Science.gov

Sample records for common cellular events

  1. The Mosaic Theory Revisited: Common Molecular Mechanisms Coordinating Diverse Organ and Cellular Events in Hypertension

    PubMed Central

    Harrison, David G.

    2012-01-01

    Over 60 years ago, Dr. Irvine Page proposed the Mosaic Theory of hypertension, which states that many factors, including genetics, environment, adaptive, neural, mechanical and hormonal perturbations interdigitate to raise blood pressure. In the past two decades, it has become clear that common molecular and cellular events in various organs underlie many features of the Mosaic Theory. Two of these are the production of reactive oxygen species (ROS) and inflammation. These factors increase neuronal firing in specific brain centers, increase sympathetic outflow, alter vascular tone and morphology and promote sodium retention in the kidney. Moreover, factors such as genetics and environment contribute to oxidant generation and inflammation. Other common cellular signals, including calcium signaling and endoplasmic reticulum stress are similarly perturbed in different cells in hypertension and contribute to components of Dr. Page’s theory. Thus, Dr. Page’s Mosaic Theory formed a framework for future studies of molecular and cellular signals in the context of hypertension, and has greatly aided our understanding of this complex disease. PMID:23321405

  2. Cellular antioxidant activity of common vegetables.

    PubMed

    Song, Wei; Derito, Christopher M; Liu, M Keshu; He, Xiangjiu; Dong, Mei; Liu, Rui Hai

    2010-06-09

    The measurement of antioxidant activity using biologically relevant assays is important to screen fruits, vegetables, natural products, and dietary supplements for potential health benefits. The cellular antioxidant activity (CAA) assay quantifies antioxidant activity using a cell culture model and was developed to meet the need for a more biologically representative method than the popular chemistry antioxidant capacity measures. The objective of the study was to determine the CAA, total phenolic contents, and oxygen radical absorbance capacity (ORAC) values of 27 vegetables commonly consumed in the United States. Beets, broccoli, and red pepper had the highest CAA values, whereas cucumber had the lowest. CAA values were significantly correlated to total phenolic content. Potatoes were found to be the largest contributors of vegetable phenolics and CAA to the American diet. Increased fruit and vegetable consumption is an effective strategy to increase antioxidant intake and decrease oxidative stress and may lead to reduced risk of developing chronic diseases, such as cancer and cardiovascular disease.

  3. Cellular events and biomarkers of wound healing

    PubMed Central

    Shah, Jumaat Mohd. Yussof; Omar, Effat; Pai, Dinker R.; Sood, Suneet

    2012-01-01

    Researchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs) and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF) is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth factors initiate fibroblast and keratinocyte proliferation. Inflammation is followed by the proliferation of fibroblasts, which lay down the extracellular matrix. Simultaneously, various white cells and other connective tissue cells release both the matrix metalloproteinases (MMPs) and the tissue inhibitors of these metalloproteinases (TIMPs). MMPs remove damaged structural proteins such as collagen, while the fibroblasts lay down fresh extracellular matrix proteins. Fluid collected from acute, healing wounds contains growth factors, and stimulates fibroblast proliferation, but fluid collected from chronic, nonhealing wounds does not. Fibroblasts from chronic wounds do not respond to chronic wound fluid, probably because the fibroblasts of these wounds have lost the receptors that respond to cytokines and growth factors. Nonhealing wounds contain high levels of IL1, IL6, and MMPs, and an abnormally high MMP/TIMP ratio. Clinical examination of wounds inconsistently predicts which wounds will heal when procedures like secondary closure are planned. Surgeons therefore hope that these chemicals can be used as biomarkers of wounds which have impaired ability to heal. There is also evidence that the application of growth factors like PDGF will help the healing of chronic, nonhealing wounds. PMID:23162220

  4. Treatment of common 'life event' traumas.

    PubMed

    Macnab, Francis

    2003-09-01

    General practitioners are confronted daily with patients who have experienced distressing 'life events'. Assisting patients through this process can present a significant challenge. This article points to the reactive symptomatology that may be overtly present or concealed in a stressful event and its aftermath reactions, sets the goal of restoring a person's functioning and their self resources, and gives guidelines of what counselling can do for a patient. People who are attempting to cope with a distressing 'life event' or the aftermath of a trauma can be effectively helped by early short term counselling. Although this task may not be one that appeals to the busy GP, many accessible interventions can restore a person's coping capacity and avoid the prospect of a continuing and deepening pathology. Many symptoms will not fit the diagnostic categories usually associated with stress disorders. Some may show impaired social engagement and social phobia; others may describe low self worth, states of unwellness, relationship dissatisfaction and maladjustments in key areas of behaviour. The task is to help the person gain a different perspective on the distressing event, their own capacities and the supportive influences around them.

  5. Pathogenesis of pulmonary emphysema - cellular and molecular events.

    PubMed

    Di Petta, Antonio

    2010-06-01

    Pulmonary emphysema is a chronic obstructive disease, resulting from important alterations in the whole distal structure of terminal bronchioles, either by enlargement of air spaces or by destruction of the alveolar wall, leading to loss of respiratory surface, decreased elastic recoil and lung hyperinflation. For many years, the hypothesis of protease-antiprotease unbalance prevailed as the central theme in the pathogenesis of pulmonary emphysema. According to this hypothesis, the release of active proteolytic enzymes, produced mainly by neutrophils and macrophages, degrades the extracellular matrix, affecting the integrity of its components, especially collagen and elastic fibers. However, new concepts involving cellular and molecular events were proposed, including oxidative stress, cell apoptosis, cellular senescence and failed lung tissue repair. The aim of this review paper was to evaluate the cellular and molecular mechanisms seen in the pathogenesis of pulmonary emphysema.

  6. Apoptotic cellular events for selenium compounds involved in cancer prevention.

    PubMed

    Rikiishi, Hidemi

    2007-02-01

    Converging data from epidemiological, ecological, and clinical studies have shown that selenium (Se) can decrease the risk for some types of human cancers. Induction of apoptosis is considered an important cellular event that can account for the cancer preventive effects of Se. Prior to occurrence of apoptosis, Se compounds alter the expression and/or activities of signaling molecules, mitochondria-associated factors, transcriptional factors, tumor suppressor genes, and cellular reduced glutathione. Mechanistic studies have demonstrated that the methylselenol metabolite pool has many desirable attributes of chemoprevention, whereas the hydrogen selenide pool with excess of selenoprotein synthesis can lead to DNA single-strand breaks. To elucidate the effects of Se on cytotoxic events, it should be remembered that the chemical forms and the dose of Se, and the experimental system used, are determinants of its biological activities. This mini-review focuses on elucidation of the molecular mechanisms of cancer prevention by Se with the apoptotic approach.

  7. Cellular Dynamic Simulator: An Event Driven Molecular Simulation Environment for Cellular Physiology

    PubMed Central

    Byrne, Michael J.; Waxham, M. Neal; Kubota, Yoshihisa

    2010-01-01

    In this paper, we present the Cellular Dynamic Simulator (CDS) for simulating diffusion and chemical reactions within crowded molecular environments. CDS is based on a novel event driven algorithm specifically designed for precise calculation of the timing of collisions, reactions and other events for each individual molecule in the environment. Generic mesh based compartments allow the creation / importation of very simple or detailed cellular structures that exist in a 3D environment. Multiple levels of compartments and static obstacles can be used to create a dense environment to mimic cellular boundaries and the intracellular space. The CDS algorithm takes into account volume exclusion and molecular crowding that may impact signaling cascades in small sub-cellular compartments such as dendritic spines. With the CDS, we can simulate simple enzyme reactions; aggregation, channel transport, as well as highly complicated chemical reaction networks of both freely diffusing and membrane bound multi-protein complexes. Components of the CDS are generally defined such that the simulator can be applied to a wide range of environments in terms of scale and level of detail. Through an initialization GUI, a simple simulation environment can be created and populated within minutes yet is powerful enough to design complex 3D cellular architecture. The initialization tool allows visual confirmation of the environment construction prior to execution by the simulator. This paper describes the CDS algorithm, design implementation, and provides an overview of the types of features available and the utility of those features are highlighted in demonstrations. PMID:20361275

  8. Cellular dynamic simulator: an event driven molecular simulation environment for cellular physiology.

    PubMed

    Byrne, Michael J; Waxham, M Neal; Kubota, Yoshihisa

    2010-06-01

    In this paper, we present the Cellular Dynamic Simulator (CDS) for simulating diffusion and chemical reactions within crowded molecular environments. CDS is based on a novel event driven algorithm specifically designed for precise calculation of the timing of collisions, reactions and other events for each individual molecule in the environment. Generic mesh based compartments allow the creation / importation of very simple or detailed cellular structures that exist in a 3D environment. Multiple levels of compartments and static obstacles can be used to create a dense environment to mimic cellular boundaries and the intracellular space. The CDS algorithm takes into account volume exclusion and molecular crowding that may impact signaling cascades in small sub-cellular compartments such as dendritic spines. With the CDS, we can simulate simple enzyme reactions; aggregation, channel transport, as well as highly complicated chemical reaction networks of both freely diffusing and membrane bound multi-protein complexes. Components of the CDS are generally defined such that the simulator can be applied to a wide range of environments in terms of scale and level of detail. Through an initialization GUI, a simple simulation environment can be created and populated within minutes yet is powerful enough to design complex 3D cellular architecture. The initialization tool allows visual confirmation of the environment construction prior to execution by the simulator. This paper describes the CDS algorithm, design implementation, and provides an overview of the types of features available and the utility of those features are highlighted in demonstrations.

  9. Raman imaging of molecular dynamics during cellular events

    NASA Astrophysics Data System (ADS)

    Fujita, Katsumasa

    2017-07-01

    To overcome the speed limitation in Raman imaging, we have developed a microscope system that detects Raman spectra from hundreds of points in a sample simultaneously. The sample was illuminated by a line-shaped focus, and Raman scattering from the illuminated positions was measured simultaneously by an imaging spectrophotometer. We applied the line-illumination technique to observe the dynamics of intracellular molecules during cellular events. We found that intracellular cytochrome c can be clearly imaged by resonant Raman scattering. We demonstrated label-free imaging of redistribution of cytochrome c during apoptosis and osteoblastic mineralization. We also proposed alkyne-tagged Raman imaging to observe small molecules in living cells. Due to its small size and the unique Raman band, alkyne can tag molecules without strong perturbation to molecular functions and with the capability to be detected separately from endogenous molecules.

  10. Early events in annelid regeneration: a cellular perspective.

    PubMed

    Bely, Alexandra E

    2014-10-01

    The ability to regenerate extensive portions of the body is widespread among the phylum Annelida and this group includes some of the most highly regenerative animals known. Knowledge of the cellular and molecular basis of regeneration in this group is thus important for understanding how regenerative processes have evolved both within the group and across animal phyla. Here, the cellular basis of annelid regeneration is reviewed, with a focus on the earliest steps of regeneration, namely wound-healing and formation of the blastema. Information from a wide range of annelids is compiled in order to identify common and variable elements. There is a large body of valuable older literature on the cellular basis of regeneration in annelids and an effort is made to review this literature in addition to more recent studies. Annelids typically seal the wound through muscular contraction and undergo some autolysis of tissue at the site of the wound. Bodily injury elicits extensive cell migration toward the wound, involving several different types of cells. Some migrating cells form a tissue-clot and phagocytize damaged tissues, whereas others are inferred to contribute to regenerated tissue, specifically mesodermal tissue. In one annelid subgroup, the clitellates, a group of mesodermal cells, sometimes referred to as neoblasts, is inferred to migrate over considerable distances, with cells moving to the wound from several segments away. Epidermis and gut epithelia severed upon amputation typically heal by fusing with like tissue, although not always. After amputation, cellular contacts with the extracellular matrix are disrupted and major changes in cell morphology and adhesion occur within tissues near the wound. Interactions of tissues at the wound appear key for initiating a blastema, with a particularly important role suggested for the ventral nerve cord, although species are variable in this regard; longer-distance effects mediated by the brain are also reported. The

  11. A common mechanism of cellular death induced by bactericidal antibiotics.

    PubMed

    Kohanski, Michael A; Dwyer, Daniel J; Hayete, Boris; Lawrence, Carolyn A; Collins, James J

    2007-09-07

    Antibiotic mode-of-action classification is based upon drug-target interaction and whether the resultant inhibition of cellular function is lethal to bacteria. Here we show that the three major classes of bactericidal antibiotics, regardless of drug-target interaction, stimulate the production of highly deleterious hydroxyl radicals in Gram-negative and Gram-positive bacteria, which ultimately contribute to cell death. We also show, in contrast, that bacteriostatic drugs do not produce hydroxyl radicals. We demonstrate that the mechanism of hydroxyl radical formation induced by bactericidal antibiotics is the end product of an oxidative damage cellular death pathway involving the tricarboxylic acid cycle, a transient depletion of NADH, destabilization of iron-sulfur clusters, and stimulation of the Fenton reaction. Our results suggest that all three major classes of bactericidal drugs can be potentiated by targeting bacterial systems that remediate hydroxyl radical damage, including proteins involved in triggering the DNA damage response, e.g., RecA.

  12. Common-Cause Failure Analysis in Event Assessment

    SciTech Connect

    Dana L. Kelly; Dale M. Rasmuson

    2008-09-01

    This paper describes the approach taken by the U. S. Nuclear Regulatory Commission to the treatment of common-cause failure in probabilistic risk assessment of operational events. The approach is based upon the Basic Parameter Model for common-cause failure, and examples are illustrated using the alpha-factor parameterization, the approach adopted by the NRC in their Standardized Plant Analysis Risk (SPAR) models. The cases of a failed component (with and without shared common-cause failure potential) and a component being unavailable due to preventive maintenance or testing are addressed. The treatment of two related failure modes (e.g., failure to start and failure to run) is a new feature of this paper. These methods are being applied by the NRC in assessing the risk significance of operational events for the Significance Determination Process (SDP) and the Accident Sequence Precursor (ASP) program.

  13. A CORBA event system for ALMA common software

    NASA Astrophysics Data System (ADS)

    Fugate, David W.

    2004-09-01

    The ALMA Common Software notification channel framework provides developers with an easy to use, high-performance, event-driven system supported across multiple programming languages and operating systems. It sits on top of the CORBA notification service and hides nearly all CORBA from developers. The system is based on a push event channel model where suppliers push events onto the channel and consumers process these asynchronously. This is a many-to-many publishing model whereby multiple suppliers send events to multiple consumers on the same channel. Furthermore, these event suppliers and consumers can be coded in C++, Java, or Python on any platform supported by ACS. There are only two classes developers need to be concerned with: SimpleSupplier and Consumer. SimpleSupplier was designed so that ALMA events (defined as IDL structures) could be published in the simplest manner possible without exposing any CORBA to the developer. Essentially all that needs to be known is the channel's name and the IDL structure being published. The API takes care of everything else. With the Consumer class, the developer is responsible for providing the channel's name as well as associating event types with functions that will handle them.

  14. Common-Cause Failure Analysis in Event Assessment

    SciTech Connect

    D. M. Rasmuson; D. L. Kelly

    2008-06-01

    This paper reviews the basic concepts of modelling common-cause failures (CCFs) in reliability and risk studies and then applies these concepts to the treatment of CCF in event assessment. The cases of a failed component (with and without shared CCF potential) and a component being unavailable due to preventive maintenance or testing are addressed. The treatment of two related failure modes (e.g. failure to start and failure to run) is a new feature of this paper, as is the treatment of asymmetry within a common-cause component group.

  15. Chronology of mitochondrial and cellular events during skeletal muscle ischemia-reperfusion

    PubMed Central

    Charles, Anne-Laure; Meyer, Alain; Lejay, Anne; Scholey, James W.; Chakfé, Nabil; Zoll, Joffrey; Geny, Bernard

    2016-01-01

    Peripheral artery disease (PAD) is a common circulatory disorder of the lower limb arteries that reduces functional capacity and quality of life of patients. Despite relatively effective available treatments, PAD is a serious public health issue associated with significant morbidity and mortality. Ischemia-reperfusion (I/R) cycles during PAD are responsible for insufficient oxygen supply, mitochondriopathy, free radical production, and inflammation and lead to events that contribute to myocyte death and remote organ failure. However, the chronology of mitochondrial and cellular events during the ischemic period and at the moment of reperfusion in skeletal muscle fibers has been poorly reviewed. Thus, after a review of the basal myocyte state and normal mitochondrial biology, we discuss the physiopathology of ischemia and reperfusion at the mitochondrial and cellular levels. First we describe the chronology of the deleterious biochemical and mitochondrial mechanisms activated by I/R. Then we discuss skeletal muscle I/R injury in the muscle environment, mitochondrial dynamics, and inflammation. A better understanding of the chronology of the events underlying I/R will allow us to identify key factors in the development of this pathology and point to suitable new therapies. Emerging data on mitochondrial dynamics should help identify new molecular and therapeutic targets and develop protective strategies against PAD. PMID:27076618

  16. Asymptomatic pulmonary embolism: a common event in high risk patients

    SciTech Connect

    Williams, J.W.; Eikman, E.A.; Greenberg, S.

    1982-03-01

    Ventilation and perfusion lung scans were obtained before and at weekly intervals following hip surgery or major amputation in 158 patients. Pulmonary arteriograms were obtained in 21 of 33 patients developing perfusion patterns strongly suggesting embolism; 19 of the 21 arteriograms demonstrated pulmonary embolism. From autopsy and clinical data, 36 patients were diagnosed as having an embolus while under study, and 12 patients were suspected of having had an embolus during their illness but prior to entry into the study. Only four of these 48 patients experienced symptoms suggestive of pulmonary embolism. We conclude that asymptomatic pulmonary embolism is a common event in the populations studied.

  17. Asymptomatic pulmonary embolism. A common event in high risk patients.

    PubMed Central

    Williams, J W; Eikman, E A; Greenberg, S

    1982-01-01

    Ventilation and perfusion lung scans were obtained before and at weekly intervals following hip surgery or major amputation in 158 patients. Pulmonary arteriograms were obtained in 21 of 33 patients developing perfusion patterns strongly suggesting embolism; 19 of the 21 arteriograms demonstrated pulmonary embolism. From autopsy and clinical data, 36 patients were diagnosed as having an embolus while under study, and 12 patients were suspected of having had an embolus during their illness but prior to entry into the study. Only four of these 48 patients experienced symptoms suggestive of pulmonary embolism. We conclude that asymptomatic pulmonary embolism is a common event in the populations studied. PMID:7059242

  18. Role of cellular events in the pathophysiology of sepsis.

    PubMed

    Bhan, Chandra; Dipankar, Pankaj; Chakraborty, Papiya; Sarangi, Pranita P

    2016-11-01

    Sepsis is a dysregulated host immune response due to an uncontrolled infection. It is a leading cause of mortality in adult intensive care units globally. When the host immune response induced against a local infection fails to contain it locally, it progresses to sepsis, severe sepsis, septic shock and death. Literature survey was performed on the roles of different innate and adaptive immune cells in the development and progression of sepsis. Additionally, the effects of septic changes on reprogramming of different immune cells were also summarized to prepare the manuscript. Scientific evidences to date suggest that the loss of balance between inflammatory and anti-inflammatory responses results in reprogramming of immune cell activities that lead to irreversible tissue damaging events and multi-organ failure during sepsis. Many surface receptors expressed on immune cells at various stages of sepsis have been suggested as biomarkers for sepsis diagnosis. Various immunomodulatory therapeutics, which could improve the functions of immune cells during sepsis, were shown to restore immunological homeostasis and improve survival in animal models of sepsis. In-depth and comprehensive knowledge on the immune cell activities and their correlation with severity of sepsis will help clinicians and scientists to design effective immunomodulatory therapeutics for treating sepsis.

  19. Integrated Circuit-Based Biofabrication with Common Biomaterials for Probing Cellular Biomechanics.

    PubMed

    Sung, Chun-Yen; Yang, Chung-Yao; Yeh, J Andrew; Cheng, Chao-Min

    2016-02-01

    Recent advances in bioengineering have enabled the development of biomedical tools with modifiable surface features (small-scale architecture) to mimic extracellular matrices and aid in the development of well-controlled platforms that allow for the application of mechanical stimulation for studying cellular biomechanics. An overview of recent developments in common biomaterials that can be manufactured using integrated circuit-based biofabrication is presented. Integrated circuit-based biofabrication possesses advantages including mass and diverse production capacities for fabricating in vitro biomedical devices. This review highlights the use of common biomaterials that have been most frequently used to study cellular biomechanics. In addition, the influence of various small-scale characteristics on common biomaterial surfaces for a range of different cell types is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Identification of the "minimal triangle" and other common event-to-event transitions in conflict and containment incidents.

    PubMed

    Bowers, Len; James, Karen; Quirk, Alan; Wright, Steve; Williams, Hilary; Stewart, Duncan

    2013-07-01

    Although individual conflict and containment events among acute psychiatric inpatients have been studied in some detail, the relationship of these events to each other has not. In particular, little is known about the temporal order of events for individual patients. This study aimed to identify the most common pathways from event to event. A sample of 522 patients was recruited from 84 acute psychiatric wards in 31 hospital locations in London and the surrounding areas during 2009-2010. Data on the order of conflict and containment events were collected for the first two weeks of admission from patients' case notes. Event-to-event transitions were tabulated and depicted diagrammatically. Event types were tested for their most common temporal placing in sequences of events. Most conflict and containment occurs within and between events of the minimal triangle (verbal aggression, de-escalation, and PRN medication), and the majority of these event sequences conclude in no further events; a minority transition to other, more severe, events. Verbal abuse and medication refusal were more likely to start sequences of disturbed behaviour. Training in the prevention and management of violence needs to acknowledge that a gradual escalation of patient behaviour does not always occur. Verbal aggression is a critical initiator of conflict events, and requires more detailed and sustained research on optimal management and prevention strategies. Similar research is required into medication refusal by inpatients.

  1. Characterization of Morphological and Cellular Events Underlying Oral Regeneration in the Sea Anemone, Nematostella vectensis.

    PubMed

    Amiel, Aldine R; Johnston, Hereroa T; Nedoncelle, Karine; Warner, Jacob F; Ferreira, Solène; Röttinger, Eric

    2015-12-01

    Cnidarians, the extant sister group to bilateria, are well known for their impressive regenerative capacity. The sea anemone Nematostella vectensis is a well-established system for the study of development and evolution that is receiving increased attention for its regenerative capacity. Nematostella is able to regrow missing body parts within five to six days after its bisection, yet studies describing the morphological, cellular, and molecular events underlying this process are sparse and very heterogeneous in their experimental approaches. In this study, we lay down the basic framework to study oral regeneration in Nematostella vectensis. Using various imaging and staining techniques we characterize in detail the morphological, cellular, and global molecular events that define specific landmarks of this process. Furthermore, we describe in vivo assays to evaluate wound healing success and the initiation of pharynx reformation. Using our described landmarks for regeneration and in vivo assays, we analyze the effects of perturbing either transcription or cellular proliferation on the regenerative process. Interestingly, neither one of these experimental perturbations has major effects on wound closure, although they slightly delay or partially block it. We further show that while the inhibition of transcription blocks regeneration in a very early step, inhibiting cellular proliferation only affects later events such as pharynx reformation and tentacle elongation.

  2. Characterization of Morphological and Cellular Events Underlying Oral Regeneration in the Sea Anemone, Nematostella vectensis

    PubMed Central

    Amiel, Aldine R.; Johnston, Hereroa T.; Nedoncelle, Karine; Warner, Jacob F.; Ferreira, Solène; Röttinger, Eric

    2015-01-01

    Cnidarians, the extant sister group to bilateria, are well known for their impressive regenerative capacity. The sea anemone Nematostella vectensis is a well-established system for the study of development and evolution that is receiving increased attention for its regenerative capacity. Nematostella is able to regrow missing body parts within five to six days after its bisection, yet studies describing the morphological, cellular, and molecular events underlying this process are sparse and very heterogeneous in their experimental approaches. In this study, we lay down the basic framework to study oral regeneration in Nematostella vectensis. Using various imaging and staining techniques we characterize in detail the morphological, cellular, and global molecular events that define specific landmarks of this process. Furthermore, we describe in vivo assays to evaluate wound healing success and the initiation of pharynx reformation. Using our described landmarks for regeneration and in vivo assays, we analyze the effects of perturbing either transcription or cellular proliferation on the regenerative process. Interestingly, neither one of these experimental perturbations has major effects on wound closure, although they slightly delay or partially block it. We further show that while the inhibition of transcription blocks regeneration in a very early step, inhibiting cellular proliferation only affects later events such as pharynx reformation and tentacle elongation. PMID:26633371

  3. Cellular events during interfascicular cambium ontogenesis in inflorescence stems of Arabidopsis.

    PubMed

    Mazur, Ewa; Kurczyńska, Ewa U; Friml, Jiři

    2014-09-01

    Development of cambium and its activity is important for our knowledge of the mechanism of secondary growth. Arabidopsis thaliana emerges as a good model plant for such a kind of study. Thus, this paper reports on cellular events taking place in the interfascicular regions of inflorescence stems of A. thaliana, leading to the development of interfascicular cambium from differentiated interfascicular parenchyma cells (IPC). These events are as follows: appearance of auxin accumulation, PIN1 gene expression, polar PIN1 protein localization in the basal plasma membrane and periclinal divisions. Distribution of auxin was observed to be higher in differentiating into cambium parenchyma cells compared to cells within the pith and cortex. Expression of PIN1 in IPC was always preceded by auxin accumulation. Basal localization of PIN1 was already established in the cells prior to their periclinal division. These cellular events initiated within parenchyma cells adjacent to the vascular bundles and successively extended from that point towards the middle region of the interfascicular area, located between neighboring vascular bundles. The final consequence of which was the closure of the cambial ring within the stem. Changes in the chemical composition of IPC walls were also detected and included changes of pectic epitopes, xyloglucans (XG) and extensins rich in hydroxyproline (HRGPs). In summary, results presented in this paper describe interfascicular cambium ontogenesis in terms of successive cellular events in the interfascicular regions of inflorescence stems of Arabidopsis.

  4. Discrimination of Dysplastic Nevi from Common Melanocytic Nevi by Cellular and Molecular Criteria.

    PubMed

    Mitsui, Hiroshi; Kiecker, Felix; Shemer, Avner; Cannizzaro, Maria Vittoria; Wang, Claire Q F; Gulati, Nicholas; Ohmatsu, Hanako; Shah, Kejal R; Gilleaudeau, Patricia; Sullivan-Whalen, Mary; Cueto, Inna; McNutt, Neil Scott; Suárez-Fariñas, Mayte; Krueger, James G

    2016-10-01

    Dysplastic nevi (DNs), also known as Clark's nevi or atypical moles, are distinguished from common melanocytic nevi by variegation in pigmentation and clinical appearance, as well as differences in tissue patterning. However, cellular and molecular differences between DNs and common melanocytic nevi are not completely understood. Using cDNA microarray, quantitative RT-PCR, and immunohistochemistry, we molecularly characterized DNs and analyzed the difference between DNs and common melanocytic nevi. A total of 111 probesets (91 annotated genes, fold change > 2.0 and false discovery rate < 0.25) were differentially expressed between the two lesions. An unexpected finding in DNs was altered differentiation and activation of epidermal keratinocytes with increased expression of hair follicle-related molecules (keratin 25, trichohyalin, ribonuclease, RNase A family, 7) and inflammation-related molecules (S100A7, S100A8) at both genomic and protein levels. The immune microenvironment of DNs was characterized by an increase of T helper type 1 (IFNγ) and T helper type 2 (IL13) cytokines as well as an upregulation of oncostatin M and CXCL1. DUSP3, which regulates cellular senescence, was identified as one of the disease discriminative genes between DNs and common melanocytic nevi by three independent statistical approaches and its altered expression was confirmed by immunohistochemistry. The molecular and cellular changes in which the epidermal-melanin unit undergoes follicular differentiation as well as upregulation of defined cytokines could drive complex immune, epidermal, and pigmentary alterations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Application of a new cellular model for bedload transporting extreme events at steep slopes

    NASA Astrophysics Data System (ADS)

    Chiari, M.; Scheidl, C.

    2015-10-01

    A cellular model for bedload transport at steep channel gradients and alluvial fans has been developed to simulate lateral distribution of erosion and deposition on alluvial fans of mountain streams. The cellular model, named FluviSed, applies a quasi-steady-state routing of a flood hydrograph over a rectangular grid. Bedload transport is calculated and the morphological changes are updated after each time step. FluviSed is designed to complement existing one-dimensional bedload transport simulation tools by using their outcome as an input for the simulation of inundated areas. The model has been evaluated against TomSed, a one-dimensional bedload transport model. Further, a back-calculation of a laboratory bedload experiment and a real flood event from 2005 at Schnannerbach in Austria are provided to test the model's suitability for reproducing morphological changes caused by flood events at high channel gradients.

  6. Disease transmission by cannibalism: rare event or common occurrence?

    PubMed

    Rudolf, Volker H W; Antonovics, Janis

    2007-05-07

    Cannibalism has been documented as a possible disease transmission route in several species, including humans. However, the dynamics resulting from this type of disease transmission are not well understood. Using a theoretical model, we explore how cannibalism (i.e. killing and consumption of dead conspecifics) and intraspecific necrophagy (i.e. consumption of dead conspecifics) affect host-pathogen dynamics. We show that group cannibalism, i.e. shared consumption of victims, is a necessary condition for disease spread by cannibalism in the absence of alternative transmission modes. Thus, endemic diseases transmitted predominantly by cannibalism are likely to be rare, except in social organisms that share conspecific prey. These results are consistent with a review of the literature showing that diseases transmitted by cannibalism are infrequent in animals, even though both cannibalism and trophic transmission are very common.

  7. Disease transmission by cannibalism: rare event or common occurrence?

    PubMed Central

    Rudolf, Volker H.W; Antonovics, Janis

    2007-01-01

    Cannibalism has been documented as a possible disease transmission route in several species, including humans. However, the dynamics resulting from this type of disease transmission are not well understood. Using a theoretical model, we explore how cannibalism (i.e. killing and consumption of dead conspecifics) and intraspecific necrophagy (i.e. consumption of dead conspecifics) affect host–pathogen dynamics. We show that group cannibalism, i.e. shared consumption of victims, is a necessary condition for disease spread by cannibalism in the absence of alternative transmission modes. Thus, endemic diseases transmitted predominantly by cannibalism are likely to be rare, except in social organisms that share conspecific prey. These results are consistent with a review of the literature showing that diseases transmitted by cannibalism are infrequent in animals, even though both cannibalism and trophic transmission are very common. PMID:17327205

  8. Calc-note for the K-reactor common cause event quantification. [Final subcontract

    SciTech Connect

    Kindinger, J.P.

    1992-07-02

    This report provides the Los Alamos National Laboratory`s (LANL) proposed input to the calc-note for the K-reactor common cause event analysis. This input describes the development of common cause parameters from expert opinion.

  9. Correlation between effects of 24 different cytochalasins on cellular structures and cellular events and those on actin in vitro

    PubMed Central

    Yahara, I; Harada, F; Sekita, S; Yoshihira, K; Natori, S

    1982-01-01

    To compare the effects of cytochalasins on the cellular level with those on the molecular level, 24 cytochalasins, 20 natural compounds and 4 derivatives, were used. The following effects were tested for each of 24 cytochalasins; (a) four high dose (2-20 muM) effects on the cellular level: rounding up of fibroblastic cells, contraction of actin cables, formation of hairy filaments containing actin, and inhibition of lymphocyte capping; (b) a low dose (0.2-2 muM) effect: inhibition of membrane ruffling; and (c) two in vitro effects: an inhibition of actin filament elongation (the high affinity effect [low dose effect] in vitro) and an effect on viscosity of actin filaments(the low affinity effect [high dose effect] in vitro). These results indicated that there are almost the same hierarchic orders of relative effectiveness of different cytochalasins between low and high dose effects and between cellular and molecular effects. From the data obtained with the 24 cytochalasins, we have calculated correlation coefficients of 0.87 and 0.79 between an effect in vivo, inhibition of capping, and an effect in vitro, inhibition of actin filament elongation, as well as between inhibition of capping and another effect in vitro, effect on viscosity of actin filaments, respectively. Furthermore, a correlation coefficient between the high affinity effect and the low affinity effect determined in vitro was calculated to be 0.90 from the data obtained in this study. The strong positive correlation among low and high dose effects in vivo and those in vitro suggests that most of the effects caused by a cytochalasin, irrespective of doses or affected phenomena, might be attributed to the interaction between the drug and the common target protein, actin. In the course of the immunofluorescence microscope study on cytochalasin-treated cells using actin antibody, we have found that aspochalasin D, a 10-isopropylcytochalasin, strongly induced the formation of rodlets containing actin in

  10. 76 FR 67456 - Common Formats for Patient Safety Data Collection and Event Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-01

    ... safety events that reached the patient, whether or not there was harm, ] Near misses or close calls... events. When used as designed, the Common Formats allow collection of information on all harms to patients: ``All-cause harm.'' The VTE format includes a description of the patient safety events to...

  11. A microfabricated piezoelectric transducer platform for mechanical characterization of cellular events

    NASA Astrophysics Data System (ADS)

    Hsu, Yu-Hsiang; Tang, William C.

    2009-09-01

    During the last decade, it was discovered that the mechanical properties and interactions of cells and their surrounding extra-cellular matrix play important roles in cellular activities. Substantial efforts have been made to develop various methodologies and tools to study cell mechanics. In this paper, we report an ongoing study on integrating the concept of a smart structure with a microfabricated thin film piezoelectric transducer for characterizing the various changes in mechanical properties associated with cellular events. A microbridge sensor integrated with a thin film piezoelectric transducer was created from silicon dioxide and zinc oxide sandwiched between two gold electrodes. The cells to be tested were cultured on the microbridge surface. The surface tractions exerted by the cells on the microbridge directly modulated the selected resonant behaviors, which were detected with the custom designed effective surface electrode. Our theory and simulation results showed, for the first time, that the application and changes in these surface tractions resulted in resonant and anti-resonant frequency shifts in the impedance response of the piezoelectric transducer. Both spatial and temporal information of dynamic cellular activities could be inferred from the changes in the impedance spectra. The design, theory, finite-element simulation, microfabrication techniques, and preliminary test results are discussed.

  12. The cellular basis of chitin synthesis in fungi and insects: common principles and differences.

    PubMed

    Merzendorfer, Hans

    2011-09-01

    Chitin is a polymer of N-acetylglucosamine, which assembles into microfibrils of about 20 sugar chains. These microfibrils serve as a structural component of natural biocomposites found in cell walls and specialized extracellular matrices such as cuticles and peritrophic membranes. Chitin synthesis is performed by a wide range of organisms including fungi and insects. The underlying biosynthetic machinery is highly conserved and involves several enzymes, of which the chitin synthase is the key enzyme. This membrane integral glycosyltransferase catalyzes the polymerization reaction. Most of what we know about chitin synthesis derives from studies of fungal and insect systems. In this review, common principles and differences will be worked out at the levels of gene organization, enzymatic properties, cellular localization and regulation. Copyright © 2011 Elsevier GmbH. All rights reserved.

  13. Commonly consumed and specialty dietary mushrooms reduce cellular proliferation in MCF-7 human breast cancer cells.

    PubMed

    Martin, Keith R; Brophy, Sara K

    2010-11-01

    Worldwide, over one million women will be newly diagnosed with breast cancer in the next year. Moreover, breast cancer is the second leading cause of cancer death in the USA. An accumulating body of evidence suggests that consumption of dietary mushrooms can protect against breast cancer. In this study, we tested and compared the ability of five commonly consumed or specialty mushrooms to modulate cell number balance in the cancer process using MCF-7 human breast cancer cells. Hot water extracts (80°C for 2 h) of maitake (MT, Grifola frondosa), crimini (CRIM, Agaricus bisporus), portabella (PORT, Agaricus bisporus), oyster (OYS, Pleurotus ostreatus) and white button (WB, Agaricus bisporus) mushrooms or water alone (5% v/v) were incubated for 24 h with MCF-7 cells. Cellular proliferation determined by bromodeoxyuridine incorporation was significantly (P < 0.05) reduced up to 33% by all mushrooms, with MT and OYS being the most effective. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction, an often used mitochondrion-dependent marker of proliferation, was unchanged although decreased (P > 0.05) by 15% with OYS extract. Lactate dehydrogenase release, as a marker of necrosis, was significantly increased after incubation with MT but not with other test mushrooms. Furthermore, MT extract significantly increased apoptosis, or programmed cell death, as determined by terminal deoxynucleotidyl end labeling method, whereas other test mushrooms displayed trends of ∼15%. The total numbers of cells per flask, determined by hemacytometry, were not different from control cultures. Overall, all test mushrooms significantly suppressed cellular proliferation, with MT further significantly inducing apoptosis and cytotoxicity in human breast cancer cells. This suggests that both common and specialty mushrooms may be chemoprotective against breast cancer.

  14. Cellular response in the dermis of common wombats (Vombatus ursinus) infected with Sarcoptes scabiei var. wombati.

    PubMed

    Skerratt, Lee F

    2003-01-01

    The cellular response in the dermis of common wombats (Vombatus ursinus) with sarcoptic mange exhibited some typical aspects of an immune response to Sarcoptes scabiei. There was an induction phase for wombats experimentally infected with S. scabiei represented by absence of a dermal inflammatory infiltrate for at least 12 days after infection. T lymphocytes, plasma cells, mast cells, and neutrophils then entered the dermis, consistent with a type IV (delayed) hypersensitivity response. In free-living wombats with severe parakeratotic sarcoptic mange eosinophils were also present in the dermis suggesting that a type I (immediate) hypersensitivity response may develop after a type IV hypersensitivity response. Absence of plasma cells and B lymphocytes in free-living wombats with severe parakeratotic sarcoptic mange compared with their presence in wombats experimentally infected with S. scabiei suggested that some immune tolerance may develop with severe infections. A large proportion of cells in the dermal response were not identified but were possibly cells of connective tissue. The thickness of the epidermis increased within 4 days in response to S. scabiei infection. Some antibodies raised against human leucocyte antigens CD3, CD5, HLA-DP, DQ, DR, and CD79b cross-reacted with leucocyte antigens of common wombats and were used to identify cell types in inflammatory infiltrates using immunohistochemistry.

  15. Monitoring Cellular Events in Living Mast Cells Stimulated with an Extremely Small Amount of Fluid on a Microchip

    NASA Astrophysics Data System (ADS)

    Munaka, Tatsuya; Abe, Hirohisa; Kanai, Masaki; Sakamoto, Takashi; Nakanishi, Hiroaki; Yamaoka, Tetsuji; Shoji, Shuichi; Murakami, Akira

    2006-07-01

    We successfully developed a measurement system for real-time analysis of cellular function using a newly designed microchip. This microchip was equipped with a micro cell incubation chamber (240 nl) and was stimulated by a very small amount of stimuli (as small as 24 nl). Using the microchip system, cultivation of mast cells was successfully carried out. Monitoring of the cellular events after stimulation with an extremely small amount of fluid on a microchip was performed. This system could be applicable for various types of cellular analysis including real-time monitoring of cellular response by stimulation.

  16. Cellular and Deafness Mechanisms Underlying Connexin Mutation-Induced Hearing Loss - A Common Hereditary Deafness.

    PubMed

    Wingard, Jeffrey C; Zhao, Hong-Bo

    2015-01-01

    Hearing loss due to mutations in the connexin gene family, which encodes gap junctional proteins, is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2) mutations are responsible for ~50% of non-syndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. Recent experiments demonstrate that congenital deafness mainly results from cochlear developmental disorders rather than hair cell degeneration and endocochlear potential reduction, while late-onset hearing loss results from reduction of active cochlear amplification, even though cochlear hair cells have no connexin expression. However, there is no apparent, demonstrable relationship between specific changes in connexin (channel) functions and the phenotypes of mutation-induced hearing loss. Moreover, new experiments further demonstrate that the hypothesized K(+)-recycling disruption is not a principal deafness mechanism for connexin deficiency induced hearing loss. Cx30 (GJB6), Cx29 (GJC3), Cx31 (GJB3), and Cx43 (GJA1) mutations can also cause hearing loss with distinct pathological changes in the cochlea. These new studies provide invaluable information about deafness mechanisms underlying connexin mutation-induced hearing loss and also provide important information for developing new protective and therapeutic strategies for this common deafness. However, the detailed cellular mechanisms underlying these pathological changes remain unclear. Also, little is known about specific mutation-induced pathological changes in vivo and little information is available for humans. Such further studies are urgently required.

  17. Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy.

    PubMed

    Kumar Pasupulati, Anil; Chitra, P Swathi; Reddy, G Bhanuprakash

    2016-12-01

    Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients and a leading cause of end-stage renal disease (ESRD). Degenerative changes such as glomerular hypertrophy, hyperfiltration, widening of basement membranes, tubulointerstitial fibrosis, glomerulosclerosis and podocytopathy manifest in various degrees of proteinuria in DN. One of the key mechanisms implicated in the pathogenesis of DN is non-enzymatic glycation (NEG). NEG is the irreversible attachment of reducing sugars onto free amino groups of proteins by a series of events, which include the formation of Schiff's base and an Amadori product to yield advanced glycation end products (AGEs). AGE modification of client proteins from the extracellular matrix induces crosslinking, which is often associated with thickening of the basement membrane. AGEs activate several intracellular signaling cascades upon interaction with receptor for AGEs (RAGE), which manifest in aberrant cellular responses such as inflammation, apoptosis and autophagy, whereas other receptors such as AGE-R1, AGE-R3 and scavenger receptors also bind to AGEs and ensue endocytosis and degradation of AGEs. Elevated levels of both serum and tissue AGEs are associated with adverse renal outcome. Increased evidence supports that attenuation of AGE formation and/or inhibition of RAGE activation manifest(s) in improving renal function. This review provides insights of NEG, discusses the cellular and molecular events triggered by AGEs, which manifest in the pathogenesis of DN including renal fibrosis, podocyte epithelial-mesenchymal transition and activation of renin-angiotensin system. Therapies designed to target AGEs, such as inhibitors of AGEs formation and crosslink breakers, are discussed.

  18. Ascidians as excellent models for studying cellular events in the chordate body plan.

    PubMed

    Ogura, Yosuke; Sasakura, Yasunori

    2013-08-01

    The larvae of non-vertebrate chordate ascidians consist of countable numbers of cells. With this feature, ascidians provide us with excellent models for studying cellular events in the construction of the chordate body. This review discusses the recent observations of morphogenetic movements and cell cycles and divisions along with tissue specifications during ascidian embryogenesis. Unequal cleavages take place at the posterior blastomeres during the early cleavage stages of ascidians, and the structure named the centrosome-attracting body restricts the position of the nuclei near the posterior pole to achieve the unequal cleavages. The most-posterior cells differentiate into the primordial germ cells. The gastrulation of ascidians starts as early as the 110-cell stage. During gastrulation, the endodermal cells show two-step changes in cell shape that are crucial for gastrulation. The ascidian notochord is composed of only 40 cells. The 40 cells align to form a single row by an event named the convergent extension, and then the notochord cells undergo vacuolation to transform the notochord into a single hollowed tube. The strictly restricted number of notochord cells is achieved by the regulated number of cell divisions coupled with the differentiation of the cells conducted by a key transcription factor, Brachyury. The dorsally located neural tube is a characteristic of chordates. During the closure of the ascidian neural tube, the epidermis surrounding the neural plate moves toward the midline to close the neural fold. This morphogenetic movement is allowed by an elongation of interphase in the epidermal cell cycles.

  19. A database of common-cause events for risk and reliability applications

    SciTech Connect

    Fleming, K.N.; Rao, S.B. )

    1992-06-01

    This report documents a common cause event database and updates an earlier version of a database that was published as EPRI report NP-3967 in June 1985. The purposes of this report are to provide more information on the original set of common cause events, to expand on both the number of events and the coverage of different component types, and to provide guidance in how to use the database to support applied risk and reliability evaluations such as the ongoing individual plant examination (IPE). Included in this report are descriptions and analyses of events that were found to be of potential importance in a common cause analysis, statistical information from which to estimate common cause failure probabilities, and examples of how the information can be used to support a plant-specific probabilistic risk assessment (PRA) or reliability evaluation, according to the PRA Procedures for Common Cause Analysis documented in NUREG/CR-4780. That procedures guide, which was developed under joint sponsorship of EPRI and the US Nuclear Regulatory Commission, was supported by EPRI research project RP2169-4.

  20. A database of common-cause events for risk and reliability applications. Final report

    SciTech Connect

    Fleming, K.N.; Rao, S.B.

    1992-06-01

    This report documents a common cause event database and updates an earlier version of a database that was published as EPRI report NP-3967 in June 1985. The purposes of this report are to provide more information on the original set of common cause events, to expand on both the number of events and the coverage of different component types, and to provide guidance in how to use the database to support applied risk and reliability evaluations such as the ongoing individual plant examination (IPE). Included in this report are descriptions and analyses of events that were found to be of potential importance in a common cause analysis, statistical information from which to estimate common cause failure probabilities, and examples of how the information can be used to support a plant-specific probabilistic risk assessment (PRA) or reliability evaluation, according to the PRA Procedures for Common Cause Analysis documented in NUREG/CR-4780. That procedures guide, which was developed under joint sponsorship of EPRI and the US Nuclear Regulatory Commission, was supported by EPRI research project RP2169-4.

  1. Common-Cause Failure Treatment in Event Assessment: Basis for a Proposed New Model

    SciTech Connect

    Dana Kelly; Song-Hua Shen; Gary DeMoss; Kevin Coyne; Don Marksberry

    2010-06-01

    Event assessment is an application of probabilistic risk assessment in which observed equipment failures and outages are mapped into the risk model to obtain a numerical estimate of the event’s risk significance. In this paper, we focus on retrospective assessments to estimate the risk significance of degraded conditions such as equipment failure accompanied by a deficiency in a process such as maintenance practices. In modeling such events, the basic events in the risk model that are associated with observed failures and other off-normal situations are typically configured to be failed, while those associated with observed successes and unchallenged components are assumed capable of failing, typically with their baseline probabilities. This is referred to as the failure memory approach to event assessment. The conditioning of common-cause failure probabilities for the common cause component group associated with the observed component failure is particularly important, as it is insufficient to simply leave these probabilities at their baseline values, and doing so may result in a significant underestimate of risk significance for the event. Past work in this area has focused on the mathematics of the adjustment. In this paper, we review the Basic Parameter Model for common-cause failure, which underlies most current risk modelling, discuss the limitations of this model with respect to event assessment, and introduce a proposed new framework for common-cause failure, which uses a Bayesian network to model underlying causes of failure, and which has the potential to overcome the limitations of the Basic Parameter Model with respect to event assessment.

  2. Sustaining Public Education Events through Partnerships: Joining Forces for a Common Goal

    NASA Astrophysics Data System (ADS)

    McCall, L. R.; Clift, S.; Moore, S. L.

    2015-12-01

    Well-designed public STEM events benefit both the subject matter experts and the broader community. But planning and conducting these events costs participants' time and energy. For 15 years, the Bureau of Economic Geology of The University of Texas at Austin has hosted an Austin Earth Science Week Career Day, in which STEM professionals showcase their knowledge, skills, and experiences for middle-school students. By establishing partnerships and assuming a leadership role, the Bureau has leveraged resources to host a sustainable series of educational events. Key to success was finding a common goal that all participants were interested in fulfilling. Engaging and educating students about careers in geoscience became that unifying goal. Governmental agency staffers, industry professionals, graduate students, and school administrators were all interested in this effort. The career theme also attracted a wide variety of professionals, many of whom have participated in the event every year. The biggest challenge is meeting the demand from schools for this type of educational experience. In early years, the event was hosted by a few Bureau scientists in their offices. As word spread about the event, new partners and a larger facility were required to accommodate the growing number of participants. Currently, new media and distance learning platforms are being explored for broadening the event to meet demand. After 15 years, the Austin Earth Science Week Career Day has now become a tradition. We hope it serves as a model to others interested in establishing a STEM event in their own community.

  3. Molecular and Cellular Events Mediating Glomerular Podocyte Dysfunction and Depletion in Diabetes Mellitus

    PubMed Central

    Anil Kumar, P.; Welsh, Gavin I.; Saleem, Moin A.; Menon, Ram K.

    2014-01-01

    The essential function of the kidney is to ensure formation of a relatively protein-free ultra-filtrate, urine. The rate of filtration and composition of the primary renal filtrate is determined by the transport of fluid and solutes across the glomerular filtration barrier consisting of endothelial cells, the glomerular basement membrane, and podocyte foot processes. In diabetes mellitus (DM), components of the kidney that enable renal filtration get structurally altered and functionally compromised resulting in proteinuria that often progresses to end-stage renal disease. Histological alterations in DM include early hypertrophy of glomerular and tubular components, subsequent thickening of basement membrane in glomeruli and tubules, progressive accumulation of extracellular matrix proteins in the glomerular mesangium and loss of podocytes, together constituting a clinical condition referred to as diabetic nephropathy (DN). The glomerulus has become the focus of research investigating the mechanism of proteinuria. In particular, the progressive dysfunction and/or loss of podocytes that is contemporaneous with proteinuria in DN have attracted intense scientific attention. The absolute number of podocytes predicts glomerular function and podocyte injury is a hallmark of various glomerular diseases. This review discusses the importance of podocytes in normal renal filtration and details the molecular and cellular events that lead to podocyte dysfunction and decreased podocyte count in DN. PMID:25309512

  4. The Molecular and Cellular Events That Take Place during Craniofacial Distraction Osteogenesis.

    PubMed

    Rachmiel, Adi; Leiser, Yoav

    2014-01-01

    Gradual bone lengthening using distraction osteogenesis principles is the gold standard for the treatment of hypoplastic facial bones. However, the long treatment time is a major disadvantage of the lengthening procedures. The aim of this study is to review the current literature and summarize the cellular and molecular events occurring during membranous craniofacial distraction osteogenesis. Mechanical stimulation by distraction induces biological responses of skeletal regeneration that is accomplished by a cascade of biological processes that may include differentiation of pluripotential tissue, angiogenesis, osteogenesis, mineralization, and remodeling. There are complex interactions between bone-forming osteoblasts and other cells present within the bone microenvironment, particularly vascular endothelial cells that may be pivotal members of a complex interactive communication network in bone. Studies have implicated number of cytokines that are intimately involved in the regulation of bone synthesis and turnover. The gene regulation of numerous cytokines (transforming growth factor-β, bone morphogenetic proteins, insulin-like growth factor-1, and fibroblast growth factor-2) and extracellular matrix proteins (osteonectin, osteopontin) during distraction osteogenesis has been best characterized and discussed. Understanding the biomolecular mechanisms that mediate membranous distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone regeneration that may lead to shorten the treatment duration.

  5. The Molecular and Cellular Events That Take Place during Craniofacial Distraction Osteogenesis

    PubMed Central

    Rachmiel, Adi

    2014-01-01

    Summary: Gradual bone lengthening using distraction osteogenesis principles is the gold standard for the treatment of hypoplastic facial bones. However, the long treatment time is a major disadvantage of the lengthening procedures. The aim of this study is to review the current literature and summarize the cellular and molecular events occurring during membranous craniofacial distraction osteogenesis. Mechanical stimulation by distraction induces biological responses of skeletal regeneration that is accomplished by a cascade of biological processes that may include differentiation of pluripotential tissue, angiogenesis, osteogenesis, mineralization, and remodeling. There are complex interactions between bone-forming osteoblasts and other cells present within the bone microenvironment, particularly vascular endothelial cells that may be pivotal members of a complex interactive communication network in bone. Studies have implicated number of cytokines that are intimately involved in the regulation of bone synthesis and turnover. The gene regulation of numerous cytokines (transforming growth factor-β, bone morphogenetic proteins, insulin-like growth factor-1, and fibroblast growth factor-2) and extracellular matrix proteins (osteonectin, osteopontin) during distraction osteogenesis has been best characterized and discussed. Understanding the biomolecular mechanisms that mediate membranous distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone regeneration that may lead to shorten the treatment duration. PMID:25289295

  6. Cellular events and behaviors after grafting of stratified squamous epithelial cell sheet onto a hydrated collagen gel.

    PubMed

    Kasai, Yoshiyuki; Takeda, Naoya; Kobayashi, Shinichiro; Takagi, Ryo; Yamato, Masayuki

    2017-05-01

    Autologous stratified squamous epithelial cell sheets have been successfully used to treat epithelial defects in tissues such as the cornea and the esophagus. However, the regenerative cellular events occurring in the grafted epithelial cells are unclear in the early stages of wound healing. In this study, we created an in vitro grafting model using cultured normal human epidermal keratinocyte (NHEK) sheets and a type I collagen gel to investigate the cellular processes that occur within the grafted cell sheet. Cultured NHEK cells successfully became a stratified squamous cell sheet resembling epithelial tissue, retained expression of cellular integrins and adhesion proteins, and adhered successfully to a type I collagen gel. After culture on the collagen gel, expression of E-cadherin, and β-catenin decreased in the cells of the basal layer of the grafted cell sheet, resembling events characteristic of a partial epithelial-mesenchymal transition (EMT). These basal cells also induced migration of the cell sheet. Those phenomena are consistent with the essential events that occur in the wound-healing process observed previously in cell studies. Therefore, the epithelial cell sheet grafted onto a type I collagen gel is a suitable model in vitro to study cellular events and behaviors. Furthermore, we also addressed the therapeutic mechanisms by which the epithelial cell sheet promotes wound healing.

  7. Ischemia-induced glomerular parietal epithelial cells hyperplasia: Commonly misdiagnosed cellular crescent in renal biopsy.

    PubMed

    Zeng, Yeting; Wang, Xinrui; Xie, Feilai; Zheng, Zhiyong

    2017-08-01

    Ischemic pseudo-cellular crescent (IPCC) that is induced by ischemia and composed of hyperplastic glomerular parietal epithelial cells resembles cellular crescent. In this study, we aimed to assess the clinical and pathological features of IPCC in renal biopsy to avoid over-diagnosis and to determine the diagnostic basis. 4 IPCC cases diagnosed over a 4-year period (2012-2015) were evaluated for the study. Meanwhile, 5 cases of ANCA-associated glomerulonephritis and 5 cases of lupus nephritis (LN) were selected as control. Appropriate clinical data, morphology, and immunohistochemical features of all cases were retrieved. Results showed that the basement membrane of glomerulus with IPCC appeared as a concentric twisted ball, and glomerular cells of the lesion were reduced even entirely absent, and the adjacent afferent arterioles showed sclerosis or luminal stenosis. Furthermore, immune globulin deposition, vasculitis, and fibrinous exudate have not been observed in IPCC. While the cellular crescents showed diverse characteristics in both morphology and immunostaining in the control group. Therefore, these results indicated that IPCC is a sort of ischemic reactive hyperplasia and associated with sclerosis, stenosis, or obstruction of adjacent afferent arterioles, which is clearly different from cellular crescents result from glomerulonephritis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  8. Cellular events during sexual development from amoeba to plasmodium in the slime mould Physarum polycephalum.

    PubMed

    Bailey, J; Anderson, R W; Dee, J

    1990-04-01

    Time-lapse cinematography and immunofluorescence microscopy were used to study cellular events during amoebal fusions and sexual plasmodium development in Physarum polycephalum. Amoebal fusions occurred frequently in mixtures of strains heteroallelic or homoallelic for the mating-type locus matA, but plasmodia developed only in the matA-heteroallelic cultures. These observations confirmed that matA controls development of fusion cells rather than cell fusion. Analysis of cell pedigrees showed that, in both types of culture, amoebae fused at any stage of the cell cycle except mitosis. In matA-heteroallelic fusion cells, nuclear fusion occurred in interphase about 2 h after cell fusion; interphase nuclear fusion did not occur in matA-homoallelic fusion cells. The diploid zygote, formed by nuclear fusion in matA-heteroallelic fusion cells, entered an extended period of cell growth which ended in the formation of a binucleate plasmodium by mitosis without cytokinesis. In contrast, no extension to the cell cycle was observed in matA-homoallelic fusion cells and mitosis was always accompanied by cytokinesis. In matA-homoallelic cultures, many of the binucleate fusion cells split apart without mitosis, regenerating pairs of uninucleate amoebae; in the remaining fusion cells, the nuclei entered mitosis synchronously and spindle fusion sometimes occurred, giving rise to a variety of products. Immunofluorescence microscopy showed that matA-heteroallelic fusion cells possessed two amoebal microtubule organizing centres, and that most zygotes possessed only one; amoebal microtubule organization was lost gradually over several cell cycles. In matA-homoallelic cultures, all the cells retained amoebal microtubule organization.

  9. Cellular and biochemical events in mammalian cells during and after recovery from physiological stress

    PubMed Central

    1986-01-01

    We have examined and compared a number of cellular and biochemical events associated with the recovery process of rat fibroblasts placed under stress by different agents. Metabolic pulse-labeling studies of cells recovering from either heat-shock treatment, exposure to sodium arsenite, or exposure to an amino acid analogue of proline, L-azetidine 2-carboxylic acid, revealed interesting differences with respect to the individual stress proteins produced, their kinetics of induction, as well as the decay in their synthesis during the recovery period. In the initial periods of recovery, the major stress-induced 72-kD protein accumulates within the altered nucleoli in close association with the pre-ribosomal-containing granular region. During the later times of recovery from stress, the nucleoli begin to regain a normal morphology, show a corresponding loss of the 72-kD protein, and the majority of the protein now begins to accumulate within the cytoplasm in three distinct locales: the perinuclear region, along the perimeter of the cells, and finally in association with large phase-dense structures. These latter structures appear to consist of large aggregates of phase-dense material with no obvious encapsulating membrane. More interestingly we show, using double-label indirect immunofluorescence analysis, that much of the perinuclear and cell perimeter-distributed 72-kD protein coincides with the distribution of the cytoplasmic ribosomes. We discuss the possible implications of the presence of the 72-kD stress proteins within the pre-ribosomal-containing granular region of the nucleolus as well as its subsequent colocalization with cytoplasmic ribosomes in terms of the translational changes which occur in cells both during and after recovery from physiological stress. PMID:3536957

  10. Big Events and Risks to Global Substance Using Populations: Unique Threats and Common Challenges.

    PubMed

    Mackey, Tim K; Strathdee, Steffanie A

    2015-01-01

    In this commentary, we review a set of "Big Events" from around the world that have adversely impacted substance using populations by first identifying common thematic areas between them, and then describing the unique challenges faced by the diverse and vulnerable populations impacted. The Big Events reviewed are multifaceted and complex in nature, and include the recent global financial crisis, economic and trade sanctions, political transition and its impact on ethnic minorities, colonialism and indigenous communities, and ecological disasters. All have led to immense trauma, displacement, and disruption to critical healthcare services/treatment for people who use drugs, populations who are left underserved in the midst of these crises. It is our hope that through this comparative assessment, global policymakers will proactively identify Big Events and prioritize the development of interventions and policy that meet the unique and immediate needs of substance using population in order to mitigate the significant negative short- and long-term impacts on global public health.

  11. Simulation of debris flow events in Sicily by cellular automata model SCIDDICA_SS3

    NASA Astrophysics Data System (ADS)

    Cancelliere, A.; Lupiano, V.; Peres, D. J.; Stancanelli, L.; Avolio, M.; Foti, E.; Di Gregorio, S.

    2013-12-01

    Debris flow models are widely used for hazard mapping or for evaluating the effectiveness of risk mitigation measures. Several models analyze the dynamics of debris flow runout solving Partial Differential Equations. In use of such models, difficulties arise in estimating kinematic geotechnical soil parameters for real phenomena. In order to overcome such difficulties, alternative semi-empirical approaches can be employed, such as macroscopic Cellular Automata (CA). In particular, for CA simulation purposes, the runout of debris flows emerges from local interactions in a dynamical system, subdivided into elementary parts, whose state evolves within a spatial and temporal discretum. The attributes of each cell (substates) describe physical characteristics. For computational reasons, the natural phenomenon is splitted into a number of elementary processes, whose proper composition makes up the CA transition function. By simultaneously applying this function to all the cells, the evolution of the phenomenon can be simulated in terms of modifications of the substates. In this study, we present an application of the macroscopic CA semi-empirical model SCIDDICA_SS3 to the Peloritani Mountains area in Sicily island, Italy. The model was applied using detailed data from the 1 October 2009 debris flow event, which was triggered by a rainfall event of about 250 mm falling in 9 hours, that caused the death of 37 persons. This region is characterized by river valleys with large hillslope angles (30°-60°), catchment basins of small extensions (0.5-12 km2) and soil composed by metamorphic material, which is easy to be eroded. CA usage implies a calibration phase, that identifies an optimal set of parameters capable of adequately play back the considered case, and a validation phase, that tests the model on a sufficient (and different) number of cases similar in terms of physical and geomorphological properties. The performance of the model can be measured in terms of a fitness

  12. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

    PubMed Central

    Chornokur, Ganna; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Amankwah, Ernest K.; Qu, Xiaotao; Tsai, Ya-Yu; Jim, Heather S. L.; Chen, Zhihua; Chen, Ann Y.; Permuth-Wey, Jennifer; Aben, Katja KH.; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bunker, Clareann H.; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F.; Eccles, Diana M.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goodman, Marc T.; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A. T.; Hillemanns, Peter; Hogdall, Claus K.; Hogdall, Estrid; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Kelemen, Linda E.; Kellar, Mellissa; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F. A. G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain; Menon, Usha; Milne, Roger L.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Pike, Malcolm C.; Poole, Elizabeth M.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Sucheston, Lara; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Thomsen, Lotte; Tangen, Ingvild L.; Tworoger, Shelley S.; van Altena, Anne M.; Vierkant, Robert A.; Vergote, Ignace; Walsh, Christine S.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wu, Anna H.; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Hasmad, Hanis N.; Berchuck, Andrew; Iversen, Edwin S.; Schildkraut, Joellen M.; Ramus, Susan J.; Goode, Ellen L.; Monteiro, Alvaro N. A.; Gayther, Simon A.; Narod, Steven A.; Pharoah, Paul D. P.; Sellers, Thomas A.; Phelan, Catherine M.

    2015-01-01

    Background Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. Methods In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. Results The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). Conclusion These results, generated on a large cohort of women, revealed associations

  13. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk.

    PubMed

    Chornokur, Ganna; Lin, Hui-Yi; Tyrer, Jonathan P; Lawrenson, Kate; Dennis, Joe; Amankwah, Ernest K; Qu, Xiaotao; Tsai, Ya-Yu; Jim, Heather S L; Chen, Zhihua; Chen, Ann Y; Permuth-Wey, Jennifer; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bunker, Clareann H; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F; Eccles, Diana M; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goodman, Marc T; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Claus K; Hogdall, Estrid; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kelemen, Linda E; Kellar, Mellissa; Kiemeney, Lambertus A; Krakstad, Camilla; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Iain; Menon, Usha; Milne, Roger L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Pike, Malcolm C; Poole, Elizabeth M; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Spiewankiewicz, Beata; Sucheston, Lara; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Thomsen, Lotte; Tangen, Ingvild L; Tworoger, Shelley S; van Altena, Anne M; Vierkant, Robert A; Vergote, Ignace; Walsh, Christine S; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Wu, Anna H; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Hasmad, Hanis N; Berchuck, Andrew; Iversen, Edwin S; Schildkraut, Joellen M; Ramus, Susan J; Goode, Ellen L; Monteiro, Alvaro N A; Gayther, Simon A; Narod, Steven A; Pharoah, Paul D P; Sellers, Thomas A; Phelan, Catherine M

    2015-01-01

    Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). These results, generated on a large cohort of women, revealed associations between inherited cellular transport

  14. Agglomerative Epigenetic Aberrations are a Common Event in Human Breast Cancer

    PubMed Central

    Petr, Novak; Taylor, Jensen; Oshiro Marc, M; Watts George, S; Kim Christina, J; Futscher Bernard, W

    2009-01-01

    Changes in DNA methylation patterns are a common characteristic of cancer cells. Recent studies suggest that DNA methylation affects not only discrete genes, but it can also affect large chromosomal regions, potentially leading to long range epigenetic silencing. It is unclear whether such long-range epigenetic events are relatively rare or frequent occurrences in cancer. Here we use a high-resolution promoter tiling array approach to analyze DNA methylation in breast cancer specimens and normal breast tissue to address this question. We identified 3506 cancer specific differentially methylated regions (DMR) in human breast cancer with 2033 being hypermethylation events and 1473 hypomethylation events. Most of these DMRs are recurrent in breast cancer; 90% of the identified DMRs occurred in at least 33% of the samples. Interestingly, we found a non-random spatial distribution of aberrantly methylated regions across the genome that showed a tendency to concentrate in relatively small genomic regions. Such agglomerates of hyper- and hypomethylated DMRs spanned up to several hundred kilobases and were frequently found at gene family clusters. The hypermethylation events usually occurred in the proximity of the transcription start site in CpG island promoters while hypomethylation events were frequently found in regions of segmental duplication. One example of a newly discovered agglomerate of hypermethylated DMRs associated with gene silencing in breast cancer that we examined in greater detail involved the protocadherin gene family clusters on chromosome 5 (PCDHA, PCDHB, and PCDHG). Taken together, our results suggest that agglomerative epigenetic aberrations are frequent events in human breast cancer. PMID:18922938

  15. Cellular Mechanisms of Tissue Fibrosis. 1. Common and organ-specific mechanisms associated with tissue fibrosis

    PubMed Central

    2013-01-01

    Fibrosis is a pathological scarring process that leads to destruction of organ architecture and impairment of organ function. Chronic loss of organ function in most organs, including bone marrow, heart, intestine, kidney, liver, lung, and skin, is associated with fibrosis, contributing to an estimated one third of natural deaths worldwide. Effective therapies to prevent or to even reverse existing fibrotic lesions are not yet available in any organ. There is hope that an understanding of common fibrosis pathways will lead to development of antifibrotic therapies that are effective in all of these tissues in the future. Here we review common and organ-specific pathways of tissue fibrosis. PMID:23255577

  16. Untethering the Nuclear Envelope and Cytoskeleton: Biologically Distinct Dystonias Arising from a Common Cellular Dysfunction

    PubMed Central

    Atai, Nadia A.; Ryan, Scott D.; Kothary, Rashmi; Breakefield, Xandra O.; Nery, Flávia C.

