WorldWideScience

Sample records for early response mechanisms

  1. Internet worm early detection and response mechanism

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In recent years, fast spreading worm has become one of the major threats to the security of the Internet and has an increasingly fierce tendency.In view of the insufficiency that based on Kalman filter worm detection algorithm is sensitive to interval, this article presents a new data collection plan and an improved worm early detection method which has some deferent intervals according to the epidemic worm propagation model, then proposes a worm response mechanism for slowing the wide and fast worm propagation effectively.Simulation results show that our methods are able to detect worms accurately and early.

  2. The temporal relationship between reduction of early imitative responses and the development of attention mechanisms

    Directory of Open Access Journals (Sweden)

    Benga Oana

    2003-12-01

    Full Text Available Abstract Background To determine whether early imitative responses fade out following the maturation of attentional mechanisms, the relationship between primitive imitation behaviors and the development of attention was examined in 4-month-old infants. They were divided into high and low imitators, based on an index of imitation. The status of attention was assessed by studying inhibition of return (IOR. Nine-month-old infants were also tested to confirm the hypothesis. Results The IOR latency data replicate previous results that infants get faster to produce a covert shift of attention with increasing age. However, those 4-month-olds who showed less imitation had more rapid saccades to the cue before target presentation. Conclusion The cortical control of saccade planning appears to be related to an apparent drop in early imitation. We interpret the results as suggesting a relationship between the status of imitation and the neural development of attention-related eye movement.

  3. Second harmonic generation analysis of early Achilles tendinosis in response to in vivo mechanical loading

    Science.gov (United States)

    2011-01-01

    Background Tenocytes have been implicated in the development of tendinosis, a chronic condition commonly seen in musculoskeletal overuse syndromes. However, the relation between abnormal tenocyte morphology and early changes in the fibrillar collagen matrix has not been closely examined in vivo. Second harmonic generation (SHG) microscopy is a recently developed technique which allows examination of fibrillar collagen structures with a high degree of specificity and resolution. The goal of this study was to examine the potential utility of SHG and multiphoton excitation fluorescence (MPEF) microscopy in understanding the relation between tenocytes and their surrounding collagenous matrix in early tendon overuse lesions. Methods Histological preparations of tendon were prepared from adult male Sprague-Dawley rats subjected to an Achilles tendon loading protocol for 12 weeks (Rat-A-PED), or from sedentary age-matched cage controls. Second harmonic generation and multiphoton excitation fluorescence were performed simultaneously on these tissue sections in at least three different areas. Results SHG microscopy revealed an association between abnormal tenocyte morphology and morphological changes in the fibrillar collagen matrix of mechanically loaded Achilles tendons. Collagen density and organization was significantly reduced in focal micro-regions of mechanically loaded tendons. These pathological changes occurred specifically in association with altered tenocyte morphology. Normal tendons displayed a regular distribution of fibre bundles, and the average size of these bundles as determined by Gaussian analysis was 0.47 μm ± 0.02. In comparison, fibre bundle measures from tendon regions in the vicinity of abnormal tenocytes could not be quantified due to a reduction in their regularity of distribution and orientation. Conclusions SHG microscopy allowed high resolution detection of focal tendon abnormalities affecting the fibrillar collagen matrix. With ongoing

  4. Second harmonic generation analysis of early Achilles tendinosis in response to in vivo mechanical loading

    Directory of Open Access Journals (Sweden)

    Fong Gloria

    2011-01-01

    Full Text Available Abstract Background Tenocytes have been implicated in the development of tendinosis, a chronic condition commonly seen in musculoskeletal overuse syndromes. However, the relation between abnormal tenocyte morphology and early changes in the fibrillar collagen matrix has not been closely examined in vivo. Second harmonic generation (SHG microscopy is a recently developed technique which allows examination of fibrillar collagen structures with a high degree of specificity and resolution. The goal of this study was to examine the potential utility of SHG and multiphoton excitation fluorescence (MPEF microscopy in understanding the relation between tenocytes and their surrounding collagenous matrix in early tendon overuse lesions. Methods Histological preparations of tendon were prepared from adult male Sprague-Dawley rats subjected to an Achilles tendon loading protocol for 12 weeks (Rat-A-PED, or from sedentary age-matched cage controls. Second harmonic generation and multiphoton excitation fluorescence were performed simultaneously on these tissue sections in at least three different areas. Results SHG microscopy revealed an association between abnormal tenocyte morphology and morphological changes in the fibrillar collagen matrix of mechanically loaded Achilles tendons. Collagen density and organization was significantly reduced in focal micro-regions of mechanically loaded tendons. These pathological changes occurred specifically in association with altered tenocyte morphology. Normal tendons displayed a regular distribution of fibre bundles, and the average size of these bundles as determined by Gaussian analysis was 0.47 μm ± 0.02. In comparison, fibre bundle measures from tendon regions in the vicinity of abnormal tenocytes could not be quantified due to a reduction in their regularity of distribution and orientation. Conclusions SHG microscopy allowed high resolution detection of focal tendon abnormalities affecting the fibrillar collagen

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

    KAUST Repository

    Yun, Kil-Young

    2010-01-25

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

  6. Target or barrier? The cell wall of early- and later- diverging plants vs cadmium toxicity: differences in the response mechanisms

    Directory of Open Access Journals (Sweden)

    Luigi eParrotta

    2015-03-01

    Full Text Available Increasing industrialization and urbanization result in emission of pollutants in the environment including toxic heavy metals, as cadmium and lead. Among the different heavy metals contaminating the environment, cadmium raises great concern, as it is ecotoxic and as such can heavily impact ecosystems. The cell wall is the first structure of plant cells to come in contact with heavy metals. Its composition, characterized by proteins, polysaccharides and in some instances lignin and other phenolic compounds, confers the ability to bind non-covalently and/or covalently heavy metals via functional groups. A strong body of evidence in the literature has shown the role of the cell wall in heavy metal response: it sequesters heavy metals, but at the same time its synthesis and composition can be severely affected. The present review analyzes the dual property of plant cell walls, i.e. barrier and target of heavy metals, by taking Cd toxicity as example. Following a summary of the known physiological and biochemical responses of plants to Cd, the review compares the wall-related mechanisms in early- and later-diverging land plants, by considering the diversity in cell wall composition. By doing so, common as well as unique response mechanisms to metal/cadmium toxicity are identified among plant phyla and discussed. After discussing the role of hyperaccumulators’ cell walls as a particular case, the review concludes by considering important aspects for plant engineering.

  7. Patterns and mechanisms of early Pliocene warmth.

    Science.gov (United States)

    Fedorov, A V; Brierley, C M; Lawrence, K T; Liu, Z; Dekens, P S; Ravelo, A C

    2013-04-04

    About five to four million years ago, in the early Pliocene epoch, Earth had a warm, temperate climate. The gradual cooling that followed led to the establishment of modern temperature patterns, possibly in response to a decrease in atmospheric CO2 concentration, of the order of 100 parts per million, towards preindustrial values. Here we synthesize the available geochemical proxy records of sea surface temperature and show that, compared with that of today, the early Pliocene climate had substantially lower meridional and zonal temperature gradients but similar maximum ocean temperatures. Using an Earth system model, we show that none of the mechanisms currently proposed to explain Pliocene warmth can simultaneously reproduce all three crucial features. We suggest that a combination of several dynamical feedbacks underestimated in the models at present, such as those related to ocean mixing and cloud albedo, may have been responsible for these climate conditions.

  8. Early response of mechanically exposed dental pulps of swine to antibacterial-hemostatic agents or diode laser irradiation.

    Science.gov (United States)

    Cannon, M; Wagner, C; Thobaben, J Z; Jurado, R; Solt, D

    2011-01-01

    The purpose of this study was to compare the effectiveness of an antibacterial and hemostatic agent to diode laser irradiation in the healing of mechanically exposed porcine pulps. The experiment required three adult swine (Sus scrofa domestica, Yorkshire) with 36 teeth prepared with occlusal penetrations into the pulpal tissues. The preparations were performed under general anesthesia and the pulps were exposed using high speed instrumentation with rubber dam isolation and a disinfected field. Following instrumentation the coronal pulpal tissue was amputated and immediately treated with ferric sulfate and chlorhexidine semi-gel (12), diluted Buckley' formocresol solution (12) for 5 minutes or laser irradiation with a diode laser (12). After treatment, hemostasis was obtained and a ZOE base applied to the treated pulps (36). The pulpal bases were all covered with a RMGI (Fuji II LC). The tissue samples were collected at 4 weeks (28 days). Following fixation, the samples were de-mineralized, sectioned, stained and histologically graded with a scale of 0-4. The treatment groups were statistically different with the Laser Treated Group demonstrating the least inflammation. Pulpotomy treatment with the KaVo Gentle Ray Diode Laser demonstrated significantly less inflammation than the other two pulpal therapy modalities. The ferric sulfate and chlorhexidine mixture demonstrated the greatest inflammation as histologically graded. Also, the histological sections of pulpotomized swine teeth treated with the ferric sulfate and chlorhexidine mixture presented with black pigmented areas in the pulp and surrounding tissue. The formocresol group (clinical standard) and the diode laser group did not present with the black precipitate.

  9. Early diabetic neuropathy: Triggers and mechanisms

    Institute of Scientific and Technical Information of China (English)

    Maxim Dobretsov; Dmitry Romanovsky; Joseph R Stimers

    2007-01-01

    Peripheral neuropathy, and specifically distal peripheral neuropathy (DPN), is one of the most frequent and troublesome complications of diabetes mellitus. It is the major reason for morbidity and mortality among diabetic patients, It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well.It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also clear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on clinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia.

  10. Mechanical Response of Thermoelectric Materials

    Energy Technology Data Exchange (ETDEWEB)

    Wereszczak, Andrew A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Case, Eldon D. [Michigan State Univ., East Lansing, MI (United States)

    2015-05-01

    A sufficient mechanical response of thermoelectric materials (TEMats) to structural loadings is a prerequisite to the exploitation of any candidate TEMat's thermoelectric efficiency. If a TEMat is mechanically damaged or cracks from service-induced stresses, then its thermal and electrical functions can be compromised or even cease. Semiconductor TEMats tend to be quite brittle and have a high coefficient of thermal expansion; therefore, they can be quite susceptible to mechanical failure when subjected to operational thermal gradients. Because of this, sufficient mechanical response (vis-a-vis, mechanical properties) of any candidate TEMat must be achieved and sustained in the context of the service-induced stress state to which it is subjected. This report provides an overview of the mechanical responses of state-of-the-art TEMats; discusses the relevant properties that are associated with those responses and their measurement; and describes important, nonequilibrium phenomena that further complicate their use in thermoelectric devices. For reference purposes, the report also includes several appendixes that list published data on elastic properties and strengths of a variety of TEMats.

  11. Response of Mouse Zygotes Treated with Mild Hydrogen Peroxide as a Model to Reveal Novel Mechanisms of Oxidative Stress-Induced Injury in Early Embryos

    Science.gov (United States)

    2016-01-01

    Our study aimed to develop embryo models to evaluate the impact of oxidative stress on embryo development. Mouse zygotes, which stayed at G1 phase, were treated with prepared culture medium (containing 0.00, 0.01, 0.02, 0.03, 0.04, 0.05, or 0.1 mM hydrogen peroxide (H2O2)) for 30 min in experiment 1. The dose-effects of H2O2 on embryo development were investigated via comparisons of the formation rate at each stage (2- and 4-cell embryos and blastocysts). Experiment 2 was carried out to compare behaviors of embryos in a mild oxidative-stressed status (0.03 mM H2O2) with those in a control (0 mM H2O2). Reactive oxygen species (ROS) levels, variation of mitochondrial membrane potential (MMP), expression of γH2AX, and cell apoptosis rate of blastocyst were detected. We observed a dose-dependent decrease on cleavage and blastocyst rates. Besides, higher level of ROS, rapid reduction of MMP, and the appearance of γH2AX revealed that embryos are injured early in mild oxidative stress. Additionally, γH2AX may involve during DNA damage response in early embryos. And the apoptotic rate of blastocyst may significantly increase when DNA damage repair is inadequate. Most importantly, our research provides embryo models to study cell cycle regulation and DNA damage response under condition of different levels of oxidative stress.

  12. Brain mechanisms in early language acquisition.

    Science.gov (United States)

    Kuhl, Patricia K

    2010-09-09

    The last decade has produced an explosion in neuroscience research examining young children's early processing of language. Noninvasive, safe functional brain measurements have now been proven feasible for use with children starting at birth. The phonetic level of language is especially accessible to experimental studies that document the innate state and the effect of learning on the brain. The neural signatures of learning at the phonetic level can be documented at a remarkably early point in development. Continuity in linguistic development from infants' earliest brain responses to phonetic stimuli is reflected in their language and prereading abilities in the second, third, and fifth year of life, a finding with theoretical and clinical impact. There is evidence that early mastery of the phonetic units of language requires learning in a social context. Neuroscience on early language learning is beginning to reveal the multiple brain systems that underlie the human language faculty.

  13. Early Mobilization of Mechanically Ventilated Patients.

    Science.gov (United States)

    Hruska, Pam

    2016-12-01

    Critically ill patients requiring mechanical ventilation are least likely to be mobilized and, as a result, are at-risk for prolonged complications from weakness. The use of bed rest and sedation when caring for mechanically ventilated patients is likely shaped by historical practice; however, this review demonstrates early mobilization, with little to no sedation, is possible and safe. Assessing readiness for mobilization in context of progressing patients from passive to active activities can lead to long-term benefits and has been achievable with resource-efficient implementations and team work.

  14. Solar mechanics thermal response capabilities.

    Energy Technology Data Exchange (ETDEWEB)

    Dobranich, Dean D.

    2009-07-01

    In many applications, the thermal response of structures exposed to solar heat loads is of interest. Solar mechanics governing equations were developed and integrated with the Calore thermal response code via user subroutines to provide this computational simulation capability. Solar heat loads are estimated based on the latitude and day of the year. Vector algebra is used to determine the solar loading on each face of a finite element model based on its orientation relative to the sun as the earth rotates. Atmospheric attenuation is accounted for as the optical path length varies from sunrise to sunset. Both direct and diffuse components of solar flux are calculated. In addition, shadowing of structures by other structures can be accounted for. User subroutines were also developed to provide convective and radiative boundary conditions for the diurnal variations in air temperature and effective sky temperature. These temperature boundary conditions are based on available local weather data and depend on latitude and day of the year, consistent with the solar mechanics formulation. These user subroutines, coupled with the Calore three-dimensional thermal response code, provide a complete package for addressing complex thermal problems involving solar heating. The governing equations are documented in sufficient detail to facilitate implementation into other heat transfer codes. Suggestions for improvements to the approach are offered.

  15. Characterization of early host responses in adults with dengue disease

    Directory of Open Access Journals (Sweden)

    Ling Ling

    2011-08-01

    Full Text Available Abstract Background While dengue-elicited early and transient host responses preceding defervescence could shape the disease outcome and reveal mechanisms of the disease pathogenesis, assessment of these responses are difficult as patients rarely seek healthcare during the first days of benign fever and thus data are lacking. Methods In this study, focusing on early recruitment, we performed whole-blood transcriptional profiling on denguevirus PCR positive patients sampled within 72 h of self-reported fever presentation (average 43 h, SD 18.6 h and compared the signatures with autologous samples drawn at defervescence and convalescence and to control patients with fever of other etiology. Results In the early dengue fever phase, a strong activation of the innate immune response related genes were seen that was absent at defervescence (4-7 days after fever debut, while at this second sampling genes related to biosynthesis and metabolism dominated. Transcripts relating to the adaptive immune response were over-expressed in the second sampling point with sustained activation at the third sampling. On an individual gene level, significant enrichment of transcripts early in dengue disease were chemokines CCL2 (MCP-1, CCL8 (MCP-2, CXCL10 (IP-10 and CCL3 (MIP-1α, antimicrobial peptide β-defensin 1 (DEFB1, desmosome/intermediate junction component plakoglobin (JUP and a microRNA which may negatively regulate pro-inflammatory cytokines in dengue infected peripheral blood cells, mIR-147 (NMES1. Conclusions These data show that the early response in patients mimics those previously described in vitro, where early assessment of transcriptional responses has been easily obtained. Several of the early transcripts identified may be affected by or mediate the pathogenesis and deserve further assessment at this timepoint in correlation to severe disease.

  16. Early growth trajectories affect sexual responsiveness.

    Science.gov (United States)

    Lee, Who-Seung; Metcalfe, Neil B; Réale, Denis; Peres-Neto, Pedro R

    2014-02-22

    The trajectory of an animal's growth in early development has been shown to have long-term effects on a range of life-history traits. Although it is known that individual differences in behaviour may also be related to certain life-history traits, the linkage between early growth or development and individual variation in behaviour has received little attention. We used brief temperature manipulations, independent of food availability, to stimulate compensatory growth in juvenile three-spined sticklebacks Gasterosteus aculeatus. Here, we examine how these manipulated growth trajectories affected the sexual responsiveness of the male fish at the time of sexual maturation, explore associations between reproductive behaviour and investment and lifespan and test whether the perceived time stress (until the onset of the breeding season) influenced such trade-offs. We found a negative impact of growth rate on sexual responsiveness: fish induced (by temperature manipulation) to grow slowest prior to the breeding season were consistently quickest to respond to the presence of a gravid female. This speed of sexual responsiveness was also positively correlated with the rate of development of sexual ornaments and time taken to build a nest. However, after controlling for effects of growth rate, those males that had the greatest sexual responsiveness to females had the shortest lifespan. Moreover, the time available to compensate in size before the onset of the breeding season (time stress) affected the magnitude of these effects. Our results demonstrate that developmental perturbations in early life can influence mating behaviour, with long-term effects on longevity.

  17. The early stress responses in fish larvae.

    Science.gov (United States)

    Pederzoli, Aurora; Mola, Lucrezia

    2016-05-01

    During the life cycle of fish the larval stages are the most interesting and variable. Teleost larvae undergo a daily increase in adaptability and many organs differentiate and become active. These processes are concerted and require an early neuro-immune-endocrine integration. In larvae communication among the nervous, endocrine and immune systems utilizes several known signal molecule families which could be different from those of the adult fish. The immune-neuroendocrine system was studied in several fish species, among which in particular the sea bass (Dicentrarchus labrax), that is a species of great commercial interest, very important in aquaculture and thus highly studied. Indeed the immune system of this species is the best known among marine teleosts. In this review the data on main signal molecules of stress carried out on larvae of fish are considered and discussed. For sea bass active roles in the early immunological responses of some well-known molecules involved in the stress, such as ACTH, nitric oxide, CRF, HSP-70 and cortisol have been proposed. These molecules and/or their receptors are biologically active mainly in the gut before complete differentiation of gut-associated lymphoid tissue (GALT), probably acting in an autocrine/paracrine way. An intriguing idea emerges from all results of these researches; the molecules involved in stress responses, expressed in the adult cells of the hypothalamic-pituitary axis, during the larval life of fish are present in several other localizations, where they perform probably the same role. It may be hypothesized that the functions performed by hypothalamic-pituitary system are particularly important for the survival of the larva and therefore they comprises several other localizations of body. Indeed the larval stages of fish are very crucial phases that include many physiological changes and several possible stress both internal and environmental.

  18. Modeling the mechanical response of PBX 9501

    Energy Technology Data Exchange (ETDEWEB)

    Ragaswamy, Partha [Los Alamos National Laboratory; Lewis, Matthew W [Los Alamos National Laboratory; Liu, Cheng [Los Alamos National Laboratory; Thompson, Darla G [Los Alamos National Laboratory

    2010-01-01

    An engineering overview of the mechanical response of Plastic-Bonded eXplosives (PBXs), specifically PBX 9501, will be provided with emphasis on observed mechanisms associated with different types of mechanical testing. Mechanical tests in the form of uniaxial tension, compression, cyclic loading, creep (compression and tension), and Hopkinson bar show strain rate and temperature dependence. A range of mechanical behavior is observed which includes small strain recoverable response in the form of viscoelasticity; change in stiffness and softening beyond peak strength due to damage in the form microcracks, debonding, void formation and the growth of existing voids; inelastic response in the form of irrecoverable strain as shown in cyclic tests, and viscoelastic creep combined with plastic response as demonstrated in creep and recovery tests. The main focus of this paper is to elucidate the challenges and issues involved in modeling the mechanical behavior of PBXs for simulating thermo-mechanical responses in engineering components. Examples of validation of a constitutive material model based on a few of the observed mechanisms will be demonstrated against three point bending, split Hopkinson pressure bar and Brazilian disk geometry.

  19. Brain Mechanisms in Early Language Acquisition

    National Research Council Canada - National Science Library

    Kuhl, Patricia K

    2010-01-01

    ... an experimentally tractable window on the roles of nature and nurture in language acquisition. Comparative studies at the phonetic level have allowed us to examine the uniqueness of humans' language processing abilities. Moreover, infants' responses to native and nonnative phonemes have documented the effects of experience as infants are bathed in a specific la...

  20. Stomatal Blue Light Response Is Present in Early Vascular Plants.

    Science.gov (United States)

    Doi, Michio; Kitagawa, Yuki; Shimazaki, Ken-ichiro

    2015-10-01

    Light is a major environmental factor required for stomatal opening. Blue light (BL) induces stomatal opening in higher plants as a signal under the photosynthetic active radiation. The stomatal BL response is not present in the fern species of Polypodiopsida. The acquisition of a stomatal BL response might provide competitive advantages in both the uptake of CO2 and prevention of water loss with the ability to rapidly open and close stomata. We surveyed the stomatal opening in response to strong red light (RL) and weak BL under the RL with gas exchange technique in a diverse selection of plant species from euphyllophytes, including spermatophytes and monilophytes, to lycophytes. We showed the presence of RL-induced stomatal opening in most of these species and found that the BL responses operated in all euphyllophytes except Polypodiopsida. We also confirmed that the stomatal opening in lycophytes, the early vascular plants, is driven by plasma membrane proton-translocating adenosine triphosphatase and K(+) accumulation in guard cells, which is the same mechanism operating in stomata of angiosperms. These results suggest that the early vascular plants respond to both RL and BL and actively regulate stomatal aperture. We also found three plant species that absolutely require BL for both stomatal opening and photosynthetic CO2 fixation, including a gymnosperm, C. revoluta, and the ferns Equisetum hyemale and Psilotum nudum.

  1. Microtrauma stimulates rat Achilles tendon healing via an early gene expression pattern similar to mechanical loading

    DEFF Research Database (Denmark)

    Hammerman, Malin; Aspenberg, Per; Eliasson, Pernilla

    2014-01-01

    . Sixteen of the 19 genes were regulated after 3 h, in the same way as after loading. In conclusion, needling increased strength, and there was a striking similarity between the gene expression response to needling and mechanical loading. This suggests that the response to loading in early tendon healing...

  2. New mechanism for neural stem cell maintenance in early embryos

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Teamning up with co-workers from Japan, UK and US,CAS biochemists have revealed a novel mechanism for maintaining neural stem cells in early embryos. Their work was published on the 6 August issue of Cell Development.

  3. Cell mechanics: integrating cell responses to mechanical stimuli.

    Science.gov (United States)

    Janmey, Paul A; McCulloch, Christopher A

    2007-01-01

    Forces are increasingly recognized as major regulators of cell structure and function, and the mechanical properties of cells are essential to the mechanisms by which cells sense forces, transmit them to the cell interior or to other cells, and transduce them into chemical signals that impact a spectrum of cellular responses. Comparison of the mechanical properties of intact cells with those of the purified cytoskeletal biopolymers that are thought to dominate their elasticity reveal the extent to which the studies of purified systems can account for the mechanical properties of the much more heterogeneous and complex cell. This review summarizes selected aspects of current work on cell mechanics with an emphasis on the structures that are activated in cell-cell contacts, that regulate ion flow across the plasma membrane, and that may sense fluid flow that produces low levels of shear stress.

  4. Optomechanical response of a nonlinear mechanical resonator

    Science.gov (United States)

    Shevchuk, Olga; Singh, Vibhor; Steele, Gary A.; Blanter, Ya. M.

    2015-11-01

    We investigate theoretically in detail the nonlinear effects in the response of an optical/microwave cavity coupled to a Duffing mechanical resonator. The cavity is driven by a laser at a red or blue mechanical subband, and a probe laser measures the reflection close to the cavity resonance. Under these conditions, we find that the cavity exhibits optomechanically induced reflection (OMIR) or absorption (OMIA) and investigate the optomechanical response in the limit of nonlinear driving of the mechanics. Similar to linear mechanical drive, in an overcoupled cavity the red sideband drive may lead to both OMIA and OMIR depending on the strength of the drive, whereas the blue sideband drive only leads to OMIR. The dynamics of the phase of the mechanical resonator leads to the difference between the shapes of the response of the cavity and the amplitude response of the driven Duffing oscillator, for example, at weak red sideband drive the OMIA dip has no inflection point. We also verify that mechanical nonlinearities beyond Duffing model have little effect on the size of the OMIA dip though they affect the width of the dip.

  5. The Cytoskeleton and Force Response Mechanisms

    Science.gov (United States)

    Allen, Philip Goodwin

    2003-01-01

    The long term aim of this project was to define the mechanisms by which cells sense and respond to the physical forces experienced at 1g and missing in microgravity. Identification and characterization of the elements of the cells force response mechanism could provide pathways and molecules to serve as targets for pharmacological intervention to mitigate the pathologic effects of microgravity. Mechanical forces experienced by the organism can be transmitted to cells through molecules that allow cells to bind to the extracellular matrix and through other types of molecules which bind cells to each other. These molecules are coupled in large complexes of proteins to structural elements such as the actin cytoskeleton that give the cell the ability to sense, resist and respond to force. Application of small forces to tissue culture cells causes local elevation of intracellular calcium through stretch activated ion channels, increased tyrosine phosphorylation and a restructuring of the actin cytoskeleton. Using collagen coated iron oxide beads and strong magnets, we can apply different levels of force to cells in culture. We have found that force application causes the cells to polymerize actin at the site of mechanical deformation and unexpectedly, to depolymerize actin across the rest of the cell. Observations of GFP- actin expressing cells demonstrate that actin accumulates at the site of deformation within the first five minutes of force application and is maintained for many tens of minutes after force is removed. Consistent with the reinforcement of the cytoskeletal structures underlying the integrin-bead interaction, force also alters the motion of bound magnetic beads. This effect is seen following the removal of the magnetic field, and is only partially ablated by actin disruption with cytochalsin B. While actin is polymerizing locally at the site of force application, force also stimulates a global reduction in actin filament content within the cells. We have

  6. Decisional responsibility for mechanical ventilation and weaning

    DEFF Research Database (Denmark)

    Rose, Louise; Blackwood, Bronagh; Egerod, Ingrid

    2011-01-01

    Optimal management of mechanical ventilation and weaning requires dynamic and collaborative decision making to minimize complications and avoid delays in the transition to extubation. In the absence of collaboration, ventilation decision making may be fragmented, inconsistent, and delayed. Our ob...... objective was to describe the professional group with responsibility for key ventilation and weaning decisions and to examine organizational characteristics associated with nurse involvement....

  7. Human Macrophage Response to L. (Viannia) panamensis: Microarray Evidence for an Early Inflammatory Response

    Science.gov (United States)

    Rojas, Ricardo; Ettinger, Nicholas A.; Tikhonova, Irina; Alexander, Neal D.; Valderrama, Liliana; Hager, Janet; Wilson, Mary E.; Lin, Aiping; Zhao, Hongyu; Saravia, Nancy G.; McMahon-Pratt, Diane

    2012-01-01

    Background Previous findings indicate that susceptibility to Leishmania (Viannia) panamensis infection of monocyte-derived macrophages from patients and asymptomatically infected individuals were associated with the adaptive immune response and clinical outcome. Methodology/Principal Findings To understand the basis for this difference we examined differential gene expression of human monocyte-derived macrophages following exposure to L. (V.) panamensis. Gene activation profiles were determined using macrophages from healthy volunteers cultured with or without stationary phase promastigotes of L. (V.) panamensis. Significant changes in expression (>1.5-fold change; p<0.05; up- or down-regulated) were identified at 0.5, 4 and 24 hours. mRNA abundance profiles varied over time, with the highest level of activation occurring at earlier time points (0.5 and 4 hrs). In contrast to observations for other Leishmania species, most significantly changed mRNAs were up- rather than down-regulated, especially at early time points. Up-regulated transcripts over the first 24 hours belonged to pathways involving eicosanoid metabolism, oxidative stress, activation of PKC through G protein coupled receptors, or mechanism of gene regulation by peroxisome proliferators via PPARα. Additionally, a marked activation of Toll-receptor mediated pathways was observed. Comparison with published microarray data from macrophages infected with L. (Leishmania) chagasi indicate differences in the regulation of genes involved in signaling, motility and the immune response. Conclusions Results show that the early (0.5 to 24 hours) human monocyte-derived macrophage response to L. (Viannia) panamensis is not quiescent, in contrast to published reports examining later response times (48–96 hours). Early macrophage responses are important for the developing cellular response at the site of infection. The kinetics and the mRNA abundance profiles induced by L. (Viannia) panamensis illustrate the

  8. Molecular mechanisms in plant abiotic stress response

    Directory of Open Access Journals (Sweden)

    Poltronieri Palmiro

    2011-01-01

    Full Text Available Improved crop varieties are needed to sustain the food supply, to fight climate changes, water scarcity, temperature increase and a high variability of rainfalls. Variability of drought and increase in soil salinity have negative effects on plant growth and abiotic stresses seriously threaten sustainable agricultural production. To overcome the influence of abiotic stresses, new tolerant plant varieties and breeding techniques using assisted selection are sought. A deep understanding of the mechanisms that respond to stress and sustain stress resistance is required. Here is presented an overview of several mechanisms that interact in the stress response. Localised synthesis of plant hormones, second messengers and local effectors of abiotic stress response and survival, the signaling pathways regulated by plant hormones are today better understood. Metabolic networks in drought stress responses, long distance signaling, cross-talk between plant organs finalised to tissue-specific expression of abiotic stress relieving genes have been at the centre of most recent studies.

  9. Genetic selection for fast growth generates bone architecture characterised by enhanced periosteal expansion and limited consolidation of the cortices but a diminution in the early responses to mechanical loading.

    Science.gov (United States)

    Rawlinson, Simon C F; Murray, Dianne H; Mosley, John R; Wright, Chris D P; Bredl, John C; Saxon, Leanne K; Loveridge, Nigel; Leterrier, Christine; Constantin, Paul; Farquharson, Colin; Pitsillides, Andrew A

    2009-08-01

    Bone strength is, in part, dependent on a mechanical input that regulates the (re)modelling of skeletal elements to an appropriate size and architecture to resist fracture during habitual use. The rate of longitudinal bone growth in juveniles can also affect fracture incidence in adulthood, suggesting an influence of growth rate on later bone quality. We have compared the effects of fast and slow growth on bone strength and architecture in the tibiotarsi of embryonic and juvenile birds. The loading-related biochemical responses (intracellular G6PD activity and NO release) to mechanical load were also determined. Further, we have analysed the proliferation and differentiation characteristics of primary tibiotarsal osteoblasts from fast and slow-growing strains. We found that bones from chicks with divergent growth rates display equal resistance to applied loads, but weight-correction revealed that the bones from juvenile fast growth birds are weaker, with reduced stiffness and lower resistance to fracture. Primary osteoblasts from slow-growing juvenile birds proliferated more rapidly and had lower alkaline phosphatase activity. Bones from fast-growing embryonic chicks display rapid radial expansion and incomplete osteonal infilling but, importantly, lack mechanical responsiveness. These findings are further evidence that the ability to respond to mechanical inputs is crucial to adapt skeletal architecture to generate a functionally appropriate bone structure and that fast embryonic and juvenile growth rates may predispose bone to particular architectures with increased fragility in the adult.

  10. Long-term effects of early life stress exposure: Role of epigenetic mechanisms.

    Science.gov (United States)

    Silberman, Dafne M; Acosta, Gabriela B; Zorrilla Zubilete, María A

    2016-07-01

    Stress is an adaptive response to demands of the environment and thus essential for survival. Exposure to stress during the first years of life has been shown to have profound effects on the growth and development of an adult individual. There are evidences demonstrating that stressful experiences during gestation or in early life can lead to enhanced susceptibility to mental disorders. Early-life stress triggers hypothalamic-pituitary-adrenocortical (HPA) axis activation and the associated neurochemical reactions following glucocorticoid release are accompanied by a rapid physiological response. An excessive response may affect the developing brain resulting in neurobehavioral and neurochemical changes later in life. This article reviews the data from experimental studies aimed to investigate hormonal, functional, molecular and epigenetic mechanisms involved in the stress response during early-life programming. We think these studies might prove useful for the identification of novel pharmacological targets for more effective treatments of mental disorders.

  11. Respiratory mechanics in ventilated preterm infants : early determinants and outcome

    NARCIS (Netherlands)

    Snepvangers, Dimphn Adriana Cornelia Maria

    2004-01-01

    The studies in this thesis show that in the current surfactant era, the majority of ventilated preterm infants are still suffering from respiratory morbidity and substantial respiratory function abnormalities throughout the early years of life. Since respiratory function testing during mechanical ve

  12. Molecular Mechanisms Regulating Macrophage Response to Hypoxia

    Directory of Open Access Journals (Sweden)

    Michal Amit Rahat

    2011-09-01

    Full Text Available Monocytes and Macrophages (Mo/Mϕ exhibit great plasticity, as they can shift between different modes of activation and, driven by their immediate microenvironment, perform divergent functions. These include, among others, patrolling their surroundings and maintaining homeostasis (resident Mo/Mϕ, combating invading pathogens and tumor cells (classically activated or M1 Mo/Mϕ, orchestrating wound healing (alternatively activated or M2 Mo/Mϕ, and restoring homeostasis after an inflammatory response (resolution Mϕ. Hypoxia is an important factor in the Mϕ microenvironment, is prevalent in many physiological and pathological conditions, and is interdependent with the inflammatory response. Although Mo/Mϕ have been studied in hypoxia, the mechanisms by which hypoxia influences the different modes of their activation, and how it regulates the shift between them, remain unclear. Here we review the current knowledge about the molecular mechanisms that mediate this hypoxic regulation of Mϕ activation. Much is known about the hypoxic transcriptional regulatory network, which includes the master regulators HIF-1 and NF-κB, as well as other transcription factors (e.g. AP-1, Erg-1, but we also highlight the role of post-transcriptional and post-translational mechanisms. These mechanisms mediate hypoxic induction of Mϕ pro-angiogenic mediators, suppress M1 Mϕ by post-transcriptionally inhibiting pro-inflammatory mediators, and help shift the classically activated Mϕ into an activation state which approximate the alternatively activated or resolution Mϕ.

  13. Robert Hooke: early respiratory physiologist, polymath, and mechanical genius.

    Science.gov (United States)

    West, John B

    2014-07-01

    Robert Hooke (1635-1703) was a polymath who made important contributions to respiratory physiology and many other scientific areas. With Robert Boyle, he constructed the first air pump that allowed measurements on small animals at a reduced atmospheric pressure, and this started the discipline of high-altitude physiology. He also built the first human low-pressure chamber and described his experiences when the pressure was reduced to the equivalent of an altitude of ∼2,400 m. Using artificial ventilation in an animal preparation, he demonstrated that movement of the lung was not essential for life. His book Micrographia describing early studies with a microscope remains a classic. He produced an exquisite drawing of the head of a fly, showing the elaborate compound eye. There is also a detailed drawing of a flea, and Hooke noted how the long, many-jointed legs enable the insect to jump so high. For 40 years, he was the curator of experiments for the newly founded Royal Society in London and contributed greatly to its intellectual ferment. His mechanical inventions covered an enormous range, including the watch spring, the wheel barometer, and the universal joint. Following the Great Fire of London in 1666, he designed many of the new buildings in conjunction with Christopher Wren. Unfortunately, Hooke had an abrasive personality, which was partly responsible for a lack of recognition of his work for many years. However, during the last 25 years, there has been renewed interest, and he is now recognized as a brilliant scientist and innovator.

  14. Epigenomic mechanisms of early adversity and HPA dysfunction: Considerations for PTSD research

    Directory of Open Access Journals (Sweden)

    Patrick O McGowan

    2013-09-01

    Full Text Available Childhood adversity can have life-long consequences for the response to stressful events later in life. Abuse or severe neglect are well known risk factors for post-traumatic stress disorder (PTSD, at least in part via changes in neural systems mediating the endocrine response to stress. Determining the biological signatures of risk for stress-related mental disorders such as PTSD is important for identifying homogenous subgroups and improving treatment options. This review will focus on epigenetic regulation in early life by adversity and parental care – prime mediators of offspring neurodevelopment - in order to address several questions: (1 what have studies of humans and analogous animal models taught us about molecular mechanisms underlying changes in stress-sensitive physiological systems in response to early life trauma? (2 What are the considerations for studies relating early adversity and PTSD risk, going forward? I will summarize studies in animals and humans that address the epigenetic response to early adversity in the brain and in peripheral tissues. In so doing, I will describe work on the Glucocorticoid Receptor (GR and other well-characterized genes within the stress response pathway and then turn to genomic studies to illustrate the use of increasingly powerful high-throughput approaches to the study of epigenomic mechanisms.

  15. Exploring early public responses to geoengineering.

    Science.gov (United States)

    Pidgeon, Nick; Corner, Adam; Parkhill, Karen; Spence, Alexa; Butler, Catherine; Poortinga, Wouter

    2012-09-13

    Proposals for geoengineering the Earth's climate are prime examples of emerging or 'upstream' technologies, because many aspects of their effectiveness, cost and risks are yet to be researched, and in many cases are highly uncertain. This paper contributes to the emerging debate about the social acceptability of geoengineering technologies by presenting preliminary evidence on public responses to geoengineering from two of the very first UK studies of public perceptions and responses. The discussion draws upon two datasets: qualitative data (from an interview study conducted in 42 households in 2009), and quantitative data (from a subsequent nationwide survey (n=1822) of British public opinion). Unsurprisingly, baseline awareness of geoengineering was extremely low in both cases. The data from the survey indicate that, when briefly explained to people, carbon dioxide removal approaches were preferred to solar radiation management, while significant positive correlations were also found between concern about climate change and support for different geoengineering approaches. We discuss some of the wider considerations that are likely to shape public perceptions of geoengineering as it enters the media and public sphere, and conclude that, aside from technical considerations, public perceptions are likely to prove a key element influencing the debate over questions of the acceptability of geoengineering proposals.

  16. The early antitumor immune response is necessary for tumor growth

    OpenAIRE

    Parmiani, Giorgio; Maccalli, Cristina

    2012-01-01

    Early events responsible of tumor growth in patients with a normal immune system are poorly understood. Here, we discuss, in the context of human melanoma, the Prehn hypothesis according to which a weak antitumor immune response may be required for tumor growth before weakly or non-immunogenic tumor cell subpopulations are selected by the immune system.

  17. Early Atomic Models - From Mechanical to Quantum (1904-1913)

    CERN Document Server

    Baily, Charles

    2012-01-01

    A complete history of early atomic models would fill volumes, but a reasonably coherent tale of the path from mechanical atoms to the quantum can be told by focusing on the relevant work of three great contributors to atomic physics, in the critically important years between 1904 and 1913: J. J. Thomson, Ernest Rutherford and Niels Bohr. We first examine the origins of Thomson's mechanical atomic models, from his ethereal vortex atoms in the early 1880's, to the myriad "corpuscular" atoms he proposed following the discovery of the electron in 1897. Beyond predictions for the periodicity of the elements, the application of Thomson's atoms to problems in scattering and absorption led to quantitative predictions that were confirmed by experiments with high-velocity electrons traversing thin sheets of metal. Still, the much more massive and energetic {\\alpha}-particles being studied by Rutherford were better suited for exploring the interior of the atom, and careful measurements on the angular dependence of their...

  18. Epigenetic mechanisms elicited by nutrition in early life.

    Science.gov (United States)

    Canani, Roberto Berni; Costanzo, Margherita Di; Leone, Ludovica; Bedogni, Giorgio; Brambilla, Paolo; Cianfarani, Stefano; Nobili, Valerio; Pietrobelli, Angelo; Agostoni, Carlo

    2011-12-01

    A growing number of studies focusing on the developmental origin of health and disease hypothesis have identified links among early nutrition, epigenetic processes and diseases also in later life. Different epigenetic mechanisms are elicited by dietary factors in early critical developmental ages that are able to affect the susceptibility to several diseases in adulthood. The studies here reviewed suggest that maternal and neonatal diet may have long-lasting effects in the development of non-communicable chronic adulthood diseases, in particular the components of the so-called metabolic syndrome, such as insulin resistance, type 2 diabetes, obesity, dyslipidaemia, hypertension, and CVD. Both maternal under- and over-nutrition may regulate the expression of genes involved in lipid and carbohydrate metabolism. Early postnatal nutrition may also represent a vital determinant of adult health by making an impact on the development and function of gut microbiota. An inadequate gut microbiota composition and function in early life seems to account for the deviant programming of later immunity and overall health status. In this regard probiotics, which have the potential to restore the intestinal microbiota balance, may be effective in preventing the development of chronic immune-mediated diseases. More recently, the epigenetic mechanisms elicited by probiotics through the production of SCFA are hypothesised to be the key to understand how they mediate their numerous health-promoting effects from the gut to the peripheral tissues.

  19. Early safety assessment using cellular systems biology yields insights into mechanisms of action.

    Science.gov (United States)

    Giuliano, Kenneth A; Gough, Albert H; Taylor, D Lansing; Vernetti, Lawrence A; Johnston, Patricia A

    2010-08-01

    The integration of high-content screening (HCS) readers with organ-specific cell models, panels of functional biomarkers, and advanced informatics is a powerful approach to identifying the toxic liabilities of compounds early in the development process and forms the basis of "early safety assessment." This cellular systems biology (CSB) approach (CellCiphr profile) has been used to integrate rodent and human cellular hepatic models with panels of functional biomarkers measured at multiple time points to profile both the potency and specificity of the cellular toxicological response. These profiles also provide initial insights on the mechanism of the toxic response. The authors describe here mechanistic assay profiles designed to further dissect the toxic mechanisms of action and elucidate subtle effects apparent in subpopulations of cells. They measured 8 key mechanisms of toxicity with multiple biomarker feature measurements made simultaneously in populations of living primary hepatocytes and HepG2 cells. Mining the cell population response from these mechanistic profiles revealed the concentration dependence and nature of the heterogeneity of the response, as well as relationships between the functional responses. These more detailed mechanistic profiles define differences in compound activities that are not apparent in the average population response. Because cells and tissues encounter wide ranges of drug doses in space and time, these mechanistic profiles build on the CellCiphr profile and better reflect the complexity of the response in vivo.

  20. Early response genes in the pathogenesis of cancer of the cervix uteri: a review

    Directory of Open Access Journals (Sweden)

    O. V. Kurmyshkina

    2011-01-01

    Full Text Available Early response genes are a group of proto-oncogenes that are the first to be activated in cell stimulation with different growth factors and to be involved in the regulation of cell proliferation and differentiation. Large amount of information supporting that altered expression of these genes is one of the central and earliest events of carcinogenesis has been accumulated. In this connection, it is promising to use early response genes as diagnostic and prognostic markers for the detection and combination therapy of cancer of the cervix uteri, one of the most common gynecological malignancies characterized by high mortality rates and difficulties in early diagnosis. The theoretical basis for these promises is the found mechanisms for the interaction of early response genes with human papillomavirus genome, the main cause of cervix uteri cancer.

  1. Early growth and postprandial appetite regulatory hormone responses

    DEFF Research Database (Denmark)

    Perälä, Mia-Maria; Kajantie, Eero; Valsta, Liisa M

    2013-01-01

    Strong epidemiological evidence suggests that slow prenatal or postnatal growth is associated with an increased risk of CVD and other metabolic diseases. However, little is known whether early growth affects postprandial metabolism and, especially, the appetite regulatory hormone system. Therefore......, we investigated the impact of early growth on postprandial appetite regulatory hormone responses to two high-protein and two high-fat content meals. Healthy, 65-75-year-old volunteers from the Helsinki Birth Cohort Study were recruited; twelve with a slow increase in BMI during the first year of life......, early growth may have a role in programming appetite regulatory hormone secretion in later life. Slow early growth is also associated with higher postprandial insulin and TAG responses but not with incretin levels....

  2. Low Oxygen Response Mechanisms in Green Organisms

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    Pierdomenico Perata

    2013-02-01

    Full Text Available Low oxygen stress often occurs during the life of green organisms, mostly due to the environmental conditions affecting oxygen availability. Both plants and algae respond to low oxygen by resetting their metabolism. The shift from mitochondrial respiration to fermentation is the hallmark of anaerobic metabolism in most organisms. This involves a modified carbohydrate metabolism coupled with glycolysis and fermentation. For a coordinated response to low oxygen, plants exploit various molecular mechanisms to sense when oxygen is either absent or in limited amounts. In Arabidopsis thaliana, a direct oxygen sensing system has recently been discovered, where a conserved N-terminal motif on some ethylene responsive factors (ERFs, targets the fate of the protein under normoxia/hypoxia. In Oryza sativa, this same group of ERFs drives physiological and anatomical modifications that vary in relation to the genotype studied. The microalga Chlamydomonas reinhardtii responses to low oxygen seem to have evolved independently of higher plants, posing questions on how the fermentative metabolism is modulated. In this review, we summarize the most recent findings related to these topics, highlighting promising developments for the future.

  3. Early

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  4. Early mechanisms in radiation-induced biological damage

    Energy Technology Data Exchange (ETDEWEB)

    Powers, E.L.

    1983-01-01

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

  5. Early knee osteoarthritis management should first address mechanical joint overload

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Arendt

    2014-03-01

    Full Text Available Early knee osteoarthritis poses a therapeutic dilemma to the musculoskeletal clinician. Despite the recent interest in arthroscopic and injectable regenerative therapies intended to repair or restore a focal target such as cartilage, meniscus, or subchondral bone, none have been shown to slow disease progression. A likely cause of these disappointing treatment outcomes is the failure to address chronic and excessive loading of the knee joint. A growing body of evidence suggests that first-line therapies for early knee osteoarthritis should emphasize unloading the knee joint since any potential therapeutic benefit of regenerative therapies will likely be attenuated by excessive mechanical demand at the knee joint. Minimally invasive medical devices such as patient-specific interpositional implants and extracapsular joint unloading implants are currently in development to address this clinical need.

  6. Early stiffening and softening of collagen: interplay of deformation mechanisms in biopolymer networks.

    Science.gov (United States)

    Kurniawan, Nicholas A; Wong, Long Hui; Rajagopalan, Raj

    2012-03-12

    Collagen networks, the main structural/mechanical elements in biological tissues, increasingly serve as biomimetic scaffolds for cell behavioral studies, assays, and tissue engineering, and yet their full spectrum of nonlinear behavior remains unclear. Here, with self-assembled type-I collagen as model, we use metrics beyond those in standard single-harmonic analysis of rheological measurements to reveal strain-softening and strain-stiffening of collagen networks both in instantaneous responses and at steady state. The results show how different deformation mechanisms, such as deformation-induced increase in the elastically active fibrils, nonlinear extension of individual fibrils, and slips in the physical cross-links in the network, can lead to the observed complex nonlinearity. We demonstrate how comprehensive rheological analyses can uncover the rich mechanical properties of biopolymer networks, including the above-mentioned softening as well as an early strain-stiffening, which are important for understanding physiological response of biological materials to mechanical loading.

  7. Early adversity and brain response to faces in young adulthood.

    Science.gov (United States)

    Lieslehto, Johannes; Kiviniemi, Vesa; Mäki, Pirjo; Koivukangas, Jenni; Nordström, Tanja; Miettunen, Jouko; Barnett, Jennifer H; Jones, Peter B; Murray, Graham K; Moilanen, Irma; Paus, Tomáš; Veijola, Juha

    2017-09-01

    Early stressors play a key role in shaping interindividual differences in vulnerability to various psychopathologies, which according to the diathesis-stress model might relate to the elevated glucocorticoid secretion and impaired responsiveness to stress. Furthermore, previous studies have shown that individuals exposed to early adversity have deficits in emotion processing from faces. This study aims to explore whether early adversities associate with brain response to faces and whether this association might associate with the regional variations in mRNA expression of the glucocorticoid receptor gene (NR3C1). A total of 104 individuals drawn from the Northern Finland Brith Cohort 1986 participated in a face-task functional magnetic resonance imaging (fMRI) study. A large independent dataset (IMAGEN, N = 1739) was utilized for reducing fMRI data-analytical space in the NFBC 1986 dataset. Early adversities were associated with deviant brain response to fearful faces (MANCOVA, P = 0.006) and with weaker performance in fearful facial expression recognition (P = 0.01). Glucocorticoid receptor gene expression (data from the Allen Human Brain Atlas) correlated with the degree of associations between early adversities and brain response to fearful faces (R(2)  = 0.25, P = 0.01) across different brain regions. Our results suggest that early adversities contribute to brain response to faces and that this association is mediated in part by the glucocorticoid system. Hum Brain Mapp 38:4470-4478, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Defining Clinical Response Criteria and Early Response Criteria for Precision Oncology: Current State-of-the-Art and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Vivek Subbiah

    2017-02-01

    Full Text Available In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for “go” versus “no go” decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords “response assessment” and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of “omics in radiology”—radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.

  9. Mechanical origins of rightward torsion in early chick brain development

    Science.gov (United States)

    Chen, Zi; Guo, Qiaohang; Dai, Eric; Taber, Larry

    2015-03-01

    During early development, the neural tube of the chick embryo undergoes a combination of progressive ventral bending and rightward torsion. This torsional deformation is one of the major organ-level left-right asymmetry events in development. Previous studies suggested that bending is mainly due to differential growth, however, the mechanism for torsion remains poorly understood. Since the heart almost always loops rightwards that the brain twists, researchers have speculated that heart looping affects the direction of brain torsion. However, direct evidence is lacking, nor is the mechanical origin of such torsion understood. In our study, experimental perturbations show that the bending and torsional deformations in the brain are coupled and that the vitelline membrane applies an external load necessary for torsion to occur. Moreover, the asymmetry of the looping heart gives rise to the chirality of the twisted brain. A computational model and a 3D printed physical model are employed to help interpret these findings. Our work clarifies the mechanical origins of brain torsion and the associated left-right asymmetry, and further reveals that the asymmetric development in one organ can induce the asymmetry of another developing organ through mechanics, reminiscent of D'Arcy Thompson's view of biological form as ``diagram of forces''. Z.C. is supported by the Society in Science - Branco Weiss fellowship, administered by ETH Zurich. L.A.T acknowledges the support from NIH Grants R01 GM075200 and R01 NS070918.

  10. Modeling mechanical response of heterogeneous materials

    Science.gov (United States)

    Pal, Siladitya

    Heterogeneous materials are ubiquitous in nature and as synthetic materials. These materials provide unique combination of desirable mechanical properties emerging from its heterogeneities at different length scales. Future structural and technological applications will require the development of advanced light weight materials with superior strength and toughness. Cost effective design of the advanced high performance synthetic materials by tailoring their microstructure is the challenge facing the materials design community. Prior knowledge of structure-property relationships for these materials is imperative for optimal design. Thus, understanding such relationships for heterogeneous materials is of primary interest. Furthermore, computational burden is becoming critical concern in several areas of heterogeneous materials design. Therefore, computationally efficient and accurate predictive tools are highly essential. In the present study, we mainly focus on mechanical behavior of soft cellular materials and tough biological material such as mussel byssus thread. Cellular materials exhibit microstructural heterogeneity by interconnected network of same material phase. However, mussel byssus thread comprises of two distinct material phases. A robust numerical framework is developed to investigate the micromechanisms behind the macroscopic response of both of these materials. Using this framework, effect of microstuctural parameters has been addressed on the stress state of cellular specimens during split Hopkinson pressure bar test. A voronoi tessellation based algorithm has been developed to simulate the cellular microstructure. Micromechanisms (microinertia, microbuckling and microbending) governing macroscopic behavior of cellular solids are investigated thoroughly with respect to various microstructural and loading parameters. To understand the origin of high toughness of mussel byssus thread, a Genetic Algorithm (GA) based optimization framework has been

  11. MECHANISMS OF IMMUNE RESPONSES IN CNIDARIANS

    Directory of Open Access Journals (Sweden)

    Iván Darío Ocampo

    2014-12-01

    Full Text Available The immune system maintains the integrity of the organisms through a complex network of molecules, cells, and tissues that recognize internal or external antigenic substances to neutralized and eliminate them. The mechanisms of immune response have evolved in a modular fashion, where members of a given module interact strongly among them, but weakly with members of other modules, providing robustness and evolvability to the immune system. Ancestral modules are the raw material for the generation of new modules through evolution. Thus, the study of immune systems in basal metazoans such as cnidarians seeks to determine the basic tool kit from which the metazoans started to construct their immune systems. In addition, understanding the immune mechanisms in cnidarians contributes to decipher the etiopathology of coral diseases of infectious nature that are affecting coral reefs worldwide.RESUMENEl sistema inmune mantiene la integridad de los organismos vivos por medio de una red compleja de moléculas, células y tejidos que reconocen sustancias antigénicas internas o externas para neutralizarlas y eliminarlas. Los mecanismos de respuesta inmune han evolucionado de una manera modular, en donde miembros de un módulo dado interactúan fuertemente entre sí, pero débilmente con componentes de otros módulos, otorgando así robustez y potencial evolutivo al sistema inmune. Módulos ancestrales representan el material básico para la generación de nuevos módulos durante el proceso evolutivo. Así, el estudio de sistemas inmunes en metazoarios basales como los cnidarios busca determinar cuales son los módulos ancestrales a partir de los cuales se constituyen los sistemas inmunes de animales derivados. Adicionalmente, el entendimiento de los mecanismos de respuesta inmune en cnidarios eventualmente contribuirá a descifrar la etiopatología de las enfermedades de corales de carácter infeccioso que está afectando los corales en el mundo.

