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Sample records for biologic mechanism involved

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

    PubMed

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

    2015-12-01

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

  2. Is synthetic biology mechanical biology?

    PubMed

    Holm, Sune

    2015-12-01

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

  3. Epigenetics: Biology's Quantum Mechanics.

    PubMed

    Jorgensen, Richard A

    2011-01-01

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

  4. 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

  5. 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.

  6. Biological clocks: mechanisms and developments.

    PubMed

    Nongkynrih, P; Sharma, V K

    1992-05-15

    Almost all organisms ranging from unicellular protists to mammals were found to show biological rhythms. Many workers have performed various kinds of experiment to understand the mechanism as well as to find the origin of the clock responsible for these rhythms. However, there is no doubt about the existence of a biologically controlled clock in almost all organisms; yet its origin and mechanism still remain a mystery. Many theories have been put forward to explain the mechanism of these biological clocks and it seems that the cell membrane may play a key role. The existence of a very high electric field of the order of 10(5) V cm-1 across the cell membrane may have some role in the mechanism of the biological clock. Of all the factors which have the effects on biological rhythms, light and temperature are found to be the most common. Also, the study of these biological clocks can help to solve the sleeping problems of international travellers and shift workers as well as to improve diagnosis, cure and prevention from diseases.

  7. 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

  8. 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

  9. 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.

  10. Collaborative explanation and biological mechanisms.

    PubMed

    Fagan, Melinda Bonnie

    2015-08-01

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

  11. 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.

  12. 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

  13. 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.

  14. Biological mechanism of shockwave in bone.

    PubMed

    Cheng, Jai-Hong; Wang, Ching-Jen

    2015-12-01

    Shockwave is a rapid, short duration acoustic wave that carries energy and can propagate through tissue medium. This kind of physical force can be a mechanical stimulus that induces biological effects in living tissue. Extracorporeal shockwave therapy (ESWT) acts as a mechanical stimulus which promotes biological healing processes through a mechanotransduction. The biological effects of ESWT are reported such as tissue regeneration, wound healing, angiogenesis, bone remodeling, and anti-inflammation. Until now, however, little is known about the basic mechanism of action of this type of therapy. This article describes the molecular mechanism on the current status of ESWT with pre-clinical and clinical applications for treating disorders in bone.

  15. 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

  16. Mechanics of hydrogels and biological tissues

    NASA Astrophysics Data System (ADS)

    Zimberlin, Jessica A.

    The relationship between cells and their environment is one of dynamic reciprocity, whereby cells can influence their surrounding and the surroundings can influence the cells. One example of this relationship arises from the effect of the mechanical properties of an environment on a cell and of a cell on its environment. Inspired by this relationship, we investigate (1) the local environment of biological materials, both native and synthetic, and (2) the forces that cell sheets exert on surfaces. We do this by developing techniques that focus on local mechanical properties and experimental strategies that provide insight into intercellular mechanics. We first focus on determining local mechanical properties of hydrogel materials by developing the Cavitation Rheology technique. This process involves inducing a cavitation event at the tip of a syringe needle. We develop theory to show that the critical pressure to cavitate can be directly related to the modulus of the material (Chapter 2). This allows us to experimentally determine the mechanical properties at arbitrary locations throughout a material scaffold over a range of length scales defined by the needle radius (Chapter 3). We then demonstrate that we can viturally elminate the energy contribution from the creation of new surface area to the critical pressure by cavitating with a media of lower surface energy (Chapter 4). In chapter 5, we show that Cavitation Rheology can be used on native biological tissues and we go on to demonstrate the importance of measuring the mechanical properties in vivo. We then focus on understanding the force development of cells as they grow to confluency on a dynamic substrate (Chapter 6). We demonstrate the method of living microlenses to measure the collective strains cell sheets attain by growing cells on a thin polystyrene film supported by a surface of microwells. The cells cause the film to buckle and the resultant buckling can be directly related to the strain. We use this

  17. 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.

  18. Bioinspiration: applying mechanical design to experimental biology.

    PubMed

    Flammang, Brooke E; Porter, Marianne E

    2011-07-01

    The production of bioinspired and biomimetic constructs has fostered much collaboration between biologists and engineers, although the extent of biological accuracy employed in the designs produced has not always been a priority. Even the exact definitions of "bioinspired" and "biomimetic" differ among biologists, engineers, and industrial designers, leading to confusion regarding the level of integration and replication of biological principles and physiology. By any name, biologically-inspired mechanical constructs have become an increasingly important research tool in experimental biology, offering the opportunity to focus research by creating model organisms that can be easily manipulated to fill a desired parameter space of structural and functional repertoires. Innovative researchers with both biological and engineering backgrounds have found ways to use bioinspired models to explore the biomechanics of organisms from all kingdoms to answer a variety of different questions. Bringing together these biologists and engineers will hopefully result in an open discourse of techniques and fruitful collaborations for experimental and industrial endeavors.

  19. Physical mechanisms of biological molecular motors

    NASA Astrophysics Data System (ADS)

    Miller, John H., Jr.; Vajrala, Vijayanand; Infante, Hans L.; Claycomb, James R.; Palanisami, Akilan; Fang, Jie; Mercier, George T.

    2009-03-01

    Biological motors generally fall into two categories: (1) those that convert chemical into mechanical energy via hydrolysis of a nucleoside triphosphate, usually adenosine triphosphate, regarded as life's chemical currency of energy and (2) membrane bound motors driven directly by an ion gradient and/or membrane potential. Here we argue that electrostatic interactions play a vital role for both types of motors and, therefore, the tools of physics can greatly contribute to understanding biological motors.

  20. [Biochemistry, molecular mechanism of action and biological effects of endotoxin].

    PubMed

    Burgmann, H; Breyer, S

    1995-01-01

    This review is a brief attempt at providing an overview of a subject of enormous complexity-endotoxins and the mediators associated with its biological effects. More specifically it deals with biochemistry and biology of endotoxin, detection of endotoxin with the Limulus amebocyte lysate test, the molecular mechanisms and biological effects, and in the last part with future aspects of therapeutical strategies. It seems certain that the subject will become even more complex and possibly controversial as scientific knowledge further involves. However, because of the high mortality rate of patients suffering from gram-negative sepsis all efforts have to be made to find effective therapeutical strategies.

  1. Mechanical versus biological aortic valve replacement strategies.

    PubMed

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

    2016-01-01

    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. 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.

  3. 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.

  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. 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.

  6. 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

  7. 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

  8. Chirality, quantum mechanics, and biological determinism

    NASA Astrophysics Data System (ADS)

    Davies, P. C. W.

    2006-08-01

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

  9. 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.

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Morange, Michel

    2012-01-01

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

  12. Modeling the mechanisms of biological GTP hydrolysis.

    PubMed

    Carvalho, Alexandra T P; Szeler, Klaudia; Vavitsas, Konstantinos; Åqvist, Johan; Kamerlin, Shina C L

    2015-09-15

    Enzymes that hydrolyze GTP are currently in the spotlight, due to their molecular switch mechanism that controls many cellular processes. One of the best-known classes of these enzymes are small GTPases such as members of the Ras superfamily, which catalyze the hydrolysis of the γ-phosphate bond in GTP. In addition, the availability of an increasing number of crystal structures of translational GTPases such as EF-Tu and EF-G have made it possible to probe the molecular details of GTP hydrolysis on the ribosome. However, despite a wealth of biochemical, structural and computational data, the way in which GTP hydrolysis is activated and regulated is still a controversial topic and well-designed simulations can play an important role in resolving and rationalizing the experimental data. In this review, we discuss the contributions of computational biology to our understanding of GTP hydrolysis on the ribosome and in small GTPases.

  13. [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.

  14. 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

  15. 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

  16. 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

  17. Biological mechanisms underlying evolutionary origins of psychotic and mood disorders.

    PubMed

    Goto, Yukiori; Lee, Young-A; Yamaguchi, Yoshie; Jas, Emanuel

    2016-10-01

    Psychotic and mood disorders are brain dysfunctions that are caused by gene environment interactions. Although these disorders are disadvantageous and involve behavioral phenotypes that decrease the reproductive success of afflicted individuals in the modern human society, the prevalence of these disorders have remained constant in the population. Here, we propose several biological mechanisms by which the genes associated with psychotic and mood disorders could be selected for in specific environmental conditions that provide evolutionary bases for explanations of when, why, and where these disorders emerged and have been maintained in humans. We discuss the evolutionary origins of psychotic and mood disorders with specific focuses on the roles of dopamine and serotonin in the conditions of social competitiveness/hierarchy and maternal care and other potential mechanisms, such as social network homophily and symbiosis.

  18. [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.

  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. 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…

  1. RNA Interference: Biology, Mechanism, and Applications

    PubMed Central

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

    2003-01-01

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

  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.

  4. Factors involved in mechanical fatigue degradation of dental resin composites.

    PubMed

    Lohbauer, U; Belli, R; Ferracane, J L

    2013-07-01

    The design of clinical trials allows for limited insights into the fatigue processes occurring in resin composites and the factors involved therein. In vitro studies, in contrast, can fundamentally narrow study interests to focus on particular degradation mechanisms and, to date, represent the major contributors to the state of knowledge on the subject. These studies show that microstructural features are important in determining strength and fracture toughness, whereas fatigue resistance is mainly related to the susceptibility of the matrix and the filler/matrix interface to mechanical and chemical degradation. In this review, we focus on fracture mechanisms occurring during fatigue, on the methods used to assess them, and on additional phenomena involved in the degradation of initial mechanical properties of resin composites.

  5. Biology: An Important Agricultural Engineering Mechanism

    ERIC Educational Resources Information Center

    Henderson, S. M.

    1974-01-01

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

  6. 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

  7. 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.

  8. Immunomodulatory effects of macrolide antibiotics - part 1: biological mechanisms.

    PubMed

    Altenburg, J; de Graaff, C S; van der Werf, T S; Boersma, W G

    2011-01-01

    Macrolide antibiotics are well known for their antibacterial and anti-inflammatory properties. This article provides an overview of the biological mechanisms through which macrolides exert this 'double effect'. Their antibacterial effect consists of the inhibition of bacterial protein synthesis, impaired bacterial biofilm synthesis, and the attenuation of other bacterial virulence factors. Apart from these direct antimicrobial effects, macrolides are known for their modulating effect on many components of the human immune system. By influencing the production of cytokines, they have a dampening effect on the proinflammatory response. Furthermore, the majority of cells involved in the immune response are, in one way or another, influenced when macrolide antibiotics are administered. Having such an obvious effect on the various aspects of the immune system, macrolides seem to be exceptionally suited for the treatment of chronic inflammatory diseases.

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

    PubMed

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

    2010-04-22

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

  10. 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.

  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. 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

  13. Regulatory mechanisms of microRNAs involvement in cancer.

    PubMed

    Fabbri, Muller; Ivan, Mircea; Cimmino, Amelia; Negrini, Massimo; Calin, George A

    2007-07-01

    MicroRNAs (miRNAs) are 19-24 nucleotide noncoding RNAs that regulate the translation and degradation of target mRNAs and are extensively involved in human cancers. One unexpected conclusion of the profiling and functional studies in tumourigenesis is that some miRNAs behave in cancer cells in a dual mode, resembling the 'Dr Jekyll and Mr Hyde' story, which centers on a conception of humanity as dual in nature. The authors and others have found that onco-miRNAs and suppressor-miRNAs can represent two different looks of the same gene, behaving as oncogenes or tumour suppressors depending on tissue type and specific targets. In this review, the authors analyse the regulatory mechanisms of the main miRNA genes involved in human tumourigenesis. PMID:17665990

  14. 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

  15. Epigenetic mechanisms involved in the pathogenesis of hepatobiliary malignancies

    PubMed Central

    Hamilton, James P

    2010-01-01

    Primary tumors of the liver and biliary tree are increasing in frequency and portend a miserable prognosis. Epigenetic regulation of gene expression has emerged as a fundamental aspect of cancer development and progression. The molecular mechanisms of carcinogenesis in hepatocellular carcinoma and cholangiocarcinoma involve a complex interplay of both genetic and epigenetic factors. Recent studies investigating the possible epigenetic mechanisms induced in the disease have shed new light on the molecular underpinnings of hepatobiliary cancers. In addition, epigenetic modifications of DNA in cancer and precancerous lesions offer hope and the promise of novel biomarkers for early cancer detection, prediction, prognosis and response to treatment. Furthermore, the reversal of epigenetic changes represents a potential target for novel therapeutic strategies and medication design. PMID:20556199

  16. 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

  17. 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

  18. Neurophysiological mechanisms involved in language learning in adults.

    PubMed

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

    2009-12-27

    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

  19. 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

  20. Mechanisms involved in metalloid transport and tolerance acquisition.

    PubMed

    Tamás, M J; Wysocki, R

    2001-08-01

    Toxic metalloids such as arsenic and antimony have always been an integral part of the natural environment. To survive in such a hostile habitat, it is crucial to develop strategies to exclude toxic substances from the cell and to acquire tolerance. Cells remove metalloids from the cytosol either by active efflux or by sequestration in an internal organelle. Controlling the influx appears to be another way of maintaining a low intracellular metalloid content. Inside the cell, the metalloid can be reduced to a form that is recognised by the expulsion system(s). In addition, metalloid complexation and compartmentalisation contributes to enhanced cellular tolerance. Finally, the presence of metalloids activates transcription of various cellular defence genes. Metalloid-containing drugs are currently used to treat protozoan infections and promyelocytic leukaemia. Since metalloid resistance hampers efficient treatment, interest in identifying the mechanisms involved in tolerance acquisition has arisen. The possibility of using genetic approaches has made the yeast Saccharomyces cerevisiae a compelling model system to investigate the basis of metalloid tolerance at a molecular level. This review describes the recent progress made in elucidating the mechanisms involved in metalloid transport and tolerance in yeast and other organisms.

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

    PubMed

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

    2014-01-01

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

  2. CRISPR-Cas: biology, mechanisms and relevance

    PubMed Central

    Hille, Frank

    2016-01-01

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

  3. CRISPR-Cas: biology, mechanisms and relevance.

    PubMed

    Hille, Frank; Charpentier, Emmanuelle

    2016-11-01

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

  4. CRISPR-Cas: biology, mechanisms and relevance.

    PubMed

    Hille, Frank; Charpentier, Emmanuelle

    2016-11-01

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

  5. Mechanics and mechano-biology of fracture healing in normal and osteoporotic bone.

    PubMed

    Augat, Peter; Simon, Ulrich; Liedert, Astrid; Claes, Lutz

    2005-03-01

    Fracture repair, which aims at regaining the functional competence of a bone, is a complex and multifactorial process. For the success of fracture repair biology and mechanics are of immense importance. The biological and mechanical environments must be compatible with the processes of cell and tissue proliferation and differentiation. The biological environment is characterized by the vascular supply and by many biochemical components, the biochemical milieu. A good vascular supply is a prerequisite for the initiation of the fracture repair process. The biochemical milieu involves complex interactions among local and systemic regulatory factors such as growth factors or cytokines. The mechanical environment is determined by the local stress and strain within the fracture. However, the local stress and strain is not accessible, and the mechanical environment, therefore, is described by global mechanical factors, e.g., gap size or interfragmentary movement. The relationship between local stress and strain and the global mechanical factors can be obtained by numerical models (Finite Element Model). Moreover, there is considerable interaction between biological factors and mechanical factors, creating a biomechanical environment for the fracture healing process. The biomechanical environment is characterized by osteoblasts and osteocytes that sense the mechanical signal and express biological markers, which effect the repair process. This review will focus on the effects of biomechanical factors on fracture repair as well as the effects of age and osteoporosis.

  6. 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

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

  8. Formation mechanism for a hybrid supramolecular network involving cooperative interactions.

    PubMed

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

    2012-04-27

    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. PMID:22680886

  9. Mechanism of Oligonucleotide Uptake by Cells: Involvement of Specific receptors?

    NASA Astrophysics Data System (ADS)

    Yakubov, Leonid A.; Deeva, Elena A.; Zarytova, Valentina F.; Ivanova, Eugenia M.; Ryte, Antonina S.; Yurchenko, Lyudmila V.; Vlassov, Valentin V.

    1989-09-01

    We have investigated the interaction of oligonucleotides and their alkylating derivatives with mammalian cells. In experiments with L929 mouse fibroblast and Krebs 2 ascites carcinoma cells, it was found that cellular uptake of oligodeoxynucleotide derivatives is achieved by an endocytosis mechanism. Uptake is considerably more efficient at low oligomer concentration (< 1 μ M), because at this concentration a significant percentage of the total oligomer pool is absorbed on the cell surface and internalized by a more efficient absorptive endocytosis process. Two modified proteins were detected in mouse fibroblasts that were treated with the alkylating oligonucleotide derivatives. The binding of the oligomers to the proteins is inhibited by other oligodeoxynucleotides, single- and double-stranded DNA, and RNA. The polyanions heparin and chondroitin sulfates A and B do not inhibit binding. These observations suggest the involvement of specific receptor proteins in binding of oligomers to mammalian cells.

  10. 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

  11. The potential biological mechanisms of arsenic-induced diabetes mellitus.

    PubMed

    Tseng, Chin-Hsiao

    2004-06-01

    Although epidemiologic studies carried out in Taiwan, Bangladesh, and Sweden have demonstrated a diabetogenic effect of arsenic, the mechanisms remain unclear and require further investigation. This paper reviewed the potential biological mechanisms of arsenic-induced diabetes mellitus based on the current knowledge of the biochemical properties of arsenic. Arsenate can substitute phosphate in the formation of adenosine triphosphate (ATP) and other phosphate intermediates involved in glucose metabolism, which could theoretically slow down the normal metabolism of glucose, interrupt the production of energy, and interfere with the ATP-dependent insulin secretion. However, the concentration of arsenate required for such reaction is high and not physiologically relevant, and these effects may only happen in acute intoxication and may not be effective in subjects chronically exposed to low-dose arsenic. On the other hand, arsenite has high affinity for sulfhydryl groups and thus can form covalent bonds with the disulfide bridges in the molecules of insulin, insulin receptors, glucose transporters (GLUTs), and enzymes involved in glucose metabolism (e.g., pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase). As a result, the normal functions of these molecules can be hampered. However, a direct effect on these molecules caused by arsenite at physiologically relevant concentrations seems unlikely. Recent evidence has shown that treatment of arsenite at lower and physiologically relevant concentrations can stimulate glucose transport, in contrary to an inhibitory effect exerted by phenylarsine oxide (PAO) or by higher doses of arsenite. Induction of oxidative stress and interferences in signal transduction or gene expression by arsenic or by its methylated metabolites are the most possible causes to arsenic-induced diabetes mellitus through mechanisms of induction of insulin resistance and beta cell dysfunction. Recent studies have shown that, in subjects with

  12. Potentiation of antidepressant-like activity with lithium: mechanism involved.

    PubMed

    Chenu, Franck; Bourin, Michel

    2006-02-01

    In the last decade, many augmentation strategies have been developed to increase the activity of antidepressant drugs or to reduce their long onset of action by acting on different targets. One of the first augmentation strategy used in psychiatric disorders is coadministration of lithium and antidepressant drugs. However, the underlaying mechanism of action involved in the potentiatory effect of lithium is still unclear and many hypotheses have been suggested such as activity on BDNF, ACTH, thyroid hormones and serotonin neurotransmission. All these systems being embedded in each other, we focused on the 5-HT neurotransmission-increase induced by lithium treatment. Based on neurobiochemical and behavioral results we tried to better understand its mechanism of action and we concluded that effect of lithium on 5-HT neurotransmission could be linked to a partial agonist activity on 5-HT1B autoreceptors, or to a modulatory activity on these receptors, located in the cortical area in the case of a short term treatment, or in the hippocampus in the case of a long term treatment. We also suggested that the anti-manic effect of lithium was linked to this activity on 5-HT1B receptors, occurring this time on 5-HT1B postsynaptic (heteroreceptors on dopaminergic pathways) receptors levels.

  13. 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.

  14. 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

  15. 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

  16. 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 ...

  17. Biological mechanisms linking Alzheimer's disease and type-2 diabetes mellitus.

    PubMed

    Mushtaq, Gohar; Khan, Jalaluddin A; Kamal, Mohammad A

    2014-01-01

    The emerging data suggest that type 2 diabetes mellitus (T2DM) can contribute significantly to the onset or progression of Alzheimer's disease (AD) either directly or as a cofactor. Various in vitro and in vivo animal and human clinical studies have provided evidence that T2DM is a major risk factor in the pathology of AD and the two diseases share common biological mechanisms at the molecular level. The biological mechanisms that are common in the pathology of both T2DM and AD include insulin resistance, impaired glucose metabolism, β-amyloid formation, oxidative stress, and the presence of advanced glycation end products. With better understanding of the degree of association between AD and T2DM and the underlying molecular mechanisms explaining this relationship, it is hoped that researchers will be able to develop effective therapeutic interventions to treat or control T2DM and, as a consequence, delay the onset or progression of AD.

  18. 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.

  19. 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.

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

    PubMed

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

    2014-01-01

    In France, the Ecophyto 2018 national action plan will set out to reduce the use of pesticides by 50% by 2018, if possible. To achieve this goal, the use of arbuscular mycorrhizal (AM) fungi could be a potential alternative method allowing the control of crop diseases. The inoculation by AM fungi has been demonstrated to protect plants against soil-borne pathogens, but little is known about their effectiveness against aerial pathogens, such as the biotrophic fungus Blumeria graminis f.sp. tritici (Bgt) causing wheat (Triticum aestivum) powdery mildew. In the present study, wheat plants were grown in pots, under controlled conditions. Using various phosphorus (P) concentrations, the effectiveness of three AM inocula (Rhizophagus irregularis (Ri), Funneliformis mosseae (Fm)) and Solrize, a mixture of Ri and Fm) in Orvantis wheat cultivar, were tested. After 42 days of culture, mycorrhizal (M) and non-mycorrhizal (NM) wheat plants were infected by Bgt. A satisfactory mycorrhizal rate was obtained with the phosphorus concentration P/5 (P corresponding to the dose used in wheat fields in = 62 mg/L). Our work shows, for the first time, (i) a protective effect of AM inoculation against wheat powdery mildew, reaching up to 73% with Fm inocula, and (ii) its ability to induce a systemic resistance in wheat. Thereafter, we investigated mechanisms involved in this protection. Control plants, M plants, infected plants by Bgt, and M-infected plants were compared at: (i) cytological level, our results revealed that papillae and whole-fluorescent cells presence was induced, conversely fungal haustorium formation in epidermal cells was reduced within M plants leaves (ii) enzymatic level-by assessing defense enzyme activities (lipoxygenase, peroxidase) known as defense markers were measured 24, 48, 72 and 96 hours after infection (hai). The importance of these activities in the defense pathways induced in wheat by AM fungi will be discussed. PMID:26080475

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

    PubMed

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

    2014-01-01

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

  2. 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

  3. 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.

  4. On the mechanics of growing thin biological membranes.

    PubMed

    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. PMID:24563551

  5. 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.

  6. 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

  7. Gas chromatography of volatile fatty acids. Method involving separation from biological material by vacuum distillation.

    PubMed

    Tyler, J E; Dibdin, G H

    1975-02-19

    A method is described for the quantitation of C2-C5 volatile fatty acids present in biological tissues. It involved recovery of the acids from their biological matrix by vacuum micro-distillation at room temperature, followed by gas phase separation of aqueous solutions on orthophosphoric acid-modified Phasepak Q columns. The subsequent gas chromatographic procedure resolved iso from normal isomers and showed a linear response for each volatile acid over the range 10-400 ng. There was no evidence of ghosting, isomer peak broadening, or peak tailing. Relative molar response values were shown to be linear with carbon number for all the volatile fatty acids studied.

  8. 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

  9. Mechanisms for control of biological electron transfer reactions

    PubMed Central

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

    2014-01-01

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

  10. Biological mechanisms of physical activity in preventing cognitive decline.

    PubMed

    Lista, I; Sorrentino, G

    2010-05-01

    In order to guarantee better conditions for competition, the nervous system has developed not only mechanisms controlling muscle effectors, but also retrograde systems that, starting from peripheral structures, may influence brain functions. Under such perspective, physical activity could play an important role in influencing cognitive brain functions including learning and memory. The results of epidemiological studies (cross-sectional, prospective and retrospective) support a positive relationship between cognition and physical activities. Recent meta-analysis confirmed a significant effect of exercise on cognitive functions. However, the biological mechanisms that underlie such beneficial effects are still to be completely elucidated. They include supramolecular mechanisms (e.g. neurogenesis, synaptogenesis, and angiogenesis) which, in turn, are controlled by molecular mechanisms, such as BDNF, IGF-1, hormone and second messengers.

  11. Generalization and Optimization of Biological and Biomimetic Ejection Mechanisms

    NASA Astrophysics Data System (ADS)

    Dabiri, John O.; Milano, Michele; Gharib, Morteza

    2003-11-01

    Unsteady mechanisms for fluid ejection are found in biological systems from jellyfish to the human heart. An understanding of these mechanisms is needed to correct pathologies in natural systems and to design biomimetic systems. In particular, the formation process of the recurring vortex ring motif must be studied. It has been previously shown that ring formation is limited by the energy available from the vortex generator, and that ejection efficiency is maximized as the limit is reached. To assess the ability of biological systems to extend this limit, we derive a set of nondimensional criteria that facilitate comparison of ejection mechanisms with dissimilar kinematics. We optimize the derived criteria by means of an evolutionary algorithm, to design optimal ejection mechanisms. The results obtained are compared with some natural systems to derive general principles for the design of better unsteady ejection mechanisms. Additionally, the generalized criteria clarify the effect of previous suggestions for extending the vortex ring formation limit. This work is supported by a grant from the National Science Foundation.

  12. 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

  13. [Mechanical properties and biological evaluation of buffalo horn material].

    PubMed

    Zhang, Quanbin; Zhou, Qunfei; Shan, Guanghua; Cao, Ping; Huang, Yaoxiong; Ao, Ningjian

    2014-12-01

    Mechanical properties and biological evaluation of buffalo horn material were examined in this study. The effects of sampling position of buffalo horn on mechanical properties were investigated with uniaxial tension and micron indentation tests. Meanwhile, the variation of element contents in different parts of buffalo horn was determined with elemental analysis, and the microstructure of the horn was measured with scanning electron microscopy. In addition, biological evaluation of buffalo horn was studied with hemolytic test, erythrocyte morphology, platelet and erythrocyte count, and implantation into mouse. Results showed that the buffalo horn had good mechanical properties and mechanical characteristic values of it gradually increased along with the growth direction of the horn, which may be closely related to its microstructure and element content of C, N, and S in different parts of the buffalo horn. On the other hand, because the buffalo horn does not have toxicity, it therefore does not cause hemolysis of erythrocyte and has a good affinity with it. Buffalo horn has good histocompatibility but meanwhile it may induce the platelet adhesion and aggregation. Even so, it does not continue to rise to induce a large number of platelet to aggregate with resulting blood clotting. Therefore, the buffalo horn material has been proved to possess good blood compatibility according to the preliminary evaluation. PMID:25868248

  14. 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.

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

    PubMed

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

    2010-12-01

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

  16. 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

  17. 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.

  18. A cascade of recently discovered molecular mechanisms involved in abiotic stress tolerance of plants.

    PubMed

    Saeed, Muhammad; Dahab, Abdel hafiz Adam; Wangzhen, Guo; Tianzhen, Zhang

    2012-04-01

    Today, agriculture is facing a tremendous threat from the climate change menace. As human survival is dependent on a constant supply of food from plants as the primary producers, we must aware of the underlying molecular mechanisms that plants have acquired as a result of molecular evolution to cope this rapidly changing environment. This understanding will help us in designing programs aimed at developing crop plant cultivars best suited to our needs of a sustainable agriculture. The field of systems biology is rapidly progressing, and new insight is coming out about the molecular mechanisms involved in abiotic stress tolerance. There is a cascade of changes in transcriptome, proteome, and metabolome of plants during these stress responses. We have tried to cover most pronounced recent developments in the field of "omics" related to abiotic stress tolerance of plants. These changes are very coordinated, and often there is crosstalk between different components of stress tolerance. The functions of various molecular entities are becoming more clear and being associated with more precise biological phenomenon.

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

    PubMed Central

    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

  20. 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

  1. 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

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

    PubMed

    Friedland, Robert P

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  4. Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection.

    PubMed

    García-Niño, Wylly Ramsés; Zazueta, Cecilia

    2015-07-01

    Traditional drugs or therapies rarely have effects on regression of chronic liver diseases, which result in many cases from sustained oxidative stress. In recent years, ellagic acid (EA) has gained attention due to its multiple biological activities and several molecular targets. This is the first review focused on the pharmacological properties and on the molecular mechanisms activated by EA in terms of liver protection. EA possesses antioxidant, antihepatotoxic, antisteatosic, anticholestatic, antifibrogenic, antihepatocarcinogenic and antiviral properties that improves the hepatic architectural and functions against toxic and pathological conditions. The molecular mechanisms that EA activates include the scavenging of free radicals, regulation of phase I and II enzymes, modulation of proinflammatory and profibrotic cytokines synthesis, the regulation of biochemical pathways involved in the synthesis and degradation of lipids as well as the maintenance of essential trace elements levels. EA also inhibits hepatic stellate cells and mast cells activation, the proliferation of transformed cells, as well as viral replication by increasing antioxidant response, induction of apoptosis, downregulation of genes involved in cell cycle and angiogenesis, and stimulation of cellular immune response. Despite the enormous therapeutic potential of EA as an innovative pharmacological strategy, the number of phase I and II trials in patients is scarce, precluding its clinical application. In these sense, the use of new delivery systems that enhances EA bioavailability would improve the results already obtained. Also it remains to be determined if treatment with urolithins instead of EA would represent a better strategy in hepatic disease treatment.

  5. Molecular and cellular mechanisms involved in the Trypanosoma cruzi/host cell interplay.

    PubMed

    Romano, Patricia Silvia; Cueto, Juan Agustín; Casassa, Ana Florencia; Vanrell, María Cristina; Gottlieb, Roberta A; Colombo, María Isabel

    2012-05-01

    The protozoan parasite Trypanosoma cruzi has a complex biological cycle that involves vertebrate and invertebrate hosts. In mammals, the infective trypomastigote form of this parasite can invade several cell types by exploiting phagocytic-like or nonphagocytic mechanisms depending on the class of cell involved. Morphological studies showed that when trypomastigotes contact macrophages, they induce the formation of plasma membrane protrusions that differ from the canonical phagocytosis that occurs in the case of noninfective epimastigotes. In contrast, when trypomastigotes infect epithelial or muscle cells, the cell surface is minimally modified, suggesting the induction of a different class of process. Lysosomal-dependent or -independent T. cruzi invasion of host cells are two different models that describe the molecular and cellular events activated during parasite entry into nonphagocytic cells. In this context, we have previously shown that induction of autophagy in host cells before infection favors T. cruzi invasion. Furthermore, we demonstrate that autophagosomes and the autophagosomal protein LC3 are recruited to the T. cruzi entry sites and that the newly formed T. cruzi parasitophorous vacuole has characteristics of an autophagolysosome. This review summarizes the current knowledge of the molecular and cellular mechanisms of T. cruzi invasion in nonphagocytic cells. Based on our findings, we propose a new model in which T. cruzi takes advantage of the upregulation of autophagy during starvation to increase its successful colonization of host cells.

  6. Molecular and Cellular Mechanisms Involved in the Trypanosoma cruzi/Host Cell Interplay

    PubMed Central

    Romano, Patricia Silvia; Cueto, Juan Agustín; Casassa, Ana Florencia; Vanrell, María Cristina; Gottlieb, Roberta A.; Colombo, María Isabel

    2013-01-01

    Summary The protozoan parasite Trypanosoma cruzi has a complex bi-ological cycle that involves vertebrate and invertebrate hosts. In mammals, the infective trypomastigote form of this parasite can invade several cell types by exploiting phagocytic-like or non-phagocytic mechanisms depending on the class of cell involved. Morphological studies showed that when trypomastigotes contact macrophages, they induce the formation of plasma membrane protrusions that differ from the canonical phagocytosis that occurs in the case of noninfective epimastigotes. In contrast, when trypomastigotes infect epithelial or muscle cells, the cell surface is minimally modified, suggesting the induction of a different class of process. Lysosomal-dependent or -independent T. cruzi invasion of host cells are two different models that describe the molecular and cellular events activated during parasite entry into nonphagocytic cells. In this context, we have previously shown that induction of autophagy in host cells before infection favors T. cruzi invasion. Furthermore, we demonstrate that autophagosomes and the autophagosomal protein LC3 are recruited to the T. cruzi entry sites and that the newly formed T. cruzi parasitophorous vacuole has characteristics of an autophagolysosome. This review summarizes the current knowledge of the molecular and cellular mechanisms of T. cruzi invasion in nonphagocytic cells. Based on our findings, we propose a new model in which T. cruzi takes advantage of the up-regulation of autophagy during starvation to increase its successful colonization of host cells. PMID:22454195

  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. Biological studies on the carcinogenic mechanisms of quartz

    SciTech Connect

    Saffiotti, U.; Daniel, L.N.; Mao, Yan; Williams, A.O.; Kaighn, M.E.; Ahmed, N.; Knapton, A.D.

    1993-12-31

    Silica-induced carcinognesis mechanisms have been investigated by several laboratories. However, most research has focused on quartz and to a lesser extent cristobalite and tridymite. This paper discusses the effects of silica in animal models exposed to quartz, cristobalite, and tridymite in vivo, including identification of patterns of tumor induction and determination of early histogenetic pathways of tumor development. The emphasis is on identification of basic mechanisms of silica-induced carcinogenesis and the eventual relevance to specific mineral properties and to specific biological host factors. Some of the research presented demonstrates that silica can bind directly to DNA and cause DNA damage and neoplastic transformation. In addition marked host differences in the susceptability to silican-induced alveolar cell hyperplasia and carcinogenesis has been noted. 75 refs., 2 figs.

  9. 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

  10. 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...

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

    PubMed

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

    2015-09-18

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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements

    PubMed Central

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

    2011-01-01

    SUMMARY Complex genomic rearrangements (CGR) consisting of two or more breakpoint junctions have been observed in genomic disorders. Recently, a chromosome catastrophe phenomenon termed chromothripsis, in which numerous genomic rearrangements are apparently acquired in one single catastrophic event, was described in multiple cancers. Here we show that constitutionally acquired CGRs share similarities with cancer chromothripsis. In the 17 CGR cases investigated we observed localization and multiple copy number changes including deletions, duplications and/or triplications, as well as extensive translocations and inversions. Genomic rearrangements involved varied in size and complexities; in one case, array comparative genomic hybridization revealed 18 copy number changes. Breakpoint sequencing identified characteristic features, including small templated insertions at breakpoints and microhomology at breakpoint junctions, which have been attributed to replicative processes. The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism’s life cycle. PMID:21925314

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

    PubMed

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

    2011-09-16

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

  2. 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

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

    PubMed

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

    2012-03-27

    Spider silk is a fascinating natural composite material. Its combination of strength and toughness is unrivalled in nature, and as a result, it has gained considerable interest from the medical, physics, and materials communities. Most of this attention has focused on the one to tens of nanometer scale: predominantly the primary (peptide sequences) and secondary (β sheets, helices, and amorphous domains) structure, with some insights into tertiary structure (the arrangement of these secondary structures) to describe the origins of the mechanical and biological performance. Starting with spider silk, and relating our findings to collagen fibrils, we describe toughening mechanisms at the hundreds of nanometer scale, namely, the fibril morphology and its consequences for mechanical behavior and the dissipation of energy. Under normal conditions, this morphology creates a nonslip fibril kinematics, restricting shearing between fibrils, yet allowing controlled local slipping under high shear stress, dissipating energy without bulk fracturing. This mechanism provides a relatively simple target for biomimicry and, thus, can potentially be used to increase fracture resistance in synthetic materials. PMID:22324287

  4. 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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Lin, M.C.

    1993-12-01

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

  7. Paraventricular hypothalamic regulation of trigeminovascular mechanisms involved in headaches.

    PubMed

    Robert, Claude; Bourgeais, Laurence; Arreto, Charles-Daniel; Condes-Lara, Miguel; Noseda, Rodrigo; Jay, Thérèse; Villanueva, Luis

    2013-05-15

    While functional imaging and deep brain stimulation studies point to a pivotal role of the hypothalamus in the pathophysiology of migraine and trigeminal autonomic cephalalgias, the circuitry and the mechanisms underlying the modulation of medullary trigeminovascular (Sp5C) neurons have not been fully identified. We investigated the existence of a direct anatomo-functional relationship between hypothalamic excitability disturbances and modifications of the activities of Sp5C neurons in the rat. Anterograde and retrograde neuronal anatomical tracing, intrahypothalamic microinjections, extracellular single-unit recordings of Sp5C neurons, and behavioral trials were used in this study. We found that neurons of the paraventricular nucleus of the hypothalamus (PVN) send descending projections to the superior salivatory nucleus, a region that gives rise to parasympathetic outflow to cephalic and ocular/nasal structures. PVN cells project also to laminae I and outer II of the Sp5C. Microinjections of the GABAA agonist muscimol into PVN inhibit both basal and meningeal-evoked activities of Sp5C neurons. Such inhibitions were reduced in acutely restrained stressed rats. GABAA antagonist gabazine infusions into the PVN facilitate meningeal-evoked responses of Sp5C neurons. PVN injections of the neuropeptide pituitary adenylate cyclase activating peptide (PACAP38) enhance Sp5C basal activities, whereas the antagonist PACAP6-38 depresses all types of Sp5C activities. 5-HT1B/D receptor agonist naratriptan infusion confined to the PVN depresses both basal and meningeal-evoked Sp5C activities. Our findings suggest that paraventricular hypothalamic neurons directly control both spontaneous and evoked activities of Sp5C neurons and could act either as modulators or triggers of migraine and/or trigeminal autonomic cephalalgias by integrating nociceptive, autonomic, and stress processing mechanisms.