    2012-01-01

    Most cases of early onset DYT1 dystonia in humans are caused by a GAG deletion in the TOR1A gene leading to loss of a glutamic acid (ΔE) in the torsinA protein, which underlies a movement disorder associated with neuronal dysfunction without apparent neurodegeneration. Mutation/deletion of the gene (Dst) encoding dystonin in mice results in a dystonic movement disorder termed dystonia musculorum, which resembles aspects of dystonia in humans. While torsinA and dystonin proteins do not share modular domain architecture, they participate in a similar function by modulating a structural link between the nuclear envelope and the cytoskeleton in neuronal cells. We suggest that through a shared interaction with the nuclear envelope protein nesprin-3α, torsinA and the neuronal dystonin-a2 isoform comprise a bridge complex between the outer nuclear membrane and the cytoskeleton, which is critical for some aspects of neuronal development and function. Elucidation of the overlapping roles of torsinA and dystonin-a2 in nuclear/endoplasmic reticulum dynamics should provide insights into the cellular mechanisms underlying the dystonic phenotype. PMID:22611399

  17. Approaches to Manipulating the Dimensionality and Physicochemical Properties of Common Cellular Scaffolds

    PubMed Central

    Bajpai, Saumendra; Kim, Na Young; Reinhart-King, Cynthia A.

    2011-01-01

    A major hurdle in studying biological systems and administering effective tissue engineered therapies is the lack of suitable cell culture models that replicate the dynamic nature of cell-microenvironment interactions. Advances in the field of surface chemistry and polymer science have allowed researchers to develop novel methodologies to manipulate materials to be extrinsically tunable. Usage of such materials in modeling tissues in vitro has offered valuable insights into numerous cellular processes including motility, invasion, and alterations in cell morphology. Here, we discuss novel techniques devised to more closely mimic cell-tissue interactions and to study cell response to distinct physico-chemical changes in biomaterials, with an emphasis on the manipulation of collagen scaffolds. The benefits and pitfalls associated with using collagen are discussed in the context of strategies proposed to control the engineered microenvironment. Tunable systems such as these offer the ability to alter individual features of the microenvironment in vitro, with the promise that the molecular basis of mechanotransduction in vivo may be laid out in future. PMID:22272094

  18. 76 FR 67764 - Common-Cause Failure Analysis in Event and Condition Assessment: Guidance and Research, Draft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-02

    ... COMMISSION Common-Cause Failure Analysis in Event and Condition Assessment: Guidance and Research, Draft...-xxxx, Revision 0, ``Common-Cause Failure Analysis in Event and Condition Assessment: Guidance and... at (301) 492-3446. FOR FURTHER INFORMATION CONTACT: Song-Hua Shen, Division of Risk Analysis,...

  19. Associations between common carotid artery diameter, Framingham risk score and cardiovascular events.

    PubMed

    Kozakova, M; Morizzo, C; La Carrubba, S; Fabiani, I; Della Latta, D; Jamagidze, J; Chiappino, D; Di Bello, V; Palombo, C

    2017-04-01

    Vascular biomarkers are associated with risk burden and are capable to predict the development of future cardiovascular (CV) events; yet, their additive predictive value over and above established risk algorithms seems to be only modest. The present study evaluated the cross-sectional associations between vascular biomarkers, 10-year Framingham risk (FR) and prevalent CV events in a population with a high prevalence of hypertension and diabetes. As many as 681 subjects (419 men, age = 60 ± 10 years, 282 diabetics, 335 hypertensives, mean FR score = 22.5 ± 16.5%) underwent an integrated vascular examination including: radiofrequency-based ultrasound of common carotid artery (cca) to measure intima-media thickness (IMT), inter-adventitial diameter (IAD) and local pulse wave velocity (PWV); applanation tonometry to assess carotid pulse pressure (PP) and augmentation index (AIx); carotid-femoral PWV (cfPWV) measurement. One hundred and thirty-five subjects (19.8%) had history of CV events, and CV events were independently associated with male sex, age, antihypertensive treatment, current smoking, HDL-cholesterol and ccaIAD. In logistic regression model, only ccaIAD was associated with prevalence of CV events after adjustment for FR score, with the OR of 1.71 [1.34-2.19] (P < 0.0001) that remained unchanged when ccaIMT was included into the model (OR = 1.76 [1.36-2.27]; P < 0.0001). The association between prevalent CV events and ccaIAD was significant (OR of 1.65 [1.24-2.20]; P = 0.0005) also in a subgroup of subjects being at a high 10-year risk of CV disease (N = 330). In a population with a high prevalence of diabetes and hypertension, ccaIAD was the only vascular measure associated with prevalent CV events, independently of FR score. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II

  20. Drosophila Neuronal Injury Follows a Temporal Sequence of Cellular Events Leading to Degeneration at the Neuromuscular Junction

    PubMed Central

    Lincoln, Barron L.; Alabsi, Sahar H.; Frendo, Nicholas; Freund, Robert; Keller, Lani C.

    2015-01-01

    Neurodegenerative diseases affect millions of people worldwide, and as the global population ages, there is a critical need to improve our understanding of the molecular and cellular mechanisms that drive neurodegeneration. At the molecular level, neurodegeneration involves the activation of complex signaling pathways that drive the active destruction of neurons and their intracellular components. Here, we use an in vivo motor neuron injury assay to acutely induce neurodegeneration in order to follow the temporal order of events that occur following injury in Drosophila melanogaster. We find that sites of injury can be rapidly identified based on structural defects to the neuronal cytoskeleton that result in disrupted axonal transport. Additionally, the neuromuscular junction accumulates ubiquitinated proteins prior to the neurodegenerative events, occurring at 24 hours post injury. Our data provide insights into the early molecular events that occur during axonal and neuromuscular degeneration in a genetically tractable model organism. Importantly, the mechanisms that mediate neurodegeneration in flies are conserved in humans. Thus, these studies have implications for our understanding of the cellular and molecular events that occur in humans and will facilitate the identification of biomedically relevant targets for future treatments. PMID:26512206

  1. Expression of transferrin receptors on mitogen-stimulated human peripheral blood lymphocytes: relation to cellular activation and related metabolic events.

    PubMed Central

    Galbraith, R M; Galbraith, G M

    1981-01-01

    Mitogen-activated normal human peripheral blood lymphocytes bind transferrin to specific membrane receptors. In this study, lymphocytes stimulated with phytohaemagglutinin for 0-66 hr were examined to determine the relation of this phenomenon to cellular activation and related metabolic events. Transferrin receptors were first detected at 20-24 hr. This event was consistently preceded by RNA and protein turnover which commenced during the first 6 hr of culture, whereas initiation of DNA synthesis was detected concurrently with the appearance of receptors or slightly later (24-30 hr). Exposure of cells to inhibitors of RNA and protein synthesis early during culture (at 0 or 24 hr) prevented the expression of transferrin receptors, but also caused generalized metabolic failure, and abrogated cellular activation. In contrast, later addition of these agents at 48 hr did not interfere significantly with the process of activation, but did suppress the terminal increase in receptor-bearing cells observed during the final 18 hr in control cultures lacking inhibitor. After deliberate thermal stripping of receptors from activated cells, the reappearance of membrance binding sites which normally occurred within 30 min, was also blocked by cycloheximide, puromycin and actinomycin D. However, similar inhibition of DNA which was induced by hydroxyurea had much less effect upon both the initial appearance of receptors and their reappearance after ligand-induced depletion. These results demonstrate that the appearance of transferrin receptors upon human lymphocytes is dependent upon cellular activation and requires synthesis of protein and RNA. PMID:6172372

  2. Cellular events during hepatocarcinogenesis in rats and the question of premalignancy.

    PubMed

    Sell, S; Hunt, J M; Knoll, B J; Dunsford, H A

    1987-01-01

    The cellular, biochemical, and genetic changes that occur in the liver of rats exposed to chemical hepatocarcinogens are reviewed. Multiple new cell types appear in the liver of carcinogen-treated rats including foci, nodules, ducts, oval cells, and atypical hyperplastic areas. The application of phenotypic markers for these cell types suggests that hepatocellular carcinomas may arise from more than one cell type, including a putative liver stem cell that proliferates following carcinogen exposure. Study of DNA, RNA, and proteins produced by hepatocellular carcinomas and putative premalignant cells has so far failed to identify a gene or gene product clearly associated with the malignant or premalignant phenotype. Understanding the cellular lineage from normal cell through putative premalignant cell to cancer is critical to understanding the process of carcinogenesis. Application of new immunological (monoclonal antibody, transplantation) and molecular biological (gene cloning, oncogene identification) approaches to this problem holds promise that the process of hepatocarcinogenesis will be better known in the near future.

  3. Comparative study on antiproliferation properties and cellular antioxidant activities of commonly consumed food legumes against nine human cancer cell lines.

    PubMed

    Xu, Baojun; Chang, Sam K C

    2012-10-01

    The aims of this work were to compare health promoting effects of commonly consumed food legumes in terms of cancer cell proliferation inhibitory effects and cellular antioxidant activities (CAA). The CAA was evaluated by fluorescence microplate reader based on in vitro animal cell cultivation. Antiproliferative properties were assayed by MTT method using in vitro cell culture system. Phytochemicals (including total phenolic, procyanidin, saponin and phytic acid) and chemical antioxidant activities (including DPPH free radical scavenging activity, oxygen radical absorbing capacity, peroxyl radical scavenging capacity (PRSC)) were also determined for comparison purposes. The results showed that different types of legumes possessed considerable variations in their phytochemicals, as well as chemical and cellular antioxidant activities. Adzuki bean exhibited the strongest antiproliferative properties in a dose-dependent manner against all digestive system cancer cell lines (CAL27, AGS, HepG2, SW480 and Caco-2), ovary cancer cell SK-OV-3 and breast cancer cell MCF-7 among all legumes tested. Black soybean exhibited the highest saponin, phytic acid content, PRSC values, and the strongest CAA values. These results indicate that commonly consumed food legumes may serve as an excellent dietary source of natural antioxidants for health promotion and cancer prevention.

  4. Correlative microscopy: a potent tool for the study of rare or unique cellular and tissue events.

    PubMed

    Mironov, A A; Beznoussenko, G V

    2009-09-01

    Biological studies have relied on two complementary microscope technologies - light (fluorescence) microscopy and electron microscopy. Light microscopy is used to study phenomena at a global scale to look for unique or rare events, and it also provides an opportunity for live imaging, whereas the forte of electron microscopy is the high resolution. Traditionally light and electron microscopy observations are carried out in different populations of cells/tissues and a 'correlative' inference is drawn. The advent of true correlative light-electron microscopy has allowed high-resolution imaging by electron microscopy of the same structure observed by light microscopy, and in advanced cases by video microscopy. Thus a rare event captured by low-resolution imaging of a population or transient events captured by live imaging can now also be studied at high resolution by electron microscopy. Here, the potential and difficulties of this approach, along with the most impressive breakthroughs obtained by these methods, are discussed.

  5. Adverse events are common on the intensive care unit: results from a structured record review.

    PubMed

    Nilsson, L; Pihl, A; Tågsjö, M; Ericsson, E

    2012-09-01

    Intensive care is advanced and highly technical, and it is essential that, despite this, patient care remains safe and of high quality. Adverse events (AEs) are supposed to be reported to internal quality control systems by health-care providers, but many are never reported. Patients on the intensive care unit (ICU) are at special risk for AEs. Our aim was to identify the incidence and characteristics of AEs in patients who died on the ICU during a 2-year period. A structured record review according to the Global Trigger Tool (GTT) was used to review charts from patients cared for at the ICU of a middle-sized Swedish hospital during 2007 and 2008 and who died during or immediately after ICU care. All identified AEs were scored according to severity and preventability. We reviewed 128 records, and 41 different AEs were identified in 25 patients (19.5%). Health care-associated infections, hypoglycaemia, pressure sores and procedural complications were the most common harmful events. Twenty two (54%) of the AEs were classified as being avoidable. Two of the 41 AEs were reported as complications according to the Swedish Intensive Care Registry, and one AE had been reported in the internal AE-reporting system. Almost one fifth of the patients who died on the ICU were subjected to harmful events. GTT has the advantage of identifying more patient injuries caused by AEs than the traditional AE-reporting systems used on many ICUs. © 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.

  6. The Destruction of Thin Stellar Disks Via Cosmologically Common Satellite Accretion Events

    NASA Astrophysics Data System (ADS)

    Purcell, Chris W.; Kazantzidis, Stelios; Bullock, James S.

    2009-04-01

    Most Galaxy-sized systems (M host sime 1012 M sun) in the ΛCDM cosmology are expected to have interacted with at least one satellite with a total mass M sat sime 1011 M sun sime 3M disk in the past 8 Gyr. Analytic and numerical investigations suggest that this is the most precarious type of accretion for the survival of thin galactic disks because more massive accretion events are relatively rare and less massive ones preserve thin disk components. We use high-resolution, dissipationless N-body simulations to study the response of an initially thin, fully formed Milky Way-type stellar disk to these cosmologically common satellite accretion events, and show that the thin disk does not survive. Regardless of orbital configuration, the impacts transform the disks into structures that are roughly three times as thick and more than twice as kinematically hot as the observed dominant thin disk component of the Milky Way. We conclude that if the Galactic thin disk is a representative case, then the presence of a stabilizing gas component is the only recourse for explaining the preponderance of disk galaxies in a ΛCDM universe; otherwise, the disk of the Milky Way must be uncommonly cold and thin for its luminosity, perhaps as a consequence of an unusually quiescent accretion history.

  7. In situ sensing and modeling of molecular events at the cellular level

    NASA Astrophysics Data System (ADS)

    Yang, Ruiguo

    We developed the Atomic Force Microscopy (AFM) based nanorobot in combination with other nanomechanical sensors for the investigation of cell signaling pathways. The AFM nanorobotics hinge on the superior spatial resolution of AFM in imaging and extends it into the measurement of biological processes and manipulation of biological matters. A multiple input single output control system was designed and implemented to solve the issues of nanomanipulation of biological materials, feedback, response frequency and nonlinearity. The AFM nanorobotic system therefore provide the human-directed position, velocity and force control with high frequency feedback, and more importantly it can feed the operator with the real-time imaging of manipulation result from the fast-imaging based local scanning. The use of the system has taken the study of cellular process at the molecular scale into a new level. The cellular response to the physiological conditions can be significantly manifested in cellular mechanics. Dynamic mechanical property has been regarded as biomarkers, sometimes even regulators of the signaling and physiological processes, thus the name mechanobiology. We sought to characterize the relationship between the structural dynamics and the molecular dynamics and the role of them in the regulation of cell behavior. We used the AFM nanorobotics to investigate the mechanical properties in real-time of cells that are stimulated by different chemical species. These reagents could result in similar ion channel responses but distinctive mechanical behaviors. We applied these measurement results to establish a model that describes the cellular stimulation and the mechanical property change, a "two-hit" model that comprises the loss of cell adhesion and the initiation of cell apoptosis. The first hit was verified by functional experiments: depletion of Calcium and nanosurgery to disrupt the cellular adhesion. The second hit was tested by a labeling of apoptotic markers that

  8. Can common adhesion molecules and microtopography affect cellular elasticity? A combined atomic force microscopy and optical study.

    PubMed

    McPhee, Gordon; Dalby, Matthew J; Riehle, Mathis; Yin, Huabing

    2010-10-01

    The phenomenon that cells respond to chemical and topographic cues in their surroundings has been widely examined and exploited in many fields ranging from basic life science research to biomedical therapeutics. Adhesion promoting molecules such as poly-L-lysine (PLL) and fibronectin (Fn) are commonly used for in vitro cell assays to promote cell spreading/proliferation on tissue culture plastic and to enhance the biocompatibility of biomedical devices. Likewise, engineered topography is often used to guide cell growth and differentiation. Little is known about how these cues affect the biomechanical properties of cells and subsequent cell function. In this study we have applied atomic force microscopy (AFM) to investigate these biomechanical properties. In the first stage of the study we formulated a rigorous approach to quantify cellular elasticity using AFM. Operational factors, including indentation depth and speed, and mathematical models for data fitting have been systematically evaluated. We then quantified how PLL, Fn and microtopography affected cellular elasticity and the organization of the cytoskeleton. Cellular elasticity after 1 day in culture was greater on a Fn-coated surface as compared to PLL or glass. These statistically significant differences disappeared after two more days in culture. In contrast, the significantly higher elasticity associated with cells grown on micrometric grooves remained for at least 3 days. This work sheds light on the apparently simple but debatable questions: "Are engineered chemical cues eventually masked by a cell's own matrix proteins and so only exert short-term influence? Does engineered topography as well as engineered chemistry affect cell elasticity?"

  9. 76 FR 70768 - Common-Cause Failure Analysis in Event and Condition Assessment: Guidance and Research, Draft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-15

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Common-Cause Failure Analysis in Event and Condition Assessment: Guidance and Research, Draft Report for Comment; Correction AGENCY: Nuclear Regulatory Commission. ACTION: Draft NUREG; request...

  10. Morphogenesis in sea urchin embryos: linking cellular events to gene regulatory network states

    PubMed Central

    Lyons, Deidre; Kaltenbach, Stacy; McClay, David R.

    2013-01-01

    Gastrulation in the sea urchin begins with ingression of the primary mesenchyme cells (PMCs) at the vegetal pole of the embryo. After entering the blastocoel the PMCs migrate, form a syncitium, and synthesize the skeleton of the embryo. Several hours after the PMCs ingress the vegetal plate buckles to initiate invagination of the archenteron. That morphogenetic process occurs in several steps. The non-skeletogenic cells produce the initial inbending of the vegetal plate. Endoderm cells then rearrange and extend the length of the gut across the blastocoel to a target near the animal pole. Finally, cells that will form part of the midgut and hindgut are added to complete gastrulation. Later, the stomodeum invaginates from the oral ectoderm and fuses with the foregut to complete the archenteron. In advance of, and during these morphogenetic events an increasingly complex gene regulatory network controls the specification and the cell biological events that conduct the gastrulation movements. PMID:23801438

  11. Remembering the past and imagining the future: common and distinct neural substrates during event construction and elaboration

    PubMed Central

    Addis, Donna Rose; Wong, Alana T.; Schacter, Daniel L.

    2007-01-01

    People can consciously re-experience past events and pre-experience possible future events. This fMRI study examined the neural regions mediating the construction and elaboration of past and future events. Participants were cued with a noun for 20 seconds and instructed to construct a past or future event within a specified time period (week, year, 5–20 years). Once participants had the event in mind, they made a button press and for the remainder of the 20 seconds elaborated on the event. Importantly, all events generated were episodic and did not differ on a number of phenomenological qualities (detail, emotionality, personal significance, field/observer perspective). Conjunction analyses indicated the left hippocampus was commonly engaged by past and future event construction, along with posterior visuospatial regions, but considerable neural differentiation was also observed during the construction phase. Future events recruited regions involved in prospective thinking and generation processes, specifically right frontopolar cortex and left ventrolateral prefrontal cortex, respectively. Furthermore, future event construction uniquely engaged the right hippocampus, possibly as a response to the novelty of these events. In contrast to the construction phase, elaboration was characterized by remarkable overlap in regions comprising the autobiographical memory retrieval network, attributable to the common processes engaged during elaboration, including self-referential processing, contextual and episodic imagery. This striking neural overlap is consistent with findings that amnesic patients exhibit deficits in both past and future thinking, and confirms that the episodic system contributes importantly to imagining the future. PMID:17126370

  12. Common links in the structure and cellular localization of Rhizobium chitolipooligosaccharides and general Rhizobium membrane phospholipid and glycolipid components.

    PubMed

    Cedergren, R A; Lee, J; Ross, K L; Hollingsworth, R I

    1995-04-04

    Several common links between the structural chemistry of the chitolipooligosaccharides of Rhizobium and the general rhizobial membrane lipid and lipopolysaccharide chemistry of these bacteria have been uncovered. Aspects of common chemistry include sulfation, methylation, and the position and extent of fatty acyl chain unsaturation. We find that bacteria which are known to synthesize sulfated chitolipooligosaccharides (such as Rhizobium meliloti strains and the broad-host-range Rhizobium species strain NGR234) also have sulfated lipopolysaccharides. Their common origins of sulfation have been demonstrated by using mutants which are known to be impaired in sulfating their chitolipooligosaccharides. In such cases, there is a corresponding diminution or complete lack of sulfation of the lipopolysaccharides. The structural diversity of the fatty acids observed in the chitolipooligosaccharides is also observed in the other membrane lipids. For instance, the doubly unsaturated fatty acids which are known to be predominant components of R. meliloti chitolipooligosaccharides were also found in the usual phospholipids and glycolipids. Also, the known functionalization of the chitolipooligosaccharides of R. sp. NGR234 by O- and N-methylation was also reflected in the lipopolysaccharide of this organism. The common structural features of chitolipooligosaccharides and membrane components are consistent with a substantial degree of biosynthetic overlap and a large degree of cellular, spatial overlap between these molecules. The latter aspect is clearly demonstrated here since we show that the chitolipooligosaccharides are, in fact, normal membrane components of Rhizobium. This increases the importance of understanding the role of the bacterial cell surface chemistry in the Rhizobium/legume symbiosis and developing a comprehensive understanding of the highly integrated membrane lipid and glycolipid chemistry of Rhizobium.

  13. Hepatoprotective effects of melatonin against pronecrotic cellular events in streptozotocin-induced diabetic rats.

    PubMed

    Grigorov, Ilijana; Bogojević, Desanka; Jovanović, Sofija; Petrović, Anja; Ivanović-Matić, Svetlana; Zolotarevski, Lidija; Poznanović, Goran; Martinović, Vesna

    2014-06-01

    Oxidative stress-mediated damage to liver tissue underlies the pathological alterations in liver morphology and function that are observed in diabetes. We examined the effects of the antioxidant action of melatonin against necrosis-inducing DNA damage in hepatocytes of streptozotocin (STZ)-induced diabetic rats. Daily administration of melatonin (0.2 mg/kg) was initiated 3 days before diabetes induction and maintained for 4 weeks. Melatonin-treated diabetic rats exhibited improved markers of liver injury (P < 0.05), alkaline phosphatase, and alanine and aspartate aminotransferases. Melatonin prevented the diabetes-related morphological deterioration of hepatocytes, DNA damage (P < 0.05), and hepatocellular necrosis. The improvement was due to containment of the pronecrotic oxygen radical load, observed as inhibition (P < 0.05) of the diabetes-induced rise in lipid peroxidation and hydrogen peroxide increase in the liver. This was accompanied by improved necrotic markers of cellular damage: a significant reduction in cleavage of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1) into necrotic 55- and 62-kDa fragments, and inhibition of nucleus-to-cytoplasm translocation and accumulation in the serum of the high-mobility group box 1 (HMGB1) protein. We conclude that melatonin is hepatoprotective in diabetes. It reduces extensive DNA damage and resulting necrotic processes. Melatonin application could thus present a viable therapeutic option in the management of diabetes-induced liver injury.

  14. Proteolytic events are relevant cellular responses during nervous system regeneration of the starfish Marthasterias glacialis.

    PubMed

    Ferraz Franco, Catarina; Santos, Romana; Varela Coelho, Ana

    2014-03-17

    The molecular pathways that trigger the amazing intrinsic regenerative ability of echinoderm nervous system are still unknown. In order to approach this subject, a 2D-DIGE proteomic strategy was used, to screen proteome changes during neuronal regeneration in vivo, using starfish (Asteroidea, Echinodermata) as a model. A total of 528 proteins showed significant variations during radial nerve cord regeneration in both soluble and membrane protein-enriched fractions. Several functional classes of proteins known to be involved in axon regeneration events in other model organisms, such as chordates, were identified for the first time in the regenerating echinoderm nervous system. Unexpectedly, most of the identified proteins presented a molecular mass either higher or lower than expected. Such results suggest a functional modulation through protein post-translational modifications, such as proteolysis. Among these are proteins involved in cytoskeleton and microtubule regulators, axon guidance molecules and growth cone modulators, protein de novo synthesis machinery, RNA binding and transport, transcription factors, kinases, lipid signaling effectors and proteins with neuroprotective functions. In summary, the impact of proteolysis during regeneration events is here shown, although requiring further studies to detail on the mechanisms involving this post-transcriptional event on nervous system regeneration. The nervous systems of some organisms present a complete inability of neurons to regrow across a lesion site, which is the case of the adult mammalian central nervous system (CNS). Expanding our knowledge on how other animals regenerate their nervous system offers great potential for groundbreaking biomedical applications towards the enhancement of mammalian CNS regeneration. In order to approach this subject, a 2D-DIGE proteomic strategy was used for the first time, to screen the proteome changes during neuronal regeneration in vivo, using starfish (Asteroidea

  15. Specimen Pooling for Efficient Use of Biospecimens in Studies of Time to a Common Event

    PubMed Central

    Saha-Chaudhuri, Paramita; Weinberg, Clarice R.

    2013-01-01

    For case-control studies that rely on expensive assays for biomarkers, specimen pooling offers a cost-effective and efficient way to estimate individual-level odds ratios. Pooling helps to conserve irreplaceable biospecimens for the future, mitigates limit-of-detection problems, and enables inclusion of individuals who have limited available volumes of biospecimen. Pooling can also allow the study of a panel of biomarkers under a fixed assay budget. Here, we extend this method for application to discrete-time survival studies. Assuming a proportional odds logistic model for risk of a common outcome, we propose a design strategy that forms pooling sets within those experiencing the outcome at the same event time. We show that the proposed design enables a cost-effective analysis to assess the association of a biomarker with the outcome. Because the standard likelihood is slightly misspecified for the proposed pooling strategy under a nonnull biomarker effect, the proposed approach produces slightly biased estimates of exposure odds ratios. We explore the extent of this bias via simulations and illustrate the method by revisiting a data set relating polychlorinated biphenyls and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene to time to pregnancy. PMID:23821316

  16. Molecular Events Involved in Cellular Invasion by Ehrlichia chaffeensis and Anaplasma phagocytophilum

    PubMed Central

    Rikihisa, Yasuko

    2009-01-01

    Ehrlichia chaffeensis and Anaplasma phagocytophilum are obligatory intracellular bacteria that preferentially replicate inside leukocytes by utilizing biological compounds and processes of these primary host defensive cells. These bacteria incorporate cholesterol from the host for their survival. Upon interaction with host monocytes and granulocytes, respectively, these bacteria usurp the lipid raft domain containing GPI-anchored protein to induce a series of signaling events that result in internalization of the bacteria. Monocytes and neutrophils usually kill invading microorganisms by fusion of the phagosomes containing the bacteria with granules containing both antimicrobial peptides and lysosomal hydrolytic enzymes and/or through sequestering vital nutrients. However, E. chaffeensis and A. phagocytophilum alter vesicular traffic to create a unique intracellular membrane-bound compartment that allows their replication in seclusion from lysosomal killing. These bacteria are quite sensitive to reactive oxygen species (ROS), so in order to survive in host cells that are primary mediators of ROS-induced killing, they inhibit activation of NADPH oxidase and assembly of this enzyme in their inclusion compartments. Moreover, host phagocyte activation and differentiation, apoptosis, and IFN-γ signaling pathways are inhibited by these bacteria. Through reductive evolution, lipopolysaccharide and peptidoglycan that activate the innate immune response, have been eliminated from these gram-negative bacteria at the genomic level. Upon interaction with new host cells, bacterial genes encoding the type IV secretion apparatus and the two-component regulatory system are upregulated to sense and adapt to the host environment. Thus dynamic signal transduction events concurrently proceed both in the host cells and in the invading E. chaffeensis and A. phagocytophilum bacteria for successful establishment of intracellular infection. Several bacterial surface exposed proteins and

  17. Manganese-superoxide dismutase (Mn-SOD) overexpression is a common event in colorectal cancers with mitochondrial microsatellite instability.

    PubMed

    Govatati, Suresh; Malempati, Sravanthi; Saradamma, Bulle; Divyamaanasa, Dasi; Naidu, B Prathap; Bramhachari, Pallaval Veera; Narayana, Nagesh; Shivaji, Sisinthy; Bhanoori, Manjula; Tamanam, Raghava Rao; Rao, Pasupuleti Sreenivasa; Nallanchakravarthula, Varadacharyulu

    2016-08-01

    Mitochondrial displacement loop (D-loop) is a hot spot for mitochondrial DNA (mtDNA) alterations that effects cellular reactive oxygen species (ROS) generation. Manganese-superoxide dismutase (Mn-SOD) is a major antioxidant enzyme that protects cells from ROS-mediated damage. In the present study, we investigated the relationship between sequence alterations of mitochondrial D-loop and Mn-SOD expression in colorectal cancer (CRC). Genotyping of entire mitochondrial D-loop (1124 bp) was carried out on mtDNA of analogous tumor and normal tissues from 35 CRC patients of south Indian origin by PCR-sequencing analysis. Tumor-specific large-scale mtDNA deletions and Mn-SOD expression was analyzed by PCR and Western blot analysis, respectively. We identified 87 polymorphisms in the D-loop region of tumor and/or control tissues. Polymorphisms were predominantly located in hypervariable region I (67.9 %) than in II (32.1 %) of D-loop. Significantly increased mtDNA microsatellite instability (mtMSI) [310'C' insertion (P = 0.00001) and T16189C (P = 0.0007)] and elevated Mn-SOD expression was observed in tumor tissues compared with controls. Interestingly, mtMSI was significantly high in tumors with Mn-SOD overexpression. Tumor-specific large-scale mtDNA deletions were not observed in CRC tissues. In conclusion, mtMSI and Mn-SOD overexpression are a common event in CRC. The analysis of mtMSI and/or Mn-SOD expression might help to identify patients at high risk for disease outcome, thereby helping to refine therapeutic decisions in CRC.

  18. 77 FR 22322 - Common Formats for Patient Safety Data Collection and Event Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ... Collection and Event Reporting AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS. ACTION: Notice... patient safety events to Patient Safety Organizations (PS0s). The purpose of this notice is to announce... events and quality of care. Information that is assembled and developed by providers for reporting...

  19. 76 FR 12358 - Common Formats for Patient Safety Data Collection and Event Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-07

    ... Collection and Event Reporting AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS. ACTION: Notice... voluntarily collect and submit standardized information regarding patient safety events. The purpose of this... report information regarding patient safety events and quality of care. Information that is assembled...

  20. 77 FR 42736 - Common Formats for Patient Safety Data Collection and Event Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-20

    ... Collection and Event Reporting AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS. ACTION: Notice... patient safety events to Patient Safety Organizations (PSOs). The purpose of this notice is to announce... facilities, and other healthcare providers may assemble information regarding patient safety events...

  1. TSQ (6-methoxy-8-p-toluenesulfonamido-quinoline), a common fluorescent sensor for cellular zinc, images zinc proteins.

    PubMed

    Meeusen, Jeffrey W; Tomasiewicz, Henry; Nowakowski, Andrew; Petering, David H

    2011-08-15

    Zn(2+) is a necessary cofactor for thousands of mammalian proteins. Research has suggested that transient fluxes of cellular Zn(2+) are also involved in processes such as apoptosis. Observations of Zn(2+) trafficking have been collected using Zn(2+) responsive fluorescent dyes. A commonly used Zn(2+) fluorophore is 6-methoxy-8-p-toluenesulfonamido-quinoline (TSQ). The chemical species responsible for TSQ's observed fluorescence in resting or activated cells have not been characterized. Parallel fluorescence microscopy and spectrofluorometry of LLC-PK(1) cells incubated with TSQ demonstrated punctate staining that concentrated around the nucleus and was characterized by an emission maximum near 470 nm. Addition of cell permeable Zn-pyrithione resulted in greatly increased, diffuse fluorescence that shifted the emission peak to 490 nm, indicative of the formation of Zn(TSQ)(2). TPEN (N,N,N'N'-tetrakis(-)[2-pyridylmethyl]-ethylenediamine), a cell permeant Zn(2+) chelator, largely quenched TSQ fluorescence returning the residual fluorescence to the 470 nm emission maximum. Gel filtration chromatography of cell supernatant from LLC-PK(1) cells treated with TSQ revealed that TSQ fluorescence (470 nm emission) eluted with the proteome fractions. Similarly, addition of TSQ to proteome prior to chromatography resulted in 470 nm fluorescence emission that was not observed in smaller molecular weight fractions. It is hypothesized that Zn-TSQ fluorescence, blue-shifted from the 490 nm emission maximum of Zn(TSQ)(2), results from ternary complex, TSQ-Zn-protein formation. As an example, Zn-carbonic anhydrase formed a ternary adduct with TSQ characterized by a fluorescence emission maximum of 470 nm and a dissociation constant of 1.55 × 10(-7) M. Quantification of TSQ-Zn-proteome fluorescence indicated that approximately 8% of cellular Zn(2+) was imaged by TSQ. These results were generalized to other cell types and model Zn-proteins.

  2. Cellular and humoral influenza-specific immune response upon vaccination in patients with common variable immunodeficiency and unclassified antibody deficiency.

    PubMed

    Hanitsch, Leif G; Löbel, Madlen; Mieves, Jan Florian; Bauer, Sandra; Babel, Nina; Schweiger, Brunhilde; Wittke, Kirsten; Grabowski, Patricia; Volk, Hans-Dieter; Scheibenbogen, Carmen

    2016-05-05

    Immunization against seasonal influenza with inactivated vaccine is recommended for patients with common variable immunodeficiency (CVID). However, humoral vaccine response in CVID patients is frequently impaired and current knowledge on T cell vaccine response in CVID and other patients with antibody deficiency is poor. In the present study, we comparatively analyzed the antibody and T cellular immune response of patients with CVID and unclassified antibody deficiency to influenza vaccination in the season 2013-2014. Eight patients with CVID, 8 patients with unclassified antibody deficiency and 9 healthy controls were vaccinated with a single dose of non-adjuvanted seasonal influenza vaccine. Before and 3 weeks after the vaccination antibody titers against the strains A/California/7/2009, A/Texas/50/2012, and B/Massachusetts/02/2012 included in the vaccine were measured by hemagglutination inhibition testing. Additionally, vaccine-specific T cell cytokine response was determined by stimulation with the complete vaccine in vitro. Whereas all healthy controls responded to vaccination with serum antibody titers, only 1/8 CVID patients and 4/8 patients with unclassified antibody deficiency showed a response against at least 1 of the 3 vaccine strains. However, 7/8 of the CVID and 6/8 of the patients with unclassified antibody deficiency had similar frequencies of vaccine-induced IFN-γ, TNF-α and IL-2 producing CD40L(+) T cells as the control group. Our data suggest that most CVID and unclassified antibody deficiency patients benefit from seasonal influenza vaccination by mounting a cellular response. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Autophagy competes for a common phosphatidylethanolamine pool with major cellular PE-consuming pathways in Saccharomyces cerevisiae.

    PubMed

    Wilson-Zbinden, Caroline; dos Santos, Aline Xavier da Silveira; Stoffel-Studer, Ingrid; van der Vaart, Aniek; Hofmann, Kay; Reggiori, Fulvio; Riezman, Howard; Kraft, Claudine; Peter, Matthias

    2015-02-01

    Autophagy is a highly regulated pathway that selectively degrades cellular constituents such as protein aggregates and excessive or damaged organelles. This transport route is characterized by engulfment of the targeted cargo by autophagosomes. The formation of these double-membrane vesicles requires the covalent conjugation of the ubiquitin-like protein Atg8 to phosphatidylethanolamine (PE). However, the origin of PE and the regulation of lipid flux required for autophagy remain poorly understood. Using a genetic screen, we found that the temperature-sensitive growth and intracellular membrane organization defects of mcd4-174 and mcd4-P301L mutants are suppressed by deletion of essential autophagy genes such as ATG1 or ATG7. MCD4 encodes an ethanolamine phosphate transferase that uses PE as a precursor for an essential step in the synthesis of the glycosylphosphatidylinositol (GPI) anchor used to link a subset of plasma membrane proteins to lipid bilayers. Similar to the deletion of CHO2, a gene encoding the enzyme converting PE to phosphatidylcholine (PC), deletion of ATG7 was able to restore lipidation and plasma membrane localization of the GPI-anchored protein Gas1 and normal organization of intracellular membranes. Conversely, overexpression of Cho2 was lethal in mcd4-174 cells grown at restrictive temperature. Quantitative lipid analysis revealed that PE levels are substantially reduced in the mcd4-174 mutant but can be restored by deletion of ATG7 or CHO2. Taken together, these data suggest that autophagy competes for a common PE pool with major cellular PE-consuming pathways such as the GPI anchor and PC synthesis, highlighting the possible interplay between these pathways and the existence of signals that may coordinate PE flux.

  4. What Caused the UK's Largest Common Dolphin (Delphinus delphis) Mass Stranding Event?

    PubMed Central

    Jepson, Paul D.; Deaville, Robert; Acevedo-Whitehouse, Karina; Barnett, James; Brownlow, Andrew; Brownell Jr., Robert L.; Clare, Frances C.; Davison, Nick; Law, Robin J.; Loveridge, Jan; Macgregor, Shaheed K.; Morris, Steven; Murphy, Sinéad; Penrose, Rod; Perkins, Matthew W.; Pinn, Eunice; Seibel, Henrike; Siebert, Ursula; Sierra, Eva; Simpson, Victor; Tasker, Mark L.; Tregenza, Nick; Cunningham, Andrew A.; Fernández, Antonio

    2013-01-01

    On 9 June 2008, the UK's largest mass stranding event (MSE) of short-beaked common dolphins (Delphinus delphis) occurred in Falmouth Bay, Cornwall. At least 26 dolphins died, and a similar number was refloated/herded back to sea. On necropsy, all dolphins were in good nutritive status with empty stomachs and no evidence of known infectious disease or acute physical injury. Auditory tissues were grossly normal (26/26) but had microscopic haemorrhages (5/5) and mild otitis media (1/5) in the freshest cases. Five lactating adult dolphins, one immature male, and one immature female tested were free of harmful algal toxins and had low chemical pollutant levels. Pathological evidence of mud/seawater inhalation (11/26), local tide cycle, and the relative lack of renal myoglobinuria (26/26) suggested MSE onset on a rising tide between 06∶30 and 08∶21 hrs (9 June). Potential causes excluded or considered highly unlikely included infectious disease, gas/fat embolism, boat strike, by-catch, predator attack, foraging unusually close to shore, chemical or algal toxin exposure, abnormal weather/climatic conditions, and high-intensity acoustic inputs from seismic airgun arrays or natural sources (e.g., earthquakes). International naval exercises did occur in close proximity to the MSE with the most intense part of the exercises (including mid-frequency sonars) occurring four days before the MSE and resuming with helicopter exercises on the morning of the MSE. The MSE may therefore have been a “two-stage process” where a group of normally pelagic dolphins entered Falmouth Bay and, after 3–4 days in/around the Bay, a second acoustic/disturbance event occurred causing them to strand en masse. This spatial and temporal association with the MSE, previous associations between naval activities and cetacean MSEs, and an absence of other identifiable factors known to cause cetacean MSEs, indicates naval activity to be the most probable cause of the Falmouth Bay MSE. PMID

  5. Association between use of warfarin with common sulfonylureas and serious hypoglycemic events: retrospective cohort analysis.

    PubMed

    Romley, John A; Gong, Cynthia; Jena, Anupam B; Goldman, Dana P; Williams, Bradley; Peters, Anne

    2015-12-07

    Is warfarin use associated with an increased risk of serious hypoglycemic events among older people treated with the sulfonylureas glipizide and glimepiride? This was a retrospective cohort analysis of pharmacy and medical claims from a 20% random sample of Medicare fee for service beneficiaries aged 65 years or older. It included 465,918 beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011 (4,355,418 person quarters); 71,895 (15.4%) patients also filled a prescription for warfarin (416,479 person quarters with warfarin use). The main outcome measure was emergency department visit or hospital admission with a primary diagnosis of hypoglycemia in person quarters with concurrent fills of warfarin and glipizide/glimepiride compared with the rates in quarters with glipizide/glimepiride fills only, Multivariable logistic regression was used to adjust for individual characteristics. Secondary outcomes included fall related fracture and altered consciousness/mental status. In quarters with glipizide/glimepiride use, hospital admissions or emergency department visits for hypoglycemia were more common in person quarters with concurrent warfarin use compared with quarters without warfarin use (294/416,479 v 1903/3,938,939; adjusted odds ratio 1.22, 95% confidence interval 1.05 to 1.42). The risk of hypoglycemia associated with concurrent use was higher among people using warfarin for the first time, as well as in those aged 65-74 years. Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visit for fall related fractures (3919/416,479 v 20,759/3,938,939; adjusted odds ratio 1.47, 1.41 to 1.54) and altered consciousness/mental status (2490/416,479 v 14,414/3,938,939; adjusted odds ratio 1.22, 1.16 to 1.29). Unmeasured factors could be correlated with both warfarin use and serious hypoglycemic events, leading to confounding. The findings may not generalize

  6. What caused the UK's largest common dolphin (Delphinus delphis) mass stranding event?

    PubMed

    Jepson, Paul D; Deaville, Robert; Acevedo-Whitehouse, Karina; Barnett, James; Brownlow, Andrew; Brownell, Robert L; Clare, Frances C; Davison, Nick; Law, Robin J; Loveridge, Jan; Macgregor, Shaheed K; Morris, Steven; Murphy, Sinéad; Penrose, Rod; Perkins, Matthew W; Pinn, Eunice; Seibel, Henrike; Siebert, Ursula; Sierra, Eva; Simpson, Victor; Tasker, Mark L; Tregenza, Nick; Cunningham, Andrew A; Fernández, Antonio

    2013-01-01

    On 9 June 2008, the UK's largest mass stranding event (MSE) of short-beaked common dolphins (Delphinus delphis) occurred in Falmouth Bay, Cornwall. At least 26 dolphins died, and a similar number was refloated/herded back to sea. On necropsy, all dolphins were in good nutritive status with empty stomachs and no evidence of known infectious disease or acute physical injury. Auditory tissues were grossly normal (26/26) but had microscopic haemorrhages (5/5) and mild otitis media (1/5) in the freshest cases. Five lactating adult dolphins, one immature male, and one immature female tested were free of harmful algal toxins and had low chemical pollutant levels. Pathological evidence of mud/seawater inhalation (11/26), local tide cycle, and the relative lack of renal myoglobinuria (26/26) suggested MSE onset on a rising tide between 06:30 and 08∶21 hrs (9 June). Potential causes excluded or considered highly unlikely included infectious disease, gas/fat embolism, boat strike, by-catch, predator attack, foraging unusually close to shore, chemical or algal toxin exposure, abnormal weather/climatic conditions, and high-intensity acoustic inputs from seismic airgun arrays or natural sources (e.g., earthquakes). International naval exercises did occur in close proximity to the MSE with the most intense part of the exercises (including mid-frequency sonars) occurring four days before the MSE and resuming with helicopter exercises on the morning of the MSE. The MSE may therefore have been a "two-stage process" where a group of normally pelagic dolphins entered Falmouth Bay and, after 3-4 days in/around the Bay, a second acoustic/disturbance event occurred causing them to strand en masse. This spatial and temporal association with the MSE, previous associations between naval activities and cetacean MSEs, and an absence of other identifiable factors known to cause cetacean MSEs, indicates naval activity to be the most probable cause of the Falmouth Bay MSE.

  7. Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression.

    PubMed

    Soo, Julia K; Mackenzie Ross, Alastair D; Kallenberg, David M; Milagre, Carla; Heung Chong, W; Chow, Jade; Hill, Lucy; Hoare, Stacey; Collinson, Rebecca S; Hossain, Mehnaz; Keith, W Nicol; Marais, Richard; Bennett, Dorothy C

    2011-06-01

    Cell senescence is a permanent growth arrest following extended proliferation. Cultured cancer cells including metastatic melanoma cells often appear immortal (proliferate indefinitely), while uncultured benign nevi (moles) show senescence markers. Here, with new explantation methods, we investigated which classes of primary pigmented lesions are typically immortal. Nevi yielded a few proliferating cells, consistent with most nevus cells being senescent. No nevus culture (0/28) appeared immortal. Some thin and thick melanoma cultures proved immortal under these conditions, but surprisingly few (4/37). All arrested cultures displayed three senescence markers in some cells: β-galactosidase, nuclear p16, and heterochromatic foci/aggregates. However, melanoma cultures also showed features of telomeric crisis (arrest because of ultrashort telomeres). Moreover, crisis markers including anaphase bridges were frequent in uncultured vertical growth-phase (VGP) melanomas. Conversely, all immortal melanoma cultures expressed telomerase reverse transcriptase and telomerase, showing aneuploidy. The findings suggest that primary melanomas are typically precrisis, with immortalization/telomere maintenance as a late event.

  8. Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression

    PubMed Central

    Soo, Julia K; MacKenzie Ross, Alastair D; Kallenberg, David M; Milagre, Carla; Heung Chong, W; Chow, Jade; Hill, Lucy; Hoare, Stacey; Collinson, Rebecca S; Hossain, Mehnaz; Keith, W Nicol; Marais, Richard; Bennett, Dorothy C

    2011-01-01

    Cell senescence is a permanent growth arrest following extended proliferation. Cultured cancer cells including metastatic melanoma cells often appear immortal (proliferate indefinitely), while uncultured benign nevi (moles) show senescence markers. Here, with new explantation methods, we investigated which classes of primary pigmented lesions are typically immortal. Nevi yielded a few proliferating cells, consistent with most nevus cells being senescent. No nevus culture (0/28) appeared immortal. Some thin and thick melanoma cultures proved immortal under these conditions, but surprisingly few (4/37). All arrested cultures displayed three senescence markers in some cells: β-galactosidase, nuclear p16, and heterochromatic foci/aggregates. However, melanoma cultures also showed features of telomeric crisis (arrest because of ultrashort telomeres). Moreover, crisis markers including anaphase bridges were frequent in uncultured vertical growth-phase (VGP) melanomas. Conversely, all immortal melanoma cultures expressed telomerase reverse transcriptase and telomerase, showing aneuploidy. The findings suggest that primary melanomas are typically precrisis, with immortalization/telomere maintenance as a late event. PMID:21418545

  9. Commonality.

    ERIC Educational Resources Information Center

    Beaton, Albert E., Jr.

    Commonality analysis is an attempt to understand the relative predictive power of the regressor variables, both individually and in combination. The squared multiple correlation is broken up into elements assigned to each individual regressor and to each possible combination of regressors. The elements have the property that the appropriate sums…

  10. Common carotid intima-media thickness relates to cardiovascular events in adults aged <45 years.

    PubMed

    Eikendal, Anouk L M; Groenewegen, Karlijn A; Anderson, Todd J; Britton, Annie R; Engström, Gunnar; Evans, Greg W; de Graaf, Jacqueline; Grobbee, Diederick E; Hedblad, Bo; Holewijn, Suzanne; Ikeda, Ai; Kitagawa, Kazuo; Kitamura, Akihiko; Lonn, Eva M; Lorenz, Matthias W; Mathiesen, Ellisiv B; Nijpels, Giel; Dekker, Jacqueline M; Okazaki, Shuhei; O'Leary, Daniel H; Polak, Joseph F; Price, Jacqueline F; Robertson, Christine; Rembold, Christopher M; Rosvall, Maria; Rundek, Tatjana; Salonen, Jukka T; Sitzer, Matthias; Stehouwer, Coen D A; Hoefer, Imo E; Peters, Sanne A E; Bots, Michiel L; den Ruijter, Hester M

    2015-04-01

    Although atherosclerosis starts in early life, evidence on risk factors and atherosclerosis in individuals aged <45 years is scarce. Therefore, we studied the relationship between risk factors, common carotid intima-media thickness (CIMT), and first-time cardiovascular events in adults aged <45 years. Our study population consisted of 3067 adults aged <45 years free from symptomatic cardiovascular disease at baseline, derived from 6 cohorts that are part of the USE-IMT initiative, an individual participant data meta-analysis of general-population-based cohort studies evaluating CIMT measurements. Information on risk factors, CIMT measurements, and follow-up of the combined end point (first-time myocardial infarction or stroke) was obtained. We assessed the relationship between risk factors and CIMT and the relationship between CIMT and first-time myocardial infarction or stroke using a multivariable linear mixed-effects model and a Cox proportional-hazards model, respectively. During a follow-up of 16.3 years, 55 first-time myocardial infarctions or strokes occurred. Median CIMT was 0.63 mm. Of the risk factors under study, age, sex, diastolic blood pressure, body mass index, total cholesterol, and high-density lipoprotein cholesterol related to CIMT. Furthermore, CIMT related to first-time myocardial infarction or stroke with a hazard ratio of 1.40 per SD increase in CIMT, independent of risk factors (95% confidence interval, 1.11-1.76). CIMT may be a valuable marker for cardiovascular risk in adults aged <45 years who are not yet eligible for standard cardiovascular risk screening. This is especially relevant in those with an increased, unfavorable risk factor burden.

  11. Photosensitivity and photodynamic events in black, red and blue tattoos are common: A 'Beach Study'.

    PubMed

    Hutton Carlsen, K; Serup, J

    2014-02-01

    To find the prevalence of complaints in people having tattoos, with emphasis on chronic complaints, photosensitivity and photodynamic events. Individuals sunbathing from June to September 2011 at the beaches of Denmark were invited to participate as they are prone to report tattoos and sun habits reliably. Sun-related and non-sun-related problems in tattoos were determined along with participants' use of sunscreen. Skin type was categorized, as were motifs and colours associated with problems. Of 467 sunbathers, 146 (31.3%) had tattoos. A total of 144 sunbathers with 301 tattoos accepted inclusion. Complaints were experienced in 60/144 (42%), of which 31/60 (52%) were sun related, such as swelling (58%), itching/stinging/pain (52%) and redness (26%). Reactions independent of sun were 29/60 (48%), such as reactions to heat 12/29 (41%) and cold 1/29 (4%). Red, blue and black tattoos predominantly caused sun-related complaints followed by the remaining colours. By number, problems in black tattoos dominated as black was far more frequent. Complaints such as swelling, itching, stinging, pain and redness are common, predominantly in black and red tattoos, but also frequent in blue tattoos, thus, not confined to one specific colour or chemical entity or class of pigment. Symptoms may switch on and off in seconds, typically not of the weal-and-flare type. Photochemical reactions to pigment or pigment-breakdown products in situ in the skin with induction of reactive oxygen species (ROS) is presumed to be one causative mechanism. Another possible mechanism especially relevant in black may be induction of ROS due to effects of aggregation of carbon black nanoparticles. © 2013 The Authors Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology.

  12. Reduction of Cellular Expression Levels Is a Common Feature of Functionally Affected Pendrin (SLC26A4) Protein Variants

    PubMed Central

    de Moraes, Vanessa C S; Bernardinelli, Emanuele; Zocal, Nathalia; Fernandez, Jhonathan A; Nofziger, Charity; Castilho, Arthur M; Sartorato, Edi L; Paulmichl, Markus; Dossena, Silvia

    2016-01-01

    Sequence alterations in the pendrin gene (SLC26A4) leading to functionally affected protein variants are frequently involved in the pathogenesis of syndromic and nonsyndromic deafness. Considering the high number of SLC26A4 sequence alterations reported to date, discriminating between functionally affected and unaffected pendrin protein variants is essential in contributing to determine the genetic cause of deafness in a given patient. In addition, identifying molecular features common to the functionally affected protein variants can be extremely useful to design future molecule-directed therapeutic approaches. Here we show the functional and molecular characterization of six previously uncharacterized pendrin protein variants found in a cohort of 58 Brazilian deaf patients. Two variants (p.T193I and p.L445W) were undetectable in the plasma membrane, completely retained in the endoplasmic reticulum and showed no transport function; four (p.P142L, p.G149R, p.C282Y and p.Q413R) showed reduced function and significant, although heterogeneous, expression levels in the plasma membrane. Importantly, total expression levels of all of the functionally affected protein variants were significantly reduced with respect to the wild-type and a fully functional variant (p.R776C), regardless of their subcellular localization. Interestingly, reduction of expression may also reduce the transport activity of variants with an intrinsic gain of function (p.Q413R). As reduction of overall cellular abundance was identified as a common molecular feature of pendrin variants with affected function, the identification of strategies to prevent reduction in expression levels may represent a crucial step of potential future therapeutic interventions aimed at restoring the transport activity of dysfunctional pendrin variants. PMID:26752218

  13. 75 FR 16140 - Common Formats for Patient Safety Data Collection and Event Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ..., Perinatal, Pressure Ulcer, and Surgery or Anesthesia. The Common Formats Version 1.1 has a defined focus on... surgery centers, and physician and practitioner offices. AHRQ's Common Formats Version 1.1...

  14. Integrated Cellular and Plasma Proteomics of Contrasting B-cell Cancers Reveals Common, Unique and Systemic Signatures.

    PubMed

    Johnston, Harvey E; Carter, Matthew J; Cox, Kerry L; Dunscombe, Melanie; Manousopoulou, Antigoni; Townsend, Paul A; Garbis, Spiros D; Cragg, Mark S

    2017-03-01

    Approximately 800,000 leukemia and lymphoma cases are diagnosed worldwide each year. Burkitt's lymphoma (BL) and chronic lymphocytic leukemia (CLL) are examples of contrasting B-cell cancers; BL is a highly aggressive lymphoid tumor, frequently affecting children, whereas CLL typically presents as an indolent, slow-progressing leukemia affecting the elderly. The B-cell-specific overexpression of the myc and TCL1 oncogenes in mice induce spontaneous malignancies modeling BL and CLL, respectively. Quantitative mass spectrometry proteomics and isobaric labeling were employed to examine the biology underpinning contrasting Eμ-myc and Eμ-TCL1 B-cell tumors. Additionally, the plasma proteome was evaluated using subproteome enrichment to interrogate biomarker emergence and the systemic effects of tumor burden. Over 10,000 proteins were identified (q<0.01) of which 8270 cellular and 2095 plasma proteins were quantitatively profiled. A common B-cell tumor signature of 695 overexpressed proteins highlighted ribosome biogenesis, cell-cycle promotion and chromosome segregation. Eμ-myc tumors overexpressed several methylating enzymes and underexpressed many cytoskeletal components. Eμ-TCL1 tumors specifically overexpressed ER stress response proteins and signaling components in addition to both subunits of the interleukin-5 (IL5) receptor. IL5 treatment promoted Eμ-TCL1 tumor proliferation, suggesting an amplification of IL5-induced AKT signaling by TCL1. Tumor plasma contained a substantial tumor lysis signature, most prominent in Eμ-myc plasma, whereas Eμ-TCL1 plasma contained signatures of immune-response, inflammation and microenvironment interactions, with putative biomarkers in early-stage cancer. These findings provide a detailed characterization of contrasting B-cell tumor models, identifying common and specific tumor mechanisms. Integrated plasma proteomics allowed the dissection of a systemic response and a tumor lysis signature present in early- and late

  15. Association of common genetic variants with risperidone adverse events in a Spanish schizophrenic population.

    PubMed

    Almoguera, B; Riveiro-Alvarez, R; Lopez-Castroman, J; Dorado, P; Vaquero-Lorenzo, C; Fernandez-Piqueras, J; Llerena, A; Abad-Santos, F; Baca-García, E; Dal-Ré, R; Ayuso, C

    2013-04-01

    Risperidone non-compliance is often high due to undesirable side effects, whose development is in part genetically determined. Studies with genetic variants involved in the pharmacokinetics and pharmacodynamics of risperidone have yielded inconsistent results. Thus, the aim of this study was to investigate the putative association of genetic markers with the occurrence of four frequently observed adverse events secondary to risperidone treatment: sleepiness, weight gain, extrapyramidal symptoms and sexual adverse events. A series of 111 schizophrenia inpatients were genotyped for genetic variants previously associated with or potentially involved in risperidone response. Presence of adverse events was the main variable and potential confounding factors were considered. Allele 16Gly of ADRB2 was significantly associated with a higher risk of sexual adverse events. There were other non-significant trends for DRD3 9Gly and SLC6A4 S alleles. Our results, although preliminary, provide new candidate variants of potential use in risperidone safety prediction.

  16. Calcium-mediated oxidative stress: a common mechanism in tight junction disruption by different types of cellular stress.

    PubMed

    Gangwar, Ruchika; Meena, Avtar S; Shukla, Pradeep K; Nagaraja, Archana S; Dorniak, Piotr L; Pallikuth, Sandeep; Waters, Christopher M; Sood, Anil; Rao, RadhaKrishna

    2017-02-20

    The role of reactive oxygen species (ROS) in osmotic stress, dextran sulfate sodium (DSS) and cyclic stretch-induced tight junction (TJ) disruption was investigated in Caco-2 cell monolayers in vitro and restraint stress-induced barrier dysfunction in mouse colon in vivo Live cell imaging showed that osmotic stress, cyclic stretch and DSS triggered rapid production of ROS in Caco-2 cell monolayers, which was blocked by depletion of intracellular Ca(2+) by 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Knockdown of CaV1.3 or TRPV6 channels blocked osmotic stress and DSS-induced ROS production and attenuated TJ disruption and barrier dysfunction. N-Acetyl l-cysteine (NAC) and l-N(G)-Nitroarginine methyl ester (l-NAME) blocked stress-induced TJ disruption and barrier dysfunction. NAC and l-NAME also blocked stress-induced activation of c-Jun N-terminal kinase (JNK) and c-Src. ROS was colocalized with the mitochondrial marker in stressed cells. Cyclosporin A blocked osmotic stress and DSS-induced ROS production, barrier dysfunction, TJ disruption and JNK activation. Mitochondria-targeted Mito-TEMPO blocked osmotic stress and DSS-induced barrier dysfunction and TJ disruption. Chronic restraint stress in mice resulted in the elevation of intracellular Ca(2+), activation of JNK and c-Src, and disruption of TJ in the colonic epithelium. Furthermore, corticosterone administration induced JNK and c-Src activation, TJ disruption and protein thiol oxidation in colonic mucosa. The present study demonstrates that oxidative stress is a common signal in the mechanism of TJ disruption in the intestinal epithelium by different types of cellular stress in vitro and bio behavioral stress in vivo. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  17. The role of well-defined nanotopography of titanium implants on osseointegration: cellular and molecular events in vivo

    PubMed Central

    Karazisis, Dimitrios; Ballo, Ahmed M; Petronis, Sarunas; Agheli, Hossein; Emanuelsson, Lena; Thomsen, Peter; Omar, Omar

    2016-01-01

    Purpose Mechanisms governing the cellular interactions with well-defined nanotopography are not well described in vivo. This is partly due to the difficulty in isolating a particular effect of nanotopography from other surface properties. This study employed colloidal lithography for nanofabrication on titanium implants in combination with an in vivo sampling procedure and different analytical techniques. The aim was to elucidate the effect of well-defined nanotopography on the molecular, cellular, and structural events of osseointegration. Materials and methods Titanium implants were nanopatterned (Nano) with semispherical protrusions using colloidal lithography. Implants, with and without nanotopography, were implanted in rat tibia and retrieved after 3, 6, and 28 days. Retrieved implants were evaluated using quantitative polymerase chain reaction, histology, immunohistochemistry, and energy dispersive X-ray spectroscopy (EDS). Results Surface characterization showed that the nanotopography was well defined in terms of shape (semispherical), size (79±6 nm), and distribution (31±2 particles/µm2). EDS showed similar levels of titanium, oxygen, and carbon for test and control implants, confirming similar chemistry. The molecular analysis of the retrieved implants revealed that the expression levels of the inflammatory cytokine, TNF-α, and the osteoclastic marker, CatK, were reduced in cells adherent to the Nano implants. This was consistent with the observation of less CD163-positive macrophages in the tissue surrounding the Nano implant. Furthermore, periostin immunostaining was frequently detected around the Nano implant, indicating higher osteogenic activity. This was supported by the EDS analysis of the retrieved implants showing higher content of calcium and phosphate on the Nano implants. Conclusion The results show that Nano implants elicit less periimplant macrophage infiltration and downregulate the early expression of inflammatory (TNF-α) and

  18. OLDER ADULTS’ COPING WITH NEGATIVE LIFE EVENTS: COMMON PROCESSES OF MANAGING HEALTH, INTERPERSONAL, AND FINANCIAL/WORK STRESSORS*

    PubMed Central

    MOOS, RUDOLF H.; BRENNAN, PENNY L.; SCHUTTE, KATHLEEN K.; MOOS, BERNICE S.

    2007-01-01

    This study examined how older adults cope with negative life events in health, interpersonal, and financial/work domains and whether common stress and coping processes hold across these three domains. On three occasions, older adults identified the most severe negative event they faced in the last year and described how they appraised and coped with that event, their ambient chronic stressors, and event and functioning outcomes. The stress and coping process was largely consistent across the three life domains. Individuals who appraised events as challenging and relied more on approach coping were more likely to report some benefit from those events. Individuals who experienced more chronic stressors and favored avoidance coping were more likely to be depressed and to have late-life drinking problems. Chronic stressors, as well as approach and avoidance coping, were predictably associated with overall outcomes in all three event domains. These findings provide a basis for preventive interventions that may help older adults’ address the most prevalent stressors of aging more effectively. PMID:16454482

  19. Transcriptional control of fungal cell cycle and cellular events by Fkh2, a forkhead transcription factor in an insect pathogen

    PubMed Central

    Wang, Juan-Juan; Qiu, Lei; Cai, Qing; Ying, Sheng-Hua; Feng, Ming-Guang

    2015-01-01

    Transcriptional control of the cell cycle by forkhead (Fkh) transcription factors is likely associated with fungal adaptation to host and environment. Here we show that Fkh2, an ortholog of yeast Fkh1/2, orchestrates cell cycle and many cellular events of Beauveria bassiana, a filamentous fungal insect pathogen. Deletion of Fkh2 in B. bassiana resulted in dramatic down-regulation of the cyclin-B gene cluster and hence altered cell cycle (longer G2/M and S, but shorter G0/G1, phases) in unicellular blastospores. Consequently, ΔFkh2 produced twice as many, but smaller, blastospores than wild-type under submerged conditions, and formed denser septa and shorter/broader cells in aberrantly branched hyphae. In these hyphae, clustered genes required for septation and conidiation were remarkedly up-regulated, followed by higher yield and slower germination of aerial conidia. Moreover, ΔFkh2 displayed attenuated virulence and decreased tolerance to chemical and environmental stresses, accompanied with altered transcripts and activities of phenotype-influencing proteins or enzymes. All the changes in ΔFkh2 were restored by Fkh2 complementation. All together, Fkh2-dependent transcriptional control is vital for the adaptation of B. bassiana to diverse habitats of host insects and hence contributes to its biological control potential against arthropod pests. PMID:25955538

  20. Common stressful life events and difficulties are associated with mental health symptoms and substance use in young adolescents

    PubMed Central

    2012-01-01

    Background Stressful life events are associated with mood disorders in adults in clinical settings. Less described in the literature is the association between common life stressors and a wide range of psychopathology in young adolescents. This study uses a large non-clinical sample of young adolescents to describe the associations among worry or stress about common life events/difficulties, mental health and substance use. Methods Data on lifetime stress or worry about common life events/difficulties (i.e., romantic breakups, family disruption, interpersonal difficulties, and personal stress (health, weight, school work)), symptoms of depression, conduct disorder symptoms, and substance use were collected from 1025 grade 7 students (mean age 12.9 years; 45% male). The association between each source of stress and each mental health and substance use indicator was modeled in separate logistic regression analyses. Results The proportion of adolescents reporting worry or stress ranged from 7% for new family to 53% for schoolwork. Romantic breakup stress was statistically significantly associated with all the mental health and substance use indicators except illicit drug use. Family disruption was statistically significantly associated with depression symptoms, marijuana use, and cigarette use. Interpersonal difficulties stress was statistically significantly associated with depression symptoms. All sources of personal stress were statistically significantly related to depression symptoms. In addition, health-related stress was inversely related to binge drinking. Conclusion Young adolescents may benefit from learning positive coping skills to manage worry or stress about common stressors and in particular, worry or stress related to romantic breakups. Appropriate management of mental health symptoms and substance use related to common stressful life events and difficulties may help reduce emerging psychopathology. PMID:22900789

  1. Common stressful life events and difficulties are associated with mental health symptoms and substance use in young adolescents.

    PubMed

    Low, Nancy Cp; Dugas, Erika; O'Loughlin, Erin; Rodriguez, Daniel; Contreras, Gisele; Chaiton, Michael; O'Loughlin, Jennifer

    2012-08-17

    Stressful life events are associated with mood disorders in adults in clinical settings. Less described in the literature is the association between common life stressors and a wide range of psychopathology in young adolescents. This study uses a large non-clinical sample of young adolescents to describe the associations among worry or stress about common life events/difficulties, mental health and substance use. Data on lifetime stress or worry about common life events/difficulties (i.e., romantic breakups, family disruption, interpersonal difficulties, and personal stress (health, weight, school work)), symptoms of depression, conduct disorder symptoms, and substance use were collected from 1025 grade 7 students (mean age 12.9 years; 45% male). The association between each source of stress and each mental health and substance use indicator was modeled in separate logistic regression analyses. The proportion of adolescents reporting worry or stress ranged from 7% for new family to 53% for schoolwork. Romantic breakup stress was statistically significantly associated with all the mental health and substance use indicators except illicit drug use. Family disruption was statistically significantly associated with depression symptoms, marijuana use, and cigarette use. Interpersonal difficulties stress was statistically significantly associated with depression symptoms. All sources of personal stress were statistically significantly related to depression symptoms. In addition, health-related stress was inversely related to binge drinking. Young adolescents may benefit from learning positive coping skills to manage worry or stress about common stressors and in particular, worry or stress related to romantic breakups. Appropriate management of mental health symptoms and substance use related to common stressful life events and difficulties may help reduce emerging psychopathology.