  12. Early bilingualism enhances mechanisms of false-belief reasoning.

    Science.gov (United States)

    Kovács, Agnes Melinda

    2009-01-01

    In their first years, children's understanding of mental states seems to improve dramatically, but the mechanisms underlying these changes are still unclear. Such 'theory of mind' (ToM) abilities may arise during development, or have an innate basis, developmental changes reflecting limitations of other abilities involved in ToM tasks (e.g. inhibition). Special circumstances such as early bilingualism may enhance ToM development or other capacities required by ToM tasks. Here we compare 3-year-old bilinguals and monolinguals on a standard ToM task, a modified ToM task and a control task involving physical reasoning. The modified ToM task mimicked a language-switch situation that bilinguals often encounter and that could influence their ToM abilities. If such experience contributes to an early consolidation of ToM in bilinguals, they should be selectively enhanced in the modified task. In contrast, if bilinguals have an advantage due to better executive inhibitory abilities involved in ToM tasks, they should outperform monolinguals on both ToM tasks, inhibitory demands being similar. Bilingual children showed an advantage on the two ToM tasks but not on the control task. The precocious success of bilinguals may be associated with their well-developed control functions formed during monitoring and selecting languages.

  13. Implementation of responsiveness to intervention in early education settings.

    Science.gov (United States)

    Justice, Laura M; McGinty, Anita; Guo, Ying; Moore, Douglas

    2009-05-01

    This article provides an overview of how response to intervention (RTI) may be used effectively within early childhood settings. Discussion is organized to address such issues regarding RTI implementation as (1) how to design and implement a high-quality Tier 1 learning environment that systematically improves children's language and literacy outcomes, (2) how to design and implement a high-quality Tier 2 supplemental learning intervention that systematically improves the language and literacy outcomes of children who are unresponsive to Tier 1, and (3) how to design and implement a comprehensive and cohesive assessment system that appropriately identifies children who show inadequate response to the Tier 1 and Tier 2 learning opportunities. A model for implementing RTI using the supplemental curriculum by Justice and McGinty, READ IT AGAIN-PREK! (2008), is presented. This tool was developed to meet the needs of early childhood programs as they seek to implement RIA in a cost-effective and scalable manner.

  14. The Early Endocrine Stress Response in Experimental Subarachnoid Hemorrhage.

    Directory of Open Access Journals (Sweden)

    Christoffer Nyberg

    Full Text Available In patients with severe illness, such as aneurysmal subarachnoid hemorrhage (SAH, a physiologic stress response is triggered. This includes activation of the hypothalamic-pituitary-adrenal (HPA axis and the sympathetic nervous system. The aim of this study was to investigate the very early responses of these systems.A porcine animal model of aneurysmal SAH was used. In this model, blood is injected slowly to the basal cisterns above the anterior skull base until the cerebral perfusion pressure is 0 mm Hg. Sampling was done from blood and urine at -10, +15, +75 and +135 minutes from time of induction of SAH. Analyses of adrenocorticotropic hormone (ACTH, cortisol, aldosterone, catecholamines and chromogranin-A were performed.Plasma ACTH, serum cortisol and plasma aldosterone increased in the samples following induction of SAH, and started to decline after 75 minutes. Urine cortisol also increased after SAH. Urine catecholamines and their metabolites were found to increase after SAH. Many samples were however below detection level, not allowing for statistical analysis. Plasma chromogranin-A peaked at 15 minutes after SAH, and thereafter decreased.The endocrine stress response after aneurysmal SAH was found to start within 15 minutes in the HPA axis with early peak values of ACTH, cortisol and aldosterone. The fact that the concentrations of the HPA axis hormones decreased 135 minutes after SAH may suggest that a similar pattern exists in SAH patients, thus making it difficult to catch these early peak values. There were also indications of early activation of the sympathetic nervous system, but the small number of valid samples made interpretation difficult.

  15. Evaluation of early imaging response criteria in glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Millar Barbara-Ann

    2011-09-01

    Full Text Available Abstract Background Early and accurate prediction of response to cancer treatment through imaging criteria is particularly important in rapidly progressive malignancies such as Glioblastoma Multiforme (GBM. We sought to assess the predictive value of structural imaging response criteria one month after concurrent chemotherapy and radiotherapy (RT in patients with GBM. Methods Thirty patients were enrolled from 2005 to 2007 (median follow-up 22 months. Tumor volumes were delineated at the boundary of abnormal contrast enhancement on T1-weighted images prior to and 1 month after RT. Clinical Progression [CP] occurred when clinical and/or radiological events led to a change in chemotherapy management. Early Radiologic Progression [ERP] was defined as the qualitative interpretation of radiological progression one month post-RT. Patients with ERP were determined pseudoprogressors if clinically stable for ≥6 months. Receiver-operator characteristics were calculated for RECIST and MacDonald criteria, along with alternative thresholds against 1 year CP-free survival and 2 year overall survival (OS. Results 13 patients (52% were found to have ERP, of whom 5 (38.5% were pseudoprogressors. Patients with ERP had a lower median OS (11.2 mo than those without (not reached (p 25% in volume or > 15% in area were most predictive of OS. Conclusions We show that while a subjective interpretation of early radiological progression from baseline is generally associated with poor outcome, true progressors cannot be distinguished from pseudoprogressors. In contrast, the magnitude of early imaging volumetric response may be a predictive and quantitative metric of favorable outcome.

  16. Evolution of attention mechanisms for early visual processing

    Science.gov (United States)

    Müller, Thomas; Knoll, Alois

    2011-03-01

    Early visual processing as a method to speed up computations on visual input data has long been discussed in the computer vision community. The general target of a such approaches is to filter nonrelevant information from the costly higher-level visual processing algorithms. By insertion of this additional filter layer the overall approach can be speeded up without actually changing the visual processing methodology. Being inspired by the layered architecture of the human visual processing apparatus, several approaches for early visual processing have been recently proposed. Most promising in this field is the extraction of a saliency map to determine regions of current attention in the visual field. Such saliency can be computed in a bottom-up manner, i.e. the theory claims that static regions of attention emerge from a certain color footprint, and dynamic regions of attention emerge from connected blobs of textures moving in a uniform way in the visual field. Top-down saliency effects are either unconscious through inherent mechanisms like inhibition-of-return, i.e. within a period of time the attention level paid to a certain region automatically decreases if the properties of that region do not change, or volitional through cognitive feedback, e.g. if an object moves consistently in the visual field. These bottom-up and top-down saliency effects have been implemented and evaluated in a previous computer vision system for the project JAST. In this paper an extension applying evolutionary processes is proposed. The prior vision system utilized multiple threads to analyze the regions of attention delivered from the early processing mechanism. Here, in addition, multiple saliency units are used to produce these regions of attention. All of these saliency units have different parameter-sets. The idea is to let the population of saliency units create regions of attention, then evaluate the results with cognitive feedback and finally apply the genetic mechanism

  17. Gene regulation in the immediate-early response process.

    Science.gov (United States)

    Bahrami, Shahram; Drabløs, Finn

    2016-09-01

    Immediate-early genes (IEGs) can be activated and transcribed within minutes after stimulation, without the need for de novo protein synthesis, and they are stimulated in response to both cell-extrinsic and cell-intrinsic signals. Extracellular signals are transduced from the cell surface, through receptors activating a chain of proteins in the cell, in particular extracellular-signal-regulated kinases (ERKs), mitogen-activated protein kinases (MAPKs) and members of the RhoA-actin pathway. These communicate through a signaling cascade by adding phosphate groups to neighboring proteins, and this will eventually activate and translocate TFs to the nucleus and thereby induce gene expression. The gene activation also involves proximal and distal enhancers that interact with promoters to simulate gene expression. The immediate-early genes have essential biological roles, in particular in stress response, like the immune system, and in differentiation. Therefore they also have important roles in various diseases, including cancer development. In this paper we summarize some recent advances on key aspects of the activation and regulation of immediate-early genes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression.

    Science.gov (United States)

    Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

    2016-11-22

    Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response.

  19. Inferring mechanisms from dose-response curves

    OpenAIRE

    Chow, Carson C.; Ong, Karen M.; Dougherty, Edward J.; Simons, S. Stoney

    2011-01-01

    The steady state dose-response curve of ligand-mediated gene induction usually appears to precisely follow a first-order Hill equation (Hill coefficient equal to 1). Additionally, various cofactors/reagents can affect both the potency and the maximum activity of gene induction in a gene-specific manner. Recently, we have developed a general theory for which an unspecified sequence of steps or reactions yields a first-order Hill dose-response curve (FHDC) for plots of the final product vs. ini...

  20. Neurochemical mechanisms underlying responses to psychostimulants

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Fowler, J.S.; Hitzemann, R.; Wang, G.J. [Brookhaven National Lab., Upton, NY (United States)]|[State Univ. of New York, Stony Brook, NY (United States)

    1994-11-01

    This study employed positron emission tomography (PET) to investigate biochemical and metabolic characteristics of the brain of individuals which could put them at risk for drug addiction. It takes advantage of the normal variability between individuals in response to psychoactive drugs to investigate relation between mental state, brain neurochemistry and metabolism and the behavioral response to drugs. We discuss its use to assess if there is an association between mental state and dompaminergic reactivity in response to the psychostimulant drug methylphenidate (MP). Changes in synaptic dopamine induced by MP were evaluated with PET and [11C]raclopride, a D{sub 2} receptor radioligand that is sensitive to endogenous dopamine. Methylpphenidate significantly decreased striatal [11C]raclopride binding. The study showed a correlation between the magnitude of the dopamine-induced changes by methylphenidate, and the mental state of the subjects. Subjects reporting high levels of anxiety and restlessness at baseline had larger changes in MP-induced dopamine changes than those that did not. Further investigations on the relation between an individual`s response to a drug and his/her mental state and personality as well as his neurochemical brain composition may enable to understand better differences in drug addiction vulnerability.

  1. Fluoride inhibits the response of bone cells to mechanical loading

    NARCIS (Netherlands)

    Willems, H.M.E.; van den Heuvel, E.G.H.M.; Castelein, S.; Keverling Buisman, J.; Bronckers, A.L.J.J.; Bakker, A.D.; Klein-Nulend, J.

    2011-01-01

    The response of bone cells to mechanical loading is mediated by the cytoskeleton. Since the bone anabolic agent fluoride disrupts the cytoskeleton, we investigated whether fluoride affects the response of bone cells to mechanical loading, and whether this is cytoskeleton mediated. The mechano-respon

  2. Fluoride inhibits the response of bone cells to mechanical loading

    NARCIS (Netherlands)

    Willems, H.M.E.; van den Heuvel, E.G.H.M.; Castelein, S.; Keverling Buisman, J.; Bronckers, A.L.J.J.; Bakker, A.D.; Klein-Nulend, J.

    2011-01-01

    The response of bone cells to mechanical loading is mediated by the cytoskeleton. Since the bone anabolic agent fluoride disrupts the cytoskeleton, we investigated whether fluoride affects the response of bone cells to mechanical loading, and whether this is cytoskeleton mediated. The

  3. DYNAMIC MECHANICAL RESPONSE OF CRAZES IN POLYSTYRENE

    Institute of Scientific and Technical Information of China (English)

    DING Jianfu; XUE Gi; CHENG Rongshi

    1994-01-01

    Dynamic mechanical analysis was used to study the mechanical properties and microstructure of crazes in polystyrene produced in air or in methanol at different temperatures. A new loss peak was found at about 82℃ ,which is assigned to glass transition peak of craze fibrils. The decrease of glass transition temperature of polymer in craze fibrils is due to the high values of surface to volume ratio. The glass transition temperature ratio of craze fibrils to bulk material(Tg'/Tg) has been expressed as a function of the fibrils diameter(d). From Tg'of craze fibrils ,the value of fibril diameter can be calculated. Annealing the crazed specimen at room temperature makes the fibrils plastically deform and cause the fibrils to thin slightly, whereas annealing the crazed specimen at the temperature near Tg of the craze fibrils makes the fibrils bundle together.

  4. Natural killer cells promote early CD8 T cell responses against cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Scott H Robbins

    2007-08-01

    Full Text Available Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. While natural killer (NK cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown. To address this question, we took advantage of the well-defined molecular interactions involved in the recognition of mouse cytomegalovirus (MCMV by NK cells. By using congenic or mutant mice and wild-type versus genetically engineered viruses, we examined the consequences on antiviral CD8 T cell responses of specific defects in the ability of the NK cells to control MCMV. This system allowed us to demonstrate, to our knowledge for the first time, that NK cells accelerate CD8 T cell responses against a viral infection in vivo. Moreover, we identify the underlying mechanism as the ability of NK cells to limit IFN-alpha/beta production to levels not immunosuppressive to the host. This is achieved through the early control of cytomegalovirus, which dramatically reduces the activation of plasmacytoid dendritic cells (pDCs for cytokine production, preserves the conventional dendritic cell (cDC compartment, and accelerates antiviral CD8 T cell responses. Conversely, exogenous IFN-alpha administration in resistant animals ablates cDCs and delays CD8 T cell activation in the face of NK cell control of viral replication. Collectively, our data demonstrate that the ability of NK cells to respond very early to cytomegalovirus infection critically contributes to balance the intensity of other innate immune responses, which dampens early immunopathology and promotes optimal initiation of antiviral CD8 T cell responses. Thus, the extent to which NK cell responses benefit the host goes beyond their direct antiviral effects and extends to the prevention of innate

  5. Host response mechanisms in periodontal diseases

    Science.gov (United States)

    SILVA, Nora; ABUSLEME, Loreto; BRAVO, Denisse; DUTZAN, Nicolás; GARCIA-SESNICH, Jocelyn; VERNAL, Rolando; HERNÁNDEZ, Marcela; GAMONAL, Jorge

    2015-01-01

    Periodontal diseases usually refer to common inflammatory disorders known as gingivitis and periodontitis, which are caused by a pathogenic microbiota in the subgingival biofilm, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola that trigger innate, inflammatory, and adaptive immune responses. These processes result in the destruction of the tissues surrounding and supporting the teeth, and eventually in tissue, bone and finally, tooth loss. The innate immune response constitutes a homeostatic system, which is the first line of defense, and is able to recognize invading microorganisms as non-self, triggering immune responses to eliminate them. In addition to the innate immunity, adaptive immunity cells and characteristic cytokines have been described as important players in the periodontal disease pathogenesis scenario, with a special attention to CD4+ T-cells (T-helper cells). Interestingly, the T cell-mediated adaptive immunity development is highly dependent on innate immunity-associated antigen presenting cells, which after antigen capture undergo into a maturation process and migrate towards the lymph nodes, where they produce distinct patterns of cytokines that will contribute to the subsequent polarization and activation of specific T CD4+ lymphocytes. Skeletal homeostasis depends on a dynamic balance between the activities of the bone-forming osteoblasts (OBLs) and bone-resorbing osteoclasts (OCLs). This balance is tightly controlled by various regulatory systems, such as the endocrine system, and is influenced by the immune system, an osteoimmunological regulation depending on lymphocyte- and macrophage-derived cytokines. All these cytokines and inflammatory mediators are capable of acting alone or in concert, to stimulate periodontal breakdown and collagen destruction via tissue-derived matrix metalloproteinases, a characterization of the progression of periodontitis as a stage that

  6. Host response mechanisms in periodontal diseases

    Directory of Open Access Journals (Sweden)

    Nora SILVA

    2015-06-01

    Full Text Available Periodontal diseases usually refer to common inflammatory disorders known as gingivitis and periodontitis, which are caused by a pathogenic microbiota in the subgingival biofilm, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola that trigger innate, inflammatory, and adaptive immune responses. These processes result in the destruction of the tissues surrounding and supporting the teeth, and eventually in tissue, bone and finally, tooth loss. The innate immune response constitutes a homeostatic system, which is the first line of defense, and is able to recognize invading microorganisms as non-self, triggering immune responses to eliminate them. In addition to the innate immunity, adaptive immunity cells and characteristic cytokines have been described as important players in the periodontal disease pathogenesis scenario, with a special attention to CD4+ T-cells (T-helper cells. Interestingly, the T cell-mediated adaptive immunity development is highly dependent on innate immunity-associated antigen presenting cells, which after antigen capture undergo into a maturation process and migrate towards the lymph nodes, where they produce distinct patterns of cytokines that will contribute to the subsequent polarization and activation of specific T CD4+ lymphocytes. Skeletal homeostasis depends on a dynamic balance between the activities of the bone-forming osteoblasts (OBLs and bone-resorbing osteoclasts (OCLs. This balance is tightly controlled by various regulatory systems, such as the endocrine system, and is influenced by the immune system, an osteoimmunological regulation depending on lymphocyte- and macrophage-derived cytokines. All these cytokines and inflammatory mediators are capable of acting alone or in concert, to stimulate periodontal breakdown and collagen destruction via tissue-derived matrix metalloproteinases, a characterization of the progression of periodontitis as

  7. Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

    Science.gov (United States)

    Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

    2016-06-01

    Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

  8. Selective impact of early parental responsivity on adolescent stress reactivity.

    Directory of Open Access Journals (Sweden)

    Daniel A Hackman

    Full Text Available Research in animals has shown that early life experience, particularly parenting behaviors, influences later-life stress reactivity. Despite the tremendous relevance of this finding to human development and brain function, it has not been tested prospectively in humans. In this study two aspects of parenting were measured at age 4 in a sample of healthy, low socioeconomic status, African American children, and stress reactivity was measured in the same children 11-14 years later using a modified version of the Trier Social Stress Test (n = 55. Salivary cortisol was measured before, during and after the stressor and data were analyzed using piecewise hierarchical linear modeling. Parental responsivity, independent of the use of physical discipline, was positively related to cortisol reactivity. Effects were independent of subjective appraisals of the stressor and were also independent of other environmental risk factors and current psychosocial functioning. Therefore this study demonstrates in a novel and precise fashion that early childhood parental responsivity prospectively and independently predicts stress reactivity in adolescence.

  9. Early prediction of blonanserin response in Japanese patients with schizophrenia.

    Science.gov (United States)

    Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

    2014-01-01

    Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (Pblonanserin response at week 4 could predict the later response at week 8.

  10. Evasion of early innate immune response by 2'-O-methylation of dengue genomic RNA.

    Science.gov (United States)

    Chang, David C; Hoang, Long T; Mohamed Naim, Ahmad Nazri; Dong, Hongping; Schreiber, Mark J; Hibberd, Martin L; Tan, Min Jie Alvin; Shi, Pei-Yong

    2016-12-01

    Dengue virus (DENV) is the most prevalent mosquito-borne virus pathogen in humans. There is currently no antiviral therapeutic or widely available vaccine against dengue infection. The DENV RNA genome is methylated on its 5' cap by its NS5 protein. DENV bearing a single E216A point mutation in NS5 loses 2'-O-methylation of its genome. While this mutant DENV is highly attenuated and immunogenic, the mechanism of this attenuation has not been elucidated. In this study, we find that replication of this mutant DENV is attenuated very early during infection. This early attenuation is not dependent on a functional type I interferon response and coincides with early activation of the innate immune response. Taken together, our data suggest that 2'-O-methylation of DENV genomic RNA is important for evasion of the host immune response during the very early stages of infection as the virus seeks to establish infection. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Plant Responses to Salt Stress: Adaptive Mechanisms

    Directory of Open Access Journals (Sweden)

    Jose Ramón Acosta-Motos

    2017-02-01

    Full Text Available This review deals with the adaptive mechanisms that plants can implement to cope with the challenge of salt stress. Plants tolerant to NaCl implement a series of adaptations to acclimate to salinity, including morphological, physiological and biochemical changes. These changes include increases in the root/canopy ratio and in the chlorophyll content in addition to changes in the leaf anatomy that ultimately lead to preventing leaf ion toxicity, thus maintaining the water status in order to limit water loss and protect the photosynthesis process. Furthermore, we deal with the effect of salt stress on photosynthesis and chlorophyll fluorescence and some of the mechanisms thought to protect the photosynthetic machinery, including the xanthophyll cycle, photorespiration pathway, and water-water cycle. Finally, we also provide an updated discussion on salt-induced oxidative stress at the subcellular level and its effect on the antioxidant machinery in both salt-tolerant and salt-sensitive plants. The aim is to extend our understanding of how salinity may affect the physiological characteristics of plants.

  12. Early transcriptional response of soybean contrasting accessions to root dehydration.

    Directory of Open Access Journals (Sweden)

    José Ribamar Costa Ferreira Neto

    Full Text Available Drought is a significant constraint to yield increase in soybean. The early perception of water deprivation is critical for recruitment of genes that promote plant tolerance. DeepSuperSAGE libraries, including one control and a bulk of six stress times imposed (from 25 to 150 min of root dehydration for drought-tolerant and sensitive soybean accessions, allowed to identify new molecular targets for drought tolerance. The survey uncovered 120,770 unique transcripts expressed by the contrasting accessions. Of these, 57,610 aligned with known cDNA sequences, allowing the annotation of 32,373 unitags. A total of 1,127 unitags were up-regulated only in the tolerant accession, whereas 1,557 were up-regulated in both as compared to their controls. An expression profile concerning the most representative Gene Ontology (GO categories for the tolerant accession revealed the expression "protein binding" as the most represented for "Molecular Function", whereas CDPK and CBL were the most up-regulated protein families in this category. Furthermore, particular genes expressed different isoforms according to the accession, showing the potential to operate in the distinction of physiological behaviors. Besides, heat maps comprising GO categories related to abiotic stress response and the unitags regulation observed in the expression contrasts covering tolerant and sensitive accessions, revealed the unitags potential for plant breeding. Candidate genes related to "hormone response" (LOX, ERF1b, XET, "water response" (PUB, BMY, "salt stress response" (WRKY, MYB and "oxidative stress response" (PER figured among the most promising molecular targets. Additionally, nine transcripts (HMGR, XET, WRKY20, RAP2-4, EREBP, NAC3, PER, GPX5 and BMY validated by RT-qPCR (four different time points confirmed their differential expression and pointed that already after 25 minutes a transcriptional reorganization started in response to the new condition, with important

  13. Early prediction of blonanserin response in Japanese patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Kishi T

    2014-09-01

    Full Text Available Taro Kishi,1 Yuki Matsuda,1 Kiyoshi Fujita,2,3 Nakao Iwata1 1Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 2Department of Psychiatry, Okehazama Hospital, Toyoake, Aichi, Japan; 3The Neuroscience Research Center, Toyoake, Aichi, Japan Background: Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. Methods: An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8.Results: Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia, and 28 (75.7% completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS total score (P<0.0001 and in positive (P<0.0001, negative (P<0.0001, and general subscale scores (P<0.0001. In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores were 88.9% and 94.1%, respectively. The specificities were 80.0% and

  14. Enhancing early child care quality and learning for toddlers at risk: the responsive early childhood program.

    Science.gov (United States)

    Landry, Susan H; Zucker, Tricia A; Taylor, Heather B; Swank, Paul R; Williams, Jeffrey M; Assel, Michael; Crawford, April; Huang, Weihua; Clancy-Menchetti, Jeanine; Lonigan, Christopher J; Phillips, Beth M; Eisenberg, Nancy; Spinrad, Tracy L; de Villiers, Jill; de Villiers, Peter; Barnes, Marcia; Starkey, Prentice; Klein, Alice

    2014-02-01

    Despite reports of positive effects of high-quality child care, few experimental studies have examined the process of improving low-quality center-based care for toddler-age children. In this article, we report intervention effects on child care teachers' behaviors and children's social, emotional, behavioral, early literacy, language, and math outcomes as well as the teacher-child relationship. The intervention targeted the use of a set of responsive teacher practices, derived from attachment and sociocultural theories, and a comprehensive curriculum. Sixty-five childcare classrooms serving low-income 2- and 3-year-old children were randomized into 3 conditions: business-as-usual control, Responsive Early Childhood Curriculum (RECC), and RECC plus explicit social-emotional classroom activities (RECC+). Classroom observations showed greater gains for RECC and RECC+ teachers' responsive practices including helping children manage their behavior, establishing a predictable schedule, and use of cognitively stimulating activities (e.g., shared book reading) compared with controls; however, teacher behaviors did not differ for focal areas such as sensitivity and positive discipline supports. Child assessments demonstrated that children in the interventions outperformed controls in areas of social and emotional development, although children's performance in control and intervention groups was similar for cognitive skills (language, literacy, and math). Results support the positive impact of responsive teachers and environments providing appropriate support for toddlers' social and emotional development. Possible explanations for the absence of systematic differences in children's cognitive skills are considered, including implications for practice and future research targeting low-income toddlers.

  15. Early Age Fracture Mechanics and Cracking of Concrete

    DEFF Research Database (Denmark)

    Østergaard, Lennart

    2003-01-01

    Modern high performance concretes have low water cement ratios and do often include silica fume. Also early age high strength cements are often applied and when all these factors sum up, it turns out that the cracking sensibility is dramatically increased in com- parison with ordinary concrete...... if applied in early age. The results are only valid after 24 hours for fast and normal hardening cements and after 48 hours for slow hardening cements. This is con¯rmed in a finite element model. The fracture properties of early age concrete have been determined. The framework of the investigations has been...

  16. Mechanical response of proton beam irradiated nitinol

    Energy Technology Data Exchange (ETDEWEB)

    Afzal, Naveed [Centre for Advanced Studies in Physics, GC University, Lahore (Pakistan); Ghauri, I.M., E-mail: ijaz.phys@gmail.co [Centre for Advanced Studies in Physics, GC University, Lahore (Pakistan); Mubarik, F.E.; Amin, F. [Centre for Advanced Studies in Physics, GC University, Lahore (Pakistan)

    2011-01-01

    The present investigation deals with the study of mechanical behavior of proton beam irradiated nitinol at room temperature. The specimens in austenitic phase were irradiated over periods of 15, 30, 45 and 60 min at room temperature using 2 MeV proton beam obtained from Pelletron accelerator. The stress-strain curves of both unirradiated and irradiated specimens were obtained using a universal testing machine at room temperature. The results of the experiment show that an intermediate rhombohedral (R) phase has been introduced between austenite and martensite phase, which resulted in the suppression of direct transformation from austenite to martensite (A-M). Stresses required to start R-phase ({sigma}{sub RS}) and martensitic phase ({sigma}{sub MS}) were observed to decrease with increase in exposure time. The hardness tests of samples before and after irradiation were also carried out using Vickers hardness tester. The comparison reveals that the hardness is higher in irradiated specimens than that of the unirradiated one. The increase in hardness is quite sharp in specimens irradiated for 15 min, which then increases linearly as the exposure time is increased up to 60 min. The generation of R-phase, variations in the transformation stresses {sigma}{sub RS} and {sigma}{sub MS} and increase in hardness of irradiated nitinol may be attributed to lattice disorder and associated changes in crystal structure induced by proton beam irradiation.

  17. Quantum Mechanical Studies of the Early Actinide Compounds

    Science.gov (United States)

    Obodo, Kingsley Onyebuchi

    This study involves the investigation of the early actinide systems using ab initio techniques based on density functional theory (DFT). It was motivated by: (i) the incomplete description of these systems using conventional DFT because they are strongly correlated, (ii) the usefulness of these systems in nuclear energy generation, (iii) the complexity that arises in experimentally studying these systems due to their inherent radioactive nature and (iv) their limited availability. The results obtained from this study are divided into two broad sections. The first comprises chapters 3 and 4 while the second comprises chapters 5 and 6. Thorium based compounds are studied in chapters 3 and 4. In the first section, the Hubbard U parameter is not necessary to accurately describe the electronic, elastic and mechanical properties of these systems. In the second, the inclusion of the Hubbard U parameter is shown to be paramount for the accurate description of most compounds considered. Chapter 3 presents the electronic, structural and bonding character of thorium based nitrides. We obtained the result that Th2N2 NH, which is crystallographically equivalent to metallic Th2N 3, is insulating. Chapter 4 demonstrates that the formation of a meta-stable thorium-titanium based alloy is plausible and also further information on bonding, electronic and elastic properties of the determined meta-stable alloy is provided. This has provided important new knowledge about these bulk systems. In Chapter 5 the DFT + U based study on Pa and its oxides is presented. The electronic, structural and bonding character of these systems was studied. We found that PaO2 is a Mott-Hubbard insulator with an indirect band gap of 3.48 eV within the generalized gradient approximation GGA + U. Chapter 6 discusses various actinide nitrides. We explored the electronic properties, elastic properties, lattice dynamics and the energetics of the various compounds using GGA + U. Also, we investigated the effect

  18. Early warning systems and rapid response to the deteriorating patient in hospital: A realist evaluation.

    Science.gov (United States)

    McGaughey, Jennifer; O'Halloran, Peter; Porter, Sam; Trinder, John; Blackwood, Bronagh

    2017-06-21

    To test the Rapid Response Systems programme theory against actual practice components of the Rapid Response Systems implemented to identify those contexts and mechanisms which have an impact on the successful achievement of desired outcomes in practice. Rapid Response Systems allow deteriorating patients to be recognized using Early Warning Systems, referred early via escalation protocols and managed at the bedside by competent staff. Realist evaluation. The research design was an embedded multiple case study approach of four wards in two hospitals in Northern Ireland which followed the principles of Realist Evaluation. We used various mixed methods including individual and focus group interviews, observation of nursing practice between June-November 2010 and document analysis of Early Warning Systems audit data between May-October 2010 and hospital acute care training records over 4.5 years from 2003-2008. Data were analysed using NiVivo8 and SPPS. A cross-case analysis highlighted similar patterns of factors which enabled or constrained successful recognition, referral and response to deteriorating patients in practice. Key enabling factors were the use of clinical judgement by experienced nurses and the empowerment of nurses as a result of organizational change associated with implementation of Early Warning System protocols. Key constraining factors were low staffing and inappropriate skill mix levels, rigid implementation of protocols and culturally embedded suboptimal communication processes. Successful implementation of Rapid Response Systems was dependent on adopting organizational and cultural changes that facilitated staff empowerment, flexible implementation of protocols and ongoing experiential learning. © 2017 John Wiley & Sons Ltd.

  19. Mechanical Response of DNA–Nanoparticle Crystals to Controlled Deformation

    Science.gov (United States)

    2016-01-01

    The self-assembly of DNA-conjugated nanoparticles represents a promising avenue toward the design of engineered hierarchical materials. By using DNA to encode nanoscale interactions, macroscale crystals can be formed with mechanical properties that can, at least in principle, be tuned. Here we present in silico evidence that the mechanical response of these assemblies can indeed be controlled, and that subtle modifications of the linking DNA sequences can change the Young’s modulus from 97 kPa to 2.1 MPa. We rely on a detailed molecular model to quantify the energetics of DNA–nanoparticle assembly and demonstrate that the mechanical response is governed by entropic, rather than enthalpic, contributions and that the response of the entire network can be estimated from the elastic properties of an individual nanoparticle. The results here provide a first step toward the mechanical characterization of DNA–nanoparticle assemblies, and suggest the possibility of mechanical metamaterials constructed using DNA. PMID:27725959

  20. Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response.

    Science.gov (United States)

    Shahin, Mohamed H; Johnson, Julie A

    2016-04-01

    Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response.

  1. Evidence for two concurrent inhibitory mechanisms during response preparation

    OpenAIRE

    Duque, Julie; Lew, David; Mazzocchio, Riccardo; Olivier, Etienne; Ivry, Richard B.

    2010-01-01

    Inhibitory mechanisms are critically involved in goal-directed behaviors. To gain further insight into how such mechanisms shape motor representations during response preparation, motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) and H-reflexes were recorded from left hand muscles during choice reaction time tasks. The imperative signal, which indicated the required response, was always preceded by a preparatory cue. During the post-cue delay period, left MEPs...

  2. Early error detection predicted by reduced pre-response control process: an ERP topographic mapping study.

    Science.gov (United States)

    Pourtois, Gilles

    2011-01-01

    Advanced ERP topographic mapping techniques were used to study error monitoring functions in human adult participants, and test whether proactive attentional effects during the pre-response time period could later influence early error detection mechanisms (as measured by the ERN component) or not. Participants performed a speeded go/nogo task, and made a substantial number of false alarms that did not differ from correct hits as a function of behavioral speed or actual motor response. While errors clearly elicited an ERN component generated within the dACC following the onset of these incorrect responses, I also found that correct hits were associated with a different sequence of topographic events during the pre-response baseline time-period, relative to errors. A main topographic transition from occipital to posterior parietal regions (including primarily the precuneus) was evidenced for correct hits ~170-150 ms before the response, whereas this topographic change was markedly reduced for errors. The same topographic transition was found for correct hits that were eventually performed slower than either errors or fast (correct) hits, confirming the involvement of this distinctive posterior parietal activity in top-down attentional control rather than motor preparation. Control analyses further ensured that this pre-response topographic effect was not related to differences in stimulus processing. Furthermore, I found a reliable association between the magnitude of the ERN following errors and the duration of this differential precuneus activity during the pre-response baseline, suggesting a functional link between an anticipatory attentional control component subserved by the precuneus and early error detection mechanisms within the dACC. These results suggest reciprocal links between proactive attention control and decision making processes during error monitoring.

  3. Susceptibility and resistance to Echinococcus granulosus infection: Associations between mouse strains and early peritoneal immune responses.

    Science.gov (United States)

    Mourglia-Ettlin, Gustavo; Merlino, Alicia; Capurro, Rafael; Dematteis, Sylvia

    2016-03-01

    In helminth infections, there are no easy associations between host susceptibility and immune responses. Interestingly, immunity to cestodes - unlike most helminths - seems to require Th1-type effectors. In this sense, we reported recently that Balb/c and C57Bl/6 mice are high and low susceptible strains, respectively, to experimental infection by Echinococcus granulosus. However, the role of the early cellular peritoneal response in such differential susceptibility is unknown. Here, we analyzed the kinetics of cytokines expression and cellular phenotypes in peritoneal cells from infected Balb/c and C57Bl/6 mice. Additionally, Principal Components Analysis (PCA) were conducted to highlight the most relevant differences between strains. Finally, the anti-parasite activities of peritoneal cells were assessed through in vitro systems. PCAs clustered C57Bl/6 mice by their early mixed IL-5/TNF-α responses and less intense expression of Th2-type cytokines. Moreover, they exhibited lower counts of eosinophils and higher numbers of macrophages and B cells. Functional studies showed that peritoneal cells from infected C57Bl/6 mice displayed greater anti-parasite activities, in accordance with higher rates of NO production and more efficient ADCC responses. In conclusion, mild Th2-responses and active cellular mechanisms are key determinants in murine resistance to E. granulosus infection, supporting the cestode immune exception among helminth parasites.

  4. Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

    KAUST Repository

    Liu, Pei

    2015-02-27

    Accumulation of reactive oxygen species (ROS) is one of the early defense responses against pathogen infection in plants. The mechanism about the initial and direct regulation of the defense signaling pathway by ROS remains elusive. Perturbation of cellular redox homeostasis by ROS is believed to alter functions of redox-sensitive proteins through their oxidative modifications. Here we report an OxiTRAQ-based proteomic study in identifying proteins whose cysteines underwent oxidative modifications in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional regulation, chromatin remodeling, RNA processing, post-translational modifications, and nucleocytoplasmic shuttling. The identification of the salicylate-/flg22-responsive redox-sensitive proteins provides a foundation from which further study can be conducted toward understanding biological significance of their oxidative modifications during the plant defense response.

  5. Single Pulse Electrical Stimulation to identify epileptogenic cortex: Clinical information obtained from early evoked responses

    NARCIS (Netherlands)

    Mouthaan, B.E.; van 't Klooster, M.A.; Keizer, D.; Hebbink, Gerrit Jan; Leijten, F.S.; Ferrier, C.H.; van Putten, Michel Johannes Antonius Maria; Zijlmans, M.; Huiskamp, G.J.

    2016-01-01

    Objective Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100 ms) that map cortical

  6. Single pulse electrical stimulation to identify epileptogenic cortex: Clinical information obtained from early evoked responses

    NARCIS (Netherlands)

    Mouthaan, B.E.; van 't Klooster, M.A.; Keizer, D.; Hebbink, Gerrit Jan; Leijten, F.S.S.; Ferrier, C.H.; van Putten, Michel Johannes Antonius Maria; Zijlmans, M.; Huiskamp, G.J.M.

    Objective: Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100 ms) that map cortical

  7. A Mechanism for Error Detection in Speeded Response Time Tasks

    Science.gov (United States)

    Holroyd, Clay B.; Yeung, Nick; Coles, Michael G. H.; Cohen, Jonathan D.

    2005-01-01

    The concept of error detection plays a central role in theories of executive control. In this article, the authors present a mechanism that can rapidly detect errors in speeded response time tasks. This error monitor assigns values to the output of cognitive processes involved in stimulus categorization and response generation and detects errors…

  8. 18F-FLT PET/CT for early response monitoring and dose escalation in oropharyngeal tumors.

    NARCIS (Netherlands)

    Troost, E.G.C.; Bussink, J.; Hoffmann, A.L.; Boerman, O.C.; Oyen, W.J.G.; Kaanders, J.H.A.M.

    2010-01-01

    Accelerated tumor cell proliferation is an important mechanism adversely affecting therapeutic outcome in head and neck cancer. 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a PET tracer to noninvasively image tumor cell proliferation. The aims of this study were to monitor early tumor response b

  9. A Dynamic Market Mechanism for Markets with Shiftable Demand Response

    DEFF Research Database (Denmark)

    Hansen, Jacob; Knudsen, Jesper Viese; Kiani, Arman

    2014-01-01

    renewables, this mechanism accommodates both consumers with a shiftable Demand Response and an adjustable Demand Response. The overall market mechanism is evaluated in a Day Ahead Market and is shown in a numerical example to result in a reduction of the cost of electricity for the consumer, as well......In this paper, we propose a dynamic market mechanism that converges to the desired market equilibrium. Both locational marginal prices and the schedules for generation and consumption are determined through a negotiation process between the key market players. In addition to incorporating...

  10. Damage response involves mechanisms conserved across plants, animals and fungi.

    Science.gov (United States)

    Hernández-Oñate, M A; Herrera-Estrella, A

    2015-08-01

    All organisms are constantly exposed to adverse environmental conditions including mechanical damage, which may alter various physiological aspects of growth, development and reproduction. In plant and animal systems, the damage response mechanism has been widely studied. Both systems posses a conserved and sophisticated mechanism that in general is aimed at repairing and preventing future damage, and causes dramatic changes in their transcriptomes, proteomes, and metabolomes. These damage-induced changes are mediated by elaborate signaling networks, which include receptors/sensors, calcium (Ca(2+)) influx, ATP release, kinase cascades, reactive oxygen species (ROS), and oxylipin signaling pathways. In contrast, our current knowledge of how fungi respond to injury is limited, even though various reports indicate that mechanical damage triggers reproductive processes. In fungi, the damage response mechanism has been studied more in depth in Trichoderma atroviride. Interestingly, these studies indicate that the mechanical damage response involves ROS, Ca(2+), kinase cascades, and lipid signaling pathways. Here we compare the response to mechanical damage in plants, animals and fungi and provide evidence that they appear to share signaling molecules and pathways, suggesting evolutionary conservation across the three kingdoms.

  11. Early detection of changes in lung mechanics with oscillometry following bariatric surgery in severe obesity.

    Science.gov (United States)

    Peters, Ubong; Hernandez, Paul; Dechman, Gail; Ellsmere, James; Maksym, Geoffrey

    2016-05-01

    Obesity is associated with respiratory symptoms that are reported to improve with weight loss, but this is poorly reflected in spirometry, and few studies have measured respiratory mechanics with oscillometry. We investigated whether early changes in lung mechanics following weight loss are detectable with oscillometry. Furthermore, we investigated whether the changes in lung mechanics measured in the supine position following weight loss are associated with changes in sleep quality. Nineteen severely obese female subjects (mean body mass index, 47.2 ± 6.6 kg/m(2)) were evaluated using spirometry, oscillometry, plethysmography, and the Pittsburgh Sleep Quality Index before and 5 weeks after bariatric surgery. These tests were conducted in both the upright and the supine position, and pre- and postbronchodilation with 200 μg of salbutamol. Five weeks after surgery, weight loss of 11.5 ± 2.5 kg was not associated with changes in spirometry and plethysmography, with the exception of functional residual capacity. There were also no changes in upright respiratory system resistance (Rrs) or reactance following weight loss. Importantly, however, in the supine position, weight loss caused a substantial reduction in Rrs. In addition, sleep quality improved significantly and was highly correlated with the reduction in supine Rrs. Prior to weight loss, subjects did not respond to the bronchodilator when assessed in the upright position with either spirometry or oscillometry; however, with modest weight loss, bronchodilator responsiveness returned to the normal range. Improvements in lung mechanics occur very early after weight loss, mostly in the supine position, resulting in improved sleep quality. These improvements are detectable with oscillometry but not with spirometry.

  12. Lung mechanics in the TIMP3 null mouse and its response to mechanical ventilation.

    Science.gov (United States)

    Martin, Erica L; Truscott, Emily A; Bailey, Timothy C; Leco, Kevin J; McCaig, Lynda A; Lewis, James F; Veldhuizen, Ruud A W

    2007-03-01

    Tissue inhibitor of metalloproteinase-3 (TIMP3) null mice develop emphysema-like airspace enlargement due to an enzymatic imbalance. This study investigates how these abnormalities alter lung mechanics and the response to 2 different mechanical ventilation strategies. Phenotypically, TIMP3 null mice had increased compliance, and decreased resistance, tissue damping, and tissue elastance over wild-type controls. Decreased compliance and increased resistance were observed following the injurious ventilation strategy; however, the TIMP3 null response to both ventilation strategies was similar to wild-type mice. In conclusion, TIMP3 null mice have significant alterations in lung mechanics; however, this does not affect their response to ventilation.

  13. Modeling thermal/chemical/mechanical response of energetic materials

    Energy Technology Data Exchange (ETDEWEB)

    Baer, M.R.; Hobbs, M.L.; Gross, R.J. [and others

    1995-07-01

    An overview of modeling at Sandia National Laboratories is presented which describes coupled thermal, chemical and mechanical response of energetic materials. This modeling addresses cookoff scenarios for safety assessment studies in systems containing energetic materials. Foundation work is discussed which establishes a method for incorporating chemistry and mechanics into multidimensional analysis. Finite element analysis offers the capabilities to simultaneously resolve reactive heat transfer and structural mechanics in complex geometries. Nonlinear conduction heat transfer, with multiple step finite-rate chemistry, is resolved using a thermal finite element code. Rate equations are solved element-by-element using a modified matrix-free stiff solver This finite element software was developed for the simulation of systems requiring large numbers of finite elements. An iterative implicit scheme, based on the conjugate gradient method, is used and a hemi-cube algorithm is employed for the determination of view factors in surface-to-surface radiation transfer The critical link between the reactive heat transfer and mechanics is the introduction of an appropriate constitutive material model providing a stress-strain relationship for quasi-static mechanics analysis. This model is formally derived from bubble nucleation theory, and parameter variations of critical model parameters indicate that a small degree of decomposition leads to significant mechanical response. Coupled thermal/chemical/mechanical analysis is presented which simulates experiments designed to probe cookoff thermal-mechanical response of energetic materials.

  14. Vestibular activation differentially modulates human early visual cortex and V5/MT excitability and response entropy.

    Science.gov (United States)

    Seemungal, Barry M; Guzman-Lopez, Jessica; Arshad, Qadeer; Schultz, Simon R; Walsh, Vincent; Yousif, Nada

    2013-01-01

    Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC.

  15. Transcriptome analysis of silkworm, Bombyx mori, during early response to Beauveria bassiana challenges.

    Science.gov (United States)

    Hou, Chengxiang; Qin, Guangxing; Liu, Ting; Geng, Tao; Gao, Kun; Pan, Zhonghua; Qian, Heying; Guo, Xijie

    2014-01-01

    Host-pathogen interactions are complex processes and it is a central challenge to reveal these interactions. Fungal infection of silkworm, Bombyx mori, may induce a variety of responsive reaction. However, little is known about the molecular mechanism of silkworm immune response against the fungal infection. To obtain an overview of the interaction between silkworm and an entomopathogenic fungus Beauveria bassiana, Digital Gene Expression profiling, a tag based high-throughput transcriptome sequencing method, was employed to screen and identify differentially expressed genes (DEGs, FDR ≤ 0.001, ∣log2ratio∣ ≥ 1) of silkworm larvae during early response against B. bassiana infection. Total 1430 DEGs including 960 up-regulated and 470 down-regulated ones were identified, of which 627 DEGs can be classified into GO categories by Gene Ontology (GO) analysis. KEGG pathways analysis of these DEGs suggested that many biological processes, such as defense and response, signal transduction, phagocytosis, regulation of gene expression, RNA splicing, biosynthesis and metabolism, protein transport etc. were involved in the interaction between the silkworm and B. bassiana. A number of differentially expressed fungal genes were also identified by mapping the sequencing tags to B. bassiana genome. These results provided new insights to the molecular mechanism of silkworm immune response to B. bassiana infection.

  16. Stomatal Blue Light Response Is Present in Early Vascular Plants1[OPEN

    Science.gov (United States)

    Doi, Michio; Kitagawa, Yuki; Shimazaki, Ken-ichiro

    2015-01-01

    Light is a major environmental factor required for stomatal opening. Blue light (BL) induces stomatal opening in higher plants as a signal under the photosynthetic active radiation. The stomatal BL response is not present in the fern species of Polypodiopsida. The acquisition of a stomatal BL response might provide competitive advantages in both the uptake of CO2 and prevention of water loss with the ability to rapidly open and close stomata. We surveyed the stomatal opening in response to strong red light (RL) and weak BL under the RL with gas exchange technique in a diverse selection of plant species from euphyllophytes, including spermatophytes and monilophytes, to lycophytes. We showed the presence of RL-induced stomatal opening in most of these species and found that the BL responses operated in all euphyllophytes except Polypodiopsida. We also confirmed that the stomatal opening in lycophytes, the early vascular plants, is driven by plasma membrane proton-translocating adenosine triphosphatase and K+ accumulation in guard cells, which is the same mechanism operating in stomata of angiosperms. These results suggest that the early vascular plants respond to both RL and BL and actively regulate stomatal aperture. We also found three plant species that absolutely require BL for both stomatal opening and photosynthetic CO2 fixation, including a gymnosperm, C. revoluta, and the ferns Equisetum hyemale and Psilotum nudum. PMID:26307440

  17. A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Sebastian Weckbach

    2012-01-01

    Full Text Available Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group were anesthetized and exposed to chest trauma (ChT, closed head injury (CHI, or Tib/Fib fracture including a soft tissue trauma (Fx + STT or to the following combination of injuries: (1 ChT; (2 ChT + Fx + STT; (3 ChT + CHI; (4 CHI; (5 polytrauma (PT = ChT + CHI + Fx + STT. Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL fluid samples. Results. Polytraumatized (PT rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma.

  18. Treatment of Glucocorticoids Inhibited Early Immune Responses and Impaired Cardiac Repair in Adult Zebrafish.

    Directory of Open Access Journals (Sweden)

    Wei-Chang Huang

    Full Text Available Myocardial injury, such as myocardial infarction (MI, can lead to drastic heart damage. Zebrafish have the extraordinary ability to regenerate their heart after a severe injury. Upon ventricle resection, fibrin clots seal the wound and serve as a matrix for recruiting myeloid-derived phagocytes. Accumulated neutrophils and macrophages not only reduce the risk of infection but also secrete cytokines and growth factors to promote tissue repair. However, the underlying cellular and molecular mechanisms for how immune responses are regulated during the early stages of cardiac repair are still unclear. We investigated the role and programming of early immune responses during zebrafish heart regeneration. We found that zebrafish treated with an anti-inflammatory glucocorticoid had significantly reduced heart regenerative capacities, consistent with findings in other higher vertebrates. Moreover, inhibiting the inflammatory response led to excessive collagen deposition. A microarray approach was used to assess the differential expression profiles between zebrafish hearts with normal or impaired healing. Combining cytokine profiling and immune-staining, our data revealed that impaired heart regeneration could be due to reduced phagocyte recruitment, leading to diminished angiogenesis and cell proliferation post-cardiac injury. Despite their robust regenerative ability, our study revealed that glucocorticoid treatment could effectively hinder cardiac repair in adult zebrafish by interfering with the inflammatory response. Our findings may help to clarify the initiation of cardiac repair, which could be used to develop a therapeutic intervention that may enhance cardiac repair in humans to compensate for the loss of cardiomyocytes after an MI.

  19. Histochemical characterization of early response to Cochliobolus sativus infection in selected barley genotypes.

    Science.gov (United States)

    Rodríguez-Decuadro, Susana; Silva, Paula; Bentancur, Oscar; Gamba, Fernanda; Pritsch, Clara

    2014-07-01

    Much effort is being made to breed barley with durable resistance to leaf spot blotch incited by Bipolaris sorokiniana (teleomorph: Cochliobolus sativus). We hypothesized that susceptibility and resistance traits in 11 diverse barley genotypes inoculated with a single C. sativus isolate might specify a range of distinct host cell responses. Quantitative descriptions of interaction microphenotypes exhibited by different barley genotype seedlings after infection with C. sativus are provided. Early oxidative responses occurring in epidermis and mesophyll leaf tissue were monitored by histochemical analysis of H2O2 accumulation at 8, 24, and 48 h after inoculation. Cell wall apposition (CWA) in epidermal cells and hypersensitive reaction (HR) of epidermal or mesophyll tissue were early defenses in both resistant and susceptible genotypes. There were differences in level, duration, and frequency of occurrence for CWA and HR for the different barley genotypes. Occurrence of HR in epidermal cells at post-penetration stages was indicative of compatibility. Patterns of cell responses were microphenotypically diverse between different resistant and susceptible genotypes. This suggests that timing and level of response are key features of microphenotypic diversity that distinguish different functional mechanisms of resistance and susceptibility present in barley.

  20. Diverse mechanisms evolved by DNA viruses to inhibit early host defenses.

    Science.gov (United States)

    Crow, Marni S; Lum, Krystal K; Sheng, Xinlei; Song, Bokai; Cristea, Ileana M

    In mammalian cells, early defenses against infection by pathogens are mounted through a complex network of signaling pathways shepherded by immune-modulatory pattern-recognition receptors. As obligate parasites, the survival of viruses is dependent on the evolutionary acquisition of mechanisms that tactfully dismantle and subvert the cellular intrinsic and innate immune responses. Here, we review the diverse mechanisms by which viruses that accommodate DNA genomes are able to circumvent activation of cellular immunity. We start by discussing viral manipulation of host defense protein levels by either transcriptional regulation or protein degradation. We next review viral strategies used to repurpose or inhibit these cellular immune factors by molecular hijacking or by regulating their post-translational modification status. Additionally, we explore the infection-induced temporal modulation of apoptosis to facilitate viral replication and spread. Lastly, the co-evolution of viruses with their hosts is highlighted by the acquisition of elegant mechanisms for suppressing host defenses via viral mimicry of host factors. In closing, we present a perspective on how characterizing these viral evasion tactics both broadens the understanding of virus-host interactions and reveals essential functions of the immune system at the molecular level. This knowledge is critical in understanding the sources of viral pathogenesis, as well as for the design of antiviral therapeutics and autoimmunity treatments.

  1. Does Early Responsive Parenting Have a Special Importance for Children's Development or Is Consistency across Early Childhood Necessary?

    Science.gov (United States)

    Landry, Susan H.; Smith, Karen E.; Swank, Paul R.; Assel, Mike A.; Vellet, Sonya

    2001-01-01

    Examined the role of early versus ongoing maternal responsiveness in predicting cognitive and social development for full-term and preterm children (low- and high-risk) at five ages. Found that children, especially preterm children, showed faster cognitive growth when mothers were consistently responsive. Social growth was similar in the…

  2. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods

    Directory of Open Access Journals (Sweden)

    Ahmed R

    2014-03-01

    Full Text Available Rafay Ahmed,1 Matthew J Oborski,2 Misun Hwang,1 Frank S Lieberman,3 James M Mountz11Department of Radiology, 2Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; 3Department of Neurology and Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAAbstract: Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12–15 months for glioblastomas and 2–5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies

  3. The Role of Early Growth Response 1 (EGR1) in Brain Plasticity and Neuropsychiatric Disorders

    Science.gov (United States)

    Duclot, Florian; Kabbaj, Mohamed

    2017-01-01

    It is now clearly established that complex interactions between genes and environment are involved in multiple aspects of neuropsychiatric disorders, from determining an individual’s vulnerability to onset, to influencing its response to therapeutic intervention. In this perspective, it appears crucial to better understand how the organism reacts to environmental stimuli and provide a coordinated and adapted response. In the central nervous system, neuronal plasticity and neurotransmission are among the major processes integrating such complex interactions between genes and environmental stimuli. In particular, immediate early genes (IEGs) are critical components of these interactions as they provide the molecular framework for a rapid and dynamic response to neuronal activity while opening the possibility for a lasting and sustained adaptation through regulation of the expression of a wide range of genes. As a result, IEGs have been tightly associated with neuronal activity as well as a variety of higher order processes within the central nervous system such as learning, memory and sensitivity to reward. The immediate early gene and transcription factor early growth response 1 (EGR1) has thus been revealed as a major mediator and regulator of synaptic plasticity and neuronal activity in both physiological and pathological conditions. In this review article, we will focus on the role of EGR1 in the central nervous system. First, we will summarize the different factors influencing its activity. Then, we will analyze the amount of data, including genome-wide, that has emerged in the recent years describing the wide variety of genes, pathways and biological functions regulated directly or indirectly by EGR1. We will thus be able to gain better insights into the mechanisms underlying EGR1’s functions in physiological neuronal activity. Finally, we will discuss and illustrate the role of EGR1 in pathological states with a particular interest in cognitive functions

  4. High grain diets perturb rumen and plasma metabolites and induce inflammatory responses in early lactation dairy cows

    Directory of Open Access Journals (Sweden)

    B. N. Ametaj

    2010-04-01

    Full Text Available Immediately after parturition dairy cows are fed diets containing high proportions of grain which are associated with high incidence of metabolic disorders. However, the reason behind these effects is not clear. The goal of this study was to investigate metabolic and immune responses of early postpartum dairy cows to feeding increasing proportions of barley grain in the diet. Rumen endotoxin content increased several fold and rumen fluid pH was lower in cows fed the highest amount of barley grain. Results indicate that feeding high proportions of barley grain in early lactation dairy cows was associated with induction of an acute phase response and changes in multiple plasma metabolites. Further research is warranted to understand the mechanism(s by which feeding of barley grain causes disturbances in plasma metabolites and stimulates an inflammatory response in dairy cows.