  8. Paraventricular hypothalamic regulation of trigeminovascular mechanisms involved in headaches.

    PubMed

    Robert, Claude; Bourgeais, Laurence; Arreto, Charles-Daniel; Condes-Lara, Miguel; Noseda, Rodrigo; Jay, Thérèse; Villanueva, Luis

    2013-05-15

    While functional imaging and deep brain stimulation studies point to a pivotal role of the hypothalamus in the pathophysiology of migraine and trigeminal autonomic cephalalgias, the circuitry and the mechanisms underlying the modulation of medullary trigeminovascular (Sp5C) neurons have not been fully identified. We investigated the existence of a direct anatomo-functional relationship between hypothalamic excitability disturbances and modifications of the activities of Sp5C neurons in the rat. Anterograde and retrograde neuronal anatomical tracing, intrahypothalamic microinjections, extracellular single-unit recordings of Sp5C neurons, and behavioral trials were used in this study. We found that neurons of the paraventricular nucleus of the hypothalamus (PVN) send descending projections to the superior salivatory nucleus, a region that gives rise to parasympathetic outflow to cephalic and ocular/nasal structures. PVN cells project also to laminae I and outer II of the Sp5C. Microinjections of the GABAA agonist muscimol into PVN inhibit both basal and meningeal-evoked activities of Sp5C neurons. Such inhibitions were reduced in acutely restrained stressed rats. GABAA antagonist gabazine infusions into the PVN facilitate meningeal-evoked responses of Sp5C neurons. PVN injections of the neuropeptide pituitary adenylate cyclase activating peptide (PACAP38) enhance Sp5C basal activities, whereas the antagonist PACAP6-38 depresses all types of Sp5C activities. 5-HT1B/D receptor agonist naratriptan infusion confined to the PVN depresses both basal and meningeal-evoked Sp5C activities. Our findings suggest that paraventricular hypothalamic neurons directly control both spontaneous and evoked activities of Sp5C neurons and could act either as modulators or triggers of migraine and/or trigeminal autonomic cephalalgias by integrating nociceptive, autonomic, and stress processing mechanisms. PMID:23678125

  9. 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

  10. 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

    2015-07-06

    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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Thermal diffusion as a mechanism for biological transport.

    PubMed

    Bonner, F J; Sundelöf, L O

    1984-06-01

    Accumulated experimental information is used to assess the possible significance of thermal diffusion to mass transport in living matter. Possible thermal gradients across membranes, a single living cell, and an ensemble of such cells (e.g. an organ, tumor, etc.) are estimated. The corresponding model calculations, although not describing the biological process in detail, lead to conclusions about the possibilities for thermal diffusion as follows. Adequate thermal gradients to support substantial thermal diffusion could exist across biological membranes. Thermal diffusive flow would become significant when ordinary Fickian diffusion is sufficiently suppressed, e.g. in more concentrated systems near critical points of solution (i.e. near incipient phase separations). Conditions favorable to thermal diffusion functioning as a mechanism for active transport appear possible. Thermal diffusion appears much more important for transport into and out of an ensemble of cells than into or out of a single cell. Such mass transport by thermal diffusion could assume a sizable magnitude for an ensemble of cells with the dimensions of an organ or a tumor.

  16. 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.

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

    PubMed

    Melkikh, Alexey V

    2014-01-01

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

  18. 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.

  19. 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

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

    PubMed Central

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

    2015-01-01

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

  1. 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

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

    PubMed

    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.

  3. TNF biology, pathogenic mechanisms and emerging therapeutic strategies

    PubMed Central

    Kalliolias, George D.; Ivashkiv, Lionel B.

    2016-01-01

    TNF is a pleiotropic cytokine with important functions in homeostasis and disease pathogenesis. Recent discoveries have provided insights into TNF biology that introduce new concepts for the development of therapeutics for TNF-mediated diseases. The model of TNF receptor signalling has been extended to include linear ubiquitination and the formation of distinct signalling complexes that are linked with different functional outcomes, such as inflammation, apoptosis and necroptosis. Our understanding of TNF-induced gene expression has been enriched by the discovery of epigenetic mechanisms and concepts related to cellular priming, tolerization and induction of ‘short-term transcriptional memory’. Identification of distinct homeostatic or pathogenic TNF-induced signalling pathways has introduced the concept of selectively inhibiting the deleterious effects of TNF while preserving its homeostatic bioactivities for therapeutic purposes. In this Review, we present molecular mechanisms underlying the roles of TNF in homeostasis and inflammatory disease pathogenesis, and discuss novel strategies to advance therapeutic paradigms for the treatment of TNF-mediated diseases. PMID:26656660

  4. 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

  5. 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.

  6. 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

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

    PubMed

    Makinodan, Manabu

    2015-01-01

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

  8. Transcriptional Analysis of a Unique Set of Genes Involved in Schistosoma mansoni Female Reproductive Biology

    PubMed Central

    Cogswell, Alexis A.; Kommer, Valerie P.; Williams, David L.

    2012-01-01

    Schistosomiasis affects more than 200 million people globally. The pathology of schistosome infections is due to chronic tissue inflammation and damage from immune generated granulomas surrounding parasite eggs trapped in host tissues. Schistosoma species are unique among trematode parasites because they are dioecious; females require paring with male parasites in order to attain reproductive maturity and produce viable eggs. Ex vivo cultured females lose the ability to produce viable eggs due to an involution of the vitellarium and loss of mature oocytes. In order to better understand schistosome reproductive biology we used data generated by serial analysis of gene expression (SAGE) to identify uncharacterized genes which have different transcript abundance in mature females, those that have been paired with males, and immature females obtained from unisexual infections. To characterize these genes we used bioinformatics, transcript localization, and transcriptional analysis during the regression of in vitro cultured females. Genes transcribed exclusively in mature females localize primarily in the vitellocytes and/or the ovary. Genes transcribed exclusively in females from single sex infections localize to vitellocytes and subtegumental cells. As female reproductive tissues regress, eggshell precursor proteins and genes involved in eggshell synthesis largely have decreased transcript abundance. However, some genes with elevated transcript abundance in mature adults have increased gene expression following regression indicating that the genes in this study function both in eggshell biology as well as vitellogenesis and maintenance of female reproductive tissues. In addition, we found that genes enriched in females from single sex infections have increased expression during regression in ex vivo females. By using these transcriptional analyses we can direct research to examine the areas of female biology that are both relevant to understanding the overall process

  9. 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

  10. Interpretation of biological activity data of bacterial endotoxins by simple molecular models of mechanism of action.

    PubMed

    Frecer, V; Ho, B; Ding, J L

    2000-02-01

    Lipid A moiety has been identified as the bioactive component of bacterial endotoxins (lipopolysaccharides). However, the molecular mechanism of biological activity of lipid A is still not fully understood. This paper contributes to understanding of the molecular mechanism of action of bacterial endotoxins by comparing molecular modelling results for two possible mechanisms with the underlying experimental data. Mechanisms of action involving specific binding of lipid A to a protein receptor as well as nonspecific intercalation into phospholipid membrane of a host cell were modelled and analysed. As the cellular receptor for endotoxin has not been identified, a model of a peptidic pseudoreceptor was proposed, based on molecular structure, symmetry of the lipid A moiety and the observed character of endotoxin-binding sites in proteins. We have studied the monomeric form of lipid A from Escherichia coli and its seven synthetic analogues with varying numbers of phosphate groups and correlated them with known biological activities determined by the Limulus assay. Gibbs free energies associated with the interaction of lipid A with the pseudoreceptor model and intercalation into phospholipid membrane calculated by molecular mechanics and molecular dynamics methods were used to compare the two possible mechanisms of action. The results suggest that specific binding of lipid A analogues to the peptidic pseudoreceptor carrying an amphipathic cationic binding pattern BHPHB (B, basic; H, hydrophobic; P, polar residue, respectively) is energetically more favourable than intercalation into the phospholipid membrane. In addition, binding affinities of lipid A analogues to the best minimum binding sequence KFSFK of the pseudoreceptor correlated with the experimental Limulus activity parameter. This correlation enabled us to rationalize the observed relationship between the number and position of the phosphate groups in the lipid A moiety and its biological activity in terms of

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

    PubMed

    Vaughan, Timothy E; Weaver, James C

    2005-05-01

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

  12. Abiotic and biological mechanisms of nitric oxide removal from waste air in biotrickling filters.

    PubMed

    Chen, Jian-Meng; Ma, Jian-Feng

    2006-01-01

    Nitric oxide (NO) may participate in the ozone layer depletion and forming of nitric acid. Abiotic and biological mechanisms of NO removal from waste gases were studied in a biotrickling filter. The abiotic NO removal rate in the biotrickling filter was estimated by a review of the literature. The abiotic and biological removals were also verified in the biotrickling filter. The result has shown that chemical oxidation and bionitrification were both involved in the NO removal. It was found that the NO removal in high concentration (approximately 1000 ppm or higher) was in large measure the result of abiotic removal in both gas-phase and liquid-phase reactions. When NO concentration is low (less than approximately 100 ppm), bionitrification was the main process in the NO removal process in the biotrickling filter.

  13. 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

  14. 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.

  15. 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

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

    PubMed

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

    2012-12-01

    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.

  17. 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

  18. Identification of B-type procyanidins in Fallopia spp. involved in biological denitrification inhibition.

    PubMed

    Bardon, Clément; Piola, Florence; Haichar, Feth el Zahar; Meiffren, Guillaume; Comte, Gilles; Missery, Boris; Balby, Manon; Poly, Franck

    2016-02-01

    Nitrogen (N) is considered as a main limiting factor in plant growth, and nitrogen losses through denitrification can be responsible for severe decreases in plant productivity. Recently, it was demonstrated that Fallopia spp. is responsible for biological denitrification inhibition (BDI) through the release of unknown secondary metabolites. Here, we investigate the secondary metabolites involved in the BDI of Fallopia spp. The antioxidant, protein precipitation capability of Fallopia spp. extracts was measured in relation to the aerobic respiration and denitrification of two bacteria (Gram positive and Gram negative). Proanthocyanidin concentrations were estimated. Proanthocyanidins in extracts were characterized by chromatographic analysis, purified and tested on the bacterial denitrification and aerobic respiration of two bacterial strains. The effect of commercial procyanidins on denitrification was tested on two different soil types. Denitrification and aerobic respiration inhibition were correlated with protein precipitation capacity and concentration of proanthocyanidins but not to antioxidant capacity. These proanthocyanidins were B-type procyanidins that inhibited denitrification more than the aerobic respiration of bacteria. In addition, procyanidins also inhibited soil microbial denitrification. We demonstrate that procyanidins are involved in the BDI of Fallopia spp. Our results pave the way to a better understanding of plant-microbe interactions and highlight future applications for a more sustainable agriculture.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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

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

    PubMed

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

    2014-04-01

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

  6. Molecular mechanisms of temperature-dependent sex determination in the context of ecological developmental biology.

    PubMed

    Matsumoto, Yuiko; Crews, David

    2012-05-01

    Temperature-dependent sex determination (TSD) is a prime example of phenotypic plasticity in that gonadal sex is determined by the temperature of the incubating egg. In the red-eared slider turtle (Trachemys scripta), the effect of temperature can be overridden by exogenous ligands, i.e., sex steroid hormones and steroid metabolism enzyme inhibitors, during the temperature-sensitive period (TSP) of development. Precisely how the physical signal of temperature is transduced into a biological signal that ultimately results in sex determination remains unknown. In this review, we discuss the sex determining pathway underlying TSD by focusing on two candidate sex determining genes, Forkhead box protein L2 (FoxL2) and Doublesex mab3- related transcription factor 1 (Dmrt1). They appear to be involved in transducing the environmental temperature signal into a biological signal that subsequently determines gonadal sex. FoxL2 and Dmrt1 exhibit gonad-typical patterns of expression in response to temperature during the TSP in the red-eared slider turtle. Further, the biologically active ligands regulate the expression of FoxL2 and Dmrt1 during development to modify gonad trajectory. The precise regulatory mechanisms of expression of these genes by temperature or exogenous ligands are not clear. However, the environment often influences developmental gene expression by altering the epigenetic status in regulatory regions. Here, we will discuss if the regulation of FoxL2 and Dmrt1 expression by environment is mediated through epigenetic mechanisms during development in species with TSD.

  7. 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.

  8. 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

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

    NASA Astrophysics Data System (ADS)

    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 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.

  10. 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.

  11. 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.

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

    PubMed

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

    2013-01-01

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

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

    PubMed

    Okajima, Tetsuya; Matsuura, Aiko; Matsuda, Tsukasa

    2008-07-01

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

  14. Antifungal characteristics of a fluorescent Pseudomonas strain involved in the biological control of Rhizoctonia solani.

    PubMed

    Pal, K K; Tilak, K V; Saxena, A K; Dey, R; Singh, C S

    2000-09-01

    A plant growth-promoting isolate of a fluorescent Pseudomonas spp. EM85 was found strongly antagonistic to Rhizoctonia solani, a causal agent of damping-off of cotton. The isolate produced HCN (HCN+), siderophore (Sid+), fluorescent pigments (Flu+) and antifungal antibiotics (Afa+). Tn5::lacZ mutagenesis of isolate EM85 resulted in the production of a series of mutants with altered production of HCN, siderophore, fluorescent pigments and antifungal antibiotics. Characterisation of these mutants revealed that the fluorescent pigment produced in PDA and the siderophore produced in CAS agar were not the same. Afa- and Flu- mutants had a smaller inhibition zone when grown with Rhizoctonia solani than the EM85 wild type. Sid- and HCN mutants failed to inhibit the pathogen in vitro. In a pot experiment, mutants deficient in HCN and siderophore production could suppress the damping-off disease by 52%. However, mutants deficient in fluorescent pigments and antifungal antibiotics failed to reduce the disease severity. Treatments with mutants that produced enhanced amounts of fluorescent pigments and antibiotics compared with EM85 wild type, exhibited an increase in biocontrol efficiency. Monitoring of the mutants in the rhizosphere using the lacZ marker showed identical proliferation of mutants and wild type. Purified antifungal compounds (fluorescent pigment and antibiotic) also inhibited the fungus appreciably in a TLC bioassay. Thus, the results indicate that fluorescent pigment and antifungal antibiotic of the fluorescent Pseudomonas spp. EM85 might be involved in the biological suppression of Rhizoctonia-induced damping-off of cotton.

  15. 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

  16. Magnesium depletion with hypo- or hyper- function of the biological clock may be involved in chronopathological forms of asthma.

    PubMed

    Durlach, J; Pagès, N; Bac, P; Bara, M; Guiet-Bara, A

    2005-03-01

    Asthma is a chronic, inflammatory disorder of the airways leading to airflow limitation. Its worldwide rise, mainly in developed countries, is a matter of concern. Nocturnal asthma (NA) frequently occurs and concerns two thirds of asthmatics. But, it remains controversial whether NA is a distinct entity or is a manifestation of more severe asthma. Generally, it is considered as an exacerbation of the underlying pathology. The pathological mechanisms most likely involve endogenous circadian rhythms with pathological consequences on both respiratory inflammation and hyperresponsiveness. A decrease in blood and tissue magnesium levels is frequently reported in asthma and often testifies to a true magnesium depletion. The link with magnesium status and chronobiology are well established. The quality of magnesium status directly influences the Biological Clock (BC) function, represented by the suprachiasmatic nuclei and the pineal gland. Conversely, BC dysrythmias influence the magnesium status. Two types of magnesium deficits must be clearly distinguished: deficiency corresponding to an insufficient intake which can be corrected through mere nutritional Mg supplementation and depletion due to a dysregulation of the magnesium status which cannot be corrected through nutritional supplementation only, but requires the more or less specific correction of the dysregulation mechanisms. Both in clinical and in animal experiments, the dysregulation mechanisms of magnesium depletion associate a reduced magnesium intake with various types of stress including biological clock dysrhythmias. The differenciation between Mg depletion forms with hyperfunction of BC (HBC) and forms with hypofunction of BC (hBC) is seminal and the main biological marker is melatonin (MT) production alteration. We hypothesize that magnesium depletion with HBC or hBC may be involved in chronopathological forms of asthma. Nocturnal asthma would be linked to HBC, represented by an increase in MT levels. The

  17. Role of Physical Mechanisms in Biological Self-Organization

    NASA Astrophysics Data System (ADS)

    Neagu, Adrian; Jakab, Karoly; Jamison, Richard; Forgacs, Gabor

    2005-10-01

    Organs form during morphogenesis, the process that gives rise to specialized biological structures of specific shape and function in early embryonic development. Morphogenesis is under strict genetic control, but shape evolution itself is a physical process. Here we report the results of experimental and modeling biophysical studies on in vitro biological structure formation. Experimentally, by controlling the interaction between cells and their embedding matrices, we were able to build living structures of definite geometry. The experimentally observed shape evolution was reproduced by Monte Carlo simulations, which also shed light on the biophysical basis of the process. Our work suggests a novel way to engineer biological structures of controlled shape.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  19. 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

  20. Biologically inspired load balancing mechanism in neocortical competitive learning.

    PubMed

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

    2014-01-01

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

  1. 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

  2. Analysis of Korean High School Students' Decision-Making Processes in Solving a Problem Involving Biological Knowledge

    ERIC Educational Resources Information Center

    Hong, Jung-Lim; Chang, Nam-Kee

    2004-01-01

    In this study, the cognitive characteristics of students' decision-making processes centered on phases, difficulties, and strategies are analysed in the personal dailylife context involving biological knowledge. The subjects were first year science and general high school students in Seoul, Korea; 6 female students and 7 male students. The…

  3. 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

  4. A transcriptomics-based biological framework for studying mechanisms of endocrine disruption in small fish species.

    PubMed

    Wang, Rong-Lin; Bencic, David; Villeneuve, Daniel L; Ankley, Gerald T; Lazorchak, Jim; Edwards, Stephen

    2010-07-01

    This study sought to construct a transcriptomics-based framework of signal transduction pathways, transcriptional regulatory networks, and the hypothalamic-pituitary gonadal (HPG) axis in zebrafish (Danio rerio) to facilitate formulation of specific, testable hypotheses regarding the mechanisms of endocrine disruption in fish. For the analyses involved, we used data from a total of more than 300 microarrays representing 58 conditions, which encompassed 4 tissue types from zebrafish of both genders exposed for 1 of 3 durations to 10 different test chemicals (17alpha-ethynyl estradiol, fadrozole, 17beta-trenbolone, fipronil, prochloraz, flutamide, muscimol, ketoconazole, trilostane, and vinclozolin). Differentially expressed genes were identified by one class t-tests for each condition, and those with false discovery rates of less than 40% and treatment/control ratios > or =1.3-fold were mapped to orthologous human, mouse, and rat pathways by Ingenuity Pathway Analysis to look for overrepresentation of known biological pathways. To complement the analysis of known biological pathways, the genes regulated by approximately 1800 transcription factors were inferred using the ARACNE mutual information-based algorithm. The resulting gene sets for all transcriptional factors, along with a group of compiled HPG-axis genes and approximately 130 publicly available biological pathways, were analyzed for their responses to the 58 treatment conditions by Gene Set Enrichment Analysis (GSEA) and its variant, Extended-GSEA. The biological pathways and transcription factors associated with multiple distinct treatments showed substantial interactions among the HPG-axis, TGF-beta, p53, and several of their cross-talking partners. These candidate networks/pathways have a variety of profound impacts on such cellular functions as stress response, cell cycle, and apoptosis.

  5. [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.

  6. Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1998 annual progress report

    SciTech Connect

    Bull, R.J.; Thrall, B.D.; Sasser, L.B.; Miller, J.H.; Schultz, I.R.

    1998-06-01

    elevations in serum insulin concentrations, as well. The increases in insulin have not been shown responsible for the induction of liver tumors. Therefore, this problem is a subject of a proposal to the Office of Biological and Environmental Research Low-Dose Initiative. However, even if this is demonstrated to be the most sensitive mechanism for liver tumor induction, it is unlikely to contribute to induction of cancer at lower doses, since this involves modification of normal endocrine function. As doses are decreased to levels that do not induce increase in serum insulin level, there should be no risk from this metabolite either. Therefore, there is clearly a rational basis for considering a margin of exposure for low dose extrapolation of liver cancer risks for TCE.'

  7. 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

  8. Structural biological materials: critical mechanics-materials connections.

    PubMed

    Meyers, Marc André; McKittrick, Joanna; Chen, Po-Yu

    2013-02-15

    Spider silk is extraordinarily strong, mollusk shells and bone are tough, and porcupine quills and feathers resist buckling. How are these notable properties achieved? The building blocks of the materials listed above are primarily minerals and biopolymers, mostly in combination; the first weak in tension and the second weak in compression. The intricate and ingenious hierarchical structures are responsible for the outstanding performance of each material. Toughness is conferred by the presence of controlled interfacial features (friction, hydrogen bonds, chain straightening and stretching); buckling resistance can be achieved by filling a slender column with a lightweight foam. Here, we present and interpret selected examples of these and other biological materials. Structural bio-inspired materials design makes use of the biological structures by inserting synthetic materials and processes that augment the structures' capability while retaining their essential features. In this Review, we explain this idea through some unusual concepts. PMID:23413348

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

    PubMed

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

    2012-11-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-02-17

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

  12. 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.

  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. 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.

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

    PubMed

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

    2015-02-09

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

  16. 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

  17. 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.

  18. 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)

  19. 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…

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  1. 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.

  2. Seminal vesicle intraepithelial involvement by prostate cancer: putative mechanism and clinicopathological significance.

    PubMed

    Miyai, Kosuke; Kristiansen, Anna; Egevad, Lars; Pina-Oviedo, Sergio; Divatia, Mukul K; Shen, Steven S; Miles, Brian J; Ayala, Alberto G; Park, Yong Wook; Ro, Jae Y

    2014-09-01

    We have recently shown seminal vesicle intraepithelial involvement of prostate cancer in cases with seminal vesicle invasion (pT3b). Based on the manner of seminal vesicle invasion, there could be 2 possible mechanisms of seminal vesicle intraepithelial involvement: direct intraepithelial invasion from prostate carcinoma in the muscular wall of seminal vesicles or intraepithelial involvement of cancer from the invaginated extraprostatic space (IES)/ejaculatory duct system to extraprostatic seminal vesicle. We aimed to clarify the manner and clinicopathological significance of seminal vesicle intraepithelial involvement. Of 1629 consecutive radical prostatectomies, 109 cases (6.7%) showed seminal vesicle invasion in whole-mounted radical prostatectomy specimens. In these pT3b cases, 18 (17%) showed seminal vesicle intraepithelial involvement by prostate cancer. Stromal invasion of the IES/ejaculatory duct system and ejaculatory duct intraepithelial invasion by prostate cancer were identified in 62 and 5 of 109 pT3b cases, respectively. However, the presence/absence of IES/ejaculatory duct system involvement by prostate cancer does not predict seminal vesicle intraepithelial involvement. No statistically significant correlation was observed between all pathologic parameters/biochemical recurrence and the presence/absence of seminal vesicle intra-epithelial involvement in the pT3b cases. These findings suggest that seminal vesicle intraepithelial involvement is more likely due to direct invasion of carcinoma from the muscular wall of seminal vesicles rather than intraepithelial extension from the ejaculatory duct system in the IES. Further studies with a substantially greater case number are needed to clarify the clinicopathological significance of seminal vesicle intraepithelial involvement in a better manner.

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

    PubMed Central

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

    2016-01-01

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

  4. Involvement of MicroRNAs in Lung Cancer Biology and Therapy

    PubMed Central

    Liu, Xi; Sempere, Lorenzo F.; Guo, Yongli; Korc, Murray; Kauppinen, Sakari; Freemantle, Sarah J.; Dmitrovsky, Ethan

    2011-01-01

    MicroRNAs (miRNAs) are a class of small RNAs that regulate gene expression. Expression profiles of specific miRNAs have improved cancer diagnosis and classification and even provided prognostic information in many human cancers, including lung cancer. Tumor suppressive and oncogenic miRNAs were uncovered in lung carcinogenesis. The biological functions of these miRNAs in lung cancer were recently validated in well characterized cellular, murine transgenic as well as transplantable lung cancer models and in human paired normal-malignant lung tissue banks and tissue arrays. Tumor suppressive and oncogenic miRNAs that were identified in lung cancer will be reviewed here. Emphasis is placed on highlighting those functionally validated miRNAs that are not only biomarkers of lung carcinogenesis, but also candidate pharmacologic targets. How these miRNA findings advance an understanding of lung cancer biology and could improve lung cancer therapy are discussed in this article. PMID:21420030

  5. 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.

  6. 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

  7. 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.

  8. Human biological monitoring for exposure assessment in response to an incident involving hazardous materials.

    PubMed

    Scheepers, Paul T J; van Brederode, Nelly E; Bos, Peter M J; Nijhuis, Nicole J; van de Weerdt, Rik H J; van der Woude, Irene; Eggens, Martin L

    2014-12-15

    Biological monitoring in humans (HBM) is widely used in the field of occupational and environmental health. In the situation of an unexpected release of hazardous materials HBM may contribute to the medical support and treatment of exposed individuals from the general population or of emergency responders. Such exposure information may also be used to respond to individual concerns such as questions about a possible relationship between the chemicals released during the incident and health effects. In The Netherlands a guideline was prepared to support early decision-making about the possible use of HBM for exposure assessment during or as soon as possible following a chemical incident. The application of HBM in such an emergency setting is not much different from situations where HBM is normally used but there are some issues that need extra attention such as the choice of the biomarker, the biological media to be sampled, the time point at which biological samples should be collected, the ethics approval and technical implementation of the study protocol and the interpretation and communication of the study results. These issues addressed in the new guideline will support the use of HBM in the management of chemical disasters.

  9. 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.

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

    PubMed

    Rajsbaum, Ricardo; García-Sastre, Adolfo

    2013-08-01

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

  11. DNA methylation, riboswitches, and transcription factor activity: fundamental mechanisms of gene-nutrient interactions involving vitamins.

    PubMed

    Huang, Janet; Vieira, Amandio

    2006-12-01

    Nutrient-gene interactions occur with a variety of nutrients including some minerals, vitamins, polyunsaturated fatty acids and other lipids. Fundamental molecular mechanisms that underlie many of the effects of nutrients on gene expression are presented herein. Two of the mechanisms described influence gene transcription: DNA methylation and transcription factor activation. Another mechanism, riboswitching, can regulate gene expression at different levels, for example, at the mRNA translation level. The first two mechanisms are widely distributed across animal phyla. Riboswitches are documented primarily in more primitive organisms, but may prove to be of wider relevance. Riboswitches are known for several vitamins; those involving thiamine are presented here. The role of folates and retinoids in DNA methylation and transcriptional factor (nuclear retinoid receptor) activities, respectively, is presented in the context of cell proliferation and differentiation, and related physiological or pathological effects during embryogenesis and cancer.

  12. 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

  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.

  14. 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

  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

    2015-07-06

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

  17. 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.

  18. 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.

  19. [Genetic and biochemical mechanisms of involvement of antioxidant defense enzymes in the development of bronchial asthma].

    PubMed

    Polonikov, A V; Ivanov, V P; Bogomazov, A D; Solodilova, M A

    2015-01-01

    In the present review we have analyzed and summarized recent literature data on genetic and biochemical mechanisms responsible for involvement of antioxidant defense enzymes in the etiology and pathogenesis of bronchial asthma. It has been shown that the mechanisms of asthma development are linked with genetically determined abnormalities in the functioning of antioxidant defense enzymes. These alterations are accompanied by a systemic imbalance between oxidative and anti-oxidative reactions with the shift of the redox state toward increased free radical production and oxidative stress, a key element in the pathogenesis of bronchial asthma. PMID:26350733

  20. [Genetic and biochemical mechanisms of involvement of antioxidant defense enzymes in the development of bronchial asthma].

    PubMed

    Polonikov, A V; Ivanov, V P; Bogomazov, A D; Solodilova, M A

    2015-01-01

    In the present review we have analyzed and summarized recent literature data on genetic and biochemical mechanisms responsible for involvement of antioxidant defense enzymes in the etiology and pathogenesis of bronchial asthma. It has been shown that the mechanisms of asthma development are linked with genetically determined abnormalities in the functioning of antioxidant defense enzymes. These alterations are accompanied by a systemic imbalance between oxidative and anti-oxidative reactions with the shift of the redox state toward increased free radical production and oxidative stress, a key element in the pathogenesis of bronchial asthma.

  1. Sequential mechanisms underlying concentration invariance in biological olfaction

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2014-01-01

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

  3. 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.

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

    PubMed Central

    Dyment, Nathaniel A.; Galloway, Jenna L.

    2015-01-01

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

  5. 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

  6. 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.

  7. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed

    Paz, Manuel M

    2009-10-01

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

  11. Cell biological mechanisms of multidrug resistance in tumors.

    PubMed

    Simon, S M; Schindler, M

    1994-04-26

    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.

  12. Degradation of Curcumin: From Mechanism to Biological Implications.

    PubMed

    Schneider, Claus; Gordon, Odaine N; Edwards, Rebecca L; Luis, Paula B

    2015-09-01

    Curcumin is the main bioactive ingredient in turmeric extract and widely consumed as part of the spice mix curry or as a dietary supplement. Turmeric has a long history of therapeutic application in traditional Asian medicine. Biomedical studies conducted in the past two decades have identified a large number of cellular targets and effects of curcumin. In vitro curcumin rapidly degrades in an autoxidative transformation to diverse chemical species, the formation of which has only recently been appreciated. This paper discusses how the degradation and metabolism of curcumin, through products and their mechanism of formation, provide a basis for the interpretation of preclinical data and clinical studies. It is suggested that the previously unrecognized diversity of its degradation products could be an important factor in explaining the polypharmacology of curcumin. PMID:25817068

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

    PubMed

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

    2015-10-01

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

  14. Degradation of curcumin: From mechanism to biological implications

    PubMed Central

    Schneider, Claus; Gordon, Odaine N.; Edwards, Rebecca L.; Luis, Paula B.

    2016-01-01

    Curcumin is the main bioactive ingredient in turmeric extract and widely consumed as part of the spice mix curry or as dietary supplement. Turmeric has a long history of therapeutic application in traditional Asian medicine. Biomedical studies conducted in the past two decades have identified a large number of cellular targets and effects of curcumin. In vitro curcumin rapidly degrades in an autoxidative transformation to diverse chemical species, formation of which has only recently been appreciated. We discuss how degradation and metabolism of curcumin, through products and their mechanism of formation, provide a basis for the interpretation of preclinical data and clinical studies. We suggest that the previously unrecognized diversity of its degradation products could be an important factor in explaining the polypharmacology of curcumin. PMID:25817068

  15. 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.

  16. Degradation of Curcumin: From Mechanism to Biological Implications.

    PubMed

    Schneider, Claus; Gordon, Odaine N; Edwards, Rebecca L; Luis, Paula B

    2015-09-01

    Curcumin is the main bioactive ingredient in turmeric extract and widely consumed as part of the spice mix curry or as a dietary supplement. Turmeric has a long history of therapeutic application in traditional Asian medicine. Biomedical studies conducted in the past two decades have identified a large number of cellular targets and effects of curcumin. In vitro curcumin rapidly degrades in an autoxidative transformation to diverse chemical species, the formation of which has only recently been appreciated. This paper discusses how the degradation and metabolism of curcumin, through products and their mechanism of formation, provide a basis for the interpretation of preclinical data and clinical studies. It is suggested that the previously unrecognized diversity of its degradation products could be an important factor in explaining the polypharmacology of curcumin.

  17. Sound and faulty arguments generated by preservice biology teachers when testing hypotheses involving unobservable entities

    NASA Astrophysics Data System (ADS)

    Lawson, Anton E.

    2002-03-01

    A sample of preservice biology teachers (biology majors) enrolled in a teaching methods course formulated and attempted to test six hypotheses to answer a causal question about why water rose in a jar inverted over a burning candle placed in a pan of water. The students submitted a lab report in which arguments and evidence for testing each hypothesis were presented in an if/then/therefore hypothetico-predictive form. Analysis of written arguments revealed considerable success when students were able to manipulate observable hypothesized causes. However, when the hypothesized causes were unobservable, such that they could be only indirectly tested, performance dropped, as shown by use of three types of faulty arguments: (a) arguments that had missing or confused elements, (b) arguments whose predictions did not follow from hypotheses and planned tests, and (c) arguments that failed to consider alternative hypotheses. Science is an enterprise in which unobservable theoretical entities and processes (e.g., atoms, genes, osmosis, and photosynthesis) are often used to explain observable phenomena. Consequently, if it is assumed that effective teaching requires prior understanding, then it follows that these future teachers have yet to develop adequate hypothesis-testing skills and sufficient awareness of the nature of science to teach science in the inquiry mode advocated by reform guidelines.

  18. 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

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  20. Early Differentiation of Causal Mechanisms Appropriate to Biological and Nonbiological Kinds.

    ERIC Educational Resources Information Center

    Springer, Ken; Keil, Frank C.

    1991-01-01

    Three investigations and one main experiment examined whether children ages four to seven differentiate between the causal mechanisms appropriate for different conceptual domains. Results suggest that preschoolers prefer natural mechanisms for color inheritance in biological kinds and recognize the importance of human intentions in producing the…

  1. 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

  2. Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking.

    PubMed

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2011-10-24

    Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation, although its detailed mechanism of action has yet to be elucidated. To further examine its potential as a CNS modulating agent as well as its mechanism of action, we investigated the effects of clavulanic acid in neuronal cells. Our results indicate that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity chromatography we were able to identify two proteins, Munc18-1 and Rab4 that potentially bind to clavulanic acid and play a critical role in neurosecretion and the vesicle trafficking process. Consistent with this result, an increase in the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid treated cells. Overall, these data suggest that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders, such as depression.

  3. Reflex hypertensive response induced by capsaicin involves endothelin-dependent mechanisms.

    PubMed

    Akella, Aparna; Deshpande, Shripad B

    2015-01-01

    Capsaicin, a nociceptive agent produces triphasic pressure response in rats. The mechanisms underlying capsaicin-induced pressure responses are not clear. Therefore, the present study was undertaken to determine the mechanisms involved in capsaicin - induced pressure responses. The trachea, jugular vein and femoral artery were cannulated in anaesthetized rats. Capsaicin (10 µg/kg; i.v) - induced reflex changes in the blood pressure, respiratory excursions and ECG were recorded before/after vagotomy in the absence/presence of antagonists. Capsaicin produced the triphasic pressure response characterized by immediate fall, recovery (intermediate phase) and delayed progressive fall. After vagotomy, the immediate hypotension was abolished and the intermediate pressure response was potentiated as a hypertensive response while the delayed hypotensive response persisted. The time-matched heart rate changes (bradycardia) and respiratory changes (tachypnea in delayed phase) were abolished after vagotomy. Pretreatment with endothelin receptor antagonist (bosentan; 10 mg/kg) blocked the capsiaicn-induced intermediate hypertensive response in vagotomised animals but not the delayed hypotension. Pretreatment with nitric oxide synthase (NOS) inhibitor (L-NAME; 30 pg/kg), prostaglandin synthase inhibitor (indomethacin; 10 mg/kg) and kinin synthase inhibitor (aprotinin; 6000 KIU) did not block the delayed hypotensive response. These results demonstrate that capsaicin-induced intermediate hypertensive response involves endothelin-dependent mechanisms and the delayed hypotensive response is independent of nitrergic, prostaglandinergic or kininergic mechanisms.

  4. Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking

    PubMed Central

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2011-01-01

    Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation, although its detailed mechanism of action has yet to be elucidated. To further examine its potential as a CNS modulating agent as well as its mechanism of action, we investigated the effects of clavulanic acid in neuronal cells. Our results indicate that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity chromatography we were able to identify two proteins, Munc18-1 and Rab4 that potentially bind to clavulanic acid and play a critical role in neurosecretion and the vesicle trafficking process. Consistent with this result, an increase in the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid treated cells. Overall, these data suggest that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders, such as depression. PMID:21964384

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

    PubMed

    O'Byrne, Kenneth

    2015-04-01

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

  6. [Biological effects of rare earth elements and their action mechanisms].

    PubMed

    He, Yuejun; Xue, Li

    2005-10-01

    This paper reviewed the effects of rare earth elements on plant root development, biomass, quality, and resistance against stress. Applying appropriate amount of rare earth elements could not only promote seed germination and root development, increase plant biomass, but also improve harvest quality and plant resistance against stress. The plant uptake characteristics of rare earth elements, as well as their contents, distribution, existing forms, and cytolocalization in plants were discussed, with the focus on the effects of rare earth elements on photosynthesis and chlorophyll formation, nutrient uptake, relationships between rare earth elements and calcium, and action mechanisms of rare earth elements on cell membrane and enzymes. Rare earth elements could enhance chlorophyll content and improve photosynthetic rate, and thus, could increase plant biomass. When an appropriate amount of rare earth elements was applied, the uptake of nutrients by plant and their transformation and utilization were promoted. Rare earth elements could replace calcium ion to participate in enzymatic reactions, maintain the osmosis and stability of cell membrane, promote the protection function of cell membrane, and enhance the plant resistance capability against stress. In the end, further researches on rare earth elements were suggested.

  7. 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

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

    PubMed

    Ramesh, Aruna C; Kumar, S

    2010-07-01

    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.

  9. 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

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

    PubMed

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

    2014-07-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-02-01

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

  13. 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

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

    PubMed

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

    2015-09-29

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

  15. Involvement of intermediate sulfur species in biological reduction of elemental sulfur under acidic, hydrothermal conditions.

    PubMed

    Boyd, Eric S; Druschel, Gregory K

    2013-03-01

    The thermoacidophile and obligate elemental sulfur (S(8)(0))-reducing anaerobe Acidilobus sulfurireducens 18D70 does not associate with bulk solid-phase sulfur during S(8)(0)-dependent batch culture growth. Cyclic voltammetry indicated the production of hydrogen sulfide (H(2)S) 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 S(8)(0) and the biologically produced H(2)S, 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 S(8)(0) was detected in the cultivation medium, a result of the hydrolysis of polysulfides in acidic medium. To examine whether soluble polysulfides and/or nanoparticulate S(8)(0) 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 S(8)(0) provided as a solid phase in the medium or with S(8)(0) sequestered in dialysis tubing. The rates of sulfide production in 7-day-old cultures with S(8)(0) 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 S(8)(0) 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 S(8)(0) 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, S(8)(0) particles formed through abiological hydrolysis of polysulfide under acidic conditions appeared to serve as a growth-promoting TEA for A. sulfurireducens.