  2. The Common Core State Standards Initiative: An Event History Analysis of State Adoption

    ERIC Educational Resources Information Center

    LaVenia, Mark; Cohen-Vogel, Lora; Lang, Laura B.

    2015-01-01

    Today, with states' near-universal adoption of the Common Core State Standards, the political system has achieved that which was not possible less than 2 decades ago. Just why this is so remains unanswered. Some observers have attributed states' embrace of the standards to the substantial financial incentives that the federal government embedded…

  3. The Common Core State Standards Initiative: An Event History Analysis of State Adoption

    ERIC Educational Resources Information Center

    LaVenia, Mark; Cohen-Vogel, Lora; Lang, Laura B.

    2015-01-01

    Today, with states' near-universal adoption of the Common Core State Standards, the political system has achieved that which was not possible less than 2 decades ago. Just why this is so remains unanswered. Some observers have attributed states' embrace of the standards to the substantial financial incentives that the federal government embedded…

  4. Cellular Events Involved in Survival of Individual Arbuscular Mycorrhizal Symbionts Growing in the Absence of the Host

    PubMed Central

    Logi, Cable; Sbrana, Cristiana; Giovannetti, Manuela

    1998-01-01

    A survival strategy operating in the absence of the host was shown in obligately biotrophic arbuscular mycorrhizal (AM) symbionts. When no host-derived signals from the surrounding environment were perceived by germinating spores, fungal hyphae underwent a programmed growth arrest and resource reallocation, allowing long-term maintenance of viability and host infection capability. The early stages of mycelial growth of AM fungi were studied by a combination of time-lapse and video-enhanced light microscopy, image analysis, and immunodetection, with the aim of acquiring knowledge of cell events leading to the arrest of mycelial growth. The time-course of growth arrest was resolved by precisely timing the growth rate and magnitude of the mycelium originating from individual spores of Glomus caledonium. Extensive mycelial growth was observed during the first 15 days; thereafter, fungal hyphae showed retraction of protoplasm from the tips, with formation of retraction septa separating viable from empty hyphal segments. This active process involved migration of nuclei and cellular organelles and appeared to be functional in the ability of the fungus to survive in the absence of a host. Immunodetection of cytoskeletal proteins, metabolic activity, and the retention of infectivity of germinated spores confirmed the developmental data. The highest amounts of tubulins were detected when hyphal growth had ceased but when retraction of protoplasm was most active. This was consistent with the role of the cytoskeleton during protoplasm retraction. Succinate dehydrogenase activity in hyphae proximal to the mother spore was still detectable in 6-month-old mycelium, which remained viable and able to form appressoria and produce symbiotic structures. PMID:9726899

  5. Stereospecific Inhibitory Effects of CCG-1423 on the Cellular Events Mediated by Myocardin-Related Transcription Factor A

    PubMed Central

    Watanabe, Bunta; Minami, Saki; Ishida, Hideaki; Yoshioka, Ryuzo; Nakagawa, Yoshiaki; Morita, Tsuyoshi; Hayashi, Ken’ichiro

    2015-01-01

    CCG-1423 suppresses several pathological processes including cancer cell migration, tissue fibrosis, and the development of atherosclerotic lesions. These suppressions are caused by inhibition of myocardin-related transcription factor A (MRTF-A), which is a critical factor for epithelial–mesenchymal transition (EMT). CCG-1423 can therefore be a potent inhibitor for EMT. CCG-1423 and related compounds, CCG-100602 and CCG-203971 possess similar biological activities. Although these compounds are comprised of two stereoisomers, the differences in their biological activities remain to be assessed. To address this issue, we stereoselectively synthesized optically pure isomers of these compounds and validated their biological activities. The S-isomer of CCG-1423 rather than the R-isomer exhibited modestly but significantly higher inhibitory effects on the cellular events triggered by MRTF-A activation including serum response factor-mediated gene expression and cell migration of fibroblasts and B16F10 melanoma cells. Accordingly, the S-isomer of CCG-1423 more potently blocked the serum-induced nuclear import of MRTF-A than the R-isomer. No such difference was observed in cells treated with each of two stereoisomers of CCG-100602 or CCG-203971. We previously reported that the N-terminal basic domain (NB), which functions as a nuclear localization signal of MRTF-A, is a binding site for CCG-1423. Consistent with the biological activities of two stereoisomers of CCG-1423, docking simulation demonstrated that the S-isomer of CCG-1423 was more likely to bind to NB than the R-isomer. This is a first report demonstrating the stereospecific biological activities of CCG-1423. PMID:26295164

  6. Microscopic analysis of the cellular events during scatter factor/hepatocyte growth factor-induced epithelial tubulogenesis.

    PubMed

    Williams, M J; Clark, P

    2003-11-01

    Scatter factor/hepatocyte growth factor (SF/HGF), a large multifunctional polypeptide growth and motility factor, is known to play important roles during embryonic development, adult tissue growth and repair. In an established three-dimensional type I collagen model, SF/HGF induces Madin-Darby canine kidney (MDCK) epithelial cysts to form long, branching tubules (tubulogenesis). In addition, the composition of the surrounding extracellular matrix (ECM) has been shown to modulate SF/HGF-induced morphogenesis, where tubulogenesis was completely abrogated in Matrigel basement membrane. Many cellular events that occur during SF/HGF-mediated remodelling, and its modulation by the ECM, remain unclear. We have investigated these mechanisms through microscopic examination of the time-course of SF/HGF-induced responses in MDCK cysts cultured in type I collagen or Matrigel. We found that early responses to SF/HGF were matrix-independent. Changes included increased paracellular spacing between normally closely apposed lateral membranes, and the formation of filopodial processes, indicating a partial motile response. Cell-cell contact was maintained, with the persistence of cell junctions. Therefore, while one or a number of ECM components are preventing SF/HGF-primed cells from undergoing an invasive and/or migratory programme, non-permissive matrices are not preventing SF/HGF signalling to the cell. Later matrix-dependent responses, which occurred in type I collagen but not Matrigel, included the formation of basal protrusions that comprise two or more neighbouring cells, which extend to form nascent tubules. Modified polarity of cells comprising the basal protrusions was evident, with a marker for the apical membrane being found in the same region as adherens junctions and desmosomes, typically localized at lateral membranes. We propose a model for SF/HGF-induced tubulogenesis in which tubules form from basal protrusions of adjacent cells. This mechanism of in vitro tubule

  7. ON THE NATURE OF EXor ACCRETION EVENTS: AN INFREQUENT MANIFESTATION OF A COMMON PHENOMENOLOGY?

    SciTech Connect

    Lorenzetti, D.; Antoniucci, S.; Giannini, T.; Li Causi, G.; Ventura, P.; Di Paola, A.; Nisini, B.; Arkharov, A. A.; Larionov, V. M.; Kopatskaya, E. N. E-mail: simone.antoniucci@oa-roma.inaf.it E-mail: gianluca.licausi@oa-roma.inaf.it E-mail: brunella.nisini@oa-roma.inaf.it E-mail: arkadi@arharov.ru E-mail: enik1346@rambler.ru

    2012-04-20

    We present the results of a comparison between classical and newly identified EXor based on literature data and aimed at recognizing possible differences or similarities between the categories. Optical and near-IR two-color diagrams, modalities of fluctuations, and derived values of the mass accretion rates are indicative of strong similarities between the two samples. We demonstrate how the difference between the outburst and the quiescence spectral energy distribution of all EXor can be well fitted with a single blackbody, as if an additional thermal component appears during the outbursting phase. Temperatures of this additional component span between 1000 and 4500 K, while the radii of the emitting regions (assumed to be a uniform disk) span between 0.01 and 0.1 AU, sizes typical of the inner portions of the circumstellar disk. Spots persisting up to 50% of the outburst duration, not exceeding 10% of the stellar surface, and with temperatures compatible with the EXor mass accretion rates, are able to account for both the appearance of the additional thermal component and the dust sublimation in the inner structures of the disk. We also compare the EXor events with the most significant color and magnitude fluctuations of active T Tauri stars finding that (1) burst accretion phenomena should also be important for this latter class and (2) EXor events could be more frequent than those accidentally discovered. A remarkable case is that of the source V2493 Cyg, a T Tauri star recently identified as a strong outbursting object: New optical and near-IR photometric and spectroscopic data are presented in an attempt to clarify its EXor or FUor nature.

  8. On the Nature of EXor Accretion Events: An Infrequent Manifestation of a Common Phenomenology?

    NASA Astrophysics Data System (ADS)

    Lorenzetti, D.; Antoniucci, S.; Giannini, T.; Li Causi, G.; Ventura, P.; Arkharov, A. A.; Kopatskaya, E. N.; Larionov, V. M.; Di Paola, A.; Nisini, B.

    2012-04-01

    We present the results of a comparison between classical and newly identified EXor based on literature data and aimed at recognizing possible differences or similarities between the categories. Optical and near-IR two-color diagrams, modalities of fluctuations, and derived values of the mass accretion rates are indicative of strong similarities between the two samples. We demonstrate how the difference between the outburst and the quiescence spectral energy distribution of all EXor can be well fitted with a single blackbody, as if an additional thermal component appears during the outbursting phase. Temperatures of this additional component span between 1000 and 4500 K, while the radii of the emitting regions (assumed to be a uniform disk) span between 0.01 and 0.1 AU, sizes typical of the inner portions of the circumstellar disk. Spots persisting up to 50% of the outburst duration, not exceeding 10% of the stellar surface, and with temperatures compatible with the EXor mass accretion rates, are able to account for both the appearance of the additional thermal component and the dust sublimation in the inner structures of the disk. We also compare the EXor events with the most significant color and magnitude fluctuations of active T Tauri stars finding that (1) burst accretion phenomena should also be important for this latter class and (2) EXor events could be more frequent than those accidentally discovered. A remarkable case is that of the source V2493 Cyg, a T Tauri star recently identified as a strong outbursting object: New optical and near-IR photometric and spectroscopic data are presented in an attempt to clarify its EXor or FUor nature. Based on observations collected at AZT-24 telescope (Campo Imperatore, Italy), AZT-8 (Crimea, Ukraine), and LX-200 (St. Petersburg, Russia).

  9. A beacon of hope in stroke therapy-Blockade of pathologically activated cellular events in excitotoxic neuronal death as potential neuroprotective strategies.

    PubMed

    Hoque, Ashfaqul; Hossain, M Iqbal; Ameen, S Sadia; Ang, Ching-Seng; Williamson, Nicholas; Ng, Dominic C H; Chueh, Anderly C; Roulston, Carli; Cheng, Heung-Chin

    2016-04-01

    Excitotoxicity, a pathological process caused by over-stimulation of ionotropic glutamate receptors, is a major cause of neuronal loss in acute and chronic neurological conditions such as ischaemic stroke, Alzheimer's and Huntington's diseases. Effective neuroprotective drugs to reduce excitotoxic neuronal loss in patients suffering from these neurological conditions are urgently needed. One avenue to achieve this goal is to clearly define the intracellular events mediating the neurotoxic signals originating from the over-stimulated glutamate receptors in neurons. In this review, we first focus on the key cellular events directing neuronal death but not involved in normal physiological processes in the neurotoxic signalling pathways. These events, referred to as pathologically activated events, are potential targets for the development of neuroprotectant therapeutics. Inhibitors blocking some of the known pathologically activated cellular events have been proven to be effective in reducing stroke-induced brain damage in animal models. Notable examples are inhibitors suppressing the ion channel activity of neurotoxic glutamate receptors and those disrupting interactions of specific cellular proteins occurring only in neurons undergoing excitotoxic cell death. Among them, Tat-NR2B9c and memantine are clinically effective in reducing brain damage caused by some acute and chronic neurological conditions. Our second focus is evaluation of the suitability of the other inhibitors for use as neuroprotective therapeutics. We also discuss the experimental approaches suitable for bridging our knowledge gap in our current understanding of the excitotoxic signalling mechanism in neurons and discovery of new pathologically activated cellular events as potential targets for neuroprotection. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. PP2A impaired activity is a common event in acute myeloid leukemia and its activation by forskolin has a potent anti-leukemic effect.

    PubMed

    Cristóbal, I; Garcia-Orti, L; Cirauqui, C; Alonso, M M; Calasanz, M J; Odero, M D

    2011-04-01

    Protein phosphatase 2A (PP2A) is a human tumor suppressor that inhibits cellular transformation by regulating the activity of several signaling proteins critical for malignant cell behavior. PP2A has been described as a potential therapeutic target in chronic myeloid leukemia, Philadelphia chromosome-positive acute lymphoblastic leukemia and B-cell chronic lymphocytic leukemia. Here, we show that PP2A inactivation is a recurrent event in acute myeloid leukemia (AML), and that restoration of PP2A phosphatase activity by treatment with forskolin in AML cells blocks proliferation, induces caspase-dependent apoptosis and affects AKT and ERK1/2 activity. Moreover, treatment with forskolin had an additive effect with Idarubicin and Ara-c, drugs used in standard induction therapy in AML patients. Analysis at protein level of the PP2A activation status in a series of patients with AML at diagnosis showed PP2A hyperphosphorylation in 78% of cases (29/37). In addition, we found that either deregulated expression of the endogenous PP2A inhibitors SET or CIP2A, overexpression of SETBP1, or downregulation of some PP2A subunits, might be contributing to PP2A inhibition in AML. In conclusion, our results show that PP2A inhibition is a common event in AML cells and that PP2A activators, such as forskolin or FTY720, could represent potential novel therapeutic targets in AML.

  11. Technical note: Common characteristics of directional spreading-steepness joint distribution in freak wave events

    NASA Astrophysics Data System (ADS)

    Liu, Shouhua; Li, Yizhen; Yue, Xinyang

    2016-06-01

    Seven freak wave incidents previously documented in the real ocean in combination with model hindcast simulations are used to study the variations associated with freak-wave-related parameters, such as wave steepness, directional spreading, and frequency bandwidth. Unlike the strong correlations between the freak wave parameters and freak waves' occurrence which were obtained in experimental and physical research, the correlations are not clear in the freak waves occurring in the real ocean. Wave directional spreading-steepness joint distribution is introduced and common visual features were found in the joint distribution when freak waves occur among seven "freakish" sea states. The visual features show that freak wave incidents occur when the steepness is large and directional spreading is small. Besides large steepness and small directional spreading, a long-duration, relatively rough sea state is also necessary for the freak wave generation. The joint distribution is more informative than any single statistical wave parameter. The continuous sea states of local large steepness and small directional spreading are supposed to generate freak waves, and two-dimensional distribution visualization is found to be a useful tool for freak waves' forecast. The common visual features of joint distributions supply an important cue for the theoretical and experimental research.

  12. Analysis of the relationship between cancer procoagulant activity and PCNA and Ki-67 expression in cases of common and cellular uterine leiomyomas.

    PubMed

    Szajda, Slawomir D; Jóźwik, Marcin; Sulkowska, Mariola; Chabielska, Ewa; Sulkowski, Stanislaw; Jóźwik, Maciej

    2006-01-01

    Histological subtypes of uterine leiomyomas may substantially differ in their cellular biology, including the intensity of synthesis of cancer markers and expression of cell proliferation markers. The present investigation aimed to determine the activity of cancer procoagulant (CP) in subtypes of leiomyomas, including cellular leiomyomas, and to verify whether these activities correlate with immunoexpression of cell proliferation markers: the proliferating cell nuclear antigen (PCNA) and Ki-67. Preoperative peripheral venous blood and postoperative tissue material were obtained from 24 women operated on in a tertiary referral academic department. The activity of CP in serum was measured with the use of a coagulative method according to Gordon and Benson, and in tissue homogenates with the use of a spectrophotometric method according to Colucci et al. The control serum values were obtained from 20 healthy women without any gynecological disease, and the control solid tissue values from histologically confirmed postoperative normal reproductive tissues obtained from six patients. PCNA and Ki-67 expression were determined immunohistochemically using monoclonal antibodies. Both the tissue and serum activity for CP was considerably higher for common leiomyomas and cellular leiomyomas than for control tissues, but did not differ significantly between the leiomyoma subtypes. Intratumor CP activity significantly correlated with PCNA expression but not with Ki-67 expression. Cellular leiomyomas do not differ substantially in the serum and intratumor CP activity from common leiomyomas. There is a relationship of intratumor CP activity with PCNA expression, a finding which requires further investigation.

  13. Oxidative stress, mitochondrial dysfunction and, inflammation common events in skin of patients with Fibromyalgia.

    PubMed

    Sánchez-Domínguez, Benito; Bullón, Pedro; Román-Malo, Lourdes; Marín-Aguilar, Fabiola; Alcocer-Gómez, Elísabet; Carrión, Angel M; Sánchez-Alcazar, José Antonio; Cordero, Mario D

    2015-03-01

    Fibromyalgia is a chronic pain syndrome with unknown etiology. Recent studies have shown some evidence demonstrating that oxidative stress, mitochondrial dysfunction and inflammation may have a role in the pathophysiology of fibromyalgia. Despite several skin-related symptoms accompanied by small fiber neuropathy have been studied in FM, these mitochondrial changes have not been yet studied in this tissue. Skin biopsies from patients showed a significant mitochondrial dysfunction with reduced mitochondrial chain activities and bioenergetics levels and increased levels of oxidative stress. These data were related to increased levels of inflammation and correlated with pain, the principal symptom of FM. All these parameters have shown a role in peripheral nerve damage which has been observed in FM as a possible responsible to allodynia. Our findings may support the role of oxidative stress, mitochondrial dysfunction and inflammation as interdependent events in the pathophysiology of FM with a special role in the peripheral alterations. Copyright © 2015 Elsevier B.V. and Mitochondria Research Society. Published by Elsevier B.V. All rights reserved.

  14. A systematic review of adverse drug events associated with administration of common asthma medications in children

    PubMed Central

    Johnson, David W.; Sperou, Arissa J.; Crotts, Jennifer; Saude, Erik; Hartling, Lisa; Stang, Antonia

    2017-01-01

    Objective To systematically review the literature and determine frequencies of adverse drug events (ADE) associated with pediatric asthma medications. Methods Following PRISMA guidelines, we systematically searched six bibliographic databases between January 1991 and January 2017. Study eligibility, data extraction and quality assessment were independently completed and verified by two reviewers. We included randomized control trials (RCT), case-control, cohort, or quasi-experimental studies where the primary objective was identifying ADE in children 1 month– 18 years old exposed to commercial asthma medications. The primary outcome was ADE frequency. Findings Our search identified 14,540 citations. 46 studies were included: 24 RCT, 15 cohort, 4 RCT pooled analyses, 1 case-control, 1 open-label trial and 1 quasi-experimental study. Studies examined the following drug classes: inhaled corticosteroids (ICS) (n = 24), short-acting beta-agonists (n = 10), long-acting beta-agonists (LABA) (n = 3), ICS + LABA (n = 3), Leukotriene Receptor Antagonists (n = 3) and others (n = 3). 29 studies occurred in North America, and 29 were industry funded. We report a detailed index of 406 ADE descriptions and frequencies organized by drug class. The majority of data focuses on ICS, with 174 ADE affecting 13 organ systems including adrenal and growth suppression. We observed serious ADE, although they were rare, with frequency ranging between 0.9–6% per drug. There were no confirmed deaths, except for 13 potential deaths in a LABA study including combined adult and pediatric participants. We identified substantial methodological concerns, particularly with identifying ADE and determining severity. No studies utilized available standardized causality, severity or preventability assessments. Conclusion The majority of studies focus on ICS, with adrenal and growth suppression described. Serious ADE are relatively uncommon, with no confirmed pediatric deaths. We identify substantial

  15. Is polyandry a common event among wild populations of the pest Ceratitis capitata?

    PubMed

    Bonizzoni, Mariangela; Gomulski, Ludvik M; Mossinson, Sigalit; Guglielmino, Carmela R; Malacrida, Anna R; Yuval, Boaz; Gasperi, Giuliano

    2006-08-01

    In many insect species, females can mate more than once and store sperm from more than one male. An assessment and understanding of polyandry in the field can be important for pest species with a high colonization potential, such as the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), which is also highly polyphagous and among the most destructive agricultural insects. The use of polymorphic microsatellite markers, combined with different statistical approaches, provides evidence that polyandry occurs in two C. capitata natural populations, one population from the Greek island of Chios and one population from Rehovot, in Israel. The observed different level of polyandry is discussed in relation to the genetic diversity, seasonality, and demography of the two populations. When polyandry is present, paternity analysis also indicates that one male, presumably the last, tends to sire most of the progeny. Polyandry and paternity skew may have important implications for the evolution of the species, in terms of maintenance of the genetic variability. Moreover, these aspects of the mating behavior, i.e., remating frequency and paternity skew, may locally affect the sterile insect technique, the most commonly applied control strategy against C. capitata.

  16. Neutropenia in Patients with Common Variable Immunodeficiency: a Rare Event Associated with Severe Outcome.

    PubMed

    Guffroy, Aurélien; Mourot-Cottet, Rachel; Gérard, Laurence; Gies, Vincent; Lagresle, Chantal; Pouliet, Aurore; Nitschké, Patrick; Hanein, Sylvain; Bienvenu, Boris; Chanet, Valérie; Donadieu, Jean; Gardembas, Martine; Karmochkine, Marina; Nove-Josserand, Raphaele; Martin, Thierry; Poindron, Vincent; Soulas-Sprauel, Pauline; Rieux-Laucat, Fréderic; Fieschi, Claire; Oksenhendler, Eric; André-Schmutz, Isabelle; Korganow, Anne-Sophie

    2017-08-26

    Common variable immunodeficiency (CVID) is characterized by infections and hypogammaglobulinemia. Neutropenia is rare during CVID. The French DEFI study enrolled patients with primary hypogammaglobulinemia. Patients with CVID and neutropenia were retrospectively analyzed. Among 473 patients with CVID, 16 patients displayed neutropenia (lowest count [0-1400]*10(6)/L). Sex ratio (M/F) was 10/6. Five patients died during the follow-up (11 years) with an increased percentage of deaths compared to the whole DEFI group (31.3 vs 3.4%, P < 0.05). Neutropenia was diagnosed for 10 patients before 22 years old. The most frequent symptoms, except infections, were autoimmune cytopenia, i.e., thrombopenia or anemia (11/16). Ten patients were affected with lymphoproliferative diseases. Two patients were in the infection only group and the others belonged to one or several other CVID groups. The median level of IgG was 2.6 g/L [0.35-4.4]. Most patients presented increased numbers of CD21(low) CD38(low) B cell, as already described in CVID autoimmune cytopenia group. Neutropenia was considered autoimmune in 11 cases. NGS for 52 genes of interest was performed on 8 patients. No deleterious mutations were found in LRBA, CTLA4, and PIK3. More than one potentially damaging variant in other genes associated with CVID were present in most patients arguing for a multigene process. Neutropenia is generally associated with another cytopenia and presumably of autoimmune origin during CVID. In the DEFI study, neutropenia is coupled with more severe clinical outcomes. It appears as an "alarm bell" considering patients' presentation and the high rate of deaths. Whole exome sequencing diagnosis should improve management.

  17. Common data elements for secondary use of electronic health record data for clinical trial execution and serious adverse event reporting.

    PubMed

    Bruland, Philipp; McGilchrist, Mark; Zapletal, Eric; Acosta, Dionisio; Proeve, Johann; Askin, Scott; Ganslandt, Thomas; Doods, Justin; Dugas, Martin

    2016-11-22

    Data capture is one of the most expensive phases during the conduct of a clinical trial and the increasing use of electronic health records (EHR) offers significant savings to clinical research. To facilitate these secondary uses of routinely collected patient data, it is beneficial to know what data elements are captured in clinical trials. Therefore our aim here is to determine the most commonly used data elements in clinical trials and their availability in hospital EHR systems. Case report forms for 23 clinical trials in differing disease areas were analyzed. Through an iterative and consensus-based process of medical informatics professionals from academia and trial experts from the European pharmaceutical industry, data elements were compiled for all disease areas and with special focus on the reporting of adverse events. Afterwards, data elements were identified and statistics acquired from hospital sites providing data to the EHR4CR project. The analysis identified 133 unique data elements. Fifty elements were congruent with a published data inventory for patient recruitment and 83 new elements were identified for clinical trial execution, including adverse event reporting. Demographic and laboratory elements lead the list of available elements in hospitals EHR systems. For the reporting of serious adverse events only very few elements could be identified in the patient records. Common data elements in clinical trials have been identified and their availability in hospital systems elucidated. Several elements, often those related to reimbursement, are frequently available whereas more specialized elements are ranked at the bottom of the data inventory list. Hospitals that want to obtain the benefits of reusing data for research from their EHR are now able to prioritize their efforts based on this common data element list.

  18. Influence of common genetic variation on blood lipid levels, cardiovascular risk, and coronary events in two British prospective cohort studies

    PubMed Central

    Shah, Sonia; Casas, Juan P.; Gaunt, Tom R.; Cooper, Jackie; Drenos, Fotios; Zabaneh, Delilah; Swerdlow, Daniel I.; Shah, Tina; Sofat, Reecha; Palmen, Jutta; Kumari, Meena; Kivimaki, Mika; Ebrahim, Shah; Smith, George Davey; Lawlor, Debbie A.; Talmud, Philippa J.; Whittaker, John; Day, Ian N.M.; Hingorani, Aroon D.; Humphries, Steve E.

    2013-01-01

    Aims The aim of this study was to quantify the collective effect of common lipid-associated single nucleotide polymorphisms (SNPs) on blood lipid levels, cardiovascular risk, use of lipid-lowering medication, and risk of coronary heart disease (CHD) events. Methods and results Analysis was performed in two prospective cohorts: Whitehall II (WHII; N = 5059) and the British Women’s Heart and Health Study (BWHHS; N = 3414). For each participant, scores were calculated based on the cumulative effect of multiple genetic variants influencing total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Compared with the bottom quintile, individuals in the top quintile of the LDL-C genetic score distribution had higher LDL-C {mean difference of 0.85 [95% confidence interval, (CI) = 0.76–0.94] and 0.63 [95% CI = 0.50–0.76] mmol/l in WHII and BWHHS, respectively}. They also tended to have greater odds of having ‘high-risk’ status (Framingham 10-year cardiovascular disease risk >20%) [WHII: odds ratio (OR) = 1.36 (0.93–1.98), BWHHS: OR = 1.49 (1.14–1.94)]; receiving lipid-lowering treatment [WHII: OR = 2.38 (1.57–3.59), BWHHS: OR = 2.24 (1.52–3.29)]; and CHD events [WHII: OR = 1.43 (1.02–2.00), BWHHS: OR = 1.31 (0.99–1.72)]. Similar associations were observed for the TC score in both studies. The TG score was associated with high-risk status and medication use in both studies. Neither HDL nor TG scores were associated with the risk of coronary events. The genetic scores did not improve discrimination over the Framingham risk score. Conclusion At the population level, common SNPs associated with LDL-C and TC contribute to blood lipid variation, cardiovascular risk, use of lipid-lowering medications and coronary events. However, their effects are too small to discriminate future lipid-lowering medication requirements or coronary events. PMID:22977227

  19. Commonalities in biological pathways, genetics, and cellular mechanism between Alzheimer Disease and other neurodegenerative diseases: An in silico-updated overview.

    PubMed

    Ahmad, Khurshid; Baig, Mohammad Hassan; Mushtaq, Gohar; Kamal, Mohammad Amjad; Greig, Nigel H; Choi, Inho

    2017-02-03

    Alzheimer's disease (AD) is the most common and well-studied neurodegenerative disease (ND). Biological pathways, pathophysiology and genetics of AD show commonalities with other NDs viz. Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Prion Disease and Dentatorubral-pallidoluysian atrophy (DRPLA). Many of the NDs, sharing the common features and molecular mechanisms suggests that pathology may be directly comparable and be implicated in disease prevention and development of highly effective therapies. In this review, a brief description of pathophysiology, clinical symptoms and available treatment of various NDs have been explored with special emphasis on AD. Commonalities in these fatal NDs provide support for therapeutic advancements and enhance the understanding of disease manifestation. The studies concentrating on the commonalities in biological pathways, cellular mechanisms and genetics may provide the scope to researchers to identify few novel common target/s for disease prevention and development of effective common drugs for multi-neurodegenerative diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Hearing evaluation of patients with head and neck cancer: Comparison of Common Terminology Criteria for Adverse Events, Brock and Chang adverse event criteria in patients receiving cisplatin.

    PubMed

    Colevas, A Dimitrios; Lira, Ruth R; Colevas, Electra A; Lavori, Philip W; Chan, Cato; Shultz, David B; Chang, Kay W

    2015-08-01

    The purpose of this study was to compare Common Terminology Criteria for Adverse Events (CTCAE), Brock and Chang hearing loss grading in patients with head and neck cancer receiving cis-diamminedichloroplatinum (CDDP). Endpoints were baseline distribution of hearing loss, interobserver consistency, and sensitivity to hearing loss after CDDP treatment. Four hundred sixty single ear audiograms in 110 patients with head and neck cancer were graded. Hearing loss at baseline, interobserver agreement rates, and changes in hearing loss after CDDP were evaluated. The Chang and Brock tools' baseline hearing loss distribution was concentrated at grade 0 (57% and 41%, respectively), whereas 47%, per the CTCAE, had grade 3 baseline hearing loss. Interobserver agreement was highest for the Brock scale (≥90%) followed by the Chang (≥89%) and CTCAE (≥75%) scales. Detection of change after CDDP was highest for Chang (48%) followed by Brock (45%) and the CTCAE (32%). The Brock and Chang tools may be superior to the CTCAE in patients with head and neck cancer receiving CDDP using baseline hearing loss distribution, interobserver agreement, and detection of hearing loss grade change as performance indicators. © 2014 Wiley Periodicals, Inc.

  1. Single-Event Upset Characterization of Common First- and Second-Order All-Digital Phase-Locked Loops

    NASA Astrophysics Data System (ADS)

    Chen, Y. P.; Massengill, L. W.; Kauppila, J. S.; Bhuva, B. L.; Holman, W. T.; Loveless, T. D.

    2017-08-01

    The single-event upset (SEU) vulnerability of common first- and second-order all-digital-phase-locked loops (ADPLLs) is investigated through field-programmable gate array-based fault injection experiments. SEUs in the highest order pole of the loop filter and fraction-based phase detectors (PDs) may result in the worst case error response, i.e., limit cycle errors, often requiring system restart. SEUs in integer-based linear PDs may result in loss-of-lock errors, while SEUs in bang-bang PDs only result in temporary-frequency errors. ADPLLs with the same frequency tuning range but fewer bits in the control word exhibit better overall SEU performance.

  2. Cellular dynamical mechanisms for encoding the time and place of events along spatiotemporal trajectories in episodic memory

    PubMed Central

    Hasselmo, Michael E.; Giocomo, Lisa M.; Yoshida, Motoharu

    2010-01-01

    Understanding the mechanisms of episodic memory requires linking behavioural data and lesion effects to data on the dynamics of cellular membrane potentials and population interactions within these brain regions. Linking behavior to specific membrane channels and neurochemicals has implications for therapeutic applications. Lesions of the hippocampus, entorhinal cortex and subcortical nuclei impair episodic memory function in humans and animals, and unit recording data from these regions in behaving animals indicate episodic memory processes. Intracellular recording in these regions demonstrates specific cellular properties including resonance, membrane potential oscillations and bistable persistent spiking that could underlie the encoding and retrieval of episodic trajectories. A model presented here shows how intrinsic dynamical properties of neurons could mediate the encoding of episodic memories as complex spatiotemporal trajectories. The dynamics of neurons allow encoding and retrieval of unique episodic trajectories in multiple continuous dimensions including temporal intervals, personal location, the spatial coordinates and sensory features of perceived objects and generated actions, and associations between these elements. The model also addresses how cellular dynamics could underlie unit firing data suggesting mechanisms for coding continuous dimensions of space, time, sensation and action. PMID:20018213

  3. Using safety data to describe common injury-producing events examples from the U.S. Air force.

    PubMed

    Copley, G Bruce; Burnham, Bruce R; Shim, Matthew J; Kemp, Philip A

    2010-01-01

    The U.S. military leadership has recently increased its efforts to reduce the number of lost-workday injuries for both the active duty and civilian employee components of the total force. The detailed causes and circumstances of those nonfatal injuries-information needed for injury prevention-has largely been unexplored. The purpose of this project was to determine the utility of Air Force safety data for nonfatal injury prevention. In 2004, events associated with injury-producing mishaps reported through the U.S. Air Force (USAF) Ground Safety Automated System from 1993-2002 (n = 32,812 injuries) were reconstructed. Essential data elements necessary to reconstruct event causes and circumstances were identified in both coded data and in free-text mishap narratives. Activities and mechanisms were coded in a format similar to that of the ICD-10. A taxonomy was then developed to identify hazard scenarios associated with injury-producing activities or mechanisms. Coded data provided only four data elements (activity, injury event/exposure, nature of injury/body part, and outcome) that were sufficiently descriptive for prevention purposes. Therefore, narrative information was coded and analyzed to obtain additional information. The assembled data enabled identification and description of hazard scenarios associated with the most common injury-producing activities and mechanisms. Safety reports from the USAF provide detailed mishap descriptions for lost-workday injuries that could support in-depth analysis and more effective preventive efforts. However, some of the most valuable information is found in the pre-text narratives that require coding and classification, such as was conducted for this report in order to be optimally useful for injury epidemiology and prevention. Published by Elsevier Inc.

  4. Cellular Composition and Organization of the Subventricular Zone and Rostral Migratory Stream in the Adult and Neonatal Common Marmoset Brain

    PubMed Central

    Sawamoto, Kazunobu; Hirota, Yuki; Alfaro-Cervello, Clara; Soriano-Navarro, Mario; He, Xiaoping; Hayakawa-Yano, Yoshika; Yamada, Masayuki; Hikishima, Keigo; Tabata, Hidenori; Iwanami, Akio; Nakajima, Kazunori; Toyama, Yoshiaki; Itoh, Toshio; Alvarez-Buylla, Arturo; Garcia-Verdugo, Jose Manuel; Okano, Hideyuki

    2014-01-01

    The adult subventricular zone (SVZ) of the lateral ventricle contains neural stem cells. In rodents, these cells generate neuroblasts that migrate as chains toward the olfactory bulb along the rostral migratory stream (RMS). The neural-stem-cell niche at the ventricular wall is conserved in various animal species, including primates. However, it is unclear how the SVZ and RMS organization in nonhuman primates relates to that of rodents and humans. Here we studied the SVZ and RMS of the adult and neonatal common marmoset (Callithrix jacchus), a New World primate used widely in neuroscience, by electron microscopy, and immunohistochemical detection of cell-type-specific markers. The marmoset SVZ contained cells similar to type B, C, and A cells of the rodent SVZ in their marker expression and morphology. The adult marmoset SVZ had a three-layer organization, as in the human brain, with ependymal, hypocellular, and astro-cyte-ribbon layers. However, the hypocellular layer was very thin or absent in the adult-anterior and neonatal SVZ. Anti-PSA-NCAM staining of the anterior SVZ in whole-mount ventricular wall preparations of adult marmosets revealed an extensive network of elongated cell aggregates similar to the neuroblast chains in rodents. Time-lapse recordings of marmoset SVZ explants cultured in Matrigel showed the neuroblasts migrating in chains, like rodent type A cells. These results suggest that some features of neurogenesis and neuronal migration in the SVZ are common to marmosets, humans, and rodents. This basic description of the adult and neonatal marmoset SVZ will be useful for future studies on adult neurogenesis in primates. PMID:21246550

  5. Lens epithelial cell apoptosis appears to be a common cellular basis for non-congenital cataract development in humans and animals

    PubMed Central

    1995-01-01

    Cataract is a major ocular disease that causes blindness in many developing countries of the world. It is well established that various factors such as oxidative stress, UV, and other toxic agents can induce both in vivo and in vitro cataract formation. However, a common cellular basis for this induction has not been previously recognized. The present study of lens epithelial cell viability suggests such a general mechanism. When lens epithelial cells from a group of 20 cataract patients 12 to 94 years old were analyzed by terminal deoxynucleotidyl transferase (TdT) labeling and DNA fragmentation assays, it was found that all of these patients had apoptotic epithelial cells ranging from 4.4 to 41.8%. By contrast, in eight normal human lenses of comparable age, very few apoptotic epithelial cells were observed. We suggest that cataract patients may have deficient defense systems against factors such as oxidative stress and UV at the onset of the disease. Such stress can trigger lens epithelial cell apoptosis that then may initiate cataract development. To test this hypothesis, it is also demonstrated here that hydrogen peroxide at concentrations previously found in some cataract patients induces both lens epithelial cell apoptosis and cortical opacity. Moreover, the temporal and spatial distribution of induced apoptotic lens epithelial cells precedes development of lens opacification. These results suggest that lens epithelial cell apoptosis may be a common cellular basis for initiation of noncongenital cataract formation. PMID:7790371

  6. Assessing the predictive value of the rodent neurofunctional assessment for commonly reported adverse events in phase I clinical trials.

    PubMed

    Mead, Andy N; Amouzadeh, Hamid R; Chapman, Kathryn; Ewart, Lorna; Giarola, Alessandra; Jackson, Samuel J; Jarvis, Philip; Jordaan, Pierre; Redfern, Will; Traebert, Martin; Valentin, Jean-Pierre; Vargas, Hugo M

    2016-10-01

    Central Nervous System (CNS)-related safety concerns are major contributors to delays and failure during the development of new candidate drugs (CDs). CNS-related safety data on 141 small molecule CDs from five pharmaceutical companies were analyzed to identify the concordance between rodent multi-parameter neurofunctional assessments (Functional Observational Battery: FOB, or Irwin test: IT) and the five most common adverse events (AEs) in Phase I clinical trials, namely headache, nausea, dizziness, fatigue/somnolence and pain. In the context of this analysis, the FOB/IT did not predict the occurrence of these particular AEs in man. For AEs such as headache, nausea, dizziness and pain the results are perhaps unsurprising, as the FOB/IT were not originally designed to predict these AEs. More unexpected was that the FOB/IT are not adequate for predicting 'somnolence/fatigue' nonclinically. In drug development, these five most prevalent AEs are rarely responsible for delaying or stopping further progression of CDs. More serious AEs that might stop CD development occurred at too low an incidence rate in our clinical dataset to enable translational analysis.

  7. Opossum carboxylesterases: sequences, phylogeny and evidence for CES gene duplication events predating the marsupial-eutherian common ancestor

    PubMed Central

    2008-01-01

    residues previously reported for human CES1 involved in catalysis, ligand binding, tertiary structure and organelle localization. Phylogenetic studies indicated the gene duplication events which generated ancestral mammalian CES genes predated the common ancestor for marsupial and eutherian mammals, and appear to coincide with the early diversification of tetrapods. PMID:18289373

  8. Opossum carboxylesterases: sequences, phylogeny and evidence for CES gene duplication events predating the marsupial-eutherian common ancestor.

    PubMed

    Holmes, Roger S; Chan, Jeannie; Cox, Laura A; Murphy, William J; VandeBerg, John L

    2008-02-20

    involved in catalysis, ligand binding, tertiary structure and organelle localization. Phylogenetic studies indicated the gene duplication events which generated ancestral mammalian CES genes predated the common ancestor for marsupial and eutherian mammals, and appear to coincide with the early diversification of tetrapods.

  9. Validation of the German patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE™).

    PubMed

    Hagelstein, V; Ortland, I; Wilmer, A; Mitchell, S A; Jaehde, U

    2016-12-01

    Integrating the patient's perspective has become an increasingly important component of adverse event reporting. The National Cancer Institute has developed a Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™). This instrument has been translated into German and linguistically validated; however, its quantitative measurement properties have not been evaluated. A German language survey that included 31 PRO-CTCAE items, as well as the EORTC QLQ-C30 and the Oral Mucositis Daily Questionnaire (OMDQ), was distributed at 10 cancer treatment settings in Germany and Austria. Item quality was assessed by analysis of acceptability and comprehensibility. Reliability was evaluated by using Cronbach's' alpha and validity by principal components analysis (PCA), multitrait-multimethod matrix (MTMM) and known groups validity techniques. Of 660 surveys distributed to the study centres, 271 were returned (return rate 41%), and data from 262 were available for analysis. Participants' median age was 59.7 years, and 69.5% of the patients were female. Analysis of item quality supported the comprehensibility of the 31 PRO-CTCAE items. Reliability was very good; Cronbach's' alpha correlation coefficients were >0.9 for almost all item clusters. Construct validity of the PRO-CTCAE core item set was shown by identifying 10 conceptually meaningful item clusters via PCA. Moreover, construct validity was confirmed by the MTMM: monotrait-heteromethod comparison showed 100% high correlation, whereas heterotrait-monomethod comparison indicated 0% high correlation. Known groups validity was supported; PRO-CTCAE scores were significantly lower for those with impaired versus preserved health-related quality of life. A set of 31 items drawn from the German PRO-CTCAE item library demonstrated favourable measurement properties. These findings add to the body of evidence that PRO-CTCAE provides a rigorous method to capture patient self-reports of

  10. 30 some years of heme oxygenase: from a "molecular wrecking ball" to a "mesmerizing" trigger of cellular events.

    PubMed

    Maines, Mahin D; Gibbs, Peter E M

    2005-12-09

    In the beginning, the microsomal HO system was presumed to be made of one isozymes, now known as HO-1, which was cytP450-dependent; and, was thought to be of physiological significance solely in the context of catalysis of hemoglobin heme to bile pigments and CO. A succession of discoveries including characterization of the system as an independent mono-oxygenase, identification of a second form, called HO-2, free radical quenching activity of bile pigments, analogous function of CO in cell signaling to NO, and characterization of the system as HSP32 cognates has led to such an impressive expansion in the number of reports dealing with the HO system that surpass anyone's expectation. This review is a compilation of certain older findings and recent events that together ensure placement of the HO system in the mainstream research for decades to come.

  11. Making vaccines more acceptable--methods to prevent and minimize pain and other common adverse events associated with vaccines.

    PubMed

    Jacobson, R M; Swan, A; Adegbenro, A; Ludington, S L; Wollan, P C; Poland, G A

    2001-03-21

    techniques have not identified ready solutions, and although jet injection appears to provoke less anxiety and cause less immediate pain, studies also indicate a somewhat greater incidence of delayed local reactogenicity including soreness and edema. Other measures to prevent or rapidly treat other common adverse events have been shown effective and should be considered as well.

  12. Clonal analysis in recurrent astrocytic, oligoastrocytic and oligodendroglial tumors implicates IDH1- mutation as common tumor initiating event.

    PubMed

    Lass, Ulrike; Nümann, Astrid; von Eckardstein, Kajetan; Kiwit, Jürgen; Stockhammer, Florian; Horaczek, Jörn A; Veelken, Julian; Herold-Mende, Christel; Jeuken, Judith; von Deimling, Andreas; Mueller, Wolf

    2012-01-01

    To investigate the dynamics of inter- and intratumoral molecular alterations during tumor progression in recurrent gliomas. To address intertumoral heterogeneity we investigated non-microdissected tumor tissue of 106 gliomas representing 51 recurrent tumors. To address intratumoral heterogeneity a set of 16 gliomas representing 7 tumor pairs with at least one recurrence, and 4 single mixed gliomas were investigated by microdissection of distinct oligodendroglial and astrocytic tumor components. All tumors and tumor components were analyzed for allelic loss of 1p/19q (LOH 1p/19q), for TP53- mutations and for R132 mutations in the IDH1 gene. The investigation of non-microdissected tumor tissue revealed clonality in 75% (38/51). Aberrant molecular alterations upon recurrence were detected in 25% (13/51). 64% (9/14) of these were novel and associated with tumor progression. Loss of previously detected alterations was observed in 36% (5/14). One tumor pair (1/14; 7%) was significant for both. Intratumoral clonality was detected in 57% (4/7) of the microdissected tumor pairs and in 75% (3/4) of single microdissected tumors. 43% (3/7) of tumor pairs and one single tumor (25%) revealed intratumoral heterogeneity. While intratumoral heterogeneity affected both the TP53- mutational status and the LOH1p/19q status, all tumors with intratumoral heterogeneity shared the R132 IDH1- mutation as a common feature in both their microdissected components. The majority of recurrent gliomas are of monoclonal origin. However, the detection of divertive tumor cell clones in morphological distinct tumor components sharing IDH1- mutations as early event may provide insight into the tumorigenesis of true mixed gliomas.

  13. The effects of okra (Abelmoschus esculentus Linn.) on the cellular events associated with Alzheimer's disease in a stably expressed HFE neuroblastoma SH-SY5Y cell line.

    PubMed

    Mairuae, Nootchanat; Connor, James R; Lee, Sang Y; Cheepsunthorn, Poonlarp; Tongjaroenbuangam, Walaiporn

    2015-08-31

    It has been reported that persons carrying the H63D variant in their hemochromatosis (HFE) gene are at increased risk of Alzheimer's disease (AD). We investigated the possibility that okra (Abelmoschus esculentus) and quercetin could mitigate this risk factor by examining its effect on AD-associated cellular events in HFE stably expressing SH-SY5Y cells. Treatment of H63D HFE cells either with okra or quercetin significantly decreased reactive oxygen species (ROS), hydrogen peroxide (H2O2), and protein oxidation compared to untreated cells. The levels of tau phosphorylation at serine-199, serine-202, and serine-396 sites were also significantly decreased when cells were treated with okra. Exposure of the H63D and wild type (WT) cells to iron increased tau phosphorylation, but this response was decreased significantly when cells were treated with okra. The mechanism responsible for these changes appears to be related to decreased glycogen synthase kinase (GSK)-3β activity, an upstream signaling kinase of tau phosphorylation. We also established that okra treatment dramatically decreases intracellular iron levels in H63D cells compared to untreated cells. Our results provide important in vitro data on the effects of okra on various AD-associated cellular processes in H63D variant HFE cells. These results suggest okra may be beneficial in people expressing the H63D variant to reduce the risk of AD and other neurodegenerative diseases related to oxidative stress. Further in vivo studies would help confirm this.

  14. Cellular basis of Alzheimer's disease.

    PubMed

    Bali, Jitin; Halima, Saoussen Ben; Felmy, Boas; Goodger, Zoe; Zurbriggen, Sebastian; Rajendran, Lawrence

    2010-12-01

    Alzheimer's disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD.

  15. Development of an event-specific hydrolysis probe quantitative real-time polymerase chain reaction assay for Embrapa 5.1 genetically modified common bean (Phaseolus vulgaris).

    PubMed

    Treml, Diana; Venturelli, Gustavo L; Brod, Fábio C A; Faria, Josias C; Arisi, Ana C M

    2014-12-10

    A genetically modified (GM) common bean event, namely Embrapa 5.1, resistant to the bean golden mosaic virus (BGMV), was approved for commercialization in Brazil. Brazilian regulation for genetically modified organism (GMO) labeling requires that any food containing more than 1% GMO be labeled. The event-specific polymerase chain reaction (PCR) method has been the primary trend for GMO identification and quantitation because of its high specificity based on the flanking sequence. This work reports the development of an event-specific assay, named FGM, for Embrapa 5.1 detection and quantitation by use of SYBR Green or hydrolysis probe. The FGM assay specificity was tested for Embrapa 2.3 event (a noncommercial GM common bean also resistant to BGMV), 46 non-GM common bean varieties, and other crop species including maize, GM maize, soybean, and GM soybean. The FGM assay showed high specificity to detect the Embrapa 5.1 event. Standard curves for the FGM assay presented a mean efficiency of 95% and a limit of detection (LOD) of 100 genome copies in the presence of background DNA. The primers and probe developed are suitable for the detection and quantitation of Embrapa 5.1.

  16. Prognostic value of T1-mapping in TAVR patients: extra-cellular volume as a possible predictor for peri- and post-TAVR adverse events.

    PubMed

    Nadjiri, Jonathan; Nieberler, Hanna; Hendrich, Eva; Will, Albrecht; Pellegrini, Costanza; Husser, Oliver; Hengstenberg, Christian; Greiser, Andreas; Martinoff, Stefan; Hadamitzky, Martin

    2016-11-01

    The benefit of a transcatheter aortic valve replacement (TAVR) can differ in patients, and therapy bears severe risks. High-degree aortic stenosis can lead to cardiac damage such as diffuse myocardial fibrosis, evaluable by extra-cellular volume (ECV) in CMR. Therefore, fibrosis might be a possible risk factor for unfavorable outcome after TAVR. We sought to assess the prognostic value of T1-mapping and ECV to predict adverse events during and after TAVR. The study population consisted of patients undergoing clinically indicated TAVR by performing additional CMR with native and contrast-enhanced T1-mapping sequences for additional evaluation of ECV. Study endpoints were congestive heart failure (CHF) and TAVR-associated conduction abnormalities defined as new onset of left bundle branch block (LBBB), AV-Block or implantation of a pacemaker. 94 patients were examined and followed. Median follow up time was 187 days (IQR 79-357 days). ECV was increased (>30 %) in 38 patients (40 %). There was no significant correlation between ECV and death, Hazard ratio (HR) 0.847 (95 % CI 0.335; 2.14), p = 0.72. ECV in patients with subsequent CHF was higher than in those without an event (33.5 ± 4.6 and 29.1 ± 4.1 %, respectively), but the difference just did not reach the level of significance HR 2.16 (95 % CI 0.969; 4.84), p = 0.06. Patients with post-TAVR conduction abnormality (LBBB, AV-block or pacemaker implantation) had statistically relevant lower ECV values compared to those without an event. Patients with an event had a mean ECV of 28.1 ± 3.16 %; patients without an event had a mean ECV of 29.8 ± 4.53, HR 0.56 (95 % CI 0.32; 0.96), p = 0.036. In this study, elevated myocardial ECV is a predictor of CHF by trend; CMR may be helpful in identifying patients with a high risk for post-TAVR cardiac decompensation benefitting from an intensified post-interventional surveillance. Patients with post-TAVR conductions abnormalities

  17. Common and Segregated Neural Substrates for Automatic Conceptual and Affective Priming as Revealed by Event-Related Functional Magnetic Resonance Imaging

    ERIC Educational Resources Information Center

    Liu, Hongyan; Hu, Zhiguo; Peng, Danling; Yang, Yanhui; Li, Kuncheng

    2010-01-01

    The brain activity associated with automatic semantic priming has been extensively studied. Thus far there has been no prior study that directly contrasts the neural mechanisms of semantic and affective priming. The present study employed event-related fMRI to examine the common and distinct neural bases underlying conceptual and affective priming…

  18. Common and Segregated Neural Substrates for Automatic Conceptual and Affective Priming as Revealed by Event-Related Functional Magnetic Resonance Imaging

    ERIC Educational Resources Information Center

    Liu, Hongyan; Hu, Zhiguo; Peng, Danling; Yang, Yanhui; Li, Kuncheng

    2010-01-01

    The brain activity associated with automatic semantic priming has been extensively studied. Thus far there has been no prior study that directly contrasts the neural mechanisms of semantic and affective priming. The present study employed event-related fMRI to examine the common and distinct neural bases underlying conceptual and affective priming…

  19. Common Neural Systems Associated with the Recognition of Famous Faces and Names: An Event-Related fMRI Study

    ERIC Educational Resources Information Center

    Nielson, Kristy A.; Seidenberg, Michael; Woodard, John L.; Durgerian, Sally; Zhang, Qi; Gross, William L.; Gander, Amelia; Guidotti, Leslie M.; Antuono, Piero; Rao, Stephen M.

    2010-01-01

    Person recognition can be accomplished through several modalities (face, name, voice). Lesion, neurophysiology and neuroimaging studies have been conducted in an attempt to determine the similarities and differences in the neural networks associated with person identity via different modality inputs. The current study used event-related…

  20. Common Neural Systems Associated with the Recognition of Famous Faces and Names: An Event-Related fMRI Study

    ERIC Educational Resources Information Center

    Nielson, Kristy A.; Seidenberg, Michael; Woodard, John L.; Durgerian, Sally; Zhang, Qi; Gross, William L.; Gander, Amelia; Guidotti, Leslie M.; Antuono, Piero; Rao, Stephen M.

    2010-01-01

    Person recognition can be accomplished through several modalities (face, name, voice). Lesion, neurophysiology and neuroimaging studies have been conducted in an attempt to determine the similarities and differences in the neural networks associated with person identity via different modality inputs. The current study used event-related…

  1. Lipoxin A sub 4 antagonizes cellular and in vivo actions of leukotriene D sub 4 in rat glomerular mesangial cells: Evidence for competition at a common receptor

    SciTech Connect

    Badr, K.F.; DeBoer, D.K.; Schwartzberg, M.; Serhan, C.N. )

    1989-05-01

    Lipoxin A{sub 4} (LXA{sub 4}) was competitive with ({sup 3}H)leukotriene D{sub 4} (LTD{sub 4}) for specific binding to cultured rat glomerular mesangial cells. Half-maximal inhibition was obtained with 100 nM LXA{sub 4}, compared with 10 nM for unlabeled LTD{sub 4}. At 10 and 50 nM LXA{sub 4} induced low, but significant, increases in mesangial-cell inositol trisphosphate generation: 48% and 44% increases as compared to vehicle controls, respectively (compared with 146% and 106% increments obtained for equimolar LTD{sub 4}), which were abolished in the presence of 100-fold concentrations of the LTD{sub 4} receptor antagonist, SKF 104353. To test the in vivo relevance of these results, the authors established a dose-response curve for the reducing effects of intrarenal arterial LTD{sub 4} on glomerular filtration rate and renal plasma flow in anesthetized rats without or with LXA{sub 4}. Mean percent decreases in glomerular filtration rate/renal plasma flow during LTD{sub 4} administration were measured. The results show LXA{sub 4} competes for ({sup 3}H)LTD{sub 4} binding to mesangial cells, its presence prevents LTD{sub 4}-induced inositol trisphosphate generation, and its own stimulation of mesangial-cell inositol trisphosphate is blocked by an LTD{sub 4} receptor antagonist. These results suggest that LTD{sub 4} and LXA{sub 4} interact at a common site on rat mesangial cells at which LXA{sub 4} provokes partial agonist responses and competitively antagonizes both the cellular and physiological actions of LTD{sub 4}. Moreover, these results provide evidence for a potential counterregulatory interaction between leukotrienes and lipoxins that may be relevant during glomerular inflammation.

  2. Ras/cAMP-dependent Protein Kinase (PKA) Regulates Multiple Aspects of Cellular Events by Phosphorylating the Whi3 Cell Cycle Regulator in Budding Yeast*

    PubMed Central

    Mizunuma, Masaki; Tsubakiyama, Ryohei; Ogawa, Takafumi; Shitamukai, Atsunori; Kobayashi, Yoshifumi; Inai, Tomomi; Kume, Kazunori; Hirata, Dai

    2013-01-01

    The Start/G1 phase in the cell cycle is an important period during which cells determine their developmental fate, onset of mitotic progression, or the switch to developmental stages in response to both external and internal signals. In the budding yeast Saccharomyces cerevisiae, Whi3, a negative regulator of the G1 cyclins, has been identified as a positive regulator of cell size control and is involved in the regulation of Start. However, the regulatory pathway of Whi3 governing the response to multiple signals remains largely unknown. Here, we show that Whi3 is phosphorylated by the Ras/cAMP-dependent protein kinase (PKA) and that phosphorylation of Ser-568 in Whi3 by PKA plays an inhibitory role in Whi3 function. Phosphorylation of Whi3 by PKA led to its decreased interaction with CLN3 G1 cyclin mRNA and was required for the promotion of G1/S progression. Furthermore, we demonstrate that the phosphomimetic S568D mutation of Whi3 prevented the developmental fate switch to sporulation or invasive growth. Thus, PKA modulated the function of Whi3 by phosphorylation, thus implicating PKA-mediated modulation of Whi3 in multiple cellular events. PMID:23471970

  3. Common and Rare Taxa of Planktonic Ciliates: Influence of Flood Events and Biogeographic Patterns in Neotropical Floodplains.

    PubMed

    Segovia, Bianca Trevizan; Dias, Juliana Déo; Cabral, Adalgisa Fernanda; Meira, Bianca Ramos; Lansac-Tôha, Fernando Miranda; Lansac-Tôha, Fabio Amodêo; Bini, Luis Mauricio; Velho, Luiz Felipe Machado

    2017-04-06

    After much discussion about the cosmopolitan nature of microbes, the great issue nowadays is to identify at which spatial extent microorganisms may display biogeographic patterns and if temporal variation is important in altering those patterns. Here, planktonic ciliates were sampled from shallow lakes of four Neotropical floodplains, distributed over a spatial extent of ca. 3000 km, during high and low water periods, along with several abiotic and biotic variables potentially affecting the ciliate community. We found that common ciliate species were more associated with environmental gradients and rare species were more related to spatial variables; however, this pattern seemed to change depending on the temporal and spatial scales considered. Environmental gradients were more important in the high waters for both common and rare species. In low waters, common species continued to be mainly driven by environmental conditions, but rare species were more associated with the spatial component, suggesting dispersal limitation likely due to differences in dispersal ability and ecological tolerance of species. We also found that common and rare species were related to different environmental variables, suggesting different ecological niches. At the largest spatial extents, rare species showed clear biogeographic patterns.

  4. The common apolipoprotein A-1 polymorphism −75A>G is associated with ethnic differences in recurrent coronary events after recovery from an acute myocardial infarction

    PubMed Central

    Block, Robert; Corsetti, James; Goldenberg, Ilan; Vorobiof, Gabriel; McNitt, Scott; Ryan, Daniel; Zareba, Wojciech; Moss, Arthur J.

    2009-01-01

    Since data regarding the relationship between a common polymorphism (SNP) of the apoA1 gene with apoA1 levels and risk of coronary artery disease are inconsistent, we hypothesized that its association with recurrent coronary events differs for White and Black individuals with diagnosed coronary heart disease. The apoA1 −75G>A SNP was genotyped in a cohort of 834 Black (n=129) and White (n=705) post-myocardial infarction patients. Recurrent coronary events (coronary-related death, non-fatal myocardial infarction, or unstable angina) were documented during an average follow-up of 28 months. Thirty percent of White and 21% of Black patients carried the SNP. Cox proportional-hazards regression analysis, adjusting for clinical and laboratory covariates, demonstrated that the SNP was not associated with recurrent events in the total cohort (HR=1.37, 95% CI 0.95–1.97; p= 0.09) but was the only variable associated with an increased risk of recurrent cardiac events in Blacks (HR=2.40, 95% CI 1.07–5.40; p= 0.034). Conversely in Whites, the SNP was not associated with recurrent events (HR=1.12, 95% CI 0.75–1.67; p= 0.59) whereas apoB (HR=1.78, 95% CI 1.20 −2.65; p= 0.0042) and calcium channel blocker use (HR=2.53, 95% CI 1.72–3.72; p<0.001) were associated; p= 0.0024 for interaction between ethnicity and the SNP. A common apoA1 SNP is associated with a significantly increased risk of recurrent cardiac events among Black, but not White, postmyocardial infarction patients. Relationships with lipoproteins may help explain this finding. PMID:21152377

  5. HIV-specific CD4-induced Antibodies Mediate Broad and Potent Antibody-dependent Cellular Cytotoxicity Activity and are Commonly Detected in Plasma from HIV-infected Humans

    PubMed Central

    Williams, Katherine L.; Cortez, Valerie; Dingens, Adam S.; Gach, Johannes S.; Rainwater, Stephanie; Weis, Julie F.; Chen, Xuemin; Spearman, Paul; Forthal, Donald N.; Overbaugh, Julie

    2015-01-01

    HIV-specific antibodies (Abs) can reduce viral burden by blocking new rounds of infection or by destroying infected cells via activation of effector cells through Fc–FcR interaction. This latter process, referred to as antibody-dependent cellular cytotoxicity (ADCC), has been associated with viral control and improved clinical outcome following both HIV and SIV infections. Here we describe an HIV viral-like particle (VLP)-based sorting strategy that led to identification of HIV-specific memory B cells encoding Abs that mediate ADCC from a subtype A-infected Kenyan woman at 914 days post-infection. Using this strategy, 12 HIV-envelope-specific monoclonal antibodies (mAbs) were isolated and three mediated potent ADCC activity when compared to well-characterized ADCC mAbs. The ADCC-mediating Abs also mediated antibody-dependent cell-mediated virus inhibition (ADCVI), which provides a net measure of Fc receptor-triggered effects against replicating virus. Two of the three ADCC-mediating Abs targeted a CD4-induced (CD4i) epitope also bound by the mAb C11; the third antibody targeted the N-terminus of V3. Both CD4i Abs identified here demonstrated strong cross-clade breadth with activity against 10 of 11 envelopes tested, including those from clades A, B, C, A/D and C/D, whereas the V3-specific antibody showed more limited breadth. Variants of these CD4i, C11-like mAbs engineered to interrupt binding to FcγRs inhibited a measurable percentage of the donor's ADCC activity starting as early as 189 days post-infection. C11-like antibodies also accounted for between 18–78% of ADCC activity in 9 chronically infected individuals from the same cohort study. Further, the two CD4i Abs originated from unique B cells, suggesting that antibodies targeting this epitope can be commonly produced. Taken together, these data provide strong evidence that CD4i, C11-like antibodies develop within the first 6 months of infection and they can arise from unique B-cell lineages in the

  6. Examination of four HLA class I pseudogenes: Common events in the evolution of HLA genes and pseudogenes

    SciTech Connect

    Geraghty, D.E.; Pei, J. ); Koller, B.H. ); Hansen, J.A. )

    1992-09-15

    The HLA class I gene family in lymphoblastoid cell line 721 has been studied in detail and a number of sequences in addition to the classical genes have been identified. The cloning, characterization, and nucleotide sequences of four sequences, all full length HLA class I pseudogenes, are described in this report. These pseudogenes, contained within 5.4-, 5.9-, 7.0-, and 9.2-kb HindIII fragments, each have the class I exon-intron structure as well as class I homology in their 5[prime] and 3[prime] flanking regions. However, all four sequences have one or more substitutions that perturb the coding region, leaving little doubt that they are in fact pseudogenes. Comparisons among these sequences and the HLA class I genes revealed that their homology with the class I genes is patchwork. Thus, although some regions have diverged, other contiguous intron-exon sequences are highly conserved. Comparisons in the 5[prime] regions indicate that the pseudogene promoters more closely resemble the classical HLA promoters than the nonclassical promoters as none of the unique structural features found in the HLA-E, -F, or -G regulatory regions are present in any of the pseudogene promoters. Further comparisons revealed that at least two putative gene conversion events, similar to those hypothesized to have occurred in the evolution of some HLA genes, may have occurred in the evolution of some of the pseudogenes. These and other hypothetical events in the evolution of the class I gene family are discussed. 47 refs., 6 figs., 2 tabs.

  7. A common mineralocorticoid receptor polymorphism (I180V) interacts with life events in relation to perfectionism in eating disorders: a pilot study.

    PubMed

    Slof-Op't Landt, Margarita C T; DeRijk, Roel H; van Son, Gabrielle E; Suchiman, H Eka D; Meulenbelt, Ingrid; Slagboom, P Eline; Van Furth, Eric F

    2014-11-01

    The stress response is regulated by the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). When the balance between GR and MR signalling is disturbed, one's capacity to cope with a stressful event is diminished. In this pilot study, we tested the hypothesis that an interaction between common variants in the MR (rs5522) or GR gene (rs41423247) and stressful life events influences perfectionism levels in a group of patients with an eating disorder (ED; n = 113). Patients carrying the minor G allele of rs5522 had a higher perfectionism score if more stressful life events were experienced [β = 0.95, t(109) = 3.75, p < 0.01]. This effect was not found for patients carrying the AA genotype. These results suggest that rs5522 G allele carriers might be vulnerable to stressful life events. When patients with an ED are carriers and experience multiple life events, this might fuel their insecurity, which in turn may engender higher levels of perfectionism. Further studies are necessary to replicate and expand our findings.

  8. Human ribosomal protein eS1 is engaged in cellular events related to processing and functioning of U11 snRNA

    PubMed Central

    Gopanenko, Alexander V.; Malygin, Alexey A.; Tupikin, Alexey E.; Laktionov, Pavel P.; Kabilov, Marsel R.

    2017-01-01

    Abstract Ribosomal proteins are involved in many cellular processes through interactions with various RNAs. Here, applying the photoactivatable-ribonucleoside-enhanced cross-linking and immunoprecipitation approach to HEK293 cells overproducing ribosomal protein (rp) eS1, we determined the products of RNU5A-1 and RNU11 genes encoding U5 and U11 snRNAs as the RNA partners of ribosome-unbound rp eS1. U11 pre-snRNA-associated rp eS1 was revealed in the cytoplasm and nucleus where rp eS1-bound U11/U12 di-snRNP was also found. Utilizing recombinant rp eS1 and 4-thiouridine-containing U11 snRNA transcript, we identified an N-terminal peptide contacting the U-rich sequence in the Sm site-containing RNA region. We also showed that the rp eS1 binding site on U11 snRNA is located in the cleft between stem-loops I and III and that its structure mimics the respective site on the 18S rRNA. It was found that cell depletion of rp eS1 leads to a decrease in the splicing efficiency of minor introns and to an increase in the level of U11 pre-snRNA with the unprocessed 3′ terminus. Our findings demonstrate the engagement of human rp eS1 in events related to the U11 snRNA processing and to minor-class splicing. Contacts of rp eS1 with U5 snRNA in the minor pre-catalytic spliceosome are discussed. PMID:28666385

  9. Common neural systems associated with the recognition of famous faces and names: an event-related fMRI study.

    PubMed

    Nielson, Kristy A; Seidenberg, Michael; Woodard, John L; Durgerian, Sally; Zhang, Qi; Gross, William L; Gander, Amelia; Guidotti, Leslie M; Antuono, Piero; Rao, Stephen M

    2010-04-01

    Person recognition can be accomplished through several modalities (face, name, voice). Lesion, neurophysiology and neuroimaging studies have been conducted in an attempt to determine the similarities and differences in the neural networks associated with person identity via different modality inputs. The current study used event-related functional-MRI in 17 healthy participants to directly compare activation in response to randomly presented famous and non-famous names and faces (25 stimuli in each of the four categories). Findings indicated distinct areas of activation that differed for faces and names in regions typically associated with pre-semantic perceptual processes. In contrast, overlapping brain regions were activated in areas associated with the retrieval of biographical knowledge and associated social affective features. Specifically, activation for famous faces was primarily right lateralized and famous names were left-lateralized. However, for both stimuli, similar areas of bilateral activity were observed in the early phases of perceptual processing. Activation for fame, irrespective of stimulus modality, activated an extensive left hemisphere network, with bilateral activity observed in the hippocampi, posterior cingulate, and middle temporal gyri. Findings are discussed within the framework of recent proposals concerning the neural network of person identification.