  5. Early genetic responses in rat vascular tissue after simulated diving.

    Science.gov (United States)

    Eftedal, Ingrid; Jørgensen, Arve; Røsbjørgen, Ragnhild; Flatberg, Arnar; Brubakk, Alf O

    2012-12-18

    Diving causes a transient reduction of vascular function, but the mechanisms behind this are largely unknown. The aim of this study was therefore to analyze genetic reactions that may be involved in acute changes of vascular function in divers. Rats were exposed to 709 kPa of hyperbaric air (149 kPa Po(2)) for 50 min followed by postdive monitoring of vascular bubble formation and full genome microarray analysis of the aorta from diving rats (n = 8) and unexposed controls (n = 9). Upregulation of 23 genes was observed 1 h after simulated diving. The differential gene expression was characteristic of cellular responses to oxidative stress, with functions of upregulated genes including activation and fine-tuning of stress-responsive transcription, cytokine/cytokine receptor signaling, molecular chaperoning, and coagulation. By qRT-PCR, we verified increased transcription of neuron-derived orphan receptor-1 (Nr4a3), plasminogen activator inhibitor 1 (Serpine1), cytokine TWEAK receptor FN14 (Tnfrsf12a), transcription factor class E basic helix-loop-helix protein 40 (Bhlhe40), and adrenomedullin (Adm). Hypoxia-inducible transcription factor HIF1 subunit HIF1-α was stabilized in the aorta 1 h after diving, and after 4 h there was a fivefold increase in total protein levels of the procoagulant plasminogen activator inhibitor 1 (PAI1) in blood plasma from diving rats. The study did not have sufficient power for individual assessment of effects of hyperoxia and decompression-induced bubbles on postdive gene expression. However, differential gene expression in rats without venous bubbles was similar to that of all the diving rats, indicating that elevated Po(2) instigated the observed genetic reactions.

  6. Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

    Science.gov (United States)

    Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

    2015-03-01

    Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

  7. Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids

    Directory of Open Access Journals (Sweden)

    Tetu Bernard

    2008-02-01

    Full Text Available Abstract Background Chemotherapy (CT resistance in ovarian cancer (OC is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155, following treatment with 10,0 μM cisplatin, 2,5 μM paclitaxel or 5,0 μM topotecan for 72 hours. Results Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism, signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes, cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Conclusion Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular

  8. Escape response of planktonic protists to fluid mechanical signals

    DEFF Research Database (Denmark)

    Jakobsen, Hans Henrik

    2001-01-01

    The escape response to fluid mechanical signals was examined in 6 protists, 4 ciliates and 2 dinoflagellates. When exposed to a siphon flow. 3 species of ciliates, Balanion comatum, Strobilidium sp., and Mesodinium pulex, responded with escape jumps. The threshold deformation rates required...

  9. Thermal, chemical, and mechanical response of rigid polyurethane foam

    Energy Technology Data Exchange (ETDEWEB)

    Hobbs, M.L.

    1997-12-01

    Rigid polyurethane foams are frequently used as encapsulants to isolate and support thermally sensitive components within weapon systems. When exposed to abnormal thermal environments, such as fire, the polyurethane foam decomposes to form products having a wide distribution of molecular weights and can dominate the overall thermal response of the system. Mechanical response of the decomposing foam, such as thermal expansion under various loading conditions created by gas generation, remains a major unsolved problem. A constitutive model of the reactive foam is needed to describe the coupling between mechanical response and chemical decomposition of foam exposed to environments such as fire. Towards this end, a reactive elastic-plastic constitutive model based on bubble mechanics describing nucleation, decomposition chemistry, and elastic/plastic mechanical behavior of rigid polyurethane foam has been developed. A local force balance, with mass continuity constraints, forms the basis of the constitutive model requiring input of temperature and the fraction of the material converted to gas. This constitutive model provides a stress-strain relationship which is applicable for a broad class of reacting materials such as explosives, propellants, pyrotechnics, and decomposing foams. The model is applied to a block of foam exposed to various thermal fluxes. The model is also applied to a sphere of foam confined in brass. The predicted mechanical deformation of the foam block and sphere are shown to qualitatively agree with experimental observations.

  10. Expression Changes of Early Response Genes in Lung Due to High Volume Ventilation

    Institute of Scientific and Technical Information of China (English)

    WANG Yuelan; YAO Shanglong; XIONG Ping

    2005-01-01

    Summary: The expression changes of early response genes due to ventilation with high volume in adult rats in vivo were observed. Forty SD male rats were randomly divided into control and 30, 60, 90 and 120 min ventilation groups, respectively (n=8 in each group). The animals were ventilated with tidal volume of 42 ml/kg and a PEEP level of 0 cmH2O at a rate of 40 breaths per minute in room air with a ventilator was given to the small animals. The expression of Egr-1, C-jun and IL-1β mRNA and proteins was detected by RT-PCR and immunohistochemical technique, respectively. The pathological changes in lung tissues were examined by HE staining. The results indicated that the expression of Egr-1, C-jun and IL-1β mRNA was detectable at 30th min after overventilation, but there was no significant difference in comparison with that in control group until overventilation for 60 min. However, at 90 and 120 min there was a significent increase as compared with 30 min or control group (P<0.05). The expression of Egr-1, C-jun and IL-1β deteced by immunohistochemical assay also showed a similar tendency of the gradual increase. In the 120 min ventilation group, the expression intensity of Egr-1, C-jun and IL-1β proteins in lung cells was the strongest and the nuclear translocation was increased markedly in comparison with any other groups (P<0.05). HE staining suggested that the degree of lung injury was aggravated gradually with the ventialtion going on and had a similar tendency to the expression of these early response genes and proteins. The current data suggested that overventilation activated and upregulated the expression of early response genes and the expression of these genes may be taken as the early signal to predict the onset and degree of lung injury. These results may demonstrated partially that the expression of early response genes induced by the mechanical stretch is associated with biochamic lung injury.

  11. Response to various periods of mechanical stimuli in Physarum plasmodium

    Science.gov (United States)

    Umedachi, Takuya; Ito, Kentaro; Kobayashi, Ryo; Ishiguro, Akio; Nakagaki, Toshiyuki

    2017-06-01

    Response to mechanical stimuli is a fundamental and critical ability for living cells to survive in hazardous conditions or to form adaptive and functional structures against force(s) from the environment. Although this ability has been extensively studied by molecular biology strategies, it is also important to investigate the ability from the viewpoint of biological rhythm phenomena so as to reveal the mechanisms that underlie these phenomena. Here, we use the plasmodium of the true slime mold Physarum polycephalum as the experimental system for investigating this ability. The plasmodium was repetitively stretched for various periods during which its locomotion speed was observed. Since the plasmodium has inherent oscillation cycles of protoplasmic streaming and thickness variation, how the plasmodium responds to various periods of external stretching stimuli can shed light on the other biological rhythm phenomena. The experimental results show that the plasmodium exhibits response to periodic mechanical stimulation and changes its locomotion speed depending on the period of the stretching stimuli.

  12. Dinoflagellate bioluminescence in response to mechanical stimuli in water flows

    Directory of Open Access Journals (Sweden)

    A. S. Cussatlegras

    2005-01-01

    Full Text Available Bioluminescence of plankton organisms induced by water movements has long been observed and is still under investigations because of its great complexity. In particular, the exact mechanism occurring at the level of the cell has not been yet fully understood. This work is devoted to the study of the bioluminescence of the dinoflagellates plankton species Pyrocystis noctiluca in response to mechanical stimuli generated by water flows. Several experiments were performed with different types of flows in a Couette shearing apparatus. All of them converge to the conclusion that stationary homogeneous laminar shear does not trigger massive bioluminescence, but that acceleration and shear are both necessary to stimulate together an intense bioluminescence response. The distribution of the experimental bioluminescence thresholds is finally calculated from the light emission response for the Pyrocystis noctiluca species.

  13. Filial responses as predisposed and learned preferences: Early attachment in chicks and babies.

    Science.gov (United States)

    Di Giorgio, Elisa; Loveland, Jasmine L; Mayer, Uwe; Rosa-Salva, Orsola; Versace, Elisabetta; Vallortigara, Giorgio

    2016-09-08

    To what extent are filial responses the outcome of spontaneous or acquired preferences? The case of domestic chicks illustrates the connection between predisposed and learned knowledge in early social responses. In the absence of specific experience, chicks prefer to approach objects that are more similar to natural social partners (e.g. they prefer face-like configurations, biological motion, self-propelled objects and those that move at variable speed). Spontaneous preferences are complemented by filial imprinting, a powerful learning mechanism that enables chicks to quickly learn the features of specific social partners. While neurobiological studies have clarified that the substrates of spontaneous and learned preferences are at least partially distinct in chicks, evidence shows that spontaneous preferences might orient and facilitate imprinting on animate stimuli, such as the mother hen, and that hormones facilitate and strengthen preferences for predisposed stimuli. Preferences towards animate stimuli are observed in human neonates as well. The remarkable consistency between the perceptual cues attended to by newborn babies and naïve chicks suggests that the attentional biases observed in babies are unlikely to result from very rapid post-natal learning, and confirms that research on precocial species can inform and guide human infant research with regards to both typical and atypical development. This has potentially important biomedical implications, opening new possibilities for the early detection of subjects at risk for autism spectrum disorders. We show how the parallel investigation of predispositions in naïve chicks and human infants, both benefiting from contact with social partners since the beginning of life, has greatly improved our understanding of early responses to social stimuli at the behavioural and neurobiological level.

  14. Early Damage Detection in Composites during Fabrication and Mechanical Testing

    Directory of Open Access Journals (Sweden)

    Neha Chandarana

    2017-06-01

    Full Text Available Fully integrated monitoring systems have shown promise in improving confidence in composite materials while reducing lifecycle costs. A distributed optical fibre sensor is embedded in a fibre reinforced composite laminate, to give three sensing regions at different levels through-the-thickness of the plate. This study follows the resin infusion process during fabrication of the composite, monitoring the development of strain in-situ and in real time, and to gain better understanding of the resin rheology during curing. Piezoelectric wafer active sensors and electrical strain gauges are bonded to the plate after fabrication. This is followed by progressive loading/unloading cycles of mechanical four point bending. The strain values obtained from the optical fibre are in good agreement with strain data collected by surface mounted strain gauges, while the sensing regions clearly indicate the development of compressive, neutral, and tensile strain. Acoustic emission event detection suggests the formation of matrix (resin cracks, with measured damage event amplitudes in agreement with values reported in published literature on the subject. The Felicity ratio for each subsequent loading cycle is calculated to track the progression of damage in the material. The methodology developed here can be used to follow the full life cycle of a composite structure, from manufacture to end-of-life.

  15. The early years of the Journal of Fluid Mechanics. Style and international impact

    Science.gov (United States)

    Moffatt, H. Keith

    2017-07-01

    The origins of the Journal of Fluid Mechanics, of which the first volume was published in 1956, are discussed, with reference to editorial correspondence during the early years of the Journal. This paper is based on a lecture given at the colloquium: A Century of Fluid Mechanics, 1870-1970, IMFT, Toulouse, France, 19-21 October 2016.

  16. Dynamic Response of Linear Mechanical Systems Modeling, Analysis and Simulation

    CERN Document Server

    Angeles, Jorge

    2012-01-01

    Dynamic Response of Linear Mechanical Systems: Modeling, Analysis and Simulation can be utilized for a variety of courses, including junior and senior-level vibration and linear mechanical analysis courses. The author connects, by means of a rigorous, yet intuitive approach, the theory of vibration with the more general theory of systems. The book features: A seven-step modeling technique that helps structure the rather unstructured process of mechanical-system modeling A system-theoretic approach to deriving the time response of the linear mathematical models of mechanical systems The modal analysis and the time response of two-degree-of-freedom systems—the first step on the long way to the more elaborate study of multi-degree-of-freedom systems—using the Mohr circle Simple, yet powerful simulation algorithms that exploit the linearity of the system for both single- and multi-degree-of-freedom systems Examples and exercises that rely on modern computational toolboxes for both numerical and symbolic compu...

  17. Adaptive response: some underlying mechanisms and open questions

    Directory of Open Access Journals (Sweden)

    Evgeniya G. Dimova

    2008-01-01

    Full Text Available Organisms are affected by different DNA damaging agents naturally present in the environment or released as a result of human activity. Many defense mechanisms have evolved in organisms to minimize genotoxic damage. One of them is induced radioresistance or adaptive response. The adaptive response could be considered as a nonspecific phenomenon in which exposure to minimal stress could result in increased resistance to higher levels of the same or to other types of stress some hours later. A better understanding of the molecular mechanism underlying the adaptive response may lead to an improvement of cancer treatment, risk assessment and risk management strategies, radiation protection, e.g. of astronauts during long-term space flights. In this mini-review we discuss some open questions and the probable underlying mechanisms involved in adaptive response: the transcription of many genes and the activation of numerous signaling pathways that trigger cell defenses - DNA repair systems, induction of proteins synthesis, enhanced detoxification of free radicals and antioxidant production.

  18. Response of mechanical properties of glasses to their chemical, thermal and mechanical histories

    DEFF Research Database (Denmark)

    Yue, Yuanzheng

    , surface, thermal history or excess entropy of the final glass state. Here I review recent progresses in understanding of the responses of mechanical properties of oxide glasses to the compositional variation, thermal history and mechanical deformation. The tensile strength, elastic modulus and hardness...... of glass fibers are dependent on the thermal history (measured as fictive temperature), tension, chemical composition and redox state. However, the fictive temperature affects the hardness of bulk glass in a complicated manner, i.e., the effect does not exhibit a clear regularity in the range...... and micro-cracks occurring during indentation of a glass is discussed briefly. Finally I describe the future perspectives and challenges in understanding responses of mechanical properties of oxide glasses to compositional variation, thermal history and mechanical deformation....

  19. Designing allostery-inspired response in mechanical networks

    Science.gov (United States)

    Rocks, Jason W.; Pashine, Nidhi; Bischofberger, Irmgard; Goodrich, Carl P.; Liu, Andrea J.; Nagel, Sidney R.

    2017-01-01

    Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ∼1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individual response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks. PMID:28223534

  20. Broad early immune response of porcine epithelial jejunal IPI-2I cells to Entamoeba histolytica.

    Science.gov (United States)

    Meurens, François; Girard-Misguich, Fabienne; Melo, Sandrine; Grave, Aurore; Salmon, Henri; Guillén, Nancy

    2009-02-01

    Amoebiasis caused by Entamoebahistolytica triggers an acute inflammatory response at early stages of intestinal infection. The patho-physiological study of intestinal amoebiasis requires the development of powerful animal models. Swine provide robust model for human diseases and they could be used to study intestinal amoebiasis. Here, we introduce an in vitro model of swine intestinal epithelial cell (IPI-2I) co-cultured with E. histolytica. Intestinal epithelial cells (IECs) have crucial roles in sensing pathogens and initiating innate immune response, which qualitatively influence adaptive immune response against them. The contact between the two cells induces marked macroscopic lesions of IEC monolayer and striking alteration of the IPI-2I cell phenotype including blebbing, such as loss of attachment before to be phagocyte by the trophozoite. Increase in Lactate Dehydrogenase (LDH) levels in the culture supernatant of IECs was observed when ameba is present and could reflect the cellular cytotoxicity exerted by the parasite. Using quantitative real-time PCR, we identified the up-regulation of cytokines/chemokines implicated in neutrophil chemoattraction and inflammation, such as CCL2, CCL20, CXCL2, CXCL3, GM-CSF, IL1 alpha, IL6 and IL8, in response to the parasite that can further regulate the immunoregulatory functions of the immune cells of the host. The study points a cardinal role of these pro-inflammatory compounds as central mediators in the interaction IECs/ameba and suggests mechanisms by which they coordinate intestinal immune response. This will focus future efforts on delineating the molecular and cellular mechanisms of other cell partners by the way of in vivo infection of swine.

  1. Nociceptive responses to thermal and mechanical stimulations in awake pigs

    DEFF Research Database (Denmark)

    di Giminiani, Pierpaolo; Petersen, Lars Jelstrup; Herskin, Mette S.

    2013-01-01

    animal studies in a large species require further examination. This manuscript describes the initial development of a porcine model of cutaneous nociception and focuses on interactions between the sensory modality, body size and the anatomical location of the stimulation site. METHODS: Pigs of different...... significantly lower pain thresholds (shorter latency to response) than large pigs to thermal and mechanical stimulations. Stimulations at the two anatomical locations elicited very distinct sets of behavioural responses, with different levels of sensitivity between the flank and the hind legs. Furthermore...

  2. Discrimination of timbre in early auditory responses of the human brain.

    Directory of Open Access Journals (Sweden)

    Jaeho Seol

    Full Text Available BACKGROUND: The issue of how differences in timbre are represented in the neural response still has not been well addressed, particularly with regard to the relevant brain mechanisms. Here we employ phasing and clipping of tones to produce auditory stimuli differing to describe the multidimensional nature of timbre. We investigated the auditory response and sensory gating as well, using by magnetoencephalography (MEG. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-five healthy subjects without hearing deficit participated in the experiments. Two different or same tones in timbre were presented through conditioning (S1-testing (S2 paradigm as a pair with an interval of 500 ms. As a result, the magnitudes of auditory M50 and M100 responses were different with timbre in both hemispheres. This result might support that timbre, at least by phasing and clipping, is discriminated in the auditory early processing. The second response in a pair affected by S1 in the consecutive stimuli occurred in M100 of the left hemisphere, whereas both M50 and M100 responses to S2 only in the right hemisphere reflected whether two stimuli in a pair were the same or not. Both M50 and M100 magnitudes were different with the presenting order (S1 vs. S2 for both same and different conditions in the both hemispheres. CONCLUSIONS/SIGNIFICANCES: Our results demonstrate that the auditory response depends on timbre characteristics. Moreover, it was revealed that the auditory sensory gating is determined not by the stimulus that directly evokes the response, but rather by whether or not the two stimuli are identical in timbre.

  3. The Venturia Apple Pathosystem: Pathogenicity Mechanisms and Plant Defense Responses

    Directory of Open Access Journals (Sweden)

    Gopaljee Jha

    2009-01-01

    Full Text Available Venturia inaequalis is the causal agent of apple scab, a devastating disease of apple. We outline several unique features of this pathogen which are useful for molecular genetics studies intended to understand plant-pathogen interactions. The pathogenicity mechanisms of the pathogen and overview of apple defense responses, monogenic and polygenic resistance, and their utilization in scab resistance breeding programs are also reviewed.

  4. Investigating Early Years Teachers' Understanding and Response to Children's Preconceptions

    Science.gov (United States)

    Kambouri, Maria

    2016-01-01

    This paper focuses on young children's scientific preconceptions and discusses teachers' identification of these preconceptions when teaching science in the early years, on which research is still limited. This paper is based on the theoretical framework of constructivism and it defines preconceptions as children's erroneous concepts prior to…

  5. Orthostatic intolerance and the cardiovascular response to early postoperative mobilization

    DEFF Research Database (Denmark)

    Bundgaard-Nielsen, M; Jørgensen, Christoffer Calov; Jørgensen, T B

    2009-01-01

    BACKGROUND: A key element in enhanced postoperative recovery is early mobilization which, however, may be hindered by orthostatic intolerance, that is, an inability to sit or stand because of symptoms of cerebral hypoperfusion as intolerable dizziness, nausea and vomiting, feeling of heat...

  6. Alcohol Expectancy Responses from Teenagers: The Early Forewarning Signals

    OpenAIRE

    B., Sandhya; B.M.S., Carol; M.S., Kotian; B, Ganaraja

    2013-01-01

    Background: The Indian population is overwhelmed by the rapid developmental activities in the new millennium. This has brought in urbanization and several banes of the faster life. Alcoholism is one among the menaces which have to be tackled at an early stage.

  7. Singaporean Early Childhood Teachers' Responses to Myths about Child Abuse

    Science.gov (United States)

    Briggs, Freda; Potter, Gillian K.

    2004-01-01

    Prior to attending seminars on child abuse and domestic violence, 86 kindergarten and 64 special education (early childhood) teachers completed a questionnaire seeking views relating to the accuracy of statements relating to all forms of child abuse. This was designed to identify the accuracy of teachers' knowledge of child abuse and neglect…

  8. Responsive feeding: establishing healthy eating behaviour early on ...

    African Journals Online (AJOL)

    2013-04-12

    Apr 12, 2013 ... facilitation of self-regulation skills early in life may predict ... foundation for the development of healthy eating behaviour and optimal skills for self-regulation and self-control of food intake. ... to verbal cues and contingencies which are appropriate ..... ethnicity may play a role in the feeding style adopted by.

  9. The effect of glycation on arterial microstructure and mechanical response.

    Science.gov (United States)

    Stephen, Elizabeth A; Venkatasubramaniam, Arundhathi; Good, Theresa A; Topoleski, L D T

    2014-08-01

    Like engineered materials, an artery's biomechanical behavior and function depend on its microstructure. Glycation is associated with both normal aging and diabetes and has been shown to increase arterial stiffness. In this study we examined the direct effect of glycation on the mechanical response of intact arteries and on the mechanical response and structure of elastin isolated from the arteries. Samples of intact arteries and isolated elastin were prepared from porcine aortas and glycated. The mechanical response of all samples was completed using a uniaxial material test system. Glycation levels were measured using ELISA. A confocal microscope was used to image differences in the structure of the glycated and untreated elastin fibers. We found that, under the conditions used in this study, glycation led to decreased stiffness of elastin isolated from arteries, which was associated with a thinning of elastin fibers as imaged by confocal microscopy. We observed no effect of glycation on collagen fibers under our treatment conditions. These results suggest that glycation leads to weakening of the elastin component of arteries that could contribute to vascular defects seen in diabetes and aging. Prevention of glycation reactions may be an important consideration for vascular health later in life.

  10. Helicobacter pylori Antigens Inducing Early Immune Response in Infants.

    Science.gov (United States)

    Seo, Ji Hyun; Youn, Jong Hyuk; Kim, Eun A; Jun, Jin Su; Park, Ji Sook; Yeom, Jung Sook; Lim, Jae Young; Woo, Hyang Ok; Youn, Hee Shang; Ko, Gyung Hyuck; Park, Jin Sik; Baik, Seung Chul; Lee, Woo Kon; Cho, Myung Je; Rhee, Kwang Ho

    2017-07-01

    To identify the Helicobacter pylori antigens operating during early infection in sera from infected infants using proteomics and immunoblot analysis. Two-dimensional (2D) large and small gel electrophoresis was performed using H. pylori strain 51. We performed 2D immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibody immunoblotting using small gels on sera collected at the Gyeongsang National University Hospital from 4-11-month-old infants confirmed with H. pylori infection by pre-embedding immunoelectron microscopy. Immunoblot spots appearing to represent early infection markers in infant sera were compared to those of the large 2D gel for H. pylori strain 51. Corresponding spots were analyzed by matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS). The peptide fingerprints obtained were searched in the National Center for Biotechnology Information (NCBI) database. Eight infant patients were confirmed with H. pylori infection based on urease tests, histopathologic examinations, and pre-embedding immunoelectron microscopy. One infant showed a 2D IgM immunoblot pattern that seemed to represent early infection. Immunoblot spots were compared with those from whole-cell extracts of H. pylori strain 51 and 18 spots were excised, digested in gel, and analyzed by MALDI-TOF-MS. Of the 10 peptide fingerprints obtained, the H. pylori proteins flagellin A (FlaA), urease β subunit (UreB), pyruvate ferredoxin oxidoreductase (POR), and translation elongation factor Ts (EF-Ts) were identified and appeared to be active during the early infection periods. These results might aid identification of serological markers for the serodiagnosis of early H. pylori infection in infants. © 2017 The Korean Academy of Medical Sciences.

  11. The elastic mechanical response of supported thin polymer films.

    Science.gov (United States)

    Chung, Peter C; Glynos, Emmanouil; Green, Peter F

    2014-12-23

    Nanoindentation studies of the mechanical properties of sufficiently thin polymer films, supported by stiff substrates, indicate that the mechanical moduli are generally higher than those of the bulk. This enhancement of the effective modulus, in the thickness range of few hundred nanometers, is indicated to be associated with the propagation and impingement of the indentation tip induced stress field with the rigid underlying substrate; this is the so-called "substrate effect". This behavior has been rationalized completely in terms of the moduli and Poisson's ratios of the individual components, for the systems investigated thus far. Here we show that for thin supported polymer films, in general, information regarding the local chain stiffness and local vibrational constants of the polymers provides an appropriate rationalization of the overall mechanical response of polymers of differing chemical structures and polymer-substrate interactions. Our study should provide impetus for atomistic simulations that carefully account for the role of intermolecular interactions on the mechanical response of supported polymer thin films.

  12. Decreased heart rate variability responses during early postoperative mobilization

    DEFF Research Database (Denmark)

    Jans, Øivind; Brinth, Louise; Kehlet, Henrik

    2015-01-01

    to postoperative autonomic dysfunction. Thus, based on a previous study on haemodynamic responses during mobilization before and after elective total hip arthroplasty (THA), we performed secondary analyses of heart rate variability (HRV) and aimed to identify possible abnormal postoperative autonomic responses...

  13. Protein aggregation as a mechanism of adaptive cellular responses.

    Science.gov (United States)

    Saarikangas, Juha; Barral, Yves

    2016-11-01

    Coalescence of proteins into different types of intracellular bodies has surfaced as a widespread adaptive mechanism to re-organize cells and cellular functions in response to specific cues. These structures, composed of proteins or protein-mRNA-complexes, regulate cellular processes through modulating enzymatic activities, gene expression or shielding macromolecules from damage. Accordingly, such bodies are associated with a wide-range of processes, including meiosis, memory-encoding, host-pathogen interactions, cancer, stress responses, as well as protein quality control, DNA replication stress and aneuploidy. Importantly, these distinct coalescence responses are controlled, and in many cases regulated by chaperone proteins. While cells can tolerate and proficiently coordinate numerous distinct types of protein bodies, some of them are also intimately linked to diseases or the adverse effects of aging. Several protein bodies that differ in composition, packing, dynamics, size, and localization were originally discovered in budding yeast. Here, we provide a concise and comparative review of their nature and nomenclature.

  14. Mechanisms regulating osteoblast response to surface microtopography and vitamin D

    Science.gov (United States)

    Bell, Bryan Frederick, Jr.

    A comprehensive understanding of the interactions between orthopaedic and dental implant surfaces with the surrounding host tissue is essential in the design of advanced biomaterials that better promote bone growth and osseointegration of implants. Dental implants with roughened surfaces and high surface energy are well known to promote osteoblast differentiation in vitro and promote increased bone-to-implant contact in vivo. In addition, increased surface roughness increases osteoblasts response to the vitamin D metabolite 1alpha,25(OH)2D3. However, the exact mechanisms mediating cell response to surface properties and 1alpha,25(OH)2D3 are still being elucidated. The central aim of the thesis is to investigate whether integrin signaling in response to rough surface microtopography enhances osteoblast differentiation and responsiveness to 1alpha,25(OH)2D3. The hypothesis is that the integrin alpha5beta1 plays a role in osteoblast response to surface microtopography and that 1alpha,25(OH) 2D3 acts through VDR-independent pathways involving caveolae to synergistically enhance osteoblast response to surface roughness and 1alpha,25(OH) 2D3. To test this hypothesis the objectives of the studies performed in this thesis were: (1) to determine if alpha5beta 1 signaling is required for osteoblast response to surface microstructure; (2) to determine if increased responsiveness to 1alpha,25(OH)2D 3 requires the vitamin D receptor, (3) to determine if rough titanium surfaces functionalized with the peptides targeting integrins (RGD) and transmembrane proteoglycans (KRSR) will enhance both osteoblast proliferation and differentiation, and (4) to determine whether caveolae, which are associated with integrin and 1alpha,25(OH)2D3 signaling, are required for enhance osteogenic response to surface microstructure and 1alpha,25(OH)2D 3. The results demonstrate that integrins, VDR, and caveolae play important roles in mediating osteoblast response to surface properties and 1alpha,25

  15. Investigating mechanisms for missing responses in competence tests

    Directory of Open Access Journals (Sweden)

    Carmen Köhler

    2015-12-01

    Full Text Available Examinees working on competence tests frequently leave questions unanswered. As the missing values usually violate the missing at random condition, they pose a threat to drawing correct inferences about person abilities. In order to account appropriately for missing responses in the scaling of competence data, the mechanism resulting in missing responses needs to be modeled adequately. So far, studies have mainly focused on the evaluation of different approaches accounting for missing responses, making assumptions about the underlying missing mechanism. A deeper understanding of how and why missing responses occur can provide valuable information on the appropriateness of these assumptions. In the current study we investigate whether the missing tendency of a person depends on the competence domain assessed, or whether it can be considered a rather person-specific trait. Furthermore, we examine how missing responses relate to ability and other personality variables. We conduct our analyses separately for not-reached and omitted items, using data from the National Educational Panel Study (NEPS. Based on an IRT approach by Holman and Glas (2005, we investigate the missing process in the competence domains information and communication technologies, science, mathematics, and reading, which were assessed in three age cohorts (fifth-graders: N = 5,193, ninth-graders: N = 15,396, adults: N = 7,256. Results demonstrate that persons’ missing propensities may, to some extent, be regarded as person-specific. The occurrence of omissions and not-reached items mainly depends on persons’ competencies, and is different for people with a migration background and for students attending different school types, even after controlling for competencies. Our findings should be considered in approaches aiming at accounting for missing responses in the scaling competence data.

  16. Cellular Mechanisms of Gravitropic Response in Higher Plants

    Science.gov (United States)

    Medvedev, Sergei; Smolikova, Galina; Pozhvanov, Gregory; Suslov, Dmitry

    The evolutionary success of land plants in adaptation to the vectorial environmental factors was based mainly on the development of polarity systems. In result, normal plant ontogenesis is based on the positional information. Polarity is a tool by which the developing plant organs and tissues are mapped and the specific three-dimensional structure of the organism is created. It is due to their polar organization plants are able to orient themselves relative to the gravity vector and different vectorial cues, and to respond adequately to various stimuli. Gravitation is one of the most important polarized environmental factor that guides the development of plant organisms in space. Every plant can "estimate" its position relative to the gravity vector and correct it, if necessary, by means of polarized growth. The direction and the magnitude of gravitational stimulus are constant during the whole plant ontogenesis. The key plant response to the action of gravity is gravitropism, i.e. the directed growth of organs with respect to the gravity vector. This response is a very convenient model to study the mechanisms of plant orientation in space. The present report is focused on the main cellular mechanisms responsible for graviropic bending in higher plants. These mechanisms and structures include electric polarization of plant cells, Ca ({2+) }gradients, cytoskeleton, G-proteins, phosphoinositides and the machinery responsible for asymmetric auxin distribution. Those mechanisms tightly interact demonstrating some hierarchy and multiple feedbacks. The Ca (2+) gradients provide the primary physiological basis of polarity in plant cells. Calcium ions influence on the bioelectric potentials, the organization of actin cytoskeleton, the activity of Ca (2+) -binding proteins and Ca (2+) -dependent protein kinases. Protein kinases modulate transcription factors activity thereby regulating the gene expression and switching the developmental programs. Actin cytoskeleton affects

  17. How does a neuron know to modulate its epigenetic machinery in response to early-life environment/experience?

    Directory of Open Access Journals (Sweden)

    Carley A Karsten

    2013-08-01

    Full Text Available Exciting information is emerging about epigenetic mechanisms and their role in long-lasting changes of neuronal gene expression. Whereas these mechanisms are active throughout life, recent findings point to a critical window of early postnatal development during which neuronal gene expression may be persistently re-programmed via epigenetic modifications. However, it remains unclear how the epigenetic machinery is modulated. Here we focus on an important example of early-life programming: the effect of sensory input from the mother on expression patterns of key stress-related genes in the developing brain. We focus on the lasting effects of this early life experience on corticotropin releasing hormone (CRH gene expression in the hypothalamus, and describe recent work that integrates organism-wide signals with cellular signals that in turn impact epigenetic regulation. We describe the operational brain networks that convey sensory input to CRH-expressing cells, and highlight the resulting re-wiring of synaptic connectivity to these neurons. We then move from intercellular to intracellular mechanisms, speculating about the induction and maintenance of lifelong CRH repression provoked by early-life experience. Elucidating such pathways is critical for understanding the enduring links between experience and gene expression. In the context of responses to stress, such mechanisms should contribute to vulnerability or resilience to post-traumatic stress disorder (PTSD and other stress-related disorders.

  18. Outcome of poor response Paediatric AML using early SCT

    DEFF Research Database (Denmark)

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas;

    2013-01-01

    treated with SCT. MATERIAL AND METHODS: Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17......) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. RESULTS: Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13...

  19. Explaining the Association between Early Adversity and Young Adults' Diabetes Outcomes: Physiological, Psychological, and Behavioral Mechanisms.

    Science.gov (United States)

    Wickrama, Kandauda A S; Bae, Dayoung; O'Neal, Catherine Walker

    2017-01-31

    Previous studies have documented that early adversity increases young adults' risk for diabetes resulting in morbidity and comorbidity with adverse health conditions. However, less is known about how inter-related physiological (e.g., body mass index [BMI]), psychological (e.g., depressive symptoms), and behavioral mechanisms (e.g., unhealthy eating and sedentary behavior) link early adversity to young adults' diabetes outcomes, although these mechanisms appear to stem from early stressful experiences. The current study tested the patterning of these longitudinal pathways leading to young adults' diabetes using a nationally representative sample of 13,286 adolescents (54% female) over a period of 13 years. The findings indicated that early adversity contributed to elevated BMI, depressive symptoms, and stress-related health behaviors. The impact of these linking mechanisms on hierarchical diabetes outcomes (i.e., prediabetes and diabetes) remained significant after taking their associations with each other into account, showing that these mechanisms operate concurrently. The findings emphasize the importance of early detection for risk factors of young adults' diabetes in order to minimize their detrimental health effects.

  20. Growth plate cartilage shows different strain patterns in response to static versus dynamic mechanical modulation.

    Science.gov (United States)

    Kaviani, Rosa; Londono, Irene; Parent, Stefan; Moldovan, Florina; Villemure, Isabelle

    2016-08-01

    Longitudinal growth of long bones and vertebrae occurs in growth plate cartilage. This process is partly regulated by mechanical forces, which are one of the underlying reasons for progression of growth deformities such as idiopathic adolescent scoliosis and early-onset scoliosis. This concept of mechanical modulation of bone growth is also exploited in the development of fusionless treatments of these deformities. However, the optimal loading condition for the mechanical modulation of growth plate remains to be identified. The objective of this study was to evaluate the effects of in vitro static versus dynamic modulation and of dynamic loading parameters, such as frequency and amplitude, on the mechanical responses and histomorphology of growth plate explants. Growth plate explants from distal ulnae of 4-week-old swines were extracted and randomly distributed among six experimental groups: baseline ([Formula: see text]), control ([Formula: see text]), static ([Formula: see text]) and dynamic ([Formula: see text]). For static and dynamic groups, mechanical modulation was performed in vitro using an Indexed CartiGen bioreactor. A stress relaxation test combined with confocal microscopy and digital image correlation was used to characterize the mechanical responses of each explant in terms of peak stress, equilibrium stress, equilibrium modulus of elasticity and strain pattern. Histomorphometrical measurements were performed on toluidine blue tissue sections using a semi-automatic custom-developed MATLAB toolbox. Results suggest that compared to dynamic modulation, static modulation changes the strain pattern of the tissue and thus is more detrimental for tissue biomechanics, while the histomorphological parameters are not affected by mechanical modulation. Also, under dynamic modulation, changing the frequency or amplitude does not affect the biomechanical response of the tissue. Results of this study will be useful in finding optimal and non-damaging parameters

  1. Turnbull - Early Detection and Rapid Response Team 2007

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Biocontrol agents and chemicals to facilitate the rapid response phase of the project will be purchased and applied and a Washington Service Corps AmeriCorps member...

  2. Turnbull - Early Detection and Rapid Response Team 2008

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Funding from this grant will allow for the purchase of biocontrol agents and chemicals to facilitate the rapid response phase of the project and to provide match for...

  3. Turnbull - Early Detection and Rapid Response Team 2010

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Funding from this grant will allow for the purchase of biocontrol agents and chemicals to facilitate the rapid response phase of the project and to provide funds to...

  4. Study on the early warning mechanism for the security of blast furnace hearths

    Science.gov (United States)

    Zhao, Hong-bo; Huo, Shou-feng; Cheng, Shu-sen

    2013-04-01

    The campaign life of blast furnace (BF) hearths has become the limiting factor for safety and high efficiency production of modern BFs. However, the early warning mechanism of hearth security has not been clear. In this article, based on heat transfer calculations, heat flux and erosion monitoring, the features of heat flux and erosion were analyzed and compared among different types of hearths. The primary detecting elements, mathematical models, evaluating standards, and warning methods were discussed. A novel early warning mechanism with the three-level quantificational standards was proposed for BF hearth security.

  5. Transcriptomic analysis of the host response to early stage salmonid alphavirus (SAV-1) infection in Atlantic salmon Salmo salar L.

    Science.gov (United States)

    Herath, Tharangani K; Bron, James E; Thompson, Kim D; Taggart, John B; Adams, Alexandra; Ireland, Jacqueline H; Richards, Randolph H

    2012-05-01

    Salmon pancreas disease, caused by salmonid alphavirus (SAV) of the family Togaviridae, is an economically important disease affecting farmed Atlantic salmon (Salmo salar L.) in Scotland, Norway, and Ireland. The virus causes characteristic lesions in the pancreas, heart, kidney and skeletal muscle of infected fish. The mechanisms responsible for the pathology and the immune responses elicited in infected Atlantic salmon are not fully understood. A microarray-based study was therefore performed to evaluate the host transcriptomic response during the early stages of an experimentally-induced SAV-1 infection. Atlantic salmon parr were injected intra-peritoneally with viral cell culture supernatant or cell culture supernatant without virus. RNA, extracted from head kidney sampled from infected and control fish at 1, 3 and 5 days post-injection (d.p.i.), was interrogated with the 17 k TRAITS/SGP cDNA microarray. The greatest number of significantly differentially expressed genes was recorded at 3 d.p.i., mainly associated with immune and defence mechanisms, including genes involved in interferon I pathways and Major Histocompatibility Complex Class I and II responses. Genes associated with apoptosis and cellular stress were also found to be differentially expressed between infected and uninfected individuals, as were genes involved in inhibiting viral attachment and replication. The microarray results were validated by follow-on analysis of eight genes by real-time PCR. The findings of the study reflect mechanisms used by the host to protect itself during the early stages of SAV-1 infection. In particular, there was evidence of rapid induction of interferon-mediated responses similar to those seen during mammalian alphavirus infections, and also early involvement of an adaptive immune response. This study provides essential knowledge to assist in the development of effective control and management strategies for SAV-1 infection.

  6. Response mechanisms of attached premixed flames subjected to harmonic forcing

    Science.gov (United States)

    Shreekrishna

    vicinity of typical screech frequencies in gas turbine combustors. The nonlinear response problem is exclusively studied in the case of equivalence ratio coupling. Various nonlinearity mechanisms are identified, amongst which the crossover mechanisms, viz., stoichiometric and flammability crossovers, are seen to be responsible in causing saturation in the overall heat release magnitude of the flame. The response physics remain the same across various preheat temperatures and reactant pressures. Finally, comparisons between the chemiluminescence transfer function obtained experimentally and the heat release transfer functions obtained from the reduced order model (ROM) are performed for lean, CH4/Air swirl-stabilized, axisymmetric V-flames. While the comparison between the phases of the experimental and theoretical transfer functions are encouraging, their magnitudes show disagreement at lower Strouhal number gains show disagreement.

  7. Microstructural mechanisms of cyclic deformation, fatigue crack initiation and early crack growth.

    Science.gov (United States)

    Mughrabi, Haël

    2015-03-28

    In this survey, the origin of fatigue crack initiation and damage evolution in different metallic materials is discussed with emphasis on the responsible microstructural mechanisms. After a historical introduction, the stages of cyclic deformation which precede the onset of fatigue damage are reviewed. Different types of cyclic slip irreversibilities in the bulk that eventually lead to the initiation of fatigue cracks are discussed. Examples of trans- and intercrystalline fatigue damage evolution in the low cycle, high cycle and ultrahigh cycle fatigue regimes in mono- and polycrystalline face-centred cubic and body-centred cubic metals and alloys and in different engineering materials are presented, and some microstructural models of fatigue crack initiation and early crack growth are discussed. The basic difficulties in defining the transition from the initiation to the growth of fatigue cracks are emphasized. In ultrahigh cycle fatigue at very low loading amplitudes, the initiation of fatigue cracks generally occupies a major fraction of fatigue life and is hence life controlling.

  8. The Electrical Response to Injury: Molecular Mechanisms and Wound Healing

    Science.gov (United States)

    Reid, Brian; Zhao, Min

    2014-01-01

    Significance: Natural, endogenous electric fields (EFs) and currents arise spontaneously after wounding of many tissues, especially epithelia, and are necessary for normal healing. This wound electrical activity is a long-lasting and regulated response. Enhancing or inhibiting this electrical activity increases or decreases wound healing, respectively. Cells that are responsible for wound closure such as corneal epithelial cells or skin keratinocytes migrate directionally in EFs of physiological magnitude. However, the mechanisms of how the wound electrical response is initiated and regulated remain unclear. Recent Advances: Wound EFs and currents appear to arise by ion channel up-regulation and redistribution, which are perhaps triggered by an intracellular calcium wave or cell depolarization. We discuss the possibility of stimulation of wound healing via pharmacological enhancement of the wound electric signal by stimulation of ion pumping. Critical Issues: Chronic wounds are a major problem in the elderly and diabetic patient. Any strategy to stimulate wound healing in these patients is desirable. Applying electrical stimulation directly is problematic, but pharmacological enhancement of the wound signal may be a promising strategy. Future Directions: Understanding the molecular regulation of wound electric signals may reveal some fundamental mechanisms in wound healing. Manipulating fluxes of ions and electric currents at wounds might offer new approaches to achieve better wound healing and to heal chronic wounds. PMID:24761358

  9. Radiation-Induced Bystander Response: Mechanism and Clinical Implications

    Science.gov (United States)

    Suzuki, Keiji; Yamashita, Shunichi

    2014-01-01

    Significance: Absorption of energy from ionizing radiation (IR) to the genetic material in the cell gives rise to damage to DNA in a dose-dependent manner. There are two types of DNA damage; by a high dose (causing acute or deterministic effects) and by a low dose (related to chronic or stochastic effects), both of which induce different health effects. Among radiation effects, acute cutaneous radiation syndrome results from cell killing as a consequence of high-dose exposure. Recent advances: Recent advances in radiation biology and oncology have demonstrated that bystander effects, which are emerged in cells that have never been exposed, but neighboring irradiated cells, are also involved in radiation effects. Bystander effects are now recognized as an indispensable component of tissue response related to deleterious effects of IR. Critical issues: Evidence has indicated that nonapoptotic premature senescence is commonly observed in various tissues and organs. Senesced cells were found to secrete various proteins, including cytokines, chemokines, and growth factors, most of which are equivalent to those identified as bystander factors. Secreted factors could trigger cell proliferation, angiogenesis, cell migration, inflammatory response, etc., which provide a tissue microenvironment assisting tissue repair and remodeling. Future directions: Understandings of the mechanisms and physiological relevance of radiation-induced bystander effects are quite essential for the beneficial control of wound healing and care. Further studies should extend our knowledge of the mechanisms of bystander effects and mode of cell death in response to IR. PMID:24761341

  10. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

    Directory of Open Access Journals (Sweden)

    Marjorie Rose Levinstein

    2014-06-01

    Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

  11. Neural regulation of the stress response: glucocorticoid feedback mechanisms

    Directory of Open Access Journals (Sweden)

    J.P. Herman

    2012-04-01

    Full Text Available The mammalian stress response is an integrated physiological and psychological reaction to real or perceived adversity. Glucocorticoids are an important component of this response, acting to redistribute energy resources to both optimize survival in the face of challenge and to restore homeostasis after the immediate challenge has subsided. Release of glucocorticoids is mediated by the hypothalamo-pituitary-adrenal (HPA axis, driven by a neural signal originating in the paraventricular nucleus (PVN. Stress levels of glucocorticoids bind to glucocorticoid receptors in multiple body compartments, including the brain, and consequently have wide-reaching actions. For this reason, glucocorticoids serve a vital function in negative feedback inhibition of their own secretion. Negative feedback inhibition is mediated by a diverse collection of mechanisms, including fast, non-genomic feedback at the level of the PVN, stress-shut-off at the level of the limbic system, and attenuation of ascending excitatory input through destabilization of mRNAs encoding neuropeptide drivers of the HPA axis. In addition, there is evidence that glucocorticoids participate in stress activation via feed-forward mechanisms at the level of the amygdala. Feedback deficits are associated with numerous disease states, underscoring the necessity for adequate control of glucocorticoid homeostasis. Thus, rather than having a single, defined feedback ‘switch’, control of the stress response requires a wide-reaching feedback ‘network’ that coordinates HPA activity to suit the overall needs of multiple body systems.

  12. Cellular Immune Responses and Viral Diversity in Individuals Treated during Acute and Early HIV-1 Infection

    Science.gov (United States)

    Altfeld, Marcus; Rosenberg, Eric S.; Shankarappa, Raj; Mukherjee, Joia S.; Hecht, Frederick M.; Eldridge, Robert L.; Addo, Marylyn M.; Poon, Samuel H.; Phillips, Mary N.; Robbins, Gregory K.; Sax, Paul E.; Boswell, Steve; Kahn, James O.; Brander, Christian; Goulder, Philip J.R.; Levy, Jay A.; Mullins, James I.; Walker, Bruce D.

    2001-01-01

    Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection. PMID:11148221

  13. The early development of human mirror mechanisms: evidence from electromyographic recordings at 3 and 6 months.

    Science.gov (United States)

    Turati, Chiara; Natale, Elena; Bolognini, Nadia; Senna, Irene; Picozzi, Marta; Longhi, Elena; Cassia, Viola Macchi

    2013-11-01

    In primates and adult humans direct understanding of others' action is provided by mirror mechanisms matching action observation and action execution (e.g. Casile, Caggiano & Ferrari, 2011). Despite the growing body of evidence detailing the existence of these mechanisms in the adult human brain, their origins and early development are largely unknown. In this study, for the first time, electromyographic (EMG) measures were used to shed light on the emergence of mirror motor mechanisms in infancy. EMG activity was recorded while 6- and 3-month-old infants watched two videos displaying an agent reaching for, grasping and bringing an object either to the mouth or to the head. Results indicate that the motor system of 6-month-olds, but not 3-month-olds, was recruited and selectively modulated during observation of the goal-directed actions, favoring the idea that mirror mechanisms driving action understanding gradually emerge during early development.

  14. Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus.

    OpenAIRE

    Waner, J L; Kong, N; Biano, S

    1983-01-01

    The lymphocytes of asymptomatic, seropositive donors demonstrated blastogenic responses to early antigens of human cytomegalovirus whether or not antibodies to early antigens were detectable. The lymphocytes of six of nine patients with active cytomegalovirus infections gave stimulation indexes of greater than or equal to 2.00 with antigens of productively infected cells, whereas only two patients demonstrated comparable stimulation indexes with early antigens. Four patients with stimulation ...

  15. Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus.

    OpenAIRE

    Waner, J L; Kong, N; Biano, S

    1983-01-01

    The lymphocytes of asymptomatic, seropositive donors demonstrated blastogenic responses to early antigens of human cytomegalovirus whether or not antibodies to early antigens were detectable. The lymphocytes of six of nine patients with active cytomegalovirus infections gave stimulation indexes of greater than or equal to 2.00 with antigens of productively infected cells, whereas only two patients demonstrated comparable stimulation indexes with early antigens. Four patients with stimulation ...

  16. Early Exercise Promotes Angiogenic Response in Mice Model of Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    Wu Guifu; Du Zhimin; Hu Chenghen; Roger J. Laham

    2005-01-01

    Objectives Little is known about the mechanism of exercise-induced angiogenic response in ischemic myocardium. This study was designed to investigate the effects of exercise training on expression of vascular endothelial growth factor and angiogenesis in infarcted heart. Methods Fifty male FVB mice were divided into three subgroups to test various responses to exercise, including timedependent response of angiogenic factors to exercise training in intact heart (n=10) and infarcted heart (n=10), as well as exercise-induced angiogenic response in heart with myocardial infarction (MI) (n=30). The mice in the exercise-training groups were allowed to exercise daily at 1 hour per day for 7 days. Results VEGF protein expression was up-regulated by exercise training in time dependent fashion in mice with MI.Angiogenesis was evident by increased myocardial microvessels observed by PECAM-1 immunohistoc-hemical staining in post-MI exercise group (16.5±3.4)/0.4 mm2 versus post-MI sedentary mice ( 10±2.1 )/0.4 mm2 (P < 0.05). Cell proliferation assessment showed significantly higher (P < 0.05) number of BrdU positive cells in post MI mice in exercise group as opposed to sedentary post MI mice. 2%TTC staining disclosed a profound difference in the size of MI (18.25±2.93)% in exercise group vs sedentary group (29.26±7.64)% (P<0.05). Conclusions Activation and up-regulation of VEGF in infarcted mice heart may contributes the angiogenic response to exercise training at the early stage of myocardial infarction. This underscores the impact of exercise on angiogenesis in post myocardial infarction setting.

  17. Perspective: Identification of genetic variants associated with dopaminergic compensatory mechanisms in early Parkinson's disease

    OpenAIRE

    2013-01-01

    Parkinson's disease (PD) is slowly progressive, and heterogeneity of its severity among individuals may be due to endogenous mechanisms that counterbalance the striatal dopamine loss. In this perspective paper, we introduce a neuroimaging-genetic approach to identify genetic variants, which may contribute to this compensation. First, we briefly review current known potential compensatory mechanisms for premotor and early disease PD, located in the striatum and other brain regions. Then, we c...

  18. Early osmotic, antioxidant, ionic, and redox responses to salinity in leaves and roots of Indian mustard (Brassica juncea L.).

    Science.gov (United States)

    Ranjit, Singh Laxmi; Manish, Pandey; Penna, Suprasanna

    2016-01-01

    Salt-stress-induced alterations in osmotic, ionic, and redox responses were studied in the early period of treatment (30 min to 5 days) in seedlings of Brassica juncea L. Roots and shoots under mild (50 mM) and severe (250 mM) NaCl stress were analyzed for growth, oxidative stress, osmolyte accumulation, antioxidant defense, and redox state. Growth reduction was less pronounced in the early time period of salt stress while oxidative damage increased linearly and in a sustained manner under severe stress up to 6 h. An early and transient reactive oxygen species (ROS) burst, as evidenced by superoxide and hydrogen peroxide level was observed, followed by activation of enzymatic antioxidant system (GPX, SOD, CAT, and GR) in both root and shoot. The enzymatic activity was not affected much under mild stress particularly at early phase; however, severe stress induced a significant increase in the activity of antioxidant enzymes. Root ascorbate was progressively accumulated, and its redox state maintained in the early time phase of treatment under mild stress while increase in root and shoot glutathione content was recorded under mild stress at 5 days when the active ascorbate pool decreased. While early period of salt stress showed significant Na(+) accumulation over control, plants subjected to mild stress measured less Na(+) accumulation up to 5 days compared to severely stressed plants. The results showed an early induction of differential responses to salt stress in roots and shoots of Brassica which include growth limitations, reduced relative water content, increased osmolytes, redox state, and antioxidant system, and a significant Na(+) increase. The results also indicate that roots and shoots may have distinct mechanisms of responses to salt stress.

  19. Early transcriptional responses to mercury: a role for ethylene in mercury-induced stress.

    Science.gov (United States)

    Montero-Palmero, M Belén; Martín-Barranco, Amanda; Escobar, Carolina; Hernández, Luis E

    2014-01-01

    Understanding the cellular mechanisms of plant tolerance to mercury (Hg) is important for developing phytoremediation strategies of Hg-contaminated soils. The early responses of alfalfa (Medicago sativa) seedlings to Hg were studied using transcriptomics analysis. A Medicago truncatula microarray was hybridized with high-quality root RNA from M. sativa treated with 3 μM Hg for 3, 6 and 24 h. The transcriptional pattern data were complementary to the measurements of root growth inhibition, lipid peroxidation, hydrogen peroxide (H2 O2 ) accumulation and NADPH-oxidase activity as stress indexes. Of 559 differentially expressed genes (DEGs), 91% were up-regulated. The majority of DEGs were shared between the 3 and 6 h (60%) time points, including the 'stress', 'secondary metabolism' and 'hormone metabolism' functional categories. Genes from ethylene metabolism and signalling were highly represented, suggesting that this phytohormone may be relevant for metal perception and homeostasis. Ethylene-insensitive alfalfa seedlings preincubated with the ethylene signalling inhibitor 1-methylcyclopronene and Arabidopsis thaliana ein2-5 mutants confirmed that ethylene participates in the early perception of Hg stress. It modulates root growth inhibition, NADPH-oxidase activity and Hg-induced apoplastic H2 O2 accumulation. Therefore, ethylene signalling attenuation could be useful in future phytotechnological applications to ameliorate stress symptoms in Hg-polluted plants.