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

    PubMed Central

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

    2013-01-01

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

  17. 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

  18. 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

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

    PubMed

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

    2013-03-01

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

  20. 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".

  1. 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.

  2. A proposed biochemical mechanism involving hemoglobin for blast overpressure-induced injury.

    PubMed

    Elsayed, N M; Gorbunov, N V; Kagan, V E

    1997-07-25

    Blast overpressure (BOP) is the abrupt, rapid, rise in atmospheric pressure resulting from explosive detonation, firing of large-caliber weapons, and accidental occupational explosions. Exposure to incident BOP waves causes internal injuries, mostly to the hollow organs, particularly the ears, lungs and gastrointestinal tract. BOP-induced injury used to be considered of military concern because it occurred mostly in military environments during military actions or training, and to a lesser extent during civilian occupational accidents. However, in recent years with the proliferation of indiscriminate terrorist bombings worldwide involving civilians, blast injury has become a societal concern, and the need to understand the biochemical and molecular mechanism(s) of injury, and to find new and effective methods for treatment gained importance. In general, past BOP research has focused on the physiological and pathological manifestations of incapacitation, thresholds of safety, and on predictive modeling. However, we have been studying the molecular mechanism of BOP-induced injury, and recently began to have an insight into that mechanism, and recognize the role of hemoglobin released during hemorrhage in catalyzing free radical reactions leading to oxidative stress. In this report we discuss the biochemical changes observed after BOP exposure in rat blood and lung tissue, and propose a biochemical mechanism for free radical-induced oxidative stress that can potentially complicate the injury. Moreover, we observed that some antioxidants can interact with Hb oxidation products (oxy-, met- and oxoferrylHb) and act as prooxidants that can increase the damage rather than decrease it.

  3. A proposed biochemical mechanism involving hemoglobin for blast overpressure-induced injury.

    PubMed

    Elsayed, N M; Gorbunov, N V; Kagan, V E

    1997-07-25

    Blast overpressure (BOP) is the abrupt, rapid, rise in atmospheric pressure resulting from explosive detonation, firing of large-caliber weapons, and accidental occupational explosions. Exposure to incident BOP waves causes internal injuries, mostly to the hollow organs, particularly the ears, lungs and gastrointestinal tract. BOP-induced injury used to be considered of military concern because it occurred mostly in military environments during military actions or training, and to a lesser extent during civilian occupational accidents. However, in recent years with the proliferation of indiscriminate terrorist bombings worldwide involving civilians, blast injury has become a societal concern, and the need to understand the biochemical and molecular mechanism(s) of injury, and to find new and effective methods for treatment gained importance. In general, past BOP research has focused on the physiological and pathological manifestations of incapacitation, thresholds of safety, and on predictive modeling. However, we have been studying the molecular mechanism of BOP-induced injury, and recently began to have an insight into that mechanism, and recognize the role of hemoglobin released during hemorrhage in catalyzing free radical reactions leading to oxidative stress. In this report we discuss the biochemical changes observed after BOP exposure in rat blood and lung tissue, and propose a biochemical mechanism for free radical-induced oxidative stress that can potentially complicate the injury. Moreover, we observed that some antioxidants can interact with Hb oxidation products (oxy-, met- and oxoferrylHb) and act as prooxidants that can increase the damage rather than decrease it. PMID:9217317

  4. Novel molecular mechanisms involved in hormonal regulation of lactate production in Sertoli cells.

    PubMed

    Regueira, Mariana; Artagaveytia, Silvana Lucía; Galardo, María Noel; Pellizzari, Eliana Herminia; Cigorraga, Selva Beatriz; Meroni, Silvina Beatriz; Riera, María Fernanda

    2015-10-01

    The aim of the study was to analyze molecular mechanisms involved in FSH and basic fibroblast growth factor (bFGF) regulation of lactate production in rat Sertoli cells. The regulation of the availability of pyruvate, which is converted to lactate, could be a mechanism utilized by hormones to ensure lactate supply to germ cells. On one hand, the regulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB) expression could result in increased glycolysis, while an increase in pyruvate availability may also result from a lower conversion to acetyl-CoA by negative regulation of pyruvate dehydrogenase complex (PDC) activity by phosphorylation. Sertoli cell cultures obtained from 20-day-old rats were used. Stimulation of the cultures with FSH or bFGF showed that FSH increases Pfkfb1 and Pfkfb3 expression while bFGF increases Pfkfb1 mRNA levels. Additionally, we observed that FSH-stimulated lactate production was inhibited in the presence of a PFKFB3 inhibitor, revealing the physiological relevance of this mechanism. As for the regulation of PDC, analysis of pyruvate dehydrogenase kinase (Pdk) expression showed that FSH increases Pdk3 and decreases Pdk4 mRNA levels while bFGF increases the expression of all Pdks. In addition, we showed that bFGF increases phosphorylated PDC levels and that bFGF-stimulated lactate production is partially inhibited in the presence of a PDK inhibitor. Altogether, these results add new information regarding novel molecular mechanisms involved in hormonal regulation of lactate production in Sertoli cells. Considering that lactate is essential for the production of energy in spermatocytes and spermatids, these mechanisms might be relevant in maintaining spermatogenesis and male fertility. PMID:26224098

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  6. 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

  7. 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.

  8. Involvement of the mechanoreceptors in the sensory mechanisms of manual and electrical acupuncture.

    PubMed

    Yamamoto, Hiromi; Kawada, Toru; Kamiya, Atsunori; Miyazaki, Shunichi; Sugimachi, Masaru

    2011-02-24

    The modalities of acupuncture can be broadly classified into manual acupuncture (MA) and electroacupuncture (EA). Although MA has been reported to cause winding of tissue around the needle and subsequent activation of the sensory mechanoreceptors and nociceptors, the sensory mechanisms of acupuncture stimulation are not fully understood. To test the hypothesis that the involvement of the mechanoreceptors in the sensory mechanism is different in MA and EA, we examined the effects of a stretch-activated channel blocker gadolinium on the hemodynamic responses to hind limb MA and EA in anesthetized rats (n = 9). Gadolinium significantly attenuated the MA-induced bradycardic response (-22 ± 5 vs. -10 ± 3 bpm, P<0.05) and tended to attenuate the MA-induced depressor response (-30 ± 5 vs. -18 ± 4 mmHg, P = 0.06). On the other hand, gadolinium significantly attenuated both the EA-induced bradycardic (-22 ± 5 vs. -9 ± 4 bpm, P<0.01) and depressor responses (-32 ± 6 vs. -15 ± 5 mmHg, P<0.01). These results indicate that the mechanoreceptors are involved in the sensory mechanisms for both MA and EA.

  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. 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.

  11. Transduction mechanism(s) of Na-saccharin in the blowfly Protophormia terraenovae: evidence for potassium and calcium conductance involvement.

    PubMed

    Masala, Carla; Solari, Paolo; Sollai, Giorgia; Crnjar, Roberto; Liscia, Anna

    2009-12-01

    The study on transduction mechanisms underlying bitter stimuli is a particularly intriguing challenge for taste researchers. The present study investigates, in the labellar chemosensilla of the blowfly Protophormia terraenovae, the transduction mechanism by which saccharin evokes the response of the "deterrent" cell, with particular attention to the contribution of K(+) and Ca(2+) current and the role of cyclic nucleotides, since second messengers modulate Ca(2+), Cl(-) and K(+) currents to different extents. As assessed by extracellular single-sensillum recordings, our results show that the addition of a Ca(2+) chelator such as EGTA or the Ca(2+) current blockers SK&F-96365, Mibefradil, Nifedipine and W-7 decrease the response of the "deterrent" cell to saccharin. A similar decreasing effect was also obtained following the addition of 4-aminopyridine, a K(+) current blocker. On the contrary, the membrane-permeable cyclic nucleotide 8-bromoguanosine 3',5'-cyclic monophosphate (8Br-cGMP) activates this cell and shows an additive effect when presented mixed with saccharin. Our results are consistent with the hypothesis that in the labellar chemosensilla of the blowfly both Ca(2+) and K(+) ions are involved in the transduction mechanism of the "deterrent" cell in response to saccharin. Our results also suggest a possible pathway common to saccharin and 8Br-cGMP.

  12. 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

  13. 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.

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

    PubMed

    Feldstein Ewing, Sarah W; Chung, Tammy

    2013-06-01

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

  15. Unifying mechanism for anticancer agents involving electron transfer and oxidative stress: clinical implications.

    PubMed

    Kovacic, Peter

    2007-01-01

    Extensive evidence supports involvement of electron transfer (ET), reactive oxygen species (ROS) and oxidative stress (OS) in the mechanism of many anticancer drugs. The common ET functionalities, usually present in the drug metabolites, are quinones (or precursors), metal complexes (or complexors), aromatic nitro compounds (or reduced hydroxylamine and nitroso derivatives), and conjugated imines (or iminium species). The ET agents function catalytically in redox cycling with formation of ROS from oxygen. Electrochemical data add support to the mechanistic viewpoint. The generated metabolites generally possess reduction potentials amenable to ET in vivo, thus giving rise to ROS. The resulting OS is a participant in destruction of the cancer cell. It is important to recognize that drug action is often multipronged. The various modes of action are summarized. Most research has been devoted to development of new and improved chemotherapeutic agents. The need for more attention to measures for cancer prevention is addressed. One of the most promising involves use of antioxidants.

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

    PubMed Central

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-11-01

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

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

    PubMed

    Rajeev, Ramanan; Sunoj, Raghavan B

    2013-07-19

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

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

    PubMed

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

    2015-03-01

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

  20. Brain structures and mechanisms involved in the generation of REM sleep.

    PubMed

    Reinoso-Suárez, Fernando; de Andrés, Isabel; Rodrigo-Angulo, Margarita L.; Garzón, Miguel

    2001-02-01

    This article reviews the central nervous mechanisms involved in the broad network that generates and maintains REM sleep. Experimental investigations have identified the pontine tegmentum as the critical substrate for REM sleep mechanisms. Several pontine structures are involved in the generation of each particular polygraphic event that characterizes REM sleep: desynchronization in the electroencephalogram, theta rhythm in the hippocampus, muscle atonia, pontogeniculooccipital waves and rapid eye movements. The pontine tegmentum also holds the region where cholinergic stimulation can trigger all the behavioural and bioelectric signs of REM sleep. The exact location has been investigated and amply discussed over the last few years. Studies in the authors> laboratory, mapping the pontine tegmentum with small volume carbachol (a cholinergic agonist) microinjections, have demonstrated that the executive neurons for REM sleep generation are neither located in the dorsal part of the pontine tegmentum, nor diffusely spread through the medial pontine reticular formation: they are concentrated in a discrete area in the ventral part of the oral pontine reticular nucleus (vRPO). In turn, the vRPO has connections with structures involved in the generation of the other states of the sleep-wake cycle as well as with structures responsible for the generation of each of the different events characterizing REM sleep. This allows us to propose the vRPO as the crucial region for REM sleep generation. Related research, with invivo and invitro experiments, into the actions of different neurotransmitters on vRPO neurones indicates that not only acetylcholine but other neurotransmitters have an active key role in vRPO REM sleep generation mechanisms.

  1. 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

  2. Mechanisms involved in the inhibitory effect of chronic alcohol exposure on pancreatic acinar thiamin uptake.

    PubMed

    Srinivasan, Padmanabhan; Subramanian, Veedamali S; Said, Hamid M

    2014-04-01

    Pancreatic acinar cells (PAC) obtain thiamin from the circulation via a carrier-mediated process that involves thiamin transporters 1 and 2 (THTR-1 and THTR-2; products of SLC19A2 and SLC19A3, respectively). Chronic alcohol exposure of PAC inhibits thiamin uptake, and, on the basis of in vitro studies, this inhibition appears to be transcriptionally mediated. The aim of this study was to confirm the involvement of a transcriptional mechanism in mediating the chronic alcohol effect in in vivo settings and to delineate the molecular mechanisms involved. Using transgenic mice carrying full-length SLC19A2 and SLC19A3 promoters, we found that chronic alcohol feeding led to a significant reduction in the activity of SLC19A2 and SLC19A3 promoters (as well as in thiamin uptake and expression of THTR-1 and -2). Similar findings were seen in 266-6 cells chronically exposed to alcohol in vitro. In the latter studies, the alcohol inhibitory effect was found to be mediated via the minimal SLC19A2 and SLC19A3 promoters and involved the cis-regulatory elements stimulating protein 1 (SP1)/gut-enriched Kruppel-like factor and SP1-GG-box and SP1/GC, respectively. Chronic alcohol exposure of PAC also led to a significant reduction in the expression of the SP1 transcription factor, which upon correction (via expression) led to the prevention of alcohol inhibitory effects on not only the activity of SLC19A2 and SLC19A3 promoters but also on the expression of THTR-1 and -2 mRNA and thiamin uptake. These results demonstrate that the inhibitory effect of chronic alcohol exposure on physiological/molecular parameters of thiamin uptake by PAC is mediated via specific cis-regulatory elements in SLC19A2 and SLC19A3 minimal promoters.

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

    PubMed

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

    2012-04-01

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

  4. 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.

  5. 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

  6. 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

  7. Cellular and intracellular mechanisms involved in the cognitive impairment of cannabinoids

    PubMed Central

    Puighermanal, Emma; Busquets-Garcia, Arnau; Maldonado, Rafael; Ozaita, Andrés

    2012-01-01

    Exogenous cannabinoids, such as delta9-tetrahydrocannabinol (THC), as well as the modulation of endogenous cannabinoids, affect cognitive function through the activation of cannabinoid receptors. Indeed, these compounds modulate a number of signalling pathways critically implicated in the deleterious effect of cannabinoids on learning and memory. Thus, the involvement of the mammalian target of rapamycin pathway and extracellular signal-regulated kinases, together with their consequent regulation of cellular processes such as protein translation, play a critical role in the amnesic-like effects of cannabinoids. In this study, we summarize the cellular and molecular mechanisms reported in the modulation of cognitive function by the endocannabinoid system. PMID:23108544

  8. Thermodynamic and mechanical timescales involved in foam film rupture and liquid foam coalescence.

    PubMed

    Rio, Emmanuelle; Biance, Anne-Laure

    2014-12-01

    Recent advances in the coalescence in liquid foams are reviewed, with a special focus on the multiscale structure of foams. Studies concerning the stability of isolated foam films, on the one hand, and the coalescence process in macroscopic foams, on the other hand, are not always in good agreement. This discrepancy reveals that two routes can induce coalescence in a foam. The first route is thermodynamic and shows that coalescence is governed by a stochastic rupture of foam films. The second route relies on a mechanically induced rupture of the films, due to the spontaneous evolution of foams. From a literature review, the evaluation of the different timescales involved in these mechanisms allows defining the limiting parameters of foam coalescence.

  9. Transcription factor abundance controlled by an auto-regulatory mechanism involving a transcription start site switch

    PubMed Central

    Ngondo, Richard Patryk; Carbon, Philippe

    2014-01-01

    A transcriptional feedback loop is the simplest and most direct means for a transcription factor to provide an increased stability of gene expression. In this work performed in human cells, we reveal a new negative auto-regulatory mechanism involving an alternative transcription start site (TSS) usage. Using the activating transcription factor ZNF143 as a model, we show that the ZNF143 low-affinity binding sites, located downstream of its canonical TSS, play the role of protein sensors to induce the up- or down-regulation of ZNF143 gene expression. We uncovered that the TSS switch that mediates this regulation implies the differential expression of two transcripts with an opposite protein production ability due to their different 5′ untranslated regions. Moreover, our analysis of the ENCODE data suggests that this mechanism could be used by other transcription factors to rapidly respond to their own aberrant expression level. PMID:24234445

  10. 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

  11. Dura-evoked neck muscle activity involves purinergic and N-methyl-D-aspartate receptor mechanisms.

    PubMed

    Yao, Dongyuan; Yoshida, Mitsuhiro; Sessle, Barry J

    2015-12-16

    We have previously demonstrated that noxious stimulation of craniofacial tissues including the frontal dura reflexly evokes significant increases in neck muscle electromyographic (EMG) activity. The primary aim of this study was to determine whether purinergic receptor mechanisms may be involved in these EMG effects, and whether N-methyl-D-aspartate (NMDA) receptor processes modulate the purinergic mechanisms. Application of the P2X1, P2X3 and P2X2/3 receptor agonist α,β-methylene ATP (but not vehicle) to the dural surface evoked a significant (P<0.05) increase in ipsilateral neck EMG activity that could be suppressed by dural or intrathecal application of the selective P2X1, P2X3 and P2X2/3 receptor antagonist 2',3'-O-(2,4,6-trinitrophenyl) ATP (TNP-ATP) but not by vehicle; the intrathecal application of 2-amino-5-phosphonopentanoic acid, an NMDA receptor antagonist, also significantly reduced the neck EMG activity evoked by dural application of α,β-methylene ATP. These data suggest that purinergic receptor mechanisms contribute to the increased neck activity that can be reflexly evoked by noxious stimulation of the frontal dura, and that NMDA as well as purinergic receptor mechanisms in the medulla may modulate these purinergic-related effects. PMID:26559728

  12. Some Novel Thought Experiments Involving Foundations of Quantum Mechanics and Quantum Information

    NASA Astrophysics Data System (ADS)

    Akhavan, Omid

    2004-02-01

    In this thesis, we have proposed some novel thought experiments involving foundations of quantum mechanics and quantum information theory, using quantum entanglement property. Concerning foundations of quantum mechanics, we have suggested some typical systems including two correlated particles which can distinguish between the two famous theories of quantum mechanics, i.e. the standard and Bohmian quantum mechanics, at the individual level of pair of particles. Meantime, the two theories present the same predictions at the ensemble level of particles. Regarding quantum information theory, two theoretical quantum communication schemes including quantum dense coding and quantum teleportation schemes have been proposed by using entangled spatial states of two EPR particles shared between two parties. It is shown that the rate of classical information gain in our dense coding scheme is greater than some previously proposed multi-qubit protocols by a logarithmic factor dependent on the dimension of Hilbert space. The proposed teleportation scheme can provide a complete wave function teleportation of an object having other degrees of freedom in our three-dimensional space, for the first time. All required unitary operators which are necessary in our state preparation and Bell state measurement processes are designed using symmetric normalized Hadamard matrix, some basic gates and one typical conditional gate, which are introduced here for the first time.

  13. 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

  14. 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.

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

    PubMed Central

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

    2016-01-01

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

  16. 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

  17. 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.

  18. Astrocytes are involved in trigeminal dynamic mechanical allodynia: potential role of D-serine.

    PubMed

    Dieb, W; Hafidi, A

    2013-09-01

    Trigeminal neuropathic pain affects millions of people worldwide. Despite decades of study on the neuronal processing of pain, mechanisms underlying enhanced pain states after injury remain unclear. N-methyl-D-aspartate (NMDA) receptor-dependent changes play a critical role in triggering central sensitization in neuropathic pain. These receptors are regulated at the glycine site through a mandatory endogenous co-agonist D-serine, which is synthesized by astrocytes. Therefore, the present study was carried out to determine whether astrocytes are involved, through D-serine secretion, in dynamic mechanical allodynia (DMA) obtained after chronic constriction of the infraorbital nerve (CCI-IoN) in rats. Two weeks after CCI-IoN, an important reaction of astrocytes was present in the medullary dorsal horn (MDH), as revealed by an up-regulation of glial fibrillary acidic protein (GFAP) in allodynic rats. In parallel, an increase in D-serine synthesis, which co-localized with its synthesis enzyme serine racemase, was strictly observed in astrocytes. Blocking astrocyte metabolism by intracisternal delivery of fluorocitrate alleviated DMA. Furthermore, the administration of D-amino-acid oxidase (DAAO), a D-serine-degrading enzyme, or that of L-serine O-sulfate (LSOS), a serine racemase inhibitor, significantly decreased pain behavior in allodynic rats. These results demonstrate that astrocytes are involved in the modulation of orofacial post-traumatic neuropathic pain via the release of the gliotransmitter D-serine.

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

    PubMed

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

    2014-10-01

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

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

    PubMed

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

    2011-09-01

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

  1. Ion channels and transporters involved in cell volume regulation and sensor mechanisms.

    PubMed

    Okada, Yasunobu

    2004-01-01

    All animal cell types have an appropriate volume. Even under physiological conditions of constant extracellular osmolarity, cells must regulate their volume. Cell volume is subjected to alterations because of persistent physicochemical osmotic load resulting from Donnan-type colloid osmotic pressure and of cell activity-associated changes in intracellular osmolarity resulting from osmolyte transport and metabolism. The strategy adopted by animal cells for coping with volume regulation on osmotic perturbation is to activate transport pathways, including channels and transporters, mainly for inorganic osmolytes to drive water flow. Under normotonic conditions, cells undergo volume regulation by pump-mediated mechanisms. Under anisotonic conditions, volume regulation occurs by additional channel/transporter-mediated mechanisms. Cell volume regulation is also attained through adjustment of intracellular levels not only of inorganic but also of organic osmolytes with changing the expression of their transporters or regulation of metabolism. In cell volume regulation mechanism, several "volume sensors" are thought to be involved. A volume-sensitive Cl- channel has lately attracted considerable attention in this regard. PMID:15475611

  2. A dp53-Dependent Mechanism Involved in Coordinating Tissue Growth in Drosophila

    PubMed Central

    Milán, Marco

    2010-01-01

    Coordination of growth between and within organs contributes to the generation of well-proportioned organs and functionally integrated adults. The mechanisms that help to coordinate the growth between different organs start to be unravelled. However, whether an organ is able to respond in a coordinated manner to local variations in growth caused by developmental or environmental stress and the nature of the underlying molecular mechanisms that contribute to generating well-proportioned adult organs under these circumstances remain largely unknown. By reducing the growth rates of defined territories in the developing wing primordium of Drosophila, we present evidence that the tissue responds as a whole and the adjacent cell populations decrease their growth and proliferation rates. This non-autonomous response occurs independently of where growth is affected, and it is functional all throughout development and contributes to generate well-proportioned adult structures. Strikingly, we underscore a central role of Drosophila p53 (dp53) and the apoptotic machinery in these processes. While activation of dp53 in the growth-depleted territory mediates the non-autonomous regulation of growth and proliferation rates, effector caspases have a unique role, downstream of dp53, in reducing proliferation rates in adjacent cell populations. These new findings indicate the existence of a stress response mechanism involved in the coordination of tissue growth between adjacent cell populations and that tissue size and cell cycle proliferation can be uncoupled and are independently and non-autonomously regulated by dp53. PMID:21179433

  3. Localization of mechanisms involved in hydropassive and hydroactive stomatal responses of Sambucus nigra to dry air.

    PubMed

    Kaiser, Hartmut; Legner, Nicole

    2007-02-01

    The response of stomata to a reduction of air humidity is composed of a hydropassive opening followed by active closure. Whereas the mechanisms behind the hydropassive opening are largely understood, the location and physiological basis of the sensing mechanisms leading to active closure are not yet known. This study attempts to evaluate the importance of a single pore's transpiration on its own response and that of adjacent pores. Selected stomata on attached intact leaves of Sambucus nigra were sealed with mineral oil and the response to a reduction of humidity was continuously observed in situ. Blocking a pore's transpiration had no appreciable effect on hydropassive opening and subsequent stomatal closure. If the adjacent stomata were additionally sealed, the closing response was reduced, but not the hydropassive opening. On the other hand, sealing the entire leaf surface, except a small area including the observed stomata, also reduced stomatal closure. These results indicate that strictly local processes triggered by a pore's own transpiration are not required to induce stomatal closure. To describe the effect of one pore's transpiration on the hydropassive and hydroactive responses of neighboring stomata, a simple spatial model was constructed. It suggests that 90% of the closing effect covers an area of approximately 0.5 mm2, whereas the effect on hydropassive opening affects an area of approximately 1 mm2. This divergence may suggest mechanisms other than or in addition to those involving changes of local leaf water potential. PMID:17158586

  4. Involvement of prolactin and somatostatin in depression and the mechanism of action of antidepressant drugs.

    PubMed

    Faron-Górecka, Agata; Kuśmider, Maciej; Solich, Joanna; Kolasa, Magdalena; Szafran, Kinga; Zurawek, Dariusz; Pabian, Paulina; Dziedzicka-Wasylewska, Marta

    2013-01-01

    Neuropeptides have been implicated in the physiology and pathophysiology of stress responses and therefore may play an important role in the pathogenesis of affective disorders such as Major Depression Disorder (MDD). The data presented in this mini-review demonstrate the role of prolactin (PRL) and somatostatin (STT) in the pathology and pharmacotherapy of MDD, focusing particularly on the response to antidepressant treatment, and compare the available data with the results obtained in our laboratory using the well-validated chronic mild stress (CMS) animal model of MDD. Despite the availability of many pharmacological therapies for depression, ca. 35% patients remain treatment resistant. This clinical situation is also true for rats subjected to CMS; some animals do not respond to antidepressant therapy and are considered treatment resistant. The most interesting results presented in this mini-review concern the changes in PRL and SST receptors in the brains of rats subjected to the full CMS procedure and IMI treatment and demonstrate the role of these receptors in the mechanisms of antidepressant action. The possible interaction between SST and PRL, the involvement of the D2 dopamine receptor, and their direct protein-protein interactions are also discussed, with the conclusion that these two neurohormones play an important role in the mechanism of resilience after stress as well as in the mechanism of action of antidepressant drugs.

  5. 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.

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

    NASA Astrophysics Data System (ADS)

    Betskii, O. V.

    1994-01-01

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

  7. 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.

  8. 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…

  9. T Cell Response in Patients with Implanted Biological and Mechanical Prosthetic Heart Valves

    PubMed Central

    Barbarash, L.; Kudryavtsev, I.; Rutkovskaya, N.; Golovkin, A.

    2016-01-01

    The study was aimed at assessing T cell subsets of peripheral blood from recipients of long-term functioning (more than 60 months) biological and mechanical heart valve prostheses. The absolute and relative number of CD4 and CD8 T cell subsets was analyzed: naïve (N, CD45RA+CD62L+), central memory (CM, CD45RA−CD62L+), effector memory (EM, CD45RA−CD62L−), and terminally differentiated CD45RA-positive effector memory (TEMRA, CD45RA+CD62L−) in 25 persons with biological and 7 with mechanical prosthesis compared with 48 apparently healthy volunteers. The relative and absolute number of central memory and naïve CD3+CD8+ in patients with biological prosthesis was decreased (p < 0.001). Meanwhile the number of CD45RA+CD62L−CD3+CD8+ and CD3+CD4+ was increased (p < 0.001). Patients with mechanical prosthesis had increased absolute and relative number of CD45RA+CD62L−CD3+CD8+ cells (p = 0.006). Also the relative number of CD3+CD4+ cells was reduced (p = 0.04). We assume that altered composition of T cell subsets points at development of xenograft rejection reaction against both mechanical and biological heart valve prostheses. PMID:26989331

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

    ERIC Educational Resources Information Center

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

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Sharma, Deepika; Kanneganti, Thirumala-Devi

    2016-06-20

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

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

    PubMed

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

    2016-01-22

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

  14. Biogenesis and Mechanism of Action of Small Non-Coding RNAs: Insights from the Point of View of Structural Biology

    PubMed Central

    Costa, Marina C.; Leitão, Ana Lúcia; Enguita, Francisco J.

    2012-01-01

    Non-coding RNAs are dominant in the genomic output of the higher organisms being not simply occasional transcripts with idiosyncratic functions, but constituting an extensive regulatory network. Among all the species of non-coding RNAs, small non-coding RNAs (miRNAs, siRNAs and piRNAs) have been shown to be in the core of the regulatory machinery of all the genomic output in eukaryotic cells. Small non-coding RNAs are produced by several pathways containing specialized enzymes that process RNA transcripts. The mechanism of action of these molecules is also ensured by a group of effector proteins that are commonly engaged within high molecular weight protein-RNA complexes. In the last decade, the contribution of structural biology has been essential to the dissection of the molecular mechanisms involved in the biosynthesis and function of small non-coding RNAs. PMID:22949860

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

    PubMed Central

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

    2009-01-01

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

  16. Mechanism involved in Danshen-induced fluid secretion in salivary glands

    PubMed Central

    Wei, Fei; Wei, Mu-Xin; Murakami, Masataka

    2015-01-01

    AIM: Danshen’s capability to induce salivary fluid secretion and its mechanisms were studied to determine if it could improve xerostomia. METHODS: Submandibular glands were isolated from male Wistar rats under systemic anesthesia with pentobarbital sodium. The artery was cannulated and vascularly perfused at a constant rate. The excretory duct was also cannulated and the secreted saliva was weighed in a cup on an electronic balance. The weight of the accumulated saliva was measured every 3 s and the salivary flow rate was calculated. In addition, the arterio-venous difference in the partial oxygen pressure was measured as an indicator of oxygen consumption. In order to assess the mechanism involved in Danshen-induced fluid secretion, either ouabain (an inhibitor of Na+/K+ ATPase) or bumetanide (an inhibitor of NKCC1) was additionally applied during the Danshen stimulation. In order to examine the involvement of the main membrane receptors, atropine was added to block the M3 muscarinic receptors, or phentolamine was added to block the α1 adrenergic receptors. In order to examine the requirement for extracellular Ca2+, Danshen was applied during the perfusion with nominal Ca2+ free solution. RESULTS: Although Danshen induced salivary fluid secretion, 88.7 ± 12.8 μL/g-min, n = 9, (the highest value around 20 min from start of DS perfusion was significantly high vs 32.5 ± 5.3 μL/g-min by carbamylcholine, P = 0.00093 by t-test) in the submandibular glands, the time course of that secretion differed from that induced by carbamylcholine. There was a latency associated with the fluid secretion induced by Danshen, followed by a gradual increase in the secretion to its highest value, which was in turn followed by a slow decline to a near zero level. The application of either ouabain or bumetanide inhibited the fluid secretion by 85% or 93%, and suppressed the oxygen consumption by 49% or 66%, respectively. These results indicated that Danshen activates Na+/K+ ATPase

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

    NASA Astrophysics Data System (ADS)

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

    2007-02-01

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

  18. Understanding the neural mechanisms involved in sensory control of voice production.

    PubMed

    Parkinson, Amy L; Flagmeier, Sabina G; Manes, Jordan L; Larson, Charles R; Rogers, Bill; Robin, Donald A

    2012-05-15

    Auditory feedback is important for the control of voice fundamental frequency (F0). In the present study we used neuroimaging to identify regions of the brain responsible for sensory control of the voice. We used a pitch-shift paradigm where subjects respond to an alteration, or shift, of voice pitch auditory feedback with a reflexive change in F0. To determine the neural substrates involved in these audio-vocal responses, subjects underwent fMRI scanning while vocalizing with or without pitch-shifted feedback. The comparison of shifted and unshifted vocalization revealed activation bilaterally in the superior temporal gyrus (STG) in response to the pitch shifted feedback. We hypothesize that the STG activity is related to error detection by auditory error cells located in the superior temporal cortex and efference copy mechanisms whereby this region is responsible for the coding of a mismatch between actual and predicted voice F0. PMID:22406500

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

    PubMed Central

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

    2011-01-01

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

  20. Recognition of mechanisms involved in bile resistance important to halting antimicrobial resistance in nontyphoidal Salmonella.

    PubMed

    Tsai, Ming-Han; Wu, Sih-Ru; Lee, Hao-Yuan; Chen, Chyi-Liang; Lin, Tzou-Yien; Huang, Yhu-Chering; Chiu, Cheng-Hsun

    2012-08-01

    Increasing antimicrobial resistance in nontyphoidal Salmonella (NTS) is a global public health problem that complicates antimicrobial therapy. As an enteric pathogen, Salmonella must endure the presence of bile in the intestinal tract during the course of infection. In this study, we sought to identify Salmonella genes necessary for bile resistance and to investigate their association with antimicrobial resistance. Four genes related to bile resistance were identified, namely rfaP, rfbK, dam and tolC. The first three genes are involved in lipopolysaccharide synthesis, and tolC is associated with an efflux pump. Antimicrobial susceptibility testing showed increased susceptibility to polymyxin B and ciprofloxacin in rfaP and tolC mutants of Salmonella, respectively. Genetic analysis of 45 clinical isolates of NTS revealed that all isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration ≥0.125 mg/L) were associated with point mutations in the quinolone resistance-determining regions of the gyrA and parC genes. The efflux pump also played a role, as evidenced by the reduction in fluoroquinolone resistance when the TolC efflux pump was inhibited by Phe-Arg-β-naphthylamide, a competitive efflux pump inhibitor. Based on these results, we conclude that an intact membrane structure and the efflux pump system provide mechanisms enabling NTS to resist bile. Caution should be taken when using ciprofloxacin and polymyxin B to treat Salmonella enteric infection, as resistance to these agents involves the same mechanisms. Addition of an efflux pump inhibitor to fluoroquinolones may be an effective strategy to deal with the increasing resistance in NTS.

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

    PubMed Central

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

    1993-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2001-01-12

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

  4. Evolution of oropharyngeal patterning mechanisms involving Dlx and endothelins in vertebrates.

    PubMed

    Kuraku, Shigehiro; Takio, Yoko; Sugahara, Fumiaki; Takechi, Masaki; Kuratani, Shigeru

    2010-05-01

    In jawed vertebrates, the Dlx code, or nested expression patterns of Dlx genes, specify the dorsoventral polarity of pharyngeal arches, downstream of endothelin-1 (Edn-1) and its effectors, Bapx1 (Nkx3.2) and dHand (Hand2). To elucidate the evolution of the specification mechanism of the oropharyngeal skeletal system, lamprey homologs of Dlx, Edn, endothelin receptor (Ednr), Bapx1, and dHand were identified. Our analysis suggested that the Edn gene family emerged at the advent of vertebrates, and that gene duplications leading to the different Edn gnathostome subtypes (Edn1-3) occurred before the cyclostome-gnathostome split. This timing of gene duplications, giving rise to multiple subtypes, was also implied for Dlx, Ednr, Hand, and Bapx. In lamprey embryos, nested expressions of Dlx genes were not observed in pharyngeal arches, nor was any focal expression of Bapx1, known in gnathostomes to specify the jaw joint. The dHand homolog, however, was expressed more intensively ventrally, as in gnathostomes. Lamprey homologs of Edn-1 and EdnrA were also shown to be expressed as described in mice, indicating involvement of this signaling pathway in the craniofacial patterning early in vertebrate evolution. These results suggest that the last common ancestor of all the extant vertebrates would have possessed basic gene repertoires involved in oropharyngeal patterning in gnathostomes, but the elaborate genetic program leading to the Dlx code is likely to have been acquired uniquely in gnathostomes. PMID:20171204

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

    PubMed Central

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

    2016-01-01

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

  6. Mechanisms Involved in Governing Adherence of Vibrio cholerae to Granular Starch▿

    PubMed Central

    Niderman-Meyer, Orly; Zeidman, Tal; Shimoni, Eyal; Kashi, Yechezkel

    2010-01-01

    Vibrio cholerae has been shown to adhere to cornstarch granules. The present work explored the mechanisms involved in this adhesion and the possibility of its occurrence in vivo. The findings suggest that both specific and nonspecific interactions are involved in the adhesion. Nonspecific hydrophobic interactions may play a role, since both V. cholerae and cornstarch granules exhibited hydrophobic properties when they were tested using a xylene-water system. In addition, the presence of bile acids reduced the adhesion. The adhesion also involves some specific carbohydrate-binding moieties on the cell surface, as reflected by reduced adhesion following pretreatment of the bacteria with proteinase K and sodium m-periodate. Further investigations supported these observations and showed that media containing low-molecular-weight carbohydrates had a significant inhibitory effect. Binding cell lysate to starch granules and removing the adhered proteins using either glucose or bile acids led to identification (by liquid chromatography-tandem mass spectrometry analysis) of several candidate V. cholerae outer membrane-associated starch-binding proteins. Different sets of proteins were isolated by removal in a glucose solution or bile acids. When the upper gastrointestinal tract conditions were simulated in vitro, both bile salts and the amylolytic activity of the pancreatic juices were found to have an inhibitory effect on the adherence of V. cholerae to starch. However, during acute diarrhea, this inhibitory effect may be significantly reduced due to dilution, suggesting that adhesion does occur in vivo. Such adhesion may contribute to the beneficial effects observed following administration of granular starch-based oral rehydration solutions to cholera patients. PMID:20023099

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

    PubMed

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

    2013-01-01

    Some small animals only use water transport mechanisms passively driven by surface energies. However, little is known about passive water transport mechanisms because it is difficult to measure the wettability of microstructures in small areas and determine the chemistry of biological surfaces. Herein, we developed to directly analyse the structural effects of wettability of chemically modified biological surfaces by using a nanoliter volume water droplet and a hi-speed video system. The wharf roach Ligia exotica transports water only by using open capillaries in its legs containing hair- and paddle-like microstructures. The structural effects of legs chemically modified with a self-assembled monolayer were analysed, so that the wharf roach has a smart water transport system passively driven by differences of wettability between the microstructures. We anticipate that this passive water transport mechanism may inspire novel biomimetic fluid manipulations with or without a gravitational field. PMID:24149467

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

    NASA Astrophysics Data System (ADS)

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

    2013-10-01

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

  9. Thermo-electrical equivalents for simulating the electro-mechanical behavior of biological tissue.

    PubMed

    Cinelli, I; Duffy, M; McHugh, P E

    2015-01-01

    Equivalence is one of most popular techniques to simulate the behavior of systems governed by the same type of differential equation. In this case, a thermo-electrical equivalence is considered as a method for modelling the inter-dependence of electrical and mechanical phenomena in biological tissue. We seek to assess this approach for multi-scale models (from micro-structure to tissue scale) of biological media, such as nerve cells and cardiac tissue, in which the electrical charge distribution is modelled as a heat distribution in an equivalent thermal system. This procedure allows for the reduction in problem complexity and it facilitates the coupling of electrical and mechanical phenomena in an efficient and practical way. Although the findings of this analysis are mainly addressed towards the electro-mechanics of tissue within the biomedical domain, the same approach could be used in other studies in which a coupled finite element analysis is required. PMID:26737163

  10. Prenatal stress and its effects on the fetus and the child: possible underlying biological mechanisms.

    PubMed

    Glover, Vivette

    2015-01-01

    Many prospective studies have shown that if a mother is depressed, anxious or stressed while pregnant, this increases the risk for her child having a wide range of adverse outcomes including emotional problems, symptoms of attention deficit hyperactivity disorder (ADHD) or impaired cognitive development. Although genetics and postnatal care clearly affect these outcomes, evidence for a prenatal causal component also is substantial. Prenatal anxiety/depression may contribute 10-15 % of the attributable load for emotional/behavioural outcomes.The mechanisms underlying these changes are just starting to be explored. One possible mediating factor is increased exposure of the fetus to cortisol, as has been shown in animal studies. However, the human hypothalamic-pituitary-adrenal (HPA) axis which makes cortisol functions differently in human pregnancy from in most animals. The maternal HPA axis becomes gradually less responsive to stress as pregnancy progresses. And there is only a weak, if any, association between a mother's prenatal mood and her cortisol level, especially later in pregnancy. Cytokines are alternative possible mediators. An additional explanation is that stress or anxiety causes increased transfer of maternal cortisol across the placenta to the fetus. The placenta plays a crucial role in moderating fetal exposure to maternal factors and presumably in preparing the fetus for the environment in which it is going to find itself. There is some evidence in both rat models and in humans that prenatal stress can reduce placental 11β-HSD2, the enzyme which metabolises cortisol to inactive cortisone. The level of cortisol in the amniotic fluid, surrounding the baby in the womb, has been shown to be inversely correlated with infant cognitive development. However, several other biological systems are likely to be involved. Serotonin is another possible mediator of prenatal stress induced programming effects on offspring neurocognitive and behavioural

  11. A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases

    PubMed Central

    Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A.