  10. Common time-frequency analysis of local field potential and pyramidal cell activity in seizure-like events of the rat hippocampus

    NASA Astrophysics Data System (ADS)

    Cotic, M.; Chiu, A. W. L.; Jahromi, S. S.; Carlen, P. L.; Bardakjian, B. L.

    2011-08-01

    To study cell-field dynamics, physiologists simultaneously record local field potentials and the activity of individual cells from animals performing cognitive tasks, during various brain states or under pathological conditions. However, apart from spike shape and spike timing analyses, few studies have focused on elucidating the common time-frequency structure of local field activity relative to surrounding cells across different periods of phenomena. We have used two algorithms, multi-window time frequency analysis and wavelet phase coherence (WPC), to study common intracellular-extracellular (I-E) spectral features in spontaneous seizure-like events (SLEs) from rat hippocampal slices in a low magnesium epilepsy model. Both algorithms were applied to 'pairs' of simultaneously observed I-E signals from slices in the CA1 hippocampal region. Analyses were performed over a frequency range of 1-100 Hz. I-E spectral commonality varied in frequency and time. Higher commonality was observed from 1 to 15 Hz, and lower commonality was observed in the 15-100 Hz frequency range. WPC was lower in the non-SLE region compared to SLE activity; however, there was no statistical difference in the 30-45 Hz band between SLE and non-SLE modes. This work provides evidence of strong commonality in various frequency bands of I-E SLEs in the rat hippocampus, not only during SLEs but also immediately before and after.

  11. Proton-dependent coniferin transport, a common major transport event in differentiating xylem tissue of woody plants.

    PubMed

    Tsuyama, Taku; Kawai, Ryo; Shitan, Nobukazu; Matoh, Toru; Sugiyama, Junji; Yoshinaga, Arata; Takabe, Keiji; Fujita, Minoru; Yazaki, Kazufumi

    2013-06-01

    Lignin biosynthesis is an essential physiological activity of vascular plants if they are to survive under various environmental stresses on land. The biosynthesis of lignin proceeds in the cell wall by polymerization of precursors; the initial step of lignin polymerization is the transportation of lignin monomers from the cytosol to the cell wall, which is critical for lignin formation. There has been much debate on the transported form of the lignin precursor, either as free monolignols or their glucosides. In this study, we performed biochemical analyses to characterize the membrane transport mechanism of lignin precursors using angiosperms, hybrid poplar (Populus sieboldii × Populus grandidentata) and poplar (Populus sieboldii), as well gymnosperms, Japanese cypress (Chamaecyparis obtusa) and pine (Pinus densiflora). Membrane vesicles prepared from differentiating xylem tissues showed clear ATP-dependent transport activity of coniferin, whereas less than 4% of the coniferin transport activity was seen for coniferyl alcohol. Bafilomycin A1 and proton gradient erasers markedly inhibited coniferin transport in hybrid poplar membrane vesicles; in contrast, vanadate had no effect. Cis-inhibition experiments suggested that this transport activity was specific for coniferin. Membrane fractionation of hybrid poplar microsomes demonstrated that transport activity was localized to the tonoplast- and endomembrane-rich fraction. Differentiating xylem of Japanese cypress exhibited almost identical transport properties, suggesting the involvement of a common endomembrane-associated proton/coniferin antiport mechanism in the lignifying tissues of woody plants, both angiosperms and gymnosperms.

  12. Proton-Dependent Coniferin Transport, a Common Major Transport Event in Differentiating Xylem Tissue of Woody Plants1[W

    PubMed Central

    Tsuyama, Taku; Kawai, Ryo; Shitan, Nobukazu; Matoh, Toru; Sugiyama, Junji; Yoshinaga, Arata; Takabe, Keiji; Fujita, Minoru; Yazaki, Kazufumi

    2013-01-01

    Lignin biosynthesis is an essential physiological activity of vascular plants if they are to survive under various environmental stresses on land. The biosynthesis of lignin proceeds in the cell wall by polymerization of precursors; the initial step of lignin polymerization is the transportation of lignin monomers from the cytosol to the cell wall, which is critical for lignin formation. There has been much debate on the transported form of the lignin precursor, either as free monolignols or their glucosides. In this study, we performed biochemical analyses to characterize the membrane transport mechanism of lignin precursors using angiosperms, hybrid poplar (Populus sieboldii × Populus grandidentata) and poplar (Populus sieboldii), as well gymnosperms, Japanese cypress (Chamaecyparis obtusa) and pine (Pinus densiflora). Membrane vesicles prepared from differentiating xylem tissues showed clear ATP-dependent transport activity of coniferin, whereas less than 4% of the coniferin transport activity was seen for coniferyl alcohol. Bafilomycin A1 and proton gradient erasers markedly inhibited coniferin transport in hybrid poplar membrane vesicles; in contrast, vanadate had no effect. Cis-inhibition experiments suggested that this transport activity was specific for coniferin. Membrane fractionation of hybrid poplar microsomes demonstrated that transport activity was localized to the tonoplast- and endomembrane-rich fraction. Differentiating xylem of Japanese cypress exhibited almost identical transport properties, suggesting the involvement of a common endomembrane-associated proton/coniferin antiport mechanism in the lignifying tissues of woody plants, both angiosperms and gymnosperms. PMID:23585651

  13. Identification of commonly expressed exoproteins and proteolytic cleavage events by proteomic mining of clinically relevant UK isolates of Staphylococcus aureus

    PubMed Central

    Smith, Debra S.; Siggins, Matthew K.; Gierula, Magdalena; Pichon, Bruno; Turner, Claire E.; Lynskey, Nicola N.; Mosavie, Mia; Kearns, Angela M.; Edwards, Robert J.

    2016-01-01

    The range of exoproteins and core exoproteome of 14 Staphylococcus aureus isolates representing major lineages associated with asymptomatic carriage and clinical disease in the UK was identified by MS proteomics using a combined database incorporating sequences derived from 39 S. aureus genomes. In all, 632 different proteins were identified and, of these, only 52 (8 %) were found in all 14 isolates whereas 144 (23 %) were found in just a single isolate. Comparison of the observed mass of each protein (based on migration by SDS-PAGE) with its predicted mass (based on amino acid sequence) suggested that 95 % of the proteins identified were not subject to any major post-translational modification. Migration of 5 % of the proteins was not as expected: 1 % of the proteins migrated at a mass greater than predicted, while 4 % appeared to have undergone proteolytic cleavage; these included SsaA2, Aur, SspP, Ebh as well as BlaR1, MecR1, FsH, OatA and LtaS. Intriguingly, a truncated SasG was produced by a single CC8 USA300-like strain. The analysis provided evidence of the marked heterogeneity in protein expression by S. aureus in broth, while yielding a core but narrow common exoproteome. PMID:28348843

  14. Copy number gains in EGFR and copy number losses in PTEN are common events in osteosarcoma tumors.

    PubMed

    Freeman, Serena S; Allen, Steven W; Ganti, Ramapriya; Wu, Jianrong; Ma, Jing; Su, Xiaoping; Neale, Geoff; Dome, Jeffrey S; Daw, Najat C; Khoury, Joseph D

    2008-09-15

    Osteosarcoma cell lines and tumors have been shown to express epidermal growth factor receptor (EGFR) and harbor amplifications at the EGFR locus. In this study, the authors further analyzed the genomic features of EGFR in osteosarcoma tumors and investigated whether they correlate with phosphatase and tensin homolog (PTEN) expression and copy number status. EGFR and PTEN expression was assessed by immunohistochemistry (n = 28), and copy number alterations at the EGFR and PTEN loci were surveyed using Affymetrix (Santa Clara, Calif) 50K single nucleotide polymorphism (SNP) arrays (n = 31) and fluorescence in situ hybridization (FISH) (n = 27). The EGFR tyrosine kinase domain was sequenced to survey for activating mutations (n = 34). In addition, EGFRvIII expression was assessed using reverse transcriptase polymerase chain reaction (n = 24). Results were correlated with available clinical information on 59 patients, with a median age of 14.1 years (range, 5-23 years) and median follow-up of 4.4 years. EGFR expression was detected in the majority of osteosarcoma tumors surveyed (23 of 28; 82%). SNP arrays revealed evidence of frequent copy number gains at 7p11.2 and losses at 10q23.21. A sizeable subset (16 of 27 cases; 59%) showed gains at the EGFR locus using FISH (amplification in 4 of 27 [15%] and balanced chromosome 7 polysomy in 12 of 27 [44%]), and 12 cases showed deletions at the PTEN locus (biallelic deletions in 4 of 27 [15%] and monoallelic deletion in 9 of 27 [33%]). No activating mutations in the EGFR tyrosine kinase domain, EGFRvIII expression, or association with clinical findings were detected. EGFR expression and genomic gains at the EGFR locus are prevalent in osteosarcoma tumors, which also commonly harbor deletions at the PTEN locus. (c) 2008 American Cancer Society.

  15. Algorithm for Screening Phasor Measurement Unit Data for Power System Events and Categories and Common Characteristics for Events Seen in Phasor Measurement Unit Relative Phase-Angle Differences and Frequency Signals

    SciTech Connect

    Allen, A.; Santoso, S.; Muljadi, E.

    2013-08-01

    A network of multiple phasor measurement units (PMU) was created, set up, and maintained at the University of Texas at Austin to obtain actual power system measurements for power system analysis. Power system analysis in this report covers a variety of time ranges, such as short- term analysis for power system disturbances and their effects on power system behavior and long- term power system behavior using modal analysis. The first objective of this report is to screen the PMU data for events. The second objective of the report is to identify and describe common characteristics extracted from power system events as measured by PMUs. The numerical characteristics for each category and how these characteristics are used to create selection rules for the algorithm are also described. Trends in PMU data related to different levels and fluctuations in wind power output are also examined.

  16. Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumors.

    PubMed

    Tahiri, Andliena; Leivonen, Suvi-Katri; Lüders, Torben; Steinfeld, Israel; Ragle Aure, Miriam; Geisler, Jürgen; Mäkelä, Rami; Nord, Silje; Riis, Margit L H; Yakhini, Zohar; Kleivi Sahlberg, Kristine; Børresen-Dale, Anne-Lise; Perälä, Merja; Bukholm, Ida R K; Kristensen, Vessela N

    2014-01-01

    MicroRNAs (miRNAs) are endogenous non-coding RNAs, which play an essential role in the regulation of gene expression during carcinogenesis. The role of miRNAs in breast cancer has been thoroughly investigated, and although many miRNAs are identified as cancer related, little is known about their involvement in benign tumors. In this study, we investigated miRNA expression profiles in the two most common types of human benign tumors (fibroadenoma/fibroadenomatosis) and in malignant breast tumors and explored their role as oncomirs and tumor suppressor miRNAs. Here, we identified 33 miRNAs with similar deregulated expression in both benign and malignant tumors compared with the expression levels of those in normal tissue, including breast cancer-related miRNAs such as let-7, miR-21 and miR-155. Additionally, messenger RNA (mRNA) expression profiles were obtained for some of the same samples. Using integrated mRNA/miRNA expression analysis, we observed that overexpression of certain miRNAs co-occurred with a significant downregulation of their candidate target mRNAs in both benign and malignant tumors. In support of these findings, in vitro functional screening of the downregulated miRNAs in non-malignant and breast cancer cell lines identified several possible tumor suppressor miRNAs, including miR-193b, miR-193a-3p, miR-126, miR-134, miR-132, miR-486-5p, miR-886-3p, miR-195 and miR-497, showing reduced growth when re-expressed in cancer cells. The finding of deregulated expression of oncomirs and tumor suppressor miRNAs in benign breast tumors is intriguing, indicating that they may play a role in proliferation. A role of cancer-related miRNAs in the early phases of carcinogenesis and malignant transformation can, therefore, not be ruled out.

  17. The role of dose rate in radiation cancer risk: evaluating the effect of dose rate at the molecular, cellular and tissue levels using key events in critical pathways following exposure to low LET radiation.

    PubMed

    Brooks, Antone L; Hoel, David G; Preston, R Julian

    2016-08-01

    This review evaluates the role of dose rate on cell and molecular responses. It focuses on the influence of dose rate on key events in critical pathways in the development of cancer. This approach is similar to that used by the U.S. EPA and others to evaluate risk from chemicals. It provides a mechanistic method to account for the influence of the dose rate from low-LET radiation, especially in the low-dose region on cancer risk assessment. Molecular, cellular, and tissues changes are observed in many key events and change as a function of dose rate. The magnitude and direction of change can be used to help establish an appropriate dose rate effectiveness factor (DREF). Extensive data on key events suggest that exposure to low dose-rates are less effective in producing changes than high dose rates. Most of these data at the molecular and cellular level support a large (2-30) DREF. In addition, some evidence suggests that doses delivered at a low dose rate decrease damage to levels below that observed in the controls. However, there are some data human and mechanistic data that support a dose-rate effectiveness factor of 1. In summary, a review of the available molecular, cellular and tissue data indicates that not only is dose rate an important variable in understanding radiation risk but it also supports the selection of a DREF greater than one as currently recommended by ICRP ( 2007 ) and BEIR VII (NRC/NAS 2006 ).

  18. Pain Flare Is a Common Adverse Event in Steroid-Naïve Patients After Spine Stereotactic Body Radiation Therapy: A Prospective Clinical Trial

    SciTech Connect

    Chiang, Andrew; Zeng, Liang; Zhang, Liying; Lochray, Fiona; Korol, Renee; Loblaw, Andrew; Chow, Edward; Sahgal, Arjun

    2013-07-15

    Purpose: To determine the incidence of pain flare after spine stereotactic body radiation therapy (SBRT) in steroid-naïve patients and identify predictive factors. Methods and Materials: Forty-one patients were treated with spine SBRT between February 2010 and April 2012. All patients had their pain assessed at baseline, during, and for 10 days after SBRT using the Brief Pain Inventory. All pain medications were recorded daily and narcotics converted to an oral morphine equivalent dose. Pain flare was defined as a 2-point increase in worst pain score as compared with baseline with no decrease in analgesic intake, a 25% increase in analgesic intake as compared with baseline with no decrease in worst pain score, or if corticosteroids were initiated at any point during or after SBRT because of pain. Results: The median age and Karnofsky performance status were 57.5 years (range, 27-80 years) and 80 (range, 50-100), respectively. Eighteen patients were treated with 20-24 Gy in a single fraction, whereas 23 patients were treated with 24-35 Gy in 2-5 fractions. Pain flare was observed in 68.3% of patients (28 of 41), most commonly on day 1 after SBRT (29%, 8 of 28). Multivariate analysis identified a higher Karnofsky performance status (P=.02) and cervical (P=.049) or lumbar (P=.02) locations as significant predictors of pain flare. In those rescued with dexamethasone, a significant decrease in pain scores over time was subsequently observed (P<.0001). Conclusions: Pain flare is a common adverse event after spine SBRT and occurs most commonly the day after treatment completion. Patients should be appropriately consented for this adverse event.

  19. Cellular basis of Alzheimer’s disease

    PubMed Central

    Bali, Jitin; Halima, Saoussen Ben; Felmy, Boas; Goodger, Zoe; Zurbriggen, Sebastian; Rajendran, Lawrence

    2010-01-01

    Alzheimer’s disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD. PMID:21369424

  20. Insulin pump-associated adverse events are common, but not associated with glycemic control, socio-economic status, or pump/infusion set type.

    PubMed

    Ross, P; Gray, A R; Milburn, J; Kumarasamy, I M; Wu, F; Farrand, S; Armishaw, J; Wiltshire, E; Rayns, J; Tomlinson, P; Wheeler, B J

    2016-12-01

    While there have been many outcome-focussed studies examining insulin pump therapy, only a few have looked at potential adverse events (AEs), with none examining the relationship between AEs and pump/infusion set type, ethnicity or socio-economic status. In addition, current data on the incidence and characteristics of pump-associated AEs are confined to one paediatric centre. We aimed to describe the incidence, characteristics and potential predictors of insulin pump-associated AEs in New Zealand adults and children with T1DM. We approached adults and families of children with T1DM on insulin pumps in four main New Zealand centres. Participants completed a questionnaire examining pump-related issues they had experienced in the preceding 12 months. Response rate was 64 % with 174 of 270 eligible people participating in the study. 84 % of subjects reported one or more AEs, with an overall AE incidence of 3.42 per person/year (95 % CI 3.14, 3.73). An event serious enough to require a hospital presentation occurred in 9.8 %, all but one reporting high ketones or diabetic ketoacidosis (DKA). Set/site problems were the AE most commonly reported (by 53 % of respondents), followed by cutaneous complications (43 %) and pump malfunction (38 %). Few predictors of AEs (of any type) were found; however, a negative binomial regression model found that a longer duration of pumping (p = 0.018) and age <18 years (p = 0.043) were both associated with fewer AEs (all types combined). Insulin pump-associated AEs are very common. However, few variables are predictive of them with no relationships seen with glycaemic control, socio-economic status, pump manufacturer or infusion set type. Based on these findings, AEs should be anticipated in both adults and children, with anticipatory patient education and training recommended for their successful and safe use.

  1. Development of the National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

    PubMed Central

    Reeve, Bryce B.; Mitchell, Sandra A.; Clauser, Steven B.; Minasian, Lori M.; Dueck, Amylou C.; Mendoza, Tito R.; Hay, Jennifer; Atkinson, Thomas M.; Abernethy, Amy P.; Bruner, Deborah W.; Cleeland, Charles S.; Sloan, Jeff A.; Chilukuri, Ram; Baumgartner, Paul; Denicoff, Andrea; St. Germain, Diane; O’Mara, Ann M.; Chen, Alice; Kelaghan, Joseph; Bennett, Antonia V.; Sit, Laura; Rogak, Lauren; Barz, Allison; Paul, Diane B.; Schrag, Deborah

    2014-01-01

    The standard approach for documenting symptomatic adverse events (AEs) in cancer clinical trials involves investigator reporting using the National Cancer Institute’s (NCI’s) Common Terminology Criteria for Adverse Events (CTCAE). Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE, called the PRO-CTCAE. This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties. A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting. For each of these, a PRO-CTCAE plain language term in English and one to three items characterizing the frequency, severity, and/or activity interference of the AE were created, rendering a library of 124 PRO-CTCAE items. These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational, racial, and geographic backgrounds. Favorable measurement properties of the items, including construct validity, reliability, responsiveness, and between-mode equivalence, were determined prospectively in a demographically diverse population of patients receiving treatments for many different tumor types. A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing. Work is ongoing to translate the PRO-CTCAE into multiple languages and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses. It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research. PMID:25265940

  2. Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE).

    PubMed

    Basch, Ethan; Reeve, Bryce B; Mitchell, Sandra A; Clauser, Steven B; Minasian, Lori M; Dueck, Amylou C; Mendoza, Tito R; Hay, Jennifer; Atkinson, Thomas M; Abernethy, Amy P; Bruner, Deborah W; Cleeland, Charles S; Sloan, Jeff A; Chilukuri, Ram; Baumgartner, Paul; Denicoff, Andrea; St Germain, Diane; O'Mara, Ann M; Chen, Alice; Kelaghan, Joseph; Bennett, Antonia V; Sit, Laura; Rogak, Lauren; Barz, Allison; Paul, Diane B; Schrag, Deborah

    2014-09-01

    The standard approach for documenting symptomatic adverse events (AEs) in cancer clinical trials involves investigator reporting using the National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE). Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE, called the PRO-CTCAE. This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties. A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting. For each of these, a PRO-CTCAE plain language term in English and one to three items characterizing the frequency, severity, and/or activity interference of the AE were created, rendering a library of 124 PRO-CTCAE items. These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational, racial, and geographic backgrounds. Favorable measurement properties of the items, including construct validity, reliability, responsiveness, and between-mode equivalence, were determined prospectively in a demographically diverse population of patients receiving treatments for many different tumor types. A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing. Work is ongoing to translate the PRO-CTCAE into multiple languages and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses. It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research. © The Author 2014. Published by Oxford University Press. All

  3. Common Phenolic Metabolites of Flavonoids, but Not Their Unmetabolized Precursors, Reduce the Secretion of Vascular Cellular Adhesion Molecules by Human Endothelial Cells123

    PubMed Central

    Warner, Emily F; Zhang, Qingzhi; Raheem, K Saki; O’Hagan, David; O’Connell, Maria A; Kay, Colin D

    2016-01-01

    Background: Flavonoids have been implicated in the prevention of cardiovascular disease; however, their mechanisms of action have yet to be elucidated, possibly because most previous in vitro studies have used supraphysiological concentrations of unmetabolized flavonoids, overlooking their more bioavailable phenolic metabolites. Objective: We aimed to explore the effects of phenolic metabolites and their precursor flavonoids at physiologically achievable concentrations, in isolation and combination, on soluble vascular cellular adhesion molecule-1 (sVCAM-1). Method: Fourteen phenolic acid metabolites and 6 flavonoids were screened at 1 μM for their relative effects on sVCAM-1 secretion by human umbilical vein endothelial cells stimulated with tumor necrosis factor alpha (TNF-α). The active metabolites were further studied for their response at different concentrations (0.01 μM–100 μM), structure-activity relationships, and effect on vascular cellular adhesion molecule (VCAM)-1 mRNA expression. In addition, the additive activity of the metabolites and flavonoids was investigated by screening 25 unique mixtures at cumulative equimolar concentrations of 1 μM. Results: Of the 20 compounds screened at 1 μM, inhibition of sVCAM-1 secretion was elicited by 4 phenolic metabolites, of which protocatechuic acid (PCA) was the most active (−17.2%, P = 0.05). Investigations into their responses at different concentrations showed that PCA significantly reduced sVCAM-1 15.2–36.5% between 1 and 100 μM, protocatechuic acid-3-sulfate and isovanillic acid reduced sVCAM-1 levels 12.2–54.7% between 10 and 100 μM, and protocatechuic acid-4-sulfate and isovanillic acid-3-glucuronide reduced sVCAM-1 secretion 27.6% and 42.8%, respectively, only at 100 μM. PCA demonstrated the strongest protein response and was therefore explored for its effect on VCAM-1 mRNA, where 78.4% inhibition was observed only after treatment with 100 μM PCA. Mixtures of the metabolites showed no

  4. Patient-Reported Outcomes in Cancer Clinical Trials: Measuring Symptomatic Adverse Events With the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

    PubMed

    Kluetz, Paul G; Chingos, Diana T; Basch, Ethan M; Mitchell, Sandra A

    2016-01-01

    Systematic capture of the patient perspective can inform the development of new cancer therapies. Patient-reported outcomes (PROs) are commonly included in cancer clinical trials; however, there is heterogeneity in the constructs, measures, and analytic approaches that have been used making these endpoints challenging to interpret. There is renewed effort to identify rigorous methods to obtain high-quality and informative PRO data from cancer clinical trials. In this setting, PROs are used to address specific research objectives, and an important objective that spans the product development life cycle is the assessment of safety and tolerability. The U.S. Food and Drug Administration's (FDA) Office of Hematology and Oncology Products (OHOP) has identified symptomatic adverse events (AEs) as a central PRO concept, and a systematic assessment of patient-reported symptomatic AEs can provide data to complement clinician reporting. The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being evaluated by multiple stakeholders, including the FDA, and is considered a promising tool to provide a standard yet flexible method to assess symptomatic AEs from the patient perspective. In this article, we briefly review the FDA OHOP's perspective on PROs in cancer trials submitted to the FDA and focus on the assessment of symptomatic AEs using PRO-CTCAE. We conclude by discussing further work that must be done to broaden the use of PRO-CTCAE as a method to provide patient-centered data that can complement existing safety and tolerability assessments across cancer clinical trials.

  5. Eliciting the child’s voice in adverse event reporting in oncology trials: Cognitive interview findings from the Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events initiative

    PubMed Central

    Reeve, Bryce B.; McFatrich, Molly; Pinheiro, Laura C.; Weaver, Meaghann S.; Sung, Lillian; Withycombe, Janice S.; Baker, Justin N.; Mack, Jennifer W.; Waldron, Mia K.; Gibson, Deborah; Tomlinson, Deborah; Freyer, David R.; Mowbray, Catriona; Jacobs, Shana; Palma, Diana; Martens, Christa E.; Gold, Stuart H.; Jackson, Kathryn D.; Hinds, Pamela S.

    2017-01-01

    Background Adverse event (AE) reporting in oncology trials is required, but current practice does not directly integrate the child’s voice. The Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being developed to assess symptomatic AEs via child/adolescent self-report or proxy-report. This qualitative study evaluates the child’s/adolescent’s understanding and ability to provide valid responses to the PRO-CTCAE to inform questionnaire refinements and confirm content validity. Procedure From seven pediatric research hospitals, children/adolescents ages 7–15 years who were diagnosed with cancer and receiving treatment were eligible, along with their parent-proxies. The Pediatric PRO-CTCAE includes 130 questions that assess 62 symptomatic AEs capturing symptom frequency, severity, interference, or presence. Cognitive interviews with retrospective probing were completed with children in the age groups of 7–8, 9–12, and 13–15 years. The children/adolescents and proxies were interviewed independently. Results Two rounds of interviews involved 81 children and adolescents and 74 parent-proxies. Fifteen of the 62 AE terms were revised after Round 1, including refinements to the questions assessing symptom severity. Most participants rated the PRO-CTCAE AE items as “very easy” or “somewhat easy” and were able to read, understand, and provide valid responses to questions. A few AE items assessing rare events were challenging to understand. Conclusions The Pediatric and Proxy PRO-CTCAE performed well among children and adolescents and their proxies, supporting its content validity. Data from PRO-CTCAE may improve symptomatic AE reporting in clinical trials and enhance the quality of care that children receive. PMID:27650708

  6. Calcitriol induced redox imbalance and DNA breakage in cells sharing a common metabolic feature of malignancies: Interaction with cellular copper (II) ions leads to the production of reactive oxygen species.

    PubMed

    Rizvi, Asim; Rizvi, Ghazala; Naseem, Imrana

    2015-05-01

    Calcitriol is known to selectively kill malignant cells, however, not much is known about the mechanism by which it kills malignant cells and spares the "normal" cells. Since elevation of cellular copper is a metabolic condition common to all malignancies, we developed a mouse model to mimic this condition and treated the animals with calcitriol. It was observed that calcitriol-copper interaction in vivo causes severe fluctuations in cellular enzymatic and nonenzymatic scavengers of reactive oxygen species (ROS). Lipid peroxidation, a well-established marker of oxidative stress, was found to increase, and a substantial cellular DNA breakage was observed. Calcitriol-copper interaction in vivo was observed to lead the cells to an apoptosis like cell death. We propose that the interaction of calcitriol and copper within malignant cells and the consequent redox scavenger fluctuations and ROS-mediated DNA breakage may be one of the several mechanisms by which calcitriol causes selective cell death of malignant cells, while sparing normal cells.

  7. The role of dose rate in radiation cancer risk: evaluating the effect of dose rate at the molecular, cellular and tissue levels using key events in critical pathways following exposure to low LET radiation

    PubMed Central

    Brooks, Antone L.; Hoel, David G.; Preston, R. Julian

    2016-01-01

    Abstract Purpose: This review evaluates the role of dose rate on cell and molecular responses. It focuses on the influence of dose rate on key events in critical pathways in the development of cancer. This approach is similar to that used by the U.S. EPA and others to evaluate risk from chemicals. It provides a mechanistic method to account for the influence of the dose rate from low-LET radiation, especially in the low-dose region on cancer risk assessment. Molecular, cellular, and tissues changes are observed in many key events and change as a function of dose rate. The magnitude and direction of change can be used to help establish an appropriate dose rate effectiveness factor (DREF). Conclusions: Extensive data on key events suggest that exposure to low dose-rates are less effective in producing changes than high dose rates. Most of these data at the molecular and cellular level support a large (2–30) DREF. In addition, some evidence suggests that doses delivered at a low dose rate decrease damage to levels below that observed in the controls. However, there are some data human and mechanistic data that support a dose-rate effectiveness factor of 1. In summary, a review of the available molecular, cellular and tissue data indicates that not only is dose rate an important variable in understanding radiation risk but it also supports the selection of a DREF greater than one as currently recommended by ICRP (2007) and BEIR VII (NRC/NAS 2006). PMID:27266588

  8. Demographic clusters identified within the northern Gulf of Mexico common bottlenose dolphin (Tursiops truncates) unusual mortality event: January 2010-June 2013.

    PubMed

    Venn-Watson, Stephanie; Garrison, Lance; Litz, Jenny; Fougeres, Erin; Mase, Blair; Rappucci, Gina; Stratton, Elizabeth; Carmichael, Ruth; Odell, Daniel; Shannon, Delphine; Shippee, Steve; Smith, Suzanne; Staggs, Lydia; Tumlin, Mandy; Whitehead, Heidi; Rowles, Teri

    2015-01-01

    A multi-year unusual mortality event (UME) involving primarily common bottlenose dolphins (Tursiops truncates) was declared in the northern Gulf of Mexico (GoM) with an initial start date of February 2010 and remains ongoing as of August 2014. To examine potential changing characteristics of the UME over time, we compared the number and demographics of dolphin strandings from January 2010 through June 2013 across the entire GoM as well as against baseline (1990-2009) GoM stranding patterns. Years 2010 and 2011 had the highest annual number of stranded dolphins since Louisiana's record began, and 2011 was one of the years with the highest strandings for both Mississippi and Alabama. Statewide, annual numbers of stranded dolphins were not elevated for GoM coasts of Florida or Texas during the UME period. Demographic, spatial, and temporal clusters identified within this UME included increased strandings in northern coastal Louisiana and Mississippi (March-May 2010); Barataria Bay, Louisiana (August 2010-December 2011); Mississippi and Alabama (2011, including a high prevalence and number of stranded perinates); and multiple GoM states during early 2013. While the causes of the GoM UME have not been determined, the location and magnitude of dolphin strandings during and the year following the 2010 Deepwater Horizon oil spill, including the Barataria Bay cluster from August 2010 to December 2011, overlap in time and space with locations that received heavy and prolonged oiling. There are, however, multiple known causes of previous GoM dolphin UMEs, including brevetoxicosis and dolphin morbillivirus. Additionally, increased dolphin strandings occurred in northern Louisiana and Mississippi before the Deepwater Horizon oil spill. Identification of spatial, temporal, and demographic clusters within the UME suggest that this mortality event may involve different contributing factors varying by location, time, and bottlenose dolphin populations that will be better discerned

  9. Cognitive interviewing of the US National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

    PubMed

    Hay, Jennifer L; Atkinson, Thomas M; Reeve, Bryce B; Mitchell, Sandra A; Mendoza, Tito R; Willis, Gordon; Minasian, Lori M; Clauser, Steven B; Denicoff, Andrea; O'Mara, Ann; Chen, Alice; Bennett, Antonia V; Paul, Diane B; Gagne, Joshua; Rogak, Lauren; Sit, Laura; Viswanath, Vish; Schrag, Deborah; Basch, Ethan

    2014-02-01

    The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a library of question items that enables patient reporting of adverse events (AEs) in clinical trials. This study contributes content validity evidence of the PRO-CTCAE by incorporating cancer patient input of the relevance and comprehensiveness of the item library. Cognitive interviews were conducted among patients undergoing chemotherapy or radiation therapy at multiple sites to evaluate comprehension, memory retrieval, judgment, and response mapping related to AE terms (e.g., nausea), attribute terms (regarding frequency, severity, or interference), response options, and recall period. Three interview rounds were conducted with ≥20 patients completing each item per round. Items were modified and retested if ≥3 patients exhibited cognitive difficulties or if experienced by ≤25% patients. One hundred and twenty-seven patients participated (35% ≤high school, 28% non-white, and 59% female). Most AE terms (63/80) generated no cognitive difficulties. The remaining 17 were modified without further difficulties by Round 3. Terms were comprehended regardless of education level. Attribute terms and response options required no modifications. Patient adherence to recall period (7 days) was improved when the reference period was incorporated. This study provides evidence confirming comprehension of the US English language versions of items in the PRO-CTCAE library for measuring symptomatic AEs from the patient perspective within the context of cancer treatment. Several minor changes were made to the items to improve item clarity, comprehension, and ease of response judgment. This study helps to establish the content validity of PRO-CTCAE items for patient reporting of AEs during cancer treatment.

  10. Cognitive interviewing of the U.S. National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

    PubMed Central

    Hay, Jennifer L.; Atkinson, Thomas M.; Reeve, Bryce B.; Mitchell, Sandra A.; Mendoza, Tito R.; Willis, Gordon; Minasian, Lori M.; Clauser, Steven B.; Denicoff, Andrea; O’Mara, Ann; Chen, Alice; Bennett, Antonia V.; Paul, Diane B.; Gagne, Joshua; Rogak, Lauren; Sit, Laura; Viswanath, Vish; Schrag, Deborah; Basch, Ethan

    2013-01-01

    Purpose The National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a library of question items that enables patient reporting of adverse events (AEs) in clinical trials. This study contributes content validity evidence of the PRO-CTCAE by incorporating cancer patient input of the relevance and comprehensiveness of the item library. Methods Cognitive interviews were conducted among patients undergoing chemotherapy or radiation therapy at multiple sites to evaluate comprehension, memory retrieval, judgment, and response mapping related to AE terms (e.g., nausea); attribute terms (regarding frequency, severity, or interference); response options; and recall period. Three interview rounds were conducted with ≥20 patients completing each item per round. Items were modified and retested if ≥3 patients exhibited cognitive difficulties or if experienced by ≤25% patients. Results 127 patients participated (35% ≤high school; 28% non-white; 59% female). Most AE terms (63/80) generated no cognitive difficulties. The remaining 17 were modified without further difficulties by Round 3. Terms were comprehended regardless of education level. Attribute terms and response options required no modifications. Patient adherence to recall period (7-days) was improved when the reference period was incorporated. Conclusions This study provides evidence confirming comprehension of the U.S. English language versions of items in the PRO-CTCAE library for measuring symptomatic AEs from the patient perspective within the context of cancer treatment. Several minor changes were made to the items to improve item clarity, comprehension, and ease of response judgment. This study helps establish the content validity of PRO-CTCAE items for patient reporting of AEs during cancer treatment. PMID:23868457

  11. Demographic Clusters Identified within the Northern Gulf of Mexico Common Bottlenose Dolphin (Tursiops truncates) Unusual Mortality Event: January 2010 - June 2013

    PubMed Central

    Venn-Watson, Stephanie; Garrison, Lance; Litz, Jenny; Fougeres, Erin; Mase, Blair; Rappucci, Gina; Stratton, Elizabeth; Carmichael, Ruth; Odell, Daniel; Shannon, Delphine; Shippee, Steve; Smith, Suzanne; Staggs, Lydia; Tumlin, Mandy; Whitehead, Heidi; Rowles, Teri

    2015-01-01

    A multi-year unusual mortality event (UME) involving primarily common bottlenose dolphins (Tursiops truncates) was declared in the northern Gulf of Mexico (GoM) with an initial start date of February 2010 and remains ongoing as of August 2014. To examine potential changing characteristics of the UME over time, we compared the number and demographics of dolphin strandings from January 2010 through June 2013 across the entire GoM as well as against baseline (1990-2009) GoM stranding patterns. Years 2010 and 2011 had the highest annual number of stranded dolphins since Louisiana’s record began, and 2011 was one of the years with the highest strandings for both Mississippi and Alabama. Statewide, annual numbers of stranded dolphins were not elevated for GoM coasts of Florida or Texas during the UME period. Demographic, spatial, and temporal clusters identified within this UME included increased strandings in northern coastal Louisiana and Mississippi (March-May 2010); Barataria Bay, Louisiana (August 2010-December 2011); Mississippi and Alabama (2011, including a high prevalence and number of stranded perinates); and multiple GoM states during early 2013. While the causes of the GoM UME have not been determined, the location and magnitude of dolphin strandings during and the year following the 2010 Deepwater Horizon oil spill, including the Barataria Bay cluster from August 2010 to December 2011, overlap in time and space with locations that received heavy and prolonged oiling. There are, however, multiple known causes of previous GoM dolphin UMEs, including brevetoxicosis and dolphin morbillivirus. Additionally, increased dolphin strandings occurred in northern Louisiana and Mississippi before the Deepwater Horizon oil spill. Identification of spatial, temporal, and demographic clusters within the UME suggest that this mortality event may involve different contributing factors varying by location, time, and bottlenose dolphin populations that will be better

  12. Decreasing electron flux through the cytochrome and/or alternative respiratory pathways triggers common and distinct cellular responses dependent on growth conditions.

    PubMed

    Kühn, Kristina; Yin, Guangkun; Duncan, Owen; Law, Simon R; Kubiszewski-Jakubiak, Szymon; Kaur, Parwinder; Meyer, Etienne; Wang, Yan; Small, Catherine Colas des Francs; Giraud, Estelle; Narsai, Reena; Whelan, James

    2015-01-01

    Diverse signaling pathways are activated by perturbation of mitochondrial function under different growth conditions.Mitochondria have emerged as an important organelle for sensing and coping with stress in addition to being the sites of important metabolic pathways. Here, responses to moderate light and drought stress were examined in different Arabidopsis (Arabidopsis thaliana) mutant plants lacking a functional alternative oxidase (alternative oxidase1a [aox1a]), those with reduced cytochrome electron transport chain capacity (T3/T7 bacteriophage-type RNA polymerase, mitochondrial, and plastidial [rpoTmp]), and double mutants impaired in both pathways (aox1a:rpoTmp). Under conditions considered optimal for growth, transcriptomes of aox1a and rpoTmp were distinct. Under adverse growth conditions, however, transcriptome changes in aox1a and rpoTmp displayed a highly significant overlap and were indicative of a common mitochondrial stress response and down-regulation of photosynthesis. This suggests that the role of mitochondria to support photosynthesis is provided through either the alternative pathway or the cytochrome pathway, and when either pathway is inhibited, such as under environmental stress, a common, dramatic, and succinct mitochondrial signal is activated to alter energy metabolism in both organelles. aox1a:rpoTmp double mutants grown under optimal conditions showed dramatic reductions in biomass production compared with aox1a and rpoTmp and a transcriptome that was distinct from aox1a or rpoTmp. Transcript data indicating activation of mitochondrial biogenesis in aox1a:rpoTmp were supported by a proteomic analysis of over 200 proteins. Under optimal conditions, aox1a:rpoTmp plants seemed to switch on many of the typical mitochondrial stress regulators. Under adverse conditions, aox1a:rpoTmp turned off these responses and displayed a biotic stress response. Taken together, these results highlight the diverse signaling pathways activated by the

  13. Hemifield-dependent N1 and event-related theta/delta oscillations: An unbiased comparison of surface Laplacian and common EEG reference choices

    PubMed Central

    Kayser, Jürgen; Tenke, Craig E.

    2015-01-01

    Surface Laplacian methodology has been used to reduce the impact of volume conduction and arbitrary choice of EEG recording reference for the analysis of surface potentials. However, the empirical implications of employing these different transformations to the same EEG data remain obscure. This study directly compared the statistical effects of four commonly-used (nose, linked mastoids, average) or recommended (reference electrode standardization technique [REST]) references and their spherical spline current source density (CSD) transformation for a large data set stemming from a well-understood experimental manipulation. ERPs (72 sites) recorded from 130 individuals during a visual half-field paradigm with highly-controlled emotional stimuli were characterized by mid-parietooccipital N1 (125 ms peak latency) and event-related synchronization (ERS) of theta/delta (160 ms), which were most robust over the contralateral hemisphere. All five data transformations were rescaled to the same covariance and submitted to a single temporal or time-frequency PCA (Varimax) to yield simplified estimates of N1 or theta/delta ERS. Unbiased nonparametric permutation tests revealed that these hemifield-dependent asymmetries were by far most focal and prominent for CSD data, despite all transformations showing maximum effects at mid-parietooccipital sites. Employing smaller subsamples (signal-to-noise) or window-based ERP/ERS amplitudes did not affect these comparisons. Furthermore, correlations between N1 and theta/delta ERS at these sites were strongest for CSD and weakest for nose-referenced data. Contrary to the common notion that the spatial high pass filter properties of a surface Laplacian reduce important contributions of neuronal generators to the EEG signal, the present findings demonstrate that instead volume conduction inherent in surface potentials weakens the representation of neuronal activation patterns at scalp that directly reflect regional brain activity. PMID

  14. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    PubMed Central

    Hermes, Gretchen; Ajioka, James W; Kelly, Krystyna A; Mui, Ernest; Roberts, Fiona; Kasza, Kristen; Mayr, Thomas; Kirisits, Michael J; Wollmann, Robert; Ferguson, David JP; Roberts, Craig W; Hwang, Jong-Hee; Trendler, Toria; Kennan, Richard P; Suzuki, Yasuhiro; Reardon, Catherine; Hickey, William F; Chen, Lieping; McLeod, Rima

    2008-01-01

    Background Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. Methods To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. Results Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus

  15. Analysis of the common deletions in the mitochondrial DNA is a sensitive biomarker detecting direct and non-targeted cellular effects of low dose ionizing radiation.

    PubMed

    Schilling-Tóth, Boglárka; Sándor, Nikolett; Kis, Eniko; Kadhim, Munira; Sáfrány, Géza; Hegyesi, Hargita

    2011-11-01

    One of the key issues of current radiation research is the biological effect of low doses. Unfortunately, low dose science is hampered by the unavailability of easily performable, reliable and sensitive quantitative biomarkers suitable detecting low frequency alterations in irradiated cells. We applied a quantitative real time polymerase chain reaction (qRT-PCR) based protocol detecting common deletions (CD) in the mitochondrial genome to assess direct and non-targeted effects of radiation in human fibroblasts. In directly irradiated (IR) cells CD increased with dose and was higher in radiosensitive cells. Investigating conditioned medium-mediated bystander effects we demonstrated that low and high (0.1 and 2Gy) doses induced similar levels of bystander responses and found individual differences in human fibroblasts. The bystander response was not related to the radiosensitivity of the cells. The importance of signal sending donor and signal receiving target cells was investigated by placing conditioned medium from a bystander response positive cell line (F11-hTERT) to bystander negative cells (S1-hTERT) and vice versa. The data indicated that signal sending cells are more important in the medium-mediated bystander effect than recipients. Finally, we followed long term effects in immortalized radiation sensitive (S1-hTERT) and normal (F11-hTERT) fibroblasts up to 63 days after IR. In F11-hTERT cells CD level was increased until 35 days after IR then reduced back to control level by day 49. In S1-hTERT cells the increased CD level was also normalized by day 42, however a second wave of increased CD incidence appeared by day 49 which was maintained up to day 63 after IR. This second CD wave might be the indication of radiation-induced instability in the mitochondrial genome of S1-hTERT cells. The data demonstrated that measuring CD in mtDNA by qRT-PCR is a reliable and sensitive biomarker to estimate radiation-induced direct and non-targeted effects.

  16. Variety Is Not the Spice of Life for People with Autism Spectrum Disorders: Frequency Ratings of Central, Variable and Inappropriate Aspects of Common Real-Life Events

    ERIC Educational Resources Information Center

    Loth, Eva; Happe, Francesca; Gomez, Juan Carlos

    2010-01-01

    This study used a novel rating task to investigate whether high-functioning individuals with autism spectrum disorder (ASD) have difficulties distinguishing essential from variable aspects of familiar events. Participants read stories about everyday events and judged how often central, variable, and inappropriate event-components normally occur in…

  17. Variety Is Not the Spice of Life for People with Autism Spectrum Disorders: Frequency Ratings of Central, Variable and Inappropriate Aspects of Common Real-Life Events

    ERIC Educational Resources Information Center

    Loth, Eva; Happe, Francesca; Gomez, Juan Carlos

    2010-01-01

    This study used a novel rating task to investigate whether high-functioning individuals with autism spectrum disorder (ASD) have difficulties distinguishing essential from variable aspects of familiar events. Participants read stories about everyday events and judged how often central, variable, and inappropriate event-components normally occur in…

  18. Magnetic resonance imaging at 7T reveals common events in age-related sarcopenia and in the homeostatic response to muscle sterile injury.

    PubMed

    Esposito, Antonio; Campana, Lara; Palmisano, Anna; De Cobelli, Francesco; Canu, Tamara; Santarella, Francesco; Colantoni, Caterina; Monno, Antonella; Vezzoli, Michela; Pezzetti, Giulio; Manfredi, Angelo A; Rovere-Querini, Patrizia; Del Maschio, Alessandro

    2013-01-01

    Skeletal muscle remodeling in response to various noxae physiologically includes structural changes and inflammatory events. The possibility to study those phenomena in-vivo has been hampered by the lack of validated imaging tools. In our study, we have relied on multiparametric magnetic resonance imaging for quantitative monitoring of muscle changes in mice experiencing age-related sarcopenia or active regeneration after sterile acute injury of tibialis anterior muscle induced by cardiotoxin (CTX) injection. The extent of myofibrils' necrosis, leukocyte infiltration, and regeneration have been evaluated and compared with parameters from magnetic resonance imaging: T2-mapping (T2 relaxation time; T2-rt), diffusion-tensor imaging (fractional anisotropy, F.A.) and diffusion weighted imaging (apparent diffusion coefficient, ADC). Inflammatory leukocytes within the perimysium and heterogeneous size of fibers characterized aged muscles. They displayed significantly increased T2-rt (P<0.05) and F.A. (P<0.05) compared with young muscles. After acute damage T2-rt increased in otherwise healthy young muscles with a peak at day 3, followed by a progressive decrease to basal values. F.A. dropped 24 hours after injury and afterward increased above the basal level in the regenerated muscle (from day 7 to day 15) returning to the basal value at the end of the follow up period. The ADC displayed opposite kinetics. T2-rt positively correlated with the number of infiltrating leucocytes retrieved by immunomagnetic bead sorting from the tissue (r = 0.92) and with the damage/infiltration score (r = 0.88) while F.A. correlated with the extent of tissue regeneration evaluated at various time points after injury (r = 0.88). Our results indicate that multiparametric MRI is a sensitive and informative tool for monitoring inflammatory and structural muscle changes in living experimental animals; particularly, it allows identifying the increase of T2-rt and F.A. as common events reflecting

  19. Validity and Reliability of the US National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

    PubMed

    Dueck, Amylou C; Mendoza, Tito R; Mitchell, Sandra A; Reeve, Bryce B; Castro, Kathleen M; Rogak, Lauren J; Atkinson, Thomas M; Bennett, Antonia V; Denicoff, Andrea M; O'Mara, Ann M; Li, Yuelin; Clauser, Steven B; Bryant, Donna M; Bearden, James D; Gillis, Theresa A; Harness, Jay K; Siegel, Robert D; Paul, Diane B; Cleeland, Charles S; Schrag, Deborah; Sloan, Jeff A; Abernethy, Amy P; Bruner, Deborah W; Minasian, Lori M; Basch, Ethan

    2015-11-01

    To integrate the patient perspective into adverse event reporting, the National Cancer Institute developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). To assess the construct validity, test-retest reliability, and responsiveness of PRO-CTCAE items. A total of 975 adults with cancer undergoing outpatient chemotherapy and/or radiation therapy enrolled in this questionnaire-based study between January 2011 and February 2012. Eligible participants could read English and had no clinically significant cognitive impairment. They completed PRO-CTCAE items on tablet computers in clinic waiting rooms at 9 US cancer centers and community oncology practices at 2 visits 1 to 6 weeks apart. A subset completed PRO-CTCAE items during an additional visit 1 business day after the first visit. Primary comparators were clinician-reported Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30). A total of 940 of 975 (96.4%) and 852 of 940 (90.6%) participants completed PRO-CTCAE items at visits 1 and 2, respectively. At least 1 symptom was reported by 938 of 940 (99.8%) participants. Participants' median age was 59 years; 57.3% were female, 32.4% had a high school education or less, and 17.1% had an ECOG PS of 2 to 4. All PRO-CTCAE items had at least 1 correlation in the expected direction with a QLQ-C30 scale (111 of 124, P<.05 for all). Stronger correlations were seen between PRO-CTCAE items and conceptually related QLQ-C30 domains. Scores for 94 of 124 PRO-CTCAE items were higher in the ECOG PS 2 to 4 vs 0 to 1 group (58 of 124, P<.05 for all). Overall, 119 of 124 items met at least 1 construct validity criterion. Test-retest reliability was 0.7 or greater for 36 of 49 prespecified items (median [range] intraclass correlation coefficient, 0.76 [0.53-.96]). Correlations between PRO-CTCAE item changes and

  20. Population structure within lineages of Wheat streak mosaic virus derived from a common founding event exhibits stochastic variation inconsistent with the deterministic quasi-species model

    SciTech Connect

    French, Roy; Stenger, Drake C. . E-mail: dstenger@unlnotes.unl.edu

    2005-12-20

    Structure of Wheat streak mosaic virus (WSMV) populations derived from a common founding event and subjected to serial passage at high multiplicity of infection (MOI) was evaluated. The founding population was generated by limiting dilution inoculation. Lineages of known pedigree were sampled at passage 9 (two populations) and at passage 15, with (three populations) or without mixing (four populations) of lineages at passage 10. Polymorphism within each population was assessed by sequencing 17-21 clones containing a 1371 nt region (WSMV-Sidney 81 nts 8001-9371) encompassing the entire coat protein cistron and flanking regions. Mutation frequency averaged {approx}5.0 x 10{sup -4}/nt across all populations and ranged from 2.4 to 11.6 x 10{sup -4}/nt within populations, but did not consistently increase or decrease with the number of passages removed from the founding population. Shared substitutions (19 nonsynonymous, 10 synonymous, and 3 noncoding) occurred at 32 sites among 44 haplotypes. Only four substitutions became fixed (frequency = 100%) within a population and nearly one third (10/32) never achieved a frequency of 10% or greater in any sampled population. Shared substitutions were randomly distributed with respect to genome position, with transitions outnumbering transversions 5.4:1 and a clear bias for A to G and U to C substitutions. Haplotype composition of each population was unique with complexity of each population varying unpredictably, in that the number and frequency of haplotypes within a lineage were not correlated with number of passages removed from the founding population or whether the population was derived from a single or mixed lineage. The simplest explanation is that plant virus lineages, even those propagated at high MOI, are subject to frequent, narrow genetic bottlenecks during systemic movement that result in low effective population size and stochastic changes in population structure upon serial passage.

  1. Common and segregated neural substrates for automatic conceptual and affective priming as revealed by event-related functional magnetic resonance imaging.

    PubMed

    Liu, Hongyan; Hu, Zhiguo; Peng, Danling; Yang, Yanhui; Li, Kuncheng

    2010-02-01

    The brain activity associated with automatic semantic priming has been extensively studied. Thus far there has been no prior study that directly contrasts the neural mechanisms of semantic and affective priming. The present study employed event-related fMRI to examine the common and distinct neural bases underlying conceptual and affective priming with a lexical decision task. A special type of emotional word, a dual-meaning word containing both conceptual meaning and affective meaning, was adopted as target. Short stimulus onset asynchrony (SOA) (50 ms) was used to emphasize automatic processing. Fifteen participants were scanned in the present study. We found that the left middle/superior temporal gyrus was the brain region involved in both automatic conceptual and affective priming effects, suggesting general lexical-semantic processing that share in the two types of priming. The left inferior frontal gyrus and right superior temporal gyrus were found to be the conceptual-specific areas in automatic priming effect, consistent with the role of these areas in more extensive within-category semantic processes. The results also revealed that the left fusiform gyrus and left insula were the affective-specific regions in automatic priming effect, demonstrating the involvement of the left fusiform gyrus in automatic affective priming effect, and clarifying the role of the insula in emotional processing rather than conceptual processing. Despite comparable behavioral effects of automatic conceptual priming and affective priming, the present study revealed a neural dissociation of the two types of priming, as well as the shared neural bases.

  2. A Comparative Study of Treatment-Emergent Adverse Events Following Use of Common Bowel Preparations Among a Colonoscopy Screening Population: Results from a Post-Marketing Observational Study.

    PubMed

    Anastassopoulos, Kathryn; Farraye, Francis A; Knight, Tyler; Colman, Sam; Cleveland, Mark vB; Pelham, Russell W

    2016-10-01

    Colonoscopy may be one of the most frequent elective procedures in older adults and is associated with a low occurrence of complications. However, reduction of risks attributable to the bowel preparation may be achieved with the use of effective and safer products. The aim of this study was to examine the incidence of treatment-emergent adverse events (TEAEs) associated with SUPREP(®) [oral sulfate solution (OSS)] and other common prescription bowel preparations (non-OSS). This real-world, observational study used de-identified health insurance claims and laboratory results to identify TEAEs in the 3 months following screening colonoscopy in adults with a prescription for a bowel preparation in the prior 60 days. The unadjusted and adjusted (controlling for patient risk factors) cumulative incidences of TEAEs were estimated using Kaplan-Meier and Poisson regression, respectively. Among patients ≥45 years, the overall cumulative incidence was significantly lower (p < 0.001) in the OSS cohort than in the non-OSS cohort (unadjusted: 2.31 vs. 2.89 %; adjusted: 1.61 vs. 1.95 %), with significantly lower acute cardiac conditions (1.56 vs. 1.90 %; p < 0.001), renal failure/other serious renal diseases (OSS: 0.21 %, non-OSS: 0.32 %; p < 0.001), and serum electrolyte abnormalities (OSS: 0.39 %, non-OSS: 0.49 %; p = 0.017). There were no significant differences between cohorts in death, seizure disorders, aggravation of gout, and ischemic colitis. Results were similar in the adjusted cumulative incidences. In actual use, the overall cumulative incidence of TEAEs was significantly lower in the OSS cohort, demonstrating that OSS is as safe as, or possibly safer than, non-OSS prescription bowel preparations.

  3. The use of global transcriptional analysis to reveal the biological and cellular events involved in distinct development phases of Trichophyton rubrum conidial germination

    PubMed Central

    Liu, Tao; Zhang, Qian; Wang, Lingling; Yu, Lu; Leng, Wenchuan; Yang, Jian; Chen, Lihong; Peng, Junping; Ma, Li; Dong, Jie; Xu, Xingye; Xue, Ying; Zhu, Yafang; Zhang, Wenliang; Yang, Li; Li, Weijun; Sun, Lilian; Wan, Zhe; Ding, Guohui; Yu, Fudong; Tu, Kang; Qian, Ziliang; Li, Ruoyu; Shen, Yan; Li, Yixue; Jin, Qi

    2007-01-01

    Background Conidia are considered to be the primary cause of infections by Trichophyton rubrum. Results We have developed a cDNA microarray containing 10250 ESTs to monitor the transcriptional strategy of conidial germination. A total of 1561 genes that had their expression levels specially altered in the process were obtained and hierarchically clustered with respect to their expression profiles. By functional analysis, we provided a global view of an important biological system related to conidial germination, including characterization of the pattern of gene expression at sequential developmental phases, and changes of gene expression profiles corresponding to morphological transitions. We matched the EST sequences to GO terms in the Saccharomyces Genome Database (SGD). A number of homologues of Saccharomyces cerevisiae genes related to signalling pathways and some important cellular processes were found to be involved in T. rubrum germination. These genes and signalling pathways may play roles in distinct steps, such as activating conidial germination, maintenance of isotropic growth, establishment of cell polarity and morphological transitions. Conclusion Our results may provide insights into molecular mechanisms of conidial germination at the cell level, and may enhance our understanding of regulation of gene expression related to the morphological construction of T. rubrum. PMID:17428342

  4. Genomic losses at 5q13.2 and 8p23.1 in dysplastic hepatocytes are common events in hepatitis B virus-related hepatocellular carcinoma

    PubMed Central

    ZHAO, ZHANG; CHEN, GUANG-YONG; LONG, JIANG; LI, HAI; HUANG, JIAN

    2015-01-01

    Chromosomal loci with genomic imbalances are frequently identified in hepatocellular carcinoma (HCC). Greater than two-thirds of hepatitis B virus (HBV)-related HCCs originate from liver cirrhosis following a duration of up to two decades. However, it is unclear whether these genomic imbalances occur and accumulate in dysplastic hepatocytes of the cirrhotic liver during the progression from regenerated nodules to preneoplastic lesions, including dysplastic nodules (DN). In the present study, high-grade DNs (HGDNs) of HBV-related liver cirrhosis were screened to identify loci with genomic imbalances, and the frequency of the identified loci in a group of HCCs was analyzed in order to determine whether there may be a genetic link between liver cirrhosis and HCC. Genomic DNA was extracted from six HGDNs of two cases of HBV-related liver cirrhosis and subjected to array comparative genomic hybridization (CGH) analysis with a NimbleGen 720K microarray. Loci with the most frequently observed genomic imbalances in DNs were further analyzed in 83 cases of HCC by differential polymerase chain reaction (PCR) and quantitative PCR. The array CGH analysis revealed that the majority of genomic imbalances in the HGDNs were genomic losses of small segments, with loss of heterozygosity (LOH) at 5q13.2 and 8p23.1 identified most frequently. Of the 83 HCC cases, 30 (36.1%) cases were identified with LOH at 5q13.2, where known tumor-associated genes are located, including general transcription factor IIH subunit 2 (GTF2H2), baculoviral IAP repeat-containing protein 1 (BIRC1) and occludin (OCLN). LOH frequency at 8p23.1 in HCC was 61.29% (D8S1130) and 68.4% (D8S503) respectively, similar to the results obtained in previous studies. In conclusion, the results of the present study provided evidence that genomic losses at 5q13.2 and 8p23.1 identified in dysplastic hepatocytes of the cirrhotic liver are common events in HCC. HCC-associated chromosomal abnormalities may occur and accumulate

  5. Cosmogenic Noble Gases and Their Production Rates in Eucrites, Diogenites, and Howardites: Common Asteroid Break-up Events 38 Ma, 21 Ma, and 6 MA Ago

    NASA Astrophysics Data System (ADS)

    Eugster, O.; Michel, Th.

    1993-07-01

    It is likely that the eucrites and their associates, the howardites and diogenites, sample the surface and shallow interior of a single parent body, possibly 4 Vesta (cf. [1] and [2]). A break-up event that reaches deep enough may, thus, eject asteroidal fragments representing meteorites from all three classes. In this work we present a comprehensive investigation of the exposure age clusters for howardites, eucrites, and diogenites (HEDs). Cosmic-ray exposure ages critically depend on the production rates for cosmic-ray produced nuclei. For eucrites shielding independent production rates for ^21Ne and ^38Ar have been determined previously [3,4]. We now present production rates of ^3He, ^21Ne, ^33Ar, ^78Kr, ^83Kr, and ^126Xe for eucrites, howardites, and diogenites as a function of shielding, where appropriate, and of target element abundances as derived on the basis of ^81Kr-Kr ages. E.g., for ^21Ne we obtain: P(sub)21 (EUC) = 8.43 P^1(sub)21 [16.1 (^22Ne/^21Ne)(sub)c - 10.3]^-1, P(sub)21 (HOW) = 6.16 P^1(sub)21 [18.1 (^22Ne/^21Ne)(sub)c - 14.1]^-1, P(sub)21 (DIO) = 4.81 P^1(sub)21 [25.7 (^22Ne/^21Ne)(sub)c - 23.7]^-1, where P^1(sub)21 = 1.63 [Mg] + 0.6 [Al] + 0.32 [Si] + 0.22 [S] + 0.07 [Ca] + 0.021 [Fe + Ni] as given by [3]. (Elemental abundance [x] in weight %, P(sub)21 in 10^10 cm^3 STP/g, Ma). Average cosmic-ray exposure ages were derived from as many nuclei as possible for 14 HEDs analyzed by us (see also [5,6]) and for those compiled by [7]. Two major exposure age clusters at 21 and 38 Ma are represented in all three meteorite classes (Fig. 1). In the cluster at 21 +- 4 Ma are 12 out of 39 eucrites, 6 out of 14 howardites, and 7out of 12 diogenites. In the cluster at 38 +- 8 Ma are 6 eucrites, 5 howardites, and 4 diogenites. A third common break-up event at 5 +- 1 Ma is indicated by the remaining diogenite, three eucrites, and one howardite. Schultz [8] found major clusters for eucrites at 13, 21, 26, and 40 Ma for howardites around 10 and 24 Ma, and for

  6. Flooding of the Great River during the Common Era: A Paleohydrological Record of High Magnitude Flood Events from the Central Mississippi River Valley

    NASA Astrophysics Data System (ADS)

    Williams, J. W.; Munoz, S. E.; Gruley, K. E.; Massie, A.

    2014-12-01

    Streamflow characteristics are known to be sensitive to changes in climate, but few continuous records of flooding exist to evaluate the response of hydrological systems to centennial- and millennia-scale climate changes. Here, we present sedimentary records from two oxbow lakes (Horseshoe Lake and Grassy Lake, Illinois, USA) in the central Mississippi River valley (CMRV) that display abrupt shifts in sediment composition and particle-size consistent with deposition by floodwaters immediately following inundation of the floodplain. The sedimentary record at Horseshoe Lake begins ca. AD 100 and displays five major flood events, with four of these occurring after ca. AD 1100. Situated 200 km downstream, the record from Grassy Lake begins later, ca. AD 800, and also shows four major flood events after ca. AD 1100. An analysis of synchronicity using Bayesian age modelling software shows high likelihoods that the four overlapping flood events occurred at the same time, confirming that these events resulted from flooding of the Mississippi River. The most recent event we record at AD 1840 ± 50 corresponds to the AD 1844 flood, the largest flood by discharge (37 m3/s) measured by the gauging station at St. Louis, Missouri, indicating that our sedimentary records document high magnitude flood events. Together, our two sedimentary records show a major shift in the frequency of high magnitude flooding in the central Mississippi River at ca. AD 1100. From AD 100 - AD 1100, only one relatively subtle flood event is recorded, but from AD 1100 - AD 1900, four high magnitude floods deposited distinctive sediment at both sites. The period of infrequent flooding corresponds to a time of agricultural intensification and population growth in the CMRV, while the entire region was abandoned when flood frequency increased. The pronounced shift in flood frequency we observe in our records at ca. AD 1100 begins during the Medieval Climate Anomaly (MCA; AD 950 - AD 1250), a period of

  7. Multi-event capture-recapture modeling of host-pathogen dynamics among European rabbit populations exposed to myxoma and Rabbit Hemorrhagic Disease Viruses: common and heterogeneous patterns.

    PubMed

    Santoro, Simone; Pacios, Isa; Moreno, Sacramento; Bertó-Moran, Alejandro; Rouco, Carlos

    2014-04-05

    Host-pathogen epidemiological processes are often unclear due both to their complexity and over-simplistic approaches used to quantify them. We applied a multi-event capture-recapture procedure on two years of data from three rabbit populations to test hypotheses about the effects on survival of, and the dynamics of host immunity to, both myxoma virus and Rabbit Hemorrhagic Disease Virus (MV and RHDV). Although the populations shared the same climatic and management conditions, MV and RHDV dynamics varied greatly among them; MV and RHDV seroprevalences were positively related to density in one population, but RHDV seroprevalence was negatively related to density in another. In addition, (i) juvenile survival was most often negatively related to seropositivity, (ii) RHDV seropositives never had considerably higher survival, and (iii) seroconversion to seropositivity was more likely than the reverse. We suggest seropositivity affects survival depending on trade-offs among antibody protection, immunosuppression and virus lethality. Negative effects of seropositivity might be greater on juveniles due to their immature immune system. Also, while RHDV directly affects survival through the hemorrhagic syndrome, MV lack of direct lethal effects means that interactions influencing survival are likely to be more complex. Multi-event modeling allowed us to quantify patterns of host-pathogen dynamics otherwise difficult to discern. Such an approach offers a promising tool to shed light on causative mechanisms.

  8. Multi-event capture–recapture modeling of host–pathogen dynamics among European rabbit populations exposed to myxoma and Rabbit Hemorrhagic Disease Viruses: common and heterogeneous patterns

    PubMed Central

    2014-01-01

    Host–pathogen epidemiological processes are often unclear due both to their complexity and over-simplistic approaches used to quantify them. We applied a multi-event capture–recapture procedure on two years of data from three rabbit populations to test hypotheses about the effects on survival of, and the dynamics of host immunity to, both myxoma virus and Rabbit Hemorrhagic Disease Virus (MV and RHDV). Although the populations shared the same climatic and management conditions, MV and RHDV dynamics varied greatly among them; MV and RHDV seroprevalences were positively related to density in one population, but RHDV seroprevalence was negatively related to density in another. In addition, (i) juvenile survival was most often negatively related to seropositivity, (ii) RHDV seropositives never had considerably higher survival, and (iii) seroconversion to seropositivity was more likely than the reverse. We suggest seropositivity affects survival depending on trade-offs among antibody protection, immunosuppression and virus lethality. Negative effects of seropositivity might be greater on juveniles due to their immature immune system. Also, while RHDV directly affects survival through the hemorrhagic syndrome, MV lack of direct lethal effects means that interactions influencing survival are likely to be more complex. Multi-event modeling allowed us to quantify patterns of host–pathogen dynamics otherwise difficult to discern. Such an approach offers a promising tool to shed light on causative mechanisms. PMID:24708296

  9. Datasets used in Oshida et al. Disruption of STAT5b-Regulated Sexual Dimorphism of the Liver Transcriptome by Diverse Factors Is a Common Event. PLOS ONE 2016 Mar 9;11(3):e0148308

    EPA Pesticide Factsheets

    Includes 1) list of genes in the STAT5b biomarker and 2) list of accession numbers for microarray datasets used in study.This dataset is associated with the following publication:Oshida, K., N. Vasani, D. Waxman, and C. Corton. Disruption of STAT5b-Regulated Sexual Dimorphism of the Liver Transcriptome by Diverse Factors Is a Common Event. PLoS ONE. Public Library of Science, San Francisco, CA, USA, 11(3): NA, (2016).