  20. Measuring Early Childhood Teacher Candidates' Conceptualizations of a Culturally Responsive Classroom Ecology

    Science.gov (United States)

    Flores, Belinda Bustos; Riojas-Cortez, Mari

    2009-01-01

    With the increase of Latino preschoolers, it is pressing that early childhood teachers are prepared to create a high quality environment in which all children can succeed. Using the frameworks of cultural responsiveness and classroom management, we developed the Early Childhood Ecology Scale (ECES) as an observational and reflective tool to…

  1. Somatosensory-evoked blink response: investigation of the physiological mechanisms.

    Science.gov (United States)

    Miwa, H; Nohara, C; Hotta, M; Shimo, Y; Amemiya, K

    1998-02-01

    The somatosensory-evoked blink response (SBR) is a newly identified blink reflex elicited by electrical stimulation of peripheral nerves. The present study was performed to investigate the physiological mechanism underlying the SBR elicited by median nerve stimulation in normal subjects. The peripheral afferents responsible for the SBR included low-threshold cutaneous fibres. In the SBR-positive subjects, the late (R2) component of the blink reflex elicited by supraorbital nerve stimulation and the SBR facilitated each other when both responses were induced at the same time, but they each caused long-lasting inhibition in the other when one stimulus was given as a conditioning stimulus. The extent of inhibition was correlated with the size of the preceding SBR. In the SBR-negative subjects, simultaneous inhibition of R2 was observed when median nerve stimulation was applied as a conditioning stimulus. Brainstem excitability, as evaluated by blink-reflex recovery studies, did not differ between SBR-positive and SBR-negative subjects. Therefore, based on anatomical and physiological findings, it appears that the reflex pathways of the SBR and R2 converge within the brainstem and compete with each other, presumably by presynaptic inhibition at the premotor level, before entering the common blink-reflex pathway. The influence of median nerve stimulation upon tonic contraction of the orbicularis oculi muscle was studied to detect the latent SBR. There was not only a facilitatory period corresponding to the SBR but also an active inhibitory period (exteroceptive suppression), suggesting that the mechanism generating the SBR is not only influenced by blink-reflex volleys but also by active exteroceptive suppression. Thus, the SBR may appear as a result of integration of facilitatory and inhibitory mechanisms within the brainstem.

  2. Proteomic responses reveal the differential effects induced by cadmium in mussels Mytilus galloprovincialis at early life stages.

    Science.gov (United States)

    Xu, Lanlan; Peng, Xiao; Yu, Deliang; Ji, Chenglong; Zhao, Jianmin; Wu, Huifeng

    2016-08-01

    Cadmium (Cd) has become an important metal contaminant and posed severe risk on the organisms in the coastal environments of the Bohai Sea. Marine mussel Mytilus galloprovincialis is widely distributed along the Bohai coast and consumed as seafood by local residents. Evidences indicate that the early stages of marine organisms are more sensitive to metal contaminants. In this study, we applied two-dimensional electrophoresis-based proteomics to characterize the biological effects of Cd (50 μg L(-1)) in the early life stages (D-shape larval and juvenile) of mussels. The different proteomic responses demonstrated the differential responsive mechanisms to Cd exposure in these two early life stages of mussels. In details, results indicated that Cd mainly induced immune and oxidative stresses in both D-shape larval and juvenile mussels via different pathways. In addition, the significant up-regulation of triosephosphate isomerase and metallothionein confirmed the enhanced energy demand and mobilized detoxification mechanism in D-shape larval mussels exposed to Cd. In juvenile mussels, Cd exposure also induced clear apoptosis. Overall, this work suggests that Cd is a potential immune toxicant to mussel M. galloprovincialis at early life stages.

  3. Glucocorticoids and the Brain: Neural Mechanisms Regulating the Stress Response.

    Science.gov (United States)

    Shirazi, Shawn N; Friedman, Aaron R; Kaufer, Daniela; Sakhai, Samuel A

    2015-01-01

    In this chapter, we describe the central role of the brain in the glucocorticoid mediated stress response. We describe the mechanisms by which the brain gauges the severity of stress, mechanisms of hypothalamic-pituitary-adrenal axis (HPA) regulation, and how various sub-systems of the brain respond to glucocorticoid (GC) signaling to regulate stress behavior. In particular, we focus on the hippocampus, pre-frontal cortex, and amygdala, where GCs can induce a series of changes. Finally, we briefly discuss an apparent paradox in GC signaling: while exposure to glucocorticoids promotes the survival of an organism during acute stress, these same hormones in chronic excess can also cause damage and promote illness.

  4. Studies of Physcomitrella patens reveal that ethylene-mediated submergence responses arose relatively early in land-plant evolution

    KAUST Repository

    Yasumura, Yuki

    2012-10-18

    Colonization of the land by multicellular green plants was a fundamental step in the evolution of life on earth. Land plants evolved from fresh-water aquatic algae, and the transition to a terrestrial environment required the acquisition of developmental plasticity appropriate to the conditions of water availability, ranging from drought to flood. Here we show that extant bryophytes exhibit submergence-induced developmental plasticity, suggesting that submergence responses evolved relatively early in the evolution of land plants. We also show that a major component of the bryophyte submergence response is controlled by the phytohormone ethylene, using a perception mechanism that has subsequently been conserved throughout the evolution of land plants. Thus a plant environmental response mechanism with major ecological and agricultural importance probably had its origins in the very earliest stages of the colonization of the land. © 2012 Blackwell Publishing Ltd.

  5. Molecular biology of the stress response in the early embryo and its stem cells.

    Science.gov (United States)

    Puscheck, Elizabeth E; Awonuga, Awoniyi O; Yang, Yu; Jiang, Zhongliang; Rappolee, Daniel A

    2015-01-01

    Stress is normal during early embryogenesis and transient, elevated stress is commonplace. Stress in the milieu of the peri-implantation embryo is a summation of maternal hormones, and other elements of the maternal milieu, that signal preparedness for development and implantation. Examples discussed here are leptin, adrenaline, cortisol, and progesterone. These hormones signal maternal nutritional status and provide energy, but also signal stress that diverts maternal and embryonic energy from an optimal embryonic developmental trajectory. These hormones communicate endocrine maternal effects and local embryonic effects although signaling mechanisms are not well understood. Other in vivo stresses affect the embryo such as local infection and inflammation, hypoxia, environmental toxins such as benzopyrene, dioxin, or metals, heat shock, and hyperosmotic stress due to dehydration or diabetes. In vitro, stresses include shear during handling, improper culture media and oxygen levels, cryopreservation, and manipulations of the embryo to introduce sperm or mitochondria. We define stress as any stimulus that slows stem cell accumulation or diminishes the ability of cells to produce normal and sufficient parenchymal products upon differentiation. Thus stress deflects downwards the normal trajectories of development, growth and differentiation. Typically stress is inversely proportional to embryonic developmental and proliferative rates, but can be proportional to induction of differentiation of stem cells in the peri-implantation embryo. When modeling stress it is most interesting to produce a 'runting model' where stress exposures slow accumulation but do not create excessive apoptosis or morbidity. Windows of stress sensitivity may occur when major new embryonic developmental programs require large amounts of energy and are exacerbated if nutritional flow decreases and removes energy from the normal developmental programs and stress responses. These windows correspond

  6. Perceived decisional responsibility for mechanical ventilation and weaning

    DEFF Research Database (Denmark)

    Haugdahl, Hege S; Storli, Sissel; Rose, Louise

    2014-01-01

    AIM: To explore variability in perceptions of nurse managers and physician directors regarding roles, responsibilities and clinical-decision making related to mechanical ventilator weaning in Norwegian intensive care units (ICUs). BACKGROUND: Effective teamwork is crucial for providing optimal...... decisions higher than physician directors: median of 7 (IQR 5-8) (nurses) versus 5 (3-6) (physicians), (p collaborated in assessment of patient response to ventilator changes and titrating...... ventilator settings: 92% of nurses and 87% of physicians, (p = 0·46), and recognizing weaning failure 84% of nurses and 84% of physicians, (p = 0·96). Physician directors perceived significantly less collaborative decision-making on weaning method (p = 0·01), weaning readiness (p = 0·04) and readiness...

  7. Evaluation of sheet mechanical response to laser welding processes

    Energy Technology Data Exchange (ETDEWEB)

    Carmignani, B.; Daneri, A.; Toselli, G. [ENEA, Bologna (Italy). Centro Ricerche Energia `E. Clementel` - Area Energia e Innovazione; Vitali, R.; Zanotelli, G.L. [Hibbit, Karlsson and Sorensen, Milan (Italy); Bellei, M. [Industrialconsult, Milan (Italy)

    1995-11-01

    The simulation of the mechanical response of steel sheets, due to the heating during welding processes by a laser source beam, obtained by Abaqus standard code, is discussed. Different hypotheses for the material behaviour at temperatures greater than the fusion one have been tested and compared; in particular, some tests have been made taking the annealing effect into account by means of an user routine UMAT developed ad hoc. This work was presented at the 8th international Abaqus Users` conference at Paris, 31 May - 2 June 1995.

  8. Neural responses to macronutrients: hedonic and homeostatic mechanisms.

    Science.gov (United States)

    Tulloch, Alastair J; Murray, Susan; Vaicekonyte, Regina; Avena, Nicole M

    2015-05-01

    The brain responds to macronutrients via intricate mechanisms. We review how the brain's neural systems implicated in homeostatic control of feeding and hedonic responses are influenced by the ingestion of specific types of food. We discuss how these neural systems are dysregulated in preclinical models of obesity. Findings from these studies can increase our understanding of overeating and, perhaps in some cases, the development of obesity. In addition, a greater understanding of the neural circuits affected by the consumption of specific macronutrients, and by obesity, might lead to new treatments and strategies for preventing unhealthy weight gain. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Mechanisms determining cholinergic neural responses in airways of young and mature rabbits.

    Science.gov (United States)

    Larsen, Gary L; Loader, Joan; Nguyen, Dee Dee; Fratelli, Cori; Dakhama, Azzeddine; Colasurdo, Giuseppe N

    2004-08-01

    Neural pathways help control airway caliber and responsiveness. Yet little is known of how neural control changes as a function of development. In rabbits, we found electrical field stimulation (EFS) of airway nerves led to more marked contractile responses in 2- vs. 13-week-old animals. This enhanced response to EFS may be due to prejunctional, junctional, and/or postjunctional neural mechanisms. We assessed these mechanisms in airways of 2- and 13-week-old rabbits. The contractile responses to methacholine did not differ in the groups, suggesting postjunctional neural events are not primarily responsible for differing responses to EFS. To address junctional events, acetylcholinesterase (AChE) was measured (spectrophotometry). AChE was elevated in 2-week-olds. However, this should lead to less and not greater responses. Prejunctionally, EFS-induced acetylcholine (ACh) release was assessed by HPLC. Airways of 2-week-old rabbits released significantly more ACh than airways from mature rabbits. Choline acetyltransferase, a marker of cholinergic nerves, was not different between groups, suggesting that more ACh release in young rabbits was not due to increased nerve density. ACh release in the presence of polyarginine increased significantly in both groups, supporting the presence of functional muscarinic autoreceptors (M2) at both ages. Because substance P (SP) increases release of ACh, SP was measured by ELISA. This neuropeptide was significantly elevated in airways of younger rabbits. Nerve growth factor (NGF) increased SP and was also significantly increased in airways from younger rabbits. This work suggests that increases in EFS-induced responsiveness in young rabbits are likely due to prejunctional events with enhanced release of ACh. Increases in NGF and SP early in life may contribute to this increased responsiveness.

  10. "Consumption and Enviromment" Early-warning Mechanism for Export of Autos Will Be Improved in China

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ As the amount of export for the complete vehicle and its components & parts from China are increasing rapidly, the early-warning mechanism for export of autos in China will have to be improved to reduce the injuries that the auto industry suffers.

  11. DNA Methylation: A Mechanism for Embedding Early Life Experiences in the Genome

    Science.gov (United States)

    Szyf, Moshe; Bick, Johanna

    2013-01-01

    Although epidemiological data provide evidence that early life experience plays a critical role in human development, the mechanism of how this works remains in question. Recent data from human and animal literature suggest that epigenetic changes, such as DNA methylation, are involved not only in cellular differentiation but also in the…

  12. DNA Methylation: A Mechanism for Embedding Early Life Experiences in the Genome

    Science.gov (United States)

    Szyf, Moshe; Bick, Johanna

    2013-01-01

    Although epidemiological data provide evidence that early life experience plays a critical role in human development, the mechanism of how this works remains in question. Recent data from human and animal literature suggest that epigenetic changes, such as DNA methylation, are involved not only in cellular differentiation but also in the…

  13. Gene Expression Responses to Mechanical Stimulation of Mesenchymal Stem Cells Seeded on Calcium Phosphate Cement

    Science.gov (United States)

    Gharibi, Borzo; Cama, Giuseppe; Capurro, Marco; Thompson, Ian; Deb, Sanjukta; Di Silvio, Lucy

    2013-01-01

    Introduction The aim of the study reported here was to investigate the molecular responses of human mesenchymal stem cells (MSC) to loading with a model that attempts to closely mimic the physiological mechanical loading of bone, using monetite calcium phosphate (CaP) scaffolds to mimic the biomechanical properties of bone and a bioreactor to induce appropriate load and strain. Methods Human MSCs were seeded onto CaP scaffolds and subjected to a pulsating compressive force of 5.5±4.5 N at a frequency of 0.1 Hz. Early molecular responses to mechanical loading were assessed by microarray and quantitative reverse transcription-polymerase chain reaction and activation of signal transduction cascades was evaluated by western blotting analysis. Results The maximum mechanical strain on cell/scaffolds was calculated at around 0.4%. After 2 h of loading, a total of 100 genes were differentially expressed. The largest cluster of genes activated with 2 h stimulation was the regulator of transcription, and it included FOSB. There were also changes in genes involved in cell cycle and regulation of protein kinase cascades. When cells were rested for 6 h after mechanical stimulation, gene expression returned to normal. Further resting for a total of 22 h induced upregulation of 63 totally distinct genes that were mainly involved in cell surface receptor signal transduction and regulation of metabolic and cell division processes. In addition, the osteogenic transcription factor RUNX-2 was upregulated. Twenty-four hours of persistent loading also markedly induced osterix expression. Mechanical loading resulted in upregulation of Erk1/2 phosphorylation and the gene expression study identified a number of possible genes (SPRY2, RIPK1, SPRED2, SERTAD1, TRIB1, and RAPGEF2) that may regulate this process. Conclusion The results suggest that mechanical loading activates a small number of immediate-early response genes that are mainly associated with transcriptional

  14. Early Biventricular Molecular Responses to an Acute Myocardial Infarction

    OpenAIRE

    Erdal, Cenk; Karakülah, Gökhan; Fermancı, Emel; Kunter, İmge; Silistreli, Erdem; Tülay CANDA; Erdal, Esra; Hepaguslar, Hasan

    2011-01-01

    Background: Acute myocardial infarction (AMI) remains as one of the most common lethal diseases in the world and therefore it is necessary to understand its effect on molecular basis. Genome-wide microarray analysis provides us to predict potential biomarkers and signaling pathways for this purpose. Objectives: The aim of this study is to understand the molecular basis of the immediate right ventricular cellular response to left ventricular AMI. Material and Methods: A rat model of left anter...

  15. Mouse early extra-embryonic lineages activate compensatory endocytosis in response to poor maternal nutrition.

    Science.gov (United States)

    Sun, Congshan; Velazquez, Miguel A; Marfy-Smith, Stephanie; Sheth, Bhavwanti; Cox, Andy; Johnston, David A; Smyth, Neil; Fleming, Tom P

    2014-03-01

    Mammalian extra-embryonic lineages perform the crucial role of nutrient provision during gestation to support embryonic and fetal growth. These lineages derive from outer trophectoderm (TE) and internal primitive endoderm (PE) in the blastocyst and subsequently give rise to chorio-allantoic and visceral yolk sac placentae, respectively. We have shown maternal low protein diet exclusively during mouse preimplantation development (Emb-LPD) is sufficient to cause a compensatory increase in fetal and perinatal growth that correlates positively with increased adult-onset cardiovascular, metabolic and behavioural disease. Here, to investigate early mechanisms of compensatory nutrient provision, we assessed the influence of maternal Emb-LPD on endocytosis within extra-embryonic lineages using quantitative imaging and expression of markers and proteins involved. Blastocysts collected from Emb-LPD mothers within standard culture medium displayed enhanced TE endocytosis compared with embryos from control mothers with respect to the number and collective volume per cell of vesicles with endocytosed ligand and fluid and lysosomes, plus protein expression of megalin (Lrp2) LDL-family receptor. Endocytosis was also stimulated using similar criteria in the outer PE-like lineage of embryoid bodies formed from embryonic stem cell lines generated from Emb-LPD blastocysts. Using an in vitro model replicating the depleted amino acid (AA) composition found within the Emb-LPD uterine luminal fluid, we show TE endocytosis response is activated through reduced branched-chain AAs (leucine, isoleucine, valine). Moreover, activation appears mediated through RhoA GTPase signalling. Our data indicate early embryos regulate and stabilise endocytosis as a mechanism to compensate for poor maternal nutrient provision.

  16. Mechanisms of impaired gallbladder contractile response in chronic acalculous cholecystitis.

    Science.gov (United States)

    Merg, Anders R; Kalinowski, Scott E; Hinkhouse, Marilyn M; Mitros, Frank A; Ephgrave, Kimberly S; Cullen, Joseph J

    2002-01-01

    The mechanisms involved in the impaired gallbladder contractile response in chronic acalculous cholecystitis are unknown. To determine the mechanisms that may lead to impaired gallbladder emptying in chronic acalculous cholecystitis, gallbladder specimens removed during hepatic resection (controls) and after cholecystectomy for chronic acalculous cholecystitis were attached to force transducers and placed in tissue baths with oxygenated Krebs solution. Electrical field stimulation (EFS) (1 to 10 Hz, 0.1 msec, 70 V) or the contractile agonists, CCK-8 (10(-9) to 10(-5)) or K(+) (80 mmol/L), were placed separately in the tissue baths and changes in tension were determined. Patients with chronic acalculous cholecystitis had a mean gallbladder ejection fraction of 12% +/- 4%. Pathologic examination of all gallbladders removed for chronic acalculous cholecystitis revealed chronic cholecystitis. Spontaneous contractile activity was present in gallbladder strips in 83% of control specimens but only 29% of gallbladder strips from patients with chronic acalculous cholecystitis (P < 0.05 vs. controls). CCK-8 contractions were decreased by 54% and EFS-stimulated contractions were decreased by 50% in the presence of chronic acalculous cholecystitis (P < 0.05 vs. controls). K(+)-induced contractions were similar between control and chronic acalculous cholecystitis gallbladder strips. The impaired gallbladder emptying in chronic acalculous cholecystitis appears to be due to diminished spontaneous contractile activity and decreased contractile responsiveness to both CCK and EFS.

  17. Response mechanisms of Brachiaria brizantha cultivars to water deficit stress

    Directory of Open Access Journals (Sweden)

    Patricia Menezes Santos

    2013-11-01

    Full Text Available Two cultivars of Brachiaria brizantha (Hochst ex. A. Rich Stapf. (Syn. Urochloa were evaluated for their adaptation to water deficit and the stress response mechanisms in a greenhouse experiment. The experimental design was in completely randomized blocks with a 2 × 2 × 4 factorial arrangement. The Marandu and BRS Piatã cultivars were evaluated under two water availability conditions, with or without water restriction. The harvests were carried out 0, 7, 14 and 28 days after the start of water restriction. For both cultivars, the water deficit stress caused a reduction in shoot biomass and leaf area and an increase in the percentage of roots in the deeper soil layers. The B. brizantha cv. Marandu reached critical levels of leaf water potential in a shorter period of water restriction than did the B. brizantha cv. BRS Piatã. The osmoregulation and deepening of the root system are mechanisms of adaptation to water stress observed in both Marandu and BRS Piatã cultivars. Besides that, the Marandu cultivar also increases its leaf senescence and, consequentially, decreases its leaf area, as a response to water deficit.

  18. Family-based association study of early growth response gene 3 with child bipolar I disorder.

    Science.gov (United States)

    Gallitano, Amelia L; Tillman, Rebecca; Dinu, Valentin; Geller, Barbara

    2012-05-01

    The risk for relapse of child bipolar I disorder (BP-I) is highly correlated with environmental factors. Immediate early genes of the early growth response (EGR) gene family are activated at high levels in the brain in response to environmental events, including stress, and mediate numerous neurobiological processes that have been associated with mental illness risk. The objective of this study is to evaluate whether single nucleotide polymorphisms (SNPs) in EGR genes are associated with the risk to develop child bipolar I disorder. To investigate whether EGR genes may influence susceptibility to child bipolar I disorder (BP-I), we used Family Based Association Tests to examine whether SNPs in each of the EGR genes were associated with illness in 49 families. Two SNPs in EGR3 displayed nominally significant associations with child BP-I (p=0.027 and p=0.028); though neither was statistically significant following correction for multiple comparisons. Haplotype association analysis indicated that these SNPs are in linkage disequilibrium (LD). None of the SNPs tested in EGR1, EGR2, or EGR4 was associated with child BP-I. This study was limited by small sample size, which resulted in it being underpowered to detect a significant association after correction for multiple comparisons. Our study revealed a preliminary finding suggesting that EGR3, a gene that translates environmental stimuli into long-term changes in the brain, warrants further investigation for association with risk for child BP-I disorder in a larger sample. Such studies may help reveal mechanisms by which environment can interact with genetic predisposition to influence this severe mental illness. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Early osmotic adjustment responses in drought-resistant and drought-sensitive oilseed rape

    Institute of Scientific and Technical Information of China (English)

    Sarah Hatzig; L Irina Zaharia; Suzanne Abrams; Marie Hohmann; Laurie Legoahec; Alain Bouchereau; Nathalie Nesi; Rod J.Snowdon

    2014-01-01

    The impact of osmotic stress on growth, physiolo-gy, and metabolism of winter oilseed rape (Brassica napus L.) was investigated by detailed analysis of biomass traits, hormone metabolites and osmolytes in two genetical y unrelated drought-tolerant genotypes and two unrelated drought-sensitive genotypes. Seedlings were grown in vitro under control ed conditions and osmotic stress was simulated by applying a gradual treatment with polyethylene glycol (PEG 6000), fol owed by hypo-osmotic treatment of variants used for metabolite determination. The results provide a basis for the identification of reliable selection criteria for drought resistance in oilseed rape. The in vitro cultivation system established during this study enabled effective discrimination of early osmotic stress responses between drought-resistant and-susceptible oilseed rape genotypes that also show large differences in relative seed yield under drought conditions in the field. Clear physiological and metabolic differences were observed between the drought-resistant and drought-sensitive genotypes, suggesting that osmotic adjustment is a key component of drought response in oilseed rape. Unexpected-ly, however, the drought-resistant genotypes did not show typical hormonal adjustment and osmolyte accumulation, suggesting that they possess alternative physiological mech-anisms enabling avoidance of stress symptoms.

  20. A hydro-mechanical framework for early warning of rainfall-induced landslides (Invited)

    Science.gov (United States)

    Godt, J.; Lu, N.; Baum, R. L.

    2013-12-01

    Landslide early warning requires an estimate of the location, timing, and magnitude of initial movement, and the change in volume and momentum of material as it travels down a slope or channel. In many locations advance assessment of landslide location, volume, and momentum is possible, but prediction of landslide timing entails understanding the evolution of rainfall and soil-water conditions, and consequent effects on slope stability in real time. Existing schemes for landslide prediction generally rely on empirical relations between landslide occurrence and rainfall amount and duration, however, these relations do not account for temporally variable rainfall nor the variably saturated processes that control the hydro-mechanical response of hillside materials to rainfall. Although limited by the resolution and accuracy of rainfall forecasts and now-casts in complex terrain and by the inherent difficulty in adequately characterizing subsurface materials, physics-based models provide a general means to quantitatively link rainfall and landslide occurrence. To obtain quantitative estimates of landslide potential from physics-based models using observed or forecasted rainfall requires explicit consideration of the changes in effective stress that result from changes in soil moisture and pore-water pressures. The physics that control soil-water conditions are transient, nonlinear, hysteretic, and dependent on material composition and history. In order to examine the physical processes that control infiltration and effective stress in variably saturated materials, we present field and laboratory results describing intrinsic relations among soil water and mechanical properties of hillside materials. At the REV (representative elementary volume) scale, the interaction between pore fluids and solid grains can be effectively described by the relation between soil suction, soil water content, hydraulic conductivity, and suction stress. We show that these relations can be

  1. Computational modeling predicts the ionic mechanism of late-onset responses in unipolar brush cells.

    Science.gov (United States)

    Subramaniyam, Sathyaa; Solinas, Sergio; Perin, Paola; Locatelli, Francesca; Masetto, Sergio; D'Angelo, Egidio

    2014-01-01

    Unipolar Brush Cells (UBCs) have been suggested to play a critical role in cerebellar functioning, yet the corresponding cellular mechanisms remain poorly understood. UBCs have recently been reported to generate, in addition to early-onset glutamate receptor-dependent synaptic responses, a late-onset response (LOR) composed of a slow depolarizing ramp followed by a spike burst (Locatelli et al., 2013). The LOR activates as a consequence of synaptic activity and involves an intracellular cascade modulating H- and TRP-current gating. In order to assess the LOR mechanisms, we have developed a UBC multi-compartmental model (including soma, dendrite, initial segment, and axon) incorporating biologically realistic representations of ionic currents and a cytoplasmic coupling mechanism regulating TRP and H channel gating. The model finely reproduced UBC responses to current injection, including a burst triggered by a low-threshold spike (LTS) sustained by CaLVA currents, a persistent discharge sustained by CaHVA currents, and a rebound burst following hyperpolarization sustained by H- and CaLVA-currents. Moreover, the model predicted that H- and TRP-current regulation was necessary and sufficient to generate the LOR and its dependence on the intensity and duration of mossy fiber activity. Therefore, the model showed that, using a basic set of ionic channels, UBCs generate a rich repertoire of bursts, which could effectively implement tunable delay-lines in the local microcircuit.

  2. Progression of Gene Expression Changes following a Mechanical Injury to Articular Cartilage as a Model of Early Stage Osteoarthritis.

    Science.gov (United States)

    McCulloch, R S; Ashwell, M S; Maltecca, C; O'Nan, A T; Mente, P L

    2014-01-01

    An impact injury model of early stage osteoarthritis (OA) progression was developed using a mechanical insult to an articular cartilage surface to evaluate differential gene expression changes over time and treatment. Porcine patellae with intact cartilage surfaces were randomized to one of three treatments: nonimpacted control, axial impaction (2000 N), or a shear impaction (500 N axial, with tangential displacement to induce shear forces). After impact, the patellae were returned to culture for 0, 3, 7, or 14 days. At the appropriate time point, RNA was extracted from full-thickness cartilage slices at the impact site. Quantitative real-time PCR was used to evaluate differential gene expression for 18 OA related genes from four categories: cartilage matrix, degradative enzymes and inhibitors, inflammatory response and signaling, and cell apoptosis. The shear impacted specimens were compared to the axial impacted specimens and showed that shear specimens more highly expressed type I collagen (Col1a1) at the early time points. In addition, there was generally elevated expression of degradative enzymes, inflammatory response genes, and apoptosis markers at the early time points. These changes suggest that the more physiologically relevant shear loading may initially be more damaging to the cartilage and induces more repair efforts after loading.

  3. Response of Endogenous Salicylic Acid and Jasmonates to Mechanical Wounding in Pea Leaves

    Institute of Scientific and Technical Information of China (English)

    LIU Yan; PAN Qiu-hong; ZHAN Ji-cheng; TIAN Rong-rong; HUANG Wei-dong

    2008-01-01

    The roles of on endogenous jasmonates (JAs) and salicylic acid (SA) in wounding response were investigated. Pea (Pisum sativum L.) seedlings were treated with three different methods including mechanical wounding, JAs application,and SA application. The contents of endogenous JAs and SA, as well as the activities of the related enzymes were detected by enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC), and spectrophotometer, respectively. The results showed that endogenous JA rapidly accumulated within 30 min after wounding. The increase in the activities of both lipoxygenase (LOX) and allene oxide synthase (AOS) lagged behind JAs burst. A second slight increase in JAs level was observed at 24 h after wounding treatment, and at the same time point,higher activities of LOX and AOS were also detected. Endogenous free SA content decreased accompanied with JAs burst. Effects of exogenous JA application were similar to those of wounding treatment on endogenous SA level and phenylalanine ammonia lyase (PAL) activity, whereas exogenous SA application led to the significant inhibition of LOX and AOS activities and the decrease of endogenous JAs level at the early stage of treatment. It is thus suggested that JAs burst and SA decrease in early response to wounding may constitute an important mechanism by which plant starts the related defense reaction and adapts to wounding stress.

  4. The Sinorhizobium (Ensifer) fredii HH103 Type 3 Secretion System Suppresses Early Defense Responses to Effectively Nodulate Soybean.

    Science.gov (United States)

    Jiménez-Guerrero, Irene; Pérez-Montaño, Francisco; Monreal, José Antonio; Preston, Gail M; Fones, Helen; Vioque, Blanca; Ollero, Francisco Javier; López-Baena, Francisco Javier

    2015-07-01

    Plants that interact with pathogenic bacteria in their natural environments have developed barriers to block or contain the infection. Phytopathogenic bacteria have evolved mechanisms to subvert these defenses and promote infection. Thus, the type 3 secretion system (T3SS) delivers bacterial effectors directly into the plant cells to alter host signaling and suppress defenses, providing an appropriate environment for bacterial multiplication. Some rhizobial strains possess a symbiotic T3SS that seems to be involved in the suppression of host defenses to promote nodulation and determine the host range. In this work, we show that the inactivation of the Sinorhizobium (Ensifer) fredii HH103 T3SS negatively affects soybean nodulation in the early stages of the symbiotic process, which is associated with a reduction of the expression of early nodulation genes. This symbiotic phenotype could be the consequence of the bacterial triggering of soybean defense responses associated with the production of salicylic acid (SA) and the impairment of the T3SS mutant to suppress these responses. Interestingly, the early induction of the transcription of GmMPK4, which negatively regulates SA accumulation and defense responses in soybean via WRKY33, could be associated with the differential defense responses induced by the parental and the T3SS mutant strain.

  5. Storey building early monitoring based on rapid seismic response analysis

    Science.gov (United States)

    Julius, Musa, Admiral; Sunardi, Bambang; Rudyanto, Ariska

    2016-05-01

    Within the last decade, advances in the acquisition, processing and transmission of data from seismic monitoring has contributed to the growth in the number structures instrumented with such systems. An equally important factor for such growth can be attributed to the demands by stakeholders to find rapid answers to important questions related to the functionality or state of "health" of structures during and immediately of a seismic events. Consequently, this study aims to monitor the storey building based on seismic response i. e. earthquake and tremor analysis at short time lapse using accelerographs data. This study used one of storey building (X) in Jakarta city that suffered the effects of Kebumen earthquake January 25th 2014, Pandeglang earthquake July 9th 2014, and Lebak earthquake November 8th 2014. Tremors used in this study are tremors after the three following earthquakes. Data processing used to determine peak ground acceleration (PGA), peak ground velocity (PGV), peak ground displacement (PGD), spectral acceleration (SA), spectral velocity (SV), spectral displacement (SD), A/V ratio, acceleration amplification and effective duration (te). Then determine the natural frequency (f0) and peak of H/V ratio using H/V ratio method.The earthquakes data processing result shows the value of peak ground motion, spectrum response, A/V ratio and acceleration amplification increases with height, while the value of the effective duration give a different viewpoint of building dynamic because duration of Kebumen earthquake shows the highest energy in the highest floor but Pandeglang and Lebak earthquake in the lowest floor. Then, tremors data processing result one month after each earthquakes shows the natural frequency of building in constant value. Increasing of peak ground motion, spectrum response, A/V ratio, acceleration amplification, then decrease of effective duration following the increase of building floors shows that the building construction supports the

  6. Anticipatory modulation of neck muscle reflex responses induced by mechanical perturbations of the human forehead.

    Science.gov (United States)

    Kuramochi, Rieko; Kimura, Toshitaka; Nakazawa, Kimitaka; Akai, Masami; Torii, Suguru; Suzuki, Shuji

    2004-08-12

    The aim of this study was to test whether anticipation of upcoming head blow stimuli, which elicit reflex responses in the neck muscle, makes the reflex responses greater or not. In nine healthy subjects the reflex responses were elicited in the sternocleidomastoid (SCM) muscle in the eyes-open (EO) and eyes-closed (EC) conditions, which corresponded to the predictable and unpredictable conditions, respectively. The subjects were instructed not to resist the perturbations after the impact. The results demonstrated that the reflex response of the SCM muscle was significantly smaller in the predictable EO condition than in the unpredictable EC condition (P component, which most probably mediated the stretch reflex pathway. In contrast, no significant difference was observed in the early component, which was presumed to be the vestibular-collic reflex. The reduced stretch reflex response was suggested to be functionally relevant to the task requirement, i.e., to let the neck extension movement occur, and not to resist after the impact of the head blow. It was concluded that the anticipation has an effect on reducing the stretch reflex responses in the neck muscle, but does not have any effect on the presumed vestibular-collic reflex under the present experimental paradigm. It is suggested that the gain of the stretch reflex pathway is modulated by anticipatory information of upcoming mechanical event.

  7. Predictors of Responsiveness to Early Literacy Intervention: A 10-Year Update

    Science.gov (United States)

    Lam, Elizabeth A.; McMaster, Kristen L.

    2014-01-01

    The purpose of this review was to update previous reviews on factors related to students' responsiveness to early literacy intervention. The 14 studies in this synthesis used experimental designs, provided small-group or one-on-one reading interventions, and analyzed factors related to responsiveness to those interventions. Participants were…

  8. The Role Played by the Family in Shaping Early and Middle Adolescent Civic Responsibility

    Science.gov (United States)

    Lenzi, Michela; Vieno, Alessio; Santinello, Massimo; Nation, Maury; Voight, Adam

    2014-01-01

    Adopting a multi-informant methodology, the current study examines the relative influence of multiple parental characteristics (civic responsibility, encouragement of civic action, parent-youth closeness) on adolescents' civic responsibility (local and global). The participants were 384 early and middle adolescents (47.9% male), randomly selected…

  9. Evidence-Based Early Reading Practices within a Response to Intervention System

    Science.gov (United States)

    Bursuck, Bill; Blanks, Brooke

    2010-01-01

    Many students who experience reading failure are inappropriately placed in special education. A promising response to reducing reading failure and the overidentification of students for special education is Response to Intervention (RTI), a comprehensive early detection and prevention system that allows teachers to identify and support struggling…

  10. Preterm Children at Early Adolescence and Continuity and Discontinuity in Maternal Responsiveness from Infancy.

    Science.gov (United States)

    Beckwith, Leila; And Others

    1992-01-01

    Children whose mothers were consistently more responsive during the children's infancy and early adolescence achieved higher IQ and arithmetic scores, had more positive self-esteem, and were reported by teachers to exhibit fewer behavior problems than children of mothers who were consistently less responsive. (BC)

  11. The Role Played by the Family in Shaping Early and Middle Adolescent Civic Responsibility

    Science.gov (United States)

    Lenzi, Michela; Vieno, Alessio; Santinello, Massimo; Nation, Maury; Voight, Adam

    2014-01-01

    Adopting a multi-informant methodology, the current study examines the relative influence of multiple parental characteristics (civic responsibility, encouragement of civic action, parent-youth closeness) on adolescents' civic responsibility (local and global). The participants were 384 early and middle adolescents (47.9% male), randomly selected…

  12. Prediction and set-dependent scaling of early postural responses in cerebellar patients.

    Science.gov (United States)

    Timmann, D; Horak, F B

    1997-02-01

    We reported previously that patients with cerebellar deficits were unable to scale the magnitude of their early automatic postural responses to the predicted amplitudes of surface translations based on central set from prior experience. The present study investigated whether this deficit in set-dependent amplitude scaling was based predominantly on the cerebellar patient's disability (i) to predict perturbation amplitudes on the basis of prior experience, (ii) to scale the gain or magnitude of upcoming postural responses or (iii) to habituate postural responses. The increase in size of the early postural response when a larger than actual platform amplitude was expected and decrease when a smaller one was expected was defined as a measure of set-dependent amplitude prediction. The suppression of the postural response when the same platform velocity was repeated was used as a measure of habituation. The correlation between the size of early postural responses and platform amplitudes when presented serially, but not randomly, tested the ability to scale the gain of postural responses based on prior experience. Results show that although cerebellar patients could predict perturbation amplitudes based on prior experience, they could not use this prediction to modify precisely the gain of responses. The ability to habituate the magnitude of postural responses was not affected by cerebellar lesions. Thus, the cerebellum might not be critical for predicting upcoming events or for habituating to repeated postural stimuli, although it is important for accurate tuning of response gain based on prediction.

  13. Numerical Study of the Mechanical Response of Turtle Shell

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Chengwei Wu; Chenzhao Zhang; Zhen Chen

    2012-01-01

    The turtle shell is an amazing structure optimized through the long-term evolution by nature.This paper reports the mechanical response of the shell (Red-ear turtle) to static and dynamic loads,respectively.It is found that the turtle shell under a compressive load yields the maximum vertical displacement at the rear end,but the vertical displacement at the front end is only half of that at the rear end.The maximum horizontal displacement of the shell also occurs at the rear end.It is believed that such a deformation pattern is helpful for protecting the turtle's internal organs and its head.The principal stress directions in the inside surface of the shell under a compressive load are almost the same as those of the biofiber distribution in the inside surface,which results in the strong bending resistance of the turtle shell.

  14. Replicative Homeostasis III: implications for antiviral therapy and mechanisms of response and non-response

    Directory of Open Access Journals (Sweden)

    Sallie Richard

    2007-03-01

    Full Text Available Abstract While improved drug regimens have greatly enhanced outcomes for patients with chronic viral infection, antiviral therapy is still not ideal due to drug toxicities, treatment costs, primary drug failure and emergent resistance. New antiviral agents, alternative treatment strategies and a better understanding of viral pathobiology, host responses and drug action are desperately needed. Interferon (IFN and ribavirin, are effective drugs used to treat hepatitis C (HCV, but the mechanism(s of their action are uncertain. Error catastrophe (EC, or precipitous loss of replicative fitness caused by genomic mutation, is postulated to mediate ribavirin action, but is a deeply flawed hypothesis lacking empirical confirmation. Paradoxically ribavirin, a proven RNA mutagen, has no impact on HCV viraemia long term, suggesting real viruses, replicating in-vitro, as opposed to mathematical models, replicating in-silico, are likely to resist EC by highly selective replication of fit (~consensus sequence genomes mediated, in part, by replicative homeostasis (RH, an epicyclic mechanism that dynamically links RNApol fidelity and processivity and other viral protein functions. Replicative homeostasis provides a rational explanation for the various responses seen during treatment of HCV, including genotype-specific and viral load-dependent differential response rates, as well as otherwise unexplained phenomena like the transient inhibition and rebound of HCV viraemia seen during ribavirin monotherapy. Replicative homeostasis also suggests a primarily non-immunological mechanism that mediates increased immune responsiveness during treatment with ribavirin (and other nucleos(tide analogues, explicating the enhanced second-phase clearance of HCV ribavirin promotes and, thus, the apparent immunomodulatory action of ribavirin. More importantly, RH suggests specific new antiviral therapeutic strategies.

  15. Response of mechanical properties of glasses to their chemical, thermal and mechanical histories

    DEFF Research Database (Denmark)

    Yue, Yuanzheng

    , surface, thermal history or excess entropy of the final glass state. Here I review recent progresses in understanding of the responses of mechanical properties of oxide glasses to the compositional variation, thermal history and mechanical deformation. The tensile strength, elastic modulus and hardness...... and hardness of glass fibers are strongly correlated with the glass composition, fictive temperature, axial tension, and redox state. This correlation is explained by considering both the bulk and the surface glass structure. Furthermore, the compositional dependence of the densification extent, plastic flow...... of glass fibers are dependent on the thermal history (measured as fictive temperature), tension, chemical composition and redox state. However, the fictive temperature affects the hardness of bulk glass in a complicated manner, i.e., the effect does not exhibit a clear regularity in the range...

  16. Mechanisms Responsible for Microwave Properties in High Performance Dielectric Materials

    Science.gov (United States)

    Zhang, Shengke

    Microwave properties of low-loss commercial dielectric materials are optimized by adding transition-metal dopants or alloying agents (i.e. Ni, Co, Mn) to tune the temperature coefficient of resonant frequency (tau f) to zero. This occurs as a result of the temperature dependence of dielectric constant offsetting the thermal expansion. At cryogenic temperatures, the microwave loss in these dielectric materials is dominated by electron paramagnetic resonance (EPR) loss, which results from the spin-excitations of d-shell electron spins in exchange-coupled clusters. We show that the origin of the observed magnetically-induced shifts in the dielectric resonator frequency originates from the same mechanism, as described by the Kramers-Kronig relations. The temperature coefficient of resonator frequency, tauf, is related to three material parameters according to the equation, tau f = - (½ tauepsilon + ½ taumu + alphaL), where tauepsilon, taumu , and alphaL are the temperature coefficient of dielectric constant, magnetic permeability, and lattice constant, respectively. Each of these parameters for dielectric materials of interest are measured experimentally. These results, in combination with density functional simulations, developed a much improved understanding of the fundamental mechanisms responsible for tau f. The same experimental methods have been used to characterize in-situ the physical nature and concentration of performance-degrading point defects in the dielectrics of superconducting planar microwave resonators.

  17. Modeling microstructural evolution and the mechanical response of superplastic materials

    Energy Technology Data Exchange (ETDEWEB)

    Lesuer, D.R.; Syn, C.K.; Cadwell, K.L.; Preuss, C.S.

    1993-01-11

    A model has been developed that accounts for grain growth during, superplastic flow and its subsequent influence on stress-strain-strain rate behavior. These studies are experimentally based and have involved two different types of superplastic materials -- a quasi-single phase metal (Coronze 638) and a microduplex metal (ultrahigh-carbon steel - UHCS). In both materials the kinetics of strain-enhanced grain growth have been studied as a function of strain, strain rate and temperature. An equation for the rate of grain growth has been developed that incorporates the influence of temperature. The evolution of the grain size distribution during superplastic deformation has also been investigated. Our model integrates grain growth laws derived from these studies with two mechanism based, rate dependent constitutive laws to predict the stress-strainstrain rate behavior of materials during superplastic deformation. The influence of crain size distribution and its evolution with strain and strain rate on the stress-strain-strain rate behavior has been represented through the use of distributed parameters. The model can capture the stress-strain-strain rate behavior over a wide range of strains and strain rates with a single set of parameters. Many subtle features of the mechanical response of these materials can be adequately predicted.

  18. Mechanical Response of Typical Cement Concrete Pavements under Impact Loading

    Directory of Open Access Journals (Sweden)

    Ding Fei

    2017-01-01

    Full Text Available In order to study the mechanical response of cement concrete pavements under impact loading, four types of typical cement concrete pavement structures are investigated experimentally and numerically under an impact load. Full-scale three-dimensional pavement slots are tested under an impact load and are monitored for the mechanical characteristics including the deflection of the pavement surface layer, the strain distribution at the bottom of the slab, and the plastic damage and cracking under the dynamic impact load. Numerical analysis is performed by developing a three-dimensional finite element model and by utilizing a cement concrete damage model. The results show that the calculation results based on the cement concrete damage model are in reasonable agreement with the experimental results based on the three-dimensional test slot experiment. The peak values of stress and strain as monitored by the sensors are analyzed and compared with the numerical results, indicating that the errors of numerical results from the proposed model are mostly within 10%. The rationality of the finite element model is verified, and the model is expected to be a suitable reference for the analysis and design of cement concrete pavements.

  19. Collecting response times using Amazon Mechanical Turk and Adobe Flash.

    Science.gov (United States)

    Simcox, Travis; Fiez, Julie A

    2014-03-01

    Crowdsourcing systems like Amazon's Mechanical Turk (AMT) allow data to be collected from a large sample of people in a short amount of time. This use has garnered considerable interest from behavioral scientists. So far, most experiments conducted on AMT have focused on survey-type instruments because of difficulties inherent in running many experimental paradigms over the Internet. This study investigated the viability of presenting stimuli and collecting response times using Adobe Flash to run ActionScript 3 code in conjunction with AMT. First, the timing properties of Adobe Flash were investigated using a phototransistor and two desktop computers running under several conditions mimicking those that may be present in research using AMT. This experiment revealed some strengths and weaknesses of the timing capabilities of this method. Next, a flanker task and a lexical decision task implemented in Adobe Flash were administered to participants recruited with AMT. The expected effects in these tasks were replicated. Power analyses were conducted to describe the number of participants needed to replicate these effects. A questionnaire was used to investigate previously undescribed computer use habits of 100 participants on AMT. We conclude that a Flash program in conjunction with AMT can be successfully used for running many experimental paradigms that rely on response times, although experimenters must understand the limitations of the method.

  20. Pluripotent Stem Cell Studies Elucidate the Underlying Mechanisms of Early Embryonic Development

    Directory of Open Access Journals (Sweden)

    Lingyu Li

    2011-03-01

    Full Text Available Early embryonic development is a multi-step process that is intensively regulated by various signaling pathways. Because of the complexity of the embryo and the interactions between the germ layers, it is very difficult to fully understand how these signals regulate embryo patterning. Recently, pluripotent stem cell lines derived from different developmental stages have provided an in vitro system for investigating molecular mechanisms regulating cell fate decisions. In this review, we summarize the major functions of the BMP, FGF, Nodal and Wnt signaling pathways, which have well-established roles in vertebrate embryogenesis. Then, we highlight recent studies in pluripotent stem cells that have revealed the stage-specific roles of BMP,FGF and Nodal pathways during neural differentiation. These findings enhance our understanding of the stepwise regulation of embryo patterning by particular signaling pathways and provide new insight into the mechanisms underlying early embryonic development.

  1. A mechanism for the early detection and management of physical asset management strategy execution failure

    Directory of Open Access Journals (Sweden)

    Stimie, Johann

    2016-11-01

    Full Text Available The purpose of this paper is to present a mechanism that can assist physical asset management (PAM practitioners and academics with the early detection and management of PAM strategy execution failure. In the pursuit of this objective, case studies were applied to develop the theory related to this topic the methodologies involved in the development of theory through case studies was were applied. The paper commences with a brief literature review of the contemporary literature on general business strategy, strategy execution, and, more specifically, PAM strategy execution failure (PAMSEF. The physical asset management strategy execution enforcement mechanism (PAMSEEM is presented next. Validation of each one of the components of the PAMSEEM takes place within the context of an organisation that is highly dependent on physical assets (PA dependent organization. The conclusion reached is that the PAMSEEM, can indeed assist organisations with the early detection and management of PAMSEF.

  2. Early cell lineage specification in a marsupial: a case for diverse mechanisms among mammals.

    Science.gov (United States)

    Frankenberg, Stephen; Shaw, Geoff; Freyer, Claudia; Pask, Andrew J; Renfree, Marilyn B

    2013-03-01

    Early cell lineage specification in eutherian mammals results in the formation of a pluripotent inner cell mass (ICM) and trophoblast. By contrast, marsupials have no ICM. Here, we present the first molecular analysis of mechanisms of early cell lineage specification in a marsupial, the tammar wallaby. There was no overt differential localisation of key lineage-specific transcription factors in cleavage and early unilaminar blastocyst stages. Pluriblast cells (equivalent to the ICM) became distinguishable from trophoblast cells by differential expression of POU5F1 and, to a greater extent, POU2, a paralogue of POU5F1. Unlike in the mouse, pluriblast-trophoblast differentiation coincided with a global nuclear-to-cytoplasmic transition of CDX2 localisation. Also unlike in the mouse, Hippo pathway factors YAP and WWTR1 showed mutually distinct localisation patterns that suggest non-redundant roles. NANOG and GATA6 were conserved as markers of epiblast and hypoblast, respectively, but some differences to the mouse were found in their mode of differentiation. Our results suggest that there is considerable evolutionary plasticity in the mechanisms regulating early lineage specification in mammals.

  3. Early and late rate of force development: differential adaptive responses to resistance training?

    DEFF Research Database (Denmark)

    Andersen, L L; Andersen, Jesper Løvind; Zebis, M K

    2010-01-01

    The objective of this study is to investigate the potentially opposing influence of qualitative and quantitative muscular adaptations in response to high-intensity resistance training on contractile rate of force development (RFD) in the early (200 ms) of rising muscle force. Fifteen healthy young...... the vastus lateralis. The main findings were that RFD in the late phase of rising muscle force increased in response to resistance training whereas early RFD remained unchanged and early relative RFD (i.e., RFD/MVC) decreased. Quantitatively, muscle fiber cross-sectional area and MVC increased whereas......-intensity resistance training due to differential influences of qualitative and quantitative muscular adaptations on early and later phases of rising muscle force....

  4. Evaluation of spleen lymphocyte responsiveness to a T-cell mitogen during early infection with larval Taenia taeniaeformis.

    Science.gov (United States)

    Letonja, T; Hammerberg, C; Schurig, G

    1987-01-01

    The effect of taeniid infection on the in vitro cellular response of the host was investigated. Infections of Taenia taeniaeformis decreased the ability of spleen cells from susceptible C3H/He mice to respond to the T-cell mitogen concanavalin A (Con A) as early as 2 days postinfection (pi) reaching a suppression peak at day 12 pi. Similar experiments performed with spleen cells from infected BALB/c mice, resistant to the infection, revealed little or no suppression of Con A stimulation. The results suggested that susceptibility to the parasite may be due to its ability to induce a partial suppression of the host's immune system. The role of adherent splenocytes from infected C3H/He mice in the production of a deficient response to Con A during early infection was studied by coculturing experiments. These experiments demonstrated that adherent populations from infected mice did not play a direct role in the Con A-suppressor mechanisms. Concomitant with the suppressor activity an increased background proliferation was observed with nonstimulated splenocytes from C3H/He mice infected with T. taeniaeformis. Plasma from infected mice was able to suppress the response of normal spleen cells to Con A and to stimulate a proliferative response in cultured splenocytes from noninfected animals. The results suggest the presence of factors in the plasma of infected mice which may be modulating the immune response to the parasite.

  5. Understanding the Mechanisms Through Which an Influential Early Childhood Program Boosted Adult Outcomes

    Science.gov (United States)

    Heckman, James; Pinto, Rodrigo

    2013-01-01

    A growing literature establishes that high quality early childhood interventions targeted toward disadvantaged children have substantial impacts on later life outcomes. Little is known about the mechanisms producing these impacts. This paper uses longitudinal data on cognitive and personality traits from an experimental evaluation of the influential Perry Preschool program to analyze the channels through which the program boosted both male and female participant outcomes. Experimentally induced changes in personality traits explain a sizable portion of adult treatment effects. PMID:24634518

  6. Zebrafish Plzf transcription factors enhance early type I IFN response induced by two non-enveloped RNA viruses.

    Science.gov (United States)

    Aleksejeva, E; Houel, A; Briolat, V; Levraud, J-P; Langevin, C; Boudinot, P

    2016-04-01

    The BTB-POZ transcription factor Promyelocytic Leukemia Zinc Finger (PLZF, or ZBTB16) has been recently identified as a major factor regulating the induction of a subset of Interferon stimulated genes in human and mouse. We show that the two co-orthologues of PLZF found in zebrafish show distinct expression patterns, especially in larvae. Although zbtb16a/plzfa and zbtb16b/plzfb are not modulated by IFN produced during viral infection, their over-expression increases the level of the early type I IFN response, at a critical phase in the race between the virus and the host response. The effect of Plzfb on IFN induction was also detectable after cell infection by different non-enveloped RNA viruses, but not after infection by the rhabdovirus SVCV. Our findings indicate that plzf implication in the regulation of type I IFN responses is conserved across vertebrates, but at multiple levels of the pathway and through different mechanisms.

  7. Early and late rate of force development: differential adaptive responses to resistance training?

    Science.gov (United States)

    Andersen, L L; Andersen, J L; Zebis, M K; Aagaard, P

    2010-02-01

    The objective of this study is to investigate the potentially opposing influence of qualitative and quantitative muscular adaptations in response to high-intensity resistance training on contractile rate of force development (RFD) in the early (200 ms) of rising muscle force. Fifteen healthy young males participated in a 14-week resistance training intervention for the lower body and 10 matched subjects participated as controls. Maximal muscle strength (MVC) and RFD were measured during maximal voluntary isometric contraction of the quadriceps femoris muscle. Muscle biopsies were obtained from the vastus lateralis. The main findings were that RFD in the late phase of rising muscle force increased in response to resistance training whereas early RFD remained unchanged and early relative RFD (i.e., RFD/MVC) decreased. Quantitatively, muscle fiber cross-sectional area and MVC increased whereas, qualitatively, the relative proportion of type IIX muscle fibers decreased. Multiple regression analysis showed that while increased MVC positively influenced both early and late RFD, decreased-type IIX negatively influenced early RFD only. In conclusion, early and late RFD responded differently to high-intensity resistance training due to differential influences of qualitative and quantitative muscular adaptations on early and later phases of rising muscle force.