    2015-01-01

    Background: A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. Objectives: We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. Methods: For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Conclusions: Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Citation: Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that

  12. Target dependency of brain mechanism involved in dispositional inference: a PET study.

    PubMed

    Sugiura, Motoaki; Gotoh, Ryoi; Okada, Ken; Yamaguchi, Keiichiroh; Itoh, Masatoshi; Fukuda, Hiroshi; Kawashima, Ryuta

    2004-04-01

    The cognitive mechanism for inference of personal dispositions, such as personality traits and abilities, is postulated to be dependent on the amount of episodic memory concerning target persons. To examine whether there is such target dependency in the brain mechanism during dispositional inference, we measured brain activity of normal volunteers while they were performing seven dispositional inference tasks, each for a target person in different categories, using positron emission tomography (PET). Effect of the target-person category on activation was significant in the posterodorsal, polar, and ventral subdivisions of medial prefrontal cortex, right orbitoinsular junction, left temporal pole and superior temporal sulcus, cerebellum, and thalamus, suggesting the existence of target dependency in activation during dispositional inference. The amount of episodic memory concerning a target person measured using the self-evaluative questionnaire was positively correlated with the activation in the polar subdivision of the medial prefrontal cortex, and negatively with that in a region in the left superior temporal sulcus. Together with the available knowledge on the functional roles of these regions and the proposed cognitive model in social psychology, our results suggest that these two regions play roles supplementary to each other in dispositional inference; a region in the superior temporal sulcus is involved in the processing of relevant episodic exemplar and the polar subdivision of the medial prefrontal cortex in the processing of summarized value information about the target person. PMID:15050563

  13. Diosgenin Mitigates Streptozotocin Diabetes-induced Vascular Dysfunction of the Rat Aorta: The Involved Mechanisms.

    PubMed

    Roghani-Dehkordi, Farshad; Roghani, Mehrdad; Baluchnejadmojarad, Tourandokht

    2015-12-01

    Chronic diabetes mellitus finally leads to serious vascular dysfunction. Diosgenin is a natural steroidal saponin with potential cardiovascular protective effect. In this study, the protective effect of diosgenin was checked on the aorta from streptozotocin-induced diabetic rats. Diabetic rats received diosgenin (40 mg·kg·d) for 7 weeks starting 1 week after intraperitoneal injection of streptozotocin (60 mg/kg). Aortic reactivity of endothelium-intact and -denuded rings to potassium chloride, phenylephrine, acetylcholine, and isosorbide dinitrate were measured and some involved mechanisms were explored. The results showed that diosgenin has a hypoglycemic effect and attenuates maximum contractile response of endothelium-intact and -denuded rings to PE. In addition, endothelium-dependent relaxation to acetylcholine was greater in diosgenin-treated diabetics with no significant change for endothelium-independent relaxation to isosorbide dinitrate and addition of N(G)-nitro-L-arginine methyl ester, as a nitric oxide synthase inhibitor eliminated this beneficial effect. Furthermore, diosgenin significantly attenuated aortic DNA fragmentation as an index of apoptosis and malondialdehyde content, lowered the aortic expression of angiotensin converting enzyme and transcription factor nuclear factor-κB and raised expression of endothelial nitric oxide synthase with no significant effect on the activity of superoxide dismutase. Taken together, our study provides insight into the mechanisms underlying the beneficial effect of diosgenin as a potential therapeutic agent to mitigate vascular dysfunction in diabetes mellitus. PMID:26309100

  14. Mechanism of microglia neuroprotection: Involvement of P2X7, TNFα, and valproic acid.

    PubMed

    Masuch, Annette; Shieh, Chu-Hsin; van Rooijen, Nico; van Calker, Dietrich; Biber, Knut

    2016-01-01

    Recently, we have demonstrated that ramified microglia are neuroprotective in N-methyl-D-aspartate (NMDA)-induced excitotoxicity in organotypic hippocampal slice cultures (OHSCs). The present study aimed to elucidate the underlying neuron-glia communication mechanism. It is shown here that pretreatment of OHSC with high concentrations of adenosine 5'-triphosphate (ATP) reduced NMDA-induced neuronal death only in presence of microglia. Specific agonists and antagonists identified the P2X7 receptor as neuroprotective receptor which was confirmed by absence of ATP-dependent neuroprotection in P2X7-deficient OHSC. Microglia replenished chimeric OHSC consisting of wild-type tissue replenished with P2X7-deficient microglia confirmed the involvement of microglial P2X7 receptor in neuroprotection. Stimulation of P2X7 in primary microglia induced tumor necrosis factor α (TNFα) release and blocking TNFα by a neutralizing antibody in OHSC abolished neuroprotection by ATP. OHSC from TNFα-deficient mice show increased exicitoxicity and activation of P2X7 did not rescue neuronal survival in the absence of TNFα. The neuroprotective effect of valproic acid (VPA) was strictly dependent on the presence of microglia and was mediated by upregulation of P2X7 in the cells. The present study demonstrates that microglia-mediated neuroprotection depends on ATP-activated purine receptor P2X7 and induction of TNFα release. This neuroprotective pathway was strengthened by VPA elucidating a novel mechanism for the neuroprotective function of VPA.

  15. Damage mechanism involved in the solid particle erosion of CVD diamond

    NASA Astrophysics Data System (ADS)

    Davies, Alun R.; Field, John E.

    2001-09-01

    Sophisticated electro-optic sensors are employed on aircraft and missiles, and it is essential to protect them from relatively high-speed impacts with airborne dust particles. A loss in transmission caused by such an event can impair guidance, and catastrophic failure may occur. Protection is afforded by the installation of a hard cover that is transparent in the relevant regime. Diamond is potentially by far the most attractive window material due to excellent optical and mechanical properties, but it is difficult to shape. Chemical vapor deposited (CVD) diamond is a polycrystalline synthetic with properties that approach those of single crystal diamond, and it can be more easily shaped. The aims of the present research were to quantify the erosion and transmission losses, and to understand the material removal mechanisms involved. Steady-state erosion rates were obtained for CVD diamond of different grain sizes, using 300-600 micrometers quartz erodent at velocities between 60 and 140 m/s. Images of CVD diamond at various stages of erosion, obtained using an optical microscope and an environmental scanning electron microscope (ESEM), reveal that erosion initially occurs at grain boundaries and that so-called micro-features also have some influence on erosion.

  16. Protein Machineries Involved in the Attachment of Heme to Cytochrome c: Protein Structures and Molecular Mechanisms

    PubMed Central

    Travaglini-Allocatelli, Carlo

    2013-01-01

    Cytochromes c (Cyt c) are ubiquitous heme-containing proteins, mainly involved in electron transfer processes, whose structure and functions have been and still are intensely studied. Surprisingly, our understanding of the molecular mechanism whereby the heme group is covalently attached to the apoprotein (apoCyt) in the cell is still largely unknown. This posttranslational process, known as Cyt c biogenesis or Cyt c maturation, ensures the stereospecific formation of the thioether bonds between the heme vinyl groups and the cysteine thiols of the apoCyt heme binding motif. To accomplish this task, prokaryotic and eukaryotic cells have evolved distinctive protein machineries composed of different proteins. In this review, the structural and functional properties of the main maturation apparatuses found in gram-negative and gram-positive bacteria and in the mitochondria of eukaryotic cells will be presented, dissecting the Cyt c maturation process into three functional steps: (i) heme translocation and delivery, (ii) apoCyt thioreductive pathway, and (iii) apoCyt chaperoning and heme ligation. Moreover, current hypotheses and open questions about the molecular mechanisms of each of the three steps will be discussed, with special attention to System I, the maturation apparatus found in gram-negative bacteria. PMID:24455431

  17. Inflammatory mechanisms involved in brain injury following cardiac arrest and cardiopulmonary resuscitation

    PubMed Central

    XIANG, YANXIAO; ZHAO, HUA; WANG, JIALI; ZHANG, LUETAO; LIU, ANCHANG; CHEN, YUGUO

    2016-01-01

    Cardiac arrest (CA) is a leading cause of fatality and long-term disability worldwide. Recent advances in cardiopulmonary resuscitation (CPR) have improved survival rates; however, the survivors are prone to severe neurological injury subsequent to successful CPR following CA. Effective therapeutic options to protect the brain from CA remain limited, due to the complexities of the injury cascades caused by global cerebral ischemia/reperfusion (I/R). Although the precise mechanisms of neurological impairment following CA-initiated I/R injury require further clarification, evidence supports that one of the key cellular pathways of cerebral injury is inflammation. The inflammatory response is orchestrated by activated glial cells in response to I/R injury. Increased release of danger-associated molecular pattern molecules and cellular dysfunction in activated microglia and astrocytes contribute to ischemia-induced cytotoxic and pro-inflammatory cytokines generation, and ultimately to delayed death of neurons. Furthermore, cytokines and adhesion molecules generated within activated microglia, as well as astrocytes, are involved in the innate immune response; modulate influx of peripheral immune and inflammatory cells into the brain, resulting in neurological injury. The present review discusses the molecular aspects of immune and inflammatory mechanisms in global cerebral I/R injury following CA and CPR, and the potential therapeutic strategies that target neuroinflammation and the innate immune system. PMID:27330748

  18. Nelfinavir and other protease inhibitors in cancer: mechanisms involved in anticancer activity

    PubMed Central

    Koltai, Tomas

    2015-01-01

    Objective: To review the mechanisms of anti-cancer activity of nelfinavir and other protease inhibitors (PIs) based on evidences reported in the published literature. Methods: We extensively reviewed the literature concerning nelfinavir (NFV) as an off target anti-cancer drug and other PIs. A classification of PIs based on anti-cancer mode of action was proposed. Controversies regarding nelfinavir mode of action were also addressed. Conclusions: The two main mechanisms involved in anti-cancer activity are endoplasmic reticulum stress-unfolded protein response pathway and Akt inhibition. However there are many other effects, partially dependent and independent of those mentioned, that may be useful in cancer treatment, including MMP-9 and MMP-2 inhibition, down-regulation of CDK-2, VEGF, bFGF, NF-kB, STAT-3, HIF-1 alfa, IGF, EGFR, survivin, BCRP, androgen receptor, proteasome, fatty acid synthase (FAS), decrease in cellular ATP concentration and upregulation of TRAIL receptor DR5, Bax, increased radiosensitivity, and autophagy. The end result of all these effects is slower growth, decreased angiogenesis, decreased invasion and increased apoptosis, which means reduced proliferation and increased cancer cells death. PIs may be classified according to their anticancer activity at clinically achievable doses, in AKT inhibitors, ER stressors and Akt inhibitors/ER stressors. Beyond the phase I trials that have been recently completed, adequately powered and well-designed clinical trials are needed in the various cancer type settings, and specific trials where NFV is tested in association with other known anti-cancer pharmaceuticals should be sought, in order to find an appropriate place for NFV in cancer treatment. The analysis of controversies on the molecular mechanisms of NFV hints to the possibility that NFV works in a different way in tumor cells and in hepatocytes and adipocytes. PMID:26097685

  19. The involvement of dual mechanisms of photoinactivation of photosystem II in Capsicum annuum L. Plants.

    PubMed

    Oguchi, Riichi; Terashima, Ichiro; Chow, Wah Soon

    2009-10-01

    For plants, light is an indispensable resource. However, it also causes a loss of photosynthetic activity associated with photoinactivation of photosystem II (PSII). In studies of the mechanism of this photoinactivation, there are two conflicting hypotheses at present. One is that excess energy received by leaves, being neither utilized by photosynthesis nor dissipated safely in non-photochemical quenching, causes the photoinactivation. The other involves a two-step mechanism in which excitation of Mn by photons is the primary cause. In the former hypothesis, photoinactivation of PSII should not occur in low light that provides little excess energy, but in the latter hypothesis it should. Therefore, we tested these two hypotheses in different irradiances. We used a system that can measure the fraction of functional PSII complexes under natural conditions and over a long period in intact leaves, which were attached to a plant treated with lincomycin taken up via the roots. The leaves were photoinactivated in low, medium or high light (30, 60 or 950 micromol m(-2) s(-1)) with white, blue, green or red light-emitting diode arrays. Our results showed that the extent of photoinactivation per photon exposure was higher in high light than in low light, consistent with the abundance of excess energy. However, photoinactivation did occur in low light with little excess energy, and blue light caused the greatest extent of photoinactivation followed by white, green and red light in this order, an order that can be predicted from the Mn absorbance spectrum. These results suggest that both mechanisms occur in the photoinactivation process.

  20. Analyses of the involvement of PKA regulation mechanism in meiotic incompetence of porcine growing oocytes.

    PubMed

    Nishimura, Takanori; Fujii, Wataru; Kano, Kiyoshi; Sugiura, Koji; Naito, Kunihiko

    2012-09-01

    Mammalian growing oocytes (GOs) lack the ability to resume meiosis, although the molecular mechanism of this limitation is not fully understood. In the present study, we cloned cDNAs of cAMP-dependent protein-kinase (PKA) subunits from porcine oocytes and analyzed the involvement of the PKA regulation mechanism in the meiotic incompetence of GOs at the molecular level. We found a cAMP-independent high PKA activity in GOs throughout the in vitro culture using a porcine PKA assay system we established, and inhibition of the activity by injection of the antisense RNA of the PKA catalytic subunit (PKA-C) induced meiotic resumption in GOs. Then we examined the possibility that the amount of the PKA regulatory subunit (PKA-R), which can bind and inhibit PKA-C, was insufficient to suppress PKA activity in GOs because of the overexpression of two PKA-Rs, PRKAR1A and PRKAR2A. We found that neither of them affected PKA activity and induced meiotic resumption in GO although PRKAR2A could inhibit PKA activity and induce meiosis in cAMP-treated full-grown oocytes (FGOs). Finally, we analyzed the subcellular localization of PKA subunits and found that all the subunits were localized in the cytoplasm during meiotic arrest and that PKA-C and PRKAR2A, but not PRKAR1A, entered into the nucleus just before meiotic resumption in FGOs, whereas all of them remained in the cytoplasm in GOs throughout the culture period. Our findings suggest that the continuous high PKA activity is a primary cause of the meiotic incompetence of porcine GOs and that this PKA activity is not simply caused by an insufficient expression level of PKA-R, but can be attributed to more complex spatial-temporal regulation mechanisms. PMID:22674394

  1. Functional responses and molecular mechanisms involved in histone-mediated platelet activation.

    PubMed

    Carestia, A; Rivadeneyra, L; Romaniuk, M A; Fondevila, C; Negrotto, S; Schattner, M

    2013-11-01

    Histones are highly alkaline proteins found in cell nuclei and they can be released by either dying or inflammatory cells. The recent observations that histones are major components of neutrophil extracellular traps and promote platelet aggregation and platelet-dependent thrombin generation have shown that these proteins are potent prothrombotic molecules. Because the mechanism(s) of platelet activation by histones are not completely understood, we explored the ability of individual recombinant human histones H1, H2A, H2B, H3 and H4 to induce platelet activation as well as the possible molecular mechanisms involved. All histones were substrates for platelet adhesion and spreading and triggered fibrinogen binding, aggregation, von Willebrand factor release, P-selectin and phosphatidylserine (PS) exposure and the formation of platelet-leukocyte aggregates; however, H4 was the most potent. Histone-mediated fibrinogen binding, P-selectin and PS exposure and the formation of mixed aggregates were potentiated by thrombin. Histones induced the activation of ERK, Akt, p38 and NFκB. Accordingly, histone-induced platelet activation was significantly impaired by pretreatment of platelets with inhibitors of ERK (U 0126), PI3K/Akt (Ly 294002), p38 (SB 203580) and NFκB (BAY 11-7082 and Ro 106-9920). Preincubation of platelets with either aspirin or dexamethasone markedly decreased fibrinogen binding and the adhesion mediated by histones without affecting P-selectin exposure. Functional platelet responses induced by H3 and H4, but not H1, H2A and H2B, were partially mediated through interaction with Toll-like receptors -2 and -4. Our data identify histones as important triggers of haemostatic and proinflammatory platelet responses, and only haemostatic responses are partially inhibited by anti-inflammatory drugs. PMID:23965842

  2. Photosynthesis Is Not Involved in the Mechanism of Action of Acifluorfen in Cucumber (Cucumis sativus L.)

    PubMed Central

    Duke, Stephen O.; Kenyon, William H.

    1986-01-01

    The possible role of photosynthesis in the mechanism of action of the herbicide acifluorfen (2-chloro-4-(trifluoromethyl)phenoxy-2-nitrobenzoate; AF) was examined. The sensitivity to AF of cotyledons of cucumber (Cucumis sativus L.) which had been grown under far red light (FR) and white light were compared. FR grown tissues which were photosynthetically imcompetent were hypersensitive to AF under white light and had approximately the same relative response to AF under blue and red light as green, white-light-grown tissues. Ultrastructural damage was apparent in FR-grown, AF-treated tissues within an hour after exposure to white light, with cytoplasmic and plastidic disorganization occurring simultaneously. In cucumber cotyledon tissue which had been greening for various time periods, there was no correlation between photosynthetic capacity and herbicidal efficacy of AF. PSII inhibitors (atrazine and DCMU) and the photophosphorylation inhibitor, tentoxin, had no effect on AF activity. Atrazine did not reduce AF activity at any concentration or light intensity tested, indicating that there is no second, photosynthetic-dependent mechanism of action operating at low AF concentrations or low fluence rates. Carbon dioxide-dependent O2 evolution of intact chloroplasts of spinach (Spinacia oleracea L.) had an AF I50 of 125 micromolar compared to 1000 micromolar for cucumber, whereas AF was much more herbicidally active in tissues of cucumber than of spinach. Differences in activity could not be accounted for by differences in uptake of AF. Our results indicate that there is no photosynthetic involvement in the mechanism of action of AF in cucumber. Images Fig. 2 PMID:16664919

  3. Functional responses and molecular mechanisms involved in histone-mediated platelet activation.

    PubMed

    Carestia, A; Rivadeneyra, L; Romaniuk, M A; Fondevila, C; Negrotto, S; Schattner, M

    2013-11-01

    Histones are highly alkaline proteins found in cell nuclei and they can be released by either dying or inflammatory cells. The recent observations that histones are major components of neutrophil extracellular traps and promote platelet aggregation and platelet-dependent thrombin generation have shown that these proteins are potent prothrombotic molecules. Because the mechanism(s) of platelet activation by histones are not completely understood, we explored the ability of individual recombinant human histones H1, H2A, H2B, H3 and H4 to induce platelet activation as well as the possible molecular mechanisms involved. All histones were substrates for platelet adhesion and spreading and triggered fibrinogen binding, aggregation, von Willebrand factor release, P-selectin and phosphatidylserine (PS) exposure and the formation of platelet-leukocyte aggregates; however, H4 was the most potent. Histone-mediated fibrinogen binding, P-selectin and PS exposure and the formation of mixed aggregates were potentiated by thrombin. Histones induced the activation of ERK, Akt, p38 and NFκB. Accordingly, histone-induced platelet activation was significantly impaired by pretreatment of platelets with inhibitors of ERK (U 0126), PI3K/Akt (Ly 294002), p38 (SB 203580) and NFκB (BAY 11-7082 and Ro 106-9920). Preincubation of platelets with either aspirin or dexamethasone markedly decreased fibrinogen binding and the adhesion mediated by histones without affecting P-selectin exposure. Functional platelet responses induced by H3 and H4, but not H1, H2A and H2B, were partially mediated through interaction with Toll-like receptors -2 and -4. Our data identify histones as important triggers of haemostatic and proinflammatory platelet responses, and only haemostatic responses are partially inhibited by anti-inflammatory drugs.

  4. Photosynthesis Is Not Involved in the Mechanism of Action of Acifluorfen in Cucumber (Cucumis sativus L.).

    PubMed

    Duke, S O; Kenyon, W H

    1986-07-01

    The possible role of photosynthesis in the mechanism of action of the herbicide acifluorfen (2-chloro-4-(trifluoromethyl)phenoxy-2-nitrobenzoate; AF) was examined. The sensitivity to AF of cotyledons of cucumber (Cucumis sativus L.) which had been grown under far red light (FR) and white light were compared. FR grown tissues which were photosynthetically imcompetent were hypersensitive to AF under white light and had approximately the same relative response to AF under blue and red light as green, white-light-grown tissues. Ultrastructural damage was apparent in FR-grown, AF-treated tissues within an hour after exposure to white light, with cytoplasmic and plastidic disorganization occurring simultaneously. In cucumber cotyledon tissue which had been greening for various time periods, there was no correlation between photosynthetic capacity and herbicidal efficacy of AF. PSII inhibitors (atrazine and DCMU) and the photophosphorylation inhibitor, tentoxin, had no effect on AF activity. Atrazine did not reduce AF activity at any concentration or light intensity tested, indicating that there is no second, photosynthetic-dependent mechanism of action operating at low AF concentrations or low fluence rates. Carbon dioxide-dependent O(2) evolution of intact chloroplasts of spinach (Spinacia oleracea L.) had an AF I(50) of 125 micromolar compared to 1000 micromolar for cucumber, whereas AF was much more herbicidally active in tissues of cucumber than of spinach. Differences in activity could not be accounted for by differences in uptake of AF. Our results indicate that there is no photosynthetic involvement in the mechanism of action of AF in cucumber.

  5. Crosstalk of Signaling Mechanisms Involved in Host Defense and Symbiosis Against Microorganisms in Rice.

    PubMed

    Akamatsu, Akira; Shimamoto, Ko; Kawano, Yoji

    2016-08-01

    Rice is one of the most important food crops, feeding about half population in the world. Rice pathogens cause enormous damage to rice production worldwide. In plant immunity research, considerable progress has recently been made in our understanding of the molecular mechanisms underlying microbe-associated molecular pattern (MAMP)-triggered immunity. Using genome sequencing and molecular techniques, a number of new MAMPs and their receptors have been identified in the past two decades. Notably, the mechanisms for chitin perception via the lysine motif (LysM) domain-containing receptor OsCERK1, as well as the mechanisms for bacterial MAMP (e.g. flg22, elf18) perception via the leucine-rich repeat (LRR) domain-containing receptors FLS2 and EFR, have been clarified in rice and Arabidopsis, respectively. In chitin signaling in rice, two direct substrates of OsCERK1, Rac/ROP GTPase guanine nucleotide exchange factor OsRacGEF1 and receptor-like cytoplasmic kinase OsRLCK185, have been identified as components of the OsCERK1 complex and are rapidly phosphorylated by OsCERK1 in response to chitin. Interestingly, OsCERK1 also participates in symbiosis with arbuscular mycorrhizal fungi (AMF) in rice and plays a role in the recognition of short-chitin molecules (CO4/5), which are symbiotic signatures included in AMF germinated spore exudates and induced by synthetic strigolactone. Thus, OsCERK1 contributes to both immunity and symbiotic responses. In this review, we describe recent studies on pathways involved in rice immunity and symbiotic signaling triggered by interactions with microorganisms. In addition, we describe recent advances in genetic engineering by using plant immune receptors and symbiotic microorganisms to enhance disease resistance of rice. PMID:27499679

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

    PubMed Central

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

    2014-01-01

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

  7. 3D deformation field in growing plant roots reveals both mechanical and biological responses to axial mechanical forces

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. Finite element simulation for the mechanical characterization of soft biological materials by atomic force microscopy.

    PubMed

    Valero, C; Navarro, B; Navajas, D; García-Aznar, J M

    2016-09-01

    The characterization of the mechanical properties of soft materials has been traditionally performed through uniaxial tensile tests. Nevertheless, this method cannot be applied to certain extremely soft materials, such as biological tissues or cells that cannot be properly subjected to these tests. Alternative non-destructive tests have been designed in recent years to determine the mechanical properties of soft biological tissues. One of these techniques is based on the use of atomic force microscopy (AFM) to perform nanoindentation tests. In this work, we investigated the mechanical response of soft biological materials to nanoindentation with spherical indenters using finite element simulations. We studied the responses of three different material constitutive laws (elastic, isotropic hyperelastic and anisotropic hyperelastic) under the same process and analyzed the differences thereof. Whereas linear elastic and isotropic hyperelastic materials can be studied using an axisymmetric simplification, anisotropic hyperelastic materials require three-dimensional analyses. Moreover, we established the limiting sample size required to determine the mechanical properties of soft materials while avoiding boundary effects. Finally, we compared the results obtained by simulation with an estimate obtained from Hertz theory. Hertz theory does not distinguish between the different material constitutive laws, and thus, we proposed corrections to improve the quantitative measurement of specific material properties by nanoindentation experiments. PMID:27214690

  10. Finite element simulation for the mechanical characterization of soft biological materials by atomic force microscopy.

    PubMed

    Valero, C; Navarro, B; Navajas, D; García-Aznar, J M

    2016-09-01

    The characterization of the mechanical properties of soft materials has been traditionally performed through uniaxial tensile tests. Nevertheless, this method cannot be applied to certain extremely soft materials, such as biological tissues or cells that cannot be properly subjected to these tests. Alternative non-destructive tests have been designed in recent years to determine the mechanical properties of soft biological tissues. One of these techniques is based on the use of atomic force microscopy (AFM) to perform nanoindentation tests. In this work, we investigated the mechanical response of soft biological materials to nanoindentation with spherical indenters using finite element simulations. We studied the responses of three different material constitutive laws (elastic, isotropic hyperelastic and anisotropic hyperelastic) under the same process and analyzed the differences thereof. Whereas linear elastic and isotropic hyperelastic materials can be studied using an axisymmetric simplification, anisotropic hyperelastic materials require three-dimensional analyses. Moreover, we established the limiting sample size required to determine the mechanical properties of soft materials while avoiding boundary effects. Finally, we compared the results obtained by simulation with an estimate obtained from Hertz theory. Hertz theory does not distinguish between the different material constitutive laws, and thus, we proposed corrections to improve the quantitative measurement of specific material properties by nanoindentation experiments.

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

    PubMed

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

    2015-01-01

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

  12. Mechanism of cancer drug resistance and the involvement of noncoding RNAs.

    PubMed

    Xia, Hongping; Hui, Kam M

    2014-01-01

    Drug resistance is one of the major reasons for the failure of cancer therapies. Although our understanding of resistance to targeted cancer drugs remains incomplete, new and more creative approaches are being exploited to intercept this phenomenon. Considerable advances have been made in our understanding that cancer drug resistance can be caused by alterations of drug efflux, increases in drug metabolism, mutations of drug targets, alterations in DNA repair and cell cycle, changes in cell apoptosis and autophagy, induction of epithelial-mesenchymal transition (EMT) and the generation of cancer stem cells (CSCs). Furthermore, intracellular signalling pathways have been shown to play key physiological roles and the abnormal activation of signalling pathways may be correlated with drug resistance. Recently, noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have emerged as important regulators of gene expression and alternative splicing, which provides cells with yet another mode to greatly increase regulatory complexity and fine-tune their transcriptome and can rapidly adjust their proteome in response to stimuli. Consequently, a wide variety of biological functions have been shown to depend on the coordinated interactions between noncoding RNAs and cellular signalling networks to achieve a concerted desired physiological outcome, whereas mutations and dysregulation of ncRNAs have been linked to diverse human diseases, including cancer drug resistance. In this review, we will discuss recent findings on the multiple molecular roles of regulatory ncRNAs on the signalling pathways involved in cancer drug resistance and the therapeutic potential of reverse drug resistance.

  13. Insights into Reference Point Indentation Involving Human Cortical Bone: Sensitivity to Tissue Anisotropy and Mechanical Behavior

    PubMed Central

    Granke, Mathilde; Coulmier, Aurélie; Uppuganti, Sasidhar; Gaddy, Jennifer A; Does, Mark D; Nyman, Jeffry S

    2014-01-01

    Reference point indentation (RPI) is a microindentation technique involving 20 cycles of loading in “force-control” that can directly assess a patient’s bone tissue properties. Even though preliminary clinical studies indicate a capability for fracture discrimination, little is known about what mechanical behavior the various RPI properties characterize and how these properties relate to traditional mechanical properties of bone. To address this, the present study investigated the sensitivity of RPI properties to anatomical location and tissue organization as well as examined to what extent RPI measurements explain the intrinsic mechanical properties of human cortical bone. Multiple indents with a target force of 10 N were done in 2 orthogonal directions (longitudinal and transverse) per quadrant (anterior, medial, posterior, and lateral) of the femoral mid-shaft acquired from 26 donors (25–101 years old). Additional RPI measurements were acquired for 3 orthogonal directions (medial only). Independent of age, most RPI properties did not vary among these locations, but they did exhibit transverse isotropy such that resistance to indentation is greater in the longitudinal (axial) direction than in the transverse direction (radial or circumferential). Next, beam specimens (~ 2 mm × 5 mm × 40 mm) were extracted from the medial cortex of femoral mid-shafts, acquired from 34 donors (21–99 years old). After monotonically loading the specimens in three-point bending to failure, RPI properties were acquired from an adjacent region outside the span. Indent direction was orthogonal to the bending axis. A significant inverse relationship was found between resistance to indentation and the apparent-level mechanical properties. Indentation distance increase (IDI) and a linear combination of IDI and the loading slope, averaged over cycles 3 through 20, provided the best explanation of the variance in ultimate stress (r2=0.25, p=0.003) and toughness (r2=0.35, p=0

  14. Involvement of medullary GABAergic system in extraterritorial neuropathic pain mechanisms associated with inferior alveolar nerve transection.

    PubMed

    Okada-Ogawa, Akiko; Nakaya, Yuka; Imamura, Yoshiki; Kobayashi, Masayuki; Shinoda, Masamichi; Kita, Kozue; Sessle, Barry J; Iwata, Koichi

    2015-05-01

    In order to determine if the functional changes in the GABAergic system in the trigeminal spinal subnucleus caudalis (Vc) are involved in the mechanisms underlying extraterritorial neuropathic pain in the orofacial region following inferior alveolar nerve transection (IANX), mechanical noxious behavior, phosphorylated extracellular signal-regulated kinase (pERK) immunohistochemistry and single neuronal activity were analyzed in vesicular GABA transporter (VGAT)-VenusA rats expressing fluorescent protein and the VGAT in Vc neurons. The number of VGAT-VenusA positive neurons was significantly reduced in IANX rats than naive and sham rats at 7days after nerve transection. The number of VGAT-VenusA positive pERK-immunoreactive (IR) cells was significantly increased in IANX rats at 21days after IAN transection compared with naive and sham rats. The background activity and mechanical-evoked responses of Vc nociceptive neurons were significantly depressed after intrathecal application of the GABA receptor agonist muscimol in sham rats but not in IANX rats. Furthermore, the expression of potassium-chloride co-transporter 2 (KCC2) in the Vc was significantly reduced in IANX rats compared with sham rats. The head-withdrawal threshold (HWT) to mechanical stimulation of the whisker pad skin was significantly decreased in IANX rats compared with sham rats on days 7 and 21 after IANX. The significant reduction of the HWT and significant increase in the number of VGAT-VenusA negative pERK-IR cells were observed in KCC2 blocker R-DIOA-injected rats compared with vehicle-injected rats on day 21 after sham treatment. These findings revealed that GABAergic Vc neurons might be reduced in their number at the early period after IANX and the functional changes might occur in GABAergic neurons from inhibitory to excitatory at the late period after IANX, suggesting that the neuroplastic changes occur in the GABAergic neuronal network in the Vc due to morphological and functional changes at

  15. Involvement of medullary GABAergic system in extraterritorial neuropathic pain mechanisms associated with inferior alveolar nerve transection.

    PubMed

    Okada-Ogawa, Akiko; Nakaya, Yuka; Imamura, Yoshiki; Kobayashi, Masayuki; Shinoda, Masamichi; Kita, Kozue; Sessle, Barry J; Iwata, Koichi

    2015-05-01

    In order to determine if the functional changes in the GABAergic system in the trigeminal spinal subnucleus caudalis (Vc) are involved in the mechanisms underlying extraterritorial neuropathic pain in the orofacial region following inferior alveolar nerve transection (IANX), mechanical noxious behavior, phosphorylated extracellular signal-regulated kinase (pERK) immunohistochemistry and single neuronal activity were analyzed in vesicular GABA transporter (VGAT)-VenusA rats expressing fluorescent protein and the VGAT in Vc neurons. The number of VGAT-VenusA positive neurons was significantly reduced in IANX rats than naive and sham rats at 7days after nerve transection. The number of VGAT-VenusA positive pERK-immunoreactive (IR) cells was significantly increased in IANX rats at 21days after IAN transection compared with naive and sham rats. The background activity and mechanical-evoked responses of Vc nociceptive neurons were significantly depressed after intrathecal application of the GABA receptor agonist muscimol in sham rats but not in IANX rats. Furthermore, the expression of potassium-chloride co-transporter 2 (KCC2) in the Vc was significantly reduced in IANX rats compared with sham rats. The head-withdrawal threshold (HWT) to mechanical stimulation of the whisker pad skin was significantly decreased in IANX rats compared with sham rats on days 7 and 21 after IANX. The significant reduction of the HWT and significant increase in the number of VGAT-VenusA negative pERK-IR cells were observed in KCC2 blocker R-DIOA-injected rats compared with vehicle-injected rats on day 21 after sham treatment. These findings revealed that GABAergic Vc neurons might be reduced in their number at the early period after IANX and the functional changes might occur in GABAergic neurons from inhibitory to excitatory at the late period after IANX, suggesting that the neuroplastic changes occur in the GABAergic neuronal network in the Vc due to morphological and functional changes at

  16. Mechanism of PP2A-mediated IKKβ dephosphorylation: a systems biological approach

    PubMed Central

    Witt, Johannes; Barisic, Sandra; Schumann, Eva; Allgöwer, Frank; Sawodny, Oliver; Sauter, Thomas; Kulms, Dagmar

    2009-01-01

    Background Biological effects of nuclear factor-κB (NFκB) can differ tremendously depending on the cellular context. For example, NFκB induced by interleukin-1 (IL-1) is converted from an inhibitor of death receptor induced apoptosis into a promoter of ultraviolet-B radiation (UVB)-induced apoptosis. This conversion requires prolonged NFκB activation and is facilitated by IL-1 + UVB-induced abrogation of the negative feedback loop for NFκB, involving a lack of inhibitor of κB (IκBα) protein reappearance. Permanent activation of the upstream kinase IKKβ results from UVB-induced inhibition of the catalytic subunit of Ser-Thr phosphatase PP2A (PP2Ac), leading to immediate phosphorylation and degradation of newly synthesized IκBα. Results To investigate the mechanism underlying the general PP2A-mediated tuning of IKKβ phosphorylation upon IL-1 stimulation, we have developed a strictly reduced mathematical model based on ordinary differential equations which includes the essential processes concerning the IL-1 receptor, IKKβ and PP2A. Combining experimental and modelling approaches we demonstrate that constitutively active, but not post-stimulation activated PP2A, tunes out IKKβ phosphorylation thus allowing for IκBα resynthesis in response to IL-1. Identifiability analysis and determination of confidence intervals reveal that the model allows reliable predictions regarding the dynamics of PP2A deactivation and IKKβ phosphorylation. Additionally, scenario analysis is used to scrutinize several hypotheses regarding the mode of UVB-induced PP2Ac inhibition. The model suggests that down regulation of PP2Ac activity, which results in prevention of IκBα reappearance, is not a direct UVB action but requires instrumentality. Conclusion The model developed here can be used as a reliable building block of larger NFκB models and offers comprehensive simplification potential for future modeling of NFκB signaling. It gives more insight into the newly discovered

  17. Energy saving mechanisms, collective behavior and the variation range hypothesis in biological systems: A review.

    PubMed

    Trenchard, Hugh; Perc, Matjaž

    2016-09-01

    Energy saving mechanisms are ubiquitous in nature. Aerodynamic and hydrodynamic drafting, vortice uplift, Bernoulli suction, thermoregulatory coupling, path following, physical hooks, synchronization, and cooperation are only some of the better-known examples. While drafting mechanisms also appear in non-biological systems such as sedimentation and particle vortices, the broad spectrum of these mechanisms appears more diversely in biological systems that include bacteria, spermatozoa, various aquatic species, birds, land animals, semi-fluid dwellers like turtle hatchlings, as well as human systems. We present the thermodynamic framework for energy saving mechanisms, and we review evidence in favor of the variation range hypothesis. This hypothesis posits that, as an evolutionary process, the variation range between strongest and weakest group members converges on the equivalent energy saving quantity that is generated by the energy saving mechanism. We also review self-organized structures that emerge due to energy saving mechanisms, including convective processes that can be observed in many systems over both short and long time scales, as well as high collective output processes in which a form of collective position locking occurs.