  10. Architected Cellular Materials

    NASA Astrophysics Data System (ADS)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  11. Lrrk2 R1441G-related Parkinson's disease: evidence of a common founding event in the seventh century in Northern Spain.

    PubMed

    Mata, Ignacio F; Hutter, Carolyn M; González-Fernández, María C; de Pancorbo, Marian M; Lezcano, Elena; Huerta, Cecilia; Blazquez, Marta; Ribacoba, Renee; Guisasola, Luis M; Salvador, Carlos; Gómez-Esteban, Juan C; Zarranz, Juan J; Infante, Jon; Jankovic, Joseph; Deng, Hao; Edwards, Karen L; Alvarez, Victoria; Zabetian, Cyrus P

    2009-10-01

    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene together represent the most common genetic determinant of Parkinson's disease (PD) identified to date. The vast majority of patients with LRRK2-related PD reported in the literature carry one of three pathogenic substitutions: G2019S, R1441C, or R1441G. While G2019S and R1441C are geographically widespread, R1441G is most prevalent in the Basque Country and is rare outside of Northern Spain. We sought to better understand the processes that have shaped the current distribution of R1441G. We performed a haplotype analysis of 29 unrelated PD patients heterozygous for R1441G and 85 wild-type controls using 20 markers that spanned 15.1 Mb across the LRRK2 region. Nine of the patients were of Basque origin and 20 were non-Basques. We inferred haplotypes using a Bayesian approach and utilized a maximum-likelihood method to estimate the age of the most recent common ancestor. Significant but incomplete allele sharing was observed over a distance of 6.0 Mb and a single, rare ten-marker haplotype 5.8 Mb in length was seen in all mutation carriers. We estimate that the most recent common ancestor lived 1,350 (95% CI, 1,020-1,740) years ago in approximately the seventh century. We hypothesize that R1441G originated in the Basque population and that dispersion of the mutation then occurred through short-range gene flow that was largely limited to nearby regions in Spain.

  12. NOTCH2 and FLT3 gene mis-splicings are common events in patients with acute myeloid leukemia (AML): new potential targets in AML

    PubMed Central

    Bar-Natan, Michal; Haibe-Kains, Benjamin; Pilarski, Patrick M.; Bach, Christian; Pevzner, Samuel; Calimeri, Teresa; Avet-Loiseau, Herve; Lode, Laurence; Verselis, Sigitas; Fox, Edward A.; Galinsky, Ilene; Mathews, Steven; Dagogo-Jack, Ibiayi; Wadleigh, Martha; Steensma, David P.; Motyckova, Gabriela; Deangelo, Daniel J.; Quackenbush, John; Tenen, Daniel G.; Stone, Richard M.; Griffin, James D.

    2014-01-01

    Our previous studies revealed an increase in alternative splicing of multiple RNAs in cells from patients with acute myeloid leukemia (AML) compared with CD34+ bone marrow cells from normal donors. Aberrantly spliced genes included a number of oncogenes, tumor suppressor genes, and genes involved in regulation of apoptosis, cell cycle, and cell differentiation. Among the most commonly mis-spliced genes (>70% of AML patients) were 2, NOTCH2 and FLT3, that encode myeloid cell surface proteins. The splice variants of NOTCH2 and FLT3 resulted from complete or partial exon skipping and utilization of cryptic splice sites. Longitudinal analyses suggested that NOTCH2 and FLT3 aberrant splicing correlated with disease status. Correlation analyses between splice variants of these genes and clinical features of patients showed an association between NOTCH2-Va splice variant and overall survival of patients. Our results suggest that NOTCH2 and FLT3 mis-splicing is a common characteristic of AML and has the potential to generate transcripts encoding proteins with altered function. Thus, splice variants of these genes might provide disease markers and targets for novel therapeutics. PMID:24574459

  13. THE FAST-ROTATING, LOW-GRAVITY SUBDWARF B STAR EC 22081-1916: REMNANT OF A COMMON ENVELOPE MERGER EVENT

    SciTech Connect

    Geier, S.; Classen, L.; Heber, U.

    2011-05-20

    Hot subdwarf B stars (sdBs) are evolved core helium-burning stars with very thin hydrogen envelopes. In order to form an sdB, the progenitor has to lose almost all of its hydrogen envelope right at the tip of the red-giant branch. In binary systems, mass transfer to the companion provides the extraordinary mass loss required for their formation. However, apparently single sdBs exist as well and their formation has been unclear for decades. The merger of helium white dwarfs (He-WDs) leading to an ignition of core helium burning or the merger of a helium core and a low-mass star during the common envelope phase have been proposed as processes leading to sdB formation. Here we report the discovery of EC 22081-1916 as a fast-rotating, single sdB star of low gravity. Its atmospheric parameters indicate that the hydrogen envelope must be unusually thick, which is at variance with the He-WD merger scenario, but consistent with a common envelope merger of a low-mass, possibly substellar object with a red-giant core.

  14. Linguistic validation of the Spanish version of the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

    PubMed

    Arnold, Benjamin; Mitchell, Sandra A; Lent, Lauren; Mendoza, Tito R; Rogak, Lauren J; Barragán, Natalie M; Willis, Gordon; Medina, Mauricio; Lechner, Suzanne; Penedo, Frank J; Harness, Jay K; Basch, Ethan M

    2016-07-01

    The U.S. NCI's PRO-CTCAE is a library of self-report items for assessing symptomatic adverse events in cancer clinical trials from the patient perspective. The aim of this study was to translate and linguistically validate a Spanish version. PRO-CTCAE's 124 items were translated from English into Spanish using multiple forward and back translations. Native Spanish speakers undergoing cancer treatment were enrolled at six cancer treatment sites. Participants each completed approximately 50 items and were then interviewed using cognitive probes. The interviews were analyzed at the item level by linguistic themes, and responses were examined for evidence of equivalence to English. Items for which ≥20 % of participants experienced difficulties were reviewed, and phrasing was revised and then retested in subsequent interviews. Items where <20 % of respondents experienced difficulties were also reviewed and were considered for rephrasing and retesting. One hundred nine participants from diverse Spanish-speaking countries were enrolled (77 in Round 1 and 32 in Round 2). A majority of items were well comprehended in Round 1. Two items presented difficulties in ≥20 % of participants and were revised/retested without further difficulties. Two items presented difficulties in <20 %, and when retested exhibited no further difficulties. Two items presented difficulties in <20 %, but were not revised due to lack of alternatives. Sixteen items presented difficulties in ≤12 % and were not revised because difficulties were minor. The Spanish PRO-CTCAE has been developed and refined for use in Spanish-speaking populations, with high levels of comprehension and equivalence to the English PRO-CTCAE. ClinicalTrials.gov:NCT01436240.

  15. Adverse events after surgery for nonmalignant colon polyps are common and associated with increased length of stay and costs.

    PubMed

    Keswani, Rajesh N; Law, Ryan; Ciolino, Jody D; Lo, Amy A; Gluskin, Adam B; Bentrem, David J; Komanduri, Sri; Pacheco, Jennifer A; Grande, David; Thompson, William K

    2016-08-01

    Endoscopic resection (ER) is a safe and effective treatment for nonmalignant complex colorectal polyps (complex polyps). Surgical resection (SR) remains prevalent despite limited outcomes data. We aimed to evaluate SR outcomes for complex polyps and compare SR outcomes to those of ER. We performed a single-center, retrospective, cohort study of all patients undergoing SR (2003-2013) and ER (2011-2013) for complex polyps. We excluded patients with invasive carcinoma from the SR cohort. Primary outcomes were 12-month adverse event (AE) rate, length of stay (LOS), and costs. SR outcomes over a 3-year period (2011-2013) were compared with the overlapping ER cohort. Over the 11-year period, 359 patients (mean [± SD] age 64 ± 11 years) underwent SR (58% laparoscopic) for complex polyps. In total, 17% experienced an AE, and 3% required additional surgery; 12-month mortality was 1%. Including readmissions, median LOS was 5 days (IQR 4-7 days), and costs were $14,528. When an AE occurred, costs ($25,557 vs $14,029; P < .0001) and LOS (11 vs 5 days; P < .0001) significantly increased. From 2011 to 2013, 198 patients were referred for ER, and 73 underwent primary SR (70% laparoscopic). There was a lower AE rate for ER versus primary SR (10% vs 18%; P = .09). ER costs (including rescue SR, when required) were lower than those of primary SR ($2152 vs $15,264; P < .0001). AEs occur in approximately one-sixth of patients after SR for complex polyps. ER-accounting for rescue SR caused by malignancy, AEs, or incomplete resection-is associated with markedly lower costs than SR. These data should be used when counseling patients about treatment options for complex polyps. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  16. Unique cellular events occurring during the initial interaction of macrophages with matrix-retained or methylated aggregated low density lipoprotein (LDL). Prolonged cell-surface contact during which ldl-cholesteryl ester hydrolysis exceeds ldl protein degradation.

    PubMed

    Buton, X; Mamdouh, Z; Ghosh, R; Du, H; Kuriakose, G; Beatini, N; Grabowski, G A; Maxfield, F R; Tabas, I

    1999-11-05

    A critical event in atherogenesis is the interaction of arterial wall macrophages with subendothelial lipoproteins. Although most studies have investigated this interaction by incubating cultured macrophages with monomeric lipoproteins dissolved in media, arterial wall macrophages encounter lipoproteins that are mostly bound to subendothelial extracellular matrix, and these lipoproteins are often aggregated or fused. Herein, we utilize a specialized cell-culture system to study the initial interaction of macrophages with aggregated low density lipoprotein (LDL) bound to extracellular matrix. The aggregated LDL remains extracellular for a relatively prolonged period of time and becomes lodged in invaginations in the surface of the macrophages. As expected, the degradation of the protein moiety of the LDL was very slow. Remarkably, however, hydrolysis of the cholesteryl ester (CE) moiety of the LDL was 3-7-fold higher than that of the protein moiety, in stark contrast to the situation with receptor-mediated endocytosis of acetyl-LDL. Similar results were obtained using another experimental system in which the degradation of aggregated LDL protein was delayed by LDL methylation rather than by retention on matrix. Additional experiments indicated the following properties of this interaction: (a) LDL-CE hydrolysis is catalyzed by lysosomal acid lipase; (b) neither scavenger receptors nor the LDL receptor appear necessary for the excess LDL-CE hydrolysis; and (c) LDL-CE hydrolysis in this system is resistant to cellular potassium depletion, which further distinguishes this process from receptor-mediated endocytosis. In summary, experimental systems specifically designed to mimic the in vivo interaction of arterial wall macrophages with subendothelial lipoproteins have demonstrated an initial period of prolonged cell-surface contact in which CE hydrolysis exceeds protein degradation.

  17. Real-time analysis of the detailed sequence of cellular events in mAb-mediated complement-dependent cytotoxicity of B-cell lines and of chronic lymphocytic leukemia B-cells.

    PubMed

    Lindorfer, Margaret A; Cook, Erika M; Tupitza, Jillian C; Zent, Clive S; Burack, Richard; de Jong, Rob N; Beurskens, Frank J; Schuurman, Janine; Parren, Paul W H I; Taylor, Ronald P

    2016-02-01

    Complement-dependent cytotoxicity is an important mechanism of action of certain mAbs used in cancer immunotherapy, including ofatumumab and rituximab. However, the detailed sequence of cellular changes that occur in nucleated cells attacked by mAb and complement has not been delineated. Recently developed CD20 mAbs, engineered to form hexamers on binding to cells, react with B-cells in serum, chelate C1q, and then activate complement and promote cell killing considerably more effectively than their wild-type precursors. We used these engineered mAbs as a model to investigate the sequence of events that occur when mAbs bind to B-cell lines and to primary cells from patients with chronic lymphocytic leukemia and then activate complement. Based on four-color confocal microscopy real-time movies and high resolution digital imaging, we find that after CD20 mAb binding and C1q uptake, C3b deposits on cells, followed by Ca(2+) influx, revealed by bright green signals generated on cells labeled with FLUO-4, a Ca(2+) indicator. The bright FLUO-4/Ca(2+) signal fades, replaced by punctate green signals in mitochondria, indicating Ca(2+) localization. This step leads to mitochondrial poisoning followed by cell death. The entire sequence is completed in <2 min for hexamerization-enhanced CD20 mAb-mediated killing. To our knowledge this is the first time the entire process has been characterized in detail in real time. By identifying multiple discrete steps in the cytotoxic pathway for nucleated cells our findings may inform future development and more effective application of complement-fixing mAbs to cancer treatment.

  18. Self-reported and parent-reported pain for common painful events in high-functioning children and adolescents with autism spectrum disorder.

    PubMed

    Bandstra, Nancy F; Johnson, Shannon A; Filliter, Jillian H; Chambers, Christine T

    2012-10-01

    Previous research suggests that children with autism spectrum disorders (ASD) are at a higher risk for painful experiences, but there is limited research examining pain in children with ASD. The current study examined self-reported and parent-reported pain in 20 high-functioning youth with ASD (17 boys; 3 girls) and 20 typically developing controls (16 boys; 4 girls) ranging in age from 9 to 18 years and matched on age and IQ. Participants with and without ASD rated their hypothetical pain in a series of pictures depicting common childhood situations. They also rated the amount of pain they would expect to feel (using the Faces Pain Scale-Revised and a Numeric Rating Scale) in a series of validated hypothetical pain situations depicted in cartooned images (eg, scraping knee on sidewalk). Parents rated the amount of pain they would expect their child to show in each of the same cartoon stimuli. There were no significant differences between pain vignette ratings of youth with ASD and their non-ASD peers or in the ratings provided by their parents. High-functioning youth with ASD were able to successfully use both of the self-report scales to rate pain. This is the first study to successfully obtain self-report of pain from youth with ASD. Implications for the understanding of pain and pain assessment in high-functioning youth with ASD are discussed.

  19. Polyandry Is a Common Event in Wild Populations of the Tsetse Fly Glossina fuscipes fuscipes and May Impact Population Reduction Measures

    PubMed Central

    Bonomi, Angelica; Bassetti, Federico; Gabrieli, Paolo; Beadell, Jon; Falchetto, Marco; Scolari, Francesca; Gomulski, Ludvik M.; Regazzini, Eugenio; Ouma, Johnson O.; Caccone, Adalgisa; Okedi, Loyce M.; Attardo, Geoffrey M.; Guglielmino, Carmela R.; Aksoy, Serap; Malacrida, Anna R.

    2011-01-01

    Background Glossina fuscipes fuscipes is the main vector of human and animal trypanosomiasis in Africa, particularly in Uganda. Attempts to control/eradicate this species using biological methods require knowledge of its reproductive biology. An important aspect is the number of times a female mates in the wild as this influences the effective population size and may constitute a critical factor in determining the success of control methods. To date, polyandry in G.f. fuscipes has not been investigated in the laboratory or in the wild. Interest in assessing the presence of remating in Ugandan populations is driven by the fact that eradication of this species is at the planning stage in this country. Methodology/Principal Findings Two well established populations, Kabukanga in the West and Buvuma Island in Lake Victoria, were sampled to assess the presence and frequency of female remating. Six informative microsatellite loci were used to estimate the number of matings per female by genotyping sperm preserved in the female spermathecae. The direct count of the minimum number of males that transferred sperm to the spermathecae was compared to Maximum Likelihood and Bayesian probability estimates. The three estimates provided evidence that remating is common in the populations but the frequency is substantially different: 57% in Kabukanga and 33% in Buvuma. Conclusions/Significance The presence of remating, with females maintaining sperm from different mates, may constitute a critical factor in cases of re-infestation of cleared areas and/or of residual populations. Remating may enhance the reproductive potential of re-invading propagules in terms of their effective population size. We suggest that population age structure may influence remating frequency. Considering the seasonal demographic changes that this fly undergoes during the dry and wet seasons, control programmes based on SIT should release large numbers of sterile males, even in residual surviving target

  20. Polyandry is a common event in wild populations of the Tsetse fly Glossina fuscipes fuscipes and may impact population reduction measures.

    PubMed

    Bonomi, Angelica; Bassetti, Federico; Gabrieli, Paolo; Beadell, Jon; Falchetto, Marco; Scolari, Francesca; Gomulski, Ludvik M; Regazzini, Eugenio; Ouma, Johnson O; Caccone, Adalgisa; Okedi, Loyce M; Attardo, Geoffrey M; Guglielmino, Carmela R; Aksoy, Serap; Malacrida, Anna R

    2011-06-01

    Glossina fuscipes fuscipes is the main vector of human and animal trypanosomiasis in Africa, particularly in Uganda. Attempts to control/eradicate this species using biological methods require knowledge of its reproductive biology. An important aspect is the number of times a female mates in the wild as this influences the effective population size and may constitute a critical factor in determining the success of control methods. To date, polyandry in G.f. fuscipes has not been investigated in the laboratory or in the wild. Interest in assessing the presence of remating in Ugandan populations is driven by the fact that eradication of this species is at the planning stage in this country. Two well established populations, Kabukanga in the West and Buvuma Island in Lake Victoria, were sampled to assess the presence and frequency of female remating. Six informative microsatellite loci were used to estimate the number of matings per female by genotyping sperm preserved in the female spermathecae. The direct count of the minimum number of males that transferred sperm to the spermathecae was compared to Maximum Likelihood and Bayesian probability estimates. The three estimates provided evidence that remating is common in the populations but the frequency is substantially different: 57% in Kabukanga and 33% in Buvuma. The presence of remating, with females maintaining sperm from different mates, may constitute a critical factor in cases of re-infestation of cleared areas and/or of residual populations. Remating may enhance the reproductive potential of re-invading propagules in terms of their effective population size. We suggest that population age structure may influence remating frequency. Considering the seasonal demographic changes that this fly undergoes during the dry and wet seasons, control programmes based on SIT should release large numbers of sterile males, even in residual surviving target populations, in the dry season.

  1. Concept Elicitation Phase for the Pediatric Patient-Reported Outcome Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Measure Development

    PubMed Central

    Weaver, Meaghann; Reeve, Bryce; Baker, Justin; Martens, Christa; McFatrich, Molly; Mowbray, Catriona; Palma, Diana; Sung, Lillian; Tomlinson, Deborah; Withycombe, Janice; Hinds, Pamela

    2015-01-01

    Background Symptoms arising from disease or treatment are subjective experiences. Insight into pediatric oncology treatment side effects or symptoms is ideally obtained from direct inquiry to the ill child. A concept elicitation phase in a patient-reported outcome instrument design provides opportunity to elicit children's voices to shape cancer symptom selection and terminology. Methods Symptom data were collected from 96 children with cancer, ages 7-20 years undergoing oncologic treatment at seven pediatric oncology sites in the United States and Canada through semi-structured, one-on-one, voice-recorded interviews. Results The mean number of symptoms reported per child over the prior seven days was 1.49 (range 0-7, median 1, SD 1.56). The most common symptoms across all age groups were: feeling tired or fatigue, nausea or vomiting, aches or pains, and weakness. There was not a statistically significant correlation between self-reported wellness and the number of symptoms reported (r= -0.156, n = 65, p = 0.215) or the number of symptoms reported based on age group or diagnosis type. Forty participants reported experiencing a change in their body in the past week with one-third of these changes unanticipated. Only by directly asking about feelings were emotional symptoms revealed, as 90.6% of interviewees who discussed feelings (n=48/53) did so only in the context of direct questioning on feelings. Adolescents were more likely than younger children to discuss feelings as part of the interview. Conclusion(s) Concept elicitation, from children and adolescents, has the potential to enable researchers to develop age-appropriate, accurately representative patient-reported outcome measures. PMID:26421973

  2. Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.

    PubMed

    Sada, Kiminori; Nishikawa, Takeshi; Kukidome, Daisuke; Yoshinaga, Tomoaki; Kajihara, Nobuhiro; Sonoda, Kazuhiro; Senokuchi, Takafumi; Motoshima, Hiroyuki; Matsumura, Takeshi; Araki, Eiichi

    2016-01-01

    We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

  3. Danish Translation and Linguistic Validation of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

    PubMed

    Bæksted, Christina; Nissen, Aase; Pappot, Helle; Bidstrup, Pernille Envold; Mitchell, Sandra A; Basch, Ethan; Dalton, Susanne Oksbjerg; Johansen, Christoffer

    2016-08-01

    The Common Terminology Criteria for Adverse Events (CTCAE) is the basis for standardized clinician-based grading and reporting of adverse events in cancer clinical trials. The U.S. National Cancer Institute has developed the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE) to incorporate patient self-reporting of symptomatic adverse events. The aim of the study was to translate and linguistically validate a Danish language version of PRO-CTCAE. The U.S. English language PRO-CTCAE was translated into Danish using forward and backward procedures with reconciliation. The linguistic validity of the PRO-CTCAE Danish was examined in two successive rounds of semistructured cognitive interviews in a sample of 56 patients equally distributed by gender and cancer type (prostate, head and neck, lung, breast, gynecological, gastrointestinal, and hematological cancer), and who were currently undergoing cancer treatment. In the first round of linguistic validation (n = 42), the phrasing of five symptomatic toxicities was adjusted, and the refined phrasing was retested in a second round of interviews (n = 14). Agreement about phrasing that was both culturally acceptable and semantically comprehensible was achieved in the second round. Statements from participants describing the meaning of the PRO-CTCAE symptomatic toxicities support conceptual equivalence to the U.S. English language version. Availability of the NCI PRO-CTCAE in languages beyond English will support international congruence in self-reporting of side effects of cancer treatment. A rigorous methodology was used to develop the Danish language version of PRO-CTCAE. Results provide preliminary support for the use of PRO-CTCAE in cancer clinical trials that include Danish speakers. Copyright © 2016 American Academy of Hospice and Palliative Medicine. All rights reserved.

  4. Common Cold

    MedlinePlus

    ... nose, coughing - everyone knows the symptoms of the common cold. It is probably the most common illness. In ... avoid colds. There is no cure for the common cold. For relief, try Getting plenty of rest Drinking ...

  5. Common cold

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000678.htm Common cold To use the sharing features on this page, please enable JavaScript. The common cold most often causes a runny nose, nasal congestion, ...

  6. Continuum representations of cellular solids

    NASA Astrophysics Data System (ADS)

    Neilsen, M. K.

    1993-09-01

    Cellular materials consist of interconnected struts or plates which form cells. The struts or plates are constructed from a variety of metals, polymers, ceramics, and wood products. Cellular materials are often used in impact limiters for shipping containers to protect the contents from accidental impact events. These materials exhibit a variety of complex behavior when subjected to crushing loads. This research focuses on the development of continuum representations of cellular solids that can be used in the finite element analysis of shipping container accidents. A significant portion of this work is the development of a new methodology to relate localized deformations to appropriate constitutive descriptions. This methodology provides the insight needed to select constitutive descriptions for cellular solids that capture the localized deformations that are observed experimentally. Constitutive relations are developed for two different cellular materials, aluminum honeycomb and polyurethane foam. These constitutive relations are based on plasticity and continuum damage theories. Plasticity is used to describe the permanent deformation exhibited by both aluminum honeycomb and polyurethane foam. Continuum damage is needed to capture the change in elastic parameters due to cracking of the polyurethane cell wall materials. The new constitutive description of polyurethane foam is implemented in both static and dynamic finite element codes, and analytical and numerical predictions are compared with available experimental data.

  7. Continuum representations of cellular solids

    SciTech Connect

    Neilsen, M.K.

    1993-09-01

    Cellular materials consist of interconnected struts or plates which form cells. The struts or plates are constructed from a variety of metals, polymers, ceramics and wood products. Cellular materials are often used in impact limiters for shipping containers to protect the contents from accidental impact events. These materials exhibit a variety of complex behavior when subjected to crushing loads. This research focuses on the development of continuum representations of cellular solids that can be used in the finite element analysis of shipping container accidents. A significant portion of this work is the development of a new methodology to relate localized deformations to appropriate constitutive descriptions. This methodology provides the insight needed to select constitutive descriptions for cellular solids that capture the localized deformations that are observed experimentally. Constitutive relations are developed for two different cellular materials, aluminum honeycomb and polyurethane foam. These constitutive relations are based on plasticity and continuum damage theories. Plasticity is used to describe the permanent deformation exhibited by both aluminum honeycomb and polyurethane foam. Continuum damage is needed to capture the change in elastic parameters due to cracking of the polyurethane cell wall materials. The new constitutive description of polyurethane foam is implemented in both static and dynamic finite element codes, and analytical and numerical predictions are compared with available experimental data.

  8. Ninety-day post-operative morbidity and mortality using the National Cancer Institute's common terminology criteria for adverse events better describe post-operative outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

    PubMed

    Alyami, Mohammad; Kim, Bradford J; Villeneuve, Laurent; Vaudoyer, Delphine; Képénékian, Vahan; Bakrin, Naoual; Gilly, Francois-Noel; Cotte, Eddy; Glehen, Olivier; Passot, Guillaume

    2017-08-24

    The post-operative morbidity and mortality after CRS-HIPEC has been widely evaluated. However, there is a major discrepancy between rates reported due to different metrics and time of analysis used. To evaluate the legitimacy of 90-day morbidity and mortality based on the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0 classification as criteria of quality for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). A prospective database of all patients undergoing CRS-HIPEC for peritoneal carcinomatosis between 2004 and 2015 was queried for 90-day morbidity and mortality and survival. Among 881 patients, the 90-day major complication rate based on NCI-CTCAE classification and Clavien-Dindo's classification were 51% (n = 447 patients) and 25% (n = 222 patients), respectively. Among patients who presented with a 90-day complication based on the NCI-CTCAE classification, 50% (n = 225 patients) presented a medical complication not reported by Clavien-Dindo's classification. After surgery, 24 patients (2.7%) died of post-operative complications, for only 10 (42%) of them the death occurred within 30-day after surgery. Occurrence of major complication based on either NCI-CTCAE classification, Clavien-Dindo's classification or the medical complication not reported by Clavien-Dindo's classification all negatively impacts the overall survival. Among commonly reported morbidity's classification, 90-day morbidity based on NCI-CTCAE classification represents a legitimate metric of CRS-HIPEC quality. Post-operative morbidity after CRS-HIPEC should be reported using 90-day NCI-CTCAE classification.

  9. Two HAP2-GCS1 homologs responsible for gamete interactions in the cellular slime mold with multiple mating types: Implication for common mechanisms of sexual reproduction shared by plants and protozoa and for male-female differentiation.

    PubMed

    Okamoto, Marina; Yamada, Lixy; Fujisaki, Yukie; Bloomfield, Gareth; Yoshida, Kentaro; Kuwayama, Hidekazu; Sawada, Hitoshi; Mori, Toshiyuki; Urushihara, Hideko

    2016-07-01

    Fertilization is a central event in sexual reproduction, and understanding its molecular mechanisms has both basic and applicative biological importance. Recent studies have uncovered the molecules that mediate this process in a variety of organisms, making it intriguing to consider conservation and evolution of the mechanisms of sexual reproduction across phyla. The social amoeba Dictyostelium discoideum undergoes sexual maturation and forms gametes under dark and humid conditions. It exhibits three mating types, type-I, -II, and -III, for the heterothallic mating system. Based on proteome analyses of the gamete membranes, we detected expression of two homologs of the plant fertilization protein HAP2-GCS1. When their coding genes were disrupted in type-I and type-II strains, sexual potency was completely lost, whereas disruption in the type-III strain did not affect mating behavior, suggesting that the latter acts as female in complex organisms. Our results demonstrate the highly conserved function of HAP2-GCS1 in gamete interactions and suggest the presence of additional allo-recognition mechanisms in D. discoideum gametes. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Aging, Cellular Senescence, and Cancer

    PubMed Central

    Campisi, Judith

    2014-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyper-plastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

  11. Aging, cellular senescence, and cancer.

    PubMed

    Campisi, Judith

    2013-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action.

  12. Clays, common

    USGS Publications Warehouse

    Virta, R.L.

    1998-01-01

    Part of a special section on the state of industrial minerals in 1997. The state of the common clay industry worldwide for 1997 is discussed. Sales of common clay in the U.S. increased from 26.2 Mt in 1996 to an estimated 26.5 Mt in 1997. The amount of common clay and shale used to produce structural clay products in 1997 was estimated at 13.8 Mt.

  13. Cellular models for Parkinson's disease.

    PubMed

    Falkenburger, Björn H; Saridaki, Theodora; Dinter, Elisabeth

    2016-10-01

    Developing new therapeutic strategies for Parkinson's disease requires cellular models. Current models reproduce the two most salient changes found in the brains of patients with Parkinson's disease: The degeneration of dopaminergic neurons and the existence of protein aggregates consisting mainly of α-synuclein. Cultured cells offer many advantages over studying Parkinson's disease directly in patients or in animal models. At the same time, the choice of a specific cellular model entails the requirement to focus on one aspect of the disease while ignoring others. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types the aspects of Parkinson's disease they model along with technical advantages and disadvantages. It might also be helpful for researchers from other fields consulting literature on cellular models of Parkinson's disease. Important models for the study of dopaminergic neuron degeneration include Lund human mesencephalic cells and primary neurons, and a case is made for the use of non-dopaminergic cells to model pathogenesis of non-motor symptoms of Parkinson's disease. With regard to α-synuclein aggregates, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques. Cellular models reproduce the two most salient changes of Parkinson's disease, the degeneration of dopaminergic neurons and the existence of α-synuclein aggregates. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types and treatments the aspects of Parkinson's disease they model along with technical advantages and disadvantages. Furthermore, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques. This article is part of a special issue on Parkinson disease.

  14. Commons Sense.

    ERIC Educational Resources Information Center

    Payne, William E.; Tyler, Charles R.

    1999-01-01

    Explains how a commons area can serve both the school and community by becoming a cost-effective, space-saving asset to the school building. Examines the commons area as a place for interaction; discusses subdividing it into smaller functional units, locating it, and related lighting and heating issues. (GR)

  15. Student Commons

    ERIC Educational Resources Information Center

    Gordon, Douglas

    2010-01-01

    Student commons are no longer simply congregation spaces for students with time on their hands. They are integral to providing a welcoming environment and effective learning space for students. Many student commons have been transformed into spaces for socialization, an environment for alternative teaching methods, a forum for large group meetings…

  16. Sipuleucel-T (Provenge): active cellular immunotherapy for advanced prostate cancer.

    PubMed

    McKarney, I

    2007-09-01

    (1) Sipuleucel-T (Provenge) is an active cellular immunotherapy (therapeutic vaccine) that is designed to stimulate the patient's T-cells to recognize and attack prostate cancer cells that express prostatic acid phosphatase (PAP) antigen. (2) Sipuleucel-T demonstrated a survival benefit in men with advanced androgen-independent prostate cancer (AIPC), although this preliminary finding requires confirmation in larger trials. (3) Mild to moderate myalgia, chills, fever, and tremor are the most commonly reported adverse events for patients receiving sipuleucel-T. These events generally resolve quickly. (4) More studies are needed to evaluate sipuleucel-T in the earlier stages of prostate cancer and in combination with conventional therapies.

  17. Cellular Phone Towers

    MedlinePlus

    ... the call. How are people exposed to the energy from cellular phone towers? As people use cell ... where people can be exposed to them. The energy from a cellular phone tower antenna, like that ...

  18. Common Cause Failures and Ultra Reliability

    NASA Technical Reports Server (NTRS)

    Jones, Harry W.

    2012-01-01

    A common cause failure occurs when several failures have the same origin. Common cause failures are either common event failures, where the cause is a single external event, or common mode failures, where two systems fail in the same way for the same reason. Common mode failures can occur at different times because of a design defect or a repeated external event. Common event failures reduce the reliability of on-line redundant systems but not of systems using off-line spare parts. Common mode failures reduce the dependability of systems using off-line spare parts and on-line redundancy.

  19. Hierarchical cellular materials

    SciTech Connect

    Gibson, L.J.

    1991-12-31

    In this paper a method for estimating the contributions of both the composite and the cellular microstructures to the overall material properties and the mechanical efficiency of natural cellular solids will be described. The method will be demonstrated by focusing on the Young`s modulus; similar techniques can be used for other material properties. The results suggest efficient microstructures for engineered cellular materials.

  20. Hierarchical cellular materials

    SciTech Connect

    Gibson, L.J.

    1991-01-01

    In this paper a method for estimating the contributions of both the composite and the cellular microstructures to the overall material properties and the mechanical efficiency of natural cellular solids will be described. The method will be demonstrated by focusing on the Young's modulus; similar techniques can be used for other material properties. The results suggest efficient microstructures for engineered cellular materials.

  1. 47 CFR 22.960 - Cellular unserved area radiotelephone licenses subject to competitive bidding.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.960 Cellular... applications for cellular unserved area Phase I and Phase II licenses filed after July 26, 1993 are subject...

  2. QCI Common

    SciTech Connect

    McCaskey, Alexander J.

    2016-11-18

    There are many common software patterns and utilities for the ORNL Quantum Computing Institute that can and should be shared across projects. Otherwise we find duplication of code which adds unwanted complexity. This is a software product seeks to alleviate this by providing common utilities such as object factories, graph data structures, parameter input mechanisms, etc., for other software products within the ORNL Quantum Computing Institute. This work enables pure basic research, has no export controlled utilities, and has no real commercial value.

  3. A Cellular Biophysics Textbook

    NASA Astrophysics Data System (ADS)

    Wilder, Alan Joseph

    2011-12-01

    In the past two decades, great advances have been made in understanding of the biophysical mechanisms of the protein machines that carry out the fundamental processes of the cell. It is now known that all major eukaryotic cellular processes require a complicated assemblage of proteins acting via a series of concerted motions. In order to grasp current understanding of cellular mechanisms, the new generation of cell biologists needs to be trained in the general characteristics of these cellular properties and the methods with which to study them. This cellular biophysics textbook, to be used in conjunction with the cellular biophysics course (MCB143) at UC-Davis, provides a great tool in the instruction of the new generation of cellular biologists. It provides a hierarchical view of the cell, from atoms to protein machines and explains in depth the mechanisms of cytoskeletal force generators as an example of these principles.

  4. Probing intra-cellular drug release event using activatable (OFF/ON) CdS:Mn/ZnS quantum dots (Qdots): spectroscopic studies to investigate interaction of Qdots with quencher

    NASA Astrophysics Data System (ADS)

    Tharkur, Jeremy; Teblum, Andrew; Basumallick, Srijita; Shah, Rikhav; Cantarero, Karishma; Maity, Niharika; Rifai, Sara; Doshi, Mona; Gesquiere, Andre J.; Santra, Swadeshmukul

    2013-02-01

    In recent years, activatable Quantum Dots (AQdots) are gaining popularity in a number of chemical and biological sensing applications. A basic design of AQdot probes involves a suitable quencher which is capable of altering optical properties of the Qdots. In our previous studies we have shown that CdS:Mn/ZnS fluorescence can be effectively quenched using small molecule quenchers (such as dopamine, chemotherapeutic drug) as well as iron oxide nanoparticle via electron/energy transfer process. We have also shown that the quenched Qdot fluorescence can be restored when the Qdots are separated from the quencher. Using Qdot based activatable probes, we detected intracellular drug release event. Qdot fluorescence was restored upon interaction with the intracellular glutathione (GSH). In this paper, we report a GSH induced quenching of water-soluble N-Acetyl Cysteine (NAC) surface-conjugated Cds:Mn/ZnS Qdots. Quenching of NAC-Qdots was due to aggregation of Qdots in solution. This aggregation induced fluorescence quenching phenomenon resembles with the self-quenching phenomenon of traditional organic fluorescence dyes at high concentrations. UV-VIS and fluorescence emission spectroscopy data support the interaction and binding of GSH with the NAC-Qdots. Increase in particle size due to GSH induced aggregation of NAC-Qdots was confirmed by the Dynamic Light Scattering (DLS) data.

  5. Activating Event Knowledge

    PubMed Central

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

    2009-01-01

    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or typically play a role in. We used short stimulus onset asynchrony priming to demonstrate that (1) event nouns prime people (sale-shopper) and objects (trip-luggage) commonly found at those events; (2) location nouns prime people/animals (hospital-doctor) and objects (barn-hay) commonly found at those locations; and (3) instrument nouns prime things on which those instruments are commonly used (key-door), but not the types of people who tend to use them (hose-gardener). The priming effects are not due to normative word association. On our account, facilitation results from event knowledge relating primes and targets. This has much in common with computational models like LSA or BEAGLE in which one word primes another if they frequently occur in similar contexts. LSA predicts priming for all six experiments, whereas BEAGLE correctly predicted that priming should not occur for the instrument-people relation but should occur for the other five. We conclude that event-based relations are encoded in semantic memory and computed as part of word meaning, and have a strong influence on language comprehension. PMID:19298961

  6. Activating event knowledge.

    PubMed

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

    2009-05-01

    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or typically play a role in. We used short stimulus onset asynchrony priming to demonstrate that (1) event nouns prime people (sale-shopper) and objects (trip-luggage) commonly found at those events; (2) location nouns prime people/animals (hospital-doctor) and objects (barn-hay) commonly found at those locations; and (3) instrument nouns prime things on which those instruments are commonly used (key-door), but not the types of people who tend to use them (hose-gardener). The priming effects are not due to normative word association. On our account, facilitation results from event knowledge relating primes and targets. This has much in common with computational models like LSA or BEAGLE in which one word primes another if they frequently occur in similar contexts. LSA predicts priming for all six experiments, whereas BEAGLE correctly predicted that priming should not occur for the instrument-people relation but should occur for the other five. We conclude that event-based relations are encoded in semantic memory and computed as part of word meaning, and have a strong influence on language comprehension.

  7. Common Difficulties with Probabilistic Reasoning.

    ERIC Educational Resources Information Center

    Hope, Jack A.; Kelly, Ivan W.

    1983-01-01

    Several common errors reflecting difficulties in probabilistic reasoning are identified, relating to ambiguity, previous outcomes, sampling, unusual events, and estimating. Knowledge of these mistakes and interpretations may help mathematics teachers understand the thought processes of their students. (MNS)

  8. Making the Common Good Common

    ERIC Educational Resources Information Center

    Chase, Barbara

    2011-01-01

    How are independent schools to be useful to the wider world? Beyond their common commitment to educate their students for meaningful lives in service of the greater good, can they educate a broader constituency and, thus, share their resources and skills more broadly? Their answers to this question will be shaped by their independence. Any…

  9. The development of hippocampal cellular assemblies.

    PubMed

    Li, Guangnan; Pleasure, Samuel J

    2014-01-01

    The proper assembly of a cohort of distinct cell types is a prerequisite for building a functional hippocampus. In this review, we describe the major molecular events of the developmental program leading to the cellular construction of the hippocampus. Data from rodent studies are used here to elaborate on our understanding of these processes.

  10. Commonly used endocrine drugs.

    PubMed

    Rosa, Mário Miguel; Dias, Teresa

    2014-01-01

    Endocrine drugs are agents directed to a malfunctioning endocrine path. Several agents are secreted in or target the nervous system, and are thus more prone to cause neurologic adverse events (AEs). This chapter focuses on commonly used endocrine agents directed to the hypothalamus-pituitary axis, thyroid, and antidiabetic agents. The therapeutic agents are discussed in terms of indication, mechanism of action, description, and frequency of AEs, and risk factors for occurrence where available. © 2014 Elsevier B.V. All rights reserved.

  11. Modelling cellular behaviour

    NASA Astrophysics Data System (ADS)

    Endy, Drew; Brent, Roger

    2001-01-01

    Representations of cellular processes that can be used to compute their future behaviour would be of general scientific and practical value. But past attempts to construct such representations have been disappointing. This is now changing. Increases in biological understanding combined with advances in computational methods and in computer power make it possible to foresee construction of useful and predictive simulations of cellular processes.

  12. In vitro effects of platinum compounds on renal cellular respiration in mice.

    PubMed

    Almarzooqi, Saeeda-S; Alfazari, Ali-S; Abdul-Kader, Hidaya-M; Saraswathiamma, Dhanya; Albawardi, Alia-S; Souid, Abdul-Kader

    2015-01-01

    Cisplatin, carboplatin and oxaliplatin are structurally-related compounds, which are commonly used in cancer therapy. Cisplatin (Platinol(®)) has Boxed Warning stating: "Cumulative renal toxicity associated with PLATINOL is severe", while carboplatin and oxaliplatin are less nephrotoxic. These drugs form platinum adducts with cellular DNA. Their bindings to cellular thiols (e.g., glutathione and metallothionein) are known to contribute to drug resistance while thiol depletion augments platinum toxicity. Using phosphorescence oxygen analyzer, this study investigated the effects of platinum drugs on renal cellular respiration (mitochondrial O2 consumption) in the presence and absence of the thiol blocking agent N-ethylmaleimide (used here as a model for thiol depletion). Renal cellular ATP was also determined. Kidney fragments from C57BL/6 mice were incubated at 37 °C in Krebs-Henseleit buffer (gassed with 95% O2:5% CO2) with and without 100 μM platinum drug in the presence and absence of 100 μM N-ethylmaleimide for ≤ 6 h. Platinum drugs alone had no effects on cellular respiration (P ≥ 0.143) or ATP (P ≥ 0.161). N-ethylmaleimide lowered cellular respiration (P ≤ 0.114) and ATP (P = 0.008). The combination of platinum drug and N-ethylmaleimide significantly lowered both cellular respiration (P ≤ 0.006) and ATP (P ≤ 0.003). Incubations with N-ethylmaleimide alone were associated with moderate-to-severe tubular necrosis. Incubations with cisplatin+N-ethylmaleimide vs. cisplatin alone produced similar severities of tubular necrosis. Tubular derangements were more prominent in carboplatin+N-ethylmaleimide vs. carboplatin alone and in oxaliplatin+N-ethylmaleimide vs. oxaliplatin alone. These results demonstrate the adverse events of thiol depletion on platinum-induced nephrotoxicities. The results suggest cellular bioenergetics is a useful surrogate biomarker for assessing drug-induced nephrotoxicities.

  13. Event Perception.

    PubMed

    Radvansky, Gabriel; Zacks, Jeffrey M

    2011-11-01

    Events are central elements of human experience. Formally, they can be individuated in terms of the entities that compose them, the features of those entities, and the relations amongst entities. Psychologically, representations of events capture their spatiotemporal location, the people and objects involved, and the relations between these elements. Here, we present an account of the nature of psychological representations of events and how they are constructed and updated. Event representations are like images in that they are isomorphic to the situations they represent. However, they are like models or language in that they are constructed of components rather than being holistic. Also, they are partial representations that leave out some elements and abstract others. Representations of individual events are informed by schematic knowledge about general classes of events. Event representations are constructed in a process that segments continuous activity into discrete events. The construction of a series of event representations forms a basis for predicting the future, planning for that future, and imagining alternatives.

  14. Event Perception

    PubMed Central

    Radvansky, Gabriel; Zacks, Jeffrey M.

    2012-01-01

    Events are central elements of human experience. Formally, they can be individuated in terms of the entities that compose them, the features of those entities, and the relations amongst entities. Psychologically, representations of events capture their spatiotemporal location, the people and objects involved, and the relations between these elements. Here, we present an account of the nature of psychological representations of events and how they are constructed and updated. Event representations are like images in that they are isomorphic to the situations they represent. However, they are like models or language in that they are constructed of components rather than being holistic. Also, they are partial representations that leave out some elements and abstract others. Representations of individual events are informed by schematic knowledge about general classes of events. Event representations are constructed in a process that segments continuous activity into discrete events. The construction of a series of event representations forms a basis for predicting the future, planning for that future, and imagining alternatives. PMID:23082236

  15. Plasmonic Nanostructured Cellular Automata

    NASA Astrophysics Data System (ADS)

    Alkhazraji, Emad; Ghalib, A.; Manzoor, K.; Alsunaidi, M. A.

    2017-03-01

    In this work, we have investigated the scattering plasmonic resonance characteristics of silver nanospheres with a geometrical distribution that is modelled by Cellular Automata using time-domain numerical analysis. Cellular Automata are discrete mathematical structures that model different natural phenomena. Two binary one-dimensional Cellular Automata rules are considered to model the nanostructure, namely rule 30 and rule 33. The analysis produces three-dimensional scattering profiles of the entire plasmonic nanostructure. For the Cellular Automaton rule 33, the introduction of more Cellular Automata generations resulted only in slight red and blue shifts in the plasmonic modes with respect to the first generation. On the other hand, while rule 30 introduced significant red shifts in the resonance peaks at early generations, at later generations however, a peculiar effect is witnessed in the scattering profile as new peaks emerge as a feature of the overall Cellular Automata structure rather than the sum of the smaller parts that compose it. We strongly believe that these features that emerge as a result adopting the different 256 Cellular Automata rules as configuration models of nanostructures in different applications and systems might possess a great potential in enhancing their capability, sensitivity, efficiency, and power utilization.

  16. Cellular Reflectarray Antenna

    NASA Technical Reports Server (NTRS)

    Romanofsky, Robert R.

    2010-01-01

    The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

  17. Cellular and synaptic network defects in autism.

    PubMed

    Peça, João; Feng, Guoping

    2012-10-01

    Many candidate genes are now thought to confer susceptibility to autism spectrum disorders (ASDs). Here we review four interrelated complexes, each composed of multiple families of genes that functionally coalesce on common cellular pathways. We illustrate a common thread in the organization of glutamatergic synapses and suggest a link between genes involved in Tuberous Sclerosis Complex, Fragile X syndrome, Angelman syndrome and several synaptic ASD candidate genes. When viewed in this context, progress in deciphering the molecular architecture of cellular protein-protein interactions together with the unraveling of synaptic dysfunction in neural networks may prove pivotal to advancing our understanding of ASDs. Copyright © 2012. Published by Elsevier Ltd.

  18. Electromagnetic cellular interactions.

    PubMed

    Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

    2011-05-01

    Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating.

  19. Linking chordate gene networks to cellular behavior in ascidians.

    PubMed

    Davidson, Brad; Christiaen, Lionel

    2006-01-27

    Embryos of simple chordates called ascidians (sea squirts) have few cells, develop rapidly, and are transparent, enabling the in vivo fluorescent imaging of labeled cell lineages. Ascidians are also simple genetically, with limited redundancy and compact regulatory regions. This cellular and genetic simplicity is now being exploited to link comprehensive gene networks to the cellular events underlying morphogenesis.

  20. Nucleosome remodelling, DNA repair and transcriptional regulation build negative feedback loops in cancer and cellular ageing.

    PubMed

    Watanabe, Reiko; Kanno, Shin-Ichiro; Mohammadi Roushandeh, Amaneh; Ui, Ayako; Yasui, Akira

    2017-10-05

    Nucleosome remodelling (NR) regulates transcription in an ATP-dependent manner, and influences gene expression required for development and cellular functions, including those involved in anti-cancer and anti-ageing processes. ATP-utilizing chromatin assembly and remodelling factor (ACF) and Brahma-associated factor (BAF) complexes, belonging to the ISWI and SWI/SNF families, respectively, are involved in various types of DNA repair. Suppression of several BAF factors makes U2OS cells significantly sensitive to X-rays, UV and especially to cisplatin, and these BAF factors contribute to the accumulation of repair proteins at various types of DNA damage and to DNA repair. Recent cancer genome sequencing and expression analysis has shown that BAF factors are frequently mutated or, more frequently, silenced in various types of cancer cells. Thus, those cancer cells are potentially X-ray- and especially cisplatin-sensitive, suggesting a way of optimizing current cancer therapy. Recent single-stem cell analysis suggests that mutations and epigenetic changes influence stem cell functionality leading to cellular ageing. Genetic and epigenetic changes in the BAF factors diminish DNA repair as well as transcriptional regulation activities, and DNA repair defects in turn negatively influence NR and transcriptional regulation. Thus, they build negative feedback loops, which accelerate both cellular senescence and transformation as common and rare cellular events, respectively, causing cellular ageing.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'. © 2017 The Author(s).

  1. Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1

    PubMed Central

    Sada, Kiminori; Nishikawa, Takeshi; Kukidome, Daisuke; Yoshinaga, Tomoaki; Kajihara, Nobuhiro; Sonoda, Kazuhiro; Senokuchi, Takafumi; Motoshima, Hiroyuki; Matsumura, Takeshi; Araki, Eiichi

    2016-01-01

    We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner. PMID:27383386

  2. Glycosylation regulates prestin cellular activity.

    PubMed

    Rajagopalan, Lavanya; Organ-Darling, Louise E; Liu, Haiying; Davidson, Amy L; Raphael, Robert M; Brownell, William E; Pereira, Fred A

    2010-03-01

    Glycosylation is a common post-translational modification of proteins and is implicated in a variety of cellular functions including protein folding, degradation, sorting and trafficking, and membrane protein recycling. The membrane protein prestin is an essential component of the membrane-based motor driving electromotility changes (electromotility) in the outer hair cell (OHC), a central process in auditory transduction. Prestin was earlier identified to possess two N-glycosylation sites (N163, N166) that, when mutated, marginally affect prestin nonlinear capacitance (NLC) function in cultured cells. Here, we show that the double mutant prestin(NN163/166AA) is not glycosylated and shows the expected NLC properties in the untreated and cholesterol-depleted HEK 293 cell model. In addition, unlike WT prestin that readily forms oligomers, prestin(NN163/166AA) is enriched as monomers and more mobile in the plasma membrane, suggesting that oligomerization of prestin is dependent on glycosylation but is not essential for the generation of NLC in HEK 293 cells. However, in the presence of increased membrane cholesterol, unlike the hyperpolarizing shift in NLC seen with WT prestin, cells expressing prestin(NN163/166AA) exhibit a linear capacitance function. In an attempt to explain this finding, we discovered that both WT prestin and prestin(NN163/166AA) participate in cholesterol-dependent cellular trafficking. In contrast to WT prestin, prestin(NN163/166AA) shows a significant cholesterol-dependent decrease in cell-surface expression, which may explain the loss of NLC function. Based on our observations, we conclude that glycosylation regulates self-association and cellular trafficking of prestin(NN163/166AA). These observations are the first to implicate a regulatory role for cellular trafficking and sorting in prestin function. We speculate that the cholesterol regulation of prestin occurs through localization to and internalization from membrane microdomains by

  3. Cellular aging and cancer

    PubMed Central

    Hornsby, Peter J.

    2010-01-01

    Aging is manifest in a variety of changes over time, including changes at the cellular level. Cellular aging acts primarily as a tumor suppressor mechanism, but also may enhance cancer development under certain circumstances. One important process of cellular aging is oncogene-induced senescence, which acts as an important anti-cancer mechanism. Cellular senescence resulting from damage caused by activated oncogenes prevents the growth or potentially neoplastic cells. Moreover, cells that have entered senescence appear to be targets for elimination by the innnate immune system. In another aspect of cellular aging, the absence of telomerase activity in normal tissues results in such cells lacking a telomere maintenance mechanism. One consequence is that in aging there is an increase in cells with shortened telomeres. In the presence of active oncogenes that cause expansion of a neoplastic clone, shortening of telomeres leading to telomere dysfunction prevents the indefinite expansion of the clone because the cells enter crisis. Crisis results from fusions and other defects caused by dysfunctional telomeres and is a terminal state of the neoplastic clone. In this way the absence of telomerase in human cells, while one cause of cellular aging, also acts as an anti-cancer mechanism. PMID:20705476

  4. Recent Advances in Cellular Glycomic Analyses

    PubMed Central

    Furukawa, Jun-ichi; Fujitani, Naoki; Shinohara, Yasuro

    2013-01-01

    A large variety of glycans is intricately located on the cell surface, and the overall profile (the glycome, given the entire repertoire of glycoconjugate-associated sugars in cells and tissues) is believed to be crucial for the diverse roles of glycans, which are mediated by specific interactions that control cell-cell adhesion, immune response, microbial pathogenesis and other cellular events. The glycomic profile also reflects cellular alterations, such as development, differentiation and cancerous change. A glycoconjugate-based approach would therefore be expected to streamline discovery of novel cellular biomarkers. Development of such an approach has proven challenging, due to the technical difficulties associated with the analysis of various types of cellular glycomes; however, recent progress in the development of analytical methodologies and strategies has begun to clarify the cellular glycomics of various classes of glycoconjugates. This review focuses on recent advances in the technical aspects of cellular glycomic analyses of major classes of glycoconjugates, including N- and O-linked glycans, derived from glycoproteins, proteoglycans and glycosphingolipids. Articles that unveil the glycomics of various biologically important cells, including embryonic and somatic stem cells, induced pluripotent stem (iPS) cells and cancer cells, are discussed. PMID:24970165

  5. Reprogramming cellular events by poly(ADP-ribose)-binding proteins

    PubMed Central

    Pic, Émilie; Ethier, Chantal; Dawson, Ted M.; Dawson, Valina L.; Masson, Jean-Yves; Poirier, Guy G.; Gagné, Jean-Philippe

    2013-01-01

    Poly(ADP-ribosyl)ation is a posttranslational modification catalyzed by the poly(ADP-ribose) polymerases (PARPs). These enzymes covalently modify glutamic, aspartic and lysine amino acid side chains of acceptor proteins by the sequential addition of ADP-ribose (ADPr) units. The poly(ADP-ribose) (pADPr) polymers formed alter the physico-chemical characteristics of the substrate with functional consequences on its biological activities. Recently, non-covalent binding to pADPr has emerged as a key mechanism to modulate and coordinate several intracellular pathways including the DNA damage response, protein stability and cell death. In this review, we describe the basis of non-covalent binding to pADPr that has led to the emerging concept of pADPr-responsive signaling pathways. This review emphasizes the structural elements and the modular strategies developed by pADPr-binding proteins to exert a fine-tuned control of a variety of pathways. Poly(ADP-ribosyl)ation reactions are highly regulated processes, both spatially and temporally, for which at least four specialized pADPr-binding modules accommodate different pADPr structures and reprogram protein functions. In this review, we highlight the role of well-characterized and newly discovered pADPr-binding modules in a diverse set of physiological functions. PMID:23268355

  6. Cellular functions of the microprocessor.

    PubMed

    Macias, Sara; Cordiner, Ross A; Cáceres, Javier F

    2013-08-01

    The microprocessor is a complex comprising the RNase III enzyme Drosha and the double-stranded RNA-binding protein DGCR8 (DiGeorge syndrome critical region 8 gene) that catalyses the nuclear step of miRNA (microRNA) biogenesis. DGCR8 recognizes the RNA substrate, whereas Drosha functions as an endonuclease. Recent global analyses of microprocessor and Dicer proteins have suggested novel functions for these components independent of their role in miRNA biogenesis. A HITS-CLIP (high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation) experiment designed to identify novel substrates of the microprocessor revealed that this complex binds and regulates a large variety of cellular RNAs. The microprocessor-mediated cleavage of several classes of RNAs not only regulates transcript levels, but also modulates alternative splicing events, independently of miRNA function. Importantly, DGCR8 can also associate with other nucleases, suggesting the existence of alternative DGCR8 complexes that may regulate the fate of a subset of cellular RNAs. The aim of the present review is to provide an overview of the diverse functional roles of the microprocessor.

  7. 47 CFR 22.960 - Cellular unserved area radiotelephone licenses subject to competitive bidding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular unserved area radiotelephone licenses... (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.960 Cellular... applications for cellular unserved area Phase I and Phase II licenses filed after July 26, 1993 are subject to...

  8. Irregular Cellular Learning Automata.

    PubMed

    Esnaashari, Mehdi; Meybodi, Mohammad Reza

    2015-08-01

    Cellular learning automaton (CLA) is a recently introduced model that combines cellular automaton (CA) and learning automaton (LA). The basic idea of CLA is to use LA to adjust the state transition probability of stochastic CA. This model has been used to solve problems in areas such as channel assignment in cellular networks, call admission control, image processing, and very large scale integration placement. In this paper, an extension of CLA called irregular CLA (ICLA) is introduced. This extension is obtained by removing the structure regularity assumption in CLA. Irregularity in the structure of ICLA is needed in some applications, such as computer networks, web mining, and grid computing. The concept of expediency has been introduced for ICLA and then, conditions under which an ICLA becomes expedient are analytically found.

  9. Epigenetics and Cellular Metabolism

    PubMed Central

    Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well. PMID:27695375

  10. Fatigue of cellular materials

    SciTech Connect

    Huang, J.S.; Lin, J.Y.

    1996-01-01

    The fatigue of cellular materials is analyzed using dimensional arguments. When the first unbroken cell wall ahead of the macrocrack tip fails after some cycles of loading, the macrocrack advances one cell diameter, giving the macrocrack growth rate of cellular materials. Paris law for microcrack propagation, Basquin law for high cycle fatigue and Coffin-Manson law for low cycle fatigue are employed in calculating the number of cycles to failure of the first unbroken cell wall ahead of the macrocrack tip. It is found that fatigue of cellular materials depends on cyclic stress intensity range, cell size, relative density and the fatigue parameters of the solid from which they are made. Theoretical modelling of fatigue of foams is compared to data in polymer foams; agreement is good.

  11. Cellular immunotherapies for cancer.

    PubMed

    Berraondo, Pedro; Labiano, Sara; Minute, Luna; Etxeberria, Iñaki; Vasquez, Marcos; Sanchez-Arraez, Alvaro; Teijeira, Alvaro; Melero, Ignacio

    2017-01-01

    Lessons learned over decades on the use of gene and cell therapies have found clinical applicability in the field of cancer immunotherapy. On December 16(th), 2016 a symposium was held in Pamplona (Spain) to analyze and discuss the critical points for the clinical success of adoptive cell transfer strategies in cancer immunotherapy. Cellular immunotherapy is being currently exploited for the development of new cancer vaccines using ex vivo manipulated dendritic cells or to enhance the number of effector cells, transferring reinvigorated NK cells or T cells. In this meeting report, we summarize the main topics covered and provide an overview of the field of cellular immunotherapy.

  12. Cellular structural biology.

    PubMed

    Ito, Yutaka; Selenko, Philipp

    2010-10-01

    While we appreciate the complexity of the intracellular environment as a general property of every living organism, we collectively lack the appropriate tools to analyze protein structures in a cellular context. In-cell NMR spectroscopy represents a novel biophysical tool to investigate the conformational and functional characteristics of biomolecules at the atomic level inside live cells. Here, we review recent in-cell NMR developments and provide an outlook towards future applications in prokaryotic and eukaryotic cells. We hope to thereby emphasize the usefulness of in-cell NMR techniques for cellular studies of complex biological processes and for structural analyses in native environments. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. EVENT SEGMENTATION

    PubMed Central

    Zacks, Jeffrey M.; Swallow, Khena M.

    2012-01-01

    One way to understand something is to break it up into parts. New research indicates that segmenting ongoing activity into meaningful events is a core component of ongoing perception, with consequences for memory and learning. Behavioral and neuroimaging data suggest that event segmentation is automatic and that people spontaneously segment activity into hierarchically organized parts and sub-parts. This segmentation depends on the bottom-up processing of sensory features such as movement, and on the top-down processing of conceptual features such as actors’ goals. How people segment activity affects what they remember later; as a result, those who identify appropriate event boundaries during perception tend to remember more and learn more proficiently. PMID:22468032

  14. Mapping cellular hierarchy by single cell analysis of the cell surface repertoire

    PubMed Central

    Guo, Guoji; Luc, Sidinh; Marco, Eugenio; Lin, Ta-Wei; Peng, Cong; Kerenyi, Marc A.; Beyaz, Semir; Kim, Woojin; Xu, Jian; Das, Partha Pratim; Neff, Tobias; Zou, Keyong; Yuan, Guo-Cheng; Orkin, Stuart H.

    2013-01-01

    SUMMARY Stem cell differentiation pathways are most often studied at the population level, whereas critical decisions are executed at the level of single cells. We have established a highly multiplexed, quantitative PCR assay to profile in an unbiased manner a panel of all commonly used cell surface markers (280 genes) from individual cells. With this method we analyzed over 1500 single cells throughout the mouse hematopoietic system, and illustrate its utility for revealing important biological insights. The comprehensive single cell dataset permits mapping of the mouse hematopoietic stem cell (HSC) differentiation hierarchy by computational lineage progression analysis. Further profiling of 180 intracellular regulators enabled construction of a genetic network to assign the earliest differentiation event during hematopoietic lineage specification. Analysis of acute myeloid leukemia elicited by MLL-AF9 uncovered a distinct cellular hierarchy containing two independent self-renewing lineages with different clonal activities. The strategy has broad applicability in other cellular systems. PMID:24035353

  15. Marine Bivalve Cellular Responses to Beta Blocker Exposures ...

    EPA Pesticide Factsheets

    β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent binding of agonists such as catecholamines to β adrenoceptors. In the absence of agonist induced activation of the receptor, adenylate cyclase is not activated which in turn limits cAMP production and protein kinase A activation, preventing increases in blood pressure and arrhythmias. After being taken therapeutically, commonly prescribed β blockers may make their way to coastal habitats via discharge from waste water treatment plants (WWTP) posing a potential risk to aquatic organisms. The aim of our research is to evaluate cellular responses of three commercially important marine bivalves - Eastern oysters, blue mussels and hard clams - upon exposure to two β blocker drugs, propranolol and metoprolol, and to find molecular initiating events (MIEs) indicative of the exposure. Bivalves were obtained from Narragansett Bay (Rhode Island, USA) and acclimated in the laboratory. Following acclimation, gills and hepatopancreas (HP) tissues were harvested and separately exposed to 0, 1, 10, 100 and 1000 ng/l of each drug. Tissues were bathed in 30 parts per thousand (ppt) filtered seawater, antibiotic mix, Leibovitz nutrient media, and the test drug. Exposures were conducted for 24 hours and samples were saved for cellular biomarker assays. A lysosomal destabilization assay, which is a marker of membrane damage, was also performed at the end of each exposure.

  16. Genetic Dominance & Cellular Processes

    ERIC Educational Resources Information Center

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  17. Genetic Dominance & Cellular Processes

    ERIC Educational Resources Information Center

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  18. Cellular genetic therapy.

    PubMed

    Del Vecchio, F; Filareto, A; Spitalieri, P; Sangiuolo, F; Novelli, G

    2005-01-01

    Cellular genetic therapy is the ultimate frontier for those pathologies that are consequent to a specific nonfunctional cellular type. A viable cure for there kinds of diseases is the replacement of sick cells with healthy ones, which can be obtained from the same patient or a different donor. In fact, structures can be corrected and strengthened with the introduction of undifferentiated cells within specific target tissues, where they will specialize into the desired cellular types. Furthermore, consequent to the recent results obtained with the transdifferentiation experiments, a process that allows the in vitro differentiation of embryonic and adult stem cells, it has also became clear that many advantages may be obtained from the use of stem cells to produce drugs, vaccines, and therapeutic molecules. Since stem cells can sustain lineage potentials, the capacity for differentiation, and better tolerance for the introduction of exogenous genes, they are also considered as feasible therapeutic vehicles for gene therapy. In fact, it is strongly believed that the combination of cellular genetic and gene therapy approaches will definitely allow the development of new therapeutic strategies as well as the production of totipotent cell lines to be used as experimental models for the cure of genetic disorders.

  19. The New Cellular Immunology

    ERIC Educational Resources Information Center

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  20. The New Cellular Immunology

    ERIC Educational Resources Information Center

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  1. Transformational Events

    ERIC Educational Resources Information Center

    Denning, Peter J.; Hiles, John E.

    2006-01-01

    Transformational Events is a new pedagogic pattern that explains how innovations (and other transformations) happened. The pattern is three temporal stages: an interval of increasingly unsatisfactory ad hoc solutions to a persistent problem (the "mess"), an offer of an invention or of a new way of thinking, and a period of widespread adoption and…

  2. Transformational Events

    ERIC Educational Resources Information Center

    Denning, Peter J.; Hiles, John E.