  8. A zebrafish larval model reveals early tissue-specific innate immune responses to Mucor circinelloides

    Directory of Open Access Journals (Sweden)

    Kerstin Voelz

    2015-11-01

    Full Text Available Mucormycosis is an emerging fungal infection that is clinically difficult to manage, with increasing incidence and extremely high mortality rates. Individuals with diabetes, suppressed immunity or traumatic injury are at increased risk of developing disease. These individuals often present with defects in phagocytic effector cell function. Research using mammalian models and phagocytic effector cell lines has attempted to decipher the importance of the innate immune system in host defence against mucormycosis. However, these model systems have not been satisfactory for direct analysis of the interaction between innate immune effector cells and infectious sporangiospores in vivo. Here, we report the first real-time in vivo analysis of the early innate immune response to mucormycete infection using a whole-animal zebrafish larval model system. We identified differential host susceptibility, dependent on the site of infection (hindbrain ventricle and swim bladder, as well as differential functions of the two major phagocyte effector cell types in response to viable and non-viable spores. Larval susceptibility to mucormycete spore infection was increased upon immunosuppressant treatment. We showed for the first time that macrophages and neutrophils were readily recruited in vivo to the site of infection in an intact host and that spore phagocytosis can be observed in real-time in vivo. While exploring innate immune effector recruitment dynamics, we discovered the formation of phagocyte clusters in response to fungal spores that potentially play a role in fungal spore dissemination. Spores failed to activate pro-inflammatory gene expression by 6 h post-infection in both infection models. After 24 h, induction of a pro-inflammatory response was observed only in hindbrain ventricle infections. Only a weak pro-inflammatory response was initiated after spore injection into the swim bladder during the same time frame. In the future, the zebrafish larva

  9. Cost effectiveness of responsive stimulation and nutrition interventions on early child development outcomes in Pakistan.

    Science.gov (United States)

    Gowani, Saima; Yousafzai, Aisha K; Armstrong, Robert; Bhutta, Zulfiqar A

    2014-01-01

    Early childhood programs are heralded as a way to improve children's health and educational outcomes. However, few studies in developing countries calculate the effectiveness of quality early childhood interventions. Even fewer estimate the associated costs of such interventions. The study here looks at the costs and effectiveness of a cluster-randomized effectiveness trial on children from birth to 24 months in rural Sindh, Pakistan. Responsive stimulation and/or enhanced nutrition interventions were integrated in the Lady Health Worker program in Pakistan. Outcomes suggest that children who receive responsive stimulation had significantly better development outcomes at 24 months than those who only received enhanced nutrition intervention. A cost-effectiveness analysis of the results verifies that early childhood interventions that include responsive stimulation are more cost effective than a nutrition intervention alone in promoting children's early development. Costs of a responsive stimulation intervention integrated in an existing community-based service providing basic health and nutrition care is approximately US$4 per month per child. We discuss these findings and make recommendations about scaling up and costs for future early child development programs. © 2014 New York Academy of Sciences.

  10. Context-dependent impact of presuppositions on early magnetic brain responses during speech perception.

    Science.gov (United States)

    Hertrich, Ingo; Kirsten, Mareike; Tiemann, Sonja; Beck, Sigrid; Wühle, Anja; Ackermann, Hermann; Rolke, Bettina

    2015-10-01

    Discourse structure enables us to generate expectations based upon linguistic material that has already been introduced. The present magnetoencephalography (MEG) study addresses auditory perception of test sentences in which discourse coherence was manipulated by using presuppositions (PSP) that either correspond or fail to correspond to items in preceding context sentences with respect to uniqueness and existence. Context violations yielded delayed auditory M50 and enhanced auditory M200 cross-correlation responses to syllable onsets within an analysis window of 1.5s following the PSP trigger words. Furthermore, discourse incoherence yielded suppression of spectral power within an expanded alpha band ranging from 6 to 16Hz. This effect showed a bimodal temporal distribution, being significant in an early time window of 0.0-0.5s following the PSP trigger and a late interval of 2.0-2.5s. These findings indicate anticipatory top-down mechanisms interacting with various aspects of bottom-up processing during speech perception.

  11. Boron deficiency in woody plants: various responses and tolerance mechanisms

    Directory of Open Access Journals (Sweden)

    Nannan eWang

    2015-10-01

    Full Text Available Boron (B is an essential microelement for higher plants, and its deficiency is widespread around the world and constrains the productivity of both agriculture and forestry. In the last decades, accumulating studies on model or herbaceous plants have contributed greatly to our understanding of the complex network of B-deficiency responses and mechanisms for tolerance. In woody plants, however, only a few studies have been conducted and they are not well synthesised. Trees have a larger body size, longer lifespan and more B reserves than do herbaceous plants, indicating that woody species might undergo long-term or mild B deficiency more commonly and that a more complicated B reserves must accordingly be developed to cope with B deficiency. In addition, the highly heterozygous genetic background of tree species suggests that they may have a more complicated mechanism of response and tolerance to B deficiency than do model plants.B-deficient trees usually exhibit two key visible symptoms: depression of growing points (root tip, bud, flower, and young leaf and deformity of organs (root, shoot, leaf, and fruit. These symptoms may be ascribed to B functioning in the cell wall and membrane, and B deficiency results in damage to vascular tissues and the suppression of both B and water transport. B deficiency also affects metabolic processes, such as increased lignin and phenol, and decreased leaf photosynthesis. These negative effects will influence the quality and quantity of wood, fruit and other agricultural products.B efficiency probably originates from a combined effect of three processes: B uptake, B translocation and retranslocation, and B utilization. Root morphology and mycorrhiza can affect the B uptake efficiency of trees. During B translocation from the root to shoot, differences in B concentration between root cell saps and xylem exudates, as well as water use efficiency, may play key roles in tolerance to B deficiency. In addition, B

  12. Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome

    Science.gov (United States)

    Uriarte, Juan J.; Meirelles, Thayna; Gorbenko del Blanco, Darya; Nonaka, Paula N.; Campillo, Noelia; Sarri, Elisabet; Navajas, Daniel; Egea, Gustavo; Farré, Ramon

    2016-01-01

    Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome. PMID:27003297

  13. EARLY RESPONSIVE to DEHYDRATION 15, a new transcription factor that integrates stress signaling pathways.

    Science.gov (United States)

    Alves, Murilo S; Fontes, Elizabeth P B; Fietto, Luciano G

    2011-12-01

    The Early Responsive to Dehydration (ERD) genes are defined as those genes that are rapidly activated during drought stress. The encoded proteins show a great structural and functional diversity, with a particular class of proteins acting as connectors of stress response pathways. Recent studies have shown that ERD15 proteins from different species of plants operate in cross-talk among different response pathways. In this mini-review, we show the recent progress on the functional role of this diverse family of proteins and demonstrate that a soybean ERD15 homolog can act as a connector in stress response pathways that trigger a programmed cell death signal.

  14. Transcriptional dynamics reveal critical roles for non-coding RNAs in the immediate-early response.

    Directory of Open Access Journals (Sweden)

    Stuart Aitken

    2015-04-01

    Full Text Available The immediate-early response mediates cell fate in response to a variety of extracellular stimuli and is dysregulated in many cancers. However, the specificity of the response across stimuli and cell types, and the roles of non-coding RNAs are not well understood. Using a large collection of densely-sampled time series expression data we have examined the induction of the immediate-early response in unparalleled detail, across cell types and stimuli. We exploit cap analysis of gene expression (CAGE time series datasets to directly measure promoter activities over time. Using a novel analysis method for time series data we identify transcripts with expression patterns that closely resemble the dynamics of known immediate-early genes (IEGs and this enables a comprehensive comparative study of these genes and their chromatin state. Surprisingly, these data suggest that the earliest transcriptional responses often involve promoters generating non-coding RNAs, many of which are produced in advance of canonical protein-coding IEGs. IEGs are known to be capable of induction without de novo protein synthesis. Consistent with this, we find that the response of both protein-coding and non-coding RNA IEGs can be explained by their transcriptionally poised, permissive chromatin state prior to stimulation. We also explore the function of non-coding RNAs in the attenuation of the immediate early response in a small RNA sequencing dataset matched to the CAGE data: We identify a novel set of microRNAs responsible for the attenuation of the IEG response in an estrogen receptor positive cancer cell line. Our computational statistical method is well suited to meta-analyses as there is no requirement for transcripts to pass thresholds for significant differential expression between time points, and it is agnostic to the number of time points per dataset.

  15. Modular Transcriptional Networks of the Host Pulmonary Response during Early and Late Pneumococcal Pneumonia.

    Science.gov (United States)

    Scicluna, Brendon P; van Lieshout, Miriam H; Blok, Dana C; Florquin, Sandrine; van der Poll, Tom

    2015-05-12

    Streptococcus pneumoniae (Spneu) remains the most lethal bacterial pathogen and the dominant agent of community-acquired pneumonia. Treatment has perennially focused on the use of antibiotics, albeit scrutinized due to the occurrence of antibiotic-resistant Spneu strains. Immunomodulatory strategies have emerged as potential treatment options. Although promising, immunomodulation can lead to improper tissue functions either at steady state or upon infectious challenge. This argues for the availability of tools to enable a detailed assessment of whole pulmonary functions during the course of infection, not only those functions biased to the defense response. Thus, through the use of an unbiased tissue microarray and bioinformatics approach, we aimed to construct a comprehensive map of whole-lung transcriptional activity and cellular pathways during the course of pneumococcal pneumonia. We performed genome-wide transcriptional analysis of whole lungs before and 6 and 48 h after Spneu infection in mice. The 4,000 most variable transcripts across all samples were used to assemble a gene coexpression network comprising 13 intercorrelating modules (clusters of genes). Fifty-four percent of this whole-lung transcriptional network was altered 6 and 48 h after Spneu infection. Canonical signaling pathway analysis uncovered known pathways imparting protection, including IL17A/IL17F signaling and previously undetected mechanisms that included lipid metabolism. Through in silico prediction of cell types, pathways were observed to enrich for distinct cell types such as a novel stromal cell lipid metabolism pathway. These cellular mechanisms were furthermore anchored at functional hub genes of cellular fate, differentiation, growth and transcription. Collectively, we provide a benchmark unsupervised map of whole-lung transcriptional relationships and cellular activity during early and late pneumococcal pneumonia.

  16. A highly specific pathogen-responsive promoter element from the immediate-early activated CMPG1 gene in Petroselinum crispum.

    Science.gov (United States)

    Kirsch, C; Logemann, E; Lippok, B; Schmelzer, E; Hahlbrock, K

    2001-04-01

    Within the complex signalling network from pathogen-derived elicitor perception to defense-related gene activation, some immediate-early responding genes may have pivotal roles in downstream transcriptional regulation. We have identified the parsley (Petroselinum crispum) ELI17 gene as a particularly fast-responding gene possessing a new type of W box-containing, elicitor-responsive promoter element, E17. Highly selective E17-mediated reporter gene expression at pathogen infection sites in transgenic Arabidopsis thaliana plants demonstrated the potential of this promoter element for designing new strategies in resistance breeding as well as for further analysis of the early components of defense-related gene activation mechanisms. The protein encoded by the ELI17 gene exhibits various structural characteristics of established transcription factors and is designated as a CMPG protein according to the first four strictly conserved amino acids defining a newly emerging class of plant-specific proteins.

  17. Bone density does not reflect mechanical properties in early-stage arthrosis

    DEFF Research Database (Denmark)

    Ding, Ming; Danielsen, CC; Hvid, I

    2001-01-01

    : medial arthrosis, lateral control, normal medial and normal lateral controls. The specimens were tested in compression to determine mechanical properties and then physical/compositional properties. Compared to the normal medial control, we found reductions in ultimate stress, Young's modulus, and failure...... cancellous bone and the 3 controls. None of the mechanical properties of arthrotic cancellous bone could be predicted by the physical/compositional properties measured. The increase in bone tissue in early-stage arthrotic cancellous bone did not make up for the loss of mechanical properties, which suggests...... energy, and an increase in ultimate strain of arthrotic cancellous bone. Bone volume fraction, apparent density, apparent ash density, and collagen density were higher in cancellous bone with arthrosis, but no differences were found in tissue density, mineral and collagen concentrations between arthrotic...

  18. Acid Stress Response Mechanisms of Group B Streptococci

    Directory of Open Access Journals (Sweden)

    Sarah Shabayek

    2017-09-01

    Full Text Available Group B streptococcus (GBS is a leading cause of neonatal mortality and morbidity in the United States and Europe. It is part of the vaginal microbiota in up to 30% of pregnant women and can be passed on to the newborn through perinatal transmission. GBS has the ability to survive in multiple different host niches. The pathophysiology of this bacterium reveals an outstanding ability to withstand varying pH fluctuations of the surrounding environments inside the human host. GBS host pathogen interations include colonization of the acidic vaginal mucosa, invasion of the neutral human blood or amniotic fluid, breaching of the blood brain barrier as well as survival within the acidic phagolysosomal compartment of macrophages. However, investigations on GBS responses to acid stress are limited. Technologies, such as whole genome sequencing, genome-wide transcription and proteome mapping facilitate large scale identification of genes and proteins. Mechanisms enabling GBS to cope with acid stress have mainly been studied through these techniques and are summarized in the current review

  19. Heavy Metal Stress and Some Mechanisms of Plant Defense Response

    Directory of Open Access Journals (Sweden)

    Abolghassem Emamverdian

    2015-01-01

    Full Text Available Unprecedented bioaccumulation and biomagnification of heavy metals (HMs in the environment have become a dilemma for all living organisms including plants. HMs at toxic levels have the capability to interact with several vital cellular biomolecules such as nuclear proteins and DNA, leading to excessive augmentation of reactive oxygen species (ROS. This would inflict serious morphological, metabolic, and physiological anomalies in plants ranging from chlorosis of shoot to lipid peroxidation and protein degradation. In response, plants are equipped with a repertoire of mechanisms to counteract heavy metal (HM toxicity. The key elements of these are chelating metals by forming phytochelatins (PCs or metallothioneins (MTs metal complex at the intra- and intercellular level, which is followed by the removal of HM ions from sensitive sites or vacuolar sequestration of ligand-metal complex. Nonenzymatically synthesized compounds such as proline (Pro are able to strengthen metal-detoxification capacity of intracellular antioxidant enzymes. Another important additive component of plant defense system is symbiotic association with arbuscular mycorrhizal (AM fungi. AM can effectively immobilize HMs and reduce their uptake by host plants via binding metal ions to hyphal cell wall and excreting several extracellular biomolecules. Additionally, AM fungi can enhance activities of antioxidant defense machinery of plants.

  20. Innate inflammatory responses in stroke: mechanisms and potential therapeutic targets

    Science.gov (United States)

    Kim, Jong Youl; Kawabori, Masahito; Yenari, Midori A.

    2014-01-01

    Stroke is a frequent cause of long-term disability and death worldwide. Ischemic stroke is more commonly encountered compared to hemorrhagic stroke, and leads to tissue death by ischemia due to occlusion of a cerebral artery. Inflammation is known to result as a result of ischemic injury, long thought to be involved in initiating the recovery and repair process. However, work over the past few decades indicates that aspects of this inflammatory response may in fact be detrimental to stroke outcome. Acutely, inflammation appears to have a detrimental effect, and anti-inflammatory treatments have been been studied as a potential therapeutic target. Chronically, reports suggest that post-ischemic inflammation is also essential for the tissue repairing and remodeling. The majority of the work in this area has centered around innate immune mechanisms, which will be the focus of this review. This review describes the different key players in neuroinflammation and their possible detrimental and protective effects in stroke. A better understanding of the roles of the different immune cells and their temporal profile of damage versus repair will help to clarify more effective modulation of inflammation post stroke. Introduction Stroke refers to conditions caused by occlusion and/or rupture of blood vessels in the brain, and is a leading cause of death and disability in the industrialized world. PMID:24372209

  1. Auditory-neurophysiological responses to speech during early childhood: Effects of background noise.

    Science.gov (United States)

    White-Schwoch, Travis; Davies, Evan C; Thompson, Elaine C; Woodruff Carr, Kali; Nicol, Trent; Bradlow, Ann R; Kraus, Nina

    2015-10-01

    Early childhood is a critical period of auditory learning, during which children are constantly mapping sounds to meaning. But this auditory learning rarely occurs in ideal listening conditions-children are forced to listen against a relentless din. This background noise degrades the neural coding of these critical sounds, in turn interfering with auditory learning. Despite the importance of robust and reliable auditory processing during early childhood, little is known about the neurophysiology underlying speech processing in children so young. To better understand the physiological constraints these adverse listening scenarios impose on speech sound coding during early childhood, auditory-neurophysiological responses were elicited to a consonant-vowel syllable in quiet and background noise in a cohort of typically-developing preschoolers (ages 3-5 yr). Overall, responses were degraded in noise: they were smaller, less stable across trials, slower, and there was poorer coding of spectral content and the temporal envelope. These effects were exacerbated in response to the consonant transition relative to the vowel, suggesting that the neural coding of spectrotemporally-dynamic speech features is more tenuous in noise than the coding of static features-even in children this young. Neural coding of speech temporal fine structure, however, was more resilient to the addition of background noise than coding of temporal envelope information. Taken together, these results demonstrate that noise places a neurophysiological constraint on speech processing during early childhood by causing a breakdown in neural processing of speech acoustics. These results may explain why some listeners have inordinate difficulties understanding speech in noise. Speech-elicited auditory-neurophysiological responses offer objective insight into listening skills during early childhood by reflecting the integrity of neural coding in quiet and noise; this paper documents typical response

  2. The NRF2-KEAP1 pathway is an early responsive gene network in arsenic exposed lymphoblastoid cells.

    Directory of Open Access Journals (Sweden)

    Emilio J Córdova

    Full Text Available Inorganic arsenic (iAs, a major environmental contaminant, has risen as an important health problem worldwide. More detailed identification of the molecular mechanisms associated with iAs exposure would help to establish better strategies for prevention and treatment. Although chronic iAs exposures have been previously studied there is little to no information regarding the early events of exposure to iAs. To better characterize the early mechanisms of iAs exposure we conducted gene expression studies using sublethal doses of iAs at two different time-points. The major transcripts differentially regulated at 2 hrs of iAs exposure included antioxidants, detoxificants and chaperones. Moreover, after 12 hrs of exposure many of the down-regulated genes were associated with DNA replication and S phase cell cycle progression. Interestingly, the most affected biological pathway by both 2 or 12 hrs of iAs exposure were the Nrf2-Keap1 pathway, represented by the highly up-regulated HMOX1 transcript, which is transcriptionally regulated by the transcription factor Nrf2. Additional Nrf2 targets included SQSTM1 and ABCB6, which were not previously associated with acute iAs exposure. Signalling pathways such as interferon, B cell receptor and AhR route were also responsive to acute iAs exposure. Since HMOX1 expression increased early (20 min and was responsive to low iAs concentrations (0.1 µM, this gene could be a suitable early biomarker for iAs exposure. In addition, the novel Nrf2 targets SQSTM1 and ABCB6 could play an important and previously unrecognized role in cellular protection against iAs.

  3. The NRF2-KEAP1 pathway is an early responsive gene network in arsenic exposed lymphoblastoid cells.

    Science.gov (United States)

    Córdova, Emilio J; Martínez-Hernández, Angélica; Uribe-Figueroa, Laura; Centeno, Federico; Morales-Marín, Mirna; Koneru, Harsha; Coleman, Matthew A; Orozco, Lorena

    2014-01-01

    Inorganic arsenic (iAs), a major environmental contaminant, has risen as an important health problem worldwide. More detailed identification of the molecular mechanisms associated with iAs exposure would help to establish better strategies for prevention and treatment. Although chronic iAs exposures have been previously studied there is little to no information regarding the early events of exposure to iAs. To better characterize the early mechanisms of iAs exposure we conducted gene expression studies using sublethal doses of iAs at two different time-points. The major transcripts differentially regulated at 2 hrs of iAs exposure included antioxidants, detoxificants and chaperones. Moreover, after 12 hrs of exposure many of the down-regulated genes were associated with DNA replication and S phase cell cycle progression. Interestingly, the most affected biological pathway by both 2 or 12 hrs of iAs exposure were the Nrf2-Keap1 pathway, represented by the highly up-regulated HMOX1 transcript, which is transcriptionally regulated by the transcription factor Nrf2. Additional Nrf2 targets included SQSTM1 and ABCB6, which were not previously associated with acute iAs exposure. Signalling pathways such as interferon, B cell receptor and AhR route were also responsive to acute iAs exposure. Since HMOX1 expression increased early (20 min) and was responsive to low iAs concentrations (0.1 µM), this gene could be a suitable early biomarker for iAs exposure. In addition, the novel Nrf2 targets SQSTM1 and ABCB6 could play an important and previously unrecognized role in cellular protection against iAs.

  4. Neurophysiological Evidence of Compensatory Brain Mechanisms in Early-Stage Multiple Sclerosis

    Science.gov (United States)

    López-Góngora, Mariana; Escartín, Antonio; Martínez-Horta, Saul; Fernández-Bobadilla, Ramón; Querol, Luis; Romero, Sergio; Mañanas, Miquel Àngel; Riba, Jordi

    2015-01-01

    Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by white matter inflammation, demyelination and neurodegeneration. Although cognitive dysfunction is a common manifestation, it may go unnoticed in recently-diagnosed patients. Prior studies suggest MS patients develop compensatory mechanisms potentially involving enhanced performance monitoring. Here we assessed the performance monitoring system in early-stage MS patients using the error-related negativity (ERN), an event-related brain potential (ERP) observed following behavioral errors. Twenty-seven early-stage MS patients and 31 controls were neuropsychologically assessed. Electroencephalography recordings were obtained while participants performed: a) a stop task and b) an auditory oddball task. Behavior and ERP measures were assessed. No differences in performance were found between groups in most neuropsychological tests or in behavior or ERP components in the auditory oddball task. However, the amplitude of the ERN associated with stop errors in the stop task was significantly higher in patients. ERN amplitude correlated positively with scores on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and negatively with the time since last relapse. Patients showed higher neuronal recruitment in tasks involving performance monitoring. Results suggest the development of compensatory brain mechanisms in early-stage MS and reflect the sensitivity of the ERN to detect these changes. PMID:26322632

  5. The early epigenetic response to ozone: impacts on DNA methylation and hydroxymethylation.

    Science.gov (United States)

    Epigenetics have been increasingly recognized as a mechanism linking environment and gene expression. Despite awareness of the role of DNA methylation and hydroxymethylation as potential drivers of the response to air pollutants, very little work has been performed investigating ...

  6. Role of mechanical stretching and lipopolysaccharide in early apoptosis and IL-8 of alveolar epithelial typeⅡ cells A549

    Institute of Scientific and Technical Information of China (English)

    Qiao-Ming Ning; Xiao-Ning Sun; Xin-Kai Zhao

    2012-01-01

    Objective:To investigate the effects of mechanical stretching and lipopolysaccharide (LPS) on the early apoptosis and IL-8 production of alveolar epithelial typeⅡ cellsA549.Methods:The experimental matrix consisted of three integrated studies.In the first study,A549 cells were subjected to different stretching strain frequency and duration time to see the effects on the early apoptosis.In the second study,A549 cells were subjected to mechanical stretch(15%4 h, 0.5Hz) andLPS(1 or100 ng/mL) to see whether mechanical strain andLPS also have an addictive effect on the early apoptosis.In the third study to investigate whether this addictive effect could be induced byLPS and mechanical stretch onIL-8 production,A549 cells were subjected to LPS(100 ng/mL) and mechanical strain(15%,0.5Hz,4 h).Real timePCR and enzyme linked immunosorbent assay were used to measure mRNA and protein level ofIL-8.The early apoptosis was detected by flow cytometry.Results:Mechanical stretch induced the early apoptosis in a force and frequency and time-dependent manner.In the presence ofLPS, mechanical stretch enhancedLPS-induced early apoptosis, especially in100 ng/mLLPS group compared with1 ng/mLLPS and the control group.Mechanical stretch increasedIL-8 production and enhancedLPS-inducedIL-8 screation both in mRNA and protein levels.Conclusions:Mechanical stretch can induce the early apoptosis andIL-8 secretion.Mechanical stretch andLPS have an addictive effect on the early apoptosis andIL-8 production in alveolar type2 cells, which is one of the mechanisms of ventilator-induced lung injury.

  7. Evidence for an Early Origin of Vernalization Responsiveness in Temperate Pooideae Grasses1[OPEN

    Science.gov (United States)

    McKeown, Meghan; Fjellheim, Siri

    2016-01-01

    The ability of plants to match their reproductive output with favorable environmental conditions has major consequences both for lifetime fitness and geographic patterns of diversity. In temperate ecosystems, some plant species have evolved the ability to use winter nonfreezing cold (vernalization) as a cue to ready them for spring flowering. However, it is unknown how important the evolution of vernalization responsiveness has been for the colonization and subsequent diversification of taxa within the northern and southern temperate zones. Grasses of subfamily Pooideae, including several important crops, such as wheat (Triticum aestivum), barley (Hordeum vulgare), and oats (Avena sativa), predominate in the northern temperate zone, and it is hypothesized that their radiation was facilitated by the early evolution of vernalization responsiveness. Predictions of this early origin hypothesis are that a response to vernalization is widespread within the subfamily and that the genetic basis of this trait is conserved. To test these predictions, we determined and reconstructed vernalization responsiveness across Pooideae and compared expression of wheat vernalization gene orthologs VERNALIZATION1 (VRN1) and VRN3 in phylogenetically representative taxa under cold and control conditions. Our results demonstrate that vernalization responsive Pooideae species are widespread, suggesting that this trait evolved early in the lineage and that at least part of the vernalization gene network is conserved throughout the subfamily. These results are consistent with the hypothesis that the evolution of vernalization responsiveness was important for the initial transition of Pooideae out of the tropics and into the temperate zone. PMID:27474116

  8. Evidence for an Early Origin of Vernalization Responsiveness in Temperate Pooideae Grasses.

    Science.gov (United States)

    McKeown, Meghan; Schubert, Marian; Marcussen, Thomas; Fjellheim, Siri; Preston, Jill C

    2016-09-01

    The ability of plants to match their reproductive output with favorable environmental conditions has major consequences both for lifetime fitness and geographic patterns of diversity. In temperate ecosystems, some plant species have evolved the ability to use winter nonfreezing cold (vernalization) as a cue to ready them for spring flowering. However, it is unknown how important the evolution of vernalization responsiveness has been for the colonization and subsequent diversification of taxa within the northern and southern temperate zones. Grasses of subfamily Pooideae, including several important crops, such as wheat (Triticum aestivum), barley (Hordeum vulgare), and oats (Avena sativa), predominate in the northern temperate zone, and it is hypothesized that their radiation was facilitated by the early evolution of vernalization responsiveness. Predictions of this early origin hypothesis are that a response to vernalization is widespread within the subfamily and that the genetic basis of this trait is conserved. To test these predictions, we determined and reconstructed vernalization responsiveness across Pooideae and compared expression of wheat vernalization gene orthologs VERNALIZATION1 (VRN1) and VRN3 in phylogenetically representative taxa under cold and control conditions. Our results demonstrate that vernalization responsive Pooideae species are widespread, suggesting that this trait evolved early in the lineage and that at least part of the vernalization gene network is conserved throughout the subfamily. These results are consistent with the hypothesis that the evolution of vernalization responsiveness was important for the initial transition of Pooideae out of the tropics and into the temperate zone.

  9. 缺氧后内皮细胞早期生长反应因子-1活化的信号机制%The Signaling Mechanism Involved in Hypoxia-induced Upregulation of Early Growth Response-1 in Endothelial Cells

    Institute of Scientific and Technical Information of China (English)

    黄春; 杨明; 施晓芸; 陈晓春

    2012-01-01

    目的 观察缺氧对内皮细胞早期生长反应因子(Egr-1)表达的影响及晚期糖基化终末产物(AGEs)及其受体(RAGE)对上述效应的可能调控机制.方法 以培养小鼠主动脉内皮细胞(MAECs)为模型,根据缺氧时间和缺氧前预处理方式,分为不同缺氧时间组[缺氧0(对照组),5,10,15,30,60,120 min组]、anti-AGE预处理组、可溶性RAGE(sRAGE)预处理组和蛋白激酶C(PKC)β抑制剂组,实时定量PCR法检测缺氧后Egr-1 mRNA含量、ELISA法检测细胞裂解液中AGEs含量、蛋白印迹法检测细胞膜蛋白中PKC各异构体的活化.结果 缺氧15 min组Egr-1 mRNA表达上调,为对照组的(14.13±0.77)倍(P=0.000 0);缺氧10~60 min内皮细胞裂解液中AGEs堆积;缺氧15 min组MAECs膜蛋白中PKCβⅡ含量为(30.57±1.86),显著高于对照组的含量(9.22±1.05)(P=0.002);anti-AGE、sRAGE和PKCβ抑制剂预处理减少缺氧诱导的Egr-1 mRNA表达上调(P=0.000 0);anti-AGE和sRAGE预处理显著减少缺氧对PKCβⅡ的活化(P=0.000 0).结论 急性缺氧诱导内皮细胞AGEs堆积、PKCβⅡ活化和Egr-1mRNA高表达,AGEs-RAGE和PKCβII信号参与急性缺氧后Egr-1诱导表达的调控.%Objective To observe the impact of hypoxia on the expression of early growth response-1 (Egr-1) in mouse aortic endothelial cells(MAECs) , and to study the underlying signaling mechanism involving advanced glycation end-products (AGEs) and its receptor (receptor for AGEs, RAGE). Methods MAECs were subjected to hypoxia treatment with a (6.0+0.5)% oxygen concentration for various periods (0, 5, 10, 15, 30, 60 or 120 min) , or -were first pre-incubated -with anti-AGEs or soluble RAGE (sRAGE) for 2 h, or LY379196 for 45 min respectively, and then subsequently exposed to hypoxia for 15 min. Egr-1 mRNA levels -were detected by real time PCR (RT-PCR), AGEs in cell lysate -were monitored by ELISA, and PKC isoformates in membrane fraction were examined by western blot. MAECs cultured -with normoxia -were

  10. Self-cementing Mechanism of CFBC Coal Ashes at Early Ages

    Institute of Scientific and Technical Information of China (English)

    SONG Yuanming; QIAN Jueshi; WANG Zhi; WANG Zhijuan

    2008-01-01

    The self-cementing mechanism at early ages of circulating fluidized bed combustion (CFBC) coal ashes was studied by X-ray diffraction (XRD), infrared (IR) spectroscopy and chemical method. The results indicate that the amorphous phase is predominant in CFBC coal ashes. The polymerization degree of [SiO4] and [AlO6] of CFBC desulphurization coal ashes is lower than that of those without desulphurization. The contents of the components with fast hydration rate of CFBC desulphurization coal ashes are significantly greater than those of the ashes without desulphurization. This work confirms that the amorphous minerals with high chemical activity are the main causes of the self-cementing property of CFBC desulphurization coal ashes at early ages.

  11. The bradykinin B2 receptor in the early immune response against Listeria infection

    NARCIS (Netherlands)

    Kaman, W.E.; Wolterink, A.F.W.M.; Bader, M.; Boele, L.C.L.; Kleij, D. van der

    2009-01-01

    The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B2 (B2R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B2R (B2R-/- mice

  12. Early Detection Rapid Response Program Targets New Noxious Weed Species in Washington State

    Science.gov (United States)

    Andreas, Jennifer E.; Halpern, Alison D.; DesCamp, Wendy C.; Miller, Timothy W.

    2015-01-01

    Early detection, rapid response is a critical component of invasive plant management. It can be challenging, however, to detect new invaders before they become established if landowners cannot identify species of concern. In order to increase awareness, eye-catching postcards were developed in Washington State as part of a noxious weed educational…

  13. Pre-Service Teacher Disposition Development: Cultural Reciprocity and Responsivity in Early Childhood Special Education Practica

    Science.gov (United States)

    Van Steenberg, Vicki

    2012-01-01

    This qualitative Case Study explored the integrative process of pre-service teachers' disposition development for cultural reciprocity and responsiveness. Over the course of ten months, pre-service teachers completed two Early Childhood Special Education practica in diverse urban communities. The pre-service teachers were placed in public…

  14. Responsive Parenting: Establishing Early Foundations for Social, Communication, and Independent Problem-Solving Skills

    Science.gov (United States)

    Landry, Susan H.; Smith, Karen E.; Swank, Paul R.

    2006-01-01

    Mothers whose infants varied in early biological characteristics (born at term, n = 120; born at very low birth weight [VLBW], n = 144) were randomized to a target group (n = 133) or developmental feedback comparison group (n = 131) to determine whether learning responsive behaviors would facilitate infant development. The target condition…

  15. Early Detection Rapid Response Program Targets New Noxious Weed Species in Washington State

    Science.gov (United States)

    Andreas, Jennifer E.; Halpern, Alison D.; DesCamp, Wendy C.; Miller, Timothy W.

    2015-01-01

    Early detection, rapid response is a critical component of invasive plant management. It can be challenging, however, to detect new invaders before they become established if landowners cannot identify species of concern. In order to increase awareness, eye-catching postcards were developed in Washington State as part of a noxious weed educational…

  16. MITOGENIC SIGNALS CONTROL TRANSLATION OF THE EARLY GROWTH-RESPONSE GENE-1 IN MYOGENIC CELLS

    NARCIS (Netherlands)

    MAASS, A; GROHE, C; OBERDORF, S; SUKHATME, VP; VETTER, H; NEYSES, L

    1994-01-01

    Muscle is a major site of expression of the early growth reponse gene-1 (Egr-1). To investigate its role in muscle proliferation and/or differentiation we studied the effect of a variety of growth factors on cultured mouse muscle So18 cells. Three groups of responses could be distinguished: 1. AII,

  17. The Confluence of Adverse Early Experience and Puberty on the Cortisol Awakening Response

    Science.gov (United States)

    Quevedo, Karina; Johnson, Anna E.; Loman, Michelle L.; LaFavor, Theresa L.; Gunnar, Megan

    2012-01-01

    Associations between early deprivation/neglect in the form of institutional care with the cortisol awakening response (CAR) were examined as a function of pubertal status among 12- and 13-year-old postinstitutionalized youth. CARs indexed hypothalamic-pituitary-adrenocortical reactivity. Postinstitutionalized youth were compared to youth adopted…

  18. Transcriptional response of bronchial epithelial cells to Pseudomonas aeruginosa: identification of early mediators of host defense.

    NARCIS (Netherlands)

    Vos, J.B.; Sterkenburg, M.A. van; Rabe, K.F.; Schalkwijk, J.; Hiemstra, P.S.; Datson, N.A.

    2005-01-01

    The airway epithelium responds to microbial exposure by altering expression of a variety of genes to increase innate host defense. We aimed to delineate the early transcriptional response in human primary bronchial epithelial cells exposed for 6 h to a mixture of IL-1beta and TNF-alpha or heat-inact

  19. Value of sympathetic skin response test in the early diagnosis of diabetic neuropathy

    Institute of Scientific and Technical Information of China (English)

    黄一宁; 贾志荣; 石昕; 孙相如

    2004-01-01

    Background Diabetic neuropathy is common in diabetes mellitus. The early stage of diabetic neuropathy is often symptomless and difficult to be treated. The aim of this study was to assess the correlation between the results of the sympathetic skin response (SSR) test and the development of diabetic neuropathy, and explore the use of SSR as an objective basis for the early diagnosis of diabetic neuropathy.Methods The latencies and amplitudes of initiation and of the N and P waves were determined by SSR testing of the extremities of 80 diabetic patients and 30 healthy controls. Results The latencies of initiation and of the N and P waves were significantly (P0.05). All but two patients (97.5%) demonstrated abnormal SSR in at least one limb. Conclusions SSR can detect early dysfunction of the small sympathetic fibers in people affected by diabetes mellitus, and may be a useful electrophysiological test for the early diagnosis of diabetic neuropathy.

  20. Early transcriptomic response of Arabidopsis thaliana to polymetallic contamination: implications for the identification of potential biomarkers of metal exposure.

    Science.gov (United States)

    Gómez-Sagasti, María T; Barrutia, Oihana; Ribas, Griselda; Garbisu, Carlos; Becerril, José M

    2016-05-01

    Heavy metal contaminated sites are frequently characterized by the simultaneous presence of several heavy metals. However, many studies report metal-induced plant responses after long-term exposure to just one metal. By contrast, whole genome expression microarrays were employed here to investigate the early (3 h) transcriptional responses of Arabidopsis thaliana plants exposed to polymetallic treatment (Pb, Hg, Cu, Cd, Co, Ni, Zn, and Mn) at low (L) and high (H) concentrations. After 3 h of exposure to polymetallic treatment, a total of 1315 noticeably (≥2-fold) and significantly (P < 0.05) differentially expressed genes were identified: 656 and 351 upregulated and 314 and 200 downregulated genes in L and H treatments, respectively. Functional analysis revealed that many genes involved in oxidative stress and perception/signalling/regulation systems were activated. Genes encoding proteins involved in hormone regulation (jasmonic acid, abscisic acid, ethylene, and auxins), glucosinolate metabolism and sulphur and nitrogen transport were also modulated. RT-qPCR analysis of four downregulated (AOP2, SAUR16, BBX31, and MTPC3) and upregulated genes (ASN1, DIN2, BT2, and EXL5), markedly responsive to both L and H treatments, validated our microarray data and suggested the potential of some of these genes (AOP2, SAUR16, ASN1, and DIN2) as early biomarkers of metal exposure. Relevant changes in gene expression occur as early as 3 h after exposure to polymetallic treatment. Four genes deserve further studies as novel putative biomarkers of early metal exposure and also owing to their potential implications in stress-related mechanisms: sulphur balance (AOP2), phytohormone regulation of plant growth and development (SAUR16), ammonium detoxification (ASN1) and senescence (DIN2).

  1. Lack of IL-6 during coxsackievirus infection heightens the early immune response resulting in increased severity of chronic autoimmune myocarditis.

    Directory of Open Access Journals (Sweden)

    Maya C Poffenberger

    Full Text Available BACKGROUND: Chronic myocarditis is often initiated by viral infection, the most common of which is coxsackievirus infection. The precise mechanism by which viral infection leads to chronic autoimmune pathology is poorly understood, however it is clear that the early immune response plays a critical role. Previous results have shown that the inflammatory cytokine interleukin (IL-6 is integral to the development of experimental-induced autoimmune myocarditis. However, the function of IL-6 during viral-mediated autoimmunity has yet to be elucidated. METHODS AND RESULTS: To address the requirement of IL-6 during disease induction, IL-6 deficient mice were infected with coxsackievirus B3 (CB3. Following infection, mice lacking IL-6 developed increased chronic autoimmune disease pathology compared to wild type controls without a corresponding change in the level of viral replication in the heart. This increase in disease severity was accompanied by elevated levels of TNF-alpha, MCP-1, IL-10, activated T cells and cardiac infiltrating macrophage/monocytes. Injection of recombinant IL-6 early following infection in the IL-6 deficient mice was sufficient to lower the serum cytokines TNF-alpha and IL-10 as well as the serum chemokines MCP-1, MIP-1beta, RANTES and MIG with a corresponding decrease in the chronic disease pathology strongly suggests an important regulatory role for IL-6 during the early response. CONCLUSIONS: While IL-6 plays a pathogenic role in experimental-induced autoimmune disease, its function following viral-induced autoimmunity is not reprised. By regulating the early immune response and thereby controlling the severity of chronic disease, IL-6 directs the outcome of chronic autoimmune myocarditis.

  2. SPOC1-Mediated Antiviral Host Cell Response Is Antagonized Early in Human Adenovirus Type 5 Infection

    Science.gov (United States)

    Schreiner, Sabrina; Kinkley, Sarah; Bürck, Carolin; Mund, Andreas; Wimmer, Peter; Schubert, Tobias; Groitl, Peter; Will, Hans; Dobner, Thomas

    2013-01-01

    Little is known about immediate phases after viral infection and how an incoming viral genome complex counteracts host cell defenses, before the start of viral gene expression. Adenovirus (Ad) serves as an ideal model, since entry and onset of gene expression are rapid and highly efficient, and mechanisms used 24–48 hours post infection to counteract host antiviral and DNA repair factors (e.g. p53, Mre11, Daxx) are well studied. Here, we identify an even earlier host cell target for Ad, the chromatin-associated factor and epigenetic reader, SPOC1, recently found recruited to double strand breaks, and playing a role in DNA damage response. SPOC1 co-localized with viral replication centers in the host cell nucleus, interacted with Ad DNA, and repressed viral gene expression at the transcriptional level. We discovered that this SPOC1-mediated restriction imposed upon Ad growth is relieved by its functional association with the Ad major core protein pVII that enters with the viral genome, followed by E1B-55K/E4orf6-dependent proteasomal degradation of SPOC1. Mimicking removal of SPOC1 in the cell, knock down of this cellular restriction factor using RNAi techniques resulted in significantly increased Ad replication, including enhanced viral gene expression. However, depletion of SPOC1 also reduced the efficiency of E1B-55K transcriptional repression of cellular promoters, with possible implications for viral transformation. Intriguingly, not exclusive to Ad infection, other human pathogenic viruses (HSV-1, HSV-2, HIV-1, and HCV) also depleted SPOC1 in infected cells. Our findings provide a general model for how pathogenic human viruses antagonize intrinsic SPOC1-mediated antiviral responses in their host cells. A better understanding of viral entry and early restrictive functions in host cells should provide new perspectives for developing antiviral agents and therapies. Conversely, for Ad vectors used in gene therapy, counteracting mechanisms eradicating incoming

  3. Early Prediction and Evaluation of Breast Cancer Response to Neoadjuvant Chemotherapy Using Quantitative DCE-MRI

    Directory of Open Access Journals (Sweden)

    Alina Tudorica

    2016-02-01

    Full Text Available The purpose is to compare quantitative dynamic contrast-enhanced (DCE magnetic resonance imaging (MRI metrics with imaging tumor size for early prediction of breast cancer response to neoadjuvant chemotherapy (NACT and evaluation of residual cancer burden (RCB. Twenty-eight patients with 29 primary breast tumors underwent DCE-MRI exams before, after one cycle of, at midpoint of, and after NACT. MRI tumor size in the longest diameter (LD was measured according to the RECIST (Response Evaluation Criteria In Solid Tumors guidelines. Pharmacokinetic analyses of DCE-MRI data were performed with the standard Tofts and Shutter-Speed models (TM and SSM. After one NACT cycle the percent changes of DCE-MRI parameters Ktrans (contrast agent plasma/interstitium transfer rate constant, ve (extravascular and extracellular volume fraction, kep (intravasation rate constant, and SSM-unique τi (mean intracellular water lifetime are good to excellent early predictors of pathologic complete response (pCR vs. non-pCR, with univariate logistic regression C statistics value in the range of 0.804 to 0.967. ve values after one cycle and at NACT midpoint are also good predictors of response, with C ranging 0.845 to 0.897. However, RECIST LD changes are poor predictors with C = 0.609 and 0.673, respectively. Post-NACT Ktrans, τi, and RECIST LD show statistically significant (P < .05 correlations with RCB. The performances of TM and SSM analyses for early prediction of response and RCB evaluation are comparable. In conclusion, quantitative DCE-MRI parameters are superior to imaging tumor size for early prediction of therapy response. Both TM and SSM analyses are effective for therapy response evaluation. However, the τi parameter derived only with SSM analysis allows the unique opportunity to potentially quantify therapy-induced changes in tumor energetic metabolism.

  4. Early versus late percutaneous dilational tracheostomy in critically ill patients anticipated requiring prolonged mechanical ventilation

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yue; LI Wen-xiong; SUI Feng; CHEN Xiu-kai; ZHANG Gui-chen; WANG Xiao-wen; ZHAO Song; SONG Yang; LIU Wei; XIN Xin

    2012-01-01

    Background Tracheostomy should be considered to replace endotracheal intubation in patients requiring prolonged mechanical ventilation (MV).However,the optimal timing for tracheostomy is still a topic of debate.The present study aimed to investigate whether early percutaneous dilational tracheostomy (PDT) can reduce duration of MV,and to further verify whether early PDT can reduce sedative use,shorten intensive care unit (ICU) stay,decrease the incidence of ventilator associated pneumonia (VAP),and increase successful weaning and ICU discharge rate.Methods A prospective,randomized controlled trial was carried out in a surgical ICU from July 2008 to June 2011 in adult patients anticipated requiring prolonged MV via endotracheal intubation.Patients meeting the inclusion criteria were randomly assigned to the early PDT group or the late PDT group on day 3 of MV.The patients in the early PDT group were tracheostomized with PDT on day 3 of MV.The patients in the late PDT group were tracheostomized with PDT on day 15 of MV if they still needed MV.The primary endpoint was ventilator-free days at day 28 after randomization.The secondary endpoints were sedation-free days,ICU-free days,successful weaning and ICU discharge rate,and incidence of VAP at day 28 after randomization.The cumulative 60-day incidence of death after randomization was also analyzed.Results Total 119 patients were randomized to either the early PDT group (n=58) or the late PDT group (n=61).The ventilator-free days was significantly increased in the early PDT group than in the late PDT group ((9.57±5.64) vs.(7.38±6.17) days,P <0.05).The sedation-free days and ICU-free days were also significantly increased in the early PDT group than in the late PDT group (20.84±2.35 vs.17.05±2.30 days,P <0.05; and 8.0 (interquartile range (IQR):5.0-12.0)vs.3.0 (IQR:0-12.0) days,P <0.001 respectively).The successful weaning and ICU discharge rate was significantly higher in early PDT group than in late PDT

  5. Dopamine D2 receptor gene variants and response to rasagiline in early Parkinson's disease: a pharmacogenetic study.

    Science.gov (United States)

    Masellis, Mario; Collinson, Shannon; Freeman, Natalie; Tampakeras, Maria; Levy, Joseph; Tchelet, Amir; Eyal, Eli; Berkovich, Elijahu; Eliaz, Rom E; Abler, Victor; Grossman, Iris; Fitzer-Attas, Cheryl; Tiwari, Arun; Hayden, Michael R; Kennedy, James L; Lang, Anthony E; Knight, Jo

    2016-07-01

    Parkinson symptoms from Weeks 12 to 36 after correction for multiple testing. This is the largest and most comprehensive pharmacogenetics study to date examining clinical response to an anti-parkinsonian drug and the first to be conducted in patients with early stage Parkinson's disease receiving monotherapy. The results indicate a clinically meaningful benefit to rasagiline in terms of the magnitude of improvement in parkinsonian symptoms for those with the favourable response genotypes. Future work is needed to elucidate the specific mechanisms through which these DRD2 variants operate in modulating the function of the nigrostriatal dopaminergic system.media-1vid110.1093/brain/aww109_video_abstractaww109_video_abstract.

  6. Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

    Science.gov (United States)

    VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

    2016-01-01

    People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

  7. Ethanol exposure alters early cardiac function in the looping heart: a mechanism for congenital heart defects?

    Science.gov (United States)

    Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Peterson, Lindsy M; Mai, Katherine; McHale, Quinn; Jenkins, Michael W; Linask, Kersti K; Rollins, Andrew M; Watanabe, Michiko

    2014-02-01

    Alcohol-induced congenital heart defects are frequently among the most life threatening and require surgical correction in newborns. The etiology of these defects, collectively known as fetal alcohol syndrome, has been the focus of much study, particularly involving cellular and molecular mechanisms. Few studies have addressed the influential role of altered cardiac function in early embryogenesis because of a lack of tools with the capability to assay tiny beating hearts. To overcome this gap in our understanding, we used optical coherence tomography (OCT), a nondestructive imaging modality capable of micrometer-scale resolution imaging, to rapidly and accurately map cardiovascular structure and hemodynamics in real time under physiological conditions. In this study, we exposed avian embryos to a single dose of alcohol/ethanol at gastrulation when the embryo is sensitive to the induction of birth defects. Late-stage hearts were analyzed using standard histological analysis with a focus on the atrio-ventricular valves. Early cardiac function was assayed using Doppler OCT, and structural analysis of the cardiac cushions was performed using OCT imaging. Our results indicated that ethanol-exposed embryos developed late-stage valvuloseptal defects. At early stages, they exhibited increased regurgitant flow and developed smaller atrio-ventricular cardiac cushions, compared with controls (uninjected and saline-injected embryos). The embryos also exhibited abnormal flexion/torsion of the body. Our evidence suggests that ethanol-induced alterations in early cardiac function have the potential to contribute to late-stage valve and septal defects, thus demonstrating that functional parameters may serve as early and sensitive gauges of cardiac normalcy and abnormalities.

  8. Thermo-mechanical simulations of early-age concrete cracking with durability predictions

    Science.gov (United States)

    Havlásek, Petr; Šmilauer, Vít; Hájková, Karolina; Baquerizo, Luis

    2017-09-01

    Concrete performance is strongly affected by mix design, thermal boundary conditions, its evolving mechanical properties, and internal/external restraints with consequences to possible cracking with impaired durability. Thermo-mechanical simulations are able to capture those relevant phenomena and boundary conditions for predicting temperature, strains, stresses or cracking in reinforced concrete structures. In this paper, we propose a weakly coupled thermo-mechanical model for early age concrete with an affinity-based hydration model for thermal part, taking into account concrete mix design, cement type and thermal boundary conditions. The mechanical part uses B3/B4 model for concrete creep and shrinkage with isotropic damage model for cracking, able to predict a crack width. All models have been implemented in an open-source OOFEM software package. Validations of thermo-mechanical simulations will be presented on several massive concrete structures, showing excellent temperature predictions. Likewise, strain validation demonstrates good predictions on a restrained reinforced concrete wall and concrete beam. Durability predictions stem from induction time of reinforcement corrosion, caused by carbonation and/or chloride ingress influenced by crack width. Reinforcement corrosion in concrete struts of a bridge will serve for validation.

  9. The Human Cytomegalovirus Major Immediate-Early Proteins as Antagonists of Intrinsic and Innate Antiviral Host Responses

    Directory of Open Access Journals (Sweden)

    Michael Nevels

    2009-11-01

    Full Text Available The major immediate-early (IE gene of human cytomegalovirus (CMV is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the 72-kDa IE1 and the 86-kDa IE2 nuclear phosphoproteins are the most abundant and important. Both proteins have long been recognized as promiscuous transcriptional regulators. More recently, a critical role of the IE1 and IE2 proteins in counteracting nonadaptive host cell defense mechanisms has been revealed. In this review we will briefly summarize the available literature on IE1- and IE2-dependent mechanisms contributing to CMV evasion from intrinsic and innate immune responses.

  10. Early developmental conditions affect stress response in juvenile but not in adult house sparrows (Passer domesticus).

    Science.gov (United States)

    Lendvai, Adám Z; Loiseau, Claire; Sorci, Gabriele; Chastel, Olivier

    2009-01-01

    The short- and long-term consequences of developmental conditions on fitness have received growing attention because the environmental conditions during early life may influence growth, condition at independence, recruitment, reproductive success or survival. We tested here, in a natural house sparrow population, if early conditions during nestling stage affected the stress response of the birds (i) shortly after fledging and (ii) next year, during their first breeding. We experimentally manipulated brood size to mimic different rearing conditions, creating reduced (-2 chicks) and enlarged broods (+2 chicks), while in a third group brood size was not manipulated. Nestling nutrition state decreased with post-manipulation brood sizes as indicated by lower body mass. Fledglings with higher body mass at the age of ten days showed lower stress response than birds that were leaner at the same age. Fledglings reared in large broods showed a higher response to stress protocol than chicks from small broods, and this effect was in significant interaction with the age of fledglings at capture. This interaction indicates that the effects of the brood size became gradually smaller as the fledglings grew older and were further from their nestling period. The effects of early conditions vanished by the next year: the stress response of adult first time breeders was unrelated to the brood size they fledged from. These results suggest that stress response may reflect the actual state of an individual, rather than its developmental history.

  11. Effect of Dietary Conjugated Linoleic Acid Supplementation on Early Inflammatory Responses during Cutaneous Wound Healing

    Directory of Open Access Journals (Sweden)

    Na-Young Park

    2010-01-01

    Full Text Available Inflammatory response is considered the most important period that regulates the entire healing process. Conjugated linoleic acid (CLA, a class of linoleic acid positional and geometric isomers, is well known for its antioxidant and anti-inflammatory properties. We hypothesized that dietary CLA supplementation accelerates cutaneous wound healing by regulating antioxidant and anti-inflammatory functions. To investigate wound closure rates and inflammatory responses, we used a full-thickness excisional wound model after 2-week treatments with control, 0.5%, or 1% CLA-supplemented diet. Mice fed dietary CLA supplementation had reduced levels of oxidative stress and inflammatory markers. Moreover, the wound closure rate was improved significantly in mice fed a 1% CLA-supplemented diet during early stage of wound healing (inflammatory stage. We conclude that dietary CLA supplementation enhances the early stage of cutaneous wound healing as a result of modulating oxidative stress and inflammatory responses.

  12. Early redox, Src family kinase, and calcium signaling integrate wound responses and tissue regeneration in zebrafish.

    Science.gov (United States)

    Yoo, Sa Kan; Freisinger, Christina M; LeBert, Danny C; Huttenlocher, Anna

    2012-10-15

    Tissue injury can lead to scar formation or tissue regeneration. How regenerative animals sense initial tissue injury and transform wound signals into regenerative growth is an unresolved question. Previously, we found that the Src family kinase (SFK) Lyn functions as a redox sensor in leukocytes that detects H(2)O(2) at wounds in zebrafish larvae. In this paper, using zebrafish larval tail fins as a model, we find that wounding rapidly activated SFK and calcium signaling in epithelia. The immediate SFK and calcium signaling in epithelia was important for late epimorphic regeneration of amputated fins. Wound-induced activation of SFKs in epithelia was dependent on injury-generated H(2)O(2). A SFK member, Fynb, was responsible for fin regeneration. This work provides a new link between early wound responses and late regeneration and suggests that redox, SFK, and calcium signaling are immediate "wound signals" that integrate early wound responses and late epimorphic regeneration.