  18. Energy saving mechanisms, collective behavior and the variation range hypothesis in biological systems: A review.

    PubMed

    Trenchard, Hugh; Perc, Matjaž

    2016-09-01

    Energy saving mechanisms are ubiquitous in nature. Aerodynamic and hydrodynamic drafting, vortice uplift, Bernoulli suction, thermoregulatory coupling, path following, physical hooks, synchronization, and cooperation are only some of the better-known examples. While drafting mechanisms also appear in non-biological systems such as sedimentation and particle vortices, the broad spectrum of these mechanisms appears more diversely in biological systems that include bacteria, spermatozoa, various aquatic species, birds, land animals, semi-fluid dwellers like turtle hatchlings, as well as human systems. We present the thermodynamic framework for energy saving mechanisms, and we review evidence in favor of the variation range hypothesis. This hypothesis posits that, as an evolutionary process, the variation range between strongest and weakest group members converges on the equivalent energy saving quantity that is generated by the energy saving mechanism. We also review self-organized structures that emerge due to energy saving mechanisms, including convective processes that can be observed in many systems over both short and long time scales, as well as high collective output processes in which a form of collective position locking occurs. PMID:27288936

  19. A renaissance in RNA synthetic biology: new mechanisms, applications and tools for the future.

    PubMed

    Chappell, James; Watters, Kyle E; Takahashi, Melissa K; Lucks, Julius B

    2015-10-01

    Since our ability to engineer biological systems is directly related to our ability to control gene expression, a central focus of synthetic biology has been to develop programmable genetic regulatory systems. Researchers are increasingly turning to RNA regulators for this task because of their versatility, and the emergence of new powerful RNA design principles. Here we review advances that are transforming the way we use RNAs to engineer biological systems. First, we examine new designable RNA mechanisms that are enabling large libraries of regulators with protein-like dynamic ranges. Next, we review emerging applications, from RNA genetic circuits to molecular diagnostics. Finally, we describe new experimental and computational tools that promise to accelerate our understanding of RNA folding, function and design. PMID:26093826

  20. [Modern evolutional developmental biology: mechanical and molecular genetic or phenotypic approaches?].

    PubMed

    Vorob'eva, É I

    2010-01-01

    Heightened interest in the evolutionary problems of developmental biology in the 1980s was due to the success of molecular genetics and disappointment in the synthetic theory of evolution, where the chapters of embryology and developmental biology seem to have been left out. Modern evo-devo, which turned out to be antipodean to the methodology of the synthetic theory of evolution, propagandized in the development of evolutionary problems only the mechanical and molecular genetic approach to the evolution of ontogenesis, based on cellular and intercellular interactions. The phonotypical approach to the evaluation of evolutionary occurrences in ontogenesis, which aids in the joining of the genetic and epigenetic levels of research, the theory of natural selection, the nomogenetic conception, and the problem of the wholeness of the organism in onto- and phylogenesis may be against this. The phenotypic approach to ontogenesis is methodologically the most perspective for evolutionary developmental biology.

  1. Mechanisms involved in p53 downregulation by leptin in trophoblastic cells.

    PubMed

    Toro, Ayelén Rayen; Pérez-Pérez, Antonio; Corrales Gutiérrez, Isabel; Sánchez-Margalet, Víctor; Varone, Cecilia Laura

    2015-11-01

    Leptin, a 16-kDa polypeptide hormone, is produced by the adipocyte and can also be synthesized by placenta. We previously demonstrated that leptin promotes proliferation and survival in placenta, in part mediated by the p53 pathway. In this work, we investigated the mechanisms involved in leptin down-regulation of p53 level. The human first trimester cytotrophoblastic Swan-71 cell line and human placental explants at term were used. In order to study the late phase of apoptosis, triggered by serum deprivation, experiments of DNA fragmentation were carried out. Exogenous leptin added to human placental explants, showed a decrease on DNA ladder formation and MAPK pathway is involved in this leptin effect. We also found that under serum deprivation condition, leptin decreases p53 levels and the inhibitory leptin effect is lost when cells were pretreated with 50 μM PD98059 or 10 μM LY29004; or were transfected with dominant negative mutants of intermediates of these pathways, suggesting that MAPK and PI3K signaling pathways are necessaries for leptin action. Additionally, leptin diminished Ser-46 p53 phosphorylation and this effect in placental explants was mediated by the activation of MAPK and PI3K pathways. Finally, in order to assess leptin effect on p53 half-life experiments with cycloheximide were performed and MDM-2 expression was analyzed. Leptin diminished p53 half-life and up-regulated MDM-2 expression. In summary, we provided evidence suggesting that leptin anti-apoptotic effect is mediated by MAPK and PI3K pathways.

  2. Mechanisms involved in the selective transfer of long chain polyunsaturated Fatty acids to the fetus.

    PubMed

    Gil-Sánchez, Alfonso; Demmelmair, Hans; Parrilla, J J; Koletzko, Berthold; Larqué, Elvira

    2011-01-01

    The concentration of long chain polyunsaturated fatty acid (LCPUFA) in the fetal brain increases dramatically from the third trimester until 18 months of life. Several studies have shown an association between the percentage of maternal plasma docosahexaenoic acid (DHA) during gestation and development of cognitive functions in the neonate. Since only very low levels of LCPUFA are synthesized in the fetus and placenta, their primary source for the fetus is the maternal circulation. Both in vitro and human in vivo studies using labeled fatty acids have shown preferential transfer of LCPUFA from the placenta to the fetus compared with other fatty acids, although the mechanisms involved are still uncertain. The placenta takes up circulating maternal non-esterified fatty acids (NEFA) and fatty acids released mainly by maternal lipoprotein lipase and endothelial lipase. These NEFA may enter the cell by passive diffusion or by means of membrane carrier proteins. Once in the cytosol, NEFA bind to cytosolic fatty acid-binding proteins for transfer to the fetal circulation or can be oxidized within the trophoblasts, and even re-esterified and stored in lipid droplets. Although trophoblast cells are not specialized for lipid storage, LCPUFA may up-regulate peroxisome proliferator activated receptor-γ (PPARγ) and hence the gene expression of fatty acid transport carriers, fatty acid acyl-CoA-synthetases and adipophilin or other enzymes involved in lipolysis, modifying the rate of placental transfer, and metabolism. The placental transfer of LCPUFA during pregnancy seems to be a key factor in the neurological development of the fetus. Increased knowledge of the factors that modify placental transfer of fatty acids would contribute to our understanding of this complex process. PMID:22303352

  3. Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms.

    PubMed

    Srinivasan, Padmanabhan; Kapadia, Rubina; Biswas, Arundhati; Said, Hamid M

    2014-11-01

    Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5'-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na(+) dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.

  4. Two Mechanisms Involved in Trigeminal CGRP Release: Implications for Migraine Treatment

    PubMed Central

    Durham, Paul L.; Masterson, Caleb G.

    2012-01-01

    Objective The goal of this study was to better understand the cellular mechanisms involved in proton stimulation of calcitonin gene-related peptide (CGRP) secretion from cultured trigeminal neurons by investigating the effects of two anti-migraine therapies, onabotulinumtoxin A and rizatriptan. Background Stimulated CGRP release from peripheral and central terminating processes of trigeminal ganglia neurons is implicated in migraine pathology by promoting inflammation and nociception. Based on models of migraine pathology, several inflammatory molecules including protons are thought to facilitate sensitization and activation of trigeminal nociceptive neurons and stimulate CGRP secretion. Despite the reported efficacy of triptans and onabotulinumtoxinA to treat acute and chronic migraine, respectively, a substantial number of migraneurs do not get adequate relief with these therapies. A possible explanation is that triptans and onabutulinumtoxinA are not able to block proton mediated CGRP secretion. Methods CGRP secretion from cultured primary trigeminal ganglia neurons was quantitated by radioimmunoassay while intracellular calcium and sodium levels were measured in neurons via live cell imaging using Fura2-AM and SBFI-AM, respectively. The expression of ASIC3 was determined by immunocytochemistry and western blot analysis. In addition, the involvement of ASICs in mediating proton stimulation of CGRP was investigated using the potent and selective ASIC3 inhibitor APETx2. Results While KCl caused a significant increase in CGRP secretion that was significantly repressed by treatment with EGTA, onabotulinumtoxinA, and rizatriptan, the stimulatory effect of protons (pH 5.5) was not suppressed by EGTA, onabotulinumtoxinA, or rizatriptan. In addition, while KCl caused a transient increase in intracellular calcium levels that was blocked by EGTA, no appreciable change in calcium levels was observed with proton treatment. However, protons did significantly increase the

  5. Enzymatic Mechanisms Involved in Phenanthrene Degradation by the White Rot Fungus Pleurotus ostreatus

    PubMed Central

    Bezalel, L.; Hadar, Y.; Cerniglia, C. E.

    1997-01-01

    The enzymatic mechanisms involved in the degradation of phenanthrene by the white rot fungus Pleurotus ostreatus were examined. Phase I metabolism (cytochrome P-450 monooxygenase and epoxide hydrolase) and phase II conjugation (glutathione S-transferase, aryl sulfotransferase, UDP-glucuronosyltransferase, and UDP-glucosyltransferase) enzyme activities were determined for mycelial extracts of P. ostreatus. Cytochrome P-450 was detected in both cytosolic and microsomal fractions at 0.16 and 0.38 nmol min(sup-1) mg of protein(sup1), respectively. Both fractions oxidized [9,10-(sup14)C]phenanthrene to phenanthrene trans-9,10-dihydrodiol. The cytochrome P-450 inhibitors 1-aminobenzotriazole (0.1 mM), SKF-525A (proadifen, 0.1 mM), and carbon monoxide inhibited the cytosolic and microsomal P-450s differently. Cytosolic and microsomal epoxide hydrolase activities, with phenanthrene 9,10-oxide as the substrate, were similar, with specific activities of 0.50 and 0.41 nmol min(sup-1) mg of protein(sup-1), respectively. The epoxide hydrolase inhibitor cyclohexene oxide (5 mM) significantly inhibited the formation of phenanthrene trans-9,10-dihydrodiol in both fractions. The phase II enzyme 1-chloro-2,4-dinitrobenzene glutathione S-transferase was detected in the cytosolic fraction (4.16 nmol min(sup-1) mg of protein(sup-1)), whereas aryl adenosine-3(prm1)-phosphate-5(prm1)-phosphosulfate sulfotransferase (aryl PAPS sulfotransferase) UDP-glucuronosyltransferase, and UDP-glucosyltransferase had microsomal activities of 2.14, 4.25, and 4.21 nmol min(sup-1) mg of protein(sup-1), respectively, with low activity in the cytosolic fraction. However, when P. ostreatus culture broth incubated with phenanthrene was screened for phase II metabolites, no sulfate, glutathione, glucoside, or glucuronide conjugates of phenanthrene metabolites were detected. These experiments indicate the involvement of cytochrome P-450 monooxygenase and epoxide hydrolase in the initial phase I oxidation of

  6. Triskelion Structure of the Gli521 Protein, Involved in the Gliding Mechanism of Mycoplasma mobile▿

    PubMed Central

    Nonaka, Takahiro; Adan-Kubo, Jun; Miyata, Makoto

    2010-01-01

    Mycoplasma mobile binds to solid surfaces and glides smoothly and continuously by a unique mechanism. A huge protein, Gli521 (521 kDa), is involved in the gliding machinery, and it is localized in the cell neck, the base of the membrane protrusion. This protein is thought to have the role of force transmission. In this study, the Gli521 protein was purified from M. mobile cells, and its molecular shape was studied. Gel filtration analysis showed that the isolated Gli521 protein forms mainly a monomer in Tween 80-containing buffer and oligomers in Triton X-100-containing buffer. Rotary shadowing electron microscopy showed that the Gli521 monomer consisted of three parts: an oval, a rod, and a hook. The oval was 15 nm long by 11 nm wide, and the filamentous part composed of the rod and the hook was 106 nm long and 3 nm in diameter. The Gli521 molecules form a trimer, producing a “triskelion” reminiscent of eukaryotic clathrin, through association at the hook end. Image averaging of the central part of the triskelion suggested that there are stable and rigid structures. The binding site of a previously isolated monoclonal antibody on Gli521 images showed that the hook end and oval correspond to the C- and N-terminal regions, respectively. Partial digestion of Gli521 showed that the molecule could be divided into three domains, which we assigned to the oval, rod, and hook of the molecular image. The Gli521 molecule's role in the gliding mechanism is discussed. PMID:19915029

  7. The central anorexigenic mechanism of adrenocorticotropic hormone involves the caudal hypothalamus in chicks.

    PubMed

    Shipp, Steven L; Yi, Jiaqing; Dridi, Sami; Gilbert, Elizabeth R; Cline, Mark A

    2015-10-01

    Adrenocorticotropic hormone (ACTH), consisting of 39 amino acids, is most well-known for its involvement in an organism's response to stress. It also participates in satiety, as exogenous ACTH causes decreased food intake in rats. However, its anorexigenic mechanism is not well understood in any species and its effect on appetite is not reported in the avian class. Thus, the present study was designed to evaluate central ACTH's effect on food intake and to elucidate the mechanism mediating this response using broiler chicks. Chicks that received intracerebroventricular (ICV) injection of 1, 2, or 4 nmol of ACTH reduced food intake, under both ad libitum and 180 min fasted conditions. Water intake was also reduced in ACTH-injected chicks under both feeding conditions, but when measured without access to feed it was not affected. Blood glucose was not affected in either feeding condition. Following ACTH injection, c-Fos immunoreactivity was quantified in key appetite-associated hypothalamic nuclei including the ventromedial hypothalamus (VMH), dorsomedial hypothalamus, lateral hypothalamus (LH), arcuate nucleus (ARC) and the parvo- and magno-cellular portions of the paraventricular nucleus. ACTH-injected chicks had increased c-Fos immunoreactivity in the VMH, LH, and ARC. Hypothalamus was collected at 1h post-injection, and real-time PCR performed to measure mRNA abundance of some appetite-associated factors. Neuropeptide Y, pro-opiomelanocortin, glutamate decarboxylase 1, melanocortin receptors 2-5, and urocortin 3 mRNA abundance was not affected by ACTH treatment. However, expression of corticotropin releasing factor (CRF), urotensin 2 (UT), agouti-related peptide (AgRP), and orexin (ORX), and melanocortin receptor 1 (MC1R) mRNA decreased in the hypothalamus of ACTH-injected chicks. In conclusion, ICV ACTH causes decreased food intake in chicks, and is associated with VMH, LH, and ARC activation, and a decrease in hypothalamic mRNA abundance of CRF, UT, AgRP, ORX

  8. Mechanisms involved in the swelling of erythrocytes caused by Pacific and Caribbean ciguatoxins.

    PubMed

    Sauviat, Martin-Pierre; Boydron-Le Garrec, Raphaële; Masson, Jean-Baptiste; Lewis, Richard L; Vernoux, Jean-Paul; Molgó, Jordi; Laurent, Dominique; Benoit, Evelyne

    2006-01-01

    The mechanisms underlying the swelling of frog red blood cells (RBC), induced by Pacific (P-CTX-1) and Caribbean (C-CTX-1) ciguatoxins (CTXs), were investigated by measuring the length, width and surface of their elliptic shape. P-CTX-1 (0.5 to 5 nM) and C-CTX-1 (1 nM) induced RBC swelling within 60 min. The CTXs-induced RBC swelling was blocked by apamin (1 microM) and by Sr(2+) (1 mM). P-CTX-1-induced RBC swelling was prevented and inhibited by H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (27 microM), an inhibitor of soluble guanylate cyclase (sGC), and NOS blockade by NG methyl-l-arginine (l-NMA; 10 microM). Cytochalasin D (cytD, 10 microM) increased RBC surface and mimicked CTX effect but did not prevent the P-CTX-1-induced l-NMA-sensitive extra increase. Calculations revealed that P-CTX-1 and cytD increase RBC total surface envelop and volume. These data strongly suggest that the molecular mechanisms underlying CTXs-induced RBC swelling involve the NO pathway by an activation of the inducible NOS, leading to sGC activation which modulates intracellular cGMP and regulates L-type Ca(2+) channels. The resulting increase in intracellular Ca(2+) content, in turn, disrupts the actin cytoskeleton, which causes a water influx and triggers a Ca(2+)-activated K(+) current through SK2 isoform channels. PMID:16364667

  9. Neural Correlates of Successful and Unsuccessful Strategical Mechanisms Involved in Uncertain Decision-Making.

    PubMed

    Giustiniani, Julie; Gabriel, Damien; Nicolier, Magali; Monnin, Julie; Haffen, Emmanuel

    2015-01-01

    The ability to develop successful long-term strategies in uncertain situations relies on complex neural mechanisms. Although lesion studies have shown some of the mechanisms involved, it is still unknown why some healthy subjects are able to make the right decision whereas others are not. The aim of our study was to investigate neurophysiological differences underlying this ability to develop a successful strategy in a group of healthy subjects playing a monetary card game called the Iowa Gambling Task (IGT). In this task, subjects have to win and earn money by choosing between four decks of cards, two were advantageous in the long term and two disadvantageous. Twenty healthy right-handed subjects performed the IGT while their cerebral activity was recorded by electroencephalography. Based on their behavioral performances, two groups of subjects could clearly be distinguished: one who selected the good decks and thus succeeded in developing a Favorable strategy (9 subjects) and one who remained Undecided (11 subjects). No neural difference was found between each group before the selection of a deck, but in both groups a greater negativity was found emerging from the right superior frontal gyrus 600 ms before a disadvantageous selection. During the processing of the feedback, an attenuation of the P200 and P300 waveforms was found for the Undecided group, and a P300 originating from the medial frontal gyrus was found in response to a loss only in the Favorable group. Our results suggest that undecided subjects are hyposensitive to the valence of the cards during gambling, which affects the feedback processing. PMID:26086196

  10. Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

    SciTech Connect

    Wang, Jun; Cao, Hui; Wang, Hongjie; Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli; Xiang, Ming

    2015-06-15

    Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation.

  11. Piezo-actuated parallel mechanism for biological cell release at high speed.

    PubMed

    Avci, Ebubekir; Hattori, Takayuki; Kamiyama, Kazuto; Kojima, Masaru; Horade, Mitsuhiro; Mae, Yasushi; Arai, Tatsuo

    2015-10-01

    In this paper, a dynamic releasing approach is proposed for high-speed biological cell manipulation. A compact parallel mechanism for grasping and releasing microobjects is used to generate controllable vibration to overcome the strong adhesion forces between the end effector and the manipulated object. To reach the required acceleration of the end effector, which is necessary for the detachment of the target object by overcoming adhesion forces, vibration in the end effector is generated by applying sinusoidal voltage to the PZT actuator of the parallel mechanism. For the necessary acceleration, we focus on the possible range of the frequency of the PZT-actuator-induced vibration, while minimizing the amplitude of the vibration (14 nm) to achieve precise positioning. The effect of the air and liquid environments on the required vibration frequency for successful release is investigated. For the first time, release results of microbeads and biological cells are compared. Release of the biological cells with 100 % success rate suggests that the proposed active release method is an appropriate solution for adhered biological cells during the release task.

  12. Exploring the MACH Model's Potential as a Metacognitive Tool to Help Undergraduate Students Monitor Their Explanations of Biological Mechanisms

    ERIC Educational Resources Information Center

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

    2016-01-01

    When undergraduate biology students learn to explain biological mechanisms, they face many challenges and may overestimate their understanding of living systems. Previously, we developed the MACH model of four components used by expert biologists to explain mechanisms: Methods, Analogies, Context, and How. This study explores the implementation of…

  13. Decitabine, a new star in epigenetic therapy: the clinical application and biological mechanism in solid tumors.

    PubMed

    Nie, Jing; Liu, Lin; Li, Xiang; Han, Weidong

    2014-11-01

    Epigenetic alterations are strongly associated with cancer development and drug resistance. The use of the DNA methylation inhibitor decitabine (Dacogen®) has been approved in the treatment of hematological malignancies, and its clinical effects on solid tumors have gained attention. Here, we present a review of the molecular regulation mechanisms, clinical experiences and biological evaluation for novel decitabine-based therapies in solid tumors. We also discuss the following questions: What is the best administration schedule of decitabine in solid tumors? Is there tumor type specificity for decitabine-based epigenetic therapy? What are the biological function and mechanism of decitabine in suppressing tumor development? Is there a correlation between DNA demethylation and clinical response? Importantly, low-dose decitabine and combined therapy show significant improvement in solid tumor treatment. However, the correlation studies are preliminary, and key biomarkers for prognosis need further investigation.

  14. The radical-pair mechanism as a paradigm for the emerging science of quantum biology

    NASA Astrophysics Data System (ADS)

    Kominis, Iannis K.

    2015-12-01

    The radical-pair mechanism (RPM) was introduced in the 1960s to explain anomalously large EPR and NMR signals in chemical reactions of organic molecules. It has evolved to the cornerstone of spin chemistry, the study of the effect electron and nuclear spins have on chemical reactions, with the avian magnetic compass mechanism and the photosynthetic reaction center dynamics being prominent biophysical manifestations of such effects. In recent years the RPM was shown to be an ideal biological system where the conceptual tools of quantum-information science can be fruitfully applied. We will here review recent work making the case that RPM is indeed a major driving force of the emerging field of quantum biology.

  15. Integrating mechanical and biological control of cell proliferation through bioinspired multieffector materials.

    PubMed

    Seras-Franzoso, Joaquin; Tatkiewicz, Witold I; Vazquez, Esther; García-Fruitós, Elena; Ratera, Imma; Veciana, Jaume; Villaverde, Antonio

    2015-01-01

    In nature, cells respond to complex mechanical and biological stimuli whose understanding is required for tissue construction in regenerative medicine. However, the full replication of such bimodal effector networks is far to be reached. Engineering substrate roughness and architecture allows regulating cell adhesion, positioning, proliferation, differentiation and survival, and the external supply of soluble protein factors (mainly growth factors and hormones) has been long applied to promote growth and differentiation. Further, bioinspired scaffolds are progressively engineered as reservoirs for the in situ sustained release of soluble protein factors from functional topographies. We review here how research progresses toward the design of integrative, holistic scaffold platforms based on the exploration of individual mechanical and biological effectors and their further combination. PMID:25816885

  16. Integrating mechanical and biological control of cell proliferation through bioinspired multieffector materials.

    PubMed

    Seras-Franzoso, Joaquin; Tatkiewicz, Witold I; Vazquez, Esther; García-Fruitós, Elena; Ratera, Imma; Veciana, Jaume; Villaverde, Antonio

    2015-01-01

    In nature, cells respond to complex mechanical and biological stimuli whose understanding is required for tissue construction in regenerative medicine. However, the full replication of such bimodal effector networks is far to be reached. Engineering substrate roughness and architecture allows regulating cell adhesion, positioning, proliferation, differentiation and survival, and the external supply of soluble protein factors (mainly growth factors and hormones) has been long applied to promote growth and differentiation. Further, bioinspired scaffolds are progressively engineered as reservoirs for the in situ sustained release of soluble protein factors from functional topographies. We review here how research progresses toward the design of integrative, holistic scaffold platforms based on the exploration of individual mechanical and biological effectors and their further combination.

  17. Determining the transport mechanism of an enzyme-catalytic complex metabolic network based on biological robustness.

    PubMed

    Wang, Lei

    2013-04-01

    Understanding the transport mechanism of 1,3-propanediol (1,3-PD) is of critical importance to do further research on gene regulation. Due to the lack of intracellular information, on the basis of enzyme-catalytic system, using biological robustness as performance index, we present a system identification model to infer the most possible transport mechanism of 1,3-PD, in which the performance index consists of the relative error of the extracellular substance concentrations and biological robustness of the intracellular substance concentrations. We will not use a Boolean framework but prefer a model description based on ordinary differential equations. Among other advantages, this also facilitates the robustness analysis, which is the main goal of this paper. An algorithm is constructed to seek the solution of the identification model. Numerical results show that the most possible transport way is active transport coupled with passive diffusion.

  18. A biological mechanism for Bayesian feature selection: Weight decay and raising the LASSO.

    PubMed

    Connor, Patrick; Hollensen, Paul; Krigolson, Olav; Trappenberg, Thomas

    2015-07-01

    Biological systems are capable of learning that certain stimuli are valuable while ignoring the many that are not, and thus perform feature selection. In machine learning, one effective feature selection approach is the least absolute shrinkage and selection operator (LASSO) form of regularization, which is equivalent to assuming a Laplacian prior distribution on the parameters. We review how such Bayesian priors can be implemented in gradient descent as a form of weight decay, which is a biologically plausible mechanism for Bayesian feature selection. In particular, we describe a new prior that offsets or "raises" the Laplacian prior distribution. We evaluate this alongside the Gaussian and Cauchy priors in gradient descent using a generic regression task where there are few relevant and many irrelevant features. We find that raising the Laplacian leads to less prediction error because it is a better model of the underlying distribution. We also consider two biologically relevant online learning tasks, one synthetic and one modeled after the perceptual expertise task of Krigolson et al. (2009). Here, raising the Laplacian prior avoids the fast erosion of relevant parameters over the period following training because it only allows small weights to decay. This better matches the limited loss of association seen between days in the human data of the perceptual expertise task. Raising the Laplacian prior thus results in a biologically plausible form of Bayesian feature selection that is effective in biologically relevant contexts. PMID:25897512

  19. Memory improving actions of gabapentin in mice: possible involvement of central muscarinic cholinergic mechanism.

    PubMed

    Boccia, M M; Acosta, G B; Baratti, C M

    2001-10-01

    Male CF-1 mice were tested 48 h after training on a one trial step-through inhibitory avoidance task. Immediately post-training, intraperitoneal (i.p.) injections of the antiepileptic gabapentin (1-(aminomethyl) cyclohexaneacetic acid) (GBP, 10 mg/kg) enhanced retention performance. The effect was prevented by atropine, a central muscarinic cholinergic receptor antagonist (0.5 mg/kg, i.p.) administered after training but 10 min prior to GBP treatment. In contrast, neither methylatropine (0.5 mg/kg, i.p.), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, i.p.) or hexamethonium (5 mg/kg, i.p.), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training GBP on retention performance. Low subeffective doses of the central acting anticholinesterase physostigmine (35 mg/kg, i.p.) administered immediately after training, and GBP (5 mg/kg, i.p.), given 10 min after training, significantly enhanced retention performance. The effects of GBP (5 mg/kg, i.p.) were not influenced by the peripherally acting anticholinesterase neostigmine (150 mg/kg, i.p.). Considered together, these findings suggest a disinhibitory action of GBP on the activity of central muscarinic cholinergic mechanisms that are involved in memory consolidation. PMID:11578817

  20. Mechanisms involved in spinal cord central synapse loss in a mouse model of spinal muscular atrophy.

    PubMed

    Tarabal, Olga; Caraballo-Miralles, Víctor; Cardona-Rossinyol, Andrea; Correa, Francisco J; Olmos, Gabriel; Lladó, Jerònia; Esquerda, Josep E; Calderó, Jordi

    2014-06-01

    Motoneuron (MN) cell death is the histopathologic hallmark of spinal muscular atrophy (SMA), although MN loss seems to be a late event. Conversely, disruption of afferent synapses on MNs has been shown to occur early in SMA. Using a mouse model of severe SMA (SMNΔ7), we examined the mechanisms involved in impairment of central synapses. We found that MNs underwent progressive degeneration in the course of SMA, with MN loss still occurring at late stages. Loss of afferent inputs to SMA MNs was detected at embryonic stages, long before MN death. Reactive microgliosis and astrogliosis were present in the spinal cord of diseased animals after the onset of MN loss. Ultrastructural observations indicate that dendrites and microglia phagocytose adjacent degenerating presynaptic terminals. Neuronal nitric oxide synthase was upregulated in SMNΔ7 MNs, and there was an increase in phosphorylated myosin light chain expression in synaptic afferents on MNs; these observations implicate nitric oxide in MN deafferentation and suggest that the RhoA/ROCK pathway is activated. Together, our observations suggest that the earliest change occurring in SMNΔ7 mice is the loss of excitatory glutamatergic synaptic inputs to MNs; reduced excitability may enhance their vulnerability to degeneration and death.

  1. Visfatin is involved in promotion of colorectal carcinoma malignancy through an inducing EMT mechanism.

    PubMed

    Yang, Jing; Zhang, Kun; Song, Haixing; Wu, Mingbo; Li, Jingyi; Yong, Ziyi; Jiang, Sheng; Kuang, Xi; Zhang, Tao

    2016-05-31

    Increasing evidences suggested visfatin, a newly discovered obesity-induced adipocytokine, is involved in promotion of cancer malignancy and correlated with worse clinical prognosis. While its effects and mechanisms on progression of colorectal cancer (CRC) remain unclear. Our clinical data show that visfatin protein is over expressed, positive associated with lymph node metastasis, high-grade tumor, and poor prognosis in 87 CRC patients. The levels of plasma visfatin are significantly upregulated in Stage IV colon cancer. Visfatin can significantly promote the in vitro migration and invasion of CRC cells via induction epithelial mesenchymal transition (EMT). It can increase the expression and nuclear translocation of Snail, a key transcription factor in regulating EMT. While silencing of Snail attenuates visfatin induced EMT. Further studies reveal visfatin can inhibit the association of Snail with GSK-3β and subsequently suppress ubiquitylation of Snail. In addition, visfatin can increase the expression and nuclear translocation of β-catenin, elevate its binding with Snail promoter, and then increase the transcription of Snail. While inhibitor of PI3K/Akt, LY294002, abolishes visfatin induced up regulation of Snail, Vimentin (Vim), β-catenin, and phosphorylated GSK-3β. In summary, our data suggest that increased expression of visfatin are associated with a more aggressive phenotype of CRC patients. It can trigger the EMT of CRC cells via Akt/GSK-3β/β-catenin signals.

  2. Identification of plant genetic loci involved in a posttranscriptional mechanism for meiotically reversible transgene silencing.

    PubMed Central

    Dehio, C; Schell, J

    1994-01-01

    Numerous reports describe phenomena of transgene silencing in plants, yet the underlying genetic and molecular mechanisms are poorly understood. We observed that regeneration of Arabidopsis thaliana plants transgenic for the rolB gene of Agrobacterium rhizogenes results in a selection for transgene silencing. Transgene silencing could be monitored in this system by reversion of the visible RolB phenotype. We report a phenotypic, molecular, and genetic characterization of a meiotically reversible transgene silencing phenomenon observed in a rolB transgenic line. In this line, the rolB gene is expressed strongly and uniformly in seedlings, but in the course of further development, the rolB gene is silenced erratically at a frequency that depends on the dosage of rolB. The silenced state is mitotically stable, while complete resetting of rolB gene expression occurs in seedlings of the following generation. The silencing of rolB correlates with a dramatic reduction of steady-state rolB transcripts, while rolB nuclear run-off transcripts are only moderately reduced. Therefore, rolB gene silencing seems to act predominantly at the posttranscriptional level. The process of rolB gene silencing was found to be affected by two extragenic modifier loci that influence both the frequency and the timing of rolB gene silencing during plant development. These genetic data demonstrate a direct involvement of defined plant genes in this form of gene silencing. Images PMID:8202523

  3. Molecular Mechanisms Involved in the Pathogenesis of Alphavirus-Induced Arthritis

    PubMed Central

    Assunção-Miranda, Iranaia; Da Poian, Andrea T.

    2013-01-01

    Arthritogenic alphaviruses, including Ross River virus (RRV), Chikungunya virus (CHIKV), Sindbis virus (SINV), Mayaro virus (MAYV), O'nyong-nyong virus (ONNV), and Barmah Forest virus (BFV), cause incapacitating and long lasting articular disease/myalgia. Outbreaks of viral arthritis and the global distribution of these diseases point to the emergence of arthritogenic alphaviruses as an important public health problem. This review discusses the molecular mechanisms involved in alphavirus-induced arthritis, exploring the recent data obtained with in vitro systems and in vivo studies using animal models and samples from patients. The factors associated to the extension and persistence of symptoms are highlighted, focusing on (a) virus replication in target cells, and tissues, including macrophages and muscle cells; (b) the inflammatory and immune responses with recruitment and activation of macrophage, NK cells and T lymphocytes to the lesion focus and the increase of inflammatory mediators levels; and (c) the persistence of virus or viral products in joint and muscle tissues. We also discuss the importance of the establishment of novel animal models to test new molecular targets and to develop more efficient and selective drugs to treat these diseases. PMID:24069610

  4. Molecular and cellular mechanisms involved in Helicobacter pylori-induced inflammation and oxidative stress.

    PubMed

    Naito, Yuji; Yoshikawa, Toshikazu

    2002-08-01

    Helicobacter pylori (H. pylori)-infection leads to different clinical and pathological outcomes in humans, including chronic gastritis, peptic ulcer disease, and gastric neoplasia. The key determinants of these outcomes are the severity and distribution of the H. pylori-induced inflammation. Antral-type gastritis is associated with excessive acid secretion and a high risk of duodenal ulcer. In contrast, gastritis that involves the acid-secreting corpus region leads to hypochlorhydria, progressive gastric atrophy, and an increased risk of gastric cancer. The key pathophysiological event in H. pylori infection is initiation and continuance of an inflammatory response. Bacteria or their products trigger this inflammatory process and the main mediators are cytokines. Identification of both host- and bacterial-factors that mediate is an intense area of interest in current researches. Recent data indicates that the cag pathogenicity island plays a crucial role in H. pylori-induced gastric inflammation via the activation of gene transcription. It has been demonstrated that oxidative and nitrosative stress associated with inflammation plays an important role in gastric carcinogenesis as a mediator of carcinogenic compound formation, DNA damage, and cell proliferation. Genetic information regulating such stress would be one of the host factors determining the outcome--particularly when the outcome is gastric cancer--of H. pylori infection, and the compound that attenuates such stress may be a candidate for use in chemoprevention. This review highlights recent advances in understanding of the mechanisms underlying chronic inflammation following infection with H. pylori.

  5. Memory improving actions of gabapentin in mice: possible involvement of central muscarinic cholinergic mechanism.

    PubMed

    Boccia, M M; Acosta, G B; Baratti, C M

    2001-10-01

    Male CF-1 mice were tested 48 h after training on a one trial step-through inhibitory avoidance task. Immediately post-training, intraperitoneal (i.p.) injections of the antiepileptic gabapentin (1-(aminomethyl) cyclohexaneacetic acid) (GBP, 10 mg/kg) enhanced retention performance. The effect was prevented by atropine, a central muscarinic cholinergic receptor antagonist (0.5 mg/kg, i.p.) administered after training but 10 min prior to GBP treatment. In contrast, neither methylatropine (0.5 mg/kg, i.p.), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, i.p.) or hexamethonium (5 mg/kg, i.p.), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training GBP on retention performance. Low subeffective doses of the central acting anticholinesterase physostigmine (35 mg/kg, i.p.) administered immediately after training, and GBP (5 mg/kg, i.p.), given 10 min after training, significantly enhanced retention performance. The effects of GBP (5 mg/kg, i.p.) were not influenced by the peripherally acting anticholinesterase neostigmine (150 mg/kg, i.p.). Considered together, these findings suggest a disinhibitory action of GBP on the activity of central muscarinic cholinergic mechanisms that are involved in memory consolidation.

  6. Molecular mechanisms involved in muscle wasting in cancer and ageing: cachexia versus sarcopenia.

    PubMed

    Argilés, Josep M; Busquets, Sílvia; Felipe, Antonio; López-Soriano, Francisco J

    2005-05-01

    The aim of the present review is to summarize and evaluate the different mechanisms and catabolic mediators involved in cancer cachexia and ageing sarcopenia since they may represent targets for future promising clinical investigations. Cancer cachexia is a syndrome characterized by a marked weight loss, anorexia, asthenia and anemia. In fact, many patients who die with advanced cancer suffer from cachexia. The degree of cachexia is inversely correlated with the survival time of the patient and it always implies a poor prognosis. Unfortunately, at the clinical level, cachexia is not treated until the patient suffers from a considerable weight loss and wasting. At this point, the cachectic syndrome is almost irreversible. The cachectic state is often associated with the presence and growth of the tumour and leads to a malnutrition status due to the induction of anorexia. In recent years, age-related diseases and disabilities have become of major health interest and importance. This holds particularly for muscle wasting, also known as sarcopenia, that decreases the quality of life of the geriatric population, increasing morbidity and decreasing life expectancy. The cachectic factors (associated with both depletion of fat stores and muscular tissue) can be divided into two categories: of tumour origin and humoural factors. In conclusion, more research should be devoted to the understanding of muscle wasting mediators, both in cancer and ageing, in particular the identification of common mediators may prove as a good therapeutic strategies for both prevention and treatment of wasting both in disease and during healthy ageing.

  7. Synthesis, mechanical and biological characterization of ionic doped carbonated hydroxyapatite/β-tricalcium phosphate mixtures.

    PubMed

    Kannan, S; Vieira, S I; Olhero, S M; Torres, P M C; Pina, S; da Cruz e Silva, O A B; Ferreira, J M F

    2011-04-01

    The influence of ionic substituents in calcium phosphates intended for bone and tooth replacement biomedical applications is an important research topic, owing to the essential roles played by trace elements in biological processes. The present study investigates the mechanical and biological evaluation of ionic doped hydroxyapatite/β-tricalcium phosphate mixtures which have been prepared by a simple aqueous precipitation method. Heat treating the resultant calcium phosphates in a carbonated atmosphere led to the formation of ionic doped carbonated hydroxyapatite/β-tricalcium phosphate mixtures containing the essential ions of biological apatite. The structural analysis determined by Rietveld refinement confirmed the presence of hydroxyapatite as the main phase, together with a considerable amount of β-tricalcium phosphate. Such phase assemblage is essentially due to the influence of substituted ions during synthesis. The results from mechanical tests proved that carbonate substitutions are detrimental for the mechanical properties of apatite-based ceramics. In vitro proliferation assays of osteoblastic-like cells (MC3T3-E1 cell line) to powders revealed that carbonate incorporation can either delay or accelerate MC3T3 proliferation, although reaching the same proliferation levels as control cells after 2 weeks in culture. Further, the powders enable pre-osteoblastic differentiation in a similar manner to control cells, as indirectly measured by ALP activity and Type-I collagen medium secretion. PMID:21146640

  8. Integration of biological data by kernels on graph nodes allows prediction of new genes involved in mitotic chromosome condensation.

