then sent for reprocessing or landfilled, whereas the biodegradable components are reduced in biological content through composting or anaerobic digestion, leaving a compost-like output (CLO). The further use of these partially degraded residues is uncertain, and in many cases it is likely that they will be landfilled. The implications of this for the future of landfill management are causing some concern because there is little evidence that the long-term emissions tail will be reduced. In this study, the CLOs from four different biological treatment processes were characterized for physical contamination through visual inspection and for biological content using a sequential digestion analysis. The results indicate that the composition of the incoming waste, dependent on the way the waste was collected/segregated, was the factor that influenced biological content most, with length of treatment process the second most important. PMID:20564995

  1. 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. PMID:25257342

  2. 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. PMID:27420171

  3. Co-morbidity and self medication in schizophrenia: involvement of endogenous morphine signaling mechanisms.

    PubMed

    Kream, Richard M; Kuzelova, Hana; Kralickova, Milena; Ptacek, Radek; Stefano, George B

    2012-10-01

    For over 30 years, empirical studies have demonstrated expression of chemically authentic morphine by diverse animal tissues and organs systems. De novo biosynthesis of endogenous morphine by animal cells displays striking similarities to the multi-enzyme mediated biosynthetic pathway previously characterized in great biochemical and molecular detail in opium poppy (Papaver somniferum). The committed enzyme step within this pathway involves an asymmetric Pictet-Spengler condensation of dopamine (DA) and 3,4 dihydroxyphenylacetaldehyde (DOPAL), the oxidation product of L- 3,4-dihydroxyphenylalanine (L-DOPA), to form the essential intermediate precursor tetrahydropapaveroline (THP). We have hypothesized that endogenous morphine is synthesized within peripheral sites via conversion of THP in a regulated biosynthetic pathway, or conversely, THP may be directly transported into the CNS and converted to endogenous morphine within a similar biosynthetic pathway. The fundamental chemical relationship of the prototype catecholamine DA and its immediate precursor L-DOPA to endogenous morphine expression indicates a novel reciprocally interactive mechanism that links catecholamine and "morphinergic" pathways in the activation and inhibition of key physiological responses, including higher order neural integration. Dysregulation of interactive DAergic and "morphinergic" signaling pathways within CNS foci may contribute to the etiological factors driving co-morbid behavioral syndromes in major psychiatric disorders. Our short review is designed to provide insights on comorbidity and self-medication in schizophrenia from a novel perspective involving endogenous morphine signaling mechanisms. PMID:22876887

  4. 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. PMID:25399920

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

    PubMed Central

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

    2015-01-01

    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. PMID:25399920

  6. [A mechanism conjugating cellular and individual adaptations could be produced from space biology].

    PubMed

    Atomi, Y

    2001-03-01

    To know a basic mechanism of biological organism on the earth, we can have a standard point to space. An example is hindlimb suspension model that could induce muscle atrophy. This model mimics adaptational changes under zero gravity; in turn the effect of gravity on the biological system developing on the earth. We can understand gravity is a stress from the specific changes of stress protein induced by mechanical stimuli depending on gravity. Recent development of fluorescent microscopy and time-lapse visual system brought us a possibility of analysis to see visualization of dynamic properties of molecular and cellular events in living cells. Especially dynamic fluctuation of cytoskeleton may include new ideas of biological strategy of living organism on the earth and possibly may suggest subtle changes in space. PMID:12101374

  7. Role of the endocannabinoid system in the mechanisms involved in the LPS-induced preterm labor.

    PubMed

    Bariani, María Victoria; Domínguez Rubio, Ana Paula; Cella, Maximiliano; Burdet, Juliana; Franchi, Ana María; Aisemberg, Julieta

    2015-12-01

    Prematurity is the leading cause of perinatal morbidity and mortality worldwide. There is a strong causal relationship between infection and preterm births. Intrauterine infection elicits an immune response involving the release of inflammatory mediators like cytokines and prostaglandins (PG) that trigger uterine contractions and parturition events. Anandamide (AEA) is an endogenous ligand for the cannabinoid receptors CB1 and CB2. Similarly to PG, endocannabinoids are implicated in different aspects of reproduction, such as maintenance of pregnancy and parturition. Little is known about the involvement of endocannabinoids on the onset of labor in an infectious milieu. Here, using a mouse model of preterm labor induced by lipopolysaccharide (LPS), we explored changes on the expression of components of endocannabinoid system (ECS). We have also determined whether AEA and CB antagonists alter PG production that induces labor. We observed an increase in uterine N-acylphosphatidylethanolamine-specific phospholipase D expression (NAPE-PLD, the enzyme that synthesizes AEA) upon LPS treatment. Activity of catabolic enzyme fatty acid amide hydrolase (FAAH) did not change significantly. In addition, we also found that LPS modulated uterine cannabinoid receptors expression by downregulating Cb2 mRNA levels and upregulating CB1 protein expression. Furthermore, LPS and AEA induced PGF2a augmentation, and this was reversed by antagonizing CB1 receptor. Collectively, our results suggest that ECS may be involved in the mechanism by which infection causes preterm birth. PMID:26347521

  8. Minocycline mechanism of neuroprotection involves the Bcl-2 gene family in optic nerve transection.

    PubMed

    Levkovitch-Verbin, Hani; Waserzoog, Yael; Vander, Shelly; Makarovsky, Daria; Ilia, Piven

    2014-10-01

    The second-generation tetracycline, minocycline, has been shown to exhibit neuroprotective therapeutic benefits in many neurodegenerative diseases including experimental glaucoma and optic nerve transection (ONT). This study investigated the mechanism underlying minocycline neuroprotection in a model of ONT. ONT was applied unilaterally in 36 Wistar rat eyes. The rats were randomly divided into a minocycline (22 mg/kg/d) treatment group and a saline treatment group (control). Treatment (minocycline or saline) was given by intraperitoneal injections initiated 3 d before ONT and continued daily until the end of the experiment. The involvement of pro-apoptotic, pro-survival and inflammatory pathways was analyzed by quantitative Real-Time Polymerase Chain Reaction at 4 h and 3 d after the transection in both treatment groups. The involvement of Bcl-2 protein was evaluated by immunohistochemistry. We found that Minocycline significantly increased the expression of the antiapoptotic gene bcl-2 4 h after transection (n = 8, p = 0.008) and decreased the expression of Bax at the same time point (n = 8, p = 0.03). Tumor Necrosis Factor α (TNFα), Inhibitor of Apoptosis Protein (IAP1) and Gadd45α were significantly upregulated in the retinas of eyes with ONTs compared to control (n = 10 for each gene, p = 0.02, p = 0.03, p = 0.04, respectively) but this effect was unaffected by minocycline. This study further support that the mechanism underlying minocycline neuroprotection involves the Bcl-2 gene family, suggesting that minocycline has antiapoptotic properties that support its value as a promising neuroprotective drug. PMID:24410139

  9. Resource Letter TTSM-1: Teaching Thermodynamics and Statistical Mechanics in Introductory Physics, Chemistry, and Biology

    NASA Astrophysics Data System (ADS)

    Dreyfus, Benjamin W.; Geller, Benjamin D.; Meltzer, David E.; Sawtelle, Vashti

    2015-01-01

    This Resource Letter draws on discipline-based education research from physics, chemistry, and biology to collect literature on the teaching of thermodynamics and statistical mechanics in the three disciplines. While the overlap among the disciplinary literatures is limited at present, we hope this Resource Letter will spark more interdisciplinary interaction.

  10. 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…