  13. Cell wall pectic arabinans influence the mechanical properties of Arabidopsis thaliana inflorescence stems and their response to mechanical stress.

    Science.gov (United States)

    Verhertbruggen, Yves; Marcus, Susan E; Chen, Jianshe; Knox, J Paul

    2013-08-01

    Little is known of the dynamics of plant cell wall matrix polysaccharides in response to the impact of mechanical stress on plant organs. The capacity of the imposition of a mechanical stress (periodic brushing) to reduce the height of the inflorescence stem of Arabidopsis thaliana seedlings has been used to study the role of pectic arabinans in the mechanical properties and stress responsiveness of a plant organ. The arabinan-deficient-1 (arad1) mutation that affects arabinan structures in epidermal cell walls of inflorescence stems is demonstrated to reduce the impact on inflorescence stem heights caused by mechanical stress. The arabinan-deficient-2 (arad2) mutation, that does not have detectable impact on arabinan structures, is also shown to reduce the impact on stem heights caused by mechanical stress. The LM13 linear arabinan epitope is specifically detected in epidermal cell walls of the younger, flexible regions of inflorescence stems and increases in abundance at the base of inflorescence stems in response to an imposed mechanical stress. The strain (percentage deformation) of stem epidermal cells in the double mutant arad1 × arad2 is lower in unbrushed plants than in wild-type plants, but rises to wild-type levels in response to brushing. The study demonstrates the complexity of arabinan structures within plant cell walls and also that their contribution to cell wall mechanical properties is a factor influencing responsiveness to mechanical stress.

  14. Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag

    Directory of Open Access Journals (Sweden)

    Woods Matthew W

    2011-11-01

    Full Text Available Abstract Background The identification and characterization of several interferon (IFN-induced cellular HIV-1 restriction factors, defined as host cellular proteins or factors that restrict or inhibit the HIV-1 life cycle, have provided insight into the IFN response towards HIV-1 infection and identified new therapeutic targets for HIV-1 infection. To further characterize the mechanism underlying restriction of the late stages of HIV-1 replication, we assessed the ability of IFNbeta-induced genes to restrict HIV-1 Gag particle production and have identified a potentially novel host factor called HECT domain and RCC1-like domain-containing protein 5 (HERC5 that blocks a unique late stage of the HIV-1 life cycle. Results HERC5 inhibited the replication of HIV-1 over multiple rounds of infection and was found to target a late stage of HIV-1 particle production. The E3 ligase activity of HERC5 was required for blocking HIV-1 Gag particle production and correlated with the post-translational modification of Gag with ISG15. HERC5 interacted with HIV-1 Gag and did not alter trafficking of HIV-1 Gag to the plasma membrane. Electron microscopy revealed that the assembly of HIV-1 Gag particles was arrested at the plasma membrane, at an early stage of assembly. The mechanism of HERC5-induced restriction of HIV-1 particle production is distinct from the mechanism underlying HIV-1 restriction by the expression of ISG15 alone, which acts at a later step in particle release. Moreover, HERC5 restricted murine leukemia virus (MLV Gag particle production, showing that HERC5 is effective in restricting Gag particle production of an evolutionarily divergent retrovirus. Conclusions HERC5 represents a potential new host factor that blocks an early stage of retroviral Gag particle assembly. With no apparent HIV-1 protein that directly counteracts it, HERC5 may represent a new candidate for HIV/AIDS therapy.

  15. A note on the Pazos-Simonsen mechanism and Kaldor's early research on Latin American inflation

    Directory of Open Access Journals (Sweden)

    Leonardo Vera

    2013-06-01

    Full Text Available In contrast with the inflationary finance story, inflation acceleration in Latin America has been explained as the result of the interaction of inflation dynamics and the frequency of wage adjustments. Accordingly, small inflation disturbances are connected with a shift from moderate to high inflation (or beyond to hyperinflation though a mechanism that makes adjustment intervals in wage contracts endogenous. Rudiger Dornbusch (1986 labeled this process the "Pazos-Simonsen mechanism". In this note we summarize the basic contribution of both Felipe Pazos (1978 and Mario Henrique Simonsen (1983 and find crucial differences between their views on wage dynamics, specifically regarding the endogeneity of the time interval between wage readjustments. A remarkable affinity with Pazos's view on wage dynamics and inflation is found in an early and almost unknown essay written by Nicholas Kaldor in 1957 (inspired in his brief experience in Latin America.

  16. Early mechanical dysfunction of the diaphragm in the muscular dystrophy with myositis (Ttnmdm) model.

    Science.gov (United States)

    Lopez, Michael A; Pardo, Patricia S; Cox, Gregory A; Boriek, Aladin M

    2008-11-01

    A complex rearrangement mutation in the mouse titin gene leads to an in-frame 83-amino acid deletion in the N2A region of titin. Autosomal recessive inheritance of the titin muscular dystrophy with myositis (Ttn(mdm/mdm)) mutation leads to a severe early-onset muscular dystrophy and premature death. We hypothesized that the N2A deletion would negatively impact the force-generating capacity and passive mechanical properties of the mdm diaphragm. We measured in vitro active isometric contractile and passive length-tension properties to assess muscle function at 2 and 6 wk of age. Micro-CT, myosin heavy chain Western blotting, and histology were used to assess diaphragm structure. Marked chest wall distortions began at 2 wk and progressively worsened until 5 wk. The percentage of myofibers with centrally located nuclei in mdm mice was significantly (P mechanical aberrations of the respiratory pump in mdm mice.

  17. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    Science.gov (United States)

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (Ppreeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. © 2015 American Heart Association, Inc.

  18. Analysis of the early adaptive response of endothelial cells to hypoxia via a long serial analysis of gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Guang-Ping; Su, Yong-Yue; Chen, Jian; Yang, Zong-Cheng [State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Liu, You-Sheng [Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Luo, Xiang-Dong, E-mail: luoxd2005@163.com [State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

    2009-07-10

    Activation of endothelial cells in humans is an early event in the response to hypoxia that may contribute to the endothelium's endogenous capacity to reduce tissue injury. To better understand the mechanism underlying this process, we utilized Long Serial Analysis of Gene Expression to study the transcriptome of human vein umbilical endothelial cells (EA.hy926) shortly after the induction of hypoxia. Of over 13,000 genes detected in each pool, 112 showed obvious differences in expression. Metabolic processes such as protein biosynthesis and proteolysis, aminoglycan metabolism, ribonucleotide biosynthesis, adenosine salvage, and lipid metabolism were reinforced. Pro-proliferation and pro-apoptotic states suggest the co-existence of pro- and anti-injury forces in endothelium shortly after the induction of hypoxia. Other adaptive responses include reinforced angiogenesis and vasodilation. Additionally, gene transcription in the endothelium shortly after the induction of hypoxia was regulated independently of HIF-1{alpha}. Our efforts to elucidate the adaptive response at an early post-hypoxia stage should contribute to further investigation of the protective processes that occur in the endothelium and has potential clinical implications.

  19. Atmospheric sulphuric acid and aerosol formation: implications from atmospheric measurements for nucleation and early growth mechanisms

    Directory of Open Access Journals (Sweden)

    S.-L. Sihto

    2006-01-01

    Full Text Available We have investigated the formation and early growth of atmospheric secondary aerosol particles building on atmospheric measurements. The measurements were part of the QUEST 2 campaign which took place in spring 2003 in Hyytiälä (Finland. During the campaign numerous aerosol particle formation events occurred of which 15 were accompanied by gaseous sulphuric acid measurements. Our detailed analysis of these 15 events is focussed on nucleation and early growth (to a diameter of 3 nm of fresh particles. It revealed that new particle formation seems to be a function of the gaseous sulphuric acid concentration to the power from one to two when the time delay between the sulphuric acid and particle number concentration is taken into account. From the time delay the growth rates of freshly nucleated particles from 1 nm to 3 nm were determined. The mean growth rate was 1.2 nm/h and it was clearly correlated with the gaseous sulphuric acid concentration. We tested two nucleation mechanisms – recently proposed cluster activation and kinetic type nucleation – as possible candidates to explain the observed dependences, and determined experimental nucleation coefficients. We found that some events are dominated by the activation mechanism and some by the kinetic mechanism. Inferred coefficients for the two nucleation mechanisms are the same order of magnitude as chemical reaction coefficients in the gas phase and they correlate with the product of gaseous sulphuric acid and ammonia concentrations. This indicates that besides gaseous sulphuric acid also ammonia has a role in nucleation.

  20. EFFECTS OF MIFEPRISTONE ON THE MECHANICAL AND ELECTRICAL ACTIVITY OF RABBIT UTERUS IN VIVO DURING EARLY-PREGNANCY

    Institute of Scientific and Technical Information of China (English)

    JIANGChang-Song; ZHOUYou-You; XIONGCheng-Liang; WUXi-Rui

    1989-01-01

    The aim of this study is to examine the effect of mifepristone on the mechanical and elec trical activitles of uterus and the sensitivity of myometrium to 15-methyl-PGF2a in early-pregnant rabbits. The effect of termination of early-pregnancy was also observed.

  1. Dual Mechanism Nonlinear Response of Selected Metal Organic Chromophores

    Science.gov (United States)

    2007-10-01

    hyperpolarizability was observed with the increase in bond length alternation (BLA) in polyenes having alternating double and single bonds which aided in...chain polyenes for which a two-level approximation model was deemed not to be valid. Further study in the early 1990’s by McWilliams and Soos 47

  2. Dynamic compressive mechanical response of a soft polymer material

    NARCIS (Netherlands)

    Fan, J.T.; Weerheijm, J.; Sluys, L.J.

    2015-01-01

    The dynamic mechanical behaviour of a soft polymer material (Clear Flex 75) was studied using a split Hopkinson pressure bar (SHPB) apparatus. Mechanical properties have been determined at moderate to high strain rates. Real time deformation and fracture were recorded using a high-speed camera. Frac

  3. Implementation of an Alert and Response System in Haiti during the Early Stage of the Response to the Cholera Epidemic

    Science.gov (United States)

    Santa-Olalla, Patricia; Gayer, Michelle; Magloire, Roc; Barrais, Robert; Valenciano, Marta; Aramburu, Carmen; Poncelet, Jean Luc; Gustavo Alonso, Juan Carlos; Van Alphen, Dana; Heuschen, Florence; Andraghetti, Roberta; Lee, Robert; Drury, Patrick; Aldighieri, Sylvain

    2013-01-01

    The start of the cholera epidemic in Haiti quickly highlighted the necessity of the implementation of an Alert and Response (A&R) System to complement the existing national surveillance system. The national system had been able to detect and confirm the outbreak etiology but required external support to monitor the spread of cholera and coordinate response, because much of the information produced was insufficiently timely for real-time monitoring and directing of a rapid, targeted response. The A&R System was designed by the Pan American Health Organization/World Health Organization in collaboration with the Haiti Ministry of Health, and it was based on a network of partners, including any institution, structure, or individual that could identify, verify, and respond to alerts. The defined objectives were to (1) save lives through early detection and treatment of cases and (2) control the spread through early intervention at the community level. The operational structure could be broken down into three principle categories: (1) alert (early warning), (2) verification and assessment of the information, and (3) efficient and timely response in coordination with partners to avoid duplication. Information generated by the A&R System was analyzed and interpreted, and the qualitative information was critical in qualifying the epidemic and defining vulnerable areas, particularly because the national surveillance system reported incomplete data for more than one department. The A&R System detected a number of alerts unrelated to cholera and facilitated rapid access to that information. The sensitivity of the system and its ability to react quickly was shown in May of 2011, when an abnormal increase in alerts coming from several communes in the Sud-Est Department in epidemiological weeks (EWs) 17 and 18 were noted and disseminated network-wide and response activities were implemented. The national cholera surveillance system did not register the increase until EWs 21 and

  4. Implementation of an alert and response system in Haiti during the early stage of the response to the cholera epidemic.

    Science.gov (United States)

    Santa-Olalla, Patricia; Gayer, Michelle; Magloire, Roc; Barrais, Robert; Valenciano, Marta; Aramburu, Carmen; Poncelet, Jean Luc; Gustavo Alonso, Juan Carlos; Van Alphen, Dana; Heuschen, Florence; Andraghetti, Roberta; Lee, Robert; Drury, Patrick; Aldighieri, Sylvain

    2013-10-01

    The start of the cholera epidemic in Haiti quickly highlighted the necessity of the implementation of an Alert and Response (A&R) System to complement the existing national surveillance system. The national system had been able to detect and confirm the outbreak etiology but required external support to monitor the spread of cholera and coordinate response, because much of the information produced was insufficiently timely for real-time monitoring and directing of a rapid, targeted response. The A&R System was designed by the Pan American Health Organization/World Health Organization in collaboration with the Haiti Ministry of Health, and it was based on a network of partners, including any institution, structure, or individual that could identify, verify, and respond to alerts. The defined objectives were to (1) save lives through early detection and treatment of cases and (2) control the spread through early intervention at the community level. The operational structure could be broken down into three principle categories: (1) alert (early warning), (2) verification and assessment of the information, and (3) efficient and timely response in coordination with partners to avoid duplication. Information generated by the A&R System was analyzed and interpreted, and the qualitative information was critical in qualifying the epidemic and defining vulnerable areas, particularly because the national surveillance system reported incomplete data for more than one department. The A&R System detected a number of alerts unrelated to cholera and facilitated rapid access to that information. The sensitivity of the system and its ability to react quickly was shown in May of 2011, when an abnormal increase in alerts coming from several communes in the Sud-Est Department in epidemiological weeks (EWs) 17 and 18 were noted and disseminated network-wide and response activities were implemented. The national cholera surveillance system did not register the increase until EWs 21 and

  5. Girls’ challenging social experiences in early adolescence predict neural response to rewards and depressive symptoms

    Directory of Open Access Journals (Sweden)

    Melynda D. Casement

    2014-04-01

    Full Text Available Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC, striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence.

  6. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

    Science.gov (United States)

    Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

    2017-06-07

    Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

  7. Co-localization hypothesis: A mechanism for the intrapancreatic activation of digestive enzymes during the early phases of acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Gijs JD van Acker; George Perides; Michael L Steer

    2006-01-01

    Acute pancreatitis is generally believed to be a disease in which the pancreas is injured by digestive enzymes that it normally produces. Most of the potentially harmful digestive enzymes produced by pancreatic acinar cells are synthesized and secreted as inactive zymogens which are normally activated only upon entry into the duodenum but, during the early stages of acute pancreatitis, those zymogens become prematurely activated within the pancreas and, presumably, that activation occurs within pancreatic acinar cells. The mechanisms responsible for intracellular activation of digestive enzyme zymogens have not been elucidated with certainty but, according to one widely recognized theory (the "co-localization hypothesis"), digestive enzyme zymogens are activated by lysosomal hydrolases when the two types of enzymes become co-localized within the same intracellular compartment. This review focuses on the evidence supporting the validity of the co-localization hypothesis as an explanation for digestive enzyme activation during the early stages of pancreatitis.The findings, summarized in this review, support the conclusion that co-localization of lysosomal hydrolases with digestive enzyme zymogens plays a critical role in permitting the intracellular activation of digestive enzymesthat leads to acinar cell injury and pancreatitis.

  8. A New Mechanism to Curb Over-reactive Immune Responses

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ The human immune system is a truly amazing constellation of responses to attacks from the outside. It could defend you against millions of bacteria, microbes, viruses, toxins and parasites that would invade your body. However, there are cases where the immune response to innocuous substances is inappropriate and over-reactive, leading to diseases such as allergies and arthritis.

  9. Emotional responses to music: the need to consider underlying mechanisms.

    Science.gov (United States)

    Juslin, Patrik N; Västfjäll, Daniel

    2008-10-01

    Research indicates that people value music primarily because of the emotions it evokes. Yet, the notion of musical emotions remains controversial, and researchers have so far been unable to offer a satisfactory account of such emotions. We argue that the study of musical emotions has suffered from a neglect of underlying mechanisms. Specifically, researchers have studied musical emotions without regard to how they were evoked, or have assumed that the emotions must be based on the "default" mechanism for emotion induction, a cognitive appraisal. Here, we present a novel theoretical framework featuring six additional mechanisms through which music listening may induce emotions: (1) brain stem reflexes, (2) evaluative conditioning, (3) emotional contagion, (4) visual imagery, (5) episodic memory, and (6) musical expectancy. We propose that these mechanisms differ regarding such characteristics as their information focus, ontogenetic development, key brain regions, cultural impact, induction speed, degree of volitional influence, modularity, and dependence on musical structure. By synthesizing theory and findings from different domains, we are able to provide the first set of hypotheses that can help researchers to distinguish among the mechanisms. We show that failure to control for the underlying mechanism may lead to inconsistent or non-interpretable findings. Thus, we argue that the new framework may guide future research and help to resolve previous disagreements in the field. We conclude that music evokes emotions through mechanisms that are not unique to music, and that the study of musical emotions could benefit the emotion field as a whole by providing novel paradigms for emotion induction.

  10. Mechanical response of collagen molecule under hydrostatic compression

    Energy Technology Data Exchange (ETDEWEB)

    Saini, Karanvir, E-mail: karans@iitrpr.ac.in; Kumar, Navin

    2015-04-01

    Proteins like collagen are the basic building blocks of various body tissues (soft and hard). Collagen molecules find their presence in the skeletal system of the body where they bear mechanical loads from different directions, either individually or along with hydroxy-apatite crystals. Therefore, it is very important to understand the mechanical behavior of the collagen molecule which is subjected to multi-axial state of loading. The estimation of strains of collagen molecule along different directions resulting from the changes in hydrostatic pressure magnitude, can provide us new insights into its mechanical behavior. In the present work, full atomistic simulations have been used to study global (volumetric) as well as local (along different directions) mechanical properties of the hydrated collagen molecule which is subjected to different hydrostatic pressure magnitudes. To estimate the local mechanical properties, the strains of collagen molecule along its longitudinal and transverse directions have been acquired at different hydrostatic pressure magnitudes. In spite of non-homogeneous distribution of atoms within the collagen molecule, the calculated values of local mechanical properties have been found to carry the same order of magnitude along the longitudinal and transverse directions. It has been demonstrated that the values of global mechanical properties like compressibility, bulk modulus, etc. as well as local mechanical properties like linear compressibility, linear elastic modulus, etc. are functions of magnitudes of applied hydrostatic pressures. The mechanical characteristics of collagen molecule based on the atomistic model have also been compared with that of the continuum model in the present work. The comparison showed up orthotropic material behavior for the collagen molecule. The information on collagen molecule provided in the present study can be very helpful in designing the future bio-materials.

  11. Mechanisms Underlying the Antidepressant Response of Acupuncture via PKA/CREB Signaling Pathway

    National Research Council Canada - National Science Library

    Huili Jiang; Xuhui Zhang; Yu Wang; Huimin Zhang; Jing Li; Xinjing Yang; Bingcong Zhao; Chuntao Zhang; Miao Yu; Mingmin Xu; Qiuyun Yu; Xingchen Liang; Xiang Li; Peng Shi; Tuya Bao

    2017-01-01

    .... The objective was to identify the mechanisms underlying the antidepressant response of acupuncture through PKA signaling pathway in depression rats by employing the PKA signaling pathway inhibitor...

  12. Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses.

    Science.gov (United States)

    Sjögren, Y M; Tomicic, S; Lundberg, A; Böttcher, M F; Björkstén, B; Sverremark-Ekström, E; Jenmalm, M C

    2009-12-01

    Among sensitized infants, those with high, as compared with low levels, of salivary secretory IgA (SIgA) are less likely to develop allergic symptoms. Also, early colonization with certain gut microbiota, e.g. Lactobacilli and Bifidobacterium species, might be associated with less allergy development. Although animal and in vitro studies emphasize the role of the commensal gut microbiota in the development of the immune system, the influence of the gut microbiota on immune development in infants is unclear. To assess whether early colonization with certain gut microbiota species associates with mucosal and systemic immune responses i.e. salivary SIgA and the spontaneous Toll-like receptor (TLR) 2 and TLR4 mRNA expression and lipopolysaccharide (LPS)-induced cytokine/chemokine responses in peripheral blood mononuclear cells (PBMCs). Fecal samples were collected at 1 week, 1 month and 2 months after birth from 64 Swedish infants, followed prospectively up to 5 years of age. Bacterial DNA was analysed with real-time PCR using primers binding to Clostridium difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis. Saliva was collected at age 6 and 12 months and at 2 and 5 years and SIgA was measured with ELISA. The PBMCs, collected 12 months after birth, were analysed for TLR2 and TLR4 mRNA expression with real-time PCR. Further, the PBMCs were stimulated with LPS, and cytokine/chemokine responses were measured with Luminex. The number of Bifidobacterium species in the early fecal samples correlated significantly with the total levels of salivary SIgA at 6 months. Early colonization with Bifidobacterium species, lactobacilli groups or C. difficile did not influence TLR2 and TLR4 expression in PBMCs. However, PBMCs from infants colonized early with high amounts of Bacteroides fragilis expressed lower levels of TLR4 mRNA spontaneously. Furthermore, LPS-induced production of inflammatory cytokines and chemokines, e.g. IL-6 and CCL4 (MIP

  13. Multimodality multiparametric imaging of early tumor response to a novel antiangiogenic therapy based on anticalins.

    Directory of Open Access Journals (Sweden)

    Reinhard Meier

    Full Text Available Anticalins are a novel class of targeted protein therapeutics. The PEGylated Anticalin Angiocal (PRS-050-PEG40 is directed against VEGF-A. The purpose of our study was to compare the performance of diffusion weighted imaging (DWI, dynamic contrast enhanced magnetic resonance imaging (DCE-MRI and positron emission tomography with the tracer [18F]fluorodeoxyglucose (FDG-PET for monitoring early response to antiangiogenic therapy with PRS-050-PEG40. 31 mice were implanted subcutaneously with A673 rhabdomyosarcoma xenografts and underwent DWI, DCE-MRI and FDG-PET before and 2 days after i.p. injection of PRS-050-PEG40 (n = 13, Avastin (n = 6 or PBS (n = 12. Tumor size was measured manually with a caliper. Imaging results were correlated with histopathology. In the results, the tumor size was not significantly different in the treatment groups when compared to the control group on day 2 after therapy onset (P = 0.09. In contrast the imaging modalities DWI, DCE-MRI and FDG-PET showed significant differences between the therapeutic compared to the control group as early as 2 days after therapy onset (P<0.001. There was a strong correlation of the early changes in DWI, DCE-MRI and FDG-PET at day 2 after therapy onset and the change in tumor size at the end of therapy (r = -0.58, 0.71 and 0.67 respectively. The imaging results were confirmed by histopathology, showing early necrosis and necroptosis in the tumors. Thus multimodality multiparametric imaging was able to predict therapeutic success of PRS-050-PEG40 and Avastin as early as 2 days after onset of therapy and thus promising for monitoring early response of antiangiogenic therapy.

  14. Mechanical and rheological response of polypropylene/boehmite nanocomposites

    CSIR Research Space (South Africa)

    Pedrazzoli, D

    2014-01-01

    Full Text Available of Mechanical Engineering, Department of Polymer Engineering, 1111 Budapest (Hungary) (c) Polymers and Composites, Materials Science and Manufacturing, Council for Scientific and Industrial Research, CSIR, P.O. Box 395, Pretoria 0001, South Africa d) MTA...

  15. Studying the mechanical responses of proteins using magnetic tweezers

    Science.gov (United States)

    Zhao, Xiaodan; Zeng, Xiangjun; Lu, Chen; Yan, Jie

    2017-10-01

    The mechanical stability of proteins has been extensively studied using AFM as a single-molecule force spectroscopy method. While this has led to many important results, these studies have been mainly limited to fast unfolding at a high-force regime due to the rapid mechanical drift in most AFM stretching experiments. Therefore, there is a gap between the knowledge obtained at a high-force regime and the mechanical properties of proteins at a lower force regime which is often more physiologically relevant. Recent studies have demonstrated that this gap can be addressed by stretching single protein molecules using magnetic tweezers, due to the excellent mechanical stability this technology offers. Here we review magnetic tweezers technology and its current application in studies of the force-dependent stability and interactions of proteins.

  16. Directionally Solidified Biopolymer Scaffolds: Mechanical Properties and Endothelial Cell Responses

    OpenAIRE

    Meghri, Nichols W.; Donius, Amalie E.; Riblett, Benjamin W.; Martin, Elizabeth J.; Clyne, Alisa Morss; Wegst, Ulrike G.K.

    2010-01-01

    Vascularization is a primary challenge in tissue engineering. To achieve it in a tissue scaffold, an environment with the appropriate structural, mechanical, and biochemical cues must be provided enabling endothelial cells to direct blood vessel growth. While biochemical stimuli such as growth factors can be added through the scaffold material, the culture medium, or both, a well-designed tissue engineering scaffold is required to provide the necessary local structural and mechanical cues. As...

  17. Loss of vascular early response gene reduces edema formation after experimental stroke

    Directory of Open Access Journals (Sweden)

    Liu Fudong

    2012-06-01

    Full Text Available Abstract Vascular Early Response Gene (Verge is an immediate early gene (IEG that is up-regulated in endothelial cells in response to a number of stressors, including ischemic stroke. Endothelial cell lines that stably express Verge show enhanced permeability. Increased Verge expression has also been associated with blood brain barrier breakdown. In this study we investigated the role of Verge in ischemic injury induced by middle cerebral artery occlusion (MCAO in both Verge knockout (KO and wild type (WT mice. Verge KO mice had significantly less cerebral edema formation after MCAO compared to WT mice. However, stroke outcome (infarct size and neurological deficit scores evaluated at either 24 or 72 hours after stroke showed no differences between the two genotypes. Verge deletion leads to decreased edema formation after ischemia; however acute stroke outcomes were unchanged.

  18. Total physical response in an early education setting : connecting literacy, movements, and families

    OpenAIRE

    Farrow, Karin Rae

    2008-01-01

    This paper documents the research and application of a new curriculum for Deaf students incorporating the theory of Asher: Total Physical Response. In the area of early education of Deaf students attempts need to be made to enhance and encourage the acquisition of American Sign Language and English. To aid in the young child's acquisition this new curriculum utilizes a method incorporating generalized movements. The addition of kinesthetic movements gives greater meaning to the new vocabulary...

  19. In vivo chemical exchange saturation transfer imaging allows early detection of a therapeutic response in glioblastoma.

    Science.gov (United States)

    Sagiyama, Koji; Mashimo, Tomoyuki; Togao, Osamu; Vemireddy, Vamsidhara; Hatanpaa, Kimmo J; Maher, Elizabeth A; Mickey, Bruce E; Pan, Edward; Sherry, A Dean; Bachoo, Robert M; Takahashi, Masaya

    2014-03-25

    Glioblastoma multiforme (GBM), which account for more than 50% of all gliomas, is among the deadliest of all human cancers. Given the dismal prognosis of GBM, it would be advantageous to identify early biomarkers of a response to therapy to avoid continuing ineffective treatments and to initiate other therapeutic strategies. The present in vivo longitudinal study in an orthotopic mouse model demonstrates quantitative assessment of early treatment response during short-term chemotherapy with temozolomide (TMZ) by amide proton transfer (APT) imaging. In a GBM line, only one course of TMZ (3 d exposure and 4 d rest) at a dose of 80 mg/kg resulted in substantial reduction in APT signal compared with untreated control animals, in which the APT signal continued to increase. Although there were no detectable differences in tumor volume, cell density, or apoptosis rate between groups, levels of Ki67 (index of cell proliferation) were substantially reduced in treated tumors. In another TMZ-resistant GBM line, the APT signal and levels of Ki67 increased despite the same course of TMZ treatment. As metabolite changes are known to occur early in the time course of chemotherapy and precede morphologic changes, these results suggest that the APT signal in glioma may be a useful functional biomarker of treatment response or degree of tumor progression. Thus, APT imaging may serve as a sensitive biomarker of early treatment response and could potentially replace invasive biopsies to provide a definitive diagnosis. This would have a major impact on the clinical management of patients with glioma.

  20. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

    2014-01-01

    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CONCLUSION: CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia....

  1. Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

    Science.gov (United States)

    Chen, Chen-Wen; Chen, Qian-Bo; Ouyang, Qing; Sun, Ji-Hu; Liu, Fang-Ting; Song, Dian-Wen; Yuan, Hong-Bin

    2012-06-25

    Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

  2. Perspective: Identification of genetic variants associated with dopaminergic compensatory mechanisms in early Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Lior eGreenbaum

    2013-04-01

    Full Text Available Parkinson's disease (PD is slowly progressive, and heterogeneity of its severity among individuals may be due to endogenous mechanisms that counterbalance the striatal dopamine loss. In this perspective paper, we introduce a neuroimaging-genetic approach to identify genetic variants, which may contribute to this compensation. First, we briefly review current known potential compensatory mechanisms for premotor and early disease PD, located in the striatum and other brain regions. Then, we claim that a mismatch between mild symptomatic disease, manifested by low motor score on the Unified PD Rating Scale (UPDRS and extensive Nigro-Striatal degeneration, manifested by reduced uptake of [123I]FP-CIT is indicative of compensatory processes. If genetic variants are associated with the severity of motor symptoms, while the level of striatal terminals degeneration measured by ligand uptake is taken into account and controlled in the analysis, then these variants may be involved in functional compensatory mechanisms for striatal dopamine deficit. To demonstrate feasibility of this approach, we performed a small "proof of concept" study (candidate gene design in a sample of 28 Jewish PD patients, and preliminary results are presented.

  3. Depressive symptoms and immune response to meningococcal conjugate vaccine in early adolescence.

    Science.gov (United States)

    O'Connor, Thomas G; Moynihan, Jan A; Wyman, Peter A; Carnahan, Jennifer; Lofthus, Gerry; Quataert, Sally A; Bowman, Melissa; Caserta, Mary T

    2014-11-01

    Research findings in psychoneuroimmunology document reliable, bidirectional linkages among psychological processes, the nervous system, and the immune system. However, available data are based almost entirely on animal and adult human studies; the application to children and adolescents is uncertain. We capitalized on the experimental leverage provided by a routine vaccination to examine the link between mood symptoms and the immune response to a vaccine challenge in early adolescence. One hundred twenty-six 11-year-olds for whom vaccine response data were available were assessed at prevaccination and 4 weeks, 3 months, and 6 months following vaccination; self-report ratings of depression and anxiety as well as measures of psychosocial and somatic risk were assessed prior to vaccine response. Analyses indicated that children's internalizing mood symptoms were associated with elevated and persistently higher antibody responses, with evidence extending to two of the four serogroups. The associations remained after controlling for multiple possible confounders (social class, body mass index, sleep, psychosocial risk, and pubertal status). The observed enhanced vaccine response associated with depressive and anxious symptoms in early adolescence may reflect an important developmental difference in immune system-brain interplay between adults and children, and it underscores the need for further developmental studies of psychoneuroimmunology.

  4. Early Eocene cyclicity at the Wilkes Land Margin, Antarctica: Orbital forcing and environmental response

    Science.gov (United States)

    Roehl, U.; Bijl, P.; Jiménez, F.; Pross, J.; Contreras, L.; Tauxe, L.; Bohaty, S. M.; Bendle, J.; Brinkhuis, H.; IODP Expedition 318 Scientists

    2011-12-01

    The early Eocene Greenhouse interval (~56-49 Ma) was punctuated by multiple transient global warming events, or hyperthermals - the most prominent of which was the Paleocene-Eocene Thermal Maximum (PETM). Additional thermal maxima identified in Eocene records exhibit negative carbon isotope excursions (CIEs), carbonate dissolution horizons, and biotic perturbations, although of reduced magnitude and duration relative to the PETM. Many hyperthermals have been identified or postulated in the early Eocene, but it is unclear which of these events are normal carbon-cycle variations that occurred at orbital frequencies and which are exceptional events outside the normal range of Eocene carbon-cycle variability. Here we present a high-resolution cyclostratigraphy for a new early Eocene drillcore from the Wilkes Land Margin in direct proximity to the Antarctic continent (Site U1356 drilled during IODP Expedition 318). Site U1356 was situated in a mid-shelf setting during the early Eocene and is characterized by a superb magnetostratigraphy and a robust biostratigraphic age control. Our investigation includes XRF core scanning and ICP-MS data as well as bulk organic carbon isotope ratios (delta13Corg) in combination with the concentration of the total organic carbon (TOC). The early Eocene at Site U1356 consists of well developed cyclic claystones including the interval of magnetochron C24 which is ideal to re-evaluate the early Eocene part of the Geomagnetic Polarity Time Scale (GPTS) and to provide new insights into the environmental responses as well as orbital configuration of early Eocene climatic cycles.

  5. Neuronal Atrophy Early in Degenerative Ataxia Is a Compensatory Mechanism to Regulate Membrane Excitability.

    Science.gov (United States)

    Dell'Orco, James M; Wasserman, Aaron H; Chopra, Ravi; Ingram, Melissa A C; Hu, Yuan-Shih; Singh, Vikrant; Wulff, Heike; Opal, Puneet; Orr, Harry T; Shakkottai, Vikram G

    2015-08-12

    Neuronal atrophy in neurodegenerative diseases is commonly viewed as an early event in a continuum that ultimately results in neuronal loss. In a mouse model of the polyglutamine disorder spinocerebellar ataxia type 1 (SCA1), we tested the hypothesis that cerebellar Purkinje neuron atrophy serves an adaptive role rather than being simply a nonspecific response to injury. In acute cerebellar slices from SCA1 mice, we find that Purkinje neuron pacemaker firing is initially normal but, with the onset of motor dysfunction, becomes disrupted, accompanied by abnormal depolarization. Remarkably, subsequent Purkinje cell atrophy is associated with a restoration of pacemaker firing. The early inability of Purkinje neurons to support repetitive spiking is due to unopposed calcium currents resulting from a reduction in large-conductance calcium-activated potassium (BK) and subthreshold-activated potassium channels. The subsequent restoration of SCA1 Purkinje neuron firing correlates with the recovery of the density of these potassium channels that accompanies cell atrophy. Supporting a critical role for BK channels, viral-mediated increases in BK channel expression in SCA1 Purkinje neurons improves motor dysfunction and partially restores Purkinje neuron morphology. Cerebellar perfusion of flufenamic acid, an agent that restores the depolarized membrane potential of SCA1 Purkinje neurons by activating potassium channels, prevents Purkinje neuron dendritic atrophy. These results suggest that Purkinje neuron dendritic remodeling in ataxia is an adaptive response to increases in intrinsic membrane excitability. Similar adaptive remodeling could apply to other vulnerable neuronal populations in neurodegenerative disease. In neurodegenerative disease, neuronal atrophy has long been assumed to be an early nonspecific event preceding neuronal loss. However, in a mouse model of spinocerebellar ataxia type 1 (SCA1), we identify a previously unappreciated compensatory role for neuronal

  6. 3D computational mechanics elucidate the evolutionary implications of orbit position and size diversity of early amphibians.

    Science.gov (United States)

    Marcé-Nogué, Jordi; Fortuny, Josep; De Esteban-Trivigno, Soledad; Sánchez, Montserrat; Gil, Lluís; Galobart, Àngel

    2015-01-01

    For the first time in vertebrate palaeontology, the potential of joining Finite Element Analysis (FEA) and Parametrical Analysis (PA) is used to shed new light on two different cranial parameters from the orbits to evaluate their biomechanical role and evolutionary patterns. The early tetrapod group of Stereospondyls, one of the largest groups of Temnospondyls is used as a case study because its orbits position and size vary hugely within the members of this group. An adult skull of Edingerella madagascariensis was analysed using two different cases of boundary and loading conditions in order to quantify stress and deformation response under a bilateral bite and during skull raising. Firstly, the variation of the original geometry of its orbits was introduced in the models producing new FEA results, allowing the exploration of the ecomorphology, feeding strategy and evolutionary patterns of these top predators. Secondly, the quantitative results were analysed in order to check if the orbit size and position were correlated with different stress patterns. These results revealed that in most of the cases the stress distribution is not affected by changes in the size and position of the orbit. This finding supports the high mechanical plasticity of this group during the Triassic period. The absence of mechanical constraints regarding the orbit probably promoted the ecomorphological diversity acknowledged for this group, as well as its ecological niche differentiation in the terrestrial Triassic ecosystems in clades as lydekkerinids, trematosaurs, capitosaurs or metoposaurs.

  7. The Early Development of Human Mirror Mechanisms: Evidence from Electromyographic Recordings at 3 and 6 Months

    Science.gov (United States)

    Turati, Chiara; Natale, Elena; Bolognini, Nadia; Senna, Irene; Picozzi, Marta; Longhi, Elena; Cassia, Viola Macchi

    2013-01-01

    In primates and adult humans direct understanding of others' action is provided by mirror mechanisms matching action observation and action execution (e.g. Casile, Caggiano & Ferrari, 2011). Despite the growing body of evidence detailing the existence of these mechanisms in the adult human brain, their origins and early development are…

  8. A review of UHMWPE wear-induced osteolysis: the role for early detection of the immune response.

    Science.gov (United States)

    Kandahari, Adrese M; Yang, Xinlin; Laroche, Kevin A; Dighe, Abhijit S; Pan, Dongfeng; Cui, Quanjun

    2016-01-01

    In a world where increasing joint arthroplasties are being performed on increasingly younger patients, osteolysis as the leading cause of failure after total joint arthroplasty (TJA) has gained considerable attention. Ultra-high molecular weight polyethylene wear-induced osteolysis is the process by which prosthetic debris mechanically released from the surface of prosthetic joints induces an immune response that favors bone catabolism, resulting in loosening of prostheses with eventual failure or fracture. The immune response initiated is innate in that it is nonspecific and self-propagating, with monocytic cells and osteoclasts being the main effectors. To date, detecting disease early enough to implement effective intervention without unwanted systemic side effects has been a major barrier. These barriers can be overcome using newer in vivo imaging techniques and modules linked with fluorescence and/or chemotherapies. We discuss the pathogenesis of osteolysis, and provide discussion of the challenges with imaging and therapeutics. We describe a positron emission tomography imaging cinnamoyl-Phe-(D)-Leu-Phe-(D)-Leu-Phe-Lys module, specific to macrophages, which holds promise in early detection of disease and localization of treatment. Further research and increased collaboration among therapeutic and three-dimensional imaging researchers are essential in realizing a solution to clinical osteolysis in TJA.

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

    Science.gov (United States)

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

    2012-09-01

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

  10. Features of structural response of mechanically loaded crystallites to irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Korchuganov, Aleksandr V., E-mail: avkor@ispms.ru [Institute of Strength Physics and Materials Science SB RAS, Tomsk, 634055 (Russian Federation); National Research Tomsk State University, Tomsk, 634050 (Russian Federation)

    2015-10-27

    A molecular dynamics method is employed to investigate the origin and evolution of plastic deformation in elastically deformed iron and vanadium crystallites due to atomic displacement cascades. Elastic stress states of crystallites result from different degrees of specimen deformation. Crystallites are deformed under constant-volume conditions. Atomic displacement cascades with the primary knock-on atom energy up to 50 keV are generated in loaded specimens. It is shown that irradiation may cause not only the Frenkel pair formation but also large-scale structural rearrangements outside the irradiated area, which prove to be similar to rearrangements proceeding by the twinning mechanism in mechanically loaded specimens.

  11. Expression of putative immune response genes during early ontogeny in the coral Acropora millepora.

    Directory of Open Access Journals (Sweden)

    Eneour Puill-Stephan

    Full Text Available BACKGROUND: Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals. METHODOLOGY/PRINCIPAL FINDINGS: Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR. Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A. millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria during winnowing processes as symbioses are fine-tuned. CONCLUSIONS/SIGNIFICANCE: Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies

  12. The crucial effect of early-stage gelation on the mechanical properties of cement hydrates

    Science.gov (United States)

    Ioannidou, Katerina; Kanduč, Matej; Li, Lunna; Frenkel, Daan; Dobnikar, Jure; Del Gado, Emanuela

    2016-07-01

    Gelation and densification of calcium-silicate-hydrate take place during cement hydration. Both processes are crucial for the development of cement strength, and for the long-term evolution of concrete structures. However, the physicochemical environment evolves during cement formation, making it difficult to disentangle what factors are crucial for the mechanical properties. Here we use Monte Carlo and Molecular Dynamics simulations to study a coarse-grained model of cement formation, and investigate the equilibrium and arrested states. We can correlate the various structures with the time evolution of the interactions between the nano-hydrates during the preparation of cement. The novel emerging picture is that the changes of the physicochemical environment, which dictate the evolution of the effective interactions, specifically favour the early gel formation and its continuous densification. Our observations help us understand how cement attains its unique strength and may help in the rational design of the properties of cement and related materials.

  13. A cell-based computational model of early embryogenesis coupling mechanical behaviour and gene regulation.

    Science.gov (United States)

    Delile, Julien; Herrmann, Matthieu; Peyriéras, Nadine; Doursat, René

    2017-01-23

    The study of multicellular development is grounded in two complementary domains: cell biomechanics, which examines how physical forces shape the embryo, and genetic regulation and molecular signalling, which concern how cells determine their states and behaviours. Integrating both sides into a unified framework is crucial to fully understand the self-organized dynamics of morphogenesis. Here we introduce MecaGen, an integrative modelling platform enabling the hypothesis-driven simulation of these dual processes via the coupling between mechanical and chemical variables. Our approach relies upon a minimal 'cell behaviour ontology' comprising mesenchymal and epithelial cells and their associated behaviours. MecaGen enables the specification and control of complex collective movements in 3D space through a biologically relevant gene regulatory network and parameter space exploration. Three case studies investigating pattern formation, epithelial differentiation and tissue tectonics in zebrafish early embryogenesis, the latter with quantitative comparison to live imaging data, demonstrate the validity and usefulness of our framework.

  14. Neuroprotective and anti-inflammatory mechanisms are activated early in optic neuritis

    DEFF Research Database (Denmark)

    Tsakiri, A; Ravanidis, S; Lagoudaki, R;

    2015-01-01

    -matched voluntary HC (n = 32). The mRNA expression of distinct cytokines and neurotrophic factors was assessed by semi/quantitative real-time PCR (RT-PCR). RESULTS: Brain- and glial cell-derived neurotrophic factor (BDNF and GDNF) and interleukin 10 (IL-10) expression was significantly increased in the CSF compared...... to the blood in both ON and HC (P BDNF and GDNF of the ON group were positively correlated with the presence of oligoclonal bands (OB). Additionally, patients with gadolinium (gd+) lesions on brain MRI showed increased levels of IL-5 in blood (P = 0.03). CONCLUSION: Our...... data indicate that both immuno-regulatory and neuroprotective mechanisms may potentially take place relatively early in the course of the ON. The presence of neurotrophic factors in healthy CSF and their overexpression already during the acute phase of ON supports the alertness of CNS defence...

  15. A cell-based computational model of early embryogenesis coupling mechanical behaviour and gene regulation

    Science.gov (United States)

    Delile, Julien; Herrmann, Matthieu; Peyriéras, Nadine; Doursat, René

    2017-01-01

    The study of multicellular development is grounded in two complementary domains: cell biomechanics, which examines how physical forces shape the embryo, and genetic regulation and molecular signalling, which concern how cells determine their states and behaviours. Integrating both sides into a unified framework is crucial to fully understand the self-organized dynamics of morphogenesis. Here we introduce MecaGen, an integrative modelling platform enabling the hypothesis-driven simulation of these dual processes via the coupling between mechanical and chemical variables. Our approach relies upon a minimal `cell behaviour ontology' comprising mesenchymal and epithelial cells and their associated behaviours. MecaGen enables the specification and control of complex collective movements in 3D space through a biologically relevant gene regulatory network and parameter space exploration. Three case studies investigating pattern formation, epithelial differentiation and tissue tectonics in zebrafish early embryogenesis, the latter with quantitative comparison to live imaging data, demonstrate the validity and usefulness of our framework.

  16. The impact of mechanical AGN feedback on the formation of massive early-type galaxies

    CERN Document Server

    Choi, Ena; Naab, Thorsten; Oser, Ludwig; Moster, Benjamin P

    2014-01-01

    We employ cosmological hydrodynamical simulations to investigate the effects of AGN feedback on the formation of massive galaxies with present-day stellar masses of $M_{stel} > 8.9 \\times 10^{10} M_{sun}$. Using smoothed particle hydrodynamics simulations with a pressure-entropy formulation that allows an improved treatment of contact discontinuities and fluid mixing, we run three sets of simulations of 20 halos with different AGN feedback models: (1) no feedback, (2) thermal feedback, and (3) mechanical and radiation feedback. We assume that seed black holes are present at early cosmic epochs at the centre of emerging dark matter halos and trace their mass growth via gas accretion and mergers with other black holes. Both feedback models successfully recover the observed M_BH - sigma relation and black hole-to-stellar mass ratio for simulated central early-type galaxies. The baryonic conversion efficiencies are reduced by a factor of two compared to models without any AGN feedback at all halo masses. However,...

  17. Mechanics of left ventricular relaxation, early diastolic lengthening, and suction investigated in a mathematical model.

    Science.gov (United States)

    Remme, Espen W; Opdahl, Anders; Smiseth, Otto A

    2011-05-01

    We investigated the determinants of ventricular early diastolic lengthening and mechanics of suction using a mathematical model of the left ventricle (LV). The model was based on a force balance between the force represented by LV pressure (LVP) and active and passive myocardial forces. The predicted lengthening velocity (e') from the model agreed well with measurements from 10 dogs during 5 different interventions (R = 0.69, P relaxation rate and systolic shortening increased, when passive stiffness was decreased, and when the rate of fall of LVP during early filling was decreased relative to the rate of fall of active stress. We first defined suction as the work the myocardium performed to pull blood into the ventricle. This occurred when contractile active forces decayed below and became weaker than restoring forces, producing a negative LVP. An alternative definition of suction is filling during falling pressure, commonly believed to be caused by release of restoring forces. However, the model showed that this phenomenon also occurred when there had been no systolic compression below unstressed length and therefore in the absence of restoring forces. In conclusion, relaxation rate, LVP, systolic shortening, and passive stiffness were all independent determinants of e'. The model generated a suction effect seen as lengthening occurring during falling pressure. However, this was not equivalent with the myocardium performing pulling work on the blood, which was performed only when restoring forces were higher than remaining active fiber force, corresponding to a negative transmural pressure.

  18. Thermo-Mechanical Methodology for Stabilizing Shape Memory Alloy Response

    Science.gov (United States)

    Padula, Santo

    2013-01-01

    This innovation is capable of significantly reducing the amount of time required to stabilize the strain-temperature response of a shape memory alloy (SMA). Unlike traditional stabilization processes that take days to weeks to achieve stabilized response, this innovation accomplishes stabilization in a matter of minutes, thus making it highly useful for the successful and practical implementation of SMA-based technologies in real-world applications. The innovation can also be applied to complex geometry components, not just simple geometries like wires or rods.

  19. Sleep Moderates the Association Between Response Inhibition and Self-Regulation in Early Childhood.

    Science.gov (United States)

    Schumacher, Allyson M; Miller, Alison L; Watamura, Sarah E; Kurth, Salome; Lassonde, Jonathan M; LeBourgeois, Monique K

    2017-01-01

    Early childhood is a time of rapid developmental changes in sleep, cognitive control processes, and the regulation of emotion and behavior. This experimental study examined sleep-dependent effects on response inhibition and self-regulation, as well as whether acute sleep restriction moderated the association between these processes. Preschool children (N = 19; 45.6 ± 2.2 months; 11 female) followed a strict sleep schedule for at least 3 days before each of 2 morning behavior assessments: baseline (habitual nap/night sleep) and sleep restriction (missed nap/delayed bedtime). Response inhibition was evaluated via a go/no-go task. Twelve self-regulation strategies were coded from videotapes of children while attempting an unsolvable puzzle. We then created composite variables representing adaptive and maladaptive self-regulation strategies. Although we found no sleep-dependent effects on response inhibition or self-regulation measures, linear mixed-effects regression showed that acute sleep restriction moderated the relationship between these processes. At baseline, children with better response inhibition were more likely to use adaptive self-regulation strategies (e.g., self-talk, alternate strategies), and those with poorer response inhibition showed increased use of maladaptive self-regulation strategies (e.g., perseveration, fidgeting); however, response inhibition was not related to self-regulation strategies following sleep restriction. Our results showing a sleep-dependent effect on the associations between response inhibition and self-regulation strategies indicate that adequate sleep facilitates synergy between processes supporting optimal social-emotional functioning in early childhood. Although replication studies are needed, findings suggest that sleep may alter connections between maturing emotional and cognitive systems, which have important implications for understanding risk for or resilience to developmental psychopathology.

  20. Responses of chromosome segregation machinery to mechanical perturbations.

    Science.gov (United States)

    Itabashi, Takeshi; Takagi, Jun; Suzuki, Kazuya; Ishiwata, Shin'ichi

    2013-01-01

    For genome stability, the proper segregation of chromosomes is required. The exquisite process of chromosome segregation has charmed a lot of cell- and molecular biologists into watching what happens inside a mitotic cell and how each molecule contributes to this process for the accomplishment of accurate cell division1. The process to partition the duplicated genome to the daughter cells in each cell division is mediated by a self-organized structure called the mitotic spindle. It is well known that the mitotic spindle is a multi-component macromolecular machine composed of microtubules, molecular motors (kinesins, cytoplasmic dynein), and other regulatory molecules (microtubule-associated proteins, kinases, etc.). In recent years, most of the protein components of the mitotic spindle have been identified and the functions of these proteins have been characterized using molecular perturbations2,3. Thus, the mechanisms for spindle assembly and chromosome segregation are being revealed rapidly. However, the chromosome segregation machinery is poorly understood from the mechanical point of view, such as how the mitotic spindle within a cell responds to a variety of mechanical forces, originating from cell-cell interactions or environmental fluctuations. Recent advances in the controlled mechanical perturbation have indicated that the mitotic spindle possesses a structural pliability, size adaptability to the applied external forces, and a strong self-organizing ability. Mechanical perturbations revealed also the mechanochemical regulation of chromosome segregation machinery, which responds to the applied forces. Here, we discuss the current progress in the biophysical research on the architectural and functional dynamics of the mitotic spindle.

  1. Early responses to deep brain stimulation in depression are modulated by anti-inflammatory drugs.

    Science.gov (United States)

    Perez-Caballero, L; Pérez-Egea, R; Romero-Grimaldi, C; Puigdemont, D; Molet, J; Caso, J-R; Mico, J-A; Pérez, V; Leza, J-C; Berrocoso, E

    2014-05-01

    Deep brain stimulation (DBS) in the subgenual cingulated gyrus (SCG) is a promising new technique that may provide sustained remission in resistant major depressive disorder (MDD). Initial studies reported a significant early improvement in patients, followed by a decline within the first month of treatment, an unexpected phenomenon attributed to potential placebo effects or a physiological response to probe insertion that remains poorly understood. Here we characterized the behavioural antidepressant-like effect of DBS in the rat medial prefrontal cortex, focusing on modifications to rodent SCG correlate (prelimbic and infralimbic (IL) cortex). In addition, we evaluated the early outcome of DBS in the SCG of eight patients with resistant MDD involved in a clinical trial. We found similar antidepressant-like effects in rats implanted with electrodes, irrespective of whether they received electrical brain stimulation or not. This effect was due to regional inflammation, as it was temporally correlated with an increase of glial-fibrillary-acidic-protein immunoreactivity, and it was blocked by anti-inflammatory drugs. Indeed, inflammatory mediators and neuronal p11 expression also changed. Furthermore, a retrospective study indicated that the early response of MDD patients subjected to DBS was poorer when they received anti-inflammatory drugs. Our study demonstrates that electrode implantation up to the IL cortex is sufficient to produce an antidepressant-like effect of a similar magnitude to that observed in rats receiving brain stimulation. Moreover, both preclinical and clinical findings suggest that the use of anti-inflammatory drugs after electrode implantation may attenuate the early anti-depressive response in patients who are subjected to DBS.

  2. Very rapid virologic response and early HCV response kinetics, as quick measures to compare efficacy and guide a personalized response-guided therapy

    Science.gov (United States)

    Yakoot, Mostafa; Abdo, Alaa M; Yousry, Ahmed; Helmy, Sherine

    2016-01-01

    Background This is the second and final report for our study designed to compare two generic sofosbuvir products for the degree and speed of virologic response to a dual anti-hepatitis C virus (HCV) treatment protocol. We aimed to test the applicability of the early virus response kinetics and the very rapid virologic response (vRVR) rate as quick outcome measures for accelerated comparative efficacy studies and as a foundation for a personalized response-guided therapy. Methods Fifty eligible chronic HCV patients were randomized to either one of two generic sofosbuvir products (Gratisovir or Grateziano) at a daily dose of one 400 mg tablet plus a weight-based ribavirin dose. Data were compared between the groups for early virus response kinetics and vRVR rates in relation to the rates of final sustained virologic response at week 12 posttreatment (SVR12). Results The Log10 transformed virus load (Log polymerase chain reaction) curves showed fairly similar rapid decline during the first 2 weeks, with no significant difference between the groups at four analysis points throughout the study by repeated-measures factorial analysis of variance test (P=0.48). The SVR12 rates were 96% (95% confidence interval, 79.6%–99.9%) in Gratisovir group (24/25) and 95.7% (95% confidence interval, 78%–99.9%) in Grateziano group (22/23). There was no statistically significant difference found by exact test (P>0.999). There was a significant association between the vRVR and the SVR12, with 100% positive predictive value (38/38 of those who had vRVR, achieved a final SVR12) and 82.6% sensitivity (among the total 46 with SVR12, 38 were having vRVR). Conclusion We can conclude from our study that the early HCV response kinetics and the vRVR rates could be used as sensitive quick markers for efficacy (with a very high positive predictive value for SVR12), based on our accelerated comparative efficacy research model. This might open the way for new models of accelerated equivalence

  3. Plant MYB Transcription Factors: Their Role in Drought Response Mechanisms

    Directory of Open Access Journals (Sweden)

    Elena Baldoni

    2015-07-01

    Full Text Available Water scarcity is one of the major causes of poor plant performance and limited crop yields worldwide and it is the single most common cause of severe food shortage in developing countries. Several molecular networks involved in stress perception, signal transduction and stress responses in plants have been elucidated so far. Transcription factors are major players in water stress signaling. In recent years, different MYB transcription factors, mainly in Arabidopsis thaliana (L. Heynh. but also in some crops, have been characterized for their involvement in drought response. For some of them there is evidence supporting a specific role in response to water stress, such as the regulation of stomatal movement, the control of suberin and cuticular waxes synthesis and the regulation of flower development. Moreover, some of these genes have also been characterized for their involvement in other abiotic or biotic stresses, an important feature considering that in nature, plants are often simultaneously subjected to multiple rather than single environmental perturbations. This review summarizes recent studies highlighting the role of the MYB family of transcription factors in the adaptive responses to drought stress. The practical application value of MYBs in crop improvement, such as stress tolerance engineering, is also discussed.