    PubMed

    Hériché, Jean-Karim; Lees, Jon G; Morilla, Ian; Walter, Thomas; Petrova, Boryana; Roberti, M Julia; Hossain, M Julius; Adler, Priit; Fernández, José M; Krallinger, Martin; Haering, Christian H; Vilo, Jaak; Valencia, Alfonso; Ranea, Juan A; Orengo, Christine; Ellenberg, Jan

    2014-08-15

    The advent of genome-wide RNA interference (RNAi)-based screens puts us in the position to identify genes for all functions human cells carry out. However, for many functions, assay complexity and cost make genome-scale knockdown experiments impossible. Methods to predict genes required for cell functions are therefore needed to focus RNAi screens from the whole genome on the most likely candidates. Although different bioinformatics tools for gene function prediction exist, they lack experimental validation and are therefore rarely used by experimentalists. To address this, we developed an effective computational gene selection strategy that represents public data about genes as graphs and then analyzes these graphs using kernels on graph nodes to predict functional relationships. To demonstrate its performance, we predicted human genes required for a poorly understood cellular function-mitotic chromosome condensation-and experimentally validated the top 100 candidates with a focused RNAi screen by automated microscopy. Quantitative analysis of the images demonstrated that the candidates were indeed strongly enriched in condensation genes, including the discovery of several new factors. By combining bioinformatics prediction with experimental validation, our study shows that kernels on graph nodes are powerful tools to integrate public biological data and predict genes involved in cellular functions of interest. PMID:24943848

  9. Integration of biological data by kernels on graph nodes allows prediction of new genes involved in mitotic chromosome condensation

    PubMed Central

    Hériché, Jean-Karim; Lees, Jon G.; Morilla, Ian; Walter, Thomas; Petrova, Boryana; Roberti, M. Julia; Hossain, M. Julius; Adler, Priit; Fernández, José M.; Krallinger, Martin; Haering, Christian H.; Vilo, Jaak; Valencia, Alfonso; Ranea, Juan A.; Orengo, Christine; Ellenberg, Jan

    2014-01-01

    The advent of genome-wide RNA interference (RNAi)–based screens puts us in the position to identify genes for all functions human cells carry out. However, for many functions, assay complexity and cost make genome-scale knockdown experiments impossible. Methods to predict genes required for cell functions are therefore needed to focus RNAi screens from the whole genome on the most likely candidates. Although different bioinformatics tools for gene function prediction exist, they lack experimental validation and are therefore rarely used by experimentalists. To address this, we developed an effective computational gene selection strategy that represents public data about genes as graphs and then analyzes these graphs using kernels on graph nodes to predict functional relationships. To demonstrate its performance, we predicted human genes required for a poorly understood cellular function—mitotic chromosome condensation—and experimentally validated the top 100 candidates with a focused RNAi screen by automated microscopy. Quantitative analysis of the images demonstrated that the candidates were indeed strongly enriched in condensation genes, including the discovery of several new factors. By combining bioinformatics prediction with experimental validation, our study shows that kernels on graph nodes are powerful tools to integrate public biological data and predict genes involved in cellular functions of interest. PMID:24943848

  10. Study of the Genes and Mechanism Involved in the Radioadaptive Response

    NASA Technical Reports Server (NTRS)

    Dasgupta, Pushan R.

    2009-01-01

    The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor

  11. A Fast Response Mechanism for Insulin Storage in Crystals May Involve a Novel Mode of Kink Generation

    NASA Astrophysics Data System (ADS)

    Vekilov, Peter

    2010-03-01

    Crystals, likely rhombohedral, of Zn-insulin hexamers form in the islets of Langerhans in the pancreases of many mammals. The suggested function of crystal formation is to protect the insulin from proteases and increase the degree of conversion of soluble proinsulin. To accomplish this, crystal growth should be fast and adaptable to rate fluctuations in the conversion reaction. Zn-insulin crystals grow layer-by-layer. Each layer spreads by the attachment of molecules to kinks located at the layers' edges, also called steps. The kinks are thought to be generated either by thermal fluctuations, as postulated by Gibbs, or by one-dimensional nucleation of new crystalline rows. The kink density determines the rate at which steps advance, and these two kink-generation mechanisms lead to weak near-linear responses of the growth rate to concentration variations. We demonstrate for the crystallization of Zn-insulin a novel mechanism of kink generation, whereby 2D clusters of several insulin molecules pre-formed on the terraces between steps associate to the steps. This mechanism results in several-fold higher kink density, faster rate of crystallization, and a high sensitivity of the kinetics to small increases of the solute concentration. If the found mechanism operates during insulin crystallization in vivo, it could be a part of the biological regulation of insulin production and function. For other crystallizing materials in biological and non-biological systems, this mechanism provides an understanding of the often seen non-linear acceleration of the kinetics.

  12. Molecular mechanisms of hormone-mediated Müllerian duct regression: involvement of beta-catenin.

    PubMed

    Allard, S; Adin, P; Gouédard, L; di Clemente, N; Josso, N; Orgebin-Crist, M C; Picard, J Y; Xavier, F

    2000-08-01

    Regression of the Müllerian duct in the male embryo is one unequivocal effect of anti-Müllerian hormone, a glycoprotein secreted by the Sertoli cells of the testis. This hormone induces ductal epithelial regression through a paracrine mechanism originating in periductal mesenchyme. To probe the mechanisms of action of anti-Müllerian hormone, we have studied the sequence of cellular and molecular events involved in duct regression. Studies were performed in male rat embryos and in transgenic mice overexpressing or lacking anti-Müllerian hormone, both in vivo and in vitro. Anti-Müllerian hormone causes regression of the cranial part of the Müllerian duct whereas it continues to grow caudally. Our work shows that this pattern of regression is correlated with a cranial to caudal gradient of anti-Müllerian hormone receptor protein, followed by a wave of apoptosis spreading along the Müllerian duct as its progresses caudally. Apoptosis is also induced by AMH in female Müllerian duct in vitro. Furthermore, apoptotic indexes are increased in Müllerian epithelium of transgenic mice of both sexes overexpressing the human anti-Müllerian hormone gene, exhibiting a positive correlation with serum hormone concentration. Inversely, apoptosis is reduced in male anti-Müllerian hormone-deficient mice. We also show that apoptosis is a decisive but not sufficient process, and that epitheliomesenchymal transformation is an important event of Müllerian regression. The most striking result of this study is that anti-Müllerian hormone action in peri-Müllerian mesenchyme leads in vivo and in vitro to an accumulation of cytoplasmic beta-catenin. The co-localization of beta-catenin with lymphoid enhancer factor 1 in the nucleus of peri-Müllerian mesenchymal cells, demonstrated in primary culture, suggests that overexpressed beta-catenin in association with lymphoid enhancer factor 1 may alter transcription of target genes and may lead to changes in mesenchymal gene expression

  13. Molecular mechanisms of tolerance in tardigrades: new perspectives for preservation and stabilization of biological material.

    PubMed

    Schill, Ralph O; Mali, Brahim; Dandekar, Thomas; Schnölzer, Martina; Reuter, Dirk; Frohme, Marcus

    2009-01-01

    Certain organisms found across a range of taxa, including bacteria, yeasts, plants and many invertebrates such as nematodes and tardigrades are able to survive almost complete loss of body water. The dry organisms may remain in this state, which is known as anhydrobiosis, for decades without apparent damage. When water again becomes available, they rapidly rehydrate and resume active life. Research in anhydrobiosis has focused mainly on sugar metabolism and stress proteins. Despite the discovery of various molecules which are involved in desiccation and water stress, knowledge of the regulatory network governing the stability of the cellular architecture and the metabolic machinery during dehydration is still fragmentary and not well understood. A combination of transcriptional, proteomic and metabolic approaches with bioinformatics tools can provide a better understanding of gene regulation that underlie the biological functions and physiology related to anhydrobiosis. The development of this concept will raise exciting possibilities and techniques for the preservation and stabilization of biological materials in the dry state.

  14. Temporal sequence learning, prediction, and control: a review of different models and their relation to biological mechanisms.

    PubMed

    Wörgötter, Florentin; Porr, Bernd

    2005-02-01

    In this review, we compare methods for temporal sequence learning (TSL) across the disciplines machine-control, classical conditioning, neuronal models for TSL as well as spike-timing-dependent plasticity (STDP). This review introduces the most influential models and focuses on two questions: To what degree are reward-based (e.g., TD learning) and correlation-based (Hebbian) learning related? and How do the different models correspond to possibly underlying biological mechanisms of synaptic plasticity? We first compare the different models in an open-loop condition, where behavioral feedback does not alter the learning. Here we observe that reward-based and correlation-based learning are indeed very similar. Machine control is then used to introduce the problem of closed-loop control (e.g., actor-critic architectures). Here the problem of evaluative (rewards) versus nonevaluative (correlations) feedback from the environment will be discussed, showing that both learning approaches are fundamentally different in the closed-loop condition. In trying to answer the second question, we compare neuronal versions of the different learning architectures to the anatomy of the involved brain structures (basal-ganglia, thalamus, and cortex) and the molecular biophysics of glutamatergic and dopaminergic synapses. Finally, we discuss the different algorithms used to model STDP and compare them to reward-based learning rules. Certain similarities are found in spite of the strongly different timescales. Here we focus on the biophysics of the different calcium-release mechanisms known to be involved in STDP. PMID:15720770

  15. Mechanism of biological denitrification inhibition: procyanidins induce an allosteric transition of the membrane-bound nitrate reductase through membrane alteration.

    PubMed

    Bardon, Clément; Poly, Franck; Piola, Florence; Pancton, Muriel; Comte, Gilles; Meiffren, Guillaume; Haichar, Feth el Zahar

    2016-05-01

    Recently, it has been shown that procyanidins from Fallopia spp. inhibit bacterial denitrification, a phenomenon called biological denitrification inhibition (BDI). However, the mechanisms involved in such a process remain unknown. Here, we investigate the mechanisms of BDI involving procyanidins, using the model strain Pseudomonas brassicacearum NFM 421. The aerobic and anaerobic (denitrification) respiration, cell permeability and cell viability of P. brassicacearum were determined as a function of procyanidin concentration. The effect of procyanidins on the bacterial membrane was observed using transmission electronic microscopy. Bacterial growth, denitrification, NO3- and NO2-reductase activity, and the expression of subunits of NO3- (encoded by the gene narG) and NO2-reductase (encoded by the gene nirS) under NO3 or NO2 were measured with and without procyanidins. Procyanidins inhibited the denitrification process without affecting aerobic respiration at low concentrations. Procyanidins also disturbed cell membranes without affecting cell viability. They specifically inhibited NO3- but not NO2-reductase.Pseudomonas brassicacearum responded to procyanidins by over-expression of the membrane-bound NO3-reductase subunit (encoded by the gene narG). Our results suggest that procyanidins can specifically inhibit membrane-bound NO3-reductase inducing enzymatic conformational changes through membrane disturbance and that P. brassicacearum responds by over-expressing membrane-bound NO3-reductase. Our results lead the way to a better understanding of BDI. PMID:26906096

  16. METHODS FOR USING 3-D ULTRASOUND SPECKLE TRACKING IN BIAXIAL MECHANICAL TESTING OF BIOLOGICAL TISSUE SAMPLES

    PubMed Central

    Yap, Choon Hwai; Park, Dae Woo; Dutta, Debaditya; Simon, Marc; Kim, Kang

    2014-01-01

    Being multilayered and anisotropic, biological tissues such as cardiac and arterial walls are structurally complex, making full assessment and understanding of their mechanical behavior challenging. Current standard mechanical testing uses surface markers to track tissue deformations and does not provide deformation data below the surface. In the study described here, we found that combining mechanical testing with 3-D ultrasound speckle tracking could overcome this limitation. Rat myocardium was tested with a biaxial tester and was concurrently scanned with high-frequency ultrasound in three dimensions. The strain energy function was computed from stresses and strains using an iterative non-linear curve-fitting algorithm. Because the strain energy function consists of terms for the base matrix and for embedded fibers, spatially varying fiber orientation was also computed by curve fitting. Using finite-element simulations, we first validated the accuracy of the non-linear curve-fitting algorithm. Next, we compared experimentally measured rat myocardium strain energy function values with those in the literature and found a matching order of magnitude. Finally, we retained samples after the experiments for fiber orientation quantification using histology and found that the results satisfactorily matched those computed in the experiments. We conclude that 3-D ultrasound speckle tracking can be a useful addition to traditional mechanical testing of biological tissues and may provide the benefit of enabling fiber orientation computation. PMID:25616585

  17. Mass balance to assess the efficiency of a mechanical-biological treatment

    SciTech Connect

    Araujo Morais, J. de; Ducom, G. Achour, F.; Rouez, M.; Bayard, R.

    2008-07-01

    Using mechanical-biological treatment of residual municipal solid waste, it is possible to significantly lower landfill volume and gas and leachate emissions. Moreover, the landfill characteristics are improved. The performance of the Mende (France) mechanical-biological treatment plant is assessed via mass balances coupled with manual sorting according to the MODECOM{sup TM} methodology and biochemical methane potential after 90 days of incubation. The site includes mechanical sorting operations, a rotary sequential bioreactor, controlled aerobic stabilisation corridors, maturation platforms, and a sanitary landfill site for waste disposal in separated cells. Results showed that several steps could be improved: after a first sieving step, about 12% of the potentially biodegradable matter is landfilled directly without any treatment; mechanical disintegration of papers and cardboards in the rotary sequential bioreactor is insufficient and leads to a high proportion of papers and cardboards being landfilled without further treatment. Two fine fractions go through stabilisation and maturation steps. At the end of the maturation step, about 54% of the potentially biodegradable matter is degraded. The biochemical methane potential after 90 days of incubation is reduced by 81% for one of the two fine fractions and reduced by 88% for the other one. Considering the whole plant, there is a reduction of nearly 20% DM of the entering residual municipal solid waste.

  18. Mass balance to assess the efficiency of a mechanical-biological treatment.

    PubMed

    de Araújo Morais, J; Ducom, G; Achour, F; Rouez, M; Bayard, R

    2008-01-01

    Using mechanical-biological treatment of residual municipal solid waste, it is possible to significantly lower landfill volume and gas and leachate emissions. Moreover, the landfill characteristics are improved. The performance of the Mende (France) mechanical-biological treatment plant is assessed via mass balances coupled with manual sorting according to the MODECOM methodology and biochemical methane potential after 90 days of incubation. The site includes mechanical sorting operations, a rotary sequential bioreactor, controlled aerobic stabilisation corridors, maturation platforms, and a sanitary landfill site for waste disposal in separated cells. Results showed that several steps could be improved: after a first sieving step, about 12% of the potentially biodegradable matter is landfilled directly without any treatment; mechanical disintegration of papers and cardboards in the rotary sequential bioreactor is insufficient and leads to a high proportion of papers and cardboards being landfilled without further treatment. Two fine fractions go through stabilisation and maturation steps. At the end of the maturation step, about 54% of the potentially biodegradable matter is degraded. The biochemical methane potential after 90 days of incubation is reduced by 81% for one of the two fine fractions and reduced by 88% for the other one. Considering the whole plant, there is a reduction of nearly 20% DM of the entering residual municipal solid waste.

  19. Chitosan fibers with improved biological and mechanical properties for tissue engineering applications.

    PubMed

    Albanna, Mohammad Z; Bou-Akl, Therese H; Blowytsky, Oksana; Walters, Henry L; Matthew, Howard W T

    2013-04-01

    The low mechanical properties of hydrogel materials such as chitosan hinder their broad utility for tissue engineering applications. Previous research efforts improved the mechanical properties of chitosan fiber through chemical and physical modifications; however, unfavorable toxicity effects on cells were reported. In this paper, we report the preparation of chitosan fibers with improved mechanical and biocompatibility properties. The structure-property relationships of extruded chitosan fibers were explored by varying acetic acid (AA) concentration, ammonia concentration, annealing temperature and degree of heparin crosslinking. Results showed that optimizing AA concentration to 2vol% improved fiber strength and stiffness by 2-fold. Extruding chitosan solution into 25wt% of ammonia solution reduced fiber diameters and improved fiber strength by 2-fold and stiffness by 3-fold, due to an increase in crystallinity as confirmed by XRD. Fiber annealing further reduced fiber diameter and improved fiber strength and stiffness as temperature increased. Chitosan fibers crosslinked with heparin had increased diameter but lower strength and stiffness properties and higher breaking strain values. When individual parameters were combined, further improvement in fiber mechanical properties was achieved. All mechanically improved fibers and heparin crosslinked fibers promoted valvular interstitial cells (VIC) attachment and growth over 10 day cultures. Our results demonstrate the ability to substantially improve the mechanical properties of chitosan fibers without adversely affecting their biological properties. The investigated treatments offer numerous advantages over previous physical/chemical modifications and thus are expected to expand the utility of chitosan fibers with tunable mechanical properties in various tissue engineering applications.

  20. Involvement of histaminergic receptor mechanisms in the stimulation of NT-3 synthesis in astrocytes.

    PubMed

    Jurič, Damijana M; Mele, Tina; Carman-Kržan, Marija

    2011-06-01

    Neurotrophin-3 (NT-3) is produced by astrocytes, in addition to neurons, and monoamine neurotransmitters play a role in controlling NT-3 synthesis. The impact of histamine (HA) on the regulation of NT-3 synthesis in cultured astrocytes has not been studied. We evaluated the involvement of histamine receptors and intracellular mechanisms in the regulation of NT-3 production by HA. Real-time PCR was performed to examine the expression of all known histamine receptor subtypes in cultured rat cortical astrocytes. Pharmacological tools, selective for the H₁, H₂ and H₃ receptors and intracellular systems, were utilized to confirm functional properties of HA receptors in histaminergic up-regulation of astrocytic NT-3 synthesis. HA potently and transiently elevated NT-3 expression and protein levels by more than twofold. In addition to H₁ and H₂ receptors, cultured astrocytes also express H₃ receptors, which activate G(i/o) proteins to inhibit adenylyl cyclase and modulate MAP kinase activity. Histaminergic stimulation was partly inhibited by selective H₁, H₂, and H₃ antagonists whereas selective H₁, H₂, and H₃ agonists or mediators of the intracellular histaminergic pathways increased NT-3 levels. Inhibitors of PKA, PKC, and CaMK II significantly reduced the HA-induced increase in NT-3 cellular levels whereas the MAP kinase cascade inhibitor completely blocked the stimulatory action of HA and all selective agonists. In conclusion, the synthesis of astrocytic NT-3 stimulated by HA is a receptor-mediated process, which is fine-tuned via subtle modulation of parallel histaminergic H₁, H₂, and H₃ pathways that converge at the level of MAP kinase activity. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.

  1. Memory-improving actions of glucose: involvement of a central cholinergic muscarinic mechanism.

    PubMed

    Kopf, S R; Baratti, C M

    1994-11-01

    Post-training intraperitoneal administration of alpha-D[+]-glucose (10-300 mg/kg) facilitated 24-h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. Glucose did not increase the retention latencies of mice that had not received a footshock during training. The effect of glucose (30 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by glucose (30 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to glucose treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training glucose on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and glucose (10 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of glucose (10 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the memory facilitation induced by post-training administration of glucose could result from an enhancement of brain acetylcholine synthesis and/or its release that, in turn, might modulate the activity of muscarinic cholinergic mechanisms that are critically involved in memory storage. PMID:7857246

  2. Memory-improving actions of glucose: involvement of a central cholinergic muscarinic mechanism.

    PubMed

    Kopf, S R; Baratti, C M

    1994-11-01

    Post-training intraperitoneal administration of alpha-D[+]-glucose (10-300 mg/kg) facilitated 24-h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. Glucose did not increase the retention latencies of mice that had not received a footshock during training. The effect of glucose (30 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by glucose (30 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to glucose treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training glucose on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and glucose (10 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of glucose (10 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the memory facilitation induced by post-training administration of glucose could result from an enhancement of brain acetylcholine synthesis and/or its release that, in turn, might modulate the activity of muscarinic cholinergic mechanisms that are critically involved in memory storage.

  3. Particle Disease: A Current Review of the Biological Mechanisms in Periprosthetic Osteolysis After Hip Arthroplasty

    PubMed Central

    Sukur, Erhan; Akman, Yunus Emre; Ozturkmen, Yusuf; Kucukdurmaz, Fatih

    2016-01-01

    Background: Inflammatory responses to wear debris cause osteolysis that leads to aseptic prosthesis loosening and hip arthroplasty failure. Although osteolysis is usually associated with aseptic loosening, it is rarely seen around stable implants. Aseptic implant loosening is a simple radiologic phenomenon, but a complex immunological process. Particulate debris produced by implants most commonly causes osteolysis, and this is called particle-associated periprosthetic osteolysis (PPO). Objective: The objective of this review is to outline the features of particle-associated periprosthetic osteolysis to allow the physician to recognise this condition and commence early treatment, thereby optimizing patient outcome. Methods: A thorough literature search was performed using available databases, including Pubmed, to cover important research published covering particle-associated PPO. Results: Although osteolysis causes bone resorption, clinical, animal, and in vitro studies of particle bioreactivity suggest that particle-associated PPO represents the culmination of several biological reactions of many cell types, rather than being caused solely by the osteoclasts. The biological activity is highly dependent on the characteristics and quantity of the wear particles. Conclusion: Despite advances in total hip arthroplasty (THA), particle-associated PPO and aseptic loosening continue to be major factors that affect prosthetic joint longevity. Biomarkers could be exploited as easy and objective diagnostic and prognostic targets that would enable testing for osteolysis after THA. Further research is needed to identify new biomarkers in PPO. A comprehensive understanding of the underlying biological mechanisms is crucial for developing new therapeutic interventions to reverse or suppress biological responses to wear particles. PMID:27499822

  4. Life Cycle Assessment of mechanical biological pre-treatment of Municipal Solid Waste: a case study.

    PubMed

    Beylot, Antoine; Vaxelaire, Stéphane; Zdanevitch, Isabelle; Auvinet, Nicolas; Villeneuve, Jacques

    2015-05-01

    The environmental performance of mechanical biological pre-treatment (MBT) of Municipal Solid Waste is quantified using Life Cycle Assessment (LCA), considering one of the 57 French plants currently in operation as a case study. The inventory is mostly based on plant-specific data, extrapolated from on-site measurements regarding mechanical and biological operations (including anaerobic digestion and composting of digestate). The combined treatment of 46,929 tonnes of residual Municipal Solid Waste and 12,158 tonnes of source-sorted biowaste (as treated in 2010 at the plant) generates 24,550 tonnes CO2-eq as an impact on climate change, 69,943kg SO2-eq on terrestrial acidification and 19,929kg NMVOC-eq on photochemical oxidant formation, in a life-cycle perspective. On the contrary MBT induces environmental benefits in terms of fossil resource depletion, human toxicity (carcinogenic) and ecotoxicity. The results firstly highlight the relatively large contribution of some pollutants, such as CH4, emitted at the plant and yet sometimes neglected in the LCA of waste MBT. Moreover this study identifies 4 plant-specific operation conditions which drive the environmental impact potentials induced by MBT: the conditions of degradation of the fermentable fraction, the collection of gaseous flows emitted from biological operations, the abatement of collected pollutants and NOx emissions from biogas combustion. Finally the results underline the relatively large influence of the operations downstream the plant (in particular residuals incineration) on the environmental performance of waste MBT.

  5. Dehydration effect on the mechanical behaviour of biological soft tissues: observations on kidney tissues.

    PubMed

    Nicolle, S; Palierne, J-F

    2010-11-01

    This paper deals with the effects of dehydration on the mechanical properties of biological soft tissues and with the validity of methods used in previous works such as a coat of petroleum jelly or silicon oil to minimise the drying of the tissue during mechanical testing. We find that the samples get stiffer as they dry but that this phenomenon is wholly reversible upon re-hydrating the samples. A bath of saline solution is the best hydration method but a coat of low-viscosity silicon oil around the free edge of the sample also proves to be a good anti-drying method. However, using petroleum jelly to prevent tissue dehydration should be banned because the jelly largely contributes to the measured mechanical moduli.

  6. Flexible mechanisms: the diverse roles of biological springs in vertebrate movement

    PubMed Central

    Roberts, Thomas J.; Azizi, Emanuel

    2011-01-01

    The muscles that power vertebrate locomotion are associated with springy tissues, both within muscle and in connective tissue elements such as tendons. These springs share in common the same simple action: they stretch and store elastic strain energy when force is applied to them and recoil to release energy when force decays. Although this elastic action is simple, it serves a diverse set of functions, including metabolic energy conservation, amplification of muscle power output, attenuation of muscle power input, and rapid mechanical feedback that may aid in stability. In recent years, our understanding of the mechanisms and importance of biological springs in locomotion has advanced significantly, and it has been demonstrated that elastic mechanisms are essential for the effective function of the muscle motors that power movement. Here, we review some recent advances in our understanding of elastic mechanisms, with an emphasis on two proposed organizing principles. First, we review the evidence that the various functions of biological springs allow the locomotor system to operate beyond the bounds of intrinsic muscle properties, including metabolic and mechanical characteristics, as well as motor control processes. Second, we propose that an energy-based framework is useful for interpreting the diverse functions of series-elastic springs. In this framework, the direction and timing of the flow of energy between the body, the elastic element and the contracting muscle determine the function served by the elastic mechanism (e.g. energy conservation vs power amplification). We also review recent work demonstrating that structures such as tendons remodel more actively and behave more dynamically than previously assumed. PMID:21228194

  7. Flexible mechanisms: the diverse roles of biological springs in vertebrate movement.

    PubMed

    Roberts, Thomas J; Azizi, Emanuel

    2011-02-01

    The muscles that power vertebrate locomotion are associated with springy tissues, both within muscle and in connective tissue elements such as tendons. These springs share in common the same simple action: they stretch and store elastic strain energy when force is applied to them and recoil to release energy when force decays. Although this elastic action is simple, it serves a diverse set of functions, including metabolic energy conservation, amplification of muscle power output, attenuation of muscle power input, and rapid mechanical feedback that may aid in stability. In recent years, our understanding of the mechanisms and importance of biological springs in locomotion has advanced significantly, and it has been demonstrated that elastic mechanisms are essential for the effective function of the muscle motors that power movement. Here, we review some recent advances in our understanding of elastic mechanisms, with an emphasis on two proposed organizing principles. First, we review the evidence that the various functions of biological springs allow the locomotor system to operate beyond the bounds of intrinsic muscle properties, including metabolic and mechanical characteristics, as well as motor control processes. Second, we propose that an energy-based framework is useful for interpreting the diverse functions of series-elastic springs. In this framework, the direction and timing of the flow of energy between the body, the elastic element and the contracting muscle determine the function served by the elastic mechanism (e.g. energy conservation vs power amplification). We also review recent work demonstrating that structures such as tendons remodel more actively and behave more dynamically than previously assumed.

  8. A computational functional genomics based self-limiting self-concentration mechanism of cell specialization as a biological role of jumping genes.

    PubMed

    Lötsch, Jörn; Ultsch, Alfred

    2016-01-01

    Specialization is ubiquitous in biological systems and its manifold mechanisms are active research topics. Although clearly adaptive, the way in which specialization of cells is realized remains incompletely understood as it requires the reshaping of a cell's genome to favor particular biological processes in the competition on a cell's functional capacity. Here, a self-specialization mechanism is identified as a possible biological role of jumping genes, in particular LINE-1 retrotransposition. The mechanism is self-limiting and consistent with its evolutionary preservation despite its likely gene-breaking effects. The scenario we studied was the need for a cell to process a longer exposition to an extraordinary situation, for example continuous exposure to the nociceptive input or the intake of addictive drugs. Both situations may evolve toward chronification. The mechanism involves competition within a gene set in which a subset of genes cooperating in particular biological processes. The subset carries a piece of information, consisting of the LINE-1 sequence, about the destruction of their functional competitor genes which are not involved in that process. During gene transcription, an active copy of LINE-1 is co-transcribed. At a certain low probability, a subsequently transcribed and thus actually exposed gene can be rendered nonfunctional by LINE-1 retrotransposition in a relevant gene part. As retrotransposition needs time it is unlikely that LINE-1 retrotranspose into its own carrier gene. This reshapes the cell genome toward self-specializing of those biological processes that are carried out with a high number of LINE-1 containing genes. Self-termination of the mechanism is achieved by allowing LINE-1 to also occasionally jump into the coding region of itself, thus destroying the information about competitor destruction by successively decreasing the number of LINE-1 until the mechanism ceases. Employing a computational functional genomics approach, we

  9. Morphological and molecular characterisation of fungal populations possibly involved in the biological alteration of stones in historical buildings.

    PubMed

    Scrano, L; Boccone, L Fraddosio; Bufo, S A; Carrieri, R; Lahoz, E; Crescenzi, A

    2012-01-01

    The deterioration process of historical building is progressive and irreversible, and the timing and mode of impact are different depending on the characteristics of building materials used, local microclimate, air pollution, presence of specific flora and fauna. The chemical and microbiological characterisation of building materials is mandatory in preventing and eventually recovering degradation effects. Ideally, the analysis of structural stones should be complete, efficient, rapid, and non destructive when dealing with a precious or unique construction. The investigation has been performed on a private historical building made using calcarenite stones and sited between the archaeological site of Lavello, a little town located in the Basilicata Region (South Italy), and the industrial area surrounding this town. To study in progress the degradation of stone materials, a new building sample (ca. 1 m3) was constructed by using the same stones (33 x 15cm), collected from a local quarry. The intact calcarenite stone was characterised by using different methods of surface analysis (XRD, XPS, SEM), and exposed to outdoor conditions. The analyses of the stone material were repeated after three and six months to early evaluate the progression of alterations and the forward modifications of calcarenite structure. After only three months of the new building sample exposure, the adopted analytical methods were able to provide a series of data, which allowed the assessment of the incipient modification of the stone surfaces. The degradation appeared worsened performing the same observations on sixth month replicates, suggesting that environmental conditions modified the structure and the compactness of stones and favoured the biological colonization of surfaces especially in the South-East direction of prevailing winds. For this reason the presence of fungi on the stones' surface was investigated and a morphological and molecular characterization of sampled fungi was

  10. Involvement of lignin and hormones in the response of woody poplar taproots to mechanical stress.

    PubMed

    Trupiano, Dalila; Di Iorio, Antonino; Montagnoli, Antonio; Lasserre, Bruno; Rocco, Mariapina; Grosso, Alessandro; Scaloni, Andrea; Marra, Mauro; Chiatante, Donato; Scippa, Gabriella S

    2012-09-01

    Mechanical stress is a widespread condition caused by numerous environmental factors that severely affect plant stability. In response to mechanical stress, plants have evolved complex response pathways able to detect mechanical perturbations and inducing a suite of modifications in order to improve anchorage. The response of woody roots to mechanical stresses has been studied mainly at the morphological and biomechanical level, whereas investigations on the factors triggering these important alterations are still at the initial stage. Populus has been widely used to study the response of stem to different mechanical stresses and, since it has the first forest tree genome to be decoded, represents a model woody plant for addressing questions on the mechanisms controlling adaptation of woody roots to changing environments. In this study, a morphological and physiological analysis was used to investigate factors controlling modifications in Populus nigra woody taproots subjected to mechanical stress. An experimental model analyzing spatial and temporal mechanical force distribution along the woody taproot axis enabled us to compare the events occurring in its above-, central- and below-bending sectors. Different morphogenetic responses and local variations of lignin and plant hormones content have been observed, and a relation with the distribution of the mechanical forces along the stressed woody taproots is hypothesized. We investigated the differences of the response to mechanical stress induction during the time; in this regard, we present data referring to the effect of mechanical stress on plant transition from its condition of winter dormancy to that of full vegetative activity.

  11. Mechanical and Biological Interactions of Implants with the Brain and Their Impact on Implant Design

    PubMed Central

    Prodanov, Dimiter; Delbeke, Jean

    2016-01-01

    Neural prostheses have already a long history and yet the cochlear implant remains the only success story about a longterm sensory function restoration. On the other hand, neural implants for deep brain stimulation are gaining acceptance for variety of disorders including Parkinsons disease and obsessive-compulsive disorder. It is anticipated that the progress in the field has been hampered by a combination of technological and biological factors, such as the limited understanding of the longterm behavior of implants, unreliability of devices, biocompatibility of the implants among others. While the field's understanding of the cell biology of interactions at the biotic-abiotic interface has improved, relatively little attention has been paid on the mechanical factors (stress, strain), and hence on the geometry that can modulate it. This focused review summarizes the recent progress in the understanding of the mechanisms of mechanical interaction between the implants and the brain. The review gives an overview of the factors by which the implants interact acutely and chronically with the tissue: blood-brain barrier (BBB) breach, vascular damage, micromotions, diffusion etc. We propose some design constraints to be considered in future studies. Aspects of the chronic cell-implant interaction will be discussed in view of the chronic local inflammation and the ways of modulating it. PMID:26903786

  12. Microwave processed nanocrystalline hydroxyapatite: Simultaneous enhancement of mechanical and biological properties

    PubMed Central

    Bose, Susmita; Dasgupta, Sudip; Tarafder, Solaiman; Bandyopadhyay, Amit

    2010-01-01

    Despite excellent bioactivity of hydroxyapatite (HA) ceramics, poor mechanical strength has limited its applications primarily to coatings and other non-load bearing areas as bone grafts. Using synthesized HA nanopowder, dense compacts with grain sizes in nanometers to micrometers were processed via microwave sintering between 1000 and 1150 °C for 20 minutes. Here we demonstrate that mechanical properties, such as compressive strength, hardness and indentation fracture toughness of HA compacts increased with a decrease in grain size. HA with 168± 86 nm grain size showed the highest compressive strength of 395±42 MPa, hardness of 8.4±0.4 GPa and indentation fracture toughness of 1.9 ±0.2 MPam1/2. To study the in vitro biological properties, HA compacts with grain size between 168 nm and 1.16 µm were assessed for in vitro bone cell-materials interactions with human osteoblast cell line. Vinculin protein expression for cell attachment and bone cell proliferation using MTT assay showed surfaces with finer grains provided better bone cell-materials interactions than coarse grained samples. Our results indicate simultaneous improvements in mechanical and biological properties in microwave sintered HA compacts with nanoscale grain size. PMID:20230922

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

    PubMed

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

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning.

  14. Features of Knowledge Building in Biology: Understanding Undergraduate Students’ Ideas about Molecular Mechanisms

    PubMed Central

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

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. PMID:26931398

  15. Newt tail regeneration: a model for gravity-dependent morphogenesis and clues to the molecular mechanisms involved.

    NASA Astrophysics Data System (ADS)

    Radugina, Elena A.; Almeida, Eduardo; Grigoryan, Eleonora

    factors and are expressed during development, we hypothesized they may play a role newt tail regenerative morphogenesis under altered g-levels. Specifically there is increasing evidence for HSPs expression changes as a result of hyper-and microgravity. HSPs are also expressed throughout regeneration, rather than just after surgery. To test this hypothesis we performed heat shock on intact and regenerating newts and collected tail tissues. In these experiments we observed that some tails had uplifted tips while others mimicked hook-like regenerates at 1g or 2g. These findings suggest that heat shock, and HSPs induction, may be involved in the mechanism responsible for gravity effects on morphogenesis, or at least interact with them. Current work underway is focused on analyzing the expression of mRNA and localization of proteins for two members of the group, Hsp70 and Hsp90. In summary, we developed and characterized a new practical animal model in which gravity mechanostimulation at 1g, versus unloading in aquaria, causes prominent effects on newt tail regenerative morphogenesis. This model can be achieved without the use of a centrifuge, significantly simplifying its research applications. Initial results using this model suggest that induction of HSPs may be involved in gravity regulation of newt tail regenerative morphogenesis. Further research based on this simple model may help to unravel mechanisms of gravity influence relevant not only to newt tail regeneration, but also to a broad range of other biological processes in amphibian models.

  16. Mechanisms involved in the psychological distress of Black Caribbeans in the United States

    NASA Astrophysics Data System (ADS)

    Govia, Ishtar O.

    The mental health of ethnic minorities in the United States is of urgent concern. The accelerated growth of groups of ethnic minorities and immigrants in the United States and the stressors to which they are exposed, implores academic researchers to investigate more deeply health disparities and the factors that exacerbate or minimize such inequalities. This dissertation attended to that concern. It used data from the National Survey of American Life (NSAL), the first survey with a national representative sample of Black Caribbeans, to explore mechanisms that involved in the psychological distress of Black Caribbeans in the United States. In a series of three studies, the dissertation investigated the role and consequence of (1) chronic discrimination, immigration factors, and closeness to ethnic and racial groups; (2) personal control and social support; and (3) family relations and social roles in the psychological distress of Black Caribbeans. Study 1 examined how the associations between discrimination and psychological distress were buffered or exacerbated by closeness to ethnic group and closeness to racial group. It also examined how these associations differed depending on immigration factors. Results indicated that the buffering or exacerbating effect of ethnic and racial group closeness varied according to the type of discrimination (subtle or severe) and were more pronounced among those born in the United States. Using the stress process framework, Study 2 tested moderation and mediation models of the effects of social support and personal control in the association between discrimination and distress. Results from a series of analyses on 579 respondents suggested that personal control served as a mediator in this relationship and that emotional support exerted a direct distress deterring function. Study 3 investigated sex differences in the associations between social roles, intergenerational family relationship perceptions and distress. Results

  17. The impact of environmental stress on male reproductive development in plants: biological processes and molecular mechanisms

    PubMed Central

    de Storme, Nico; Geelen, Danny

    2014-01-01

    In plants, male reproductive development is extremely sensitive to adverse climatic environments and (a)biotic stress. Upon exposure to stress, male gametophytic organs often show morphological, structural and metabolic alterations that typically lead to meiotic defects or premature spore abortion and male reproductive sterility. Depending on the type of stress involved (e.g. heat, cold, drought) and the duration of stress exposure, the underlying cellular defect is highly variable and either involves cytoskeletal alterations, tapetal irregularities, altered sugar utilization, aberrations in auxin metabolism, accumulation of reactive oxygen species (ROS; oxidative stress) or the ectopic induction of programmed cell death (PCD). In this review, we present the critically stress-sensitive stages of male sporogenesis (meiosis) and male gametogenesis (microspore development), and discuss the corresponding biological processes involved and the resulting alterations in male reproduction. In addition, this review also provides insights into the molecular and/or hormonal regulation of the environmental stress sensitivity of male reproduction and outlines putative interaction(s) between the different processes involved. PMID:23731015

  18. The impact of environmental stress on male reproductive development in plants: biological processes and molecular mechanisms.