    2006-01-01

    Transformational Events is a new pedagogic pattern that explains how innovations (and other transformations) happened. The pattern is three temporal stages: an interval of increasingly unsatisfactory ad hoc solutions to a persistent problem (the "mess"), an offer of an invention or of a new way of thinking, and a period of widespread adoption and…

  3. Effect of lysosomotropic molecules on cellular homeostasis.

    PubMed

    Kuzu, Omer F; Toprak, Mesut; Noory, M Anwar; Robertson, Gavin P

    2017-03-01

    Weak bases that readily penetrate through the lipid bilayer and accumulate inside the acidic organelles are known as lysosomotropic molecules. Many lysosomotropic compounds exhibit therapeutic activity and are commonly used as antidepressant, antipsychotic, antihistamine, or antimalarial agents. Interestingly, studies also have shown increased sensitivity of cancer cells to certain lysosomotropic agents and suggested their mechanism of action as a promising approach for selective destruction of cancer cells. However, their chemotherapeutic utility may be limited due to various side effects. Hence, understanding the homeostatic alterations mediated by lysosomotropic compounds has significant importance for revealing their true therapeutic potential as well as toxicity. In this review, after briefly introducing the concept of lysosomotropism and classifying the lysosomotropic compounds into two major groups according to their cytotoxicity on cancer cells, we focused on the subcellular alterations mediated by class-II lysosomotropic compounds. Briefly, their effect on intracellular cholesterol homeostasis, autophagy and lysosomal sphingolipid metabolism was discussed. Accordingly, class-II lysosomotropic molecules inhibit intracellular cholesterol transport, leading to the accumulation of cholesterol inside the late endosomal-lysosomal cell compartments. However, the accumulated lysosomal cholesterol is invisible to the cellular homeostatic circuits, hence class-II lysosomotropic molecules also upregulate cholesterol synthesis pathway as a downstream event. Considering the fact that Niemann-Pick disease, a lysosomal cholesterol storage disorder, also triggers similar pathologic abnormalities, this review combines the knowledge obtained from the Niemann-Pick studies and lysosomotropic compounds. Taken together, this review is aimed at allowing readers a better understanding of subcellular alterations mediated by lysosomotropic drugs, as well as their potential

  4. Diverse system stresses: common mechanisms of chromosome fragmentation.

    PubMed

    Stevens, J B; Abdallah, B Y; Liu, G; Ye, C J; Horne, S D; Wang, G; Savasan, S; Shekhar, M; Krawetz, S A; Hüttemann, M; Tainsky, M A; Wu, G S; Xie, Y; Zhang, K; Heng, H H Q

    2011-06-30

    Chromosome fragmentation (C-Frag) is a newly identified MCD (mitotic cell death), distinct from apoptosis and MC (mitotic catastrophe). As different molecular mechanisms can induce C-Frag, we hypothesize that the general mechanism of its induction is a system response to cellular stress. A clear link between C-Frag and diverse system stresses generated from an array of molecular mechanisms is shown. Centrosome amplification, which is also linked to diverse mechanisms of stress, is shown to occur in association with C-Frag. This led to a new model showing that diverse stresses induce common, MCD. Specifically, different cellular stresses target the integral chromosomal machinery, leading to system instability and triggering of MCD by C-Frag. This model of stress-induced cell death is also applicable to other types of cell death. The current study solves the previously confusing relationship between the diverse molecular mechanisms of chromosome pulverization, suggesting that incomplete C-Frag could serve as the initial event responsible for forms of genome chaos including chromothripsis. In addition, multiple cell death types are shown to coexist with C-Frag and it is more dominant than apoptosis at lower drug concentrations. Together, this study suggests that cell death is a diverse group of highly heterogeneous events that are linked to stress-induced system instability and evolutionary potential.

  5. Complexity, dynamic cellular network, and tumorigenesis.

    PubMed

    Waliszewski, P

    1997-01-01

    A holistic approach to tumorigenesis is proposed. The main element of the model is the existence of dynamic cellular network. This network comprises a molecular and an energetistic structure of a cell connected through the multidirectional flow of information. The interactions within dynamic cellular network are complex, stochastic, nonlinear, and also involve quantum effects. From this non-reductionist perspective, neither tumorigenesis can be limited to the genetic aspect, nor the initial event must be of molecular nature, nor mutations and epigenetic factors are mutually exclusive, nor a link between cause and effect can be established. Due to complexity, an unstable stationary state of dynamic cellular network rather than a group of unrelated genes determines the phenotype of normal and transformed cells. This implies relativity of tumor suppressor genes and oncogenes. A bifurcation point is defined as an unstable state of dynamic cellular network leading to the other phenotype-stationary state. In particular, the bifurcation point may be determined by a change of expression of a single gene. Then, the gene is called bifurcation point gene. The unstable stationary state facilitates the chaotic dynamics. This may result in a fractal dimension of both normal and tumor tissues. The co-existence of chaotic dynamics and complexity is the essence of cellular processes and shapes differentiation, morphogenesis, and tumorigenesis. In consequence, tumorigenesis is a complex, unpredictable process driven by the interplay between self-organisation and selection.

  6. Regulation of cellular chromatin state

    PubMed Central

    Mishra, Rakesh K; Dhawan, Jyotsna

    2010-01-01

    The identity and functionality of eukaryotic cells is defined not just by their genomic sequence which remains constant between cell types, but by their gene expression profiles governed by epigenetic mechanisms. Epigenetic controls maintain and change the chromatin state throughout development, as exemplified by the setting up of cellular memory for the regulation and maintenance of homeotic genes in proliferating progenitors during embryonic development. Higher order chromatin structure in reversibly arrested adult stem cells also involves epigenetic regulation and in this review we highlight common trends governing chromatin states, focusing on quiescence and differentiation during myogenesis. Together, these diverse developmental modules reveal the dynamic nature of chromatin regulation providing fresh insights into the role of epigenetic mechanisms in potentiating development and differentiation. PMID:20592864

  7. Cellular compartmentalization of secondary metabolism

    PubMed Central

    Kistler, H. Corby; Broz, Karen

    2015-01-01

    Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g., amino acids, acetyl CoA, NADPH), enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported. PMID:25709603

  8. Warburg, me and Hexokinase 2: Multiple discoveries of key molecular events underlying one of cancers' most common phenotypes, the "Warburg Effect", i.e., elevated glycolysis in the presence of oxygen.

    PubMed

    Pedersen, Peter L

    2007-06-01

    As a new faculty member at The Johns Hopkins University, School of Medicine, the author began research on cancer in 1969 because this frequently fatal disease touched many whom he knew. He was intrigued with its viscous nature, the failure of all who studied it to find a cure, and also fascinated by the pioneering work of Otto Warburg, a biochemical legend and Nobel laureate. Warburg who died 1 year later in 1970 had shown in the 1920s that the most striking biochemical phenotype of cancers is their aberrant energy metabolism. Unlike normal tissues that derive most of their energy (ATP) by metabolizing the sugar glucose to carbon dioxide and water, a process that involves oxygen-dependent organelles called "mitochondria", Warburg showed that cancers frequently rely less on mitochondria and obtain as much as 50% of their ATP by metabolizing glucose directly to lactic acid, even in the presence of oxygen. This frequent phenotype of cancers became known as the "Warburg effect", and the author of this review strongly believed its understanding would facilitate the discovery of a cure. Following in the final footsteps of Warburg and caught in the midst of an unpleasant anti-Warburg, anti-metabolic era, the author and his students/collaborators began quietly to identify the key molecular events involved in the "Warburg effect". Here, the author describes via a series of sequential discoveries touching five decades how despite some impairment in the respiratory capacity of malignant tumors, that hexokinase 2 (HK-2), its mitochondrial receptor (VDAC), and the gene that encodes HK-2 (HK-2 gene) play the most pivotal and direct roles in the "Warburg effect". They discovered also that like a "Trojan horse" the simple lactic acid analog 3-bromopyruvate selectively enters the cells of cancerous animal tumors that exhibit the "Warburg effect" and quickly dissipates their energy (ATP) production factories (i.e., glycolysis and mitochondria) resulting in tumor destruction without

  9. 47 CFR 22.917 - Emission limitations for cellular equipment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Emission limitations for cellular equipment. 22.917 Section 22.917 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER... equipment. The rules in this section govern the spectral characteristics of emissions in the Cellular...

  10. Rare Events

    DTIC Science & Technology

    2009-10-01

    terrorists are likely to acquire and use WMDs over the next ten years. • Provide means to target areas, entities and persons facilitating adver - sary WMD...complicated and unpredictable to begin with, but also that human adver - saries (unlike physical disasters) will react and adapt to our planning to try to make...virulent vaccine strain (Keim et al., 2001). The latter might not be regarded as a bioterrorism event, even though it caused seven deaths and incited

  11. Predictability in cellular automata.

    PubMed

    Agapie, Alexandru; Andreica, Anca; Chira, Camelia; Giuclea, Marius

    2014-01-01

    Modelled as finite homogeneous Markov chains, probabilistic cellular automata with local transition probabilities in (0, 1) always posses a stationary distribution. This result alone is not very helpful when it comes to predicting the final configuration; one needs also a formula connecting the probabilities in the stationary distribution to some intrinsic feature of the lattice configuration. Previous results on the asynchronous cellular automata have showed that such feature really exists. It is the number of zero-one borders within the automaton's binary configuration. An exponential formula in the number of zero-one borders has been proved for the 1-D, 2-D and 3-D asynchronous automata with neighborhood three, five and seven, respectively. We perform computer experiments on a synchronous cellular automaton to check whether the empirical distribution obeys also that theoretical formula. The numerical results indicate a perfect fit for neighbourhood three and five, which opens the way for a rigorous proof of the formula in this new, synchronous case.

  12. Probabilistic cellular automata.

    PubMed

    Agapie, Alexandru; Andreica, Anca; Giuclea, Marius

    2014-09-01

    Cellular automata are binary lattices used for modeling complex dynamical systems. The automaton evolves iteratively from one configuration to another, using some local transition rule based on the number of ones in the neighborhood of each cell. With respect to the number of cells allowed to change per iteration, we speak of either synchronous or asynchronous automata. If randomness is involved to some degree in the transition rule, we speak of probabilistic automata, otherwise they are called deterministic. With either type of cellular automaton we are dealing with, the main theoretical challenge stays the same: starting from an arbitrary initial configuration, predict (with highest accuracy) the end configuration. If the automaton is deterministic, the outcome simplifies to one of two configurations, all zeros or all ones. If the automaton is probabilistic, the whole process is modeled by a finite homogeneous Markov chain, and the outcome is the corresponding stationary distribution. Based on our previous results for the asynchronous case-connecting the probability of a configuration in the stationary distribution to its number of zero-one borders-the article offers both numerical and theoretical insight into the long-term behavior of synchronous cellular automata.

  13. Semantic Event Correlation Using Ontologies

    NASA Astrophysics Data System (ADS)

    Moser, Thomas; Roth, Heinz; Rozsnyai, Szabolcs; Mordinyi, Richard; Biffl, Stefan

    Complex event processing (CEP) is a software architecture paradigm that aims at low latency, high throughput, and quick adaptability of applications for supporting and improving event-driven business processes. Events sensed in real time are the basic information units on which CEP applications operate and react in self-contained decision cycles based on defined processing logic and rules. Event correlation is necessary to relate events gathered from various sources for detecting patterns and situations of interest in the business context. Unfortunately, event correlation has been limited to syntactically identical attribute values instead of addressing semantically equivalent attribute meanings. Semantic equivalence is particularly relevant if events come from organizations that use different terminologies for common concepts.

  14. Cellular Senescence, Neurological Function, and Redox State.

    PubMed

    Maciel-Barón, Luis Ángel; Moreno-Blas, Daniel; Morales-Rosales, Sandra Lizbeth; González-Puertos, Viridiana Yazmín; López-Díazguerrero, Norma Edith; Torres, Claudio; Castro-Obregón, Susana; Königsberg, Mina

    2017-06-08

    Cellular senescence, characterized by permanent cell cycle arrest, has been extensively studied in mitotic cells such as fibroblasts. However, senescent cells have also been observed in the brain. Even though it is recognized that cellular energetic metabolism and redox homeostasis are perturbed in the aged brain and neurodegenerative diseases (NDDs), it is still unknown which alterations in the overall physiology can stimulate cellular senescence induction and their relationship with the former events. Recent Advances: Recent findings have shown that during prolonged inflammatory and pathologic events, the blood-brain barrier could be compromised and immune cells might enter the brain; this fact along with the brain's high oxygen dependence might result in oxidative damage to macromolecules and therefore senescence induction. Thus, cellular senescence in different brain cell types is revised here. Most information related to cellular senescence in the brain has been obtained from research in glial cells since it has been assumed that the senescent phenotype is a feature exclusive to mitotic cells. Nevertheless, neurons with senescence hallmarks have been observed in old mouse brains. Therefore, although this is a controversial topic in the field, here we summarize and integrate the observations from several studies and propose that neurons indeed senesce. It is still unknown which alterations in the overall metabolism can stimulate senescence induction in the aged brain, what are the mechanisms and signaling pathways, and what is their relationship to NDD development. The understanding of these processes will expose new targets to intervene age-associated pathologies.-Antioxid. Redox Signal. 00, 000-000.

  15. Cellular Communication through Light

    PubMed Central

    Fels, Daniel

    2009-01-01

    Information transfer is a fundamental of life. A few studies have reported that cells use photons (from an endogenous source) as information carriers. This study finds that cells can have an influence on other cells even when separated with a glass barrier, thereby disabling molecule diffusion through the cell-containing medium. As there is still very little known about the potential of photons for intercellular communication this study is designed to test for non-molecule-based triggering of two fundamental properties of life: cell division and energy uptake. The study was performed with a cellular organism, the ciliate Paramecium caudatum. Mutual exposure of cell populations occurred under conditions of darkness and separation with cuvettes (vials) allowing photon but not molecule transfer. The cell populations were separated either with glass allowing photon transmission from 340 nm to longer waves, or quartz being transmittable from 150 nm, i.e. from UV-light to longer waves. Even through glass, the cells affected cell division and energy uptake in neighboring cell populations. Depending on the cuvette material and the number of cells involved, these effects were positive or negative. Also, while paired populations with lower growth rates grew uncorrelated, growth of the better growing populations was correlated. As there were significant differences when separating the populations with glass or quartz, it is suggested that the cell populations use two (or more) frequencies for cellular information transfer, which influences at least energy uptake, cell division rate and growth correlation. Altogether the study strongly supports a cellular communication system, which is different from a molecule-receptor-based system and hints that photon-triggering is a fine tuning principle in cell chemistry. PMID:19340303

  16. Formin’ cellular structures

    PubMed Central

    Bogdan, Sven; Schultz, Jörg; Grosshans, Jörg

    2014-01-01

    Members of the Diaphanous (Dia) protein family are key regulators of fundamental actin driven cellular processes, which are conserved from yeast to humans. Researchers have uncovered diverse physiological roles in cell morphology, cell motility, cell polarity, and cell division, which are involved in shaping cells into tissues and organs. The identification of numerous binding partners led to substantial progress in our understanding of the differential functions of Dia proteins. Genetic approaches and new microscopy techniques allow important new insights into their localization, activity, and molecular principles of regulation. PMID:24719676

  17. Ultradiscrete Systems (Cellular Automata)

    NASA Astrophysics Data System (ADS)

    Tokihiro, Tetsuji

    Ultradiscretization is a limiting procedure which allows one to obtain a cellular automaton (CA) from continuous equations. Using this method, we can construct integrable CAs from integrable partial difference equations. In this course, we focus on a typical integrable CA, called a Box and Ball system (BBS), and review its peculiar features. Since a BBS is an ultradiscrete limit of the discrete KP equation and discrete Toda equation, we can obtain explicit solutions and conserved quantities for the BBS. Furthermore the BBS is also regarded as a limit (crystallization) of an integrable lattice model. Recent topics, and a periodic BBS in particular are also reviewed.

  18. Review of cellular mechanotransduction

    NASA Astrophysics Data System (ADS)

    Wang, Ning

    2017-06-01

    Living cells and tissues experience physical forces and chemical stimuli in the human body. The process of converting mechanical forces into biochemical activities and gene expression is mechanochemical transduction or mechanotransduction. Significant advances have been made in understanding mechanotransduction at the cellular and molecular levels over the last two decades. However, major challenges remain in elucidating how a living cell integrates signals from mechanotransduction with chemical signals to regulate gene expression and to generate coherent biological responses in living tissues in physiological conditions and diseases.

  19. Cellular mechanics and motility

    NASA Astrophysics Data System (ADS)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

  20. Oral Cellular Neurothekeoma

    PubMed Central

    Emami, Nader; Zawawi, Faisal; Ywakim, Rania; Daniel, Sam J.

    2013-01-01

    Cellular neurothekeoma is known as a cutaneous tumor with uncertain histogenesis. Very little involvement of mucosal membrane has been reported in the literature so far. This is a case report of an intraoral lesion in a 15-years-old girl. Histopathologic evaluation showed a tumor-consists of spindle to epitheloid cells forming micronodules in a concentric whorled shape pattern. Tumor cells were positive for CD63, vimentin, and NKI-C3. Total excision was performed and no recurrence happened after 16-month followup. PMID:23691398

  1. Cells anticipate periodic events

    NASA Astrophysics Data System (ADS)

    Nakagaki, Toshiyuki

    2009-03-01

    We show that an amoeboid organism can anticipate the timing of periodic events. The plasmodium of the true slime mold Physarum polycephalum moves rapidly under favourable conditions, but stops moving when transferred to less-favourable conditions. Plasmodia exposed to unfavourable conditions, presented in three consecutive pulses at constant intervals, reduced their locomotive speed in response to each episode. When subsequently subjected to favourable conditions, the plasmodia spontaneously reduced their locomotive speed at the time point when the next unfavourable episode would have occurred. This implied anticipation of impending environmental change. After this behaviour had been evoked several times, the locomotion of the plasmodia returned to normal; however, the anticipatory response could subsequently be induced by a single unfavourable pulse, implying recall of the memorized periodicity. We explored the mechanisms underlying these behaviours from a dynamical systems perspective. Our results hint at the cellular origins of primitive intelligence and imply that simple dynamics might be sufficient to explain its emergence.

  2. Cellular Mechanisms of Somatic Stem Cell Aging

    PubMed Central

    Jung, Yunjoon

    2014-01-01

    Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

  3. A scientific role for Space Station Freedom: Research at the cellular level

    NASA Technical Reports Server (NTRS)

    Johnson, Terry C.; Brady, John N.

    1993-01-01

    The scientific importance of Space Station Freedom is discussed in light of the valuable information that can be gained in cellular and developmental biology with regard to the microgravity environment on the cellular cytoskeleton, cellular responses to extracellular signal molecules, morphology, events associated with cell division, and cellular physiology. Examples of studies in basic cell biology, as well as their potential importance to concerns for future enabling strategies, are presented.

  4. Vaccines for the common cold.

    PubMed

    Simancas-Racines, Daniel; Guerra, Claudia V; Hidalgo, Ricardo

    2013-06-12

    The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat and fever (usually < 37.8˚C). The widespread morbidity it causes worldwide is related to its ubiquitousness rather than its severity. The development of vaccines for the common cold has been difficult because of antigenic variability of the common cold virus and the indistinguishable multiple other viruses and even bacteria acting as infective agents. There is uncertainty regarding the efficacy and safety of interventions for preventing the common cold in healthy people. To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people. We searched CENTRAL (2012, Issue 12), MEDLINE (1948 to January week 1, 2013), EMBASE (1974 to January 2013), CINAHL (1981 to January 2013) and LILACS (1982 to January 2013). Randomised controlled trials (RCTs) of any virus vaccines to prevent the common cold in healthy people. Two review authors independently evaluated methodological quality and extracted trial data. Disagreements were resolved by discussion or by consulting a third review author. This review included one RCT with 2307 healthy participants; all of them were analysed. This trial compared the effect of an adenovirus vaccine against a placebo. No statistically significant difference in common cold incidence was found: there were 13 events in 1139 participants in the vaccines group and 14 events in 1168 participants in the placebo group; risk ratio (RR) 0.95, 95% confidence interval (CI) 0.45 to 2.02, P = 0.90). No adverse events related to the live vaccine were reported. This Cochrane review has found a lack of evidence on the effects of vaccines for the common cold in healthy people. Only one RCT was found and this did not show differences between comparison groups; it also had a high risk of bias. There are no conclusive data to support the use of

  5. Cellular Analogs of Operant Behavior

    DTIC Science & Technology

    1990-12-31

    activity rather than by a cellular reinforcement process. We have always required as critical evidence of cellular reinforcement that noncontingent or... reinforcement process. We have always required as critical evidence of cellular reinforcement that noncortingent or random presentations of the positive...the burst- ing of hippocampal pyramidal cells. One approach is to attempt to reinforce hippocamp- al bursting with a nonspecific depolarizing agent

  6. Geophysical events

    NASA Astrophysics Data System (ADS)

    This is a summary of SEAN Bulletin, 13(2), February 29, 1988, a publication of the Smithsonian Institution's Scientific Event Alert Network. The complete bulletin is available in the microfiche edition of Eos as a microfiche supplement or as a paper reprint. For the microfiche, order document E88-002 at $2.50 (U.S.) by writing to AGU Orders, 2000 Florida Avenue, N.W., Washington, DC 20009 or by calling toll free on 800-424-2488. For the paper reprint, order SEAN Bulletin (giving volume and issue numbers and issue date) through the same address; the price is $3.50 for one copy of each issue number for those who do not have a deposit account, $2 for those who do; additional copies of each issue number are $ 1.

  7. Multifunctional periodic cellular metals.

    PubMed

    Wadley, Haydn N G

    2006-01-15

    Periodic cellular metals with honeycomb and corrugated topologies are widely used for the cores of light weight sandwich panel structures. Honeycombs have closed cell pores and are well suited for thermal protection while also providing efficient load support. Corrugated core structures provide less efficient and highly anisotropic load support, but enable cross flow heat exchange opportunities because their pores are continuous in one direction. Recent advances in topology design and fabrication have led to the emergence of lattice truss structures with open cell structures. These three classes of periodic cellular metals can now be fabricated from a wide variety of structural alloys. Many topologies are found to provide adequate stiffness and strength for structural load support when configured as the cores of sandwich panels. Sandwich panels with core relative densities of 2-10% and cell sizes in the millimetre range are being assessed for use as multifunctional structures. The open, three-dimensional interconnected pore networks of lattice truss topologies provide opportunities for simultaneously supporting high stresses while also enabling cross flow heat exchange. These highly compressible structures also provide opportunities for the mitigation of high intensity dynamic loads created by impacts and shock waves in air or water. By filling the voids with polymers and hard ceramics, these structures have also been found to offer significant resistance to penetration by projectiles.

  8. Cellular Array Processing Simulation

    NASA Astrophysics Data System (ADS)

    Lee, Harry C.; Preston, Earl W.

    1981-11-01

    The Cellular Array Processing Simulation (CAPS) system is a high-level image language that runs on a multiprocessor configuration. CAPS is interpretively decoded on a conventional minicomputer with all image operation instructions executed on an array processor. The synergistic environment that exists between the minicomputer and the array processor gives CAPS its high-speed throughput, while maintaining a convenient conversational user language. CAPS was designed to be both modular and table driven so that it can be easily maintained and modified. CAPS uses the image convolution operator as one of its primitives and performs this cellular operation by decomposing it into parallel image steps that are scheduled to be executed on the array processor. Among its features is the ability to observe the imagery in real time as a user's algorithm is executed. This feature reduces the need for image storage space, since it is feasible to retain only original images and produce resultant images when needed. CAPS also contains a language processor that permits users to develop re-entrant image processing subroutines or algorithms.

  9. Triangles bridge the scales: Quantifying cellular contributions to tissue deformation

    NASA Astrophysics Data System (ADS)

    Merkel, Matthias; Etournay, Raphaël; Popović, Marko; Salbreux, Guillaume; Eaton, Suzanne; Jülicher, Frank

    2017-03-01

    In this article, we propose a general framework to study the dynamics and topology of cellular networks that capture the geometry of cell packings in two-dimensional tissues. Such epithelia undergo large-scale deformation during morphogenesis of a multicellular organism. Large-scale deformations emerge from many individual cellular events such as cell shape changes, cell rearrangements, cell divisions, and cell extrusions. Using a triangle-based representation of cellular network geometry, we obtain an exact decomposition of large-scale material deformation. Interestingly, our approach reveals contributions of correlations between cellular rotations and elongation as well as cellular growth and elongation to tissue deformation. Using this triangle method, we discuss tissue remodeling in the developing pupal wing of the fly Drosophila melanogaster.

  10. The cellularity yield of three different 22-gauge endoscopic ultrasound fine needle aspiration needles.

    PubMed

    Othman, Mohamed O; Abdelfatah, Mohamed M; Padilla, Osvaldo; Hussinat, Maha; Elhanafi, Sherif; Eloliby, Mohamed; Torabi, Alireza; Hakim, Nawar; Boman, Darius A

    2017-05-01

    Endoscopic ultrasound (EUS) fine needle aspiration (FNA) is an integral part in the diagnosis of pancreatic, intestinal and extra-intestinal masses or lesions. There is no clear data on the superiority of the core biopsy needle over standard 22-gauge needles. The aim of this study is to prospectively compare the cellularity yield of three commonly used 22-gauge FNA needles available in the US market. This is a prospective, randomized study comparing the cellularity yield of three commercially available EUS needles (two standard FNA needles and core biopsy needle). Two blinded pathologists evaluated the cytology specimens based on an already agreed upon cytology score. We included adult patients (18-80 years old) who presented to our endoscopy unit for FNA of pancreatic or extrapancreatic masses. 109 patients (57 F, 52 M) were recruited to the study, 88 lesions were pancreatic lesions. 39 patients were recruited in the EZ Shot 2™ group, 36 in the Procore(®) group and 34 in the Expect™ group. The average cellularity score and the mean number of passes (SD) were not different between the three needles; P = 0.91 and P = 0.16, respectively. There was no difference between the three needles in obtaining an onsite diagnosis (P = 0.627) and no difference in reported adverse events between the three groups. The cellularity yields, the mean number of passes and reported adverse events were similar in the three compared 22-gauge needles. Diagn. Cytopathol. 2017;45:426-432. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Intravital microscopy: new insights into cellular interactions.

    PubMed

    Gavins, Felicity N E

    2012-10-01

    Inflammation is the body's way of combating invading pathogens or noxious stimuli. Under normal conditions, the complex host response of rubor, dolor, calor, tumor, and functio laesa is essential for survival and the return to homeostasis. However, unregulated inflammation is all too often observed in diseases such as rheumatoid arthritis, stroke, and cancer. The host inflammatory response is governed by a number of tightly regulated processes that enable cellular trafficking to occur at the sites of damage to ultimately ensure the resolution of inflammation. Intravital microscopy (IVM) provides quantitative, qualitative, and dynamic insights into cell biology and these cellular interactions. This review highlights the pros and cons of this specialized technique and how it has evolved to help understand the physiology and pathophysiology of inflammatory events in a number of different disease states, leading to a number of potential therapeutic targets for drug discovery. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. 47 CFR 22.228 - Cellular rural service area licenses subject to competitive bidding.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Licensing Requirements and Procedures Competitive Bidding... initial applications for Cellular Rural Service Area licenses are subject to competitive bidding....

  13. Events diary

    NASA Astrophysics Data System (ADS)

    2000-01-01

    as Imperial College, the Royal Albert Hall, the Royal College of Art, the Natural History and Science Museums and the Royal Geographical Society. Under the heading `Shaping the future together' BA2000 will explore science, engineering and technology in their wider cultural context. Further information about this event on 6 - 12 September may be obtained from Sandra Koura, BA2000 Festival Manager, British Association for the Advancement of Science, 23 Savile Row, London W1X 2NB (tel: 0171 973 3075, e-mail: sandra.koura@britassoc.org.uk ). Details of the creating SPARKS events may be obtained from creating.sparks@britassoc.org.uk or from the website www.britassoc.org.uk . Other events 3 - 7 July, Porto Alegre, Brazil VII Interamerican conference on physics education: The preparation of physicists and physics teachers in contemporary society. Info: IACPE7@if.ufrgs.br or cabbat1.cnea.gov.ar/iacpe/iacpei.htm 27 August - 1 September, Barcelona, Spain GIREP conference: Physics teacher education beyond 2000. Info: www.blues.uab.es/phyteb/index.html

  14. Cellular inactivation by ultrasound.

    PubMed

    Li, G C; Hahn, G M; Tolmach, L J

    1977-05-12

    The lethal effect of ultrasound (US) on mammalian cells has received relatively little attention. Understandably, potential genetic aspects of US have been of prime concern to physicians who use US as a diagnostic tool; at the average power densities involved (<1 W cm(-2)) little, if any cell killing is to be expected. There have been sporadic attempts to use higher intensities ( approximately 1 W cm(-2)) as a treatment modality in cancer therapy, but those experiments seem to have been based on inadequate cellular studies. The effects of US usually were evaluated in terms of morphological criteria rather than on quantitative determination of the loss of viability as measured by colony formation. There are few reports of the effects of US on survival of mammalian cells, and none specifically examine hyperthermic interaction. With the increased interest in hyperthermia for tumour therapy, attention has been directed towards the use of ultrasound to achieve tumour heating. In preliminary experiments in which US was used to heat the EMT6 sarcoma and KHJJ carcinoma in mice, we found a high percentage of tumour cures with short (approximately 30 min) treatments at temperatures (43-44 degrees C) where in vitro results of hyperthermia-induced cell killing would not have led to a prediction of any cures. We therefore initiated an investigation of the effects of US on survival of Chinese hamster cells to see if direct cell killing by US could explain our in vivo results, or, as in the case of radiofrequency (RF) electromagnetic heating, we would be forced to invoke host response(8). In particular, we examined the thermal and non-thermal components of cellular inactivation by US. We report here that there is a definite non-thermal cytotoxic effect of US. Its relative contribution to cell killing is a highly nonlinear function of the temperature of the cellular milieu. The survival curves show clearly that, beyond an initial threshold, small changes in temperature and/or US

  15. Integrated cellular systems

    NASA Astrophysics Data System (ADS)

    Harper, Jason C.

    The generation of new three-dimensional (3D) matrices that enable integration of biomolecular components and whole cells into device architectures, without adversely altering their morphology or activity, continues to be an expanding and challenging field of research. This research is driven by the promise that encapsulated biomolecules and cells can significantly impact areas as diverse as biocatalysis, controlled delivery of therapeutics, environmental and industrial process monitoring, early warning of warfare agents, bioelectronics, photonics, smart prosthetics, advanced physiological sensors, portable medical diagnostic devices, and tissue/organ replacement. This work focuses on the development of a fundamental understanding of the biochemical and nanomaterial mechanisms that govern the cell directed assembly and integration process. It was shown that this integration process relies on the ability of cells to actively develop a pH gradient in response to evaporation induced osmotic stress, which catalyzes silica condensation within a thin 3D volume surrounding the cells, creating a functional bio/nano interface. The mechanism responsible for introducing functional foreign membrane-bound proteins via proteoliposome addition to the silica-lipid-cell matrix was also determined. Utilizing this new understanding, 3D cellular immobilization capabilities were extended using sol-gel matrices endowed with glycerol, trehalose, and media components. The effects of these additives, and the metabolic phase of encapsulated S. cerivisiase cells, on long-term viability and the rate of inducible gene expression was studied. This enabled the entrapment of cells within a novel microfluidic platform capable of simultaneous colorimetric, fluorescent, and electrochemical detection of a single analyte, significantly improving confidence in the biosensor output. As a complementary approach, multiphoton protein lithography was utilized to engineer 3D protein matrices in which to

  16. Cellular Morphogenesis In Silico

    PubMed Central

    Shinbrot, Troy; Chun, Young; Caicedo-Carvajal, Carlos; Foty, Ramsey

    2009-01-01

    Abstract We describe a model that simulates spherical cells of different types that can migrate and interact either attractively or repulsively. We find that both expected morphologies and previously unreported patterns spontaneously self-assemble. Among the newly discovered patterns are a segmented state of alternating discs, and a “shish-kebab” state, in which one cell type forms a ring around a second type. We show that these unique states result from cellular attraction that increases with distance (e.g., as membranes stretch viscoelastically), and would not be seen in traditional, e.g., molecular, potentials that diminish with distance. Most of the states found computationally have been observed in vitro, and it remains to be established what role these self-assembled states may play in in vivo morphogenesis. PMID:19686642

  17. [Senescence and cellular immortality].

    PubMed

    Trentesaux, C; Riou, J-F

    2010-11-01

    Senescence was originally described from the observation of the limited ability of normal cells to grow in culture, and may be generated by telomere erosion, accumulation of DNA damages, oxidative stress and modulation of oncogenes or tumor suppressor genes. Senescence corresponds to a cellular response aiming to control tumor progression by limiting cell proliferation and thus constitutes an anticancer barrier. Senescence is observed in pre-malignant tumor stages and disappears from malignant tumors. Agents used in standard chemotherapy also have the potential to induce senescence, which may partly explain their therapeutic activities. It is possible to restore senescence in tumors using targeted therapies that triggers telomere dysfunction or reactivates suppressor genes functions, which are essential for the onset of senescence.

  18. Cardiac Troponin and Tropomyosin: Structural and Cellular Perspectives to Unveil the Hypertrophic Cardiomyopathy Phenotype

    PubMed Central

    Marques, Mayra de A.; de Oliveira, Guilherme A. P.

    2016-01-01

    Inherited myopathies affect both skeletal and cardiac muscle and are commonly associated with genetic dysfunctions, leading to the production of anomalous proteins. In cardiomyopathies, mutations frequently occur in sarcomeric genes, but the cause-effect scenario between genetic alterations and pathological processes remains elusive. Hypertrophic cardiomyopathy (HCM) was the first cardiac disease associated with a genetic background. Since the discovery of the first mutation in the β-myosin heavy chain, more than 1400 new mutations in 11 sarcomeric genes have been reported, awarding HCM the title of the “disease of the sarcomere.” The most common macroscopic phenotypes are left ventricle and interventricular septal thickening, but because the clinical profile of this disease is quite heterogeneous, these phenotypes are not suitable for an accurate diagnosis. The development of genomic approaches for clinical investigation allows for diagnostic progress and understanding at the molecular level. Meanwhile, the lack of accurate in vivo models to better comprehend the cellular events triggered by this pathology has become a challenge. Notwithstanding, the imbalance of Ca2+ concentrations, altered signaling pathways, induction of apoptotic factors, and heart remodeling leading to abnormal anatomy have already been reported. Of note, a misbalance of signaling biomolecules, such as kinases and tumor suppressors (e.g., Akt and p53), seems to participate in apoptotic and fibrotic events. In HCM, structural and cellular information about defective sarcomeric proteins and their altered interactome is emerging but still represents a bottleneck for developing new concepts in basic research and for future therapeutic interventions. This review focuses on the structural and cellular alterations triggered by HCM-causing mutations in troponin and tropomyosin proteins and how structural biology can aid in the discovery of new platforms for therapeutics. We highlight the

  19. Geophysical events

    NASA Astrophysics Data System (ADS)

    This is a summary of SEAN Bulletin, 13 (6), June 30, 1988, a publication of the Smithsonian Institution's Scientific Event Alert Network. The complete bulletin is available in the microfiche edition of Eos as a microfiche supplement or as a paper reprint. For the microfiche, order document E88-005 at $2.50 (U.S.) by writing to AGU Orders, 2000 Florida Avenue, N.W., Washington, DC 20009 or by calling toll free on 800-424-2488. For the paper reprint, order SEAN Bulletin (giving volume and issue numbers and issue date) through the same address; the price is $3.50 for one copy of each issue number for those who do not have a deposit account, $2 for those who do; additional copies of each issue number are $ 1. Subscriptions to SEAN Bulletin are also available from AGU-Orders; the price is $18 for 12 monthly issues mailed to a U.S. address, $28 if mailed elsewhere, and must be prepaid. SEAN Bulletin is available on Kosmos. Type CHECK SEAN on Part A of Kosmos.

  20. Geophysical events

    NASA Astrophysics Data System (ADS)

    This is a summary of SEAN Bulletin, 25(10), October 31, 1988, a publication of the Smithsonian Institution's Scientific Event Alert Network. The complete bulletin is available in the microfiche edition of Eos as a microfiche supplement or as a paper reprint. For the microfiche, order document E88-010 at $2.50 (U.S.) by writing to AGU Orders, 2000 Florida Avenue, N.W., Washington, DC 20009 or by calling toll free on 800-424-2488. For the paper reprint, order SEAN Bulletin (giving volume and issue numbers and issue date) through the same address; the price is $3.50 for one copy of each issue number for those who do not have a deposit account, $2 for those who do; additional copies of each issue number are $ 1 . Subscriptions to SEAN Bulletin are also available from AGU-Orders; the price is $18 for 12 monthly issues mailed to a U.S. address, $28 if mailed elsewhere, and must be prepaid. SEAN Bulletin is available on Kosmos. Type CHECK SEAN on Part A of Kosmos

  1. Geophysical events

    NASA Astrophysics Data System (ADS)

    This is a summary of SEAN Bulletin, 13(3), March 31, 1988, a publication of the Smithsonian Institution's Scientific Event Alert Network. The complete bulletin is available in the microfiche edition of Eos as a microfiche supplement or as a paper reprint. For the microfiche, order document E88-002 at $2.50 (U.S.) by writing to AGU Orders, 2000 Florida Avenue, N.W., Washington, DC 20009 or by calling toll free on 800-424-2488. For the paper reprint, order SEAN Bulletin (giving volume and issue numbers and issue date) through the same address; the price is $3.50 for one copy of each issue number for those who do not have a deposit account, $2 for those who do; additional copies of each issue number are $1. Subscriptions to SEAN Bulletin are also available from AGU-Orders; the price is $18 for 12 monthly issues mailed to a U.S. address, $28 if mailed elsewhere, and must be prepaid.

  2. Geophysical events

    NASA Astrophysics Data System (ADS)

    This is a summary of SEAN Bulletin, 13 (7), July 31, 1988, a publication of the Smithsonian Institution's Scientific Event Alert Network. The complete bulletin is available in the microfiche edition of Eos as a microfiche supplement or as a paper reprint. For the microfiche, order document E88-007 at $2.50 (U.S.) by writing to AGU Orders, 2000 Florida Avenue, N.W., Washington, DC 20009 or by calling toll free on 800-424-2488. For the paper reprint, order SEAN Bulletin (giving volume and issue numbers and issue date) through the same address; the price is $3.50 for one copy of each issue number for those who do not have a deposit account, $2 for those who do; additional copies of each issue number are $1. Subscriptions to SEAN Bulletin are also available from AGU-Orders; the price is $18 for 12 monthly issues mailed to a U.S. address, $28 if mailed elsewhere, and must be prepaid. SEAN Bulletin is available on Kosmos. Type CHECK SEAN on Part A of Kosmos.

  3. Geophysical events

    NASA Astrophysics Data System (ADS)

    This is a summary of SEAN Bulletin, 13 (1), January 31, 1988, a publication of the Smithsonian Institution's Scientific Event Alert Network. The complete bulletin is available in the microfiche edition of Eos as a microfiche supplement or as a paper reprint. For the microfiche, order document E88-001 at $2.50 (U.S.) by writing to AGU Orders, 2000 Florida Avenue, N.W., Washington, DC 20009 or by calling toll free on 800-424-2488. For the paper reprint, order SEAN Bulletin (giving volume and issue numbers and issue date) through the same address; the price is $3.50 for one copy of each issue number for those who do not have a deposit account, $2 for those who do; additional copies of each issue number are $ 1. Subscriptions to SEAN Bulletin are also available from AGU Orders; the price is $18 for 12 monthly issues mailed to a U.S. address, $28 if mailed elsewhere, and must be prepaid.

  4. Geophysical events

    NASA Astrophysics Data System (ADS)

    This is a summary of SEAN Bulletin, 13(9), September 30, 1988, a publication of the Smithsonian Institution's Scientific Event Alert Network. The complete bulletin is available in the microfiche edition of Eos as a microfiche supplement or as a paper reprint. For the microfiche, order document E88-013 at $2.50 (U.S.) by writing to AGU Orders, 2000 Florida Avenue, N.W., Washington, DC 20009 or by calling toll free on 800-424-2488. For the paper reprint, order SEAN Bulletin (giving volume and issue numbers and issue date) through the same address; the price is $3.50 for one copy of each issue number for those who do not have a deposit account, $2 for those who do; additional copies of each issue number are $1. Subscriptions to SEAN Bulletin are also available from AGU-Orders; the price is $18 for 12 monthly issues mailed to a U.S. address, $28 if mailed elsewhere, and must be prepaid. SEAN Bulletin is available on Kosmos. Type CHECK SEAN on Part A of Kosmos.

  5. Geophysical events

    NASA Astrophysics Data System (ADS)

    This is a summary of SEAN Bulletin, 13 (5), May 31, 1988, a publication of the Smithsonian Institution's Scientific Event Alert Network. The complete bulletin is available in the microfiche edition of Eos as a microfiche supplement or as a paper reprint. For the microfiche, order document E88-004 at $2.50 (U.S.) by writing to AGU Orders, 2000 Florida Avenue, N.W., Washington, DC 20009 or by calling toll free on 800-424-2488. For the paper reprint, order SEAN Bulletin (giving volume and issue numbers and issue date) through the same address; the price is $3.50 for one copy of each issue number for those who do not have a deposit account, $2 for those who do; additional copies of each issue number are $ 1. Subscriptions to SEAN Bulletin are also available from AGU-Orders; the price is $18 for 12 monthly issues mailed to a U.S. address, $28 if mailed elsewhere, and must be prepaid. SEAN Bulletin is available on Kosmos. Type CHECK SEAN on Part A of Kosmos.

  6. No Common Opinion on the Common Core

    ERIC Educational Resources Information Center

    Henderson, Michael B.; Peterson, Paul E.; West, Martin R.

    2015-01-01

    According to the three authors of this article, the 2014 "EdNext" poll yields four especially important new findings: (1) Opinion with respect to the Common Core has yet to coalesce. The idea of a common set of standards across the country has wide appeal, and the Common Core itself still commands the support of a majority of the public.…

  7. Atypical cellular blue nevi (cellular blue nevi with atypical features): lack of consensus for diagnosis and distinction from cellular blue nevi and malignant melanoma ("malignant blue nevus").

    PubMed

    Barnhill, Raymond L; Argenyi, Zsolt; Berwick, Marianne; Duray, Paul H; Erickson, Lori; Guitart, Joan; Horenstein, Marcello G; Lowe, Lori; Messina, Jane; Paine, Susan; Piepkorn, Michael W; Prieto, Victor; Rabkin, Michael S; Schmidt, Birgitta; Selim, Angelica; Shea, Chris R; Trotter, Martin J

    2008-01-01

    The distinction of cellular blue nevi (CBN) with atypical features ["atypical" CBN (ACBN)] from conventional CBN and malignant melanomas related to or derived from CBN remains a difficult problem. Here, we report on the diagnosis of various cellular blue melanocytic neoplasms by 14 dermatopathologists who routinely examine melanocytic lesions. Three parameters were assessed: (1) for between rater analyses, we calculated interobserver agreement by the kappa statistic (regardless of whether the diagnosis was correct). (2) For each individual lesion, we reported whether a majority agreement (>50%) was reached and, if so, whether the majority agreed with the gold standard diagnosis, derived from standardized histopathologic criteria for melanoma, definitive outcome such as metastatic event or death of disease, or disease-free follow-up for > or =4 years. (3) For the individual pathologists, we calculated sensitivity and specificity for each type of lesion. The study set included 26 melanocytic lesions: (1) 6 malignant melanomas developing in or with attributes of CBN; (2) 11 CBN with atypical features and indeterminate biologic potential (ACBN); (3) 8 conventional CBN; and (4) 1 common BN. The kappa values for interrater agreement varied from 0.52 (95% confidence interval 0.45, 0.58) for melanoma to 0.02 (0.05, 0.08) for ACBN and 0.20 (0.13, 0.28) for CBN. The kappa for all lesions was 0.25 (0.22, 0.28). The pathologists' sensitivities were 68.6% (61.0%, 76.1%) for melanoma, 33.1% (21.0%, 45.2%) for ACBN, and 44.6% (29.0%, 60.3%) for CBN. The specificities were 65.7% (55.8%, 75.6%) for melanoma, 84.7% (77.3%, 92.2%) for ACBN, and 89.9% (82.7%, 97.1%) for CBN. Overall, greater than 50% of the pathologists agreed and were correct in their diagnosis 38.5% (10 lesions) of the time. There was a majority agreement, but with an incorrect diagnosis, another 26.9% (7 lesions) of the time. Six of the 7 majority agreements with an incorrect diagnosis were for ACBN lesions. In

  8. 47 CFR 22.939 - Site availability requirements for applications competing with cellular renewal applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... competing with cellular renewal applications. 22.939 Section 22.939 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.939 Site availability requirements for applications competing with cellular renewal applications. In...

  9. Reference materials for cellular therapeutics.

    PubMed

    Bravery, Christopher A; French, Anna

    2014-09-01

    The development of cellular therapeutics (CTP) takes place over many years, and, where successful, the developer will anticipate the product to be in clinical use for decades. Successful demonstration of manufacturing and quality consistency is dependent on the use of complex analytical methods; thus, the risk of process and method drift over time is high. The use of reference materials (RM) is an established scientific principle and as such also a regulatory requirement. The various uses of RM in the context of CTP manufacturing and quality are discussed, along with why they are needed for living cell products and the analytical methods applied to them. Relatively few consensus RM exist that are suitable for even common methods used by CTP developers, such as flow cytometry. Others have also identified this need and made proposals; however, great care will be needed to ensure any consensus RM that result are fit for purpose. Such consensus RM probably will need to be applied to specific standardized methods, and the idea that a single RM can have wide applicability is challenged. Written standards, including standardized methods, together with appropriate measurement RM are probably the most appropriate way to define specific starting cell types. The characteristics of a specific CTP will to some degree deviate from those of the starting cells; consequently, a product RM remains the best solution where feasible. Each CTP developer must consider how and what types of RM should be used to ensure the reliability of their own analytical measurements.

  10. Different Kinds of Causality in Event Cognition

    ERIC Educational Resources Information Center

    Radvansky, Gabriel A.; Tamplin, Andrea K.; Armendarez, Joseph; Thompson, Alexis N.

    2014-01-01

    Narrative memory is better for information that is more causally connected and occurs at event boundaries, such as a causal break. However, it is unclear whether there are common or distinct influences of causality. For the event boundaries that arise as a result of causal breaks, the events that follow may subsequently become more causally…

  11. New cellular mechanisms of gap junction degradation and recycling.

    PubMed

    Carette, Diane; Gilleron, Jérôme; Denizot, Jean-Pierre; Grant, Kirsty; Pointis, Georges; Segretain, Dominique

    2015-07-01

    Connexins (Cxs), the constitutive proteins of gap junctions, are key actors of many physiological processes. Therefore, alterations of Cx expression and degradation lead to the development of physiopathological disorders. Because of the formation of a double membrane vesicle termed annular gap junction (AGJ), gap junction degradation is a unique physiological process for which many cellular aspects remain unclear. By using a combination of time-lapse fluorescence microscopy and high-resolution transmission electron microscopy, we evidenced new specific cellular events concerning gap junction degradation and recycling. Indeed, by time lapse video microscopy we demonstrated, for the first time to our knowledge, that an entire AGJ can be fully recycled back to the plasma membrane. Moreover, we dissected the degradative processes of gap junction by electron microscopy approaches. Interestingly, in addition to canonical autophagy and heterophagy pathways, previously described, we discovered that both pathways could sometimes intermingle. Strikingly, our results also highlighted a new lysosome-based autophagy pathway that could play a pivotal role in common autophagy degradation. The present investigation reveals that AGJ degradation is a more complex process that it was previously thought. First, a complete recycling of the gap junction plaque after its internalisation could occur. Second, the degradation of this peculiar double membrane structure is possible through autophagy, heterophagy, hetero-autophagy or by lysosomal-based autophagy. Altogether, this work underlines novel aspects of gap junction degradation that could be extended to other cell biology processes. © 2015 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  12. Laminin 332 processing impacts cellular behavior

    PubMed Central

    Rousselle, Patricia; Beck, Konrad

    2013-01-01

    Laminin 332, composed of the α3, β3 and γ2 chains, is an epithelial-basement membrane specific laminin variant. Its main role in normal tissues is the maintenance of epithelial-mesenchymal cohesion in tissues exposed to external forces, including skin and stratified squamous mucosa. After being secreted and deposited in the extracellular matrix, laminin 332 undergoes physiological maturation processes consisting in the proteolytic processing of domains located within the α3 and the γ2 chains. These maturation events are essential for laminin 332 integration into the basement membrane where it plays an important function in the nucleation and maintenance of anchoring structures. Studies in normal and pathological situations have revealed that laminin 332 can trigger distinct cellular events depending on the level of its proteolytic cleavages. In this review, the biological and structural characteristics of laminin 332 domains are presented and we discuss whether they trigger specific functions. PMID:23263634

  13. Reactive nitrogen species in cellular signaling

    PubMed Central

    Adams, Levi; Franco, Maria C

    2015-01-01

    The transduction of cellular signals occurs through the modification of target molecules. Most of these modifications are transitory, thus the signal transduction pathways can be tightly regulated. Reactive nitrogen species are a group of compounds with different properties and reactivity. Some reactive nitrogen species are highly reactive and their interaction with macromolecules can lead to permanent modifications, which suggested they were lacking the specificity needed to participate in cell signaling events. However, the perception of reactive nitrogen species as oxidizers of macromolecules leading to general oxidative damage has recently evolved. The concept of redox signaling is now well established for a number of reactive oxygen and nitrogen species. In this context, the post-translational modifications introduced by reactive nitrogen species can be very specific and are active participants in signal transduction pathways. This review addresses the role of these oxidative modifications in the regulation of cell signaling events. PMID:25888647

  14. Fibre based cellular transfection.

    PubMed

    Tsampoula, X; Taguchi, K; Cizmár, T; Garces-Chavez, V; Ma, N; Mohanty, S; Mohanty, K; Gunn-Moore, F; Dholakia, K

    2008-10-13

    Optically assisted transfection is emerging as a powerful and versatile method for the delivery of foreign therapeutic agents to cells at will. In particular the use of ultrashort pulse lasers has proved an important route to transiently permeating the cell membrane through a multiphoton process. Though optical transfection has been gaining wider usage to date, all incarnations of this technique have employed free space light beams. In this paper we demonstrate the first system to use fibre delivery for the optical transfection of cells. We engineer a standard optical fibre to generate an axicon tip with an enhanced intensity of the remote output field that delivers ultrashort (~ 800 fs) pulses without requiring the fibre to be placed in very close proximity to the cell sample. A theoretical model is also developed in order to predict the light propagation from axicon tipped and bare fibres, in both air and water environments. The model proves to be in good agreement with the experimental findings and can be used to establish the optimum fibre parameters for successful cellular transfection. We readily obtain efficiencies of up to 57 % which are comparable with free space transfection. This advance paves the way for optical transfection of tissue samples and endoscopic embodiments of this technique.

  15. Cellular energy metabolism

    SciTech Connect

    Glaser, M.

    1991-06-01

    Studies have been carried out on adenylate kinase which is an important enzyme in determining the concentrations of the adenine nucleotides. An efficient method has been developed to clone mutant adenylate kinase genes in E. coli. Site-specific mutagenesis of the wild type gene also has been used to obtain forms of adenylate kinase with altered amino acids. The wild type and mutant forms of adenylate kinase have been overexpressed and large quantities were readily isolated. The kinetic and fluorescence properties of the different forms of adenylate kinase were characterized. This has led to a new model for the location of the AMP and ATP bindings sites on the enzyme and a proposal for the mechanism of substrate inhibition. Crystals of the wild type enzyme were obtained that diffract to at least 2.3 {angstrom} resolution. Experiments were also initiated to determine the function of adenylate kinase in vivo. In one set of experiments, E. coli strains with mutations in adenylate kinase showed large changes in cellular nucleotides after reaching the stationary phase in a low phosphate medium. This was caused by selective proteolytic degradation of the mutant adenylate kinase caused by phosphate starvation.

  16. Event segmentation ability uniquely predicts event memory.

    PubMed

    Sargent, Jesse Q; Zacks, Jeffrey M; Hambrick, David Z; Zacks, Rose T; Kurby, Christopher A; Bailey, Heather R; Eisenberg, Michelle L; Beck, Taylor M

    2013-11-01

    Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan.

  17. Atypical cellular blue nevus or malignant blue nevus?*

    PubMed Central

    Daltro, Luise Ribeiro; Yaegashi, Lygia Bertalha; Freitas, Rodrigo Abdalah; Fantini, Bruno de Carvalho; Souza, Cacilda da Silva

    2017-01-01

    Blue nevus is a benign melanocytic lesion whose most frequent variants are dendritic (common) blue nevus and cellular blue nevus. Atypical cellular blue nevus presents an intermediate histopathology between the typical and a rare variant of malignant blue nevus/melanoma arising in a cellular blue nevus. An 8-year-old child presented a pigmented lesion in the buttock since birth, but with progressive growth in the last two years. After surgical excision, histopathological examination revealed atypical cellular blue nevus. Presence of mitoses, ulceration, infiltration, cytological atypia or necrosis may occur in atypical cellular blue nevus, making it difficult to differentiate it from melanoma. The growth of blue nevus is unusual and considered of high-risk for malignancy, being an indicator for complete resection and periodic follow-up of these patients. PMID:28225968

  18. [Cellular therapy and leg ulcers: Future approaches].

    PubMed

    Senet, P

    2015-01-01

    The prevalence of leg ulcers, which are most commonly caused by venous insufficiency, is high in Europe. Current treatments are fairly unsatisfactory, with long healing times in many cases, as well as a high risk of relapse. Over the last 15 years, improved understanding of the cellular and molecular mechanisms at work in delayed wound healing has contributed to the development of cellular therapy in this field. The use of keratinocytes or cultured fibroblasts, whether autogenic or allogenic, has been of little value in terms of either healing times or rates of complete healing. For the moment, there are very few allogenic skin substitutes available; they are expensive and have been insufficiently studied in the indication of leg ulcers. Pluripotent mesenchymal adult stem cells have proved capable of accelerating wound healing in animal models and their study in chronic wounds in humans is currently awaited.

  19. Ceramide glycosylation potentiates cellular multidrug resistance.

    PubMed

    Liu, Y Y; Han, T Y; Giuliano, A E; Cabot, M C

    2001-03-01

    Ceramide glycosylation, through glucosylceramide synthase (GCS), allows cellular escape from ceramide-induced programmed cell death. This glycosylation event confers cancer cell resistance to cytotoxic anticancer agents [Liu, Y. Y., Han, T. Y., Giuliano, A. E., and M. C. Cabot. (1999) J. Biol. Chem. 274, 1140-1146]. We previously found that glucosylceramide, the glycosylated form of ceramide, accumulates in adriamycin-resistant breast carcinoma cells, in vinblastine-resistant epithelioid carcinoma cells, and in tumor specimens from patients showing poor response to chemotherapy. Here we show that multidrug resistance can be increased over baseline and then totally reversed in human breast cancer cells by GCS gene targeting. In adriamycin-resistant MCF-7-AdrR cells, transfection of GCS upgraded multidrug resistance, whereas transfection of GCS antisense markedly restored cellular sensitivity to anthracyclines, Vinca alkaloids, taxanes, and other anticancer drugs. Sensitivity to the various drugs by GCS antisense transfection increased 7- to 240-fold and was consistent with the resumption of ceramide-caspase-apoptotic signaling. GCS targeting had little influence on cellular sensitivity to either 5-FU or cisplatin, nor did it modify P-glycoprotein expression or rhodamine-123 efflux. GCS antisense transfection did enhance rhodamine-123 uptake compared with parent MCF-7-AdrR cells. This study reveals that GCS is a novel mechanism of multidrug resistance and positions GCS antisense as an innovative force to overcome multidrug resistance in cancer chemotherapy.

  20. [Cellular and molecular mechanisms of memory].

    PubMed

    Laroche, Serge

    2010-01-01

    A defining characteristic of the brain is its remarkable capacity to undergo activity-dependent functional and morphological remodelling via mechanisms of plasticity that form the basis of our capacity to encode and retain memories. Today, it is generally accepted that one key neurobiological mechanism underlying the formation of memories reside in activity-driven modifications of synaptic strength and structural remodelling of neural networks activated during learning. The discovery and detailed report of the phenomenon generally known as long-term potentiation, a long-lasting activity-dependent form of synaptic strengthening, opened a new chapter in the study of the neurobiological substrate of memory in the vertebrate brain, and this form of synaptic plasticity has now become the dominant model in the search for the cellular bases of learning and memory. To date, the key events in the cellular and molecular mechanisms underlying synaptic plasticity and memory formation are starting to be identified. They require the activation of specific receptors and of several molecular cascades to convert extracellular signals into persistent functional changes in neuronal connectivity. Accumulating evidence suggests that the rapid activation of neuronal gene programs is a key mechanism underlying the enduring modification of neural networks required for the laying down of memory. The recent developments in the search for the cellular and molecular mechanisms of memory storage are reviewed.

  1. [Cellular and molecular mechanisms of memory].

    PubMed

    Laroche, S

    2001-01-01

    There has been nearly a century of interest in the idea that information is encoded in the brain as specific spatio-temporal patterns of activity in distributed networks and stored as changes in the efficacy of synaptic connections on neurons that are activated during learning. The discovery and detailed report of the phenomenon generally known as long-term potentiation opened a new chapter in the study of synaptic plasticity in the vertebrate brain, and this form of synaptic plasticity has now become the dominant model in the search for the cellular bases of learning and memory. To date, the key events in the cellular and molecular mechanisms underlying synaptic plasticity are starting to be identified. They require the activation of specific receptors and of several molecular cascades to convert extracellular signals into persistent functional changes in neuronal connectivity. Accumulating evidence suggests that the rapid activation of the genetic machinery is a key mechanism underlying the enduring modification of neural networks required for the laying down of memory. The recent developments in the search for the cellular and molecular mechanisms of memory storage are reviewed.

  2. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets...

  3. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets...

  4. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  5. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  6. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  7. Dynamics of Cellular Responses to Radiation

    PubMed Central

    Wodarz, Dominik; Sorace, Ron; Komarova, Natalia L.

    2014-01-01

    Understanding the consequences of exposure to low dose ionizing radiation is an important public health concern. While the risk of low dose radiation has been estimated by extrapolation from data at higher doses according to the linear non-threshold model, it has become clear that cellular responses can be very different at low compared to high radiation doses. Important phenomena in this respect include radioadaptive responses as well as low-dose hyper-radiosensitivity (HRS) and increased radioresistance (IRR). With radioadaptive responses, low dose exposure can protect against subsequent challenges, and two mechanisms have been suggested: an intracellular mechanism, inducing cellular changes as a result of the priming radiation, and induction of a protected state by inter-cellular communication. We use mathematical models to examine the effect of these mechanisms on cellular responses to low dose radiation. We find that the intracellular mechanism can account for the occurrence of radioadaptive responses. Interestingly, the same mechanism can also explain the existence of the HRS and IRR phenomena, and successfully describe experimentally observed dose-response relationships for a variety of cell types. This indicates that different, seemingly unrelated, low dose phenomena might be connected and driven by common core processes. With respect to the inter-cellular communication mechanism, we find that it can also account for the occurrence of radioadaptive responses, indicating redundancy in this respect. The model, however, also suggests that the communication mechanism can be vital for the long term survival of cell populations that are continuously exposed to relatively low levels of radiation, which cannot be achieved with the intracellular mechanism in our model. Experimental tests to address our model predictions are proposed. PMID:24722167

  8. Common Cause Failure Modeling

    NASA Technical Reports Server (NTRS)

    Hark, Frank; Britton, Paul; Ring, Robert; Novack, Steven

    2015-01-01

    Space Launch System (SLS) Agenda: Objective; Key Definitions; Calculating Common Cause; Examples; Defense against Common Cause; Impact of varied Common Cause Failure (CCF) and abortability; Response Surface for various CCF Beta; Takeaways.

  9. MSAT and cellular hybrid networking

    NASA Technical Reports Server (NTRS)

    Baranowsky, Patrick W., II

    1993-01-01

    Westinghouse Electric Corporation is developing both the Communications Ground Segment and the Series 1000 Mobile Phone for American Mobile Satellite Corporation's (AMSC's) Mobile Satellite (MSAT) system. The success of the voice services portion of this system depends, to some extent, upon the interoperability of the cellular network and the satellite communication circuit switched communication channels. This paper will describe the set of user-selectable cellular interoperable modes (cellular first/satellite second, etc.) provided by the Mobile Phone and described how they are implemented with the ground segment. Topics including roaming registration and cellular-to-satellite 'seamless' call handoff will be discussed, along with the relevant Interim Standard IS-41 Revision B Cellular Radiotelecommunications Intersystem Operations and IOS-553 Mobile Station - Land Station Compatibility Specification.

  10. Modeling cellular deformations using the level set formalism

    PubMed Central

    Yang, Liu; Effler, Janet C; Kutscher, Brett L; Sullivan, Sarah E; Robinson, Douglas N; Iglesias, Pablo A

    2008-01-01

    Background Many cellular processes involve substantial shape changes. Traditional simulations of these cell shape changes require that grids and boundaries be moved as the cell's shape evolves. Here we demonstrate that accurate cell shape changes can be recreated using level set methods (LSM), in which the cellular shape is defined implicitly, thereby eschewing the need for updating boundaries. Results We obtain a viscoelastic model of Dictyostelium cells using micropipette aspiration and show how this viscoelastic model can be incorporated into LSM simulations to recreate the observed protrusion of cells into the micropipette faithfully. We also demonstrate the use of our techniques by simulating the cell shape changes elicited by the chemotactic response to an external chemoattractant gradient. Conclusion Our results provide a simple but effective means of incorporating cellular deformations into mathematical simulations of cell signaling. Such methods will be useful for simulating important cellular events such as chemotaxis and cytokinesis. PMID:18652669

  11. Creating Special Events

    ERIC Educational Resources Information Center

    deLisle, Lee

    2009-01-01

    "Creating Special Events" is organized as a systematic approach to festivals and events for students who seek a career in event management. This book looks at the evolution and history of festivals and events and proceeds to the nuts and bolts of event management. The book presents event management as the means of planning, organizing, directing,…

  12. Creating Special Events

    ERIC Educational Resources Information Center

    deLisle, Lee

    2009-01-01

    "Creating Special Events" is organized as a systematic approach to festivals and events for students who seek a career in event management. This book looks at the evolution and history of festivals and events and proceeds to the nuts and bolts of event management. The book presents event management as the means of planning, organizing, directing,…

  13. Traumatic-event headaches

    PubMed Central

    2004-01-01

    Background Chronic headaches from head trauma and whiplash injury are well-known and common, but chronic headaches from other sorts of physical traumas are not recognized. Methods Specific information was obtained from the medical records of 15 consecutive patients with chronic headaches related to physically injurious traumatic events that did not include either head trauma or whiplash injury. The events and the physical injuries produced by them were noted. The headaches' development, characteristics, duration, frequency, and accompaniments were recorded, as were the patients' use of pain-alleviative drugs. From this latter information, the headaches were classified by the diagnostic criteria of the International Headache Society as though they were naturally-occurring headaches. The presence of other post-traumatic symptoms and litigation were also recorded. Results The intervals between the events and the onset of the headaches resembled those between head traumas or whiplash injuries and their subsequent headaches. The headaches themselves were, as a group, similar to those after head trauma and whiplash injury. Thirteen of the patients had chronic tension-type headache, two had migraine. The sustained bodily injuries were trivial or unidentifiable in nine patients. Fabrication of symptoms for financial remuneration was not evident in these patients of whom seven were not even seeking payments of any kind. Conclusions This study suggests that these hitherto unrecognized post-traumatic headaches constitute a class of headaches characterized by a relation to traumatic events affecting the body but not including head or whiplash traumas. The bodily injuries per se can be discounted as the cause of the headaches. So can fabrication of symptoms for financial remuneration. Altered mental states, not systematically evaluated here, were a possible cause of the headaches. The overall resemblance of these headaches to the headaches after head or whiplash traumas implies

  14. Common Career Technical Core: Common Standards, Common Vision for CTE

    ERIC Educational Resources Information Center

    Green, Kimberly

    2012-01-01

    This article provides an overview of the National Association of State Directors of Career Technical Education Consortium's (NASDCTEc) Common Career Technical Core (CCTC), a state-led initiative that was created to ensure that career and technical education (CTE) programs are consistent and high quality across the United States. Forty-two states,…

  15. Common Career Technical Core: Common Standards, Common Vision for CTE

    ERIC Educational Resources Information Center

    Green, Kimberly

    2012-01-01

    This article provides an overview of the National Association of State Directors of Career Technical Education Consortium's (NASDCTEc) Common Career Technical Core (CCTC), a state-led initiative that was created to ensure that career and technical education (CTE) programs are consistent and high quality across the United States. Forty-two states,…

  16. Hippocampal ensemble dynamics timestamp events in long-term memory

    PubMed Central

    Rubin, Alon; Geva, Nitzan; Sheintuch, Liron; Ziv, Yaniv

    2015-01-01

    The capacity to remember temporal relationships between different events is essential to episodic memory, but little is currently known about its underlying mechanisms. We performed time-lapse imaging of thousands of neurons over weeks in the hippocampal CA1 of mice as they repeatedly visited two distinct environments. Longitudinal analysis exposed ongoing environment-independent evolution of episodic representations, despite stable place field locations and constant remapping between the two environments. These dynamics time-stamped experienced events via neuronal ensembles that had cellular composition and activity patterns unique to specific points in time. Temporally close episodes shared a common timestamp regardless of the spatial context in which they occurred. Temporally remote episodes had distinct timestamps, even if they occurred within the same spatial context. Our results suggest that days-scale hippocampal ensemble dynamics could support the formation of a mental timeline in which experienced events could be mnemonically associated or dissociated based on their temporal distance. DOI: http://dx.doi.org/10.7554/eLife.12247.001 PMID:26682652

  17. A new technical approach to monitor the cellular physiology by atomic force microscopy.

    PubMed

    Jeong, Kyung Hwan; Lee, Sang Ho

    2012-12-01

    Atomic force microscopy (AFM) has become an important medical and biological tool for non-invasive imaging and measuring the mechanical changes of cells since its invention by Binnig et al. AFM can be used to investigate the mechanical properties of cellular events in individual living cells on a nanoscale level. In addition, the dynamic cellular movements induced by biochemical activation of specific materials can be detected in real time with three dimensional resolution. Force measurement with the use of AFM has become the tool of choice to monitor the mechanical changes of variable cellular events. In addition, the AFM approach can be applied to measure cellular adhesion properties. Moreover, the information gathered from AFM is important to understanding the mechanisms related to cellular movement and mechanical regulation. This review will discuss recent contributions of AFM to cellular physiology with a focus on monitoring the effects of antihypertensive agents in kidney cells.