  4. Plant MYB Transcription Factors: Their Role in Drought Response Mechanisms.

    Science.gov (United States)

    Baldoni, Elena; Genga, Annamaria; Cominelli, Eleonora

    2015-07-13

    Water scarcity is one of the major causes of poor plant performance and limited crop yields worldwide and it is the single most common cause of severe food shortage in developing countries. Several molecular networks involved in stress perception, signal transduction and stress responses in plants have been elucidated so far. Transcription factors are major players in water stress signaling. In recent years, different MYB transcription factors, mainly in Arabidopsis thaliana (L.) Heynh. but also in some crops, have been characterized for their involvement in drought response. For some of them there is evidence supporting a specific role in response to water stress, such as the regulation of stomatal movement, the control of suberin and cuticular waxes synthesis and the regulation of flower development. Moreover, some of these genes have also been characterized for their involvement in other abiotic or biotic stresses, an important feature considering that in nature, plants are often simultaneously subjected to multiple rather than single environmental perturbations. This review summarizes recent studies highlighting the role of the MYB family of transcription factors in the adaptive responses to drought stress. The practical application value of MYBs in crop improvement, such as stress tolerance engineering, is also discussed.

  5. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence

    Science.gov (United States)

    Guyer, Amanda E.; Jarcho, Johanna M.; Pérez-Edgar, Koraly; Degnan, Kathryn A.; Pine, Daniel S.; Fox, Nathan A.; Nelson, Eric E.

    2015-01-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children’s caregiving context. The convergence of a child’s temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (Mage = 17.89 years, N= 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development. PMID:25588884

  6. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence.

    Science.gov (United States)

    Guyer, Amanda E; Jarcho, Johanna M; Pérez-Edgar, Koraly; Degnan, Kathryn A; Pine, Daniel S; Fox, Nathan A; Nelson, Eric E

    2015-07-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children's caregiving context. The convergence of a child's temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (M(age) = 17.89 years, N = 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development.

  7. Early COPD patients with lung hyperinflation associated with poorer lung function but better bronchodilator responsiveness

    Directory of Open Access Journals (Sweden)

    Chen C

    2016-10-01

    Full Text Available Chunlan Chen,* Wenhua Jian,* Yi Gao, Yanqing Xie, Yan Song, Jinping Zheng State Key Laboratory of Respiratory Disease, China National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: It is unknown whether aggressive medication strategies should be used for early COPD with or without lung hyperinflation. We aimed to explore the characteristics and bronchodilator responsiveness of early COPD patients (stages I and II with/without lung hyperinflation.Methods: Four hundred and six patients with COPD who performed both lung volume and bronchodilation tests were retrospectively analyzed. Residual volume to total lung capacity >120% of predicted values indicated lung hyperinflation. The characteristics and bronchodilator responsiveness were compared between the patients with and without lung hyperinflation across all stages of COPD.Results: The percentages of patients with lung hyperinflation were 72.7% in the entire cohort, 19.4% in stage I, 68.5% in stage II, 95.3% in stage III, and 100.0% in stage IV. The patients with lung hyperinflation exhibited poorer lung function but better bronchodilator responsiveness of both forced expiratory volume in 1 second and forced vital capacity than those without lung hyperinflation during early COPD (t=2.21–5.70, P=0.000–0.029, especially in stage I, while age, body mass index, smoking status, smoking history, and disease duration were similar between the two subgroups in the same stages. From stages I to IV of subgroups with lung hyperinflation, stage I patients had the best bronchodilator responsiveness. Use of bronchodilator responsiveness of forced vital capacity to detect the presence of lung hyperinflation in COPD patients showed relatively high sensitivities (69.5%–75.3% and specificities (70.3%

  8. Electrical Response of Cement-Based Piezoelectric Ceramic Composites under Mechanical Loadings

    Directory of Open Access Journals (Sweden)

    Biqin Dong

    2011-01-01

    Full Text Available Electrical responses of cement-based piezoelectric ceramic composites under mechanical loadings are studied. A simple high order model is presented to explain the nonlinear phenomena, which is found in the electrical response of the composites under large mechanical loadings. For general situation, this nonlinear piezoelectric effect is quite small, and the composite is suitable for dynamic mechanical sensor as holding high static stability. The experimental results are consistent with the relationship quite well. The study shows that cement-based piezoelectric composite is suitable for potential application as dynamic mechanical sensor with excellent dynamic response and high static stability.

  9. Simple mechanisms of early life - simulation model on the origin of semi-cells.

    Science.gov (United States)

    Klein, Adrian; Bock, Martin; Alt, Wolfgang

    2017-01-01

    The development of first cellular structures played an important role in the early evolution of life. Early evolution of life probably took place on a molecular level in a reactive environment. The iron-sulfur theory postulates the formation of cell-like structures on catalytic surfaces. Experiments show that H2S together with FeS and other metallic centers drive auto-catalytic surface reactions, in which organic molecules such as pyruvic and amino acids occur. It is questionable which mechanisms are needed to form cell-like structures under these conditions. To address this question, we implemented a model system featuring the fundamentals of molecular dynamics: heat, attraction, repulsion and formation of covalent bonds. Our basic model exhibits a series of essential processes: self-organization of lipid micelles and bilayers, formation of fluid filled cavities, flux of molecules along membranes, transport of energized groups towards sinks and whole colonies of cell-like structures on a larger scale. The results demonstrate that only a few features are sufficient for discovering hitherto non described phenomena of self-assembly and dynamics of cell-like structures as candidates for early evolving proto-cells. Significance statement The quest for a possible origin of life continues to be one of the most fascinating problems in biology. In one theoretical scenario, early life originated from a solution of reactive chemicals in the ancient deep sea, similar to conditions as to be found in thermal vents. Experiments have shown that a variety of organic molecules, the building blocks of life, form under these conditions. Based on such experiments, the iron-sulfur theory postulates the growth of cell-like structures at certain catalytic surfaces. For an explanation and proof of such a process we have developed a computer model simulating molecular assembly of lipid bilayers and formation of semi-cell cavities. The results demonstrate the possibility of cell-like self

  10. Allergen-specific IL-5 responses in early childhood predict asthma at age eight.

    Directory of Open Access Journals (Sweden)

    Christina Weber-Chrysochoou

    Full Text Available BACKGROUND: The pattern of development of allergen-specific T cell cytokine responses in early childhood and their relation to later disease is poorly understood. Here we describe longitudinal changes in allergen-stimulated T cell cytokine responses and their relation to asthma and allergic disease during the first 8 years of life. METHODS: Subjects with a family history of asthma, who were enrolled antenatally in the Childhood Asthma Prevention Study (public trials registration number ACTRN12605000042640, had skin prick tests, clinical evaluation for asthma and eczema, and in vitro assessment of T cell cytokine responses to HDM extract performed at ages 18 months (n = 281, 3 years (n = 349, 5 years (n = 370 and 8 years (n = 275. We measured interleukin (IL- 13 at 3, 5 and 8 years, and IL-5, IL-10, and interferon-γ (IFN-γ, at 18 months, 3, 5 and 8 years by ELISA. A cohort analysis was undertaken. Independent effects of cytokine responses at each age on the risk of asthma and allergic outcomes at age 8 years were estimated by multivariable logistic regression. RESULTS: HDM-specific IL-5 responses increased with age. HDM-specific IL-13 and IL-10 responses peaked at age 5 years. HDM-specific IL-5 responses at 3 years, 5 years and 8 years were significantly associated with the presence of asthma and atopy at 8 years. IL-13 responses at 3 years, 5 years and 8 years were significantly associated with atopy at 8 years, but this association was not independent of the effect of IL-5. Other HDM-specific cytokine responses were not independently related to asthma or eczema at 8 years. CONCLUSION: HDM-specific IL-5 responses at age 3 years or later are the best measure of T cell function for predicting asthma at age 8 years.

  11. Dermoscopic hemorrhagic dots: an early predictor of response of psoriasis to biologic agents

    Science.gov (United States)

    Lallas, Aimilios; Argenziano, Giuseppe; Zalaudek, Iris; Apalla, Zoe; Ardigo, Marco; Chellini, Patricia; Cordeiro, Natalia; Guimaraes, Mariana; Kyrgidis, Athanassios; Lazaridou, Elizabeth; Longo, Caterina; Moscarella, Elvira; Papadimitriou, Ilias; Pellacani, Giovanni; Sotiriou, Elena; Vakirlis, Efstratios; Ioannides, Dimitrios

    2016-01-01

    Background Biologic agents are routinely used in the treatment of severe psoriasis. The evaluation of treatment response is mainly based on the physician’s global clinical assessment. Objective To investigate whether dermoscopy might enhance the assessment of response of psoriasis to treatment with biologic agents. Methods Patients with severe psoriasis scheduled to receive a biologic agent were enrolled in the study. A target lesion from each patient was clinically and dermoscopically documented at baseline and after one, two and six months. The clinical response was evaluated by the recruiting clinicians at all visits, while dermoscopic images were evaluated by two independent investigators, blinded to the clinical information. Chi Square test was used for cross-tabulation comparisons, while odds ratios, 95% confidence intervals and p values were calculated using univariate logistic regression. Results Overall, there was a significant correlation between clinical response and vessel distribution at all time points: a regular vessel distribution correlated with no response, a clustered distribution with partial response, and the dermoscopic absence of vessels with complete response. The presence of dermoscopic hemorrhagic dots was a potent predictor of favorable clinical response at the subsequent visit at all time points. Among lesions initially clinically responding and later recurring, 87.5% displayed dermoscopic dotted vessels despite the macroscopic remission. Conclusion Dermoscopy might be a useful additional tool for evaluating the response of psoriatic patients to biologic agents. Hemorrhagic dots represent an early predictor of clinical response, while the persistence or reappearance of dotted vessels might predict clinical persistence or recurrence, respectively. PMID:27867739

  12. Tensile mechanical response of polyethylene – clay nanocomposites.

    Directory of Open Access Journals (Sweden)

    2007-03-01

    Full Text Available In this work we report on the microstructural and the mechanical characteristics of high density polyethylene (HDPE-clay nanocomposites, with particular attention to the creep behaviour. The samples were prepared through melt compounding, using two high-density polyethylenes with different melt flow rate (MFR, two different organo-modified clays, and changing the relative amount of a polyethylene grafted with maleic anhydride (PEgMA compatibilizer. The intercalation process is more effective as the matrix melt viscosity decreases (higher MFR, while the clay interlamellar spacing increases as the compatibilizer amount increases. The relative stiffness of the nanocomposites increases with the addition of clay, with a limited enhancement of the relative yield stress. The better intercalation obtained by the addition of the compatibilizer is not accompanied by a concurrent improvement of the tensile mechanical properties. The creep resistance is enhanced by the introduction of clay, with an appreciable dependence on both the polyethylene and the clay type.

  13. Early warning systems and rapid response to the deteriorating patient in hospital: A systematic realist review.

    Science.gov (United States)

    McGaughey, Jennifer; O'Halloran, Peter; Porter, Sam; Blackwood, Bronagh

    2017-07-20

    To determine the Rapid Response System programme theory and investigate how the mechanisms of implementation and the characteristics of context combine to enable or constrain the implementation of Rapid Response Systems and the achievement of desired outcomes. Rapid Response Systems have been implemented internationally to improve the recognition and management of patient deterioration, reduce the need for cardiopulmonary resuscitation and improve patient outcomes. Realist review. We searched DARE, CENTRAL, NHSEED, MEDLINE, Medline In Process, EMBASE, CINAHL, PubMed, Scopus, The Web of Science and PychInfo databases from 1997 - 2017 in addition to purposively searching the grey literature looking for articles supporting, refuting or explaining Rapid Response System programme theories. Included studies were critically appraised and graded using the Critical Appraisal Skills Programme tool. Data extraction and synthesis investigated the Rapid Response System theoretical propositions against the empirical evidence to refine Rapid Response System programme theories. The review found that the Rapid Response System programme theory achieved desired outcomes when there were sufficient skills mix of experienced staff, EWS protocols were used flexibly alongside clinical judgement and staff had access to ongoing, multiprofessional, competency-based education. However, ward cultures, hierarchical referral systems, workload and staffing resources had a negative impact on the implementation of the Rapid Response System. To improve the recognition and management of patient deterioration, policymakers need to address those cultural, educational and organizational factors that have an impact on the successful implementation of Rapid Response Systems in practice. © 2017 John Wiley & Sons Ltd.

  14. Involvement of two microRNAs in the early immune response to DNA vaccination against a fish rhabdovirus

    DEFF Research Database (Denmark)

    Bela-ong, Dennis Berbulla; Schyth, Brian Dall; Zou, Jun

    2015-01-01

    Mechanisms that account for the high protective efficacy in teleost fish of a DNA vaccine expressing the glycoprotein (G) of Viral hemorrhagic septicemia virus (VHSV) are thought to involve early innate immune responses mediated by interferons (IFNs). Microribonucleic acids (miRNAs) are a diverse...... trout infected with VHSV. In this study, we analyzed the expression of these miRNAs in fish following administration of the DNA vaccine and their potential functions. Quantitative RT-PCR analysis revealed the increased levels of miR-462, and miR-731 in the skeletal muscle tissue at the site of vaccine...... administration and in the liver of vaccinated fish relative to empty plasmid backbone-injected controls. The increased expression of these miRNAs in the skeletal muscle correlated with the increased levels of the type I interferon (IFN)-inducible gene Mx, type I IFN and IFN-γ genes at the vaccination site...

  15. Metastatic bone cancer as a recurrence of early gastric cancer - characteristics and possible mechanisms

    Institute of Scientific and Technical Information of China (English)

    Michiya Kobayashi; Takehiro Okabayashi; Takeshi Sano; Keijiro Araki

    2005-01-01

    The surgical outcome of most early gastric cancer (EGC)is usually satisfactory. Some cases show bone metastasis even though the depth of cancer invasion is confined to the mucosa. The most frequent site for recurrence of EGC is the liver. Cases of EGC with bone metastasis are reviewed to clarify the clinicopathological characteristics of EGC giving rise to bone metastasis. Possible mechanisms and risk factors underlying this rare condition are proposed.Forty-six cases of bone metastasis from EGC are reviewed from published reports and meeting proceedings in Japan.This investigation suggests that risk factors for bone metastasis from EGC include depressed-type signet-ring cell carcinoma, poorly differentiated carcinoma, and/or the likely involvement of lymph node metastasis, even though the cancer is confined to the gastric mucosa. The risk factors do not include recurrence of EGC in the liver. We speculate that the mechanism of bone metastasis from EGC is via lymphatic channels and systemic circulation. Postoperative follow-up of cases should consider the development of bone metastasis from EGC. We propose the use of elevated alkaline phosphatase levels for the detection of bone metastasis and recommend bone scintigraphy in positive cases.

  16. Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

    Science.gov (United States)

    Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

    2016-07-01

    Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

  17. DNA Damage Response and Immune Defence: Links and Mechanisms

    Directory of Open Access Journals (Sweden)

    Björn Schumacher

    2016-08-01

    Full Text Available DNA damage plays a causal role in numerous human pathologies including cancer, premature aging and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signalling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signalling. We highlight evidence gained into (i which molecular and cellular pathways of DDR activate immune signalling, (ii how DNA damage drives chronic inflammation, and (iii how chronic inflammation causes DNA damage and pathology in humans.

  18. Tumor Interstitial Fluid Pressure as an Early-Response Marker for Anticancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Stephane Ferretti

    2009-09-01

    Full Text Available Solid tumors have a raised interstitial fluid pressure (IFP due to high vessel permeability, low lymphatic drainage, poor perfusion, and high cell density around the blood vessels. To investigate tumor IFP as an early-response biomarker, we have tested the effect of seven anticancer chemotherapeutics including cytotoxics and targeted cytostatics in 13 experimental tumor models. IFP was recorded with the wick-in-needle method. Models were either ectopic or orthotopic and included mouse and rat syngeneic as well as human xenografts in nude mice. The mean basal IFP was between 4.4 and 15.2mm Hg; IFP was lowest in human tumor xenografts and highest in rat syngeneic models. Where measured, basal IFP correlated positively with relative tumor blood volume (rTBV determined by dynamic contrast-enhanced magnetic resonance imaging. Most chemotherapeutics sooner (2 or 3 days or later (6 or 7 days lowered tumor IFP significantly, and the cytotoxic patupilone caused the greatest decrease in IFP. In rat mammary orthotopic BN472 tumors, significant drug-induced decreases in IFP and rTBV correlated positively with each other for both patupilone and the cytostatic vatalanib. In the two orthotopic models studied, early decreases in IFP were significantly (P ≤ .005 correlated with late changes in tumor volume. Thus, drug-induced decreases in tumor IFP are an early marker of response to therapy, which could aid clinical development.

  19. Tumor interstitial fluid pressure as an early-response marker for anticancer therapeutics.

    Science.gov (United States)

    Ferretti, Stephane; Allegrini, Peter R; Becquet, Mike M; McSheehy, Paul Mj

    2009-09-01

    Solid tumors have a raised interstitial fluid pressure (IFP) due to high vessel permeability, low lymphatic drainage, poor perfusion, and high cell density around the blood vessels. To investigate tumor IFP as an early-response biomarker, we have tested the effect of seven anticancer chemotherapeutics including cytotoxics and targeted cytostatics in 13 experimental tumor models. IFP was recorded with the wick-in-needle method. Models were either ectopic or orthotopic and included mouse and rat syngeneic as well as human xenografts in nude mice. The mean basal IFP was between 4.4 and 15.2mm Hg; IFP was lowest in human tumor xenografts and highest in rat syngeneic models. Where measured, basal IFP correlated positively with relative tumor blood volume (rTBV) determined by dynamic contrast-enhanced magnetic resonance imaging. Most chemotherapeutics sooner (2 or 3 days) or later (6 or 7 days) lowered tumor IFP significantly, and the cytotoxic patupilone caused the greatest decrease in IFP. In rat mammary orthotopic BN472 tumors, significant drug-induced decreases in IFP and rTBV correlated positively with each other for both patupilone and the cytostatic vatalanib. In the two orthotopic models studied, early decreases in IFP were significantly (P tumor volume. Thus, drug-induced decreases in tumor IFP are an early marker of response to therapy, which could aid clinical development.

  20. Simulation of the mechanical response of cells on micropost substrates.

    Science.gov (United States)

    Ronan, William; Pathak, Amit; Deshpande, Vikram S; McMeeking, Robert M; McGarry, J Patrick

    2013-10-01

    Experimental studies where cells are seeded on micropost arrays in order to quantify their contractile behavior are becoming increasingly common. Interpretation of the data generated by this experimental technique is difficult, due to the complexity of the processes underlying cellular contractility and mechanotransduction. In the current study, a coupled framework that considers strain rate dependent contractility and remodeling of the cytoskeleton is used in tandem with a thermodynamic model of tension dependent focal adhesion formation to investigate the biomechanical response of cells adhered to micropost arrays. Computational investigations of the following experimental studies are presented: cell behavior on different sized arrays with a range of post stiffness; stress fiber and focal adhesion formation in irregularly shaped cells; the response of cells to deformations applied locally to individual posts; and the response of cells to equibiaxial stretching of micropost arrays. The predicted stress fiber and focal adhesion distributions; in addition to the predicted post tractions are quantitatively and qualitatively supported by previously published experimental data. The computational models presented in this study thus provide a framework for the design and interpretation of experimental micropost studies.

  1. Recognition of Immune Response for the Early Diagnosis and Treatment of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Adrese M. Kandahari

    2015-01-01

    Full Text Available Osteoarthritis is a common and debilitating joint disease that affects up to 30 million Americans, leading to significant disability, reduction in quality of life, and costing the United States tens of billions of dollars annually. Classically, osteoarthritis has been characterized as a degenerative, wear-and-tear disease, but recent research has identified it as an immunopathological disease on a spectrum between healthy condition and rheumatoid arthritis. A systematic literature review demonstrates that the disease pathogenesis is driven by an early innate immune response which progressively catalyzes degenerative changes that ultimately lead to an altered joint microenvironment. It is feasible to detect this infiltration of cells in the early, and presumably asymptomatic, phase of the disease through noninvasive imaging techniques. This screening can serve to aid clinicians in potentially identifying high-risk patients, hopefully leading to early effective management, vast improvements in quality of life, and significant reductions in disability, morbidity, and cost related to osteoarthritis. Although the diagnosis and treatment of osteoarthritis routinely utilize both invasive and non-invasive strategies, imaging techniques specific to inflammatory cells are not commonly employed for these purposes. This review discusses this paradigm and aims to shift the focus of future osteoarthritis-related research towards early diagnosis of the disease process.

  2. An Experimental Study in the Mechanical Response of Polymer Modified Geopolymers

    Science.gov (United States)

    2012-04-01

    AFRL-RX-TY-TR-2012-0057 AN EXPERIMENTAL STUDY IN THE MECHANICAL RESPONSE OF POLYMER MODIFIED GEOPOLYMERS Benjamin Valera...03-JUN-2010 -- 02-MAR-2012 An Experimental Study in the Mechanical Response of Polymer Modified Geopolymers FA4819-10-C-0020 0909999F GOVT D0 QD101005...molecular weight of Poly Ethylene Glycol (PEG), Carboxy Methyl Cellulose (CMC) on metakaolin and F type fly ash sodium based geopolymers in heir mechanical

  3. Wolbachia Blocks Viral Genome Replication Early in Infection without a Transcriptional Response by the Endosymbiont or Host Small RNA Pathways.

    Directory of Open Access Journals (Sweden)

    Stephanie M Rainey

    2016-04-01

    Full Text Available The intracellular endosymbiotic bacterium Wolbachia can protect insects against viral infection, and is being introduced into mosquito populations in the wild to block the transmission of arboviruses that infect humans and are a major public health concern. To investigate the mechanisms underlying this antiviral protection, we have developed a new model system combining Wolbachia-infected Drosophila melanogaster cell culture with the model mosquito-borne Semliki Forest virus (SFV; Togaviridae, Alphavirus. Wolbachia provides strong antiviral protection rapidly after infection, suggesting that an early stage post-infection is being blocked. Wolbachia does appear to have major effects on events distinct from entry, assembly or exit as it inhibits the replication of an SFV replicon transfected into the cells. Furthermore, it causes a far greater reduction in the expression of proteins from the 3' open reading frame than the 5' non-structural protein open reading frame, indicating that it is blocking the replication of viral RNA. Further to this separation of the replicase proteins and viral RNA in transreplication assays shows that uncoupling of viral RNA and replicase proteins does not overcome Wolbachia's antiviral activity. This further suggests that replicative processes are disrupted, such as translation or replication, by Wolbachia infection. This may occur by Wolbachia mounting an active antiviral response, but the virus did not cause any transcriptional response by the bacterium, suggesting that this is not the case. Host microRNAs (miRNAs have been implicated in protection, but again we found that host cell miRNA expression was unaffected by the bacterium and neither do our findings suggest any involvement of the antiviral siRNA pathway. We conclude that Wolbachia may directly interfere with early events in virus replication such as translation of incoming viral RNA or RNA transcription, and this likely involves an intrinsic (as opposed to

  4. Systemic Inflammatory Response Syndrome After Major Abdominal Surgery Predicted by Early Upregulation of TLR4 and TLR5.

    Science.gov (United States)

    Lahiri, Rajiv; Derwa, Yannick; Bashir, Zora; Giles, Edward; Torrance, Hew D T; Owen, Helen C; O'Dwyer, Michael J; O'Brien, Alastair; Stagg, Andrew J; Bhattacharya, Satyajit; Foster, Graham R; Alazawi, William

    2016-05-01

    To study innate immune pathways in patients undergoing hepatopancreaticobiliary surgery to understand mechanisms leading to enhanced inflammatory responses and identifying biomarkers of adverse clinical consequences. Patients undergoing major abdominal surgery are at risk of life-threatening systemic inflammatory response syndrome (SIRS) and sepsis. Early identification of at-risk patients would allow tailored postoperative care and improve survival. Two separate cohorts of patients undergoing major hepatopancreaticobiliary surgery were studied (combined n = 69). Bloods were taken preoperatively, on day 1 and day 2 postoperatively. Peripheral blood mononuclear cells and serum were separated and immune phenotype and function assessed ex vivo. Early innate immune dysfunction was evident in 12 patients who subsequently developed SIRS (postoperative day 6) compared with 27 who did not, when no clinical evidence of SIRS was apparent (preoperatively or days 1 and 2). Serum interleukin (IL)-6 concentration and monocyte Toll-like receptor (TLR)/NF-κB/IL-6 functional pathways were significantly upregulated and overactive in patients who developed SIRS (P SIRS. Increased TLR4 and TLR5 gene expression in whole blood was demonstrated in a separate validation cohort of 30 patients undergoing similar surgery. Expression of TLR4/5 on monocytes, particularly intermediate CD14CD16 monocytes, on day 1 or 2 predicted SIRS with accuracy 0.89 to 1.0 (areas under receiver operator curves). These data demonstrate the mechanism for IL-6 overproduction in patients who develop postoperative SIRS and identify markers that predict patients at risk of SIRS 5 days before the onset of clinical signs.

  5. Wolbachia Blocks Viral Genome Replication Early in Infection without a Transcriptional Response by the Endosymbiont or Host Small RNA Pathways.

    Science.gov (United States)

    Rainey, Stephanie M; Martinez, Julien; McFarlane, Melanie; Juneja, Punita; Sarkies, Peter; Lulla, Aleksei; Schnettler, Esther; Varjak, Margus; Merits, Andres; Miska, Eric A; Jiggins, Francis M; Kohl, Alain

    2016-04-01

    The intracellular endosymbiotic bacterium Wolbachia can protect insects against viral infection, and is being introduced into mosquito populations in the wild to block the transmission of arboviruses that infect humans and are a major public health concern. To investigate the mechanisms underlying this antiviral protection, we have developed a new model system combining Wolbachia-infected Drosophila melanogaster cell culture with the model mosquito-borne Semliki Forest virus (SFV; Togaviridae, Alphavirus). Wolbachia provides strong antiviral protection rapidly after infection, suggesting that an early stage post-infection is being blocked. Wolbachia does appear to have major effects on events distinct from entry, assembly or exit as it inhibits the replication of an SFV replicon transfected into the cells. Furthermore, it causes a far greater reduction in the expression of proteins from the 3' open reading frame than the 5' non-structural protein open reading frame, indicating that it is blocking the replication of viral RNA. Further to this separation of the replicase proteins and viral RNA in transreplication assays shows that uncoupling of viral RNA and replicase proteins does not overcome Wolbachia's antiviral activity. This further suggests that replicative processes are disrupted, such as translation or replication, by Wolbachia infection. This may occur by Wolbachia mounting an active antiviral response, but the virus did not cause any transcriptional response by the bacterium, suggesting that this is not the case. Host microRNAs (miRNAs) have been implicated in protection, but again we found that host cell miRNA expression was unaffected by the bacterium and neither do our findings suggest any involvement of the antiviral siRNA pathway. We conclude that Wolbachia may directly interfere with early events in virus replication such as translation of incoming viral RNA or RNA transcription, and this likely involves an intrinsic (as opposed to an induced

  6. Responsive parenting: establishing early foundations for social, communication, and independent problem-solving skills.

    Science.gov (United States)

    Landry, Susan H; Smith, Karen E; Swank, Paul R

    2006-07-01

    Mothers whose infants varied in early biological characteristics (born at term, n = 120; born at very low birth weight [VLBW], n = 144) were randomized to a target group (n = 133) or developmental feedback comparison group (n = 131) to determine whether learning responsive behaviors would facilitate infant development. The target condition included videotaped examples, problem-solving activities, and mothers' critique of their own behaviors through video procedures across 10 home visits. All target versus comparison mothers showed greater increases across multiple responsiveness behaviors observed in 4 assessments conducted across 6-13 months of age; changes in emotionally supportive behaviors were strongest for target mothers of infants born at VLBW. Increased maternal responsiveness facilitated greater growth in target infants' social, emotional, communication, and cognitive competence, supporting a causal role for responsiveness on infant development. Although benefits were generally comparable across risk groups, aspects of social and emotional skills showed greater change for those born at VLBW. Evidence for responsiveness as a multidimensional construct was provided as well as the importance of different aspects of responsiveness mediating the effect of the intervention on different infant skill domains.

  7. Ternary blended cement concrete. Part I: early age properties and mechanical strength

    Directory of Open Access Journals (Sweden)

    Irassar, E. F.

    2006-12-01

    Full Text Available While there is ample information in the literature on the mechanical performance and durability of concrete made with either limestone or granulated blast furnace slag,very little is known about the effect of the combined action of these two additions on concrete properties. The present paper evaluates the early stage properties and mechanical strength of binary and ternary cement concrete containing up to 18% limestone and 20% granulated blast furnace slag. The results show that the use of ternary cements has no substantial effect on concrete setting time, although it does reduce bleeding and enhance mechanical strength with respect to unadditioned Portland and/or binary cement concrete.En la bibliografía existe abundante información acerca del comportamiento mecánico y durable de hormigones elaborados con la incorporación individual de caliza y de escoria granulada de alto horno. Sin embargo, la modificación de las propiedades por la acción conjunta de las mismas es prácticamente desconocida. En este trabajo se evalúan las propiedades en estado fresco y el comportamiento mecánico de hormigones elaborados con cementos compuestos binarios y ternarios conteniendo hasta 18% de caliza y 20% de escoria granulada de alto horno. Los resultados indican que la utilización de cementos ternarios en hormigones no modifican sustancialmente el tiempo de fraguado, disminuyen la exudación y presentan un mejor comportamiento mecánico que los hormigones elaborados con cemento Portland sin adición y/o binarios.

  8. Arthritis induces early bone high turnover, structural degradation and mechanical weakness.

    Directory of Open Access Journals (Sweden)

    Bruno Vidal

    Full Text Available We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone.Twenty eight Wistar adjuvant-induced arthritis (AIA rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers.AIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046. Histomorphometry showed a lower trabecular thickness (p = 0.0002 and bone volume (p = 0.0003 and higher trabecular sepa-ration (p = 0.0009 in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively in the arthritic group.We have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness.

  9. Arthritis induces early bone high turnover, structural degradation and mechanical weakness.

    Science.gov (United States)

    Vidal, Bruno; Cascão, Rita; Vale, Ana Catarina; Cavaleiro, Inês; Vaz, Maria Fátima; Brito, José Américo Almeida; Canhão, Helena; Fonseca, João Eurico

    2015-01-01

    We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months) inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone. Twenty eight Wistar adjuvant-induced arthritis (AIA) rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers. AIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively) and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046). Histomorphometry showed a lower trabecular thickness (p = 0.0002) and bone volume (p = 0.0003) and higher trabecular sepa-ration (p = 0.0009) in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively) in the arthritic group. We have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness.

  10. Environmental Stress Response and Adaptation Mechanisms in Rhizobia

    Directory of Open Access Journals (Sweden)

    Sanja Kajić

    2016-11-01

    Full Text Available Rhizobia are bacteria that can fixate atmospheric nitrogen in association within the root or the stem nodules of legume plants and transform atmospheric nitrogen to ammonia. Soil environmental conditions are critical factors for the persistence and survival of rhizobia in the soil. The changes in the rhizosphere environment can affect both growth and saprophytic competence, which will influence competitiveness and persistence. Environmental stress imposes a major threat to symbiotic nitrogen fixation and agriculture that can be limited by soil and climatic factors such as salinity, drought, temperature, acidity/alkalinity and heavy metals. In this review we present several different mechanisms in rhizobia adaptation under stress factors.

  11. Mechanisms responsible for decreased glomerular filtration in hibernation and hypothermia

    Science.gov (United States)

    Tempel, G. E.; Musacchia, X. J.; Jones, S. B.

    1977-01-01

    Measurements of blood pressure, heart rate, red blood cell and plasma volumes, and relative distribution of cardiac output were made on hibernating and hypothermic adult male and female golden hamsters weighing 120-140 g to study the mechanisms underlying the elimination or marked depression of renal function in hibernation and hypothermia. The results suggest that the elimination or marked depression in renal function reported in hibernation and hypothermia may partly be explained by alterations in cardiovascular system function. Renal perfusion pressure which decreases nearly 60% in both hibernation and hypothermia and a decrease in plasma volume of roughly 35% in the hypothermic animal might both be expected to markedly alter glomerular function.

  12. Voids by Mechanical Entrapment in Liquid Molding Processes: Mechanism of Formation, Influence in the Mechanical Response and Reduction

    Directory of Open Access Journals (Sweden)

    Juan D. Vanegas-Jaramillo

    2013-06-01

    Full Text Available The voids by mechanical entrapment become as one of the most common type of defects in the liquid molding processing of composites. Because of the strong influence of those kind of voids in the general performance of the manufactured part, an important amount of researches have focused on the study of the mechanisms of formation of those voids, of the influence of the those ones on the mechanical properties of the composite and of the strategies for their reduction during the process. The present paper aims to do a review of some relevant investigations that have been done in the topic of voids caused by mechanical entrapment of air in the processing of composites by LCM (Liquid composites molding with the purpose of generate a reference material addressed to researchers that are interested in this important subject matter related to the areas of processing and mechanical behavior of composites materials. They will be addressed some topics like: the mechanism of void formation by imbalance among macroflow and microflow and its relationship with the modified capillary number and the sink effect; the phenomena of compressibility, dissolution and mobilization of bubbles in dual-scale preforms; the influence of voids on the mechanical properties of the composites and on the damage mechanisms; and the most common strategies that can be implemented in the industry for the reduction of this sort of defects.

  13. Response of Late Carboniferous and Early Permian Plant Communities to Climate Change

    Science.gov (United States)

    Dimichele, William A.; Pfefferkorn, Hermann W.; Gastaldo, Robert A.

    Late Carboniferous and Early Permian strata record the transition from a cold interval in Earth history, characterized by the repeated periods of glaciation and deglaciation of the southern pole, to a warm-climate interval. Consequently, this time period is the best available analogue to the Recent in which to study patterns of vegetational response, both to glacial-interglacial oscillation and to the appearance of warm climate. Carboniferous wetland ecosystems were dominated by spore-producing plants and early gymnospermous seed plants. Global climate changes, largely drying, forced vegetational changes, resulting in a change to a seed plant-dominated world, beginning first at high latitudes during the Carboniferous, reaching the tropics near the Permo-Carboniferous boundary. For most of this time plant assemblages were very conservative in their composition. Change in the dominant vegetation was generally a rapid process, which suggests that environmental thresholds were crossed, and involved little mixing of elements from the wet and dry floras.

  14. Response of Late Carboniferous and Early Permian plant communities to climate change

    Energy Technology Data Exchange (ETDEWEB)

    DiMichele, W.A.; Pfefferkorn, H.W.; Gastaldo, R.A. [Smithsonian Institute, Washington, DC (USA). National Museum of National History

    2001-07-01

    Late Carboniferous and Early Permian strata record the transition from a cold interval in Earth history, characterized by the repeated periods of glaciation and deglaciation of the southern pole, to a warm-climate interval. Consequently, this time period is the best available analogue to the Recent in which to study patterns of vegetational response, both to glacial-interglacial oscillation and to the appearance of warm climate. Carboniferous wetland ecosystems were dominated by spore-producing plants and early gymnospermous seed plants. Global climate changes, largely drying, forced vegetational changes, resulting in a change to a seed plant-dominated world, beginning first at high latitudes during the Carboniferous, reaching the tropics near the Permo-Carboniferous boundary. For most of this time plant assemblages were very conservative in their composition. Change in the dominant vegetation was generally a rapid process, which suggests that environmental thresholds were crossed, and involved little mixing of elements from the wet and dry floras.

  15. Lung function and bronchial responsiveness after Mycoplasma pneumoniae infection in early childhood

    DEFF Research Database (Denmark)

    Kjaer, B.B.; Jensen, J.S.; Nielsen, K.G.

    2008-01-01

    .17 versus 1.21 (kPa sec), P=0.45; and mean change in specific resistance was 13% versus 9%, P= 0.42. In conclusion, M. pneumoniae infection in early childhood was not associated with long-term effects on lung function and bronchial hyperresponsiveness 2 years after infection Udgivelsesdato: 2008/6......Mycoplasma (M.) pneumoniae has been associated with exacerbation of symptoms in asthmatic school children and adults; and an etiological role in asthma has been suggested. The purpose of this study was to investigate whether infection with M. pneumoniae in early childhood has a long-term influence...... on lung function and bronchial responsiveness. In a retrospective, clinical cohort-study children younger than 5 years-of-age when PCR-tested for M. pneumoniae were enrolled. Sixty-five children with clinical symptoms suggesting infection with M. pneumoniae during an epidemic season completed a clinical...

  16. Photoelectric recording of mechanical responses of cardiac myocytes.

    Science.gov (United States)

    Meyer, R; Wiemer, J; Dembski, J; Haas, H G

    1987-04-01

    A method to monitor contraction of isolated myocytes by transmicroscopic photometry is illustrated. Two photodiodes are mounted inside an inverse microscope used for visual control of a cell. Illumination of one diode varies in proportion to changes in cell length. The contraction signal is amplified in a comparator circuit. Spatial resolution of the device is in the order of 1 micron which corresponds to about 5% of cell shortening in the fully activated state of contraction. The method was tested on isolated myocytes from guinea-pig ventricle. Optical records of contraction in response to action potentials or during voltage clamp compare well with the contractile behavior of multicellular preparations.

  17. Responses of diseased muscle to electrical and mechanical intervention.

    Science.gov (United States)

    Dubowitz, V

    1988-01-01

    It is well established that the properties of muscle fibres are influenced by their neurons and that this is at least in part mediated by the pattern of activity. Application of this knowledge has led to the experimental trial of electrical stimulation in diseased muscle, both in the dystrophic mouse and in children with Duchenne muscular dystrophy. This has shown a beneficial effect of slow frequency stimulation. Another route through which muscle properties can be influenced is by changing the load by procedures such as tenotomy. This has been studied by complete tenotomy in normal animals and recently by selective partial procedures in human disease. Y. Rideau has shown that release of early shortening (contractures) of several muscles, a consistent feature in Duchenne muscular dystrophy, has a beneficial effect on muscle function. From personal observations on a number of Rideau's patients who have undergone this procedure the improvement in function seems disproportionate to what could be explained on simple biomechanical grounds alone and suggests some more fundamental change in the contractile properties of the muscle.

  18. Early Career Boot Camp: a novel mechanism for enhancing early career development for psychologists in academic healthcare.

    Science.gov (United States)

    Foran-Tuller, Kelly; Robiner, William N; Breland-Noble, Alfiee; Otey-Scott, Stacie; Wryobeck, John; King, Cheryl; Sanders, Kathryn

    2012-03-01

    The purpose of this article is to describe a pilot mentoring program for Early Career Psychologists (ECPs) working in Academic Health Centers (AHCs) and synthesize the lessons learned to contribute to future ECP and AHC career development training programs. The authors describe an early career development model, named the Early Career Boot Camp. This intensive experience was conducted as a workshop meant to build a supportive network and to provide mentorship and survival tools for working in AHCs. Four major components were addressed: professional effectiveness, clinical supervision, strategic career planning, and academic research. Nineteen attendees who were currently less than 5 years post completion of doctoral graduate programs in psychology participated in the program. The majority of boot camp components were rated as good to excellent, with no component receiving below average ratings. Of the components offered within the boot camp, mentoring and research activities were rated the strongest, followed by educational activities, challenges in AHCS, and promotion and tenure. The article describes the purpose, development, implementation, and assessment of the program in detail in an effort to provide an established outline for future organizations to utilize when mentoring ECPs.

  19. Semantic mechanisms may be responsible for developing synesthesia

    Directory of Open Access Journals (Sweden)

    Aleksandra eMroczko-Wąsowicz

    2014-08-01

    Full Text Available Currently, little is known about how synesthesia develops and which aspects of synesthesia can be acquired through a learning process. We review the increasing evidence for the role of semantic representations in the induction of synesthesia, and argue for the thesis that synesthetic abilities are developed and modified by semantic mechanisms. That is, in certain people semantic mechanisms associate concepts with perception-like experiences—and this association occurs in an extraordinary way. This phenomenon can be referred to as higher synesthesia or ideasthesia. The present analysis suggests that synesthesia develops during childhood and is being enriched further throughout the synesthetes’ lifetime; for example, the already existing concurrents may be adopted by novel inducers or new concurrents may be formed. For a deeper understanding of the origin and nature of synesthesia we propose to focus future research on two aspects: i the similarities between synesthesia and ordinary phenomenal experiences based on concepts, and ii the tight entanglement of perception, cognition and the conceptualization of the world. Most importantly, an explanation of how biological systems get to generate experiences, synesthetic or not, may have to involve an explanation of how we form semantic networks in general and what their role is in our ability to be aware of the surrounding world.

  20. Semantic mechanisms may be responsible for developing synesthesia.

    Science.gov (United States)

    Mroczko-Wąsowicz, Aleksandra; Nikolić, Danko

    2014-01-01

    Currently, little is known about how synesthesia develops and which aspects of synesthesia can be acquired through a learning process. We review the increasing evidence for the role of semantic representations in the induction of synesthesia, and argue for the thesis that synesthetic abilities are developed and modified by semantic mechanisms. That is, in certain people semantic mechanisms associate concepts with perception-like experiences-and this association occurs in an extraordinary way. This phenomenon can be referred to as "higher" synesthesia or ideasthesia. The present analysis suggests that synesthesia develops during childhood and is being enriched further throughout the synesthetes' lifetime; for example, the already existing concurrents may be adopted by novel inducers or new concurrents may be formed. For a deeper understanding of the origin and nature of synesthesia we propose to focus future research on two aspects: (i) the similarities between synesthesia and ordinary phenomenal experiences based on concepts; and (ii) the tight entanglement of perception, cognition and the conceptualization of the world. Importantly, an explanation of how biological systems get to generate experiences, synesthetic or not, may have to involve an explanation of how semantic networks are formed in general and what their role is in the ability to be aware of the surrounding world.

  1. Directionally solidified biopolymer scaffolds: Mechanical properties and endothelial cell responses

    Science.gov (United States)

    Meghri, Nicholas W.; Donius, Amalie E.; Riblett, Benjamin W.; Martin, Elizabeth J.; Clyne, Alisa Morss; Wegst, Ulrike G. K.

    2010-07-01

    Vascularization is a primary challenge in tissue engineering. To achieve it in a tissue scaffold, an environment with the appropriate structural, mechanical, and biochemical cues must be provided enabling endothelial cells to direct blood vessel growth. While biochemical stimuli such as growth factors can be added through the scaffold material, the culture medium, or both, a well-designed tissue engineering scaffold is required to provide the necessary local structural and mechanical cues. As chitosan is a well-known carrier for biochemical stimuli, the focus of this study was on structure-property correlations, to evaluate the effects of composition and processing conditions on the three-dimensional architecture and properties of freeze-cast scaffolds; to establish whether freeze-east scaffolds are promising candidates as constructs promoting vascularization; and to conduct initial tissue culture studies with endothelial cells on flat substrates of identical compositions as those of the scaffolds to test whether these are biocompatible and promote cell attachment and proliferation.

  2. Early lactation feed intake and milk yield responses of dairy cows offered grass silages harvested at early maturity stages.

    Science.gov (United States)

    Randby, A T; Weisbjerg, M R; Nørgaard, P; Heringstad, B

    2012-01-01

    The main objective was to evaluate the potential of grass silages of very high quality to support a high milk yield with a low or moderate, or even without concentrate supplementation. Production responses to increased levels of concentrate supplementation with 3 primary growth grass silages differing in digestibility were studied using 66 Norwegian Red dairy cows. Roundbale silage was produced from a timothy-dominated sward at very early (H1), early (H2), and normal (H3) stages of crop maturity. Crops were rapidly wilted (silages were restrictedly fermented. Silage digestible organic matter in dry matter (DM) values were 747, 708, and 647 g/kg of DM for H1, H2, and H3, respectively. Dietary treatments were fed in a 3×3 factorial arrangement of the 3 silages supplemented with 3 concentrate levels (4, 8, and 12 kg/d) and, additionally, H1 was offered without concentrates and H3 with 16 kg/d, giving a total of 11 diets. Cows, blocked according to parity and calving date, were introduced to the experiment before calving and kept in the experiment until wk 16 of lactation. Silage was offered ad libitum in loose housing and concentrate was available in automatic feed stations. Intake of grass silage when fed as the sole feed was 16.9 kg of DM on average for lactation wk 1 to 16. When H1 was supplemented with 4 or 8 kg of concentrates, silage DM intake did not change, but total DM intake increased to 20.6 and 23.7 kg/d, respectively. Energy-corrected milk (ECM) yield increased from 23.4 kg when H1 was offered without concentrate supplement to 29.1 and 32.8 kg when supplemented with 4 or 8 kg concentrate, respectively. None of the other diets equaled the yield obtained by H1 plus 8 kg of concentrate. Feed intake and yield of cows offered H3 plus 4 kg of concentrates were strongly constrained by high dietary fiber concentration. They consumed 16.5 g of neutral detergent fiber/kg of body weight and spent more time eating silage than cows offered other diets. The highest

  3. Full-Breadth Analysis of CD8+ T-Cell Responses in Acute Hepatitis C Virus Infection and Early Therapy

    Science.gov (United States)

    Lauer, Georg M.; Lucas, Michaela; Timm, Joerg; Ouchi, Kei; Kim, Arthur Y.; Day, Cheryl L.; zur Wiesch, Julian Schulze; Paranhos-Baccala, Glaucia; Sheridan, Isabelle; Casson, Deborah R.; Reiser, Markus; Gandhi, Rajesh T.; Li, Bin; Allen, Todd M.; Chung, Raymond T.; Klenerman, Paul; Walker, Bruce D.

    2005-01-01

    Multispecific CD8+ T-cell responses are thought to be important for the control of acute hepatitis C virus (HCV) infection, but to date little information is actually available on the breadth of responses at early time points. Additionally, the influence of early therapy on these responses and their relationships to outcome are controversial. To investigate this issue, we performed comprehensive analysis of the breadth and frequencies of virus-specific CD8+ T-cell responses on the single epitope level in eight acutely infected individuals who were all started on early therapy. During the acute phase, responses against up to five peptides were identified. During therapy, CD8+ T-cell responses decreased rather than increased as virus was controlled, and no new specificities emerged. A sustained virological response following completion of treatment was independent of CD8+ T-cell responses, as well as CD4+ T-cell responses. Rapid recrudescence also occurred despite broad CD8+ T-cell responses. Importantly, in vivo suppression of CD3+ T cells using OKT3 in one subject did not result in recurrence of viremia. These data suggest that broad CD8+ T-cell responses alone may be insufficient to contain HCV replication, and also that early therapy is effective independent of such responses. PMID:16189000

  4. Early vs. asymptotic growth responses of herbaceous plants to elevated CO[sub 2

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, S.C.; Jasienski, M.; Bazzaz, F.A. (Harvard Univ., Cambridge, MA (United States). Dept. of Organismic and Evolutionary Biology)

    1999-07-01

    Although many studies have examined the effects of elevated carbon dioxide on plant growth,'' the dynamics of growth involve at least two parameters, namely, an early rate of exponential size increase and an asymptotic size reached late in plant ontogeny. The common practice of quantifying CO[sub 2] responses as a single response ratio thus obscures two qualitatively distinct kinds of effects. The present experiment examines effects of elevated CO[sub 2] on both early and asymptotic growth parameters in eight C[sub 3] herbaceous plant species (Abutilon theophrasti, Cassia obtusifolia, Plantago major, Rumex crispus, Taraxacum officinale, Dactylis glomerata, Lolium multiflorum, and Panicum dichotomoflorum). Plants were grown for 118--172 d in a factorial design of CO[sub 2] (350 and 700 [micro]L/L) and plant density (individually grown vs. high-density monocultures) under edaphic conditions approximating those of coastal areas in Massachusetts. For Abutilon theophrasti, intraspecific patterns of plant response were also assessed using eight genotypes randomly sampled from a natural population and propagated as inbred lines.

  5. Developmental changes in mismatch responses to mandarin consonants and lexical tones from early to middle childhood.

    Directory of Open Access Journals (Sweden)

    Huei-Mei Liu

    Full Text Available The purpose of this study was to use mismatch responses (MMRs to explore the dynamic changes of Mandarin speech perception abilities from early to middle childhood. Twenty preschoolers, 18 school-aged children, and 26 adults participated in this study. Two sets of synthesized speech stimuli varying in Mandarin consonant (alveolo-palatal affricate vs. fricative and lexical tone features (rising vs. contour tone were used to examine the developmental course of speech perception abilities. The results indicated that only the adult group demonstrated typical early mismatch negativity (MMN responses, suggesting that the ability to discriminate specific speech cues in Mandarin consonant and lexical tone is a continuing process in preschool- and school-aged children. Additionally, distinct MMR patterns provided evidence indicating diverse developmental courses to different speech characteristics. By incorporating data from the two speech conditions, we propose using MMR profiles consisting of mismatch negativity (MMN, positive mismatch response (p-MMR, and late discriminative negativity (LDN as possible brain indices to investigate speech perception development.

  6. The p66(Shc adaptor protein controls oxidative stress response in early bovine embryos.

    Directory of Open Access Journals (Sweden)

    Dean H Betts

    Full Text Available The in vitro production of mammalian embryos suffers from high frequencies of developmental failure due to excessive levels of permanent embryo arrest and apoptosis caused by oxidative stress. The p66Shc stress adaptor protein controls oxidative stress response of somatic cells by regulating intracellular ROS levels through multiple pathways, including mitochondrial ROS generation and the repression of antioxidant gene expression. We have previously demonstrated a strong relationship with elevated p66Shc levels, reduced antioxidant levels and greater intracellular ROS generation with the high incidence of permanent cell cycle arrest of 2-4 cell embryos cultured under high oxygen tensions or after oxidant treatment. The main objective of this study was to establish a functional role for p66Shc in regulating the oxidative stress response during early embryo development. Using RNA interference in bovine zygotes we show that p66Shc knockdown embryos exhibited increased MnSOD levels, reduced intracellular ROS and DNA damage that resulted in a greater propensity for development to the blastocyst stage. P66Shc knockdown embryos were stress resistant exhibiting significantly reduced intracellular ROS levels, DNA damage, permanent 2-4 cell embryo arrest and diminished apoptosis frequencies after oxidant treatment. The results of this study demonstrate that p66Shc controls the oxidative stress response in early mammalian embryos. Small molecule inhibition of p66Shc may be a viable clinical therapy to increase the developmental potential of in vitro produced mammalian embryos.

  7. Transcriptome Analysis of Early Responsive Genes in Rice during Magnaporthe oryzae Infection

    Directory of Open Access Journals (Sweden)

    Yiming Wang

    2014-12-01

    Full Text Available Rice blast disease caused by Magnaporthe oryzae is one of the most serious diseases of cultivated rice (Oryza sativa L. in most rice-growing regions of the world. In order to investigate early response genes in rice, we utilized the transcriptome analysis approach using a 300 K tilling microarray to rice leaves infected with compatible and incompatible M. oryzae strains. Prior to the microarray experiment, total RNA was validated by measuring the differential expression of rice defense-related marker genes (chitinase 2, barwin, PBZ1, and PR-10 by RT-PCR, and phytoalexins (sakuranetin and momilactone A with HPLC. Microarray analysis revealed that 231 genes were up-regulated (>2 fold change, p < 0.05 in the incompatible interaction compared to the compatible one. Highly expressed genes were functionally characterized into metabolic processes and oxidation-reduction categories. The oxidative stress response was induced in both early and later infection stages. Biotic stress overview from MapMan analysis revealed that the phytohormone ethylene as well as signaling molecules jasmonic acid and salicylic acid is important for defense gene regulation. WRKY and Myb transcription factors were also involved in signal transduction processes. Additionally, receptor-like kinases were more likely associated with the defense response, and their expression patterns were validated by RT-PCR. Our results suggest that candidate genes, including receptor-like protein kinases, may play a key role in disease resistance against M. oryzae attack.