    PubMed

    De Storme, Nico; Geelen, Danny

    2014-01-01

    In plants, male reproductive development is extremely sensitive to adverse climatic environments and (a)biotic stress. Upon exposure to stress, male gametophytic organs often show morphological, structural and metabolic alterations that typically lead to meiotic defects or premature spore abortion and male reproductive sterility. Depending on the type of stress involved (e.g. heat, cold, drought) and the duration of stress exposure, the underlying cellular defect is highly variable and either involves cytoskeletal alterations, tapetal irregularities, altered sugar utilization, aberrations in auxin metabolism, accumulation of reactive oxygen species (ROS; oxidative stress) or the ectopic induction of programmed cell death (PCD). In this review, we present the critically stress-sensitive stages of male sporogenesis (meiosis) and male gametogenesis (microspore development), and discuss the corresponding biological processes involved and the resulting alterations in male reproduction. In addition, this review also provides insights into the molecular and/or hormonal regulation of the environmental stress sensitivity of male reproduction and outlines putative interaction(s) between the different processes involved.

  19. Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments

    PubMed Central

    de Mattos, Bruno Rafael Ramos; Garcia, Maellin Pereira Gracindo; Nogueira, Julia Bier; Paiatto, Lisiery Negrini; Albuquerque, Cassia Galdino; Souza, Caique Lopes; Fernandes, Luís Gustavo Romani; Tamashiro, Wirla Maria da Silva Cunha; Simioni, Patricia Ucelli

    2015-01-01

    Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn's disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn's disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules. PMID:26339135

  20. Another look at the mechanism involving trimeric dUTPases in Staphylococcus aureus pathogenicity island induction involves novel players in the party

    PubMed Central

    Maiques, Elisa; Quiles-Puchalt, Nuria; Donderis, Jorge; Ciges-Tomas, J. Rafael; Alite, Christian; Bowring, Janine Z.; Humphrey, Suzanne; Penadés, José R.; Marina, Alberto

    2016-01-01

    We have recently proposed that the trimeric staphylococcal phage encoded dUTPases (Duts) are signaling molecules that act analogously to eukaryotic G-proteins, using dUTP as a second messenger. To perform this regulatory role, the Duts require their characteristic extra motif VI, present in all the staphylococcal phage coded trimeric Duts, as well as the strongly conserved Dut motif V. Recently, however, an alternative model involving Duts in the transfer of the staphylococcal islands (SaPIs) has been suggested, questioning the implication of motifs V and VI. Here, using state-of the-art techniques, we have revisited the proposed models. Our results confirm that the mechanism by which the Duts derepress the SaPI cycle depends on dUTP and involves both motifs V and VI, as we have previously proposed. Surprisingly, the conserved Dut motif IV is also implicated in SaPI derepression. However, and in agreement with the proposed alternative model, the dUTP inhibits rather than inducing the process, as we had initially proposed. In summary, our results clarify, validate and establish the mechanism by which the Duts perform regulatory functions. PMID:27112567

  1. Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation.

    PubMed

    Finnerty, Justin John; Peyser, Alexander; Carloni, Paolo

    2015-01-01

    Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores. PMID:26460827

  2. Developments in sclerostin biology: regulation of gene expression, mechanisms of action, and physiological functions.

    PubMed

    Weivoda, Megan M; Oursler, Merry Jo

    2014-03-01

    The SOST gene, which encodes the protein sclerostin, was identified through genetic linkage analysis of sclerosteosis and van Buchem's disease patients. Sclerostin is a secreted glycoprotein that binds to the low-density lipoprotein receptor-related proteins 4, 5, and 6 to inhibit Wnt signaling. Since the initial discovery of sclerostin, much understanding has been gained into the role of this protein in the regulation of skeletal biology. In this article, we discuss the latest findings in the regulation of SOST expression, sclerostin mechanisms of action, and the potential utility of targeting sclerostin in conditions of low bone mass.

  3. Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation

    PubMed Central

    Finnerty, Justin John

    2015-01-01

    Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores. PMID:26460827

  4. [The influences of anterior disc displacement on oral mandibular function and morphology and their biological mechanisms].

    PubMed

    Xia, Wendi; Fu, Kiayuan

    2016-03-01

    Anterior disc displacement is a common subtype seen in temporomandibular disorders (TMD) patients. It may cause mandibular movement disorders, such as clicking of joint, intermittent closed lock, limitation of mouth opening, etc. These disorders may affect the life qualities of patients. Anterior disc displacement may also cause mandibular malformations, especially among adolescents, which may affect the growth of condyle, therefore may have a correlation with mandibular retrusion or mandibular deviation when grown up. This paper going to review the influences of anterior disc displacement on oral mandibular function and morphology and their biological mechanisms. PMID:26980658

  5. [The influences of anterior disc displacement on oral mandibular function and morphology and their biological mechanisms].

    PubMed

    Xia, Wendi; Fu, Kiayuan

    2016-03-01

    Anterior disc displacement is a common subtype seen in temporomandibular disorders (TMD) patients. It may cause mandibular movement disorders, such as clicking of joint, intermittent closed lock, limitation of mouth opening, etc. These disorders may affect the life qualities of patients. Anterior disc displacement may also cause mandibular malformations, especially among adolescents, which may affect the growth of condyle, therefore may have a correlation with mandibular retrusion or mandibular deviation when grown up. This paper going to review the influences of anterior disc displacement on oral mandibular function and morphology and their biological mechanisms.

  6. Involvement of mast cells and proteinase-activated receptor 2 in oxaliplatin-induced mechanical allodynia in mice.

    PubMed

    Sakamoto, Ayumi; Andoh, Tsugunobu; Kuraishi, Yasushi

    2016-03-01

    The chemotherapeutic agent oxaliplatin induces neuropathic pain, a dose-limiting side effect, but the underlying mechanisms are not fully understood. Here, we show the potential involvement of cutaneous mast cells in oxaliplatin-induced mechanical allodynia in mice. A single intraperitoneal injection of oxaliplatin induced mechanical allodynia, which peaked on day 10 after injection. Oxaliplatin-induced mechanical allodynia was almost completely prevented by congenital mast cell deficiency. The numbers of total and degranulated mast cells was significantly increased in the skin after oxaliplatin administration. Repetitive topical application of the mast cell stabilizer azelastine hydrochloride inhibited mechanical allodynia and the degranulation of mast cells without affecting the number of mast cells in oxaliplatin-treated mice. The serine protease inhibitor camostat mesilate and the proteinase-activated receptor 2 (PAR2) antagonist FSLLRY-NH2 significantly inhibited oxaliplatin-induced mechanical allodynia. However, it was not inhibited by the H1 histamine receptor antagonist terfenadine. Single oxaliplatin administration increased the activity of cutaneous serine proteases, which was attenuated by camostat and mast cell deficiency. Depletion of the capsaicin-sensitive primary afferents by neonatal capsaicin treatment almost completely prevented oxaliplatin-induced mechanical allodynia, the increase in the number of mast cells, and the activity of cutaneous serine proteases. These results suggest that serine protease(s) released from mast cells and PAR2 are involved in oxaliplatin-induced mechanical allodynia. Therefore, oxaliplatin may indirectly affect the functions of mast cells through its action on capsaicin-sensitive primary afferents.

  7. Involvement of mast cells and proteinase-activated receptor 2 in oxaliplatin-induced mechanical allodynia in mice.

    PubMed

    Sakamoto, Ayumi; Andoh, Tsugunobu; Kuraishi, Yasushi

    2016-03-01

    The chemotherapeutic agent oxaliplatin induces neuropathic pain, a dose-limiting side effect, but the underlying mechanisms are not fully understood. Here, we show the potential involvement of cutaneous mast cells in oxaliplatin-induced mechanical allodynia in mice. A single intraperitoneal injection of oxaliplatin induced mechanical allodynia, which peaked on day 10 after injection. Oxaliplatin-induced mechanical allodynia was almost completely prevented by congenital mast cell deficiency. The numbers of total and degranulated mast cells was significantly increased in the skin after oxaliplatin administration. Repetitive topical application of the mast cell stabilizer azelastine hydrochloride inhibited mechanical allodynia and the degranulation of mast cells without affecting the number of mast cells in oxaliplatin-treated mice. The serine protease inhibitor camostat mesilate and the proteinase-activated receptor 2 (PAR2) antagonist FSLLRY-NH2 significantly inhibited oxaliplatin-induced mechanical allodynia. However, it was not inhibited by the H1 histamine receptor antagonist terfenadine. Single oxaliplatin administration increased the activity of cutaneous serine proteases, which was attenuated by camostat and mast cell deficiency. Depletion of the capsaicin-sensitive primary afferents by neonatal capsaicin treatment almost completely prevented oxaliplatin-induced mechanical allodynia, the increase in the number of mast cells, and the activity of cutaneous serine proteases. These results suggest that serine protease(s) released from mast cells and PAR2 are involved in oxaliplatin-induced mechanical allodynia. Therefore, oxaliplatin may indirectly affect the functions of mast cells through its action on capsaicin-sensitive primary afferents. PMID:26804251

  8. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research

    PubMed Central

    Leon, Benjamin M; Maddox, Thomas M

    2015-01-01

    The incidence of diabetes mellitus (DM) continues to rise and has quickly become one of the most prevalent and costly chronic diseases worldwide. A close link exists between DM and cardiovascular disease (CVD), which is the most prevalent cause of morbidity and mortality in diabetic patients. Cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia are common in patients with DM, placing them at increased risk for cardiac events. In addition, many studies have found biological mechanisms associated with DM that independently increase the risk of CVD in diabetic patients. Therefore, targeting CV risk factors in patients with DM is critical to minimize the long-term CV complications of the disease. This paper summarizes the relationship between diabetes and CVD, examines possible mechanisms of disease progression, discusses current treatment recommendations, and outlines future research directions. PMID:26468341

  9. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research.

    PubMed

    Leon, Benjamin M; Maddox, Thomas M

    2015-10-10

    The incidence of diabetes mellitus (DM) continues to rise and has quickly become one of the most prevalent and costly chronic diseases worldwide. A close link exists between DM and cardiovascular disease (CVD), which is the most prevalent cause of morbidity and mortality in diabetic patients. Cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia are common in patients with DM, placing them at increased risk for cardiac events. In addition, many studies have found biological mechanisms associated with DM that independently increase the risk of CVD in diabetic patients. Therefore, targeting CV risk factors in patients with DM is critical to minimize the long-term CV complications of the disease. This paper summarizes the relationship between diabetes and CVD, examines possible mechanisms of disease progression, discusses current treatment recommendations, and outlines future research directions. PMID:26468341

  10. TRIENNIAL LACTATION SYMPOSIUM: Systems biology of regulatory mechanisms of nutrient metabolism in lactation.

    PubMed

    McNamara, J P

    2015-12-01

    A major role of the dairy cow is to convert low-quality plant materials into high-quality protein and other nutrients for humans. We must select and manage cows with the goal of having animals of the greatest efficiency matched to their environment. We have increased efficiency tremendously over the years, yet the variation in productive and reproductive efficiency among animals is still large. In part, this is because of a lack of full integration of genetic, nutritional, and reproductive biology into management decisions. However, integration across these disciplines is increasing as the biological research findings show specific control points at which genetics, nutrition, and reproduction interact. An ordered systems biology approach that focuses on why and how cells regulate energy and N use and on how and why organs interact through endocrine and neurocrine mechanisms will speed improvements in efficiency. More sophisticated dairy managers will demand better information to improve the efficiency of their animals. Using genetic improvement and animal management to improve milk productive and reproductive efficiency requires a deeper understanding of metabolic processes throughout the life cycle. Using existing metabolic models, we can design experiments specifically to integrate data from global transcriptional profiling into models that describe nutrient use in farm animals. A systems modeling approach can help focus our research to make faster and larger advances in efficiency and determine how this knowledge can be applied on the farms.

  11. TRIENNIAL LACTATION SYMPOSIUM: Systems biology of regulatory mechanisms of nutrient metabolism in lactation.

    PubMed

    McNamara, J P

    2015-12-01

    A major role of the dairy cow is to convert low-quality plant materials into high-quality protein and other nutrients for humans. We must select and manage cows with the goal of having animals of the greatest efficiency matched to their environment. We have increased efficiency tremendously over the years, yet the variation in productive and reproductive efficiency among animals is still large. In part, this is because of a lack of full integration of genetic, nutritional, and reproductive biology into management decisions. However, integration across these disciplines is increasing as the biological research findings show specific control points at which genetics, nutrition, and reproduction interact. An ordered systems biology approach that focuses on why and how cells regulate energy and N use and on how and why organs interact through endocrine and neurocrine mechanisms will speed improvements in efficiency. More sophisticated dairy managers will demand better information to improve the efficiency of their animals. Using genetic improvement and animal management to improve milk productive and reproductive efficiency requires a deeper understanding of metabolic processes throughout the life cycle. Using existing metabolic models, we can design experiments specifically to integrate data from global transcriptional profiling into models that describe nutrient use in farm animals. A systems modeling approach can help focus our research to make faster and larger advances in efficiency and determine how this knowledge can be applied on the farms. PMID:26641166

  12. Biological Targets and Mechanisms of Action of Natural Products from Marine Cyanobacteria

    PubMed Central

    Salvador-Reyes, Lilibeth A.

    2015-01-01

    Marine cyanobacteria are an ancient group of organisms and prolific producers of bioactive secondary metabolites. These compounds are presumably optimized by evolution over billions of years to exert high affinity for their intended biological target in the ecologically relevant organism but likely also possess activity in different biological contexts such as human cells. Screening of marine cyanobacterial extracts for bioactive natural products has largely focused on cancer cell viability; however, diversification of the screening platform led to the characterization of many new bioactive compounds. Targets of compounds have oftentimes been elusive if the compounds were discovered through phenotypic assays. Over the past few years, technology has advanced to determine mechanism of action (MOA) and targets through reverse chemical genetic and proteomic approaches, which has been applied to certain cyanobacterial compounds and will be discussed in this review. Some cyanobacterial molecules are the most-potent-in-class inhibitors and therefore may become valuable tools for chemical biology to probe protein function but also be templates for novel drugs, assuming in vitro potency translates into cellular and in vivo activity. Our review will focus on compounds for which the direct targets have been deciphered or which were found to target a novel pathway, and link them to disease states where target modulation may be beneficial. PMID:25571978

  13. Biological roles and functional mechanisms of arenavirus Z protein in viral replication.

    PubMed

    Wang, Jialong; Danzy, Shamika; Kumar, Naveen; Ly, Hinh; Liang, Yuying

    2012-09-01

    Arenaviruses can cause severe hemorrhagic fever diseases in humans, with limited prophylactic or therapeutic measures. A small RING-domain viral protein Z has been shown to mediate the formation of virus-like particles and to inhibit viral RNA synthesis, although its biological roles in an infectious viral life cycle have not been directly addressed. By taking advantage of the available reverse genetics system for a model arenavirus, Pichinde virus (PICV), we provide the direct evidence for the essential biological roles of the Z protein's conserved residues, including the G2 myristylation site, the conserved C and H residues of RING domain, and the poorly characterized C-terminal L79 and P80 residues. Dicodon substitutions within the late (L) domain (PSAPPYEP) of the PICV Z protein, although producing viable mutant viruses, have significantly reduced virus growth, a finding suggestive of an important role for the intact L domain in viral replication. Further structure-function analyses of both PICV and Lassa fever virus Z proteins suggest that arenavirus Z proteins have similar molecular mechanisms in mediating their multiple functions, with some interesting variations, such as the role of the G2 residue in blocking viral RNA synthesis. In summary, our studies have characterized the biological roles of the Z protein in an infectious arenavirus system and have shed important light on the distinct functions of its domains in virus budding and viral RNA regulation, the knowledge of which may lead to the development of novel antiviral drugs.

  14. A few nascent methods for measuring mechanical properties of the biological cell.

    SciTech Connect

    Thayer, Gayle Echo; de Boer, Maarten Pieter; Corvalan, Carlos; Corwin, Alex David; Campanella, Osvaldo H. (Purdue University, West Lafayette, IN); Nivens, David (Purdue University, West Lafayette, IN); Werely, Steven (Purdue University, West Lafayette, IN); Sumali, Anton Hartono; Koch, Steven John

    2006-01-01

    This report summarizes a survey of several new methods for obtaining mechanical and rheological properties of single biological cells, in particular: (1) The use of laser Doppler vibrometry (LDV) to measure the natural vibrations of certain cells. (2) The development of a novel micro-electro-mechanical system (MEMS) for obtaining high-resolution force-displacement curves. (3) The use of the atomic force microscope (AFM) for cell imaging. (4) The adaptation of a novel squeezing-flow technique to micro-scale measurement. The LDV technique was used to investigate the recent finding reported by others that the membranes of certain biological cells vibrate naturally, and that the vibration can be detected clearly with recent instrumentation. The LDV has been reported to detect motions of certain biological cells indirectly through the motion of a probe. In this project, trials on Saccharomyces cerevisiae tested and rejected the hypothesis that the LDV could measure vibrations of the cell membranes directly. The MEMS investigated in the second technique is a polysilicon surface-micromachined force sensor that is able to measure forces to a few pN in both air and water. The simple device consists of compliant springs with force constants as low as 0.3 milliN/m and Moire patterns for nanometer-scale optical displacement measurement. Fields from an electromagnet created forces on magnetic micro beads glued to the force sensors. These forces were measured and agreed well with finite element prediction. It was demonstrated that the force sensor was fully functional when immersed in aqueous buffer. These results show the force sensors can be useful for calibrating magnetic forces on magnetic beads and also for direct measurement of biophysical forces on-chip. The use of atomic force microscopy (AFM) for profiling the geometry of red blood cells was the third technique investigated here. An important finding was that the method commonly used for attaching the cells to a

  15. Diverse Mechanisms of Sp1-Dependent Transcriptional Regulation Potentially Involved in the Adaptive Response of Cancer Cells to Oxygen-Deficient Conditions

    PubMed Central

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    The inside of a tumor often contains a hypoxic area caused by a limited supply of molecular oxygen due to aberrant vasculature. Hypoxia-inducible factors (HIFs) are major transcription factors that are required for cancer cells to adapt to such stress conditions. HIFs, complexed with the aryl hydrocarbon receptor nuclear translocator, bind to and activate target genes as enhancers of transcription. In addition to this common mechanism, the induction of the unfolded protein response and mTOR signaling in response to endoplasmic reticulum stress is also known to be involved in the adaptation to hypoxia conditions. Sp1 is a ubiquitously-expressed transcription factor that plays a vital role in the regulation of numerous genes required for normal cell function. In addition to the well-characterized stress response mechanisms described above, increasing experimental evidence suggests that Sp1 and HIFs collaborate to drive gene expression in cancer cells in response to hypoxia, thereby regulating additional adaptive responses to cellular oxygen deficiency. However, these characteristics of Sp1 and their biological merits have not been summarized. In this review, we will discuss the diverse mechanisms of transcriptional regulation by Sp1 and their potential involvement in the adaptive response of cancer cells to hypoxic tumor microenvironments. PMID:26703734

  16. Superior in vitro biological response and mechanical properties of an implantable nanostructured biomaterial: Nanohydroxyapatite-silicone rubber composite.

    PubMed

    Thein-Han, W W; Shah, J; Misra, R D K

    2009-09-01

    A potential approach to achieving the objective of favorably modulating the biological response of implantable biopolymers combined with good mechanical properties is to consider compounding the biopolymer with a bioactive nanocrystalline ceramic biomimetic material with high surface area. The processing of silicone rubber (SR)-nanohydroxyapatite (nHA) composite involved uniform dispersion of nHA via shear mixing and ultrasonication, followed by compounding at sub-ambient temperature, and high-pressure solidification when the final curing reaction occurs. The high-pressure solidification approach enabled the elastomer to retain the high elongation of SR even in the presence of the reinforcement material, nHA. The biological response of the nanostructured composite in terms of initial cell attachment, cell viability and proliferation was consistently greater on SR-5wt.% nHA composite surface compared to pure SR. Furthermore, in the nanocomposite, cell spreading, morphology and density were distinctly different from that of pure SR. Pre-osteoblasts grown on SR-nHA were well spread, flat, large in size with a rough cell surface, and appeared as a group. In contrast, these features were less pronounced in SR (e.g. smooth cell surface, not well spread). Interestingly, an immunofluorescence study illustrated distinct fibronectin expression level, and stronger vinculin focal adhesion contacts associated with abundant actin stress fibers in pre-osteoblasts grown on the nanocomposite compared to SR, implying enhanced cell-substrate interaction. This finding was consistent with the total protein content and SDS-PAGE analysis. The study leads us to believe that further increase in nHA content in the SR matrix beyond 5wt.% will encourage even greater cellular response. The integration of cellular and molecular biology with materials science and engineering described herein provides a direction for the development of a new generation of nanostructured materials. PMID:19435616

  17. Mechanical properties and structure of the biological multilayered material system, Atractosteus spatula scales.

    PubMed

    Allison, P G; Chandler, M Q; Rodriguez, R I; Williams, B A; Moser, R D; Weiss, C A; Poda, A R; Lafferty, B J; Kennedy, A J; Seiter, J M; Hodo, W D; Cook, R F

    2013-02-01

    During recent decades, research on biological systems such as abalone shell and fish armor has revealed that these biological systems employ carefully arranged hierarchical multilayered structures to achieve properties of high strength, high ductility and light weight. Knowledge of such structures may enable pathways to design bio-inspired materials for various applications. This study was conducted to investigate the spatial distribution of structure, chemical composition and mechanical properties in mineralized fish scales of the species Atractosteus spatula. Microindentation tests were conducted, and cracking patterns and damage sites in the scales were examined to investigate the underlying protective mechanisms of fish scales under impact and penetration loads. A difference in nanomechanical properties was observed, with a thinner, stiffer and harder outer layer (indentation modulus ∼69 GPa and hardness ∼3.3 GPa) on a more compliant and thicker inner layer (indentation modulus ∼14.3 GPa and hardness ∼0.5 GPa). High-resolution scanning electron microscopy imaging of a fracture surface revealed that the outer layer contained oriented nanorods embedded in a matrix, and that the nanostructure of the inner layer contained fiber-like structures organized in a complex layered pattern. Damage patterns formed during microindentation show complex deformation mechanisms. Images of cracks identify growth through the outer layer, then deflection along the interface before growing and arresting in the inner layer. High-magnification images of the crack tip in the inner layer show void-linking and fiber-bridging exhibiting inelastic behavior. The observed difference in mechanical properties and unique nanostructures of different layers may have contributed to the resistance of fish scales to failure by impact and penetration loading. PMID:23149253

  18. Involvement of a glibenclamide-sensitive mechanism in the nitrergic neurotransmission of the pig intravesical ureter

    PubMed Central

    Hernández, Medardo; Prieto, Dolores; Orensanz, Luis M; Barahona, María Victoria; Jiménez-Cidre, Miguel; Rivera, Luis; García-Sacristán, Albino; Simonsen, Ulf

    1997-01-01

    The present study was designed to investigate whether potassium (K+) channels are involved in the relaxations to nitric oxide (NO) of pig intravesical ureteral preparations suspended in organ baths for isometric tension recordings. In ureteral strips treated with guanethidine (10−5 M) and atropine (10−7 M) to block adrenergic neurotransmission and muscarinic receptors, respectively, NO was either released from nitrergic nerves by electrical field stimulation (EFS, 0.5–10 Hz, 1 ms duration, 20 s trains), or exogenously-applied as an acidified solution of sodium nitrite (NaNO2, 10−6–10−3 M).Incubation with an inhibitor of guanylate cyclase activation by NO, methylene blue (10−5 M) did not change the basal tension of intravesical ureteral strips but inhibited the relaxation induced by EFS or exogenous NO on ureteral preparations contracted with the thromboxane analogue U46619 (10−7 M).Incubation with charybdotoxin (3×10−8 M) and apamin (5×10−7 M), which are inhibitors of large and small conductance calcium (Ca2+)-activated K+ channels, respectively, did not modify basal tension or the relaxations induced by EFS and exogenous NO. Treatment with charybdotoxin or apamin plus methylene blue (10−5 M) significantly reduced the relaxations to EFS and exogenous NO. However, in both cases the reductions were similar to the inhibition evoked by methylene blue alone. The combined addition of charybdotoxin plus apamin did not change the relaxations to EFS or exogenously added NO of the porcine intravesical ureter.Cromakalim (10−8–3×10−6 M), an opener of ATP-sensitive K+ channels, evoked a dose-dependent relaxation with a pD2 of 7.3±0.2 and maximum relaxant effect of a 71.8±4.2% of the contraction induced by U46619 in the pig intravesical ureter. The blocker of ATP-sensitive K+ channels, glibenclamide (10−6 M), inhibited markedly the relaxations to cromakalim.Glibenclamide (10−6 M) had no effect on the basal tone of

  19. Introducing mechanical biological waste treatment in South Africa: a comparative study.

    PubMed

    Trois, C; Griffith, M; Brummack, J; Mollekopf, N

    2007-01-01

    This paper presents the results of the first pilot project on mechanical biological waste treatment (MBWT) in South Africa. The study has shown that biological waste treatment in windrows using a passive aeration system that utilises thermal convection to drive the aeration process within a windrow of waste is appropriate for South Africa, in relation to low capital costs, low energy inputs, limited plant requirements and potential for labour-intensive operations. The influence of climate, waste composition and operational facilities was evaluated to optimise the treatment technique to local conditions. The maximum temperatures reached during the intensive thermophilic stage were effectively equivalent to the German experience. The lower CO2 production experienced in the South African trials was attributed to a different waste stream (high presence of plastics) due to the absence of a proper source separated waste collection system. An accurate adjustment of the input material (structural matter in particular) to the specific ambient conditions and irrigation during composting should result in higher organic carbon degradation efficiency in equivalent timeframes. This preliminary experience suggests that the applicability of MBWT in emerging countries, such as South Africa, is directly dependant on the mechanical treatment steps, available operational facilities and nature of the input material.

  20. Organic fraction of municipal solid waste from mechanical selection: biological stabilization and recovery options.

    PubMed

    Cesaro, Alessandra; Russo, Lara; Farina, Anna; Belgiorno, Vincenzo

    2016-01-01

    Although current trends address towards prevention strategies, the organic fraction of municipal solid waste is greatly produced, especially in high-income contexts. Its recovery-oriented collection is a common practice, but a relevant portion of the biodegradable waste is not source selected. Mechanical and biological treatments (MBT) are the most common option to sort and stabilize the biodegradable matter ending in residual waste stream. Following the changes of the framework around waste management, this paper aimed at analyzing the quality of the mechanically selected organic waste produced in MBT plants, in order to discuss its recovery options. The material performance was obtained by its composition as well as by its main chemical and physical parameters; biological stability was also assessed by both aerobic and anaerobic methods. On this basis, the effectiveness of an aerobic biostabilization process was assessed at pilot scale. After 21 days of treatment, results proved that the biomass had reached an acceptable biostabilization level, with a potential Dynamic Respirometric Index (DRIP) value lower than the limit required for its use as daily or final landfill cover material. However, the final stabilization level was seen to be influenced by scaling factors and the 21 days of treatment turned to be not so adequate when applied in the existing full-scale facility.

  1. Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

    PubMed Central

    Sart, Sébastien; Tsai, Ang-Chen; Li, Yan

    2014-01-01

    Mesenchymal stem cells (MSCs) are primary candidates in cell therapy and tissue engineering and are being tested in clinical trials for a wide range of diseases. Originally isolated and expanded as plastic adherent cells, MSCs have intriguing properties of in vitro self-assembly into three-dimensional (3D) aggregates reminiscent of skeletal condensation in vivo. Recent studies have shown that MSC 3D aggregation improved a range of biological properties, including multilineage potential, secretion of therapeutic factors, and resistance against ischemic condition. Hence, the formation of 3D MSC aggregates has been explored as a novel strategy to improve cell delivery, functional activation, and in vivo retention to enhance therapeutic outcomes. This article summarizes recent reports of MSC aggregate self-assembly, characterization of biological properties, and their applications in preclinical models. The cellular and molecular mechanisms underlying MSC aggregate formation and functional activation are discussed, and the areas that warrant further investigation are highlighted. These analyses are combined to provide perspectives for identifying the controlling mechanisms and refining the methods of aggregate fabrication and expansion for clinical applications. PMID:24168395

  2. Organic fraction of municipal solid waste from mechanical selection: biological stabilization and recovery options.

    PubMed

    Cesaro, Alessandra; Russo, Lara; Farina, Anna; Belgiorno, Vincenzo

    2016-01-01

    Although current trends address towards prevention strategies, the organic fraction of municipal solid waste is greatly produced, especially in high-income contexts. Its recovery-oriented collection is a common practice, but a relevant portion of the biodegradable waste is not source selected. Mechanical and biological treatments (MBT) are the most common option to sort and stabilize the biodegradable matter ending in residual waste stream. Following the changes of the framework around waste management, this paper aimed at analyzing the quality of the mechanically selected organic waste produced in MBT plants, in order to discuss its recovery options. The material performance was obtained by its composition as well as by its main chemical and physical parameters; biological stability was also assessed by both aerobic and anaerobic methods. On this basis, the effectiveness of an aerobic biostabilization process was assessed at pilot scale. After 21 days of treatment, results proved that the biomass had reached an acceptable biostabilization level, with a potential Dynamic Respirometric Index (DRIP) value lower than the limit required for its use as daily or final landfill cover material. However, the final stabilization level was seen to be influenced by scaling factors and the 21 days of treatment turned to be not so adequate when applied in the existing full-scale facility. PMID:26377969

  3. Opto-Mechanical Coupling in Interfaces under Static and Propagative Conditions and Its Biological Implications

    PubMed Central

    Shrivastava, Shamit; Schneider, Matthias F.

    2013-01-01

    Fluorescent dyes are vital for studying static and dynamic patterns and pattern formation in cell biology. Emission properties of the dyes incorporated in a biological interface are known to be sensitive to their local environment. We report that the fluorescence intensity of dye molecules embedded in lipid interfaces is indeed a thermodynamic observable of the system. Opto-mechanical coupling of lipid-dye system was measured as a function of the thermodynamic state of the interface. The corresponding state diagrams quantify the thermodynamic coupling between intensity I and lateral pressure π. We further demonstrate that the coupling is conserved upon varying the temperature T. Notably, the observed opto-mechanical coupling is not limited to equilibrium conditions, but also holds for propagating pressure pulses. The non-equilibrium data show, that fluorescence is especially sensitive to dynamic changes in state such as the LE-LC phase transition. We conclude that variations in the thermodynamic state (here π and T, in general pH, membrane potential V, etc also) of lipid membranes are capable of controlling fluorescence intensity. Therefore, interfacial thermodynamic state diagrams of I should be obtained for a proper interpretation of intensity data. PMID:23861769

  4. [Effects and molecular mechanisms of the biological action of weak and extremely weak magnetic fields].

    PubMed

    Novikov, V V; Ponomarev, V O; Novikov, G V; Kuvichkin, V V; Iablokova, E V; Fesenko, E E

    2010-01-01

    A number of effects of weak combined (static and alternating) magnetic fields with an alternating component of tens and hundreds nT at a collinear static field of 42 microT, which is equivalent to the geomagnetic field, have been found: the activation of fission and regeneration of planarians Dugesia tigrina, the inhibition of the growth of the Ehrlich ascites carcinoma in mice, the stimulation of the production of the tumor necrosis factor by macrophages, a decrease in the protection of chromatin against the action of DNase 1, and the enhancement of protein hydrolysis in systems in vivo and in vitro. The frequency and amplitude ranges for the alternating component of weak combined magnetic fields have been determined at which it affects various biological systems. Thus, the optimal amplitude at a frequency of 4.4 Hz is 100 nT (effective value); at a frequency of 16.5 Hz, the range of effective amplitudes is broader, 150-300 nT; and at a frequency of 1 (0.5) Hz, it is 300 nT. The sum of close frequencies (e.g., 16 and 17 Hz) produces a similar biological effect as the product of the modulating (0.5 Hz) and carrying frequencies (16.5 Hz), which is explained by the ratio A = A0sin omega1t + A0sin omega2t = A0sin(omega1 + omega2)t/2cos(omega1 - omega2)t/2. The efficiency of magnetic signals with pulsations (the sum of close frequencies) is more pronounced than that of sinusoidal frequencies. These data may indicate the presence of several receptors of weak magnetic fields in biological systems and, as a consequence, a higher efficiency of the effect at the simultaneous adjustment to these frequencies by the field. Even with consideration of these facts, the mechanism of the biological action of weak combined magnetic fields remains still poorly understood. PMID:20968074

  5. Effect of calcium hydroxide on mechanical strength and biological properties of bioactive glass.

    PubMed

    Shah, Asma Tufail; Batool, Madeeha; Chaudhry, Aqif Anwar; Iqbal, Farasat; Javaid, Ayesha; Zahid, Saba; Ilyas, Kanwal; Bin Qasim, Saad; Khan, Ather Farooq; Khan, Abdul Samad; Ur Rehman, Ihtesham

    2016-08-01

    In this manuscript for the first time calcium hydroxide (Ca(OH)2) has been used for preparation of bioactive glass (BG-2) by co-precipitation method and compared with glass prepared using calcium nitrate tetrahydrate Ca(NO3)2·4H2O (BG-1), which is a conventional source of calcium. The new source positively affected physical, biological and mechanical properties of BG-2. The glasses were characterized by Fourier transform infrared (FTIR), X-Ray Diffractometer (XRD), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis/Differential Scanning Calorimetry (TGA-DSC), BET surface area analysis and Knoop hardness. The results showed that BG-2 possessed relatively larger surface properties (100m(2)g(-1) surface area) as compared to BG-1 (78m(2)g(-1)), spherical morphology and crystalline phases (wollastonite and apatite) after sintering at lower than conventional temperature. These properties contribute critical role in both mechanical and biological properties of glasses. The Knoop hardness measurements revealed that BG-2 possessed much better hardness (0.43±0.06GPa at 680°C and 2.16±0.46GPa at 980°C) than BG-1 (0.24±0.01 at 680°C and 0.57±0.07GPA at 980°C) under same conditions. Alamar blue Assay and confocal microscopy revealed that BG-2 exhibited better attachment and proliferation of MG63 cells. Based on the improved biological properties of BG-2 as a consequent of novel calcium source selection, BG-2 is proposed as a bioactive ceramic for hard tissue repair and regeneration applications. PMID:27068802

  6. Mechanical Restrictions on Biological Responses by Adherent Cells within Collagen Gels

    PubMed Central

    Simon, D.D.; Horgan, C.O.; Humphrey, J.D.

    2012-01-01

    Cell-seeded collagen and fibrin gels represent excellent assays for studying interactions between adherent interstitial cells and the three-dimensional extracellular matrix in which they reside. Over one hundred papers have employed the free-floating collagen gel assay alone since its introduction in 1979 and much has been learned about mechanobiological responses of diverse types of cells. Yet, given that mechanobiology is the study of biological responses by cells to mechanical stimuli that must respect the basic laws of mechanics, we must quantify better the mechanical conditions that are imposed on or arise in cell-seeded gels. In this paper, we suggest that cell responses and associated changes in matrix organization within the classical free-floating gel assay are highly restricted by the mechanics. In particular, many salient but heretofore unexplained or misinterpreted observations in free-floating gels can be understood in terms of apparent cell-mediated residual stress fields that satisfy quasi-static equilibria and continuity of tractions. There is a continuing need, therefore, to bring together the allied fields of mechanobiology and biomechanics as we continue to elucidate cellular function within both native connective tissues and tissue equivalents that are used in basic scientific investigations or regenerative medicine. PMID:23022259

  7. A Mechanism for Land-Atmosphere Feedback Involving Planetary Wave Structures

    NASA Technical Reports Server (NTRS)

    Koster, Randal D.; Chang, Yehui; Schubert, Siegfried D.

    2014-01-01

    While the ability of land surface conditions to influence the atmosphere has been demonstrated in various modeling and observational studies, the precise mechanisms by which land-atmosphere feedback occurs are still largely unknown particularly the mechanisms that allow land moisture state in one region to affect atmospheric conditions in another. Such remote impacts are examined here in the context of atmospheric general circulation model (AGCM) simulations, leading to the identification of one potential mechanism: the phase-locking and amplification of a planetary wave through the imposition of a spatial pattern of soil moisture at the land surface. This mechanism, shown here to be relevant in the AGCM, apparently also operates in nature, as suggested by supporting evidence found in reanalysis data.