  18. Top-down cellular pyramids

    SciTech Connect

    Wu, A.Y.; Rosenfeld, A.

    1982-07-01

    A cellular pyramid is an exponentially tapering stack of arrays of processors ('cells'), where each cell is connected to its neighbors ('siblings') on its own level, to a 'parent' on the level above, and to its 'children' on the level below. It is shown that in some situations, if information flows top-down only, from fathers to sons, then a cellular pyramid may be no faster than a one-level cellular array; but it may be possible to use simpler cells in the pyramid case.

  19. Four faces of cellular senescence

    PubMed Central

    Rodier, Francis

    2011-01-01

    Cellular senescence is an important mechanism for preventing the proliferation of potential cancer cells. Recently, however, it has become apparent that this process entails more than a simple cessation of cell growth. In addition to suppressing tumorigenesis, cellular senescence might also promote tissue repair and fuel inflammation associated with aging and cancer progression. Thus, cellular senescence might participate in four complex biological processes (tumor suppression, tumor promotion, aging, and tissue repair), some of which have apparently opposing effects. The challenge now is to understand the senescence response well enough to harness its benefits while suppressing its drawbacks. PMID:21321098

  20. Event group importance measures for top event frequency analyses

    SciTech Connect

    1995-07-31

    Three traditional importance measures, risk reduction, partial derivative, nd variance reduction, have been extended to permit analyses of the relative importance of groups of underlying failure rates to the frequencies of resulting top events. The partial derivative importance measure was extended by assessing the contribution of a group of events to the gradient of the top event frequency. Given the moments of the distributions that characterize the uncertainties in the underlying failure rates, the expectation values of the top event frequency, its variance, and all of the new group importance measures can be quantified exactly for two familiar cases: (1) when all underlying failure rates are presumed independent, and (2) when pairs of failure rates based on common data are treated as being equal (totally correlated). In these cases, the new importance measures, which can also be applied to assess the importance of individual events, obviate the need for Monte Carlo sampling. The event group importance measures are illustrated using a small example problem and demonstrated by applications made as part of a major reactor facility risk assessment. These illustrations and applications indicate both the utility and the versatility of the event group importance measures.

  1. Mechanism of cellular growth

    NASA Astrophysics Data System (ADS)

    David, Shaquan D.

    The purpose of this thesis is to investigate the effects of weak static and inhomogeneous magnetic fields on the growth and behavior of living organisms. We studied three common bacterial species of human flora in attempt to relate the effect of bacteria to human health. We measured the effects of various intensities of electromagnetic and randomly distributed fields to the physiological adaptation of the bacteria in relation to its environment. We also notice the different growth patterns of the three bacteria species when exposed to magnetic fields at a fixed temperature. The application of quantum electrodynamics describes the electrochemical interaction between the molecular bonding of the ions within the cell membrane and inorganic ions extracellular to the membrane. External magnetic fields contribute to the breaking and forming of covalent bonds to modify the time difference of DNA replication and metabolism of nutrients available for growth and sustainability. In short, we conclude that weak magnetic fields in a controlled environment affect the physiology and growth of cells.

  2. Targeting cellular metabolism to improve cancer therapeutics

    PubMed Central

    Zhao, Y; Butler, E B; Tan, M

    2013-01-01

    The metabolic properties of cancer cells diverge significantly from those of normal cells. Energy production in cancer cells is abnormally dependent on aerobic glycolysis. In addition to the dependency on glycolysis, cancer cells have other atypical metabolic characteristics such as increased fatty acid synthesis and increased rates of glutamine metabolism. Emerging evidence shows that many features characteristic to cancer cells, such as dysregulated Warburg-like glucose metabolism, fatty acid synthesis and glutaminolysis are linked to therapeutic resistance in cancer treatment. Therefore, targeting cellular metabolism may improve the response to cancer therapeutics and the combination of chemotherapeutic drugs with cellular metabolism inhibitors may represent a promising strategy to overcome drug resistance in cancer therapy. Recently, several review articles have summarized the anticancer targets in the metabolic pathways and metabolic inhibitor-induced cell death pathways, however, the dysregulated metabolism in therapeutic resistance, which is a highly clinical relevant area in cancer metabolism research, has not been specifically addressed. From this unique angle, this review article will discuss the relationship between dysregulated cellular metabolism and cancer drug resistance and how targeting of metabolic enzymes, such as glucose transporters, hexokinase, pyruvate kinase M2, lactate dehydrogenase A, pyruvate dehydrogenase kinase, fatty acid synthase and glutaminase can enhance the efficacy of common therapeutic agents or overcome resistance to chemotherapy or radiotherapy. PMID:23470539

  3. Pirin Inhibits Cellular Senescence in Melanocytic Cells

    PubMed Central

    Licciulli, Silvia; Luise, Chiara; Scafetta, Gaia; Capra, Maria; Giardina, Giuseppina; Nuciforo, Paolo; Bosari, Silvano; Viale, Giuseppe; Mazzarol, Giovanni; Tonelli, Chiara; Lanfrancone, Luisa; Alcalay, Myriam

    2011-01-01

    Cellular senescence has been widely recognized as a tumor suppressing mechanism that acts as a barrier to cancer development after oncogenic stimuli. A prominent in vivo model of the senescence barrier is represented by nevi, which are composed of melanocytes that, after an initial phase of proliferation induced by activated oncogenes (most commonly BRAF), are blocked in a state of cellular senescence. Transformation to melanoma occurs when genes involved in controlling senescence are mutated or silenced and cells reacquire the capacity to proliferate. Pirin (PIR) is a highly conserved nuclear protein that likely functions as a transcriptional regulator whose expression levels are altered in different types of tumors. We analyzed the expression pattern of PIR in adult human tissues and found that it is expressed in melanocytes and has a complex pattern of regulation in nevi and melanoma: it is rarely detected in mature nevi, but is expressed at high levels in a subset of melanomas. Loss of function and overexpression experiments in normal and transformed melanocytic cells revealed that PIR is involved in the negative control of cellular senescence and that its expression is necessary to overcome the senescence barrier. Our results suggest that PIR may have a relevant role in melanoma progression. PMID:21514450

  4. Targeting cellular metabolism to improve cancer therapeutics.

    PubMed

    Zhao, Y; Butler, E B; Tan, M

    2013-03-07

    The metabolic properties of cancer cells diverge significantly from those of normal cells. Energy production in cancer cells is abnormally dependent on aerobic glycolysis. In addition to the dependency on glycolysis, cancer cells have other atypical metabolic characteristics such as increased fatty acid synthesis and increased rates of glutamine metabolism. Emerging evidence shows that many features characteristic to cancer cells, such as dysregulated Warburg-like glucose metabolism, fatty acid synthesis and glutaminolysis are linked to therapeutic resistance in cancer treatment. Therefore, targeting cellular metabolism may improve the response to cancer therapeutics and the combination of chemotherapeutic drugs with cellular metabolism inhibitors may represent a promising strategy to overcome drug resistance in cancer therapy. Recently, several review articles have summarized the anticancer targets in the metabolic pathways and metabolic inhibitor-induced cell death pathways, however, the dysregulated metabolism in therapeutic resistance, which is a highly clinical relevant area in cancer metabolism research, has not been specifically addressed. From this unique angle, this review article will discuss the relationship between dysregulated cellular metabolism and cancer drug resistance and how targeting of metabolic enzymes, such as glucose transporters, hexokinase, pyruvate kinase M2, lactate dehydrogenase A, pyruvate dehydrogenase kinase, fatty acid synthase and glutaminase can enhance the efficacy of common therapeutic agents or overcome resistance to chemotherapy or radiotherapy.

  5. QUANTITATIVE IN VITRO MEASUREMENT OF CELLULAR PROCESSES CRITICAL TO THE DEVELOPMENT OF NEURAL CONNECTIVITY USING HCA.

    EPA Science Inventory

    New methods are needed to screen thousands of environmental chemicals for toxicity, including developmental neurotoxicity. In vitro, cell-based assays that model key cellular events have been proposed for high throughput screening of chemicals for developmental neurotoxicity. Whi...

  6. QUANTITATIVE IN VITRO MEASUREMENT OF CELLULAR PROCESSES CRITICAL TO THE DEVELOPMENT OF NEURAL CONNECTIVITY USING HCA.

    EPA Science Inventory

    New methods are needed to screen thousands of environmental chemicals for toxicity, including developmental neurotoxicity. In vitro, cell-based assays that model key cellular events have been proposed for high throughput screening of chemicals for developmental neurotoxicity. Whi...

  7. [Cellular senescence and chronic inflammation].

    PubMed

    Ohtani, Naoko

    2014-01-01

    It has recently become apparent that obesity is associated with chronic inflammation and several common types of cancer development. Although several events were proposed to be involved in these pathologies, the precise mechanisms underlying obesity-associated inflammation and cancer largely remain unclear. Here, we show that senescence-associated secretory phenotype (SASP) plays crucial roles in promoting obesity-associated hepatocellular carcinoma (HCC) development in mice. Dietary or genetic obesity induces alterations of gut microbiota, thereby increasing the levels of a bacterial metabolite that cause DNA damage. The enterohepatic circulation of the bacterial metabolites provokes SASP phenotype in hepatic stellate cells (HSCs), which in turn, secretes various inflammatory and tumour promoting factors in the liver, thus facilitating HCC development in mice after exposure to chemical carcinogen. Importantly, reducing gut bacteria efficiently prevents HCC development in obese mice. Similar results were also observed in mice lacking an SASP inducer or depleted of senescent HSCs, indicating that the induction of SASP by the gut bacterial metabolite in HSCs plays key roles in obesity-associated HCC development. Interestingly, moreover, signs of SASP were also observed in the HSCs in the area of HCC arising in patients with nonalcoholic steatohepatitis (NASH), implying that a similar pathway may contribute to at least certain aspects of obesity-associated HCC development in humans as well. These findings provide valuable new insights into the development of obesity-associated cancer.

  8. Vaccines for the common cold.

    PubMed

    Simancas-Racines, Daniel; Franco, Juan Va; Guerra, Claudia V; Felix, Maria L; Hidalgo, Ricardo; Martinez-Zapata, Maria José

    2017-05-18

    The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat, and fever (usually < 37.8º C). The widespread morbidity caused by the common cold worldwide is related to its ubiquitousness rather than its severity. The development of vaccines for the common cold has been difficult because of antigenic variability of the common cold virus and the indistinguishable multiple other viruses and even bacteria acting as infective agents. There is uncertainty regarding the efficacy and safety of interventions for preventing the common cold in healthy people. This is an update of a Cochrane review first published in 2011 and previously updated in 2013. To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (September 2016), MEDLINE (1948 to September 2016), Embase (1974 to September 2016), CINAHL (1981 to September 2016), and LILACS (1982 to September 2016). We also searched three trials registers for ongoing studies and four websites for additional trials (February 2017). We included no language or date restrictions. Randomised controlled trials (RCTs) of any virus vaccines compared with placebo to prevent the common cold in healthy people. Two review authors independently evaluated methodological quality and extracted trial data. We resolved disagreements by discussion or by consulting a third review author. We found no additional RCTs for inclusion in this update. This review includes one RCT dating from the 1960s with an overall high risk of bias. The RCT included 2307 healthy participants, all of whom were included in analyses. This trial compared the effect of an adenovirus vaccine against placebo. No statistically significant difference in common cold incidence was found: there were 13 (1.14%) events in 1139 participants in the

  9. A Course in Cellular Bioengineering.

    ERIC Educational Resources Information Center

    Lauffenburger, Douglas A.

    1989-01-01

    Gives an overview of a course in chemical engineering entitled "Cellular Bioengineering," dealing with how chemical engineering principles can be applied to molecular cell biology. Topics used are listed and some key references are discussed. Listed are 85 references. (YP)

  10. The cellular microscopy phenotype ontology.

    PubMed

    Jupp, Simon; Malone, James; Burdett, Tony; Heriche, Jean-Karim; Williams, Eleanor; Ellenberg, Jan; Parkinson, Helen; Rustici, Gabriella

    2016-01-01

    Phenotypic data derived from high content screening is currently annotated using free-text, thus preventing the integration of independent datasets, including those generated in different biological domains, such as cell lines, mouse and human tissues. We present the Cellular Microscopy Phenotype Ontology (CMPO), a species neutral ontology for describing phenotypic observations relating to the whole cell, cellular components, cellular processes and cell populations. CMPO is compatible with related ontology efforts, allowing for future cross-species integration of phenotypic data. CMPO was developed following a curator-driven approach where phenotype data were annotated by expert biologists following the Entity-Quality (EQ) pattern. These EQs were subsequently transformed into new CMPO terms following an established post composition process. CMPO is currently being utilized to annotate phenotypes associated with high content screening datasets stored in several image repositories including the Image Data Repository (IDR), MitoSys project database and the Cellular Phenotype Database to facilitate data browsing and discoverability.

  11. Origami interleaved tube cellular materials

    NASA Astrophysics Data System (ADS)

    Cheung, Kenneth C.; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

    2014-09-01

    A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis.

  12. A Course in Cellular Bioengineering.

    ERIC Educational Resources Information Center

    Lauffenburger, Douglas A.

    1989-01-01

    Gives an overview of a course in chemical engineering entitled "Cellular Bioengineering," dealing with how chemical engineering principles can be applied to molecular cell biology. Topics used are listed and some key references are discussed. Listed are 85 references. (YP)

  13. Dynamic Triggering of Microseismic Events

    NASA Astrophysics Data System (ADS)

    Lu, H.; Van der Baan, M.

    2015-12-01

    Microseismic events are commonly recorded during hydraulic fracturing experiments. In microseismic interpretations, each event is often regarded as independent and uncorrelated to neighboring ones. In reality, both the rock deformation (static stresses) and transient wave motion (dynamic stresses) associated with microseismic events add to the stress field together with the external loading (fluid injection). We believe the resulting static and dynamic stress perturbations will influence both the timing and spatial evolution of the microseismic cloud. We study the dynamic triggering of microseismicity using numerical simulations of a biaxial deformation test by means of a bonded particle method (Potyondy and Cundall, 2004), where crack development can be tracked and analyzed independently. Our methodology is to compare the stress changes due to one specific event with the occurrence of the next few events in the numerical simulations. In addition, we compute the dynamic stress perturbations for recorded large events analytically given their (non-double couple) failure mechanisms. Our results show that cracks following a major event tend to form in zones affected by the dynamic stresses by promoting new failure in areas that are critically stressed. This confirms that dynamic triggering during hydraulic fracturing operations but also larger scale seismicity is likely. It also demonstrates the often complex interplay between the dynamic and static stress changes and their effect on the temporal and spatial evolution of rock deformation at all scales.

  14. Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity

    PubMed Central

    Dalmasso, Giovanni; Marin Zapata, Paula Andrea; Brady, Nathan Ryan; Hamacher-Brady, Anne

    2017-01-01

    Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis) and the removal of damaged mitochondria by selective autophagy (mitophagy). While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM) to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1) mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2) restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3) maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4) our model suggests sources of, and stress conditions amplifying

  15. Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

    PubMed

    Dalmasso, Giovanni; Marin Zapata, Paula Andrea; Brady, Nathan Ryan; Hamacher-Brady, Anne

    2017-01-01

    Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis) and the removal of damaged mitochondria by selective autophagy (mitophagy). While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM) to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1) mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2) restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3) maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4) our model suggests sources of, and stress conditions amplifying

  16. Monkey hybrid stem cells develop cellular features of Huntington's disease

    PubMed Central

    2010-01-01

    Background Pluripotent stem cells that are capable of differentiating into different cell types and develop robust hallmark cellular features are useful tools for clarifying the impact of developmental events on neurodegenerative diseases such as Huntington's disease. Additionally, a Huntington's cell model that develops robust pathological features of Huntington's disease would be valuable for drug discovery research. Results To test this hypothesis, a pluripotent Huntington's disease monkey hybrid cell line (TrES1) was established from a tetraploid Huntington's disease monkey blastocyst generated by the fusion of transgenic Huntington's monkey skin fibroblast and a wild-type non-transgenic monkey oocyte. The TrES1 developed key Huntington's disease cellular pathological features that paralleled neural development. It expressed mutant huntingtin and stem cell markers, was capable of differentiating to neural cells, and developed teratoma in severely compromised immune deficient (SCID) mice. Interestingly, the expression of mutant htt, the accumulation of oligomeric mutant htt and the formation of intranuclear inclusions paralleled neural development in vitro , and even mutant htt was ubiquitously expressed. This suggests the development of Huntington's disease cellular features is influenced by neural developmental events. Conclusions Huntington's disease cellular features is influenced by neural developmental events. These results are the first to demonstrate that a pluripotent stem cell line is able to mimic Huntington's disease progression that parallels neural development, which could be a useful cell model for investigating the developmental impact on Huntington's disease pathogenesis. PMID:20132560

  17. Mathematical Modeling of Cellular Metabolism.

    PubMed

    Berndt, Nikolaus; Holzhütter, Hermann-Georg

    Cellular metabolism basically consists of the conversion of chemical compounds taken up from the extracellular environment into energy (conserved in energy-rich bonds of organic phosphates) and a wide array of organic molecules serving as catalysts (enzymes), information carriers (nucleic acids), and building blocks for cellular structures such as membranes or ribosomes. Metabolic modeling aims at the construction of mathematical representations of the cellular metabolism that can be used to calculate the concentration of cellular molecules and the rates of their mutual chemical interconversion in response to varying external conditions as, for example, hormonal stimuli or supply of essential nutrients. Based on such calculations, it is possible to quantify complex cellular functions as cellular growth, detoxification of drugs and xenobiotic compounds or synthesis of exported molecules. Depending on the specific questions to metabolism addressed, the methodological expertise of the researcher, and available experimental information, different conceptual frameworks have been established, allowing the usage of computational methods to condense experimental information from various layers of organization into (self-) consistent models. Here, we briefly outline the main conceptual frameworks that are currently exploited in metabolism research.

  18. Assessing Special Events.

    ERIC Educational Resources Information Center

    Neff, Bonita Dostal

    Special events defined as being "newsworthy events" are becoming a way of American life. They are also a means for making a lot of money. Examples of special events that are cited most frequently are often the most minor of events; e.g., the open house, the new business opening day gala, or a celebration of some event in an organization.…

  19. Event Segmentation Ability Uniquely Predicts Event Memory

    PubMed Central

    Sargent, Jesse Q.; Zacks, Jeffrey M.; Hambrick, David Z.; Zacks, Rose T.; Kurby, Christopher A.; Bailey, Heather R.; Eisenberg, Michelle L.; Beck, Taylor M.

    2013-01-01

    Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79 years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan. PMID:23942350

  20. Coordination of cellular differentiation, polarity, mitosis and meiosis - New findings from early vertebrate oogenesis.

    PubMed

    Elkouby, Yaniv M; Mullins, Mary C

    2017-10-15

    A mechanistic dissection of early oocyte differentiation in vertebrates is key to advancing our knowledge of germline development, reproductive biology, the regulation of meiosis, and all of their associated disorders. Recent advances in the field include breakthroughs in the identification of germline stem cells in Medaka, in the cellular architecture of the germline cyst in mice, in a mechanistic dissection of chromosomal pairing and bouquet formation in meiosis in mice, in tracing oocyte symmetry breaking to the chromosomal bouquet of meiosis in zebrafish, and in the biology of the Balbiani body, a universal oocyte granule. Many of the major events in early oogenesis are universally conserved, and some are co-opted for species-specific needs. The chromosomal events of meiosis are of tremendous consequence to gamete formation and have been extensively studied. New light is now being shed on other aspects of early oocyte differentiation, which were traditionally considered outside the scope of meiosis, and their coordination with meiotic events. The emerging theme is of meiosis as a common groundwork for coordinating multifaceted processes of oocyte differentiation. In an accompanying manuscript we describe methods that allowed for investigations in the zebrafish ovary to contribute to these breakthroughs. Here, we review these advances mostly from the zebrafish and mouse. We discuss oogenesis concepts across established model organisms, and construct an inclusive paradigm for early oocyte differentiation in vertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Signalling scaffolds and local organization of cellular behaviour.

    PubMed

    Langeberg, Lorene K; Scott, John D

    2015-04-01

    Cellular responses to environmental cues involve the mobilization of GTPases, protein kinases and phosphoprotein phosphatases. The spatial organization of these signalling enzymes by scaffold proteins helps to guide the flow of molecular information. Allosteric modulation of scaffolded enzymes can alter their catalytic activity or sensitivity to second messengers in a manner that augments, insulates or terminates local cellular events. This Review examines the features of scaffold proteins and highlights examples of locally organized groups of signalling enzymes that drive essential physiological processes, including hormone action, heart rate, cell division, organelle movement and synaptic transmission.

  2. Therapeutic Implications of Cellular Heterogeneity and Plasticity in Breast Cancer

    PubMed Central

    Brooks, Michael D.; Burness, Monika L.; Wicha, Max S.

    2015-01-01

    Summary Cellular heterogeneity represents one of the greatest challenges in cancer therapeutics. In many malignancies, this heterogeneity is generated during tumor evolution through a combination of genetic alterations and epigenetic events that recapitulate normal developmental processes including stem cell self-renewal and differentiation. Many, if not most, tumors display similar hierarchal organization, at the apex of which are “stem-like cells” that drive tumor growth, mediate metastasis and contribute to treatment resistance. Using breast cancer as a model, we discuss how an improved understanding of tumor cellular heterogeneity and plasticity may lead to development of more effective therapeutic strategies. PMID:26340526

  3. Senescence-messaging secretome: SMS-ing cellular stress.

    PubMed

    Kuilman, Thomas; Peeper, Daniel S

    2009-02-01

    Oncogene-induced cellular senescence constitutes a strong anti-proliferative response, which can be set in motion following either oncogene activation or loss of tumour suppressor signalling. It serves to limit the expansion of early neoplastic cells and as such is a potent cancer-protective response to oncogenic events. Recently emerging evidence points to a crucial role in oncogene-induced cellular senescence for the 'senescence-messaging secretome' or SMS, setting the stage for cross-talk between senescent cells and their environment. How are such signals integrated into a coordinated response and what are the implications of this unexpected finding?

  4. Finding Common Ground with the Common Core

    ERIC Educational Resources Information Center

    Moisan, Heidi

    2015-01-01

    This article examines the journey of museum educators at the Chicago History Museum in understanding the Common Core State Standards and implementing them in our work with the school audience. The process raised questions about our teaching philosophy and our responsibility to our audience. Working with colleagues inside and outside of our…

  5. How Common Is the Common Core?

    ERIC Educational Resources Information Center

    Thomas, Amande; Edson, Alden J.

    2014-01-01

    Since the introduction of the Common Core State Standards for Mathematics (CCSSM) in 2010, stakeholders in adopting states have engaged in a variety of activities to understand CCSSM standards and transition from previous state standards. These efforts include research, professional development, assessment and modification of curriculum resources,…

  6. Finding Common Ground with the Common Core

    ERIC Educational Resources Information Center

    Moisan, Heidi

    2015-01-01

    This article examines the journey of museum educators at the Chicago History Museum in understanding the Common Core State Standards and implementing them in our work with the school audience. The process raised questions about our teaching philosophy and our responsibility to our audience. Working with colleagues inside and outside of our…

  7. Holter and Event Monitors

    MedlinePlus

    ... Share this page from the NHLBI on Twitter. Holter and Event Monitors Also known as ambulatory EKG; continuous EKG; EKG event monitors. Holter and event monitors are small, portable electrocardiogram devices ...

  8. Event-Based Science.

    ERIC Educational Resources Information Center

    Wright, Russell G.

    1992-01-01

    Suggests that an event-based science curriculum can provide the framework for deciding what to retain in an overloaded science curriculum. Provides examples of current events and the science concepts explored related to the event. (MDH)

  9. BLOOD COAGULATION, FIBRINOLYSIS AND CELLULAR HAEMOSTASIS

    PubMed Central

    Piazza, Gregory; Fanikos, John; Zayaruzny, Maksim; Goldhaber, Samuel Z.

    2010-01-01

    SUMMARY The number of acutely ill hospitalized medical patients at risk for acute venous thromboembolism (VTE) has not been well defined. Therefore, we used the 2003 United States Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample database to estimate VTE events among hospitalized medical patients. We then modeled the potential reduction in VTE with universal utilization of appropriate pharmacological thromboprophylaxis. We calculated that 8,077,919 acutely ill hospitalized medical patients were at risk for VTE. Heart failure, respiratory failure, pneumonia, and cancer were the most common medical diagnoses. We estimated that 196,134 VTE-related events occurred in 2003, afflicting two out of every 100 acutely ill hospitalized medical patients. These VTE-related events were comprised of 122,235 symptomatic deep vein thromboses, 32,654 symptomatic episodes of pulmonary embolism, and 41,245 deaths due to VTE. In our model, rates of pharmacological thromboprophylaxis prescription were low for various acute medical illnesses, ranging from 15.3% to 49.2%. However, with universal thromboprophylaxis, 114,174 VTE-related events would have been prevented. In conclusion, acutely ill medical patients represent a large population vulnerable to the development of VTE during hospitalization. The number of VTE-related events would be halved with universal thromboprophylaxis. Further efforts focused on improving VTE prevention strategies in hospitalized medical patients are warranted. PMID:19718471

  10. Canonical Commonality Analysis.

    ERIC Educational Resources Information Center

    Leister, K. Dawn

    Commonality analysis is a method of partitioning variance that has advantages over more traditional "OVA" methods. Commonality analysis indicates the amount of explanatory power that is "unique" to a given predictor variable and the amount of explanatory power that is "common" to or shared with at least one predictor…

  11. Knowledge representation for commonality

    NASA Technical Reports Server (NTRS)

    Yeager, Dorian P.

    1990-01-01

    Domain-specific knowledge necessary for commonality analysis falls into two general classes: commonality constraints and costing information. Notations for encoding such knowledge should be powerful and flexible and should appeal to the domain expert. The notations employed by the Commonality Analysis Problem Solver (CAPS) analysis tool are described. Examples are given to illustrate the main concepts.

  12. Cellular and molecular connections between sleep and synaptic plasticity.

    PubMed

    Benington, Joel H; Frank, Marcos G

    2003-02-01

    The hypothesis that sleep promotes learning and memory has long been a subject of active investigation. This hypothesis implies that sleep must facilitate synaptic plasticity in some way, and recent studies have provided evidence for such a function. Our knowledge of both the cellular neurophysiology of sleep states and of the cellular and molecular mechanisms underlying synaptic plasticity has expanded considerably in recent years. In this article, we review findings in these areas and discuss possible mechanisms whereby the neurophysiological processes characteristic of sleep states may serve to facilitate synaptic plasticity. We address this issue first on the cellular level, considering how activation of T-type Ca(2+) channels in nonREM sleep may promote either long-term depression or long-term potentiation, as well as how cellular events of REM sleep may influence these processes. We then consider how synchronization of neuronal activity in thalamocortical and hippocampal-neocortical networks in nonREM sleep and REM sleep could promote differential strengthening of synapses according to the degree to which activity in one neuron is synchronized with activity in other neurons in the network. Rather than advocating one specific cellular hypothesis, we have intentionally taken a broad approach, describing a range of possible mechanisms whereby sleep may facilitate synaptic plasticity on the cellular and/or network levels. We have also provided a general review of evidence for and against the hypothesis that sleep does indeed facilitate learning, memory, and synaptic plasticity.

  13. Cellular telephone-based radiation detection instrument

    DOEpatents

    Craig, William W.; Labov, Simon E.

    2011-06-14

    A network of radiation detection instruments, each having a small solid state radiation sensor module integrated into a cellular phone for providing radiation detection data and analysis directly to a user. The sensor module includes a solid-state crystal bonded to an ASIC readout providing a low cost, low power, light weight compact instrument to detect and measure radiation energies in the local ambient radiation field. In particular, the photon energy, time of event, and location of the detection instrument at the time of detection is recorded for real time transmission to a central data collection/analysis system. The collected data from the entire network of radiation detection instruments are combined by intelligent correlation/analysis algorithms which map the background radiation and detect, identify and track radiation anomalies in the region.

  14. Molecular and cellular mechanisms of heterotopic ossification.

    PubMed

    Ramirez, Diana M; Ramirez, Melissa R; Reginato, Anthony M; Medici, Damian

    2014-10-01

    Heterotopic ossification (HO) is a debilitating condition in which cartilage and bone forms in soft tissues such as muscle, tendon, and ligament causing immobility. This process is induced by inflammation associated with traumatic injury. In an extremely rare genetic disorder called fibrodysplasia ossificans progessiva (FOP), a combination of inflammation associated with minor soft tissue injuries and a hereditary genetic mutation causes massive HO that progressively worsens throughout the patients' lifetime leading to the formation of an ectopic skeleton. An activating mutation in the BMP type I receptor ALK2 has been shown to contribute to the heterotopic lesions in FOP patients, yet recent studies have shown that other events are required to stimulate HO including activation of sensory neurons, mast cell degranulation, lymphocyte infiltration, skeletal myocyte cell death, and endothelial-mesenchymal transition (EndMT). In this review, we discuss the recent evidence and mechanistic data that describe the cellular and molecular mechanisms that give rise to heterotopic bone.

  15. Molecular and cellular mechanisms of heterotopic ossification

    PubMed Central

    Ramirez, Diana M.; Ramirez, Melissa R.; Reginato, Anthony M.; Medici, Damian

    2015-01-01

    Summary Heterotopic ossification (HO) is a debilitating condition in which cartilage and bone forms in soft tissues such as muscle, tendon, and ligament causing immobility. This process is induced by inflammation associated with traumatic injury. In an extremely rare genetic disorder called fibrodysplasia ossificans progessiva (FOP), a combination of inflammation associated with minor soft tissue injuries and a hereditary genetic mutation causes massive HO that progressively worsens throughout the patients’ lifetime leading to the formation of an ectopic skeleton. An activating mutation in the BMP type I receptor ALK2 has been shown to contribute to the heterotopic lesions in FOP patients, yet recent studies have shown that other events are required to stimulate HO including activation of sensory neurons, mast cell degranulation, lymphocyte infiltration, skeletal myocyte cell death, and endothelial-mesenchymal transition (EndMT). In this review, we discuss the recent evidence and mechanistic data that describe the cellular and molecular mechanisms that give rise to heterotopic bone. PMID:24796520

  16. Rethinking the regulation of cellular metabolism.

    PubMed

    Thompson, C B

    2011-01-01

    Most biologists working today have not considered the problem of how signal transduction events, which commit cells to energetically demanding processes such as growth and division, are connected to cellular metabolism. The primary reason for this is that we have believed for the last 30 or more years that the metabolism of cells is a homeostatic, self-regulating process that does not depend on any extracellular input. The traditional view is that a mammalian cell decides to take up nutrients whenever its bioenergetic and synthetic reserves are depleted. However, a considerable body of evidence now exists that challenges the notion that the nutrient uptake and metabolism of metazoan cells are cell-autonomous.

  17. Mechanisms of cellular invasion by intracellular parasites.

    PubMed

    Walker, Dawn M; Oghumu, Steve; Gupta, Gaurav; McGwire, Bradford S; Drew, Mark E; Satoskar, Abhay R

    2014-04-01

    Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.

  18. Cellular commitment in the developing cerebellum

    PubMed Central

    Marzban, Hassan; Del Bigio, Marc R.; Alizadeh, Javad; Ghavami, Saeid; Zachariah, Robby M.; Rastegar, Mojgan

    2014-01-01

    The mammalian cerebellum is located in the posterior cranial fossa and is critical for motor coordination and non-motor functions including cognitive and emotional processes. The anatomical structure of cerebellum is distinct with a three-layered cortex. During development, neurogenesis and fate decisions of cerebellar primordium cells are orchestrated through tightly controlled molecular events involving multiple genetic pathways. In this review, we will highlight the anatomical structure of human and mouse cerebellum, the cellular composition of developing cerebellum, and the underlying gene expression programs involved in cell fate commitments in the cerebellum. A critical evaluation of the cell death literature suggests that apoptosis occurs in ~5% of cerebellar cells, most shortly after mitosis. Apoptosis and cellular autophagy likely play significant roles in cerebellar development, we provide a comprehensive discussion of their role in cerebellar development and organization. We also address the possible function of unfolded protein response in regulation of cerebellar neurogenesis. We discuss recent advancements in understanding the epigenetic signature of cerebellar compartments and possible connections between DNA methylation, microRNAs and cerebellar neurodegeneration. Finally, we discuss genetic diseases associated with cerebellar dysfunction and their role in the aging cerebellum. PMID:25628535

  19. The origins of cellular life.

    PubMed

    Koonin, Eugene V

    2014-07-01

    All life on earth can be naturally classified into cellular life forms and virus-like selfish elements, the latter being fully dependent on the former for their reproduction. Cells are reproducers that not only replicate their genome but also reproduce the cellular organization that depends on semipermeable, energy-transforming membranes and cannot be recovered from the genome alone, under the famous dictum of Rudolf Virchow, Omnis cellula e cellula. In contrast, simple selfish elements are replicators that can complete their life cycles within the host cell starting from genomic RNA or DNA alone. The origin of the cellular organization is the central and perhaps the hardest problem of evolutionary biology. I argue that the origin of cells can be understood only in conjunction with the origin and evolution of selfish genetic elements. A scenario of precellular evolution is presented that involves cohesion of the genomes of the emerging cellular life forms from primordial pools of small genetic elements that eventually segregated into hosts and parasites. I further present a model of the coevolution of primordial membranes and membrane proteins, discuss protocellular and non-cellular models of early evolution, and examine the habitats on the primordial earth that could have been conducive to precellular evolution and the origin of cells.

  20. Classifying cellular automata using grossone

    NASA Astrophysics Data System (ADS)

    D'Alotto, Louis

    2016-10-01

    This paper proposes an application of the Infinite Unit Axiom and grossone, introduced by Yaroslav Sergeyev (see [7] - [12]), to the development and classification of one and two-dimensional cellular automata. By the application of grossone, new and more precise nonarchimedean metrics on the space of definition for one and two-dimensional cellular automata are established. These new metrics allow us to do computations with infinitesimals. Hence configurations in the domain space of cellular automata can be infinitesimally close (but not equal). That is, they can agree at infinitely many places. Using the new metrics, open disks are defined and the number of points in each disk computed. The forward dynamics of a cellular automaton map are also studied by defined sets. It is also shown that using the Infinite Unit Axiom, the number of configurations that follow a given configuration, under the forward iterations of cellular automaton maps, can now be computed and hence a classification scheme developed based on this computation.

  1. Sound attenuation characteristics of cellular metamaterials

    NASA Astrophysics Data System (ADS)

    Varanasi, Satya Surya Srinivas

    The objectives of this work were to develop lightweight barrier and compact absorbing material systems for controlling low frequency noise (say below 2 kHz). The solutions explored fell into the broad category of segmented cellular materials in which local resonances are built-in attributes. The body of the work was divided into four parts. First, a cellular metamaterial concept for lightweight barrier materials was proposed, then, secondly, the concept was experimentally verified by testing application-scale designs in a diffuse sound field setup. In the remaining two parts of the work, the idea of shifting sound energy emporally and spatially was explored as a means of improving the performance of metamaterial-based barrier solutions and of compact sound absorbers, respectively. The high sound transmission loss (STL) metamaterials described to-date commonly require the introduction of relatively heavy resonating or constraining components which runs counter to the desire to create lightweight barrier solutions. It was proposed here that a cellular panel comprising a periodic arrangement of unit cells consisting of plates held in a grid-like frame, which itself is unsupported, can possess a high STL within a specified frequency range without an undue mass penalty. It was numerically demonstrated that such a cellular panel can yield enhanced STL if the unit cell mass is apportioned appropriately between the unit cell plate and the surrounding grid-like frame. The concept of planar cellular metamaterials was verified through diffuse field experiments on application-scale specimens by using intensity methods. Two cellular panel designs were tested and their behavior was compared with that of a reference limp panel. It was found that the predicted benefit of the cellular panels could be realized by increasing the mass contrast in the designs, and that the benefit was reduced with increasing diffuseness of the sound field. It was also found that the loss in performance

  2. Connecting Photosynthesis and Cellular Respiration: Preservice Teachers' Conceptions

    ERIC Educational Resources Information Center

    Brown, Mary H.; Schwartz, Renee S.

    2009-01-01

    The biological processes of photosynthesis and plant cellular respiration include multiple biochemical steps, occur simultaneously within plant cells, and share common molecular components. Yet, learners often compartmentalize functions and specialization of cell organelles relevant to these two processes, without considering the interconnections…

  3. Using partial least squares regression to analyze cellular response data.

    PubMed

    Kreeger, Pamela K

    2013-04-16

    This Teaching Resource provides lecture notes, slides, and a problem set for a lecture introducing the mathematical concepts and interpretation of partial least squares regression (PLSR) that were part of a course entitled "Systems Biology: Mammalian Signaling Networks." PLSR is a multivariate regression technique commonly applied to analyze relationships between signaling or transcriptional data and cellular behavior.

  4. 47 CFR 32.5003 - Cellular mobile revenue.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Cellular mobile revenue. 32.5003 Section 32.5003 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003...

  5. 47 CFR 32.5003 - Cellular mobile revenue.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Cellular mobile revenue. 32.5003 Section 32.5003 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003...

  6. 47 CFR 32.5003 - Cellular mobile revenue.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Cellular mobile revenue. 32.5003 Section 32.5003 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003...

  7. 47 CFR 32.5003 - Cellular mobile revenue.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Cellular mobile revenue. 32.5003 Section 32.5003 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003...

  8. Connecting Photosynthesis and Cellular Respiration: Preservice Teachers' Conceptions

    ERIC Educational Resources Information Center

    Brown, Mary H.; Schwartz, Renee S.

    2009-01-01

    The biological processes of photosynthesis and plant cellular respiration include multiple biochemical steps, occur simultaneously within plant cells, and share common molecular components. Yet, learners often compartmentalize functions and specialization of cell organelles relevant to these two processes, without considering the interconnections…

  9. Common ecology quantifies human insurgency.

    PubMed

    Bohorquez, Juan Camilo; Gourley, Sean; Dixon, Alexander R; Spagat, Michael; Johnson, Neil F

    2009-12-17

    Many collective human activities, including violence, have been shown to exhibit universal patterns. The size distributions of casualties both in whole wars from 1816 to 1980 and terrorist attacks have separately been shown to follow approximate power-law distributions. However, the possibility of universal patterns ranging across wars in the size distribution or timing of within-conflict events has barely been explored. Here we show that the sizes and timing of violent events within different insurgent conflicts exhibit remarkable similarities. We propose a unified model of human insurgency that reproduces these commonalities, and explains conflict-specific variations quantitatively in terms of underlying rules of engagement. Our model treats each insurgent population as an ecology of dynamically evolving, self-organized groups following common decision-making processes. Our model is consistent with several recent hypotheses about modern insurgency, is robust to many generalizations, and establishes a quantitative connection between human insurgency, global terrorism and ecology. Its similarity to financial market models provides a surprising link between violent and non-violent forms of human behaviour.

  10. Mobilization of a common source of smooth muscle Ca2+ by norepinephrine and methylxanthines.

    PubMed

    Deth, R C; Lynch, C J

    1981-05-01

    The ability of norepinephrine (NE), caffeine (CAF), theophylline (THEO), dinitrophenol (DNP), and potassium (high K) to mobilize cellular Ca2+ in rabbit aorta was examined using 45Ca-efflux techniques. After 10 min of Ca2+ deprivation using either Ca-free EGTA or Ca-free lanthanum (La3+) buffers, NE, CAF, and DNP still caused an increase in 45Ca-efflux rate, indicating a cellular source of 45Ca, while high K did not. Contractile behavior after Ca removal paralleled 45Ca-efflux events. CAF (10 mM) inhibited NE contractile responses, and this inhibition was associated with the depletion of the NE-releasable Ca2+ store. Previous exposure to CAF during 45Ca efflux reduced subsequent stimulation of 45Ca efflux was not additive. THEO caused a stimulation of 45Ca efflux similar to CAF. CAF, THEO, and 3-isobutyl-l-methylxanthine caused a two- to threefold increase in cAMP levels in association with their stimulation of 45Ca efflux. These results suggest that NE and methylxanthines mobilize a common cellular Ca2+ source that is associated with contraction in the case of NE but relaxation in the case of methylxanthines.

  11. Common Tests for Arrhythmia

    MedlinePlus

    ... more about Cardiac Event Recorders . Treadmill testing (Exercise Stress Test or Stress Test) This is an option that provokes arrhythmias and ... rhythm are monitored. Learn more about the exercise stress test . Tilt-Table Test A tilt test may be ...

  12. Viral Activation of Cellular Metabolism

    PubMed Central

    Sanchez, Erica L.; Lagunoff, Michael

    2015-01-01

    To ensure optimal environments for their replication and spread, viruses have evolved to alter many host cell pathways. In the last decade, metabolomic studies have shown that eukaryotic viruses induce large-scale alterations in host cellular metabolism. Most viruses examined to date induce aerobic glycolysis also known as the Warburg effect. Many viruses tested also induce fatty acid synthesis as well as glutaminolysis. These modifications of carbon source utilization by infected cells can increase available energy for virus replication and virion production, provide specific cellular substrates for virus particles and create viral replication niches while increasing infected cell survival. Each virus species also likely requires unique metabolic changes for successful spread and recent research has identified additional virus-specific metabolic changes induced by many virus species. A better understanding of the metabolic alterations required for each virus may lead to novel therapeutic approaches through targeted inhibition of specific cellular metabolic pathways. PMID:25812764

  13. Fracture mechanics of cellular glass

    NASA Technical Reports Server (NTRS)

    Zwissler, J. G.; Adams, M. A.

    1981-01-01

    The fracture mechanics of cellular glasses (for the structural substrate of mirrored glass for solr concentrator reflecting panels) are discussed. Commercial and developmental cellular glasses were tested and analyzed using standard testing techniques and models developed from linear fracture mechanics. Two models describing the fracture behavior of these materials were developed. Slow crack growth behavior in cellular glass was found to be more complex than that encountered in dense glasses or ceramics. The crack velocity was found to be strongly dependent upon water vapor transport to the tip of the moving crack. The existence of a static fatigue limit was not conclusively established, however, it is speculated that slow crack growth behavior in Region 1 may be slower, by orders of magnitude, than that found in dense glasses.

  14. Cellular-based preemption system

    NASA Technical Reports Server (NTRS)

    Bachelder, Aaron D. (Inventor)

    2011-01-01

    A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

  15. Cellular basis for QT dispersion.

    PubMed

    Antzelevitch, C; Shimizu, W; Yan, G X; Sicouri, S

    1998-01-01

    The cellular basis for the dispersion of the QT interval recorded at the body surface is incompletely understood. Contributing to QT dispersion are heterogeneities of repolarization time in the three-dimensional structure of the ventricular myocardium, which are secondary to regional differences in action potential duration (APD) and activation time. While differences in APD occur along the apicobasal and anteroposterior axes in both epicardium and endocardium of many species, transitions are usually gradual. Recent studies have also demonstrated important APD gradients along the transmural axis. Because transmural heterogeneities in repolarization time are more abrupt than those recorded along the surfaces of the heart, they may represent a more onerous substrate for the development of arrhythmias, and their quantitation may provide a valuable tool for evaluation of arrhythmia risk. Our data, derived from the arterially perfused canine left ventricular wedge preparation, suggest that transmural gradients of voltage during repolarization contribute importantly to the inscription of the T wave. The start of the T wave is caused by a more rapid decline of the plateau, or phase 2 of the epicardial action potential, creating a voltage gradient across the wall. The gradient increases as the epicardial action potential continues to repolarize, reaching a maximum with full repolarization of epicardium; this juncture marks the peak of the T wave. The next region to repolarize is endocardium, giving rise to the initial descending limb of the upright T wave. The last region to repolarize is the M region, contributing to the final segment of the T wave. Full repolarization of the M region marks the end of the T wave. The time interval between the peak and the end of the T wave therefore represents the transmural dispersion of repolarization. Conditions known to augment QTc dispersion, including acquired long QT syndrome (class IA or III antiarrhythmics) lead to augmentation

  16. Cellular automaton for chimera states

    NASA Astrophysics Data System (ADS)

    García-Morales, Vladimir

    2016-04-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the system spontaneously splitting into stable domains separated by static boundaries, some synchronously oscillating and the others incoherent. When the coupling range is local, nontrivial coherent structures with different periodicities are formed.

  17. Cellular automata for traffic simulations

    NASA Astrophysics Data System (ADS)

    Wolf, Dietrich E.

    1999-02-01

    Traffic phenomena such as the transition from free to congested flow, lane inversion and platoon formation can be accurately reproduced using cellular automata. Being computationally extremely efficient, they simulate large traffic systems many times faster than real time so that predictions become feasible. A riview of recent results is given. The presence of metastable states at the jamming transition is discussed in detail. A simple new cellular automation is introduced, in which the interaction between cars is Galilei-invariant. It is shown that this type of interaction accounts for metastable states in a very natural way.

  18. Synthetic biology in cellular immunotherapy

    PubMed Central

    Chakravarti, Deboki; Wong, Wilson W.

    2015-01-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. Here, we first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. PMID:26088008

  19. Reprogramming cellular behavior with RNA controllers responsive to endogenous proteins.

    PubMed

    Culler, Stephanie J; Hoff, Kevin G; Smolke, Christina D

    2010-11-26

    Synthetic genetic devices that interface with native cellular pathways can be used to change natural networks to implement new forms of control and behavior. The engineering of gene networks has been limited by an inability to interface with native components. We describe a class of RNA control devices that overcome these limitations by coupling increased abundance of particular proteins to targeted gene expression events through the regulation of alternative RNA splicing. We engineered RNA devices that detect signaling through the nuclear factor κB and Wnt signaling pathways in human cells and rewire these pathways to produce new behaviors, thereby linking disease markers to noninvasive sensing and reprogrammed cellular fates. Our work provides a genetic platform that can build programmable sensing-actuation devices enabling autonomous control over cellular behavior.

  20. Learning to Describe Events.

    ERIC Educational Resources Information Center

    Duchan, Judith Felson

    1986-01-01

    The article discusses language structures of three hierarchical levels of event descriptions: (1) single-action events (semantic relations, aspectual meaning and lexical verbs or verb phrases, (2) event relations (tense markers, conjunctions, adverbs, perfect tense); (3) event schemas (lexical terms and phrases marking beginnings and endings). A…

  1. Event-by-event jet quenching

    SciTech Connect

    Fries, R.J.; Rodriguez, R.; Ramirez, E.

    2010-08-14

    High momentum jets and hadrons can be used as probes for the quark gluon plasma (QGP) formed in nuclear collisions at high energies. We investigate the influence of fluctuations in the fireball on jet quenching observables by comparing propagation of light quarks and gluons through averaged, smooth QGP fireballs with event-by-event jet quenching using realistic inhomogeneous fireballs. We find that the transverse momentum and impact parameter dependence of the nuclear modification factor R{sub AA} can be fit well in an event-by-event quenching scenario within experimental errors. However the transport coefficient {cflx q} extracted from fits to the measured nuclear modification factor R{sub AA} in averaged fireballs underestimates the value from event-by-event calculations by up to 50%. On the other hand, after adjusting {cflx q} to fit R{sub AA} in the event-by-event analysis we find residual deviations in the azimuthal asymmetry v{sub 2} and in two-particle correlations, that provide a possible faint signature for a spatial tomography of the fireball. We discuss a correlation function that is a measure for spatial inhomogeneities in a collision and can be constrained from data.

  2. Common structure and toxic function of amyloid oligomers implies a common mechanism of pathogenesis.

    PubMed

    Glabe, Charles G; Kayed, Rakez

    2006-01-24

    Recent findings indicate that soluble amyloid oligomers may represent the primary pathologic species in degenerative diseases. These amyloid oligomers share common structural features and the ability to permeabilize membranes, suggesting that they also share a common primary mechanism of pathogenesis. Membrane permeabilization by amyloid oligomers may initiate a common group of downstream pathologic processes, including intracellular calcium dyshomeostasis, production of reactive oxygen species, altered signaling pathways, and mitochondrial dysfunction that represent key effectors of cellular dysfunction and cell death in amyloid-associated degenerative disease, such as sporadic inclusion-body myositis.

  3. The developing oligodendrocyte: key cellular target in brain injury in the premature infant.

    PubMed

    Volpe, Joseph J; Kinney, Hannah C; Jensen, Frances E; Rosenberg, Paul A

    2011-06-01

    Brain injury in the premature infant, a problem of enormous importance, is associated with a high risk of neurodevelopmental disability. The major type of injury involves cerebral white matter and the principal cellular target is the developing oligodendrocyte. The specific phase of the oligodendroglial lineage affected has been defined from study of both human brain and experimental models. This premyelinating cell (pre-OL) is vulnerable because of a series of maturation-dependent events. The pathogenesis of pre-OL injury relates to operation of two upstream mechanisms, hypoxia-ischemia and systemic infection/inflammation, both of which are common occurrences in premature infants. The focus of this review and of our research over the past 15-20 years has been the cellular and molecular bases for the maturation-dependent vulnerability of the pre-OL to the action of the two upstream mechanisms. Three downstream mechanisms have been identified, i.e., microglial activation, excitotoxicity and free radical attack. The work in both experimental models and human brain has identified a remarkable confluence of maturation-dependent factors that render the pre-OL so exquisitely vulnerable to these downstream mechanisms. Most importantly, elucidation of these factors has led to delineation of a series of potential therapeutic interventions, which in experimental models show marked protective properties. The critical next step, i.e., clinical trials in the living infant, is now on the horizon.

  4. Cellular factors controlling neuronal vulnerability in the brain: a lesson from the striatum.

    PubMed

    Calabresi, P; Centonze, D; Bernardi, G

    2000-11-14

    In many acute and chronic neurologic disorders, both deficits in energy metabolism and defects in glutamate-mediated excitatory synaptic transmission have been proposed as important pathogenic factors. Brain cells, however, express variable vulnerability to these insults, as indicated by the fact that certain brain areas and even different cell types in the same area are preferentially spared until the very late stages of various diseases. This can be clearly seen in the striatum, where GABAergic projection cells but not cholinergic interneurons are precociously damaged in the course of both acute metabolic insults (such as hypoxia, hypoglycemia, and ischemia) and chronic neurodegenerative disorders (such as Huntington's disease). A well-mapped pattern of cell loss, in fact, is a common finding in the striatum of patients suffering from these pathologic conditions. Physiologic and molecular studies have been directed in recent years to the identification of the cellular mechanisms underlying the cell-type specific vulnerability of striatal cells. These studied recognized that, in striatal spiny and aspiny cells, specific membrane ion channels, glutamate receptor subtypes and subunits, and intracellular enzymatic activities are involved in the cascade of events responsible for opposite responses and vulnerabilities to oxygen or glucose deprivation and to glutamate receptor-mediated toxicity. Specific molecules able to target these cellular factors might be employed as therapeutic agents during acute and chronic neurologic disorders affecting this brain area.

  5. Quantum biology at the cellular level--elements of the research program.

    PubMed

    Bordonaro, Michael; Ogryzko, Vasily

    2013-04-01

    Quantum biology is emerging as a new field at the intersection between fundamental physics and biology, promising novel insights into the nature and origin of biological order. We discuss several elements of QBCL (quantum biology at cellular level) - a research program designed to extend the reach of quantum concepts to higher than molecular levels of biological organization. We propose a new general way to address the issue of environmentally induced decoherence and macroscopic superpositions in biological systems, emphasizing the 'basis-dependent' nature of these concepts. We introduce the notion of 'formal superposition' and distinguish it from that of Schroedinger's cat (i.e., a superposition of macroscopically distinct states). Whereas the latter notion presents a genuine foundational problem, the former one contradicts neither common sense nor observation, and may be used to describe cellular 'decision-making' and adaptation. We stress that the interpretation of the notion of 'formal superposition' should involve non-classical correlations between molecular events in a cell. Further, we describe how better understanding of the physics of Life can shed new light on the mechanism driving evolutionary adaptation (viz., 'Basis-Dependent Selection', BDS). Experimental tests of BDS and the potential role of synthetic biology in closing the 'evolvability mechanism' loophole are also discussed.

  6. A Longitudinal Study of Whole Body, Tissue and Cellular Physiology in a Mouse Model of Fibrosing NASH with High Fidelity to the Human Condition.

    PubMed

    Krishnan, Anuradha; Abdullah, Tasduq Sheikh; Mounajjed, Taofic; Hartono, Stella P; McConico, Andrea; White, Thomas A; LeBrasseur, Nathan K; Lanza, Ian R; Nair, Sreekumaran; Gores, Gregory J; Charlton, Michael

    2017-02-23

    The sequence of events that lead to inflammation and fibrosing nonalcoholic steatohepatitis (NASH) are incompletely understood. We investigated the chronology of whole body, tissue and cellular events that occur during the evolution of diet-induced NASH.

  7. Biological (molecular and cellular) markers of toxicity

    SciTech Connect

    Shugart, L.R.

    1990-10-01

    The overall objective of this study is to evaluate the use of the small aquarium fish, Japanese Medaka (Oryzias latipes), as a predictor of potential genotoxicity following exposure to carcinogens. This will be accomplished by quantitatively investigating the early molecular events associated with genotoxicity of various tissues of Medaka subsequent to exposure of the organism to several known carcinogens, such as diethylnitrosamine (DEN) and benzo(a)pyrene (BaP). Because of the often long latent period between initial contact with certain chemical and physical agents in our environment and subsequent expression of deleterious health or ecological impact, the development of sensitive methods for detecting and estimating early exposure is needed so that necessary interventions can ensue. A promising biological endpoint for detecting early exposure to damaging chemicals is the interaction of these compounds with cellular macromolecules such as Deoxyribonucleic acids (DNA). This biological endpoint assumes significance because it can be one of the critical early events leading eventually to adverse effects (neoplasia) in the exposed organism.

  8. Symmetry of integrable cellular automaton

    NASA Astrophysics Data System (ADS)

    Hikami, Kazuhiro; Inoue, Rei

    2001-03-01

    We study an integrable cellular automaton which is called the box-ball system (BBS). The BBS can be derived directly from the integrable differential-difference equation by either ultradiscretization or crystallization. We clarify the integrable structure and the hidden symmetry of the BBS.

  9. Fracture mechanics of cellular glass

    SciTech Connect

    Zwissler, J.G.; Adams, M.A.

    1981-02-01

    Cellular glasses are prime candidate materials for the structural substrate of mirrored glass for solar concentrator reflecting panels. These materials are brittle, however, and susceptible to mechanical failure from slow crack growth caused by a stress corrosion mechanism. The results are detailed of one part of a program established to develop improved cellular glasses and to characterize the behavior of these and commercially available materials. Commercial and developmental cellular glasses were tested and analyzed using standard testing techniques and models developed from linear fracture mechanics. Two models describing the fracture behavior of these materials are developed. Slow crack growth behavior in cellular glass was found to be more complex than that encountered in dense glasses or ceramics. The crack velocity was found to be strongly dependent upon water vapor transport to the tip of the moving crack. The existence of a static fatigue limit was not conclusively established, however, it is speculated that slow crack growth behavior in Region I may be slower, by orders of magnitude, than that found in dense glasses.

  10. Cellular Automata and the Humanities.

    ERIC Educational Resources Information Center

    Gallo, Ernest

    1994-01-01

    The use of cellular automata to analyze several pre-Socratic hypotheses about the evolution of the physical world is discussed. These hypotheses combine characteristics of both rigorous and metaphoric language. Since the computer demands explicit instructions for each step in the evolution of the automaton, such models can reveal conceptual…

  11. Fat tissue, aging, and cellular senescence

    PubMed Central

    Tchkonia, Tamara; Morbeck, Dean E; von Zglinicki, Thomas; van Deursen, Jan; Lustgarten, Joseph; Scrable, Heidi; Khosla, Sundeep; Jensen, Michael D; Kirkland, James L

    2010-01-01

    Fat tissue, frequently the largest organ in humans, is at the nexus of mechanisms involved in longevity and age-related metabolic dysfunction. Fat distribution and function change dramatically throughout life. Obesity is associated with accelerated onset of diseases common in old age, while fat ablation and certain mutations affecting fat increase life span. Fat cells turn over throughout the life span. Fat cell progenitors, preadipocytes, are abundant, closely related to macrophages, and dysdifferentiate in old age, switching into a pro-inflammatory, tissue-remodeling, senescent-like state. Other mesenchymal progenitors also can acquire a pro-inflammatory, adipocyte-like phenotype with aging. We propose a hypothetical model in which cellular stress and preadipocyte overutilization with aging induce cellular senescence, leading to impaired adipogenesis, failure to sequester lipotoxic fatty acids, inflammatory cytokine and chemokine generation, and innate and adaptive immune response activation. These pro-inflammatory processes may amplify each other and have systemic consequences. This model is consistent with recent concepts about cellular senescence as a stress-responsive, adaptive phenotype that develops through multiple stages, including major metabolic and secretory readjustments, which can spread from cell to cell and can occur at any point during life. Senescence could be an alternative cell fate that develops in response to injury or metabolic dysfunction and might occur in nondividing as well as dividing cells. Consistent with this, a senescent-like state can develop in preadipocytes and fat cells from young obese individuals. Senescent, pro-inflammatory cells in fat could have profound clinical consequences because of the large size of the fat organ and its central metabolic role. PMID:20701600

  12. Visual pattern discovery in timed event data

    NASA Astrophysics Data System (ADS)

    Schaefer, Matthias; Wanner, Franz; Mansmann, Florian; Scheible, Christian; Stennett, Verity; Hasselrot, Anders T.; Keim, Daniel A.

    2011-01-01

    Business processes have tremendously changed the way large companies conduct their business: The integration of information systems into the workflows of their employees ensures a high service level and thus high customer satisfaction. One core aspect of business process engineering are events that steer the workflows and trigger internal processes. Strict requirements on interval-scaled temporal patterns, which are common in time series, are thereby released through the ordinal character of such events. It is this additional degree of freedom that opens unexplored possibilities for visualizing event data. In this paper, we present a flexible and novel system to find significant events, event clusters and event patterns. Each event is represented as a small rectangle, which is colored according to categorical, ordinal or intervalscaled metadata. Depending on the analysis task, different layout functions are used to highlight either the ordinal character of the data or temporal correlations. The system has built-in features for ordering customers or event groups according to the similarity of their event sequences, temporal gap alignment and stacking of co-occurring events. Two characteristically different case studies dealing with business process events and news articles demonstrate the capabilities of our system to explore event data.

  13. Flexible substrata for the detection of cellular traction forces

    NASA Technical Reports Server (NTRS)

    Beningo, Karen A.; Wang, Yu-Li

    2002-01-01

    By modulating adhesion signaling and cytoskeletal organization, mechanical forces play an important role in various cellular functions, from propelling cell migration to mediating communication between cells. Recent developments have resulted in several new approaches for the detection, analysis and visualization of mechanical forces generated by cultured cells. Combining these methods with other approaches, such as green-fluorescent protein (GFP) imaging and gene manipulation, proves to be particularly powerful for analyzing the interplay between extracellular physical forces and intracellular chemical events.

  14. Flexible substrata for the detection of cellular traction forces

    NASA Technical Reports Server (NTRS)

    Beningo, Karen A.; Wang, Yu-Li

    2002-01-01

    By modulating adhesion signaling and cytoskeletal organization, mechanical forces play an important role in various cellular functions, from propelling cell migration to mediating communication between cells. Recent developments have resulted in several new approaches for the detection, analysis and visualization of mechanical forces generated by cultured cells. Combining these methods with other approaches, such as green-fluorescent protein (GFP) imaging and gene manipulation, proves to be particularly powerful for analyzing the interplay between extracellular physical forces and intracellular chemical events.

  15. sCNAphase: using haplotype resolved read depth to genotype somatic copy number alterations from low cellularity aneuploid tumors.

    PubMed

    Chen, Wenhan; Robertson, Alan J; Ganesamoorthy, Devika; Coin, Lachlan J M

    2017-03-17

    Accurate identification of copy number alterations is an essential step in understanding the events driving tumor progression. While a variety of algorithms have been developed to use high-throughput sequencing data to profile copy number changes, no tool is able to reliably characterize ploidy and genotype absolute copy number from tumor samples that contain less than 40% tumor cells. To increase our power to resolve the copy number profile from low-cellularity tumor samples, we developed a novel approach that pre-phases heterozygote germline single nucleotide polymorphisms (SNPs) in order to replace the commonly used 'B-allele frequency' with a more powerful 'parental-haplotype frequency'. We apply our tool-sCNAphase-to characterize the copy number and loss-of-heterozygosity profiles of four publicly available breast cancer cell-lines. Comparisons to previous spectral karyotyping and microarray studies revealed that sCNAphase reliably identified overall ploidy as well as the individual copy number mutations from each cell-line. Analysis of artificial cell-line mixtures demonstrated the capacity of this method to determine the level of tumor cellularity, consistently identify sCNAs and characterize ploidy in samples with as little as 10% tumor cells. This novel methodology has the potential to bring sCNA profiling to low-cellularity tumors, a form of cancer unable to be accurately studied by current methods. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. sCNAphase: using haplotype resolved read depth to genotype somatic copy number alterations from low cellularity aneuploid tumors

    PubMed Central

    Chen, Wenhan; Robertson, Alan J.; Ganesamoorthy, Devika

    2017-01-01

    Abstract Accurate identification of copy number alterations is an essential step in understanding the events driving tumor progression. While a variety of algorithms have been developed to use high-throughput sequencing data to profile copy number changes, no tool is able to reliably characterize ploidy and genotype absolute copy number from tumor samples that contain less than 40% tumor cells. To increase our power to resolve the copy number profile from low-cellularity tumor samples, we developed a novel approach that pre-phases heterozygote germline single nucleotide polymorphisms (SNPs) in order to replace the commonly used ‘B-allele frequency’ with a more powerful ‘parental-haplotype frequency’. We apply our tool—sCNAphase—to characterize the copy number and loss-of-heterozygosity profiles of four publicly available breast cancer cell-lines. Comparisons to previous spectral karyotyping and microarray studies revealed that sCNAphase reliably identified overall ploidy as well as the individual copy number mutations from each cell-line. Analysis of artificial cell-line mixtures demonstrated the capacity of this method to determine the level of tumor cellularity, consistently identify sCNAs and characterize ploidy in samples with as little as 10% tumor cells. This novel methodology has the potential to bring sCNA profiling to low-cellularity tumors, a form of cancer unable to be accurately studied by current methods. PMID:27903916

  17. Common Pine Shoot Beetle

    Treesearch

    Robert A. Haack; Daniel Kucera; Steven Passoa

    1993-01-01

    The common (or larger) pine shoot beetle, Tomicus (=Blastophagus) piniperda (L.), was discovered near Cleveland, Ohio in July 1992. As of this writing, it is now in six states: Illinois, Indiana, Michigan, New York, Ohio, and Pennsylvania. Adults of the common pine shoot beetle are cylindrical and range from 3 to 5 mm in length (about the size of a match head). Their...

  18. Conceptualizing an Information Commons.

    ERIC Educational Resources Information Center

    Beagle, Donald

    1999-01-01

    Concepts from Strategic Alignment, a technology-management theory, are used to discuss the Information Commons as a new service-delivery model in academic libraries. The Information Commons, as a conceptual, physical, and instructional space, involves an organizational realignment from print to the digital environment. (Author)

  19. Campus Common Law

    ERIC Educational Resources Information Center

    Bakken, Gordon Morris

    1976-01-01

    Discusses the legal principle of common law as it applies to the personnel policies of colleges and universities in an attempt to define the parameters of campus common law and to clarify its relationship to written university policies and relevant state laws. (JG)

  20. Sialidases as regulators of bioengineered cellular surfaces.

    PubMed

    Zamora, Cristina Y; Ryan, Matthew J; d'Alarcao, Marc; Kumar, Krishna

    2015-07-01

    Human sialidases (NEUs) catalyze the removal of N-acetyl neuraminic acids from the glycome of the cell and regulate a diverse repertoire of nominal cellular functions, such as cell signaling and adhesion. A greater understanding of their substrate permissivity is of interest in order to discern their physiological functions in disease states and in the design of specific and effective small molecule inhibitors. Towards this, we have synthesized soluble fluorogenic reporters of mammalian sialidase activity bearing unnatural sialic acids commonly incorporated into the cellular glycocalyx via metabolic glycoengineering. We found cell-surface sialidases in Jurkat capable of cleaving unnatural sialic acids with differential activities toward a variety of R groups on neuraminic acid. In addition, we observed modulated structure-activity relationships when cell-surface sialidases were presented glycans with unnatural bulky, hydrophobic or fluorinated moieties incorporated directly via glycoengineering. Our results confirm the importance of cell-surface sialidases in glycoengineering incorporation data. We demonstrate the flexibility of human NEUs toward derivatized sugars and highlight the importance of native glycan presentation to sialidase binding and activity. These results stand to inform not only metabolic glycoengineering efforts but also inhibitor design.

  1. Sialidases as regulators of bioengineered cellular surfaces

    PubMed Central

    Zamora, Cristina Y; Ryan, Matthew J; d'Alarcao, Marc; Kumar, Krishna

    2015-01-01

    Human sialidases (NEUs) catalyze the removal of N-acetyl neuraminic acids from the glycome of the cell and regulate a diverse repertoire of nominal cellular functions, such as cell signaling and adhesion. A greater understanding of their substrate permissivity is of interest in order to discern their physiological functions in disease states and in the design of specific and effective small molecule inhibitors. Towards this, we have synthesized soluble fluorogenic reporters of mammalian sialidase activity bearing unnatural sialic acids commonly incorporated into the cellular glycocalyx via metabolic glycoengineering. We found cell-surface sialidases in Jurkat capable of cleaving unnatural sialic acids with differential activities toward a variety of R groups on neuraminic acid. In addition, we observed modulated structure–activity relationships when cell-surface sialidases were presented glycans with unnatural bulky, hydrophobic or fluorinated moieties incorporated directly via glycoengineering. Our results confirm the importance of cell-surface sialidases in glycoengineering incorporation data. We demonstrate the flexibility of human NEUs toward derivatized sugars and highlight the importance of native glycan presentation to sialidase binding and activity. These results stand to inform not only metabolic glycoengineering efforts but also inhibitor design. PMID:25795684

  2. The cellular and molecular pathogenesis of coronaviruses.

    PubMed

    Compton, S R; Barthold, S W; Smith, A L

    1993-02-01

    Coronaviruses cause a wide spectrum of diseases in humans and animals but generally fall into two classes, with respiratory or enteric tropisms. Mouse hepatitis virus (MHV) and rat coronaviruses are the viruses most frequently encountered in the laboratory animal setting. This review focuses primarily on the cellular and molecular aspects of MHV pathogenesis. The high mutation and recombination rates of coronaviruses lead to a diverse, ever-changing population of MHV strains. The spike (S) protein is the most variable coronavirus protein and is responsible for binding to cell surface receptors, inducing cell fusion and humoral and cellular immunity. Differences within the S protein of different MHV strains have been linked to their variable tropisms. Since immunity to MHV is strain-specific, seropositive mice can be reinfected with different strains of MHV. Natural infections with MHV are acute, with persistence occurring at the population level, not within an individual mouse, unless it is immunocompromised. Age, genotype, immunologic status of the mouse, and MHV strain influence the type and severity of disease caused by MHV. Interference with research by MHV has been reported primarily in the fields of immunology and tumor biology and may be a reflection of MHV's capacity to grow in several types of immune cells. While many methods are available to diagnose coronavirus infection, serologic tests, primarily ELISA and IFA, are the most commonly used. MHV is best managed on a preventive basis. Elimination of MHV from a population requires cessation of breeding and halting the introduction of naive mice into the population.

  3. Animal and cellular models of familial dysautonomia.

    PubMed

    Lefcort, Frances; Mergy, Marc; Ohlen, Sarah B; Ueki, Yumi; George, Lynn

    2017-08-01

    Since Riley and Day first described the clinical phenotype of patients with familial dysautonomia (FD) over 60 years ago, the field has made considerable progress clinically, scientifically, and translationally in treating and understanding the etiology of FD. FD is classified as a hereditary sensory and autonomic neuropathy (HSAN type III) and is both a developmental and a progressive neurodegenerative condition that results from an autosomal recessive mutation in the gene IKBKAP, also known as ELP1. FD primarily impacts the peripheral nervous system but also manifests in central nervous system disruption, especially in the retina and optic nerve. While the disease is rare, the rapid progress being made in elucidating the molecular and cellular mechanisms mediating the demise of neurons in FD should provide insight into degenerative pathways common to many neurological disorders. Interestingly, the protein encoded by IKBKAP/ELP1, IKAP or ELP1, is a key scaffolding subunit of the six-subunit Elongator complex, and variants in other Elongator genes are associated with amyotrophic lateral sclerosis (ALS), intellectual disability, and Rolandic epilepsy. Here we review the recent model systems that are revealing the molecular and cellular pathophysiological mechanisms mediating FD. These powerful model systems can now be used to test targeted therapeutics for mitigating neuronal loss in FD and potentially other disorders.

  4. Rhabdomyosarcoma: Advances in Molecular and Cellular Biology.

    PubMed

    Sun, Xin; Guo, Wei; Shen, Jacson K; Mankin, Henry J; Hornicek, Francis J; Duan, Zhenfeng

    2015-01-01

    Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in childhood and adolescence. The two major histological subtypes of RMS are alveolar RMS, driven by the fusion protein PAX3-FKHR or PAX7-FKHR, and embryonic RMS, which is usually genetically heterogeneous. The prognosis of RMS has improved in the past several decades due to multidisciplinary care. However, in recent years, the treatment of patients with metastatic or refractory RMS has reached a plateau. Thus, to improve the survival rate of RMS patients and their overall well-being, further understanding of the molecular and cellular biology of RMS and identification of novel therapeutic targets are imperative. In this review, we describe the most recent discoveries in the molecular and cellular biology of RMS, including alterations in oncogenic pathways, miRNA (miR), in vivo models, stem cells, and important signal transduction cascades implicated in the development and progression of RMS. Furthermore, we discuss novel potential targeted therapies that may improve the current treatment of RMS.

  5. Small-molecule inducers of Aβ-42 peptide production share a common mechanism of action

    PubMed Central

    Bettayeb, Karima; Oumata, Nassima; Zhang, Yuanyuan; Luo, Wenjie; Bustos, Victor; Galons, Hervé; Greengard, Paul; Meijer, Laurent; Flajolet, Marc

    2012-01-01

    The pathways leading specifically to the toxic Aβ42 peptide production, a key event in Alzheimer's disease (AD), are unknown. While searching for pathways that mediate pathological increases of Aβ42, we identified Aftin-4, a new compound that selectively and potently increases Aβ42 compared to DMSO (N2a cells: 7-fold; primary neurons: 4-fold; brain lysates: 2-fold) with an EC50 of 30 μM. These results were confirmed by ELISA and IP-WB. Using affinity chromatography and mass spectrometry, we identified 3 proteins (VDAC1, prohibitin, and mitofilin) relevant to AD that interact with Aftin-4, but not with a structurally similar but inactive molecule. Electron microscopy studies demonstrated that Aftin-4 induces a reversible mitochondrial phenotype reminiscent of the one observed in AD brains. Sucrose gradient fractionation showed that Aftin-4 perturbs the subcellular localization of γ-secretase components and could, therefore, modify γ-secretase specificity by locally altering its membrane environment. Remarkably, Aftin-4 shares all these properties with two other “AD accelerator” compounds. In summary, treatment with three Aβ42 raising agents induced similar biochemical alterations that lead to comparable cellular phenotypes in vitro, suggesting a common mechanism of action involving three structural cellular targets.—Bettayeb, K., Oumata, N., Zhang, Y., Luo, W., Bustos, V., Galons, H., Greengard, P., Meijer, L., Flajolet, M. Small-molecule inducers of Aβ-42 peptide production share a common mechanism of action. PMID:22972917

  6. Episodes, events, and models

    PubMed Central

    Khemlani, Sangeet S.; Harrison, Anthony M.; Trafton, J. Gregory

    2015-01-01

    We describe a novel computational theory of how individuals segment perceptual information into representations of events. The theory is inspired by recent findings in the cognitive science and cognitive neuroscience of event segmentation. In line with recent theories, it holds that online event segmentation is automatic, and that event segmentation yields mental simulations of events. But it posits two novel principles as well: first, discrete episodic markers track perceptual and conceptual changes, and can be retrieved to construct event models. Second, the process of retrieving and reconstructing those episodic markers is constrained and prioritized. We describe a computational implementation of the theory, as well as a robotic extension of the theory that demonstrates the processes of online event segmentation and event model construction. The theory is the first unified computational account of event segmentation and temporal inference. We conclude by demonstrating now neuroimaging data can constrain and inspire the construction of process-level theories of human reasoning. PMID:26578934

  7. Arrayed cellular environments for stem cells and regenerative medicine.

    PubMed

    Titmarsh, Drew M; Chen, Huaying; Wolvetang, Ernst J; Cooper-White, Justin J

    2013-02-01

    The behavior and composition of both multipotent and pluripotent stem cell populations are exquisitely controlled by a complex, spatiotemporally variable interplay of physico-chemical, extracellular matrix, cell-cell interaction, and soluble factor cues that collectively define the stem cell niche. The push for stem cell-based regenerative medicine models and therapies has fuelled demands for increasingly accurate cellular environmental control and enhanced experimental throughput, driving an evolution of cell culture platforms away from conventional culture formats toward integrated systems. Arrayed cellular environments typically provide a set of discrete experimental elements with variation of one or several classes of stimuli across elements of the array. These are based on high-content/high-throughput detection, small sample volumes, and multiplexing of environments to increase experimental parameter space, and can be used to address a range of biological processes at the cell population, single-cell, or subcellular level. Arrayed cellular environments have the capability to provide an unprecedented understanding of the molecular and cellular events that underlie expansion and specification of stem cell and therapeutic cell populations, and thus generate successful regenerative medicine outcomes. This review focuses on recent key developments of arrayed cellular environments and their contribution and potential in stem cells and regenerative medicine.

  8. Radiogenic metabolism: an alternative cellular energy source.

    PubMed

    Benford, M S

    2001-01-01

    The concept of 'healing energy' is commonly used in complementary and alternative medicine; however, efforts to define this concept using contemporary scientific theory, and measure it using modern scientific methods, have been limited to date. Recent experimental testing by Benford et al. observed a uniform, substantial, and consistent decrease in gamma radiation during alternative healing sessions, thus supporting a new energy-balance paradigm hypothesizing ionizing radiation as an alternative cellular energy source. This hypothesis extends the known elements of radiogenic metabolism to potentially explain a number of presumably biopositive energy-related phenomena, including fasting and radiation hormesis, as well as to demystify unexplained anomalies such as idiopathic thermogenesis, halos and auras, and incorruptibility of human corpses.

  9. A view of early cellular evolution.

    PubMed

    Mikelsaar, R

    1987-01-01

    Some recent puzzling data on mitochondria put in question their place on the phylogenetic tree. A hypothesis, the archigenetic hypothesis, is presented, which generally agrees with Woese-Fox's concept of the common origin of eubacteria, archaebacteria, and eukaryotic hosts. However, for the first time, a case is made for the evolution of mitochondria from the ancient predecessors of pro- and eukaryotes (protobionts), not from eubacteria. Animal, fungal, and plant mitochondria are considered to be endosymbionts derived from independent free-living cells (mitobionts), which, having arisen at different developmental stages of protobionts, retained some of their ancient primitive features of the genetic code and the transcription-translation systems. The molecular-biological, bioenergetic, and paleontological aspects of this new concept of cellular evolution are discussed.

  10. EBNA1 regulates cellular gene expression by binding cellular promoters.

    PubMed

    Canaan, Allon; Haviv, Izhak; Urban, Alexander E; Schulz, Vincent P; Hartman, Steve; Zhang, Zhengdong; Palejev, Dean; Deisseroth, Albert B; Lacy, Jill; Snyder, Michael; Gerstein, Mark; Weissman, Sherman M

    2009-12-29

    Epstein-Barr virus (EBV) is associated with several types of lymphomas and epithelial tumors including Burkitt's lymphoma (BL), HIV-associated lymphoma, posttransplant lymphoproliferative disorder, and nasopharyngeal carcinoma. EBV nuclear antigen 1 (EBNA1) is expressed in all EBV associated tumors and is required for latency and transformation. EBNA1 initiates latent viral replication in B cells, maintains the viral genome copy number, and regulates transcription of other EBV-encoded latent genes. These activities are mediated through the ability of EBNA1 to bind viral-DNA. To further elucidate the role of EBNA1 in the host cell, we have examined the effect of EBNA1 on cellular gene expression by microarray analysis using the B cell BJAB and the epithelial 293 cell lines transfected with EBNA1. Analysis of the data revealed distinct profiles of cellular gene changes in BJAB and 293 cell lines. Subsequently, chromatin immune-precipitation revealed a direct binding of EBNA1 to cellular promoters. We have correlated EBNA1 bound promoters with changes in gene expression. Sequence analysis of the 100 promoters most enriched revealed a DNA motif that differs from the EBNA1 binding site in the EBV genome.

  11. Monitoring Cellular Phosphorylation Signaling Pathways into Chromatin and Down to the Gene Level*

    PubMed Central

    Han, Yumiao; Yuan, Zuo-Fei; Molden, Rosalynn C.; Garcia, Benjamin A.

    2016-01-01

    Protein phosphorylation, one of the most common and important modifications of acute and reversible regulation of protein function, plays a dominant role in almost all cellular processes. These signaling events regulate cellular responses, including proliferation, differentiation, metabolism, survival, and apoptosis. Several studies have been successfully used to identify phosphorylated proteins and dynamic changes in phosphorylation status after stimulation. Nevertheless, it is still rather difficult to elucidate precise complex phosphorylation signaling pathways. In particular, how signal transduction pathways directly communicate from the outer cell surface through cytoplasmic space and then directly into chromatin networks to change the transcriptional and epigenetic landscape remains poorly understood. Here, we describe the optimization and comparison of methods based on thiophosphorylation affinity enrichment, which can be utilized to monitor phosphorylation signaling into chromatin by isolation of phosphoprotein containing nucleosomes, a method we term phosphorylation-specific chromatin affinity purification (PS-ChAP). We utilized this PS-ChAP1 approach in combination with quantitative proteomics to identify changes in the phosphorylation status of chromatin-bound proteins on nucleosomes following perturbation of transcriptional processes. We also demonstrate that this method can be employed to map phosphoprotein signaling into chromatin containing nucleosomes through identifying the genes those phosphorylated proteins are found on via thiophosphate PS-ChAP-qPCR. Thus, our results showed that PS-ChAP offers a new strategy for studying cellular signaling and chromatin biology, allowing us to directly and comprehensively investigate phosphorylation signaling into chromatin to investigate if these pathways are involved in altering gene expression. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the data set

  12. Bayesian analysis of rare events

    NASA Astrophysics Data System (ADS)

    Straub, Daniel; Papaioannou, Iason; Betz, Wolfgang

    2016-06-01

    In many areas of engineering and science there is an interest in predicting the probability of rare events, in particular in applications related to safety and security. Increasingly, such predictions are made through computer models of physical systems in an uncertainty quantification framework. Additionally, with advances in IT, monitoring and sensor technology, an increasing amount of data on the performance of the systems is collected. This data can be used to reduce uncertainty, improve the probability estimates and consequently enhance the management of rare events and associated risks. Bayesian analysis is the ideal method to include the data into the probabilistic model. It ensures a consistent probabilistic treatment of uncertainty, which is central in the prediction of rare events, where extrapolation from the domain of observation is common. We present a framework for performing Bayesian updating of rare event probabilities, termed BUS. It is based on a reinterpretation of the classical rejection-sampling approach to Bayesian analysis, which enables the use of established methods for estimating probabilities of rare events. By drawing upon these methods, the framework makes use of their computational efficiency. These methods include the First-Order Reliability Method (FORM), tailored importance sampling (IS) methods and Subset Simulation (SuS). In this contribution, we briefly review these methods in the context of the BUS framework and investigate their applicability to Bayesian analysis of rare events in different settings. We find that, for some applications, FORM can be highly efficient and is surprisingly accurate, enabling Bayesian analysis of rare events with just a few model evaluations. In a general setting, BUS implemented through IS and SuS is more robust and flexible.

  13. Communication and common interest.

    PubMed

    Godfrey-Smith, Peter; Martínez, Manolo

    2013-01-01

    Explaining the maintenance of communicative behavior in the face of incentives to deceive, conceal information, or exaggerate is an important problem in behavioral biology. When the interests of agents diverge, some form of signal cost is often seen as essential to maintaining honesty. Here, novel computational methods are used to investigate the role of common interest between the sender and receiver of messages in maintaining cost-free informative signaling in a signaling game. Two measures of common interest are defined. These quantify the divergence between sender and receiver in their preference orderings over acts the receiver might perform in each state of the world. Sampling from a large space of signaling games finds that informative signaling is possible at equilibrium with zero common interest in both senses. Games of this kind are rare, however, and the proportion of games that include at least one equilibrium in which informative signals are used increases monotonically with common interest. Common interest as a predictor of informative signaling also interacts with the extent to which agents' preferences vary with the state of the world. Our findings provide a quantitative description of the relation between common interest and informative signaling, employing exact measures of common interest, information use, and contingency of payoff under environmental variation that may be applied to a wide range of models and empirical systems.

  14. 47 CFR 22.939 - Site availability requirements for applications competing with cellular renewal applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Site availability requirements for applications competing with cellular renewal applications. 22.939 Section 22.939 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service §...

  15. Cellular Changes in Diabetic and Idiopathic Gastroparesis

    PubMed Central

    2011-01-01

    Background Cellular changes associated with diabetic and idiopathic gastroparesis are not well described. Aim Describe histologic abnormalities in gastroparesis and compare findings in idiopathic versus diabetic gastroparesis. Methods Full thickness gastric body biopsies were obtained from 40 gastroparetics (20 diabetic) and matched controls. Sections were stained for H&E and trichrome, and immunolabeled with antibodies against PGP 9.5, nNOS, VIP, substance P and tyrosine hydroxylase to quantify nerves, S100β for glia, Kit for interstitial cells of Cajal (ICC), CD45 and CD68, for immune cells and smoothelin for smooth muscle cells. Tissue was also examined by transmission electron microscopy (TEM). Results Histological abnormalities were found in 83% of patients. Most common defects were loss of ICC with remaining ICC showing injury, an abnormal immune infiltrate containing macrophages, and decreased nerve fibers. On light microscopy, no significant differences were found between diabetic and idiopathic gastroparesis with the exception of nNOS expression which was decreased in more idiopathic gastroparetics (40%) compared to diabetic (20%) patients by visual grading. On electron microscopy, a markedly increased connective tissue stroma was present in both disorders. Conclusion This study suggests that on full thickness biopsies, cellular abnormalities are found in the majority of patients with gastroparesis. Most common findings were loss of Kit expression suggesting loss of ICC and an increase in CD45 and CD68 immunoreactivity. These findings suggest that examination of tissue can lead to valuable insights into the pathophysiology of these disorders and offers hope that new therapeutic targets can be found. PMID:21300066

  16. Oxidation events and skin aging.

    PubMed

    Kammeyer, A; Luiten, R M

    2015-05-01

    The rate of skin aging, or that of tissue in general, is determined by a variable predominance of tissue degeneration over tissue regeneration. This review discusses the role of oxidative events of tissue degeneration and aging in general, and for the skin in particular. The mechanisms involved in intrinsic and extrinsic (photo-) aging are described. Since photoaging is recognized as an important extrinsic aging factor, we put special emphasize on the effects of UV exposure on aging, and its variable influence according to global location and skin type. We here summarise direct photochemical effects of UV on DNA, RNA, proteins and vitamin D, the factors contributing to UV-induced immunosuppression, which may delay aging, the nature and origin of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as indirect contributors for aging, and the consequences of oxidative events for extracellular matrix (ECM) degradation, such as that of collagen. We conclude that conflicting data on studies investigating the validity of the free radical damage theory of aging may reflect variations in the level of ROS induction which is difficult to quantify in vivo, and the lack of targeting of experimental ROS to the relevant cellular compartment. Also mitohormesis, an adaptive response, may arise in vivo to moderate ROS levels, further complicating interpretation of in vivo results. We here describes how skin aging is mediated both directly and indirectly by oxidative degeneration.This review indicates that skin aging events are initiated and often propagated by oxidation events, despite recently recognized adaptive responses to oxidative stress. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. ACS: ALMA Common Software

    NASA Astrophysics Data System (ADS)

    Chiozzi, Gianluca; Šekoranja, Matej

    2013-02-01

    ALMA Common Software (ACS) provides a software infrastructure common to all ALMA partners and consists of a documented collection of common patterns and components which implement those patterns. The heart of ACS is based on a distributed Component-Container model, with ACS Components implemented as CORBA objects in any of the supported programming languages. ACS provides common CORBA-based services such as logging, error and alarm management, configuration database and lifecycle management. Although designed for ALMA, ACS can and is being used in other control systems and distributed software projects, since it implements proven design patterns using state of the art, reliable technology. It also allows, through the use of well-known standard constructs and components, that other team members whom are not authors of ACS easily understand the architecture of software modules, making maintenance affordable even on a very large project.

  18. Common Mental Health Issues

    ERIC Educational Resources Information Center

    Stock, Susan R.; Levine, Heidi

    2016-01-01

    This chapter provides an overview of common student mental health issues and approaches for student affairs practitioners who are working with students with mental illness, and ways to support the overall mental health of students on campus.

  19. Commonly Consumed Food Commodities

    EPA Pesticide Factsheets

    Commonly consumed foods are those ingested for their nutrient properties. Food commodities can be either raw agricultural commodities or processed commodities, provided that they are the forms that are sold or distributed for human consumption. Learn more.

  20. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2004-01-01

    Part of the 2003 industrial minerals review. The legislation, production, and consumption of common clay and shale are discussed. The average prices of the material and outlook for the market are provided.

  1. Genomic Data Commons launches

    Cancer.gov

    The Genomic Data Commons (GDC), a unified data system that promotes sharing of genomic and clinical data between researchers, launched today with a visit from Vice President Joe Biden to the operations center at the University of Chicago.

  2. Student Commons Areas.

    ERIC Educational Resources Information Center

    Owens, Rhonda

    2001-01-01

    Explores the new philosophy, lighting arrangements, and planning considerations behind the next generation of school common area design. Designs that enhance safety and security, and that can be flexible for other school functions are also discussed. (GR)

  3. Common Mental Health Issues

    ERIC Educational Resources Information Center

    Stock, Susan R.; Levine, Heidi

    2016-01-01

    This chapter provides an overview of common student mental health issues and approaches for student affairs practitioners who are working with students with mental illness, and ways to support the overall mental health of students on campus.

  4. Common Causes of Stillbirth

    MedlinePlus

    ... one of the most common placental problems. The placenta separates (partially or completely) from the uterine wall ... or abnormal placement of the cord into the placenta. This can deprive the baby of oxygen. Infectious ...

  5. Barry Commoner Assails Petrochemicals

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1973

    1973-01-01

    Discusses Commoner's ideas on the social value of the petrochemical industry and his suggestions for curtailment or elimination of its productive operation to produce a higher environmental quality for mankind at a relatively low loss in social benefit. (CC)

  6. Barry Commoner Assails Petrochemicals

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1973

    1973-01-01

    Discusses Commoner's ideas on the social value of the petrochemical industry and his suggestions for curtailment or elimination of its productive operation to produce a higher environmental quality for mankind at a relatively low loss in social benefit. (CC)

  7. Common Misconceptions about Cholesterol

    MedlinePlus

    ... Venous Thromboembolism Aortic Aneurysm More Common Misconceptions about Cholesterol Updated:Apr 3,2017 Cholesterol can be both ... misconceptions about cholesterol. Click on each misconception about cholesterol to see the truth: My choices about diet ...

  8. Peroxisome Metabolism and Cellular Aging

    PubMed Central

    Titorenko, Vladimir I.; Terlecky, Stanley R.

    2010-01-01

    The essential role of peroxisomes in fatty acid oxidation, anaplerotic metabolism, and hydrogen peroxide turnover is well established. Recent findings suggest these and other related biochemical processes governed by the organelle may also play a critical role in regulating cellular aging. The goal of this review is to summarize and integrate into a model, the evidence that peroxisome metabolism actually helps define the replicative and chronological age of a eukaryotic cell. In this model, peroxisomal reactive oxygen species (ROS) are seen as altering organelle biogenesis and function, and eliciting changes in the dynamic communication networks that exist between peroxisomes and other cellular compartments. At low levels, peroxisomal ROS activate an anti-aging program in the cell; at concentrations beyond a specific threshold, a pro-aging course is triggered. PMID:21083858

  9. Cellular solidification of transparent monotectics

    NASA Technical Reports Server (NTRS)

    Kaulker, W. F.

    1986-01-01

    Understanding how liquid phase particles are engulfed or pushed during freezing of a monotectic is addressed. The additional complication is that the solid-liquid interface is nonplanar due to constitutional undercooling. Some evidence of particle pushing where the particles are the liquid phase of the montectic was already observed. Cellular freezing of the succinonitrile-glycerol system also occurred. Only a few compositions were tested at that time. The starting materials were not especially pure so that cellular interface observed was likely due to the presence of unkown impurities, the major portion of which was water. Topics addressed include: the effort of modeling the particle pushing process using the computer, establishing an apparatus for the determination of phase diagrams, and the measurement of the temperature gradients with a specimen which will solidify on the temperature gradient microscope stage.

  10. Energetic costs of cellular computation.

    PubMed

    Mehta, Pankaj; Schwab, David J

    2012-10-30

    Cells often perform computations in order to respond to environmental cues. A simple example is the classic problem, first considered by Berg and Purcell, of determining the concentration of a chemical ligand in the surrounding media. On general theoretical grounds, it is expected that such computations require cells to consume energy. In particular, Landauer's principle states that energy must be consumed in order to erase the memory of past observations. Here, we explicitly calculate the energetic cost of steady-state computation of ligand concentration for a simple two-component cellular network that implements a noisy version of the Berg-Purcell strategy. We show that learning about external concentrations necessitates the breaking of detailed balance and consumption of energy, with greater learning requiring more energy. Our calculations suggest that the energetic costs of cellular computation may be an important constraint on networks designed to function in resource poor environments, such as the spore germination networks of bacteria.

  11. Energetic costs of cellular computation

    PubMed Central

    Mehta, Pankaj; Schwab, David J.

    2012-01-01

    Cells often perform computations in order to respond to environmental cues. A simple example is the classic problem, first considered by Berg and Purcell, of determining the concentration of a chemical ligand in the surrounding media. On general theoretical grounds, it is expected that such computations require cells to consume energy. In particular, Landauer’s principle states that energy must be consumed in order to erase the memory of past observations. Here, we explicitly calculate the energetic cost of steady-state computation of ligand concentration for a simple two-component cellular network that implements a noisy version of the Berg–Purcell strategy. We show that learning about external concentrations necessitates the breaking of detailed balance and consumption of energy, with greater learning requiring more energy. Our calculations suggest that the energetic costs of cellular computation may be an important constraint on networks designed to function in resource poor environments, such as the spore germination networks of bacteria. PMID:23045633

  12. Optofluidic Detection for Cellular Phenotyping

    PubMed Central

    Tung, Yi-Chung; Huang, Nien-Tsu; Oh, Bo-Ram; Patra, Bishnubrata; Pan, Chi-Chun; Qiu, Teng; Paul, K. Chu; Zhang, Wenjun; Kurabayashi, Katsuo

    2012-01-01

    Quantitative analysis of the output of processes and molecular interactions within a single cell is highly critical to the advancement of accurate disease screening and personalized medicine. Optical detection is one of the most broadly adapted measurement methods in biological and clinical assays and serves cellular phenotyping. Recently, microfluidics has obtained increasing attention due to several advantages, such as small sample and reagent volumes, very high throughput, and accurate flow control in the spatial and temporal domains. Optofluidics, which is the attempt to integrate optics with microfluidic, shows great promise to enable on-chip phenotypic measurements with high precision, sensitivity, specificity, and simplicity. This paper reviews the most recent developments of optofluidic technologies for cellular phenotyping optical detection. PMID:22854915

  13. Hox Targets and Cellular Functions

    PubMed Central

    Sánchez-Herrero, Ernesto

    2013-01-01

    Hox genes are a group of genes that specify structures along the anteroposterior axis in bilaterians. Although in many cases they do so by modifying a homologous structure with a different (or no) Hox input, there are also examples of Hox genes constructing new organs with no homology in other regions of the body. Hox genes determine structures though the regulation of targets implementing cellular functions and by coordinating cell behavior. The genetic organization to construct or modify a certain organ involves both a genetic cascade through intermediate transcription factors and a direct regulation of targets carrying out cellular functions. In this review I discuss new data from genome-wide techniques, as well as previous genetic and developmental information, to describe some examples of Hox regulation of different cell functions. I also discuss the organization of genetic cascades leading to the development of new organs, mainly using Drosophila melanogaster as the model to analyze Hox function. PMID:24490109

  14. Modal equations for cellular convection

    NASA Technical Reports Server (NTRS)

    Gough, D. O.; Spiegel, E. A.; Toomre, J.

    1975-01-01

    We expand the fluctuating flow variables of Boussinesq convection in the planform functions of linear theory. Our proposal is to consider a drastic truncation of this expansion as a possible useful approximation scheme for studying cellular convection. With just one term included, we obtain a fairly simple set of equations which reproduces some of the qualitative properties of cellular convection and whose steady-state form has already been derived by Roberts (1966). This set of 'modal equations' is analyzed at slightly supercritical and at very high Rayleigh numbers. In the latter regime the Nusselt number varies with Rayleigh number just as in the mean-field approximation with one horizontal scale when the boundaries are rigid. However, the Nusselt number now depends also on the Prandtl number in a way that seems compatible with experiment. The chief difficulty with the approach is the absence of a deductive scheme for deciding which planforms should be retained in the truncated expansion.

  15. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2011-01-01

    The article discusses the latest developments in the global common clay and shale industry, particularly in the U.S. It claims that common clay and shale is mainly used in the manufacture of heavy clay products like brick, flue tile and sewer pipe. The main producing states in the U.S. include North Carolina, New York and Oklahoma. Among the firms that manufacture clay and shale-based products are Mid America Brick & Structural Clay Products LLC and Boral USA.

  16. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2006-01-01

    At present, 150 companies produce common clay and shale in 41 US states. According to the United States Geological Survey (USGS), domestic production in 2005 reached 24.8 Mt valued at $176 million. In decreasing order by tonnage, the leading producer states include North Carolina, Texas, Alabama, Georgia and Ohio. For the whole year, residential and commercial building construction remained the major market for common clay and shale products such as brick, drain tile, lightweight aggregate, quarry tile and structural tile.

  17. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  18. Cellular Analogs of Operant Behavior.

    DTIC Science & Technology

    1992-07-31

    selective PI antagonist SCH23390, blocks CAI cellular operant FIG. 4. Chlorpromazine blocks dopamine-reintorced operant conditioning conditioning in...hand. when I mM REINF). When I rn’M chlorpromazine was added to the dopamine solution SCH23390 i I mM) was added to the dopamine solution (DA + SCH...rate was suppressed below the saline control. Neurons that had treatment gro’- !icated in parentheses. *Differs from SALINE, received chlorpromazine

  19. Cellular Detection of Infrared Sources

    DTIC Science & Technology

    1990-02-27

    depending on wavelength) is 2 to 10 Urn. Phototaxis is measured by the quantitation of the locomotion of the cells in tlic vicinity of the beam. PROGRESS...Northwestern University Medical School, Chicago CONTRACT TITLE: Cellular Detection of Infrared Sources RESEARCH OBJECTIVE: a. Test for phototaxis of...passes. The wavelength of the beam is variable and its diameter (depending on wavelength) is 2 to 10 am. Phototaxis is measured by the quantitation of the

  20. Xtoys: Cellular automata on xwindows

    SciTech Connect

    Creutz, M.

    1995-08-15

    Xtoys is a collection of xwindow programs for demonstrating simulations of various statistical models. Included are xising, for the two dimensional Ising model, xpotts, for the q-state Potts model, xautomalab, for a fairly general class of totalistic cellular automata, xsand, for the Bak-Tang-Wiesenfield model of self organized criticality, and xfires, a simple forest fire simulation. The programs should compile on any machine supporting xwindows.

  1. Plant-Herbivore Interaction: Dissection of the Cellular Pattern of Tetranychus urticae Feeding on the Host Plant

    PubMed Central

    Bensoussan, Nicolas; Santamaria, M. Estrella; Zhurov, Vladimir; Diaz, Isabel; Grbić, Miodrag; Grbić, Vojislava

    2016-01-01

    The two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is one of the most polyphagous herbivores feeding on cell contents of over 1100 plant species including more than 150 crops. It is being established as a model for chelicerate herbivores with tools that enable tracking of reciprocal responses in plant-spider mite interactions. However, despite their important pest status and a growing understanding of the molecular basis of interactions with plant hosts, knowledge of the way mites interface with the plant while feeding and the plant damage directly inflicted by mites is lacking. Here, utilizing histology and microscopy methods, we uncovered several key features of T. urticae feeding. By following the stylet path within the plant tissue, we determined that the stylet penetrates the leaf either in between epidermal pavement cells or through a stomatal opening, without damaging the epidermal cellular layer. Our recordings of mite feeding established that duration of the feeding event ranges from several minutes to more than half an hour, during which time mites consume a single mesophyll cell in a pattern that is common to both bean and Arabidopsis plant hosts. In addition, this study determined that leaf chlorotic spots, a common symptom of mite herbivory, do not form as an immediate consequence of mite feeding. Our results establish a cellular context for the plant-spider mite interaction that will support our understanding of the molecular mechanisms and cell signaling associated with spider mite feeding. PMID:27512397

  2. Plant-Herbivore Interaction: Dissection of the Cellular Pattern of Tetranychus urticae Feeding on the Host Plant.

    PubMed

    Bensoussan, Nicolas; Santamaria, M Estrella; Zhurov, Vladimir; Diaz, Isabel; Grbić, Miodrag; Grbić, Vojislava

    2016-01-01

    The two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is one of the most polyphagous herbivores feeding on cell contents of over 1100 plant species including more than 150 crops. It is being established as a model for chelicerate herbivores with tools that enable tracking of reciprocal responses in plant-spider mite interactions. However, despite their important pest status and a growing understanding of the molecular basis of interactions with plant hosts, knowledge of the way mites interface with the plant while feeding and the plant damage directly inflicted by mites is lacking. Here, utilizing histology and microscopy methods, we uncovered several key features of T. urticae feeding. By following the stylet path within the plant tissue, we determined that the stylet penetrates the leaf either in between epidermal pavement cells or through a stomatal opening, without damaging the epidermal cellular layer. Our recordings of mite feeding established that duration of the feeding event ranges from several minutes to more than half an hour, during which time mites consume a single mesophyll cell in a pattern that is common to both bean and Arabidopsis plant hosts. In addition, this study determined that leaf chlorotic spots, a common symptom of mite herbivory, do not form as an immediate consequence of mite feeding. Our results establish a cellular context for the plant-spider mite interaction that will support our understanding of the molecular mechanisms and cell signaling associated with spider mite feeding.

  3. Innate cellular immunity and xenotransplantation

    PubMed Central

    Wang, Hui; Yang, Yong-Guang

    2012-01-01

    Purpose of review This review assesses the recent progress in xenograft rejection by innate immune responses, with a focus on innate cellular xenoreactivity. Recent findings Current literature was reviewed for new insights into the role of innate cellular immunity in xenograft rejection. Increasing evidence confirms that vigorous innate immune cell activation is accounted for by a combination of xenoantigen recognition by activating receptors, and incompatibility in inhibitory receptor-ligand interactions. Although both innate humoral and cellular xenoimmune responses are predominantly elicited by preformed and induced xenoreactive antibodies in nonhuman primates following porcine xenotransplantation, innate immune cells can also be activated by xenografts in the absence of antibodies. The latter antibody-independent response will likely persist in recipients even when adaptive xenoimmune responses are suppressed. In addition to xenograft rejection by recipient innate immune cells, phagocytic cells within liver xenografts are also deleterious to recipients by causing thrombocytopenia. Summary Strategies of overcoming innate immune responses are required for successful clinical xenotransplantation. In addition to developing better immunosuppressive and tolerance induction protocols, endeavors towards further genetic modifications of porcine source animals are ultimately important for successful clinical xenotransplantation. PMID:22262106

  4. Cellular Functions of Tissue Transglutaminase

    PubMed Central

    Nurminskaya, Maria V.; Belkin, Alexey M.

    2013-01-01

    Transglutaminase 2 (TG2 or tissue transglutaminase) is a highly complex multifunctional protein that acts as transglutaminase, GTPase/ATPase, protein disulfide isomerase, and protein kinase. Moreover, TG2 has many well-documented nonenzymatic functions that are based on its noncovalent interactions with multiple cellular proteins. A vast array of biochemical activities of TG2 accounts for its involvement in a variety of cellular processes, including adhesion, migration, growth, survival, apoptosis, differentiation, and extracellular matrix organization. In turn, the impact of TG2 on these processes implicates this protein in various physiological responses and pathological states, contributing to wound healing, inflammation, autoimmunity, neurodegeneration, vascular remodeling, tumor growth and metastasis, and tissue fibrosis. TG2 is ubiquitously expressed and is particularly abundant in endothelial cells, fibroblasts, osteoblasts, monocytes/macrophages, and smooth muscle cells. The protein is localized in multiple cellular compartments, including the nucleus, cytosol, mitochondria, endolysosomes, plasma membrane, and cell surface and extracellular matrix, where Ca2+, nucleotides, nitric oxide, reactive oxygen species, membrane lipids, and distinct protein–protein interactions in the local microenvironment jointly regulate its activities. In this review, we discuss the complex biochemical activities and molecular interactions of TG2 in the context of diverse subcellular compartments and evaluate its wide ranging and cell type-specific biological functions and their regulation. PMID:22364871

  5. [Cellular phones and public health].

    PubMed

    Leventhal, Alex; Karsenty, Eric; Sadetzki, Siegal

    2004-08-01

    The increased use of mobile cellular phone by the public is associated with a wave of contradictory reports about the possible health effects, due to the exposure of the users to electromagnetic non-ionizing radiation. This article reviews the state of the art of the present knowledge concerning the biological and medical effects of exposure to cellular phones, with an emphasis on its possible carcinogenic effect. Health conditions, which have been ascribed to the use of mobile phones mainly include some types of cancer and changes of brain activity. However, the balance of evidence from available studies has not yet supported these claims. Following the recommendation of special international expert committees, the IARC (International Association for Research on Cancer) is conducting a multi-center study to determine the possible effect of cellular phone use on brain and salivary gland tumors. Israel is one of the participants of this study. The only established health effect associated with the use of such technology is an increased risk for road accidents, unrelated to the amount of radiation emitted by phone. The challenge posed by this new technology to health authorities all over the world has lead to the definition of a new principle, the so-called "prudent avoidance", used as guidelines for the definition of an adequate public health policy. The public policy in Israel has used the prudent avoidance principles, while awaiting the results of the multi-national epidemiological studies.

  6. Viral activation of cellular metabolism.

    PubMed

    Sanchez, Erica L; Lagunoff, Michael

    2015-05-01

    To ensure optimal environments for their replication and spread, viruses have evolved to alter many host cell pathways. In the last decade, metabolomic studies have shown that eukaryotic viruses induce large-scale alterations in host cellular metabolism. Most viruses examined to date induce aerobic glycolysis also known as the Warburg effect. Many viruses tested also induce fatty acid synthesis as well as glutaminolysis. These modifications of carbon source utilization by infected cells can increase available energy for virus replication and virion production, provide specific cellular substrates for virus particles and create viral replication niches while increasing infected cell survival. Each virus species also likely requires unique metabolic changes for successful spread and recent research has identified additional virus-specific metabolic changes induced by many virus species. A better understanding of the metabolic alterations required for the replication of each virus may lead to novel therapeutic approaches through targeted inhibition of specific cellular metabolic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Event Logic Assistant (Elan)

    DTIC Science & Technology

    2008-07-14

    as a basis for Phase II research. 2 Background 2.1 Event logic 2.1.1 Event structures Intuitively, an event structure is an abstract algebraic ...Theoretical Computer Science, 149:257–298, 1995. [2] Uri Abraham. Models for Concurrency, volume 11 of Algebra , Logic and Applications Series. Gordon...the ordering of events in a distributed system. Comms. ACM, 21(7):558–65, 1978. [28] Leslie Lamport. Hybrid systems in TLA+. In Grossman , Nerode, Ravn

  8. Zinc for the common cold.

    PubMed

    Singh, Meenu; Das, Rashmi R

    2011-02-16

    The common cold is one of the most widespread illnesses and is a leading cause of visits to the doctor and absenteeism from school and work. Trials conducted since 1984 investigating the role of zinc for the common cold symptoms have had mixed results. Inadequate treatment masking and reduced bioavailability of zinc from some formulations have been cited as influencing results. To assess the effect of zinc on common cold symptoms. We searched CENTRAL (2010, Issue 2) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May week 3, 2010) and EMBASE (1974 to June 2010). Randomised, double-blind, placebo-controlled trials using zinc for at least five consecutive days to treat, or for at least five months to prevent the common cold. Two review authors independently extracted data and assessed trial quality. We included 13 therapeutic trials (966 participants) and two preventive trials (394 participants). Intake of zinc is associated with a significant reduction in the duration (standardized mean difference (SMD) -0.97; 95% confidence interval (CI) -1.56 to -0.38) (P = 0.001), and severity of common cold symptoms (SMD -0.39; 95% CI -0.77 to -0.02) (P = 0.04). There was a significant difference between the zinc and control group for the proportion of participants symptomatic after seven days of treatment (OR 0.45; 95% CI 0.2 to 1.00) (P = 0.05). The incidence rate ratio (IRR) of developing a cold (IRR 0.64; 95% CI 0.47 to 0.88) (P = 0.006), school absence (P = 0.0003) and prescription of antibiotics (P < 0.00001) was lower in the zinc group. Overall adverse events (OR 1.59; 95% CI 0.97 to 2.58) (P = 0.06), bad taste (OR 2.64; 95% CI 1.91 to 3.64) (P < 0.00001) and nausea (OR 2.15; 95% CI 1.44 to 3.23) (P = 0.002) were higher in the zinc group. Zinc administered within 24 hours of onset of symptoms reduces the duration and severity of the common cold in healthy people. When supplemented for at least five months, it reduces cold

  9. Cellular senescence in the Penna model of aging

    NASA Astrophysics Data System (ADS)

    Periwal, Avikar

    2013-11-01

    Cellular senescence is thought to play a major role in age-related diseases, which cause nearly 67% of all human deaths worldwide. Recent research in mice showed that exercising mice had higher levels of telomerase, an enzyme that helps maintain telomere length, than nonexercising mice. A commonly used model for biological aging was proposed by Penna. I propose a modification of the Penna model that incorporates cellular senescence and find an analytical steady-state solution following Coe, Mao, and Cates [Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.89.288103 89, 288103 (2002)]. I find that models corresponding to delayed cellular senescence have younger populations that live longer. I fit the model to the United Kingdom's death distribution, which the original Penna model cannot do.

  10. Antihistamines for the common cold.

    PubMed

    De Sutter, An I M; Saraswat, Avadhesh; van Driel, Mieke L

    2015-11-29

    .23, 95% CI -0.39 to -0.06 on a four- or five-point severity scale; sneezing on day three: MD -0.35, 95% CI -0.49 to -0.20 on a four-point severity scale), but this effect is clinically non-significant. Adverse events such as sedation were more commonly reported with sedating antihistamines although the differences were not statistically significant. Only two trials included children and the results were conflicting. The majority of the trials had a low risk of bias although some lacked sufficient trial quality information. Antihistamines have a limited short-term (days one and two of treatment) beneficial effect on severity of overall symptoms but not in the mid to long term. There is no clinically significant effect on nasal obstruction, rhinorrhoea or sneezing. Although side effects are more common with sedating antihistamines, the difference is not statistically significant. There is no evidence of effectiveness of antihistamines in children.

  11. Cellular dynamics of RNA modification.

    PubMed

    Yi, Chengqi; Pan, Tao

    2011-12-20

    Five decades of research have identified more than 100 ribonucleosides that are post-transcriptionally modified. Many modified nucleosides are conserved throughout bacteria, archaea, and eukaryotes, while some are unique to each branch of life. However, the cellular and functional dynamics of RNA modification remain largely unexplored, mostly because of the lack of functional hypotheses and experimental methods for quantification and large-scale analysis. Many RNA modifications are not essential for life, which parallels the observation that many well-characterized protein and DNA modifications are not essential for life. Instead, increasing evidence indicates that RNA modifications can play regulatory roles in cells, especially in response to stress conditions. In this Account, we review some examples of RNA modification that are dynamically controlled in cells. We also discuss some recently developed methods that have enhanced the ability to study the cellular dynamics of RNA modification. We discuss four specific examples of RNA modification in detail here. We begin with 4-thio uridine (s(4)U), which can act as a cellular sensor of near-UV light. Then we consider queuosine (Q), which is a potential biomarker for malignancy. Next we examine N(6)-methyl adenine (m(6)A), which is the prevalent modification in eukaryotic messenger RNAs (mRNAs). Finally, we discuss pseudouridine (ψ), which is inducible by nutrient deprivation. We then consider two recent technical advances that have stimulated the study of the cellular dynamics in modified ribonucleosides. The first is a genome-wide method that combines primer extension with a microarray. It was used to study the N(1)-methyl adenine (m(1)A) hypomodification in human transfer RNA (tRNA). The second is a quantitative mass spectrometric method used to investigate dynamic changes in a wide range of tRNA modifications under stress conditions in yeast. In addition, we discuss potential mechanisms that control dynamic

  12. Ancient horizontal gene transfer and the last common ancestors.

    PubMed

    Fournier, Gregory P; Andam, Cheryl P; Gogarten, Johann Peter

    2015-04-22

    The genomic history of prokaryotic organismal lineages is marked by extensive horizontal gene transfer (HGT) between groups of organisms at all taxonomic levels. These HGT events have played an essential role in the origin and distribution of biological innovations. Analyses of ancient gene families show that HGT existed in the distant past, even at the time of the organismal last universal common ancestor (LUCA). Most gene transfers originated in lineages that have since gone extinct. Therefore, one cannot assume that the last common ancestors of each gene were all present in the same cell representing the cellular ancestor of all extant life. Organisms existing as part of a diverse ecosystem at the time of LUCA likely shared genetic material between lineages. If these other lineages persisted for some time, HGT with the descendants of LUCA could have continued into the bacterial and archaeal lineages. Phylogenetic analyses of aminoacyl-tRNA synthetase protein families support the hypothesis that the molecular common ancestors of the most ancient gene families did not all coincide in space and time. This is most apparent in the evolutionary histories of seryl-tRNA synthetase and threonyl-tRNA synthetase protein families, each containing highly divergent "rare" forms, as well as the sparse phylogenetic distributions of pyrrolysyl-tRNA synthetase, and the bacterial heterodimeric form of glycyl-tRNA synthetase. These topologies and phyletic distributions are consistent with horizontal transfers from ancient, likely extinct branches of the tree of life. Of all the organisms that may have existed at the time of LUCA, by definition only one lineage is survived by known progeny; however, this lineage retains a genomic record of heterogeneous genetic origins. The evolutionary histories of aminoacyl-tRNA synthetases (aaRS) are especially informative in detecting this signal, as they perform primordial biological functions, have undergone several ancient HGT events, and

  13. Inflight Medical Events in the Shuttle Program

    NASA Technical Reports Server (NTRS)

    Baisden, Denise L.; Effenhauser, R. K.; Wear, Mary L.

    1999-01-01

    Since the first launch of the Space Shuttle in 1981, the astronauts and their flight surgeons have dealt with a variety of inflight medical issues. A review will be provided of these issues as well as medications used in the treatment of these medical problems. Detailed medical debriefs are conducted by the flight ,surgeon with the individual crewmembers three days after landing. These debriefs were review for Shuttle flights from 1988 through 1999 to determine the frequency of inflight medical events. Medical events were grouped by ICD category and the frequency of medical events within those categories were reviewed. The ICD category of Symptoms, Signs and Ill-defined Conditions had the most medical events. Facial fullness and headache were the most common complaints within this category. The ICD category of Respiratory System had the next most common medical events with sinus congestion being the most common complaint. This was followed by Digestive System complaints and Nervous System/Sense Organ complaints. A variety of inflight medical events have occurred throughout the Shuttle program. Fortunately, the majority of these problems have been minor and have been well within the capability of the medical equipment flown and the skills of the Crew Medical Officers. Medical ,problems/procedures that are routine on the ground often present unique problems in the space flight environment. It is important that the flight surgeon understand the common medical problems encountered.

  14. Inflight Medical Events in the Shuttle Program

    NASA Technical Reports Server (NTRS)

    Baisden, Denise L.; Effenhauser, R. K.; Wear, Mary L.

    1999-01-01

    Since the first launch of the Space Shuttle in 1981, the astronauts and their flight surgeons have dealt with a variety of inflight medical issues. A review will be provided of these issues as well as medications used in the treatment of these medical problems. Detailed medical debriefs are conducted by the flight ,surgeon with the individual crewmembers three days after landing. These debriefs were review for Shuttle flights from 1988 through 1999 to determine the frequency of inflight medical events. Medical events were grouped by ICD category and the frequency of medical events within those categories were reviewed. The ICD category of Symptoms, Signs and Ill-defined Conditions had the most medical events. Facial fullness and headache were the most common complaints within this category. The ICD category of Respiratory System had the next most common medical events with sinus congestion being the most common complaint. This was followed by Digestive System complaints and Nervous System/Sense Organ complaints. A variety of inflight medical events have occurred throughout the Shuttle program. Fortunately, the majority of these problems have been minor and have been well within the capability of the medical equipment flown and the skills of the Crew Medical Officers. Medical ,problems/procedures that are routine on the ground often present unique problems in the space flight environment. It is important that the flight surgeon understand the common medical problems encountered.

  15. Cellular basis of gravity resistance in plants

    NASA Astrophysics Data System (ADS)

    Hoson, Takayuki; Matsumoto, Shouhei; Inui, Kenichi; Zhang, Yan; Soga, Kouichi; Wakabayashi, Kazuyuki; Hashimoto, Takashi

    Mechanical resistance to the gravitational force is a principal gravity response in plants distinct from gravitropism. In the final step of gravity resistance, plants increase the rigidity of their cell walls via modifications to the cell wall metabolism and apoplastic environment. We studied cellular events that are related to the cell wall changes under hypergravity conditions produced by centrifugation. Hypergravity induced reorientation of cortical microtubules from transverse to longitudinal directions in epidermal cells of stem organs. In Arabidopsis tubulin mutants, the percentage of cells with longitudinal microtubules was high even at 1 g, and it was further increased by hypergravity. Hypocotyls of tubulin mutants also showed either left-handed or right-handed helical growth at 1 g, and the degree of twisting phenotype was intensified under hypergravity conditions. The left-handed helical growth mutants had right-handed microtubule arrays, whereas the right-handed mutant had left-handed arrays. There was a close correlation between the alignment angle of epidermal cell files and the alignment of cortical microtubules. Gadolinium ions suppressed both the twisting phenotype and reorientation of microtubules in tubulin mutants. These results support the hypothesis that cortical microtubules play an es-sential role in maintenance of normal growth phenotype against the gravitational force, and suggest that mechanoreceptors are involved in modifications to morphology and orientation of microtubule arrays by hypergravity. Actin microfilaments, in addition to microtubules, may be involved in gravity resistance. The nucleus of epidermal cells of azuki bean epicotyls, which is present almost in the center of the cell at 1 g, was displaced to the cell bottom by increasing the magnitude of gravity. Cytochalasin D stimulated the sedimentation by hypergravity of the nu-cleus, suggesting that the positioning of the nucleus is regulated by actin microfilaments, which is

  16. New PHOBOS results on event-by-event fluctuations

    SciTech Connect

    Alver, B.; Ballintijn, M.; Busza, W.; Decowski, M. P.; Gulbrandsen, K.; Henderson, C.; Kane, J. L.; Kulinich, P.; Li, W.; Loizides, C.; Reed, C.; Roland, C.; Roland, G.; Rosenberg, L.; Sarin, P.; Stephans, G. S. F.; Vale, C.; Nieuwenhuizen, G. J. van; Vaurynovich, S. S.; Verdier, R.

    2006-04-11

    We present new results from the PHOBOS experiment at RHIC on event-by-event fluctuations of particle multiplicities and angular distributions in nucleus-nucleus collisions at RHIC. Our data for Au+Au collisions at {radical}(s{sub NN}) = 200 GeV show that at a level of 10-4 or less, no rare, large-amplitude fluctuations in the total multiplicity distributions or the shape of the pseudorapidity distributions are observed. We however find significant short-range multiplicity correlations in these data, that can be described as particle production in clusters. In Cu+Cu collisions, we observe large final-state azimuthal anisotropies {nu}2. A common scaling behavior for Cu+Cu and Au+Au for these anisotropies emerges when fluctuations in the initial state geometry are taken into account.

  17. Lobular breast cancer--the most common special subtype or a most special common subtype?

    PubMed

    Lehmann, Ulrich

    2015-07-28

    Lobular breast cancer is not only the second most common breast cancer subtype, known for decades, but also a tumour entity that still poses many unresolved questions. These include questions about the targets and cooperation partners of E-cadherin, the best model systems for translational research, and the best tools for detection, surveillance and therapy. Leading experts review the molecular and cellular bases, the model systems, the histopathology and profiling approaches, risk factors, imaging tools and therapeutic options for lobular breast cancer.

  18. The common cold.

    PubMed

    Heikkinen, Terho; Järvinen, Asko

    2003-01-04

    Despite great advances in medicine, the common cold continues to be a great burden on society in terms of human suffering and economic losses. Of the several viruses that cause the disease, the role of rhinoviruses is most prominent. About a quarter of all colds are still without proven cause, and the recent discovery of human metapneumovirus suggests that other viruses could remain undiscovered. Research into the inflammatory mechanisms of the common cold has elucidated the complexity of the virus-host relation. Increasing evidence is also available for the central role of viruses in predisposing to complications. New antivirals for the treatment of colds are being developed, but optimum use of these agents would require rapid detection of the specific virus causing the infection. Although vaccines against many respiratory viruses could also become available, the ultimate prevention of the common cold seems to remain a distant aim.

  19. Power system commonality study

    NASA Astrophysics Data System (ADS)

    Littman, Franklin D.

    1992-07-01

    A limited top level study was completed to determine the commonality of power system/subsystem concepts within potential lunar and Mars surface power system architectures. A list of power system concepts with high commonality was developed which can be used to synthesize power system architectures which minimize development cost. Examples of potential high commonality power system architectures are given in this report along with a mass comparison. Other criteria such as life cycle cost (which includes transportation cost), reliability, safety, risk, and operability should be used in future, more detailed studies to select optimum power system architectures. Nineteen potential power system concepts were identified and evaluated for planetary surface applications including photovoltaic arrays with energy storage, isotope, and nuclear power systems. A top level environmental factors study was completed to assess environmental impacts on the identified power system concepts for both lunar and Mars applications. Potential power system design solutions for commonality between Mars and lunar applications were identified. Isotope, photovoltaic array (PVA), regenerative fuel cell (RFC), stainless steel liquid-metal cooled reactors (less than 1033 K maximum) with dynamic converters, and in-core thermionic reactor systems were found suitable for both lunar and Mars environments. The use of SP-100 thermoelectric (TE) and SP-100 dynamic power systems in a vacuum enclosure may also be possible for Mars applications although several issues need to be investigated further (potential single point failure of enclosure, mass penalty of enclosure and active pumping system, additional installation time and complexity). There are also technical issues involved with development of thermionic reactors (life, serviceability, and adaptability to other power conversion units). Additional studies are required to determine the optimum reactor concept for Mars applications. Various screening

  20. ATR inhibition rewires cellular signaling networks induced by replication stress.

    PubMed

    Wagner, Sebastian A; Oehler, Hannah; Voigt, Andrea; Dalic, Denis; Freiwald, Anja; Serve, Hubert; Beli, Petra

    2016-02-01

    The slowing down or stalling of replication forks is commonly known as replication stress and arises from multiple causes such as DNA lesions, nucleotide depletion, RNA-DNA hybrids, and oncogene activation. The ataxia telangiectasia and Rad3-related kinase (ATR) plays an essential role in the cellular response to replication stress and inhibition of ATR has emerged as therapeutic strategy for the treatment of cancers that exhibit high levels of replication stress. However, the cellular signaling induced by replication stress and the substrate spectrum of ATR has not been systematically investigated. In this study, we employed quantitative MS-based proteomics to define the cellular signaling after nucleotide depletion-induced replication stress and replication fork collapse following ATR inhibition. We demonstrate that replication stress results in increased phosphorylation of a subset of proteins, many of which are involved in RNA splicing and transcription and have previously not been associated with the cellular replication stress response. Furthermore, our data reveal the ATR-dependent phosphorylation following replication stress and discover novel putative ATR target sites on MCM6, TOPBP1, RAD51AP1, and PSMD4. We establish that ATR inhibition rewires cellular signaling networks induced by replication stress and leads to the activation of the ATM-driven double-strand break repair signaling.

  1. Common Cause Failure Modes

    NASA Technical Reports Server (NTRS)

    Wetherholt, Jon; Heimann, Timothy J.; Anderson, Brenda

    2011-01-01

    High technology industries with high failure costs commonly use redundancy as a means to reduce risk. Redundant systems, whether similar or dissimilar, are susceptible to Common Cause Failures (CCF). CCF is not always considered in the design effort and, therefore, can be a major threat to success. There are several aspects to CCF which must be understood to perform an analysis which will find hidden issues that may negate redundancy. This paper will provide definition, types, a list of possible causes and some examples of CCF. Requirements and designs from NASA projects will be used in the paper as examples.

  2. Host Event Based Network Monitoring

    SciTech Connect

    Jonathan Chugg

    2013-01-01

    The purpose of INL’s research on this project is to demonstrate the feasibility of a host event based network monitoring tool and the effects on host performance. Current host based network monitoring tools work on polling which can miss activity if it occurs between polls. Instead of polling, a tool could be developed that makes use of event APIs in the operating system to receive asynchronous notifications of network activity. Analysis and logging of these events will allow the tool to construct the complete real-time and historical network configuration of the host while the tool is running. This research focused on three major operating systems commonly used by SCADA systems: Linux, WindowsXP, and Windows7. Windows 7 offers two paths that have minimal impact on the system and should be seriously considered. First is the new Windows Event Logging API, and, second, Windows 7 offers the ALE API within WFP. Any future work should focus on these methods.

  3. Simulation Modeling by Classification of Problems: A Case of Cellular Manufacturing

    NASA Astrophysics Data System (ADS)

    Afiqah, K. N.; Mahayuddin, Z. R.

    2016-02-01

    Cellular manufacturing provides good solution approach to manufacturing area by applying Group Technology concept. The evolution of cellular manufacturing can enhance performance of the cell and to increase the quality of the product manufactured but it triggers other problem. Generally, this paper highlights factors and problems which emerge commonly in cellular manufacturing. The aim of the research is to develop a thorough understanding of common problems in cellular manufacturing. A part from that, in order to find a solution to the problems exist using simulation technique, this classification framework is very useful to be adapted during model building. Biology evolution tool was used in the research in order to classify the problems emerge. The result reveals 22 problems and 25 factors using cladistic technique. In this research, the expected result is the cladogram established based on the problems in cellular manufacturing gathered.

  4. 47 CFR 22.970 - Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. 22.970 Section...-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. (a) Definition... the 800 MHz band from cellular radiotelephone or part 90-800 MHz cellular systems will be deemed to...

  5. 4D Cellular Automaton Track Finder in the CBM Experiment

    NASA Astrophysics Data System (ADS)

    Akishina, Valentina; Kisel, Ivan

    2016-11-01

    The CBM experiment (FAIR/GSI, Darmstadt, Germany) will focus on the measurement of rare probes at interaction rates up to 10MHz with data flow of up to 1 TB/s. It requires a novel read-out and data-acquisition concept with self-triggered electronics and free-streaming data. In this case resolving different collisions is a non-trivial task and event building must be performed in software online. That requires full online event reconstruction and selection not only in space, but also in time, so-called 4D event building and selection. This is a task of the First-Level Event Selection (FLES). The FLES reconstruction and selection package consists of several modules: track finding, track fitting, short-lived particles finding, event building and event selection. The Cellular Automaton (CA) track finder algorithm was adapted towards time-based reconstruction. In this article, we describe in detail the modification done to the algorithm, as well as the performance of the developed time-based CA approach.

  6. Event Reconstruction Techniques in NOvA

    NASA Astrophysics Data System (ADS)

    Baird, M.; Bian, J.; Messier, M.; Niner, E.; Rocco, D.; Sachdev, K.

    2015-12-01

    The NOvA experiment is a long-baseline neutrino oscillation experiment utilizing the NuMI beam generated at Fermilab. The experiment will measure the oscillations within a muon neutrino beam in a 300 ton Near Detector located underground at Fermilab and a functionally-identical 14 kiloton Far Detector placed 810 km away. The detectors are liquid scintillator tracking calorimeters with a fine-grained cellular structure that provides a wealth of information for separating the different particle track and shower topologies. Each detector has its own challenges with the Near Detector seeing multiple overlapping neutrino interactions in each event and the Far Detector having a large background of cosmic rays due to being located on the surface. A series of pattern recognition techniques have been developed to go from event records, to spatially and temporally separating individual interactions, to vertexing and tracking, and particle identification. This combination of methods to achieve the full event reconstruction will be discussed.

  7. Primitive control of cellular metabolism

    NASA Technical Reports Server (NTRS)

    Mitz, M. A.

    1974-01-01

    It is pointed out that control substances must have existed from the earliest times in the evolution of life and that the same control mechanisms must exist today. The investigation reported is concerned with the concept that carbon dioxide is a primitive regulator of cell function. The effects of carbon dioxide on cellular materials are examined, taking into account questions of solubilization, dissociation, changes of charge, stabilization, structural changes, wettability, the exclusion of other gases, the activation of compounds, changes in plasticity, and changes in membrane permeability.

  8. Cellular immune responses to HIV

    NASA Astrophysics Data System (ADS)

    McMichael, Andrew J.; Rowland-Jones, Sarah L.

    2001-04-01

    The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

  9. Primitive control of cellular metabolism

    NASA Technical Reports Server (NTRS)

    Mitz, M. A.

    1974-01-01

    It is pointed out that control substances must have existed from the earliest times in the evolution of life and that the same control mechanisms must exist today. The investigation reported is concerned with the concept that carbon dioxide is a primitive regulator of cell function. The effects of carbon dioxide on cellular materials are examined, taking into account questions of solubilization, dissociation, changes of charge, stabilization, structural changes, wettability, the exclusion of other gases, the activation of compounds, changes in plasticity, and changes in membrane permeability.

  10. Symmetry analysis of cellular automata

    NASA Astrophysics Data System (ADS)

    García-Morales, V.

    2013-01-01

    By means of B-calculus [V. García-Morales, Phys. Lett. A 376 (2012) 2645] a universal map for deterministic cellular automata (CAs) has been derived. The latter is shown here to be invariant upon certain transformations (global complementation, reflection and shift). When constructing CA rules in terms of rules of lower range a new symmetry, “invariance under construction” is uncovered. Modular arithmetic is also reformulated within B-calculus and a new symmetry of certain totalistic CA rules, which calculate the Pascal simplices modulo an integer number p, is then also uncovered.

  11. Therapeutic cloning and cellular reprogramming.

    PubMed

    Rodriguez, Ramon M; Ross, Pablo J; Cibelli, Jose B

    2012-01-01

    Embryonic stem cells are capable of differentiating into any cell-type present in an adult organism, and constitute a renewable source of tissue for regenerative therapies. The transplant of allogenic stem cells is challenging due to the risk of immune rejection. Nevertheless, somatic cell reprogramming techniques allow the generation of isogenic embryonic stem cells, genetically identical to the patient. In this chapter we will discuss the cellular reprogramming techniques in the context of regenerative therapy and the biological and technical barriers that they will need to overcome before clinical use.

  12. Finding the Common Ground.

    ERIC Educational Resources Information Center

    Wallace, Dawn

    1980-01-01

    Describes an attempt to combine secondary English instruction emphasizing United States literature with science and history by finding "common ground" between these disciplines in (1) the separation of truth from falsehood and (2) logical thinking. Biographies combined history and literature, and science fiction combined science and English;…

  13. Does Common Enrollment Work?

    ERIC Educational Resources Information Center

    Carpenter, Dick M., II; Clayton, Grant

    2016-01-01

    In this article, researchers Dick M. Carpenter II and Grant Clayton explore common enrollment systems (CESs)--how they work and what school leaders can learn from districts that have implemented CESs. Denver, New Orleans, and Newark (New Jersey) have rolled out this centralized enrollment process for all district-run and charter schools in their…

  14. Common Carrier Services.

    ERIC Educational Resources Information Center

    Federal Communications Commission, Washington, DC.

    This bulletin outlines the Federal Communications Commission's (FCC) responsibilities in regulating the interstate and foreign common carrier communication via electrical means. Also summarized are the history, technological development, and current capabilities and prospects of telegraph, wire telephone, radiotelephone, satellite communications,…

  15. Common File Formats.

    PubMed

    Mills, Lauren

    2014-03-21

    An overview of the many file formats commonly used in bioinformatics and genome sequence analysis is presented, including various data file formats, alignment file formats, and annotation file formats. Example workflows illustrate how some of the different file types are typically used.

  16. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2001-01-01

    Part of the 2000 annual review of the industrial minerals sector. A general overview of the common clay and shale industry is provided. In 2000, U.S. production increased by 5 percent, while sales or use declined to 23.6 Mt. Despite the slowdown in the economy, no major changes are expected for the market.

  17. Navagating the Common Core

    ERIC Educational Resources Information Center

    McShane, Michael Q.

    2014-01-01

    This article presents a debate over the Common Core State Standards Initiative as it has rocketed to the forefront of education policy discussions around the country. The author contends that there is value in having clear cross state standards that will clarify the new online and blended learning that the growing use of technology has provided…

  18. Solving Common Mathematical Problems

    NASA Technical Reports Server (NTRS)

    Luz, Paul L.

    2005-01-01

    Mathematical Solutions Toolset is a collection of five software programs that rapidly solve some common mathematical problems. The programs consist of a set of Microsoft Excel worksheets. The programs provide for entry of input data and display of output data in a user-friendly, menu-driven format, and for automatic execution once the input data has been entered.

  19. Common Standards for All

    ERIC Educational Resources Information Center

    Principal, 2010

    2010-01-01

    About three-fourths of the states have already adopted the Common Core State Standards, which were designed to provide more clarity about and consistency in what is expected of student learning across the country. However, given the brief time since the standards' final release in June, questions persist among educators, who will have the…

  20. Human Commonalities and Art

    ERIC Educational Resources Information Center

    Passmore, Kaye

    2008-01-01

    Educator Ernest Boyer believed that well-educated students should do more than master isolated facts. They should understand the "connectedness of things." He suggested organizing curriculum thematically around eight commonalities shared by people around the world. In the book "The Basic School: A Community for Learning," Boyer recommends that…