  8. Toward modular biological models: defining analog modules based on referent physiological mechanisms

    PubMed Central

    2014-01-01

    Background Currently, most biomedical models exist in isolation. It is often difficult to reuse or integrate models or their components, in part because they are not modular. Modular components allow the modeler to think more deeply about the role of the model and to more completely address a modeling project’s requirements. In particular, modularity facilitates component reuse and model integration for models with different use cases, including the ability to exchange modules during or between simulations. The heterogeneous nature of biology and vast range of wet-lab experimental platforms call for modular models designed to satisfy a variety of use cases. We argue that software analogs of biological mechanisms are reasonable candidates for modularization. Biomimetic software mechanisms comprised of physiomimetic mechanism modules offer benefits that are unique or especially important to multi-scale, biomedical modeling and simulation. Results We present a general, scientific method of modularizing mechanisms into reusable software components that we call physiomimetic mechanism modules (PMMs). PMMs utilize parametric containers that partition and expose state information into physiologically meaningful groupings. To demonstrate, we modularize four pharmacodynamic response mechanisms adapted from an in silico liver (ISL). We verified the modularization process by showing that drug clearance results from in silico experiments are identical before and after modularization. The modularized ISL achieves validation targets drawn from propranolol outflow profile data. In addition, an in silico hepatocyte culture (ISHC) is created. The ISHC uses the same PMMs and required no refactoring. The ISHC achieves validation targets drawn from propranolol intrinsic clearance data exhibiting considerable between-lab variability. The data used as validation targets for PMMs originate from both in vitro to in vivo experiments exhibiting large fold differences in time scale

  9. Sensitizing Children to the Social and Emotional Mechanisms Involved in Racism: A Program Evaluation

    ERIC Educational Resources Information Center

    Triliva, Sofia; Anagnostopoulou, Tanya; Vleioras, Georgios

    2014-01-01

    This paper describes and discusses the results of an intervention aiming to sensitize children to the social and emotional processes involved in racism. The intervention was applied and evaluated in 10 Greek elementary schools. The goals and the intervention methods of the program modules are briefly outlined and the results of the program…

  10. Cumulative asbestos exposure for US automobile mechanics involved in brake repair (circa 1950s-2000).

    PubMed

    Finley, Brent L; Richter, Richard O; Mowat, Fionna S; Mlynarek, Steve; Paustenbach, Dennis J; Warmerdam, John M; Sheehan, Patrick J

    2007-11-01

    We analyzed cumulative lifetime exposure to chrysotile asbestos experienced by brake mechanics in the US during the period 1950-2000. Using Monte Carlo methods, cumulative exposures were calculated using the distribution of 8-h time-weighted average exposure concentrations for brake mechanics and the distribution of job tenure data for automobile mechanics. The median estimated cumulative exposures for these mechanics, as predicted by three probabilistic models, ranged from 0.16 to 0.41 fibers per cubic centimeter (f/cm(3)) year for facilities with no dust-control procedures (1970s), and from 0.010 to 0.012 f/cm(3) year for those employing engineering controls (1980s). Upper-bound (95%) estimates for the 1970s and 1980s were 1.96 to 2.79 and 0.07-0.10 f/cm(3) year, respectively. These estimates for US brake mechanics are consistent with, but generally slightly lower than, those reported for European mechanics. The values are all substantially lower than the cumulative exposure of 4.5 f/cm(3) year associated with occupational exposure to 0.1 f/cm(3) of asbestos for 45 years that is currently permitted under the current occupational exposure limits in the US. Cumulative exposures were usually about 100- to 1,000-fold less than those of other occupational groups with asbestos exposure for similar time periods. The cumulative lifetime exposure estimates presented here, combined with the negative epidemiology data for brake mechanics, could be used to refine the risk assessments for chrysotile-exposed populations.

  11. A Journey with Elie Metchnikoff: From Innate Cell Mechanisms in Infectious Diseases to Quantum Biology

    PubMed Central

    Merien, Fabrice

    2016-01-01

    Many reviews of Elie Metchnikoff’s work have been published, all unanimously acknowledging the significant contributions of his cellular theory to the fields of immunology and infectious diseases. In 1883, he published a key paper describing phagocytic cells in frogs. His descriptions were not just about phagocytes involved in host defense, he also described how these specialized cells eliminated degenerating or dying cells of the host. This perspective focuses on key concepts developed by Metchnikoff by presenting relevant excerpts of his 1883 paper and matching these concepts with challenges of modern immunology. A new approach to macrophage polarization is included to introduce some creative thinking about the exciting emerging area of quantum biology. PMID:27379227

  12. Evaluation of forcefields for molecular mechanics/dynamics calculations involving halogenated anesthetics.

    PubMed

    Trudell, J R; Bertaccini, E

    1998-11-23

    (1) Successful application of molecular mechanics and molecular dynamics calculations to the binding of halogenated anesthetics requires forcefields with correct parameters for halocarbons. (2) Unfortunately, our survey of six popular forcefields revealed that some of them provide a very poor representation of electrostatic interactions for the halogens. (3) This problem is due to poor or missing assignments of partial atomic charges to the halogen atoms. (4) We describe the forcefields most appropriate for use with halogenated anesthetics and suggest a general method for editing the assignment of partial atomic charges by performing an initial quantum mechanics calculation. PMID:10049174

  13. Tibolone protects astrocytic cells from glucose deprivation through a mechanism involving estrogen receptor beta and the upregulation of neuroglobin expression.

    PubMed

    Avila-Rodriguez, Marco; Garcia-Segura, Luis Miguel; Hidalgo-Lanussa, Oscar; Baez, Eliana; Gonzalez, Janneth; Barreto, George E

    2016-09-15

    Tibolone, a synthetic steroid used for the prevention of osteoporosis and the treatment of climacteric symptoms in post-menopausal women, may exert tissue selective estrogenic actions acting on estrogen receptors (ERs). We previously showed that tibolone protects human T98G astroglial cells against glucose deprivation (GD). In this study we have explored whether the protective effect of tibolone on these cells is mediated by ERs. Experimental studies showed that both ERα and ERβ were involved in the protection by tibolone on GD cells, being ERβ preferentially involved on these actions over ERα. Tibolone increased viability of GD cells by a mechanism fully blocked by an ERβ antagonist and partially blocked by an ERα antagonist. Furthermore, ERβ inhibition prevented the effect of tibolone on nuclear fragmentation, ROS and mitochondrial membrane potential in GD cells. The protective effect of tibolone was mediated by neuroglobin. Tibolone upregulated neuroglobin in T98G cells and primary mouse astrocytes by a mechanism involving ERβ and neuroglobin silencing prevented the protective action of tibolone on GD cells. In summary, tibolone protects T98G cells by a mechanism involving ERβ and the upregulation of neuroglobin. PMID:27250720

  14. Biodegradation of endocrine-disrupting compounds by ligninolytic fungi: mechanisms involved in the degradation.

    PubMed

    Cajthaml, Tomáš

    2015-12-01

    Without any doubt, endocrine-disrupting compounds (EDCs) represent an environmental risk for wildlife and human beings. Endocrine-disrupting effects were found for many chemicals in products for personal use, industrial compounds and even in classical persistent organic pollutants (POPs). In order to understand the fate of EDCs in the environment, it is highly important to identify and to clarify the biodegradation mechanisms that can lead to their decomposition. Ligninolytic fungi (LF) are interesting microorganisms that are capable of participating in a variety of versatile decomposition mechanisms. The microorganisms represent a useful model group and, moreover, LF or their enzymes can be actively used for decontamination. Potential optimization of the decontamination process provides another important reason why it is necessary for understanding the mechanisms of EDC transformation. This minireview summarizes current knowledge about the LF biodegradation mechanisms of the most important micropollutants (xenoestrogens), including nonylphenols, bisphenol A and 17α-ethinylestradiol and polychlorinated biphenyls as POPs with endocrine-disrupting potency. Generally, LF exhibit the ability to either polymerize the target pollutants or to substantially decompose the original structure using ligninolytic enzymes and cytochrome P-450. Moreover, most of the transformation processes are accompanied by reduction of the endocrine-disrupting activity or ecotoxicity. PMID:24650234

  15. Biodegradation of endocrine-disrupting compounds by ligninolytic fungi: mechanisms involved in the degradation.

    PubMed

    Cajthaml, Tomáš

    2015-12-01

    Without any doubt, endocrine-disrupting compounds (EDCs) represent an environmental risk for wildlife and human beings. Endocrine-disrupting effects were found for many chemicals in products for personal use, industrial compounds and even in classical persistent organic pollutants (POPs). In order to understand the fate of EDCs in the environment, it is highly important to identify and to clarify the biodegradation mechanisms that can lead to their decomposition. Ligninolytic fungi (LF) are interesting microorganisms that are capable of participating in a variety of versatile decomposition mechanisms. The microorganisms represent a useful model group and, moreover, LF or their enzymes can be actively used for decontamination. Potential optimization of the decontamination process provides another important reason why it is necessary for understanding the mechanisms of EDC transformation. This minireview summarizes current knowledge about the LF biodegradation mechanisms of the most important micropollutants (xenoestrogens), including nonylphenols, bisphenol A and 17α-ethinylestradiol and polychlorinated biphenyls as POPs with endocrine-disrupting potency. Generally, LF exhibit the ability to either polymerize the target pollutants or to substantially decompose the original structure using ligninolytic enzymes and cytochrome P-450. Moreover, most of the transformation processes are accompanied by reduction of the endocrine-disrupting activity or ecotoxicity.

  16. A moving image of flagella: news and views on the mechanisms involved in axonemal beating.

    PubMed

    Cosson, J

    1996-02-01

    Beating of cilia and flagellae allows movement of the fluid surrounding isolated cells (for example: protists) or epithelia (bronchial tissue) but is also responsible for the movement of unicellular organisms in this medium (such as spermatozoa or protists). This paper aims to describe: (1) the biochemical and structural elements of the '9 + 2' structure called the axoneme; (2) the mechanisms of wave generation and propagation along the axoneme of cilia and flagellae are then described, stating that in most models of wave propagation, a clear distinction is made between the dynein-dependent microtubule sliding which represents the oscillatory motor and the bending mechanism which regulates wave propagation. In current models, the bending propagation is supported by a bind/relax cyclic mechanism which propagates in register, but frame-shifted, with the powering action of the dynein motor along the axoneme. While a large amount of knowledge was accumulated about the motor, little is known about the resisting elements regulating the bending. (3) The present study also puts forward ideas as to how these organelles have been highly conserved throughout eucaryotic evolution, and concludes with suggestions for further fields of investigation into this unique mechanical device used for cell movement.

  17. Mechanically Durable and Biologically Favorable Protein Hydrogel Based on Elastic Silklike Protein Derived from Sea Anemone.

    PubMed

    Yang, Yun Jung; Kim, Chang Sup; Choi, Bong-Hyuk; Cha, Hyung Joon

    2015-12-14

    As biodegradable scaffolds, protein hydrogels have considerable potential, particularly for bioartificial organs and three-dimensional space-filling materials. However, their low strength and stiffness have been considered to be limitations for enduring physiological stimuli. Therefore, protein hydrogels have been commonly utilized as delivery vehicles rather than as supporting materials. In this work, sea anemone tentacle-derived recombinant silk-like protein (aneroin) was evaluated as a potential material for a mechanically durable protein hydrogel. Inspired by the natural hardening mechanism, photoinitiated dityrosine cross-linking was employed to fabricate an aneroin hydrogel. It was determined that the fabricated aneroin hydrogel was approximately 10-fold stiffer than mammalian cardiac or skeletal muscle. The aneroin hydrogel provided not only structural support but also an adequate environment for cells. It exhibited an adequate swelling ability and microstructure, which are beneficial for facilitating mass transport and cell proliferation. Based on its mechanical and biological properties, this aneroin hydrogel could be used in various biomedical applications, such as cell-containing patches, biomolecule carriers, and artificial extracellular matrices. PMID:26539814

  18. Biological mechanisms underlying the role of physical fitness in health and resilience.

    PubMed

    Silverman, Marni N; Deuster, Patricia A

    2014-10-01

    Physical fitness, achieved through regular exercise and/or spontaneous physical activity, confers resilience by inducing positive psychological and physiological benefits, blunting stress reactivity, protecting against potentially adverse behavioural and metabolic consequences of stressful events and preventing many chronic diseases. In this review, we discuss the biological mechanisms underlying the beneficial effects of physical fitness on mental and physical health. Physical fitness appears to buffer against stress-related disease owing to its blunting/optimizing effects on hormonal stress responsive systems, such as the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. This blunting appears to contribute to reduced emotional, physiological and metabolic reactivity as well as increased positive mood and well-being. Another mechanism whereby regular exercise and/or physical fitness may confer resilience is through minimizing excessive inflammation. Chronic psychological stress, physical inactivity and abdominal adiposity have been associated with persistent, systemic, low-grade inflammation and exert adverse effects on mental and physical health. The anti-inflammatory effects of regular exercise/activity can promote behavioural and metabolic resilience, and protect against various chronic diseases associated with systemic inflammation. Moreover, exercise may benefit the brain by enhancing growth factor expression and neural plasticity, thereby contributing to improved mood and cognition. In summary, the mechanisms whereby physical fitness promotes increased resilience and well-being and positive psychological and physical health are diverse and complex. PMID:25285199

  19. Evolution in biological and nonbiological systems under different mechanisms of generation and inheritance.

    PubMed

    Salazar-Ciudad, Isaac

    2008-11-01

    The majority of definitions of life and evolution include the notion that part of an organism has to be copied to its offspring and that this includes some form of coded information. This article presents the thesis that this conception is too restrictive and that evolution can occur in systems in which there is no copy of information between generations. For that purpose, this article introduces a new set of concepts and a theoretical framework that is designed to be equally applicable to the study of the evolution of biological and nonbiological systems. In contrast to some theoretical approaches in evolution, like neo-Darwinism, the approach presented here is not focused on the transmission and change of hereditary information that can be copied (like in the case of DNA). Instead, multiple mechanisms by which a system can generate offspring (with and without copying) and by which information in it affects the structure and evolution of its offspring are considered. The first part of this article describes in detail these new concepts. The second part of this article discusses how these concepts are directly applicable to the diversity of systems that can evolve. The third part introduces hypotheses concerning (1) how different mechanisms of generation and inheritance can arise from each other during evolution, and (2) how the existence of several inheritance mechanisms in an organism can affect its evolution.

  20. Hybrid PGS-PCL microfibrous scaffolds with improved mechanical and biological properties.

    PubMed

    Sant, Shilpa; Hwang, Chang Mo; Lee, Sang-Hoon; Khademhosseini, Ali

    2011-04-01

    Poly(glycerol sebacate) (PGS) is a biodegradable elastomer that has generated great interest as a scaffold material due to its desirable mechanical properties. However, the use of PGS in tissue engineering is limited by difficulties in casting micro- and nanofibrous structures, due to high temperatures and vacuum required for its curing and limited solubility of the cured polymer. In this paper, we developed microfibrous scaffolds made from blends of PGS and poly(ε-caprolactone) (PCL) using a standard electrospinning set-up. At a given PGS:PCL ratio, higher voltage resulted in significantly smaller fibre diameters (reduced from ∼4 µm to 2.8 µm; p < 0.05). Further increase in voltage resulted in the fusion of fibres. Similarly, higher PGS concentrations in the polymer blend resulted in significantly increased fibre diameter (p < 0.01). We further compared the mechanical properties of electrospun PGS:PCL scaffolds with those made from PCL. Scaffolds with higher PGS concentrations showed higher elastic modulus (EM), ultimate tensile strength (UTS) and ultimate elongation (UE) (p < 0.01) without the need for thermal curing or photocrosslinking. Biological evaluation of these scaffolds showed significantly improved HUVEC attachment and proliferation compared to PCL-only scaffolds (p < 0.05). Thus, we have demonstrated that simple blends of PGS prepolymer with PCL can be used to fabricate microfibrous scaffolds with mechanical properties in the range of a human aortic valve leaflet. PMID:20669260

  1. Mechanical and biological properties of chitosan/carbon nanotube nanocomposite films

    PubMed Central

    Aryaei, Ashkan; Jayatissa, Ahalapitiya H.; Jayasuriya, Ambalangodage C.

    2015-01-01

    In this paper, different concentrations of multi-walled carbon nanotube (MWCNT) were homogeneously dispersed throughout the chitosan (CS) matrix. A simple solvent-cast method was used to fabricate chitosan films with 0.1, 0.5, and 1% of MWCNT with the average diameter around 30 nm. The CS/MWCNT films were characterized for structural, viscous and mechanical properties with optical microscopy, wide-angle X-ray diffraction, Raman spectroscopy, tensile test machine, and microindentation testing machine. Murine osteoblasts were used to examine the cell viability and attachment of the nanocomposite films at two time points. In comparison to the pure chitosan film, the mechanical properties, including the tensile modulus and strength of the films were greatly improved by increasing the percentage of MWCNT. Furthermore, adding MWCNT up to 1% increased the viscosity of the chitosan solution by 15%. However, adding MWCNT decreased the samples ductility and transparency. In biological point of view, no toxic effect on osteoblasts was observed in the presence of different percentages of MWCNT at day 3 and day 7. This investigation suggested MWCNT could be a promising candidate for improving chitosan mechanical properties without inducing remarkable cytotoxicity on bone cells. PMID:24108584

  2. Designing Laboratory Exercises for the Undergraduate Molecular Biology/Biochemistry Student: Techniques and Ethical Implications Involved in Personalized Medicine

    ERIC Educational Resources Information Center

    Weinlander, Kenneth M.; Hall, David J.

    2010-01-01

    Personalized medicine refers to medical care that involves genetically screening patients for their likelihood to develop various disorders. Commercial genome screening only involves identifying a consumer's genotype for a few single nucleotide polymorphisms. A phenotype (such as an illness) is greatly influenced by three factors: genes, gene…

  3. Studying chemical reactions in biological systems with MBN Explorer: implementation of molecular mechanics with dynamical topology

    NASA Astrophysics Data System (ADS)

    Sushko, Gennady B.; Solov'yov, Ilia A.; Verkhovtsev, Alexey V.; Volkov, Sergey N.; Solov'yov, Andrey V.

    2016-01-01

    The concept of molecular mechanics force field has been widely accepted nowadays for studying various processes in biomolecular systems. In this paper, we suggest a modification for the standard CHARMM force field that permits simulations of systems with dynamically changing molecular topologies. The implementation of the modified force field was carried out in the popular program MBN Explorer, and, to support the development, we provide several illustrative case studies where dynamical topology is necessary. In particular, it is shown that the modified molecular mechanics force field can be applied for studying processes where rupture of chemical bonds plays an essential role, e.g., in irradiation- or collision-induced damage, and also in transformation and fragmentation processes involving biomolecular systems. Contribution to the Topical Issue "COST Action Nano-IBCT: Nano-scale Processes Behind Ion-Beam Cancer Therapy", edited by Andrey V. Solov'yov, Nigel Mason, Gustavo Garcia and Eugene Surdutovich.

  4. Heavy-ion radiobiology: new approaches to delineate mechanisms underlying enhanced biological effectiveness.

    PubMed

    Blakely, E A; Kronenberg, A

    1998-11-01

    Shortly after the discovery of polonium and radium by Marie Curie and her husband and colleague, Pierre Curie, it was learned that exposure to these alpha-particle emitters produced deleterious biological effects. The mechanisms underlying the increased biological effectiveness of densely ionizing radiations, including alpha particles, neutrons and highly energetic heavy charged particles, remain an active area of investigation. In this paper, we review recent advances in several areas of the radiobiology of these densely ionizing radiations, also known as heavy ions. Advances are described in the areas of DNA damage and repair, chromosome aberrations, mutagenesis, neoplastic transformation in vitro, genomic instability, normal tissue radiobiology and carcinogenesis in vivo. We focus on technical innovations, including novel applications of pulsed-field gel electrophoresis, fluorescence in situ hybridization (FISH), linkage analysis, and studies of gene expression and protein expression. We also highlight the use of new cellular and animal systems, including those with defined DNA repair deficiencies, as well as epithelial cell model systems to assess neoplastic transformation both in vitro and in vivo. The studies reviewed herein have had a substantial impact on our understanding of the genotoxic effects of heavy ions as well as their distinct effects on tissue homeostasis. The use of these radiations in cancer therapy is also discussed. The use of both heavy-ion and proton therapy is on the upswing in several centers around the world, due to their unique energy deposition characteristics that enhance the therapeutic effect and help reduce damage to normal tissue.

  5. Heavy-ion radiobiology: new approaches to delineate mechanisms underlying enhanced biological effectiveness

    NASA Technical Reports Server (NTRS)

    Blakely, E. A.; Kronenberg, A.; Chatterjee, A. (Principal Investigator)

    1998-01-01

    Shortly after the discovery of polonium and radium by Marie Curie and her husband and colleague, Pierre Curie, it was learned that exposure to these alpha-particle emitters produced deleterious biological effects. The mechanisms underlying the increased biological effectiveness of densely ionizing radiations, including alpha particles, neutrons and highly energetic heavy charged particles, remain an active area of investigation. In this paper, we review recent advances in several areas of the radiobiology of these densely ionizing radiations, also known as heavy ions. Advances are described in the areas of DNA damage and repair, chromosome aberrations, mutagenesis, neoplastic transformation in vitro, genomic instability, normal tissue radiobiology and carcinogenesis in vivo. We focus on technical innovations, including novel applications of pulsed-field gel electrophoresis, fluorescence in situ hybridization (FISH), linkage analysis, and studies of gene expression and protein expression. We also highlight the use of new cellular and animal systems, including those with defined DNA repair deficiencies, as well as epithelial cell model systems to assess neoplastic transformation both in vitro and in vivo. The studies reviewed herein have had a substantial impact on our understanding of the genotoxic effects of heavy ions as well as their distinct effects on tissue homeostasis. The use of these radiations in cancer therapy is also discussed. The use of both heavy-ion and proton therapy is on the upswing in several centers around the world, due to their unique energy deposition characteristics that enhance the therapeutic effect and help reduce damage to normal tissue.

  6. Mechanical homeostasis of a DOPA-enriched biological coating from mussels in response to metal variation

    PubMed Central

    Schmitt, Clemens N. Z.; Winter, Alette; Bertinetti, Luca; Masic, Admir; Strauch, Peter; Harrington, Matthew J.

    2015-01-01

    Protein–metal coordination interactions were recently found to function as crucial mechanical cross-links in certain biological materials. Mussels, for example, use Fe ions from the local environment coordinated to DOPA-rich proteins to stiffen the protective cuticle of their anchoring byssal attachment threads. Bioavailability of metal ions in ocean habitats varies significantly owing to natural and anthropogenic inputs on both short and geological spatio-temporal scales leading to large variations in byssal thread metal composition; however, it is not clear how or if this affects thread performance. Here, we demonstrate that in natural environments mussels can opportunistically replace Fe ions in the DOPA coordination complex with V and Al. In vitro removal of the native DOPA–metal complexes with ethylenediaminetetraacetic acid and replacement with either Fe or V does not lead to statistically significant changes in cuticle performance, indicating that each metal ion is equally sufficient as a DOPA cross-linking agent, able to account for nearly 85% of the stiffness and hardness of the material. Notably, replacement with Al ions also leads to full recovery of stiffness, but only 82% recovery of hardness. These findings have important implications for the adaptability of this biological material in a dynamically changing and unpredictable habitat. PMID:26311314

  7. Statistical mechanics in biology: how ubiquitous are long-range correlations?

    NASA Astrophysics Data System (ADS)

    Stanley, H. E.; Buldyrev, S. V.; Goldberger, A. L.; Goldberger, Z. D.; Havlin, S.; Mantegna, R. N.; Ossadnik, S. M.; Peng, C.-K.; Simons, M.

    1994-04-01

    The purpose of this opening talk is to describe examples of recent progress in applying statistical mechanics to biological systems. We first briefly review several biological systems, and then focus on the fractal features characterized by the long-range correlations found recently in DNA sequences containing non-coding material. We discuss the evidence supporting the finding that for sequences containing only coding regions, there are no long-range correlations. We also discuss the recent finding that the exponent α characterizing the long-range correlations increases with evolution, and we discuss two related models, the insertion model and the insertion-deletion model, that may account for the presence of long-range correlations. Finally, we summarize the analysis of long-term data on human heartbeats (up to 10 4 heart beats) that supports the possibility that the successive increments in the cardiac beat-to-beat intervals of healthy subjects display scale-invariant, long-range “anti-correlations” (a tendency to beat faster is balanced by a tendency to beat slower later on). In contrast, for a group of subjects with severe heart disease, long-range correlations vanish. This finding suggests that the classical theory of homeostasis, according to which stable physiological processes seek to maintain “constancy,” should be extended to account for this type of dynamical, far from equilibrium, behavior.

  8. Enhancing combined biological nitrogen and phosphorus removal from wastewater by applying mechanically disintegrated excess sludge.

    PubMed

    Zubrowska-Sudol, Monika; Walczak, Justyna

    2015-06-01

    The goal of the study was to evaluate the possibility of applying disintegrated excess sludge as a source of organic carbon to enhance biological nitrogen and phosphorus removal. The experiment, performed in a sequencing batch reactor, consisted of two two-month series, without and with applying mechanically disintegrated excess sludge, respectively. The effects on carbon, nitrogen and phosphorus removal were observed. It was shown that the method allows enhancement of combined nitrogen and phosphorus removal. After using disintegrated sludge, denitrification effectiveness increased from 49.2 ± 6.8% to 76.2 ± 2.3%, which resulted in a decline in the NOx-N concentration in the effluent from the SBR by an average of 21.4 mg NOx-N/L. Effectiveness of biological phosphorus removal increased from 28.1 ± 11.3% to 96.2 ± 2.5%, thus resulting in a drop in the [Formula: see text] concentration in the effluent by, on average, 6.05 mg PO4(3-)-P/L. The application of disintegrated sludge did not deteriorate effluent quality in terms of COD and NH4(+)-N. The concentration of NH4(+)-N in both series averaged 0.16 ± 0.11 mg NH4(+)-N/L, and the concentration of COD was 15.36 ± 3.54 mg O2/L.

  9. Enhancing combined biological nitrogen and phosphorus removal from wastewater by applying mechanically disintegrated excess sludge.

    PubMed

    Zubrowska-Sudol, Monika; Walczak, Justyna

    2015-06-01

    The goal of the study was to evaluate the possibility of applying disintegrated excess sludge as a source of organic carbon to enhance biological nitrogen and phosphorus removal. The experiment, performed in a sequencing batch reactor, consisted of two two-month series, without and with applying mechanically disintegrated excess sludge, respectively. The effects on carbon, nitrogen and phosphorus removal were observed. It was shown that the method allows enhancement of combined nitrogen and phosphorus removal. After using disintegrated sludge, denitrification effectiveness increased from 49.2 ± 6.8% to 76.2 ± 2.3%, which resulted in a decline in the NOx-N concentration in the effluent from the SBR by an average of 21.4 mg NOx-N/L. Effectiveness of biological phosphorus removal increased from 28.1 ± 11.3% to 96.2 ± 2.5%, thus resulting in a drop in the [Formula: see text] concentration in the effluent by, on average, 6.05 mg PO4(3-)-P/L. The application of disintegrated sludge did not deteriorate effluent quality in terms of COD and NH4(+)-N. The concentration of NH4(+)-N in both series averaged 0.16 ± 0.11 mg NH4(+)-N/L, and the concentration of COD was 15.36 ± 3.54 mg O2/L. PMID:25776916

  10. Ultra-weak photon emission from biological samples: definition, mechanisms, properties, detection and applications.

    PubMed

    Cifra, Michal; Pospíšil, Pavel

    2014-10-01

    This review attempts to summarize molecular mechanisms, spectral and intensity properties, detection techniques and applications of ultra-weak photon emission. Ultra-weak photon emission is the chemiluminescence from biological systems where electronically excited species are formed during oxidative metabolic or oxidative stress processes. It is generally accepted that photons are emitted (1) at near UVA, visible, and near IR spectral ranges from 350 to 1300nm and (2) at the intensity of photon emission in the range of several units to several hundreds (oxidative metabolic process) and several hundreds to several thousands (oxidative stress process) photons s(-1)cm(-2). Current development in detection using low-noise photomultiplier tubes and imaging using highly sensitive charge coupled device cameras allows temporal and spatial visualization of oxidative metabolic or oxidative stress processes, respectively. As the phenomenon of ultra-weak photon emission reflects oxidative metabolic or oxidative stress processes, it can be widely used as a non-invasive tool for monitoring of the physiological state of biological systems.

  11. Heavy-ion radiobiology: new approaches to delineate mechanisms underlying enhanced biological effectiveness.

    PubMed

    Blakely, E A; Kronenberg, A

    1998-11-01

    Shortly after the discovery of polonium and radium by Marie Curie and her husband and colleague, Pierre Curie, it was learned that exposure to these alpha-particle emitters produced deleterious biological effects. The mechanisms underlying the increased biological effectiveness of densely ionizing radiations, including alpha particles, neutrons and highly energetic heavy charged particles, remain an active area of investigation. In this paper, we review recent advances in several areas of the radiobiology of these densely ionizing radiations, also known as heavy ions. Advances are described in the areas of DNA damage and repair, chromosome aberrations, mutagenesis, neoplastic transformation in vitro, genomic instability, normal tissue radiobiology and carcinogenesis in vivo. We focus on technical innovations, including novel applications of pulsed-field gel electrophoresis, fluorescence in situ hybridization (FISH), linkage analysis, and studies of gene expression and protein expression. We also highlight the use of new cellular and animal systems, including those with defined DNA repair deficiencies, as well as epithelial cell model systems to assess neoplastic transformation both in vitro and in vivo. The studies reviewed herein have had a substantial impact on our understanding of the genotoxic effects of heavy ions as well as their distinct effects on tissue homeostasis. The use of these radiations in cancer therapy is also discussed. The use of both heavy-ion and proton therapy is on the upswing in several centers around the world, due to their unique energy deposition characteristics that enhance the therapeutic effect and help reduce damage to normal tissue. PMID:9806616

  12. [Biological preparations with different mechanism of action for protecting potato against fungal diseases].

    PubMed

    Kulikov, S N; Alimova, F K; Zakharova, N G; Nemtsev, S V; Varlamov, V P

    2006-01-01

    Mycological analysis throughout the vegetation period of potato (Solanum tuberosum) made it possible to study in detail the structure of micromycete community, to determine typical dominant (frequency, more than 60%), typical common (frequency, 30 to 60%), typical rare (frequency, 10 to 30%), and casual (frequency, less than 10%) species and to estimate changes in the microorganism community caused by plant protection preparations with different mechanisms of action. It was shown that, as a result of occurrence of resistant forms, synthetic preparations against fungal pathogens of potato (such as TMTD, Ridomil gold MC, and Cupricol) were only slightly more effective than biological preparations (Trichodermin and AgroChit), with the former considerably changing the natural saprophytic mycological community. An increase in the soil pool of Trichoderma harzianum as a result of application of a biological preparation based on this antagonistic fungus correlated with its effectiveness against the soil pathogen Fusarium sp., which causes root rots. A chitosan-based elicitor preparation more effectively suppressed the development of early (Alternaria sp. and Macrosporium sp.) and late (Phytophthora sp.) blights of leaves and had a weaker effect on the soil microflora.

  13. A systems biology approach to defining regulatory mechanisms for cartilage and tendon cell phenotypes

    PubMed Central

    Mueller, A. J.; Tew, S. R.; Vasieva, O.; Clegg, P. D.; Canty-Laird, E. G.

    2016-01-01

    Phenotypic plasticity of adult somatic cells has provided emerging avenues for the development of regenerative therapeutics. In musculoskeletal biology the mechanistic regulatory networks of genes governing the phenotypic plasticity of cartilage and tendon cells has not been considered systematically. Additionally, a lack of strategies to effectively reproduce in vitro functional models of cartilage and tendon is retarding progress in this field. De- and redifferentiation represent phenotypic transitions that may contribute to loss of function in ageing musculoskeletal tissues. Applying a systems biology network analysis approach to global gene expression profiles derived from common in vitro culture systems (monolayer and three-dimensional cultures) this study demonstrates common regulatory mechanisms governing de- and redifferentiation transitions in cartilage and tendon cells. Furthermore, evidence of convergence of gene expression profiles during monolayer expansion of cartilage and tendon cells, and the expression of key developmental markers, challenges the physiological relevance of this culture system. The study also suggests that oxidative stress and PI3K signalling pathways are key modulators of in vitro phenotypes for cells of musculoskeletal origin. PMID:27670352

  14. Biological, mechanical, and technological considerations affecting the longevity of intracortical electrode recordings.

    PubMed

    Harris, James P; Tyler, Dustin J

    2013-01-01

    Intracortical electrodes are important tools, with applications ranging from fundamental laboratory studies to potential solutions to intractable clinical applications. However, the longevity and reliability of the interfaces remain their major limitation to the wider implementation and adoption of this technology, especially in broader translational work. Accordingly, this review summarizes the most significant biological and technical factors influencing the long-term performance of intracortical electrodes. In a laboratory setting, intracortical electrodes have been used to study the normal and abnormal function of the brain. This improved understanding has led to valuable insights regarding many neurological conditions. Likewise, clinical applications of intracortical brain-machine interfaces offer the ability to improve the quality of life of many patients afflicted with high-level paralysis from spinal cord injury, brain stem stroke, amyotrophic lateral sclerosis, or other conditions. It is widely hypothesized that the tissue response to the electrodes, including inflammation, limits their longevity. Many studies have examined and modified the tissue response to intracortical electrodes to improve future intracortical electrode technologies. Overall, the relationship between biological, mechanical, and technological considerations are crucial for the fidelity of chronic electrode recordings and represent a presently active area of investigation in the field of neural engineering.

  15. In situ activity recovery of aging biofilm in biological aerated filter: Surfactants treatment and mechanisms study.

    PubMed

    Yu, Qisheng; Huang, Hui; Ren, Hongqiang; Ding, Lili; Geng, Jinju

    2016-11-01

    In situ activity recovery of aging biofilm in the biological aerated filter (BAF) is an important but underappreciated problem. Lab-scaled BAFs were established in this study and three kinds of surfactants containing sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS) and rhamnolipid were employed. Multiple indicators including effluent qualities, dissolved organic matters, biofilm physiology and morphology characteristics were investigated to explore the mechanisms. Results showed that removal rates of effluent COD in test groups significantly recovered to the level before aging. Compared with the control, effluent in SDBS and rhamnolipid-treated groups obtained more protein-like and humic-like substances, respectively. Furthermore, great live cell ratio, smooth surface and low adhesion force of biofilm were observed after rhamnolipid treatment, which was in consistent with good effluent qualities in the same group. This is the first report of applying rhamnolipid for in situ activity recovery of aging biofilm in bioreactors. PMID:27513646

  16. Biological mechanism for the toxicity of haloacetic acid drinking water disinfection byproducts.

    PubMed

    Pals, Justin A; Ang, Justin K; Wagner, Elizabeth D; Plewa, Michael J

    2011-07-01

    The halogenated acetic acids are a major class of drinking water disinfection byproducts (DBPs) with five haloacetic acids regulated by the U.S. EPA. These agents are cytotoxic, genotoxic, mutagenic, and teratogenic. The decreasing toxicity rank order of the monohalogenated acetic acids (monoHAAs) is iodo- > bromo- > chloroacetic acid. We present data that the monoHAAs inhibit glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity in a concentration-dependent manner with the same rank order as above. The rate of inhibition of GAPDH and the toxic potency of the monoHAAs are highly correlated with their alkylating potential and the propensity of the halogen leaving group. This strong association between GAPDH inhibition and the monoHAA toxic potency supports a comprehensive mechanism for the adverse biological effects by this widely occurring class of regulated DBPs.

  17. Microwave absorption by magnetite: a possible mechanism for coupling nonthermal levels of radiation to biological systems.

    PubMed

    Kirschvink, J L

    1996-01-01

    The presence of trace amounts of biogenic magnetite (Fe3O4) in animal and human tissues and the observation that ferromagnetic particles are ubiquitous in laboratory materials (including tissue culture media) provide a physical mechanism through which microwave radiation might produce or appear to produce biological effects. Magnetite is an excellent absorber of microwave radiation at frequencies between 0.5 and 10.0 GHz through the process of ferromagnetic resonance, where the magnetic vector of the incident field causes precession of Bohr magnetons around the internal demagnetizing field of the crystal. Energy absorbed by this process is first transduced into acoustic vibrations at the microwave carrier frequency within the crystal lattice via the magnetoacoustic effect; then, the energy should be dissipated in cellular structures in close proximity to the magnetite crystals. Several possible methods for testing this hypothesis experimentally are discussed. Studies of microwave dosimetry at the cellular level should consider effects of biogenic magnetite.

  18. Untangling nociceptive, neuropathic and neuroplastic mechanisms underlying the biological domain of back pain.

    PubMed

    Hush, Julia M; Stanton, Tasha R; Siddall, Philip; Marcuzzi, Anna; Attal, Nadine

    2013-05-01

    SUMMARY Current clinical practice guidelines advocate a model of diagnostic triage for back pain, underpinned by the biopsychosocial paradigm. However, limitations of this clinical model have become apparent: it can be difficult to classify patients into the diagnostic triage categories; patients with 'nonspecific back pain' are clearly not a homogenous group; and mean effects of treatments based on this approach are small. In this article, it is proposed that the biological domain of the biopsychosocial model needs to be reconceptualized using a neurobiological mechanism-based approach. Recent evidence about nociceptive and neuropathic contributors to back pain is outlined in the context of maladaptive neuroplastic changes of the somatosensory system. Implications for clinical practice and research are discussed.

  19. Racism, society, and disease: an exploration of the social and biological mechanisms of differential mortality.

    PubMed

    Cooper, R; Steinhauer, M; Miller, W; David, R; Schatzkin, A

    1981-01-01

    Racial differentials in mortality provide important insight into the nature of mass disease in capitalist society. Not only are the differentials sizable in magnitude, they are consistent for multiple causes of death and appear to evolve in response to social development. The relationships among social factors and the biological and physical agents of disease can be identified through racial contrasts and a pattern of causation which applies to both the minority and majority populations described. Furthermore, the impact of exploitation as the primary disease-mediating factor under capitalist social relations can be estimated. This paper attempts to combine an analysis of bio-medical mechanisms with Marxist social theory in a comprehensive framework for the study of the social origins of racial differentials.

  20. Racism, society, and disease: an exploration of the social and biological mechanisms of differential mortality.

    PubMed

    Cooper, R; Steinhauer, M; Miller, W; David, R; Schatzkin, A

    1981-01-01

    Racial differentials in