  8. Early Prediction of Long-Term Response to Cabergoline in Patients with Macroprolactinomas

    Directory of Open Access Journals (Sweden)

    Youngki Lee

    2014-09-01

    Full Text Available BackgroundCabergoline is typically effective for treating prolactinomas; however, some patients display cabergoline resistance, and the early characteristics of these patients remain unclear. We analyzed early indicators predicting long-term response to cabergoline.MethodsWe retrospectively reviewed the cases of 44 patients with macroprolactinomas who received cabergoline as first-line treatment; the patients were followed for a median of 16 months. The influence of various clinical parameters on outcomes was evaluated.ResultsForty patients (90.9% were treated medically and displayed tumor volume reduction (TVR of 74.7%, a prolactin normalization (NP rate of 81.8%, and a complete response (CR; TVR >50% with NP, without surgery rate of 70.5%. Most patients (93.1% with TVR ≥25% and NP at 3 months eventually achieved CR, whereas only 50% of patients with TVR ≥25% without NP and no patients with TVR 25% at 3 months without NP, particularly those with huge prolactinomas, because a delayed response may be achieved. As surgery can reduce the cabergoline dose necessary for successful disease control, it should be considered for cabergoline-resistant patients.

  9. Early pregnancy alters the metabolic responses to restricted nutrition in sheep.

    Science.gov (United States)

    Sosa, C; Abecia, J A; Carriquiry, M; Forcada, F; Martin, G B; Palacín, I; Meikle, A

    2009-01-01

    This study investigated whether a 27-day period of nutrition at half-maintenance during early pregnancy (up to Day 14) could alter maternal endocrine responses. Forty-six ewes were fed all or half of their maintenance requirements and slaughtered on Day 14 of the oestrous cycle or pregnancy. We used real time RT-PCR to study gene expression of growth hormone receptor (GHR) and leptin in adipose tissue and GHR, GHR1A and of the insulin-like growth factor I (IGF-I) in the liver. Blood profiles of metabolites and metabolic hormones were also determined. Throughout the experiment, underfed animals presented lower body weight and body condition, greater plasma concentrations of non-esterified fatty acids (NEFA), and lower plasma concentrations of leptin, compared to adequately fed animals. Undernutrition affected the patterns of gene expression in adipose and hepatic tissues, and the responses differed between pregnant and non-pregnant ewes. In adequately fed ewes, pregnancy up-regulated leptin mRNA expression in adipose tissue, a response that was impaired in underfed ewes. The hepatic expression of IGF-I mRNA was increased by pregnancy in underfed animals while no effect was observed in adequately fed ewes. It remains to be determined whether the changes in the endocrine milieu are paralleled by modifications in uterine gene expression that could alter the environment of the embryo during early pregnancy.

  10. [Establishment of malaria early warning system in Jiangsu Province III effect of automatic early warning information system on the response of malaria elimination].

    Science.gov (United States)

    Wang, Wei-Ming; Zhou, Hua-Yun; Liu, Yao-Bao; Cao, Yuan-Yuan; Cao, Jun; Gao, Qi

    2014-02-01

    To evaluate the effect of automatic early warning information system on the response of malaria elimination in Jiangsu Province through the operation of the national automatic early warning system of infectious diseases. The malaria early warning information was collected from the automatic early warning information subsystem in the national information system for diseases control and prevention. Malaria early warning signals were analyzed from September 1 to December 31, 2012. The statistical analysis was conducted for the completion rates of case investigation within 3 days before and after the application of malaria early warning information system. Jiangsu Province received 85 mobile phone short messages (SMS) of malaria case from early warning system from September 1 to December 31, 2012. After judgments, 23 cases were deleted including 8 repeated cases and 15 cases that were excluded through the microscopy examination and epidemiological investigation by the confirmation of county CDC. From July to December in 2012, the monthly completion rates of case investigation within 3 days were 55.56%, 78.57%, 90.00%, 100%, 100% and 100%, respectively. The completion rates of case investigation within 3 days in July, August, September and October were significantly different by chi2 test ( chi2 = 10.66, P system. The malaria warning system from the national infectious diseases can effectively improve the response to malaria cases for primary CDC. It also plays an important role for the timely confirmation and diagnosis of malaria cases.

  11. Early α-fetoprotein response predicts survival in patients with advanced hepatocellular carcinoma treated with sorafenib

    Directory of Open Access Journals (Sweden)

    Lee SH

    2015-04-01

    in AFP responders than in non-responders (72.1% vs 47.0%, respectively; P=0.007. In a sub-group with SD, OS (median 12.7 vs 5.8 months, respectively and PFS (median 9.1 vs 3.7 months, respectively were significantly longer in AFP responders than in non-responders (all P<0.05. Conclusion: Early AFP response may be useful for predicting survival in patients with advanced HCC treated with sorafenib. Keywords: α-fetoprotein, hepatocellular carcinoma, response, prognosis, treatment outcome, sorafenib

  12. Effects of Part- and Whole-Object Primes on Early MEG Responses to Mooney Faces and Houses.

    Science.gov (United States)

    Steinberg Lowe, Mara; Lewis, Gwyneth A; Poeppel, David

    2016-01-01

    Results from neurophysiological experiments suggest that face recognition engages a sensitive mechanism that is reflected in increased amplitude and decreased latency of the MEG M170 response compared to non-face visual targets. Furthermore, whereas recognition of objects (e.g., houses) has been argued to be based on individual features (e.g., door, window), face recognition may depend more on holistic information. Here we analyzed priming effects of component and holistic primes on 20 participants' early MEG responses to two-tone (Mooney) images to determine whether face recognition in this context engages "featural" or "configural" processing. Although visually underspecified, the Mooney images in this study elicited M170 responses that replicate the typical face vs. house effect. However, we found a distinction between holistic vs. component primes that modulated this effect dependent upon compatibility (match) between the prime and target. The facilitatory effect of holistic faces and houses for Mooney faces and houses, respectively, suggests that both Mooney face and house recognition-both low spatial frequency stimuli-are based on holistic information.

  13. Interpreting Bananaworld: A response to Bub's Quantum Mechanics for Primates

    CERN Document Server

    Mohrhoff, Ulrich

    2012-01-01

    The interpretative principle proposed by Bub in 1211.3062v1 [quant-ph] is justified only for all practical purposes (Bell's "FAPP trap"). An alternative interpretative principle is proposed. It brings to light those features of the quantum world because of which the fundamental theoretical framework of physics is a "mere" probability calculus, and it amply justifies Bohr's insistence that quantum-mechanical observables cannot be defined without reference to the experimental conditions in which they are measured. It implies that the spatial distinctions we make cannot be intrinsic to space, that regions "of space" must be realized by macroscopic objects, that the spatiotemporal differentiation of the physical world is incomplete, that the positions of macroscopic objects (suitably defined) are definite in a nonclassical sense, and that unconditional factuality can be consistently attributed to them.

  14. Early establishment of trees at the alpine treeline: idiosyncratic species responses to temperature-moisture interactions.

    Science.gov (United States)

    Loranger, Hannah; Zotz, Gerhard; Bader, Maaike Y

    2016-01-01

    On a global scale, temperature is the main determinant of arctic and alpine treeline position. However on a local scale, treeline form and position vary considerably due to other climatic factors, tree species ecology and life-stage-dependent responses. For treelines to advance poleward or uphill, the first steps are germination and seedling establishment. These earliest life stages may be major bottlenecks for treeline tree populations and will depend differently on climatic conditions than adult trees. We investigated the effect of soil temperature and moisture on germination and early seedling survival in a field experiment in the French Alps near the local treeline (2100 m a.s.l.) using passive temperature manipulations and two watering regimes. Five European treeline tree species were studied: Larix decidua, Picea abies, Pinus cembra, Pinus uncinata and Sorbus aucuparia In addition, we monitored the germination response of three of these species to low temperatures under controlled conditions in growth chambers. The early establishment of these trees at the alpine treeline was limited either by temperature or by moisture, the sensitivity to one factor often depending on the intensity of the other. The results showed that the relative importance of the two factors and the direction of the effects are highly species-specific, while both factors tend to have consistent effects on both germination and early seedling survival within each species. We show that temperature and water availability are both important contributors to establishment patterns of treeline trees and hence to species-specific forms and positions of alpine treelines. The observed idiosyncratic species responses highlight the need for studies including several species and life-stages to create predictive power concerning future treeline dynamics.

  15. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    Directory of Open Access Journals (Sweden)

    Cui Zhi-Hua

    2012-03-01

    Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

  16. Computed tomography assessment of early response to neoadjuvant therapy in colon cancer

    DEFF Research Database (Denmark)

    Dam, Claus; Lund-Rasmussen, Vera; Pløen, John

    2015-01-01

    INTRODUCTION: Using multidetector computed tomography, we aimed to assess the early response of neoadjuvant drug therapy for locally advanced colon cancer. METHODS: Computed tomography with IV contrast was acquired from 67 patients before and after up to three cycles of preoperative treatment. All...... patients had histologically confirmed colon cancer, a T4 or T3 tumour with extramural invasion ≥ 5 mm and no distant metastases or peritoneal nodules. The patients were treated with oxaliplatin and capecitabine. In addition, those with no mutations in the KRAS, BRAF and PIK3CA genes were also treated...

  17. Early Versus Late Onset of Cannabis Use: Differences in Striatal Response to Cannabis Cues

    Science.gov (United States)

    Wetherill, Reagan R.; Hager, Nathan; Jagannathan, Kanchana; Mashhoon, Yasmin; Pater, Heather; Childress, Anna Rose; Franklin, Teresa R.

    2017-01-01

    Addiction theories posit that addiction is the result of a progressive transition from voluntary to habitual, compulsive drug use—changes that have been linked, in animals, to a shift from ventral to dorsal striatal control over drug-seeking behavior. Thus, we hypothesized that early-onset (EOs) cannabis users versus late-onset (LOs) cannabis users might exhibit, respectively, greater dorsal versus ventral striatal response to drug cues. We used functional magnetic resonance imaging and an event-related blood oxygen level-dependent backward-masking task to evaluate striatal responses to backward-masked cannabis cues (vs. neutral cues) in EOs (cannabis use patterns. Direct comparisons revealed that EOs showed greater response to cannabis cues in the dorsal striatum than LOs (p 50 voxels). Within-group analyses revealed that EOs showed greater neural response to cannabis cues in the dorsal striatum, whereas LOs exhibited greater neural response to cannabis cues in the ventral striatum. Although cross-sectional, these findings are consistent with recent addiction theories suggesting a progressive shift from ventral to dorsal striatal control over drug-seeking behavior and highlight the importance of age of onset of cannabis use on the brain and cognition.

  18. The stress response to surgery: release mechanisms and the modifying effect of pain relief

    DEFF Research Database (Denmark)

    Kehlet, H

    1989-01-01

    This short review updates information on the release mechanisms of the systemic response to surgical injury and the modifying effect of pain relief. Initiation of the response is primarily due to afferent nerve impulses combined with release of humoral substances (such as prostaglandins, kinins...... in releasing the classical endocrine catabolic response, while humoral factors are important for the hyperthermic response, changes in coagulation and fibrinolysis immunofunction, and capillary permeability. The modifying effect of pain relief on the surgical stress response is dependent upon the technique...... on the stress response. In summary, pain alleviation itself may not necessarily lead to an important modification of the stress response, and a combined approach with inhibition of the neural and humoral release mechanisms is necessary for a pronounced inhibition or prevention of the response to surgical injury....

  19. Early and late nasal symptom response to allergen challenge. The effect of pretreatment with a glucocorticosteroid spray

    DEFF Research Database (Denmark)

    Grønborg, H; Bisgaard, H; Rømeling, Frans

    1993-01-01

    with the glucocorticosteroid budesonide (200 micrograms twice daily) for 14 d and with placebo in a double-blind, cross-over trial. The early response, consisting of sneezing, discharge, and blockage, was followed by a weak late response, consisting of a few sneezes and nose-blowings, and of a sustained nasal blockage......We challenged 30 pollen-sensitive volunteers with allergen, recorded symptoms and signs over a 10-h period, and rechallenged them after 24 h, in order to characterize the early and late allergic symptom response in the nose. The challenge was performed after topical pretreatment....... These symptoms did not have a well-defined peak in time, and a biphasic symptom curve could not be identified. The rechallenge response showed increased nasal responsiveness. The degree of budesonide effect on the early response varied, depending on the symptom; there was a marked effect on sneezing (72...

  20. Response prediction for modified mechanical systems based on in-situ frequency response functions: Theoretical and numerical studies

    Science.gov (United States)

    Wang, Zengwei; Zhu, Ping

    2017-07-01

    In this paper, a general method using in-situ frequency response functions (FRFs) is proposed for predicting operational responses of modified mechanical systems. In the method responses of modified mechanical systems can be calculated by using the delta dynamic stiffness matrix, the subsystem FRF matrix and responses of the original system, even though operational forces are unknown. The proposed method is derived theoretically in a general form as well as for six specific scenarios. The six scenarios correspond respectively to: (a) modifications made on the mass; (b) changes made on the stiffness values of the link between a degree-of-freedom (DOF) and the ground; (c) the fully rigid link between a DOF and the ground; (d) changes made on the stiffness values of the link between two DOFs; (e) the null link between two DOFs and (f) the fully rigid link between two DOFs. It is found that for scenarios (a), (b) and (d) the delta dynamic stiffness matrix is required when predicting responses of the modified mechanical system. But for scenarios (c), (e) and (f), no delta dynamic stiffness matrix is required and the new system responses can be calculated solely using the subsystem FRF matrix and responses of the original system. The proposed method is illustrated by a numerical example and validated using data generated by finite element simulations. The work in this paper will be beneficial to solving vibration and noise engineering problems.

  1. Real-time performance of probabilistic, first-motion earthquake mechanisms to improve tsunami early-warning

    Science.gov (United States)

    Lomax, Anthony; Michelni, Alberto; Bernardi, Fabrizio; Scognamiglio, Laura

    2017-04-01

    The first tsunami warning messages are typically based on simple earthquake parameters: epicenter location, hypocenter depth, and magnitude. The addition of early information on the faulting mechanism can enable more reliable estimates of seafloor uplift, tsunami excitation, tsunami potential and impact, and earlier, real-time tsunami scenario forecasting. Full-waveform, centroid moment tensor solutions (CMT) are typically available in 3-15min for local/near-regional earthquakes and in 10-30min for regional/teleseismic distances. In contrast, classic, P first-motion (FM) focal-mechanisms can be available within 3min for local/near-regional events and in 5-10 min for regional/teleseismic distances. We present fmamp, a robust, probabilistic, adaptive grid-search, FM mechanism determination procedure which generates a comprehensive set of "acceptable" FM mechanisms and related uncertainties. This FM solution, combined with fast magnitude estimates such as Mwp, forms a CMT proxy for rapid source characterization and analysis before a definitive, waveform CMT is available. Currently, fmamp runs in real-time in Early-est*, the module for rapid earthquake detection, location and analysis at the INGV tsunami alert center (CAT, "Centro di Allerta Tsunami"), part of the Italian, candidate Tsunami Watch Provider. We show the real-time performance of fmamp and compare its speed and accuracy to CMT results. For large earthquakes in areas of sparse seismic station coverage, fmamp mechanisms are typically available in 5-10min, while CMT results take 10-30min. The fmamp solutions usually agree with CMT results for larger events, but sometimes differ, due to insufficient or noisy FM readings, or real difference between the FM mechanism, representing the faulting at the hypocenter, and the CMT mechanism representing some average, centroid faulting. * http://early-est.alomax.net, http://early-est.rm.ingv.it, http://alomax.free.fr/posters/early-est

  2. Seagull feather shaft: Correlation between structure and mechanical response.

    Science.gov (United States)

    Wang, Bin; Meyers, Marc André

    2017-01-15

    Flight feathers are unique among a variety of keratinous appendages in that they are lightweight, stiff and strong. They are designed to withstand aerodynamic forces, but their morphology and structure have been oversimplified and thus understudied historically. Here we present an investigation of the shaft from seagull primary feathers, elucidate the hierarchical fibrous and porous structure along the shaft length, and correlate the tensile and nanomechanical properties to the fiber orientation. An analysis of the compressive behavior of the rachis based on a square-section model shows a good fit with experimental results, and demonstrates the synergy between the cortex and medulla. Flexural properties of the shaft along the shaft length, analyzed as a sandwich composite, reveal that although all flexural parameters decrease towards the distal shaft, the specific equivalent flexural modulus and strength increase by factors of 2 and 3, respectively. The failure mode in flexure for all specimens is buckling on the compressive surface, whereas the foamy medulla prevents destructive axial cracking and introduces important toughening mechanisms: crack deflection, fiber bridging, and microcracking.

  3. High-Strain Rate Mechanical Response of Cured Epoxy Networks

    Science.gov (United States)

    Sirk, Timothy; Khare, Ketan; Karim, Mir; Lenhart, Joseph; Khare, Rajesh; Andzelm, Jan

    2013-03-01

    Chemically cross-linked polymer networks are increasingly common in high performance composites, adhesives and other applications involving high-impact loading conditions or ballistic collisions. The mechanical behavior of epoxy and other polymer networks exhibit a strong dependence on strain rate near the glass transition temperature (Tg); however, the elastic modulus at strain rates greater than 105 1/s is difficult to capture with experimental techniques. We present computational results of Di-Glycidyl Ether of Bisphenol A (DGEBA) and Jeffamine diamines (D230) from molecular dynamics simulation, which is intrinsically well-suited to model material deformation at high strain rates. Our results show that the experimental Tg can be reproduced from molecular dynamics, and the Williams-Landel-Ferry equation is useful in rationalizing the shift of Tg due to fast annealing and high strain rates. Temperature sweeps of elastic modulus show the glass-rubber transition to occur over a significantly wider temperature range compared with experimental measurements at low strain rates.

  4. Two distinct neural mechanisms in early visual cortex determine subsequent visual processing.

    Science.gov (United States)

    Jacobs, Christianne; de Graaf, Tom A; Sack, Alexander T

    2014-10-01

    Neuroscience research has conventionally focused on how the brain processes sensory information, after the information has been received. Recently, increased interest focuses on how the state of the brain upon receiving inputs determines and biases their subsequent processing and interpretation. Here, we investigated such 'pre-stimulus' brain mechanisms and their relevance for objective and subjective visual processing. Using non-invasive focal brain stimulation [transcranial magnetic stimulation (TMS)] we disrupted spontaneous brain state activity within early visual cortex (EVC) before onset of visual stimulation, at two different pre-stimulus-onset-asynchronies (pSOAs). We found that TMS pulses applied to EVC at either 20 msec or 50 msec before onset of a simple orientation stimulus both prevented this stimulus from reaching visual awareness. Interestingly, only the TMS-induced visual suppression following TMS at a pSOA of ?20 msec was retinotopically specific, while TMS at a pSOA of ?50 msec was not. In a second experiment, we used more complex symbolic arrow stimuli, and found TMS-induced suppression only when disrupting EVC at a pSOA of ? ?60 msec, which, in line with Experiment 1, was not retinotopically specific. Despite this topographic unspecificity of the ?50 msec effect, the additional control measurements as well as tracking and removal of eye blinks, suggested that also this effect was not the result of an unspecific artifact, and thus neural in origin. We therefore obtained evidence of two distinct neural mechanisms taking place in EVC, both determining whether or not subsequent visual inputs are successfully processed by the human visual system.

  5. The Vallecas Project: a cohort to identify early markers and mechanisms of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Javier eOlazarán

    2015-09-01

    Full Text Available Introduction. Alzheimer’s disease (AD is a major threat for the well-being of an increasingly aged world population. The physiopathological mechanisms of late-onset AD are multiple, possibly heterogeneous, and not well understood. Different combinations of variables from several domains (i.e., clinical, neuropsychological, structural, and biochemical markers may predict dementia conversion, according to distinct physiopathological pathways, in different groups of subjects. Methods. We launched the Vallecas Project (VP, a cohort study of non-demented people aged 70 to 85, to characterize the social, clinical, neuropsychological, structural, and biochemical underpinnings of AD inception. Given the exploratory nature of the VP, multidimensional and machine learning techniques will be applied, in addition to the traditional multivariate statistical methods. Results. A total of 1,169 subjects were recruited between October 2011 and December 2013. Mean age was 74.4 years (SD 3.9, 63.5% of the subjects were women, and 17.9% of the subjects were carriers of at least one ε4 allele of the apolipoprotein E (APOE gene. Cognitive diagnoses at inclusion were as follows: normal cognition 93.0% and mild cognitive impairment (MCI 7.0% (3.1% amnestic MCI, 0.1% non-amnestic MCI, 3.8% mixed MCI. Blood samples were obtained and stored for future determinations in 99.9% of the subjects and 3T magnetic resonance imaging (MRI study was conducted in 89.9% of the volunteers. The cohort is being followed up annually for four years after the baseline. Conclusion. We have established a valuable homogeneous single-center cohort which, by identifying groups of variables associated with high risk of MCI or dementia conversion, should help to clarify the early physiopathological mechanisms of AD and should provide avenues for prompt diagnosis and AD prevention.

  6. Involvement of metabolites in early defense mechanism of oil palm (Elaeis guineensis Jacq.) against Ganoderma disease.

    Science.gov (United States)

    Nusaibah, S A; Siti Nor Akmar, A; Idris, A S; Sariah, M; Mohamad Pauzi, Z

    2016-12-01

    Understanding the mechanism of interaction between the oil palm and its key pathogen, Ganoderma spp. is crucial as the disease caused by this fungal pathogen leads to a major loss of revenue in leading palm oil producing countries in Southeast Asia. Here in this study, we assess the morphological and biochemical changes in Ganoderma disease infected oil palm seedling roots in both resistant and susceptible progenies. Rubber woodblocks fully colonized by G. boninense were applied as a source of inoculum to artificially infect the roots of resistant and susceptible oil palm progenies. Gas chromatography-mass spectrometry was used to measure an array of plant metabolites in 100 resistant and susceptible oil palm seedling roots treated with pathogenic Ganoderma boninense fungus. Statistical effects, univariate and multivariate analyses were used to identify key-Ganoderma disease associated metabolic agitations in both resistant and susceptible oil palm root tissues. Ganoderma disease related defense shifts were characterized based on (i) increased antifungal activity in crude extracts, (ii) increased lipid levels, beta- and gamma-sitosterol particularly in the resistant progeny, (iii) detection of heterocyclic aromatic organic compounds, benzo [h] quinoline, pyridine, pyrimidine (iv) elevation in antioxidants, alpha- and beta-tocopherol (iv) degraded cortical cell wall layers, possibly resulting from fungal hydrolytic enzyme activity needed for initial penetration. The present study suggested that plant metabolites mainly lipids and heterocyclic aromatic organic metabolites could be potentially involved in early oil palm defense mechanism against G. boninense infection, which may also highlight biomarkers for disease detection, treatment, development of resistant variety and monitoring. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Nisqually - Early Detection Rapid Response, Monitoring and Mapping of High Priority Invasives with Refuge Weed Warriors 2006

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This project plan was to initiate a program for early detection and response, monitoring and mapping of invasive species on Grays Harbor NWR and continued current...

  8. Nisqually - Early Detection Rapid Response, Monitoring and Mapping of High Priority Invasive Species with Nisqually NWRC Weed Warriors 2007

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This project continues a successful program of early detection and rapid response, monitoring and mapping of invasive species on Nisqually NWRC (NNWRC) by Weed...

  9. Nisqually - Early Detection Rapid Response, Monitoring and Mapping of High Priority Invasive Species with Nisqually NWRC Weed Warriors 2008

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This project will continue a successful program of early detection and rapid response, monitoring and mapping of invasive species on Nisqually NWRC by Weed Warrior...

  10. Early Growth Response gene 1 (Egr-1) regulates HSV-1 ICP4 and ICP22 gene expression

    Institute of Scientific and Technical Information of China (English)

    Gautam R Bedadala; Rajeswara C Pinnoji; Shao-Chung V Hsia

    2007-01-01

    The molecular mechanisms mediating herpes simplex virus type 1 (HSV-1) gene silencing during latent infection are not clear. Five copies of early growth response gene 1 (Egr-1) binding elements were identified in the intron of HSV-1 ICP22 (infected cell protein No. 22) gene, leading to the hypothesis that Egr-1 binds to the viral genome and regulates the viral gene expression. Transient co-transfection assays indicated that Egr-1 negatively regulated the transcription of both full-length and intron-removed ICP22 promoters. The same assays also revealed that Egr-1 repressed ICP4 (infected cell protein No. 4) promoter activity in a dose-dependent manner but showed less inhibition when the intron was removed.Histone deacetylation was not involved in this regulation since histone deacetylase inhibitor trichostatin A did not exhibit any effect on Egr-1-mediated repression. Chromatin immunoprecipitation assays showed that Egr-1 reduced the binding of Sp1 to the promoters and that the co-repressor Nab2 (NGFI-A/EGR1-binding protein) was recruited to the proximity of ICP4 in the presence of Egr-1. These results suggested that the multi functional transcription factor Egr-1 can repress HSV-1 immediate-early gene expression through the recruitment of co-repressor Nab2 and reduction of Sp1 occupancy,and thus may play a critical role in HSV-1 gene silencing during latency.

  11. Early educational foundations for the development of civic responsibility: an African experience.

    Science.gov (United States)

    Serpell, Robert; Mumba, Paul; Chansa-Kabali, Tamara

    2011-01-01

    An innovative curriculum designed to foster the development of social responsibility among pre-adolescent children was introduced at a rural Zambian primary school. The curriculum invoked Child-to-Child principles focusing on health education, advancing a synthesis of Western psychological theories and African cultural traditions. The teacher sought to democratize the educational process through cooperative learning in mixed-gender, mixed-social-class, and mixed-ability study groups. Learners engaged in community service activities and contributed to the nurturant care of younger children. Young adults interviewed seventeen years after completing the program recalled their experience and reflected on how it had promoted their personal agency, cooperative disposition, and civic responsibility in early adulthood.

  12. Computed tomography assessment of early response to neoadjuvant therapy in colon cancer

    DEFF Research Database (Denmark)

    Dam, Claus; Lund-Rasmussen, Vera; Pløen, John;

    2015-01-01

    INTRODUCTION: Using multidetector computed tomography, we aimed to assess the early response of neoadjuvant drug therapy for locally advanced colon cancer. METHODS: Computed tomography with IV contrast was acquired from 67 patients before and after up to three cycles of preoperative treatment. All...... patients had histologically confirmed colon cancer, a T4 or T3 tumour with extramural invasion ≥ 5 mm and no distant metastases or peritoneal nodules. The patients were treated with oxaliplatin and capecitabine. In addition, those with no mutations in the KRAS, BRAF and PIK3CA genes were also treated.......1, 45% (95% CI: 34-57) of the patients had a response and 55% (95% CI: 43-67) had stable disease. None of the patients showed progressive disease. CONCLUSION: Using CT, we demonstrated a significant reduction in tumour size, extramural tumour invasion, number and size of enlarged lymph nodes following...

  13. Comparisons of early transcriptome responses to low-oxygen environments in three dicotyledonous plant species

    Science.gov (United States)

    Christianson, Jed A; Llewellyn, Danny J; Dennis, Elizabeth S

    2010-01-01

    Waterlogging is a serious impediment to crop productivity worldwide which acts to reduce oxygen levels in the rhizosphere due to the low diffusion rate of molecular oxygen in water. Plants respond to low oxygen through rapid and specific changes at both the transcriptional and translational levels. Transcriptional changes to low-oxygen (hypoxia) stress have been studied in a number of plant species using whole genome microarrays. Using transcriptome data from root tissue from early time points (4–5 h) from cotton (Gossypium hirsutum), Arabidopsis and gray poplar (Populus x canescens), we have identified a core set of orthologous genes that responded to hypoxia in similar ways between species, and others that showed species specific responses. Responses to hypoxia were most similar between Arabidopsis and cotton, while the waterlogging tolerant poplar species exhibited some significant differences. PMID:20724824

  14. Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood.

    Science.gov (United States)

    Parker, Matthew O; Evans, Alexandra M-D; Brock, Alistair J; Combe, Fraser J; Teh, Muy-Teck; Brennan, Caroline H

    2016-01-01

    Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and μ-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning.

  15. Advanced response surface method for mechanical reliability analysis

    Institute of Scientific and Technical Information of China (English)

    L(U) Zhen-zhou; ZHAO Jie; YUE Zhu-feng

    2007-01-01

    Based on the classical response surface method (RSM), a novel RSM using improved experimental points (EPs) is presented for reliability analysis. Two novel points are included in the presented method. One is the use of linear interpolation, from which the total EPs for determining the RS are selected to be closer to the actual failure surface;the other is the application of sequential linear interpolation to control the distance between the surrounding EPs and the center EP, by which the presented method can ensure that the RS fits the actual failure surface in the region of maximum likelihood as the center EPs converge to the actual most probable point (MPP). Since the fitting precision of the RS to the actual failure surface in the vicinity of the MPP, which has significant contribution to the probability of the failure surface being exceeded, is increased by the presented method, the precision of the failure probability calculated by RS is increased as well. Numerical examples illustrate the accuracy and efficiency of the presented method.

  16. Mechanisms governing the responses to anthracnose pathogen in Juglans spp.

    Science.gov (United States)

    Pollegioni, P; Van der Linden, G; Belisario, A; Gras, M; Anselmi, N; Olimpieri, I; Luongo, L; Santini, A; Turco, E; Scarascia Mugnozza, G; Malvolti, M E

    2012-06-30

    Juglans nigra and Juglans regia are two highly economically important species for wood and fruit production that are susceptible to anthracnose caused by Gnomonia leptostyla. The identification of genotypes resistant to anthracnose could represent a valid alternative to agronomic and chemical management. In this study, we analyzed 72 walnut genotypes that showed a variety of resistance phenotypes in response to natural infection. According to the disease severity rating and microsatellite fingerprinting analysis, these genotypes were divided into three main groups: (40) J. nigra resistant, (1) J. nigra susceptible, and (31) J. regia susceptible. Data on leaf emergence rates and analysis of in vivo pathogenicity indicated that the incidence of anthracnose disease in the field might be partially conditioned by two key factors: the age and/or availability of susceptible leaves during the primary infection of fungus (avoidance by late flushing) and partial host resistance. NBS profiling approach, based on PCR amplification with an adapter primer for an adapter matching a restriction enzyme site and a degenerate primer targeting the conserved motifs present in the NBS domain of NBS-LRR genes, was applied. The results revealed the presence of a candidate marker that correlated to a reduction in anthracnose incidence in 72 walnut genotypes. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Mechanisms Underlying the Association Between Early-Life Adversity and Physical Health: Charting a Course for the Future.

    Science.gov (United States)

    Bush, Nicole R; Lane, Richard D; McLaughlin, Katie A

    Early-life adversities (ELA) are associated with subsequent pervasive alterations across a wide range of neurobiological systems and psychosocial factors that contribute to accelerated onset of health problems and diseases. In this article, we provide an integrated perspective on recent developments in research on ELA, based on the articles published in this Special Issue of Psychosomatic Medicine. We focus on the following: 1) the distinction between specific versus general aspects of ELA with regard to the nature of exposure (e.g., physical and sexual abuse, emotional abuse or neglect, relative socioeconomic deprivation), biological and behavioral correlates of ELA, and differences across diseases; 2) the importance of timing in the critical phases of exposure to ELA; and 3) adaptive versus dysfunctional responses to ELA and their consequences for biological and behavioral risk factors for adverse health outcomes. This article concludes with outlining important new targets for research in this area, including the neurobiology of affect as a mechanism linking ELA to adverse health outcomes, and the need for large-scale longitudinal investigations of multisystem processes relevant to ELA in diverse samples, starting prenatally, continuing to late adolescence, and with long-term follow-up assessments that enable evaluation of incident disease outcomes.

  18. TLR9 Activation Dampens the Early Inflammatory Response to Paracoccidioides brasiliensis, Impacting Host Survival

    Science.gov (United States)

    Menino, João Filipe; Saraiva, Margarida; Gomes-Alves, Ana G.; Lobo-Silva, Diogo; Sturme, Mark; Gomes-Rezende, Jéssica; Saraiva, Ana Laura; Goldman, Gustavo H.; Cunha, Cristina; Carvalho, Agostinho; Romani, Luigina; Pedrosa, Jorge; Castro, António Gil; Rodrigues, Fernando

    2013-01-01

    Background Paracoccidioides brasiliensis causes paracoccidioidomycosis, one of the most prevalent systemic mycosis in Latin America. Thus, understanding the characteristics of the protective immune response to P. brasiliensis is of interest, as it may reveal targets for disease control. The initiation of the immune response relies on the activation of pattern recognition receptors, among which are TLRs. Both TLR2 and TLR4 have been implicated in the recognition of P. brasiliensis and regulation of the immune response. However, the role of TLR9 during the infection by this fungus remains unclear. Methodology/Principal findings We used in vitro and in vivo models of infection by P. brasiliensis, comparing wild type and TLR9 deficient (−/−) mice, to assess the contribution of TLR9 on cytokine induction, phagocytosis and outcome of infection. We show that TLR9 recognizes either the yeast form or DNA from P. brasiliensis by stimulating the expression/production of pro-inflammatory cytokines by bone marrow derived macrophages, also increasing their phagocytic ability. We further show that TLR9 plays a protective role early after intravenous infection with P. brasiliensis, as infected TLR9−/− mice died at higher rate during the first 48 hours post infection than wild type mice. Moreover, TLR9−/− mice presented tissue damage and increased expression of several cytokines, such as TNF-α and IL-6. The increased pattern of cytokine expression was also observed during intraperitoneal infection of TLR9−/− mice, with enhanced recruitment of neutrophils. The phenotype of TLR9−/− hosts observed during the early stages of P. brasiliensis infection was reverted upon a transient, 48 hours post-infection, neutrophil depletion. Conclusions/Significance Our results suggest that TLR9 activation plays an early protective role against P. brasiliensis, by avoiding a deregulated type of inflammatory response associated to neutrophils that may lead to tissue damage. Thus

  19. Very rapid virologic response and early HCV response kinetics, as quick measures to compare efficacy and guide a personalized response-guided therapy

    Directory of Open Access Journals (Sweden)

    Yakoot M

    2016-08-01

    Full Text Available Mostafa Yakoot,1,2 Alaa M Abdo,3 Ahmed Yousry,4,5 Sherine Helmy6 1Green Clinical Research Center, 2Abbas Helmy Clinics, 3Tropical Medicine and Hepatology Department, Alexandria Faculty of Medicine, 4Microbiology Department, High Institute of Public Health, Alexandria University, 5Mabarat Asafra Labs, 6Pharco Corporation, Alexandria, Egypt Background: This is the second and final report for our study designed to compare two generic sofosbuvir products for the degree and speed of virologic response to a dual anti-hepatitis C virus (HCV treatment protocol. We aimed to test the applicability of the early virus response kinetics and the very rapid virologic response (vRVR rate as quick outcome measures for accelerated comparative efficacy studies and as a foundation for a personalized response-guided therapy.Methods: Fifty eligible chronic HCV patients were randomized to either one of two generic sofosbuvir products (Gratisovir or Grateziano at a daily dose of one 400 mg tablet plus a weight-based ribavirin dose. Data were compared between the groups for early virus response kinetics and vRVR rates in relation to the rates of final sustained virologic response at week 12 posttreatment (SVR12.Results: The Log10 transformed virus load (Log polymerase chain reaction curves showed fairly similar rapid decline during the first 2 weeks, with no significant difference between the groups at four analysis points throughout the study by repeated-measures factorial analysis of variance test (P=0.48. The SVR12 rates were 96% (95% confidence interval, 79.6%–99.9% in Gratisovir group (24/25 and 95.7% (95% confidence interval, 78%–99.9% in Grateziano group (22/23. There was no statistically significant difference found by exact test (P>0.999. There was a significant association between the vRVR and the SVR12, with 100% positive predictive value (38/38 of those who had vRVR, achieved a final SVR12 and 82.6% sensitivity (among the total 46 with SVR12, 38 were

  20. Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia.

    Science.gov (United States)

    Rawstron, Andy C; Kennedy, Ben; Moreton, Paul; Dickinson, Anita J; Cullen, Matthew J; Richards, Stephen J; Jack, Andrew S; Hillmen, Peter

    2004-03-15

    Alemtuzumab therapy is effective for some refractory chronic lymphocytic leukemia (CLL), but identifying responders requires at least 8 weeks of therapy. Early identification of nonresponders would minimize toxicity and/or facilitate more effective strategies. The aim of this study was to identify a minimally invasive method for early prediction of response and relapse. Flow cytometric monitoring was performed in 887 blood samples and 201 marrow samples from 43 patients undergoing intravenous alemtuzumab therapy. Although the absolute lymphocytosis was resolved in all patients by week 4, significant depletion of bone marrow tumor only occurred if circulating B-lymphocyte counts were persistently less than 0.001 x 10(9)/L, which was rare in nonresponders. The majority of patients (16/28) who did not benefit from a full course of therapy were identified with 100% positive predictive value using the following algorithm: peripheral B-cell count greater than 0.001 x 10(9)/L at week 2 with less than 1 log depletion of circulating B cells between weeks 2 and 4. Monitoring CLL levels after treatment identified patients at risk of early disease progression and could potentially improve patient management. During alemtuzumab therapy, bone marrow CLL depletion only occurs after abrogation of circulating tumor, requiring close monitoring of circulating B-cell levels. If validated in prospective studies, blood monitoring at 2 and 4 weeks may be used to optimize therapy.

  1. Fifty years of tobacco carcinogenesis research: from mechanisms to early detection and prevention of lung cancer.

    Science.gov (United States)

    Hecht, Stephen S; Szabo, Eva

    2014-01-01

    The recognition of the link between cigarette smoking and lung cancer in the 1964 Surgeon General's Report initiated definitive and comprehensive research on the identification of carcinogens in tobacco products and the relevant mechanisms of carcinogenesis. The resultant comprehensive data clearly illustrate established pathways of cancer induction involving carcinogen exposure, metabolic activation, DNA adduct formation, and consequent mutation of critical genes along with the exacerbating influences of inflammation, cocarcinogenesis, and tumor promotion. This mechanistic understanding has provided a framework for the regulation of tobacco products and for the development of relevant tobacco carcinogen and toxicant biomarkers that can be applied in cancer prevention. Simultaneously, the recognition of the link between smoking and lung cancer paved the way for two additional critical approaches to cancer prevention that are discussed here: detection of lung cancer at an early, curable stage, and chemoprevention of lung cancer. Recent successes in more precisely identifying at-risk populations and in decreasing lung cancer mortality with helical computed tomography screening are notable, and progress in chemoprevention continues, although challenges with respect to bringing these approaches to the general population exist. Collectively, research performed since the 1964 Report demonstrates unequivocally that the majority of deaths from lung cancer are preventable.

  2. Paracrine mechanisms involved in the control of early stages of mammalian spermatogenesis

    Directory of Open Access Journals (Sweden)

    Pellegrino eRossi

    2013-11-01

    Full Text Available Within the testis, Sertoli cell is the primary target of pituitary FSH. Several growth factors have been described to be produced specifically by Sertoli cells and modulate male germ cell development through paracrine mechanisms. Some have been shown to act directly on spermatogonia such as GDNF, which acts on self-renewal of spermatogonial stem cells (SSCs while inhibiting their differentiation; BMP4, which has both a proliferative and differentiative effect on these cells, and KL, which stimulates the KIT tyrosine-kinase receptor expressed by differentiating spermatogonia (but not by SSCs. KL not only controls the proliferative cycles of KIT positive spermatogonia, but it also stimulates the expression of genes that are specific of the early phases of meiosis, whereas the expression of typical spermatogonial markers is down-regulated. On the contrary, FGF9 acts as a meiotic inhibiting substance both in fetal gonocytes and in post-natal spermatogonia through the induction of the RNA-binding protein NANOS2. Vitamin A, which is metabolized to Retinoic Acid in Sertoli cells, controls both SSCs differentiation through KIT induction and NANOS2 inhibition, and meiotic entry of differentiating spermatogonia through STRA8 upregulation.

  3. A cell-based computational model of early embryogenesis coupling mechanical behaviour and gene regulation

    Science.gov (United States)

    Delile, Julien; Herrmann, Matthieu; Peyriéras, Nadine; Doursat, René

    2017-01-01

    The study of multicellular development is grounded in two complementary domains: cell biomechanics, which examines how physical forces shape the embryo, and genetic regulation and molecular signalling, which concern how cells determine their states and behaviours. Integrating both sides into a unified framework is crucial to fully understand the self-organized dynamics of morphogenesis. Here we introduce MecaGen, an integrative modelling platform enabling the hypothesis-driven simulation of these dual processes via the coupling between mechanical and chemical variables. Our approach relies upon a minimal ‘cell behaviour ontology' comprising mesenchymal and epithelial cells and their associated behaviours. MecaGen enables the specification and control of complex collective movements in 3D space through a biologically relevant gene regulatory network and parameter space exploration. Three case studies investigating pattern formation, epithelial differentiation and tissue tectonics in zebrafish early embryogenesis, the latter with quantitative comparison to live imaging data, demonstrate the validity and usefulness of our framework. PMID:28112150

  4. Improvements of postburn renal function by early enteral feeding and their possible mechanisms in rats

    Institute of Scientific and Technical Information of China (English)

    Li Zhu; Zong-Cheng Yang; De-Chang Chen

    2003-01-01

    AIM: To investigate the protective effects of early enteral feeding (EEF) on postburn impairments of renal function and their possible mechanisms.METHODS: Wistar rats with 30 % of total body surface area (TBSA) full-thickness burn were adopted as the experimental model. The effects of EEF on the postburn changes of gastric intramucosal pH (pHi), endotoxin levels in portal vein, water contents of renal tissue, and blood concentrations of tumor necrosis factor (TNF-α), urea nitrogen (BUN), creatinine (Ct), as well as the changes of clearance of creatinine (CCr) were dynamically observed within 48 h postburn.RESULTS: EEF could significantly improve gastric mucosal acidosis, reduce portal vein endotoxin levels and water contents of renal tissue, as well as blood concentrations of TNF<α after severe burns (P<0.01). The postburn elevations of BUN and BCr were not found to be recovered by EEF.However, the CCr in EEF group was greatly increased by 4.67-fold compared with that of the non-feeding burned control (16.43±2.90 vs. 3.52±0.79, P<0.01).CONCLUSION: EEF has beneficial effects on the improvement of renal function in severely burned rats, which may be related to its increase of splanchnic blood flow,decrease of the translocation of gut-origin endotoxin and the release of inflammatory mediators.

  5. Targeting Young Stars with Kepler: Planet Formation, Migration Mechanisms and the Early History of Planetary Systems

    CERN Document Server

    Lloyd, James P; Mamajek, Eric; Spiegel, David S; Covey, Kevin R; Shkolnik, Evgenya L; Walkowicz, Lucianne; Chavez, Miguel; Bertone, Emanuele; Aguilar, Jose Manuel Olmedo

    2013-01-01

    This white paper discusses a repurposed mission for the Kepler spacecraft that focusses on solving outstanding problems in planet formation and evolution by targeting the study of the hot Jupiter population of young stars. This mission can solve the question of the mode of migration of hot Jupiters, address the problem of whether Jupiters form by hot-start (gravitational instability) or cold-start (core accretion) mechanisms, and provide a wealth of data on the early stages of planetary system evolution during the active phases of stars which impact planetary habitability. In one year of observations of three weeks dwell time per field, Kepler would increase by more than an order of magnitude the number of known hot Jupiters, which can be followed up with fast cadence observations to to search for transit timing variations and to perform asteroseismological characterization of the host stars. This mission scenario continues to operate Kepler in the photometric monitoring mode for which it was designed, and is...

  6. Salivary cortisol response to psychological stress in children with early childhood caries

    Directory of Open Access Journals (Sweden)

    Kambalimath Halaswamy

    2010-01-01

    Full Text Available Aims and Objectives: Early Childhood Caries (ECC is a multi-factorial disease and has numerous biological, psychological, and behavioral risk factors. In this study, we have attempted to study psychological stress as a risk factor for early childhood caries by investigating and comparing the response of event-related stress on salivary cortisol level in children with ECC and those without ECC and also compared the adaptability to various dental procedures in children with early childhood caries and without early childhood caries. Materials and Methods: One hundred children aged between four and five years were examined in the school and 16 pairs of children with caries and without caries were selected after cross-matching them on various risk factors for Early Childhood Caries. Oral prophylaxis and topical fluoride treatment procedures were used as stressors and salivary samples were collected at the time of arrival for the treatment, after Oral Prophylaxis and Fluoride treatment. The salivary samples were analyzed by radioimmunoassay for an unbound plasma cortisol level. Results: Statistical analysis was performed using a paired t-test, on the collected data, to compare the mean values of the salivary cortisol across the group and within the groups to evaluate the cortisol response to stress. No significant differences were found between the salivary cortisol levels prior to treatment, post oral prophylaxis, or post fluoride treatment at the first and second appointments of both groups. At the first appointment, the fluoride treatment caused a significant increase in the salivary cortisol level over the pretreatment level, in both the groups, but it was not evident in either of the two groups studied at the second appointment. Conclusion: We have concluded that the stress produced by different dental procedures was similar in children from the two groups studied, and the coping ability of the children was also similar in both the groups. Small

  7. Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies

    Directory of Open Access Journals (Sweden)

    Stefan eNiewiesk

    2014-09-01

    Full Text Available Neonates have an immature immune system which cannot adequately protect against infectious diseases. Early in life, immune protection is accomplished by maternal antibodies transferred from mother to offspring. However, decaying maternal antibodies inhibit vaccination as is examplified by the inhibition of seroconversion after measles vaccination. This phenomenon has been described in both human and veterinary medicine and is independent of the type of vaccine being used. This review will discuss the use of animal models for vaccine research. I will review clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines. These are based on new mechanistic insight about the inhibitory mechanism of maternal antibodies. Maternal antibodies inhibit the generation of antibodies whereas the T cell response is usually unaffected. B cell inhibition is mediated through a cross-link between B-cell receptor (BCR with the Fcg receptor IIB (FcgRIIB by a vaccine-antibody complex. In animal experiments, this inhibition can be partially overcome by injection of a vaccine-specific monoclonal IgM antibody. IgM stimulates the B-cell directly through cross-linking the BCR via complement protein C3d and antigen to the complement receptor 2 (CR2 signaling complex. In addition, it was shown that interferon alpha binds to the CD21 chain of CR2 as well as the interferon receptor and that this dual receptor usage drives B cell responses in the presence of maternal antibodies. In lieu of immunizing the infant the concept of maternal immunization as a strategy to protect neonates has been proposed. This approach would still not solve the question of how to immunize in the presence of maternal antibodies but would defer the time of infection to an age where infection might not have such a detrimental outcome as in neonates. I will review successful examples and potential challenges of implementing

  8. Solanum lycopersicum AUXIN RESPONSE FACTOR 9 regulates cell division activity during early tomato fruit development

    Science.gov (United States)

    de Jong, Maaike; Wolters-Arts, Mieke; Schimmel, Bernardus C. J.; Stultiens, Catharina L. M.; de Groot, Peter F. M.; Powers, Stephen J.; Tikunov, Yury M.; Bovy, Arnoud G.; Mariani, Celestina; Vriezen, Wim H.; Rieu, Ivo

    2015-01-01

    The transformation of the ovary into a fruit after successful completion of pollination and fertilization has been associated with many changes at transcriptomic level. These changes are part of a dynamic and complex regulatory network that is controlled by phytohormones, with a major role for auxin. One of the auxin-related genes differentially expressed upon fruit set and early fruit development in tomato is Solanum lycopersicum AUXIN RESPONSE FACTOR 9 (SlARF9). Here, the functional analysis of this ARF is described. SlARF9 expression was found to be auxin-responsive and SlARF9 mRNA levels were high in the ovules, placenta, and pericarp of pollinated ovaries, but also in other plant tissues with high cell division activity, such as the axillary meristems and root meristems. Transgenic plants with increased SlARF9 mRNA levels formed fruits that were smaller than wild-type fruits because of reduced cell division activity, whereas transgenic lines in which SlARF9 mRNA levels were reduced showed the opposite phenotype. The expression analysis, together with the phenotype of the transgenic lines, suggests that, in tomato, ARF9 negatively controls cell division during early fruit development. PMID:25883382

  9. Solanum lycopersicum AUXIN RESPONSE FACTOR 9 regulates cell division activity during early tomato fruit development.

    Science.gov (United States)

    de Jong, Maaike; Wolters-Arts, Mieke; Schimmel, Bernardus C J; Stultiens, Catharina L M; de Groot, Peter F M; Powers, Stephen J; Tikunov, Yury M; Bovy, Arnoud G; Mariani, Celestina; Vriezen, Wim H; Rieu, Ivo

    2015-06-01

    The transformation of the ovary into a fruit after successful completion of pollination and fertilization has been associated with many changes at transcriptomic level. These changes are part of a dynamic and complex regulatory network that is controlled by phytohormones, with a major role for auxin. One of the auxin-related genes differentially expressed upon fruit set and early fruit development in tomato is Solanum lycopersicum AUXIN RESPONSE FACTOR 9 (SlARF9). Here, the functional analysis of this ARF is described. SlARF9 expression was found to be auxin-responsive and SlARF9 mRNA levels were high in the ovules, placenta, and pericarp of pollinated ovaries, but also in other plant tissues with high cell division activity, such as the axillary meristems and root meristems. Transgenic plants with increased SlARF9 mRNA levels formed fruits that were smaller than wild-type fruits because of reduced cell division activity, whereas transgenic lines in which SlARF9 mRNA levels were reduced showed the opposite phenotype. The expression analysis, together with the phenotype of the transgenic lines, suggests that, in tomato, ARF9 negatively controls cell division during early fruit development. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  10. Functional response of U.S. grasslands to the early 21st-century drought.

    Science.gov (United States)

    Moran, M Susan; Ponce-Campos, Guillermo E; Huete, Alfredo; McClaran, Mitchel P; Zhang, Yongguang; Hamerlynck, Erik P; Augustine, David J; Gunter, Stacey A; Kitchen, Stanley G; Peters, Debra P C; Starks, Patrick J; Hernandez, Mariano

    2014-08-01

    Grasslands across the United States play a key role in regional livelihood and national food security. Yet, it is still unclear how this important resource will respond to the prolonged warm droughts and more intense rainfall events predicted with climate change. The early 21st-century drought in the southwestern United States resulted in hydroclimatic conditions that are similar to those expected with future climate change. We investigated the impact of the early 21st-century drought on aboveground net primary production (ANPP) of six desert and plains grasslands dominated by C4 (warm season) grasses in terms of significant deviations between observed and expected ANPP. In desert grasslands, drought-induced grass mortality led to shifts in the functional response to annual total precipitation (P(T)), and in some cases, new species assemblages occurred that included invasive species. In contrast, the ANPP in plains grasslands exhibited a strong linear function of the current-year P(T) and the previous-year ANPP, despite prolonged warm drought. We used these results to disentangle the impacts of interannual total precipitation, intra-annual precipitation patterns, and grassland abundance on ANPP, and thus generalize the functional response of C4 grasslands to predicted climate change. This will allow managers to plan for predictable shifts in resources associated with climate change related to fire risk, loss of forage, and ecosystem services.

  11. Radiofrequency ablation of liver cancer: early evaluation of therapeutic response with contrast-enhanced ultrasonography

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Dong Gil; Lim, Hyo K.; Lee, Won Jae; Kim, Seung Hoon; Kim, Min Ju; Kim, Seung Kwon; Jang, Kyung Mi; Lee, Ji Yeon; Lim, Jae Hoon [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2004-09-15

    The early assessment of the therapeutic response after percutaneous radiofrequency (RF) ablation is important, in order to correctly decide whether further treatment is necessary. The residual unablated tumor is usually depicted on contrast-enhanced multiphase helical computed tomography (CT) as a focal enhancing structure during the arterial and portal venous phases. Contrast-enhanced color Doppler and power Doppler ultrasonography (US) have also been used to detect residual tumors. Contrast-enhanced gray-scale US, using a harmonic technology which has recently been introduced, allows for the detection of residual tumors after ablation, without any of the blooming or motion artifacts usually seen on contrast-enhanced color or power Doppler US. Based on our experience and reports in the literature, we consider that contrast-enhanced gray-scale harmonic US constitutes a reliable alternative to contrast-enhanced multiphase CT for the early evaluation of the therapeutic response to RF ablation for liver cancer. This technique was also useful in targeting any residual unablated tumors encountered during additional ablation.

  12. Density-dependent coral recruitment displays divergent responses during distinct early life-history stages.

    Science.gov (United States)

    Doropoulos, Christopher; Evensen, Nicolas R; Gómez-Lemos, Luis A; Babcock, Russell C

    2017-05-01

    Population growth involves demographic bottlenecks that regulate recruitment success during various early life-history stages. The success of each early life-history stage can vary in response to population density, interacting with intrinsic (e.g. behavioural) and environmental (e.g. competition, predation) factors. Here, we used the common reef-building coral Acropora millepora to investigate how density-dependence influences larval survival and settlement in laboratory experiments that isolated intrinsic effects, and post-settlement survival in a field experiment that examined interactions with environmental factors. Larval survival was exceptionally high (greater than 80%) and density-independent from 2.5 to 12 days following spawning. By contrast, there was a weak positive effect of larval density on settlement, driven by gregarious behaviour at the highest density. When larval supply was saturated, settlement was three times higher in crevices compared with exposed microhabitats, but a negative relationship between settler density and post-settlement survival in crevices and density-independent survival on exposed surfaces resulted in similar recruit densities just one month following settlement. Moreover, a negative relationship was found between turf algae and settler survival in crevices, whereas gregarious settlement improved settler survival on exposed surfaces. Overall, our findings reveal divergent responses by coral larvae and newly settled recruits to density-dependent regulation, mediated by intrinsic and environmental interactions.

  13. Long Non-coding RNA in Neurons: New Players in Early Response to BDNF Stimulation.

    Science.gov (United States)

    Aliperti, Vincenza; Donizetti, Aldo

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin family member that is highly expressed and widely distributed in the brain. BDNF is critical for neural survival and plasticity both during development and in adulthood, and dysfunction in its signaling may contribute to a number of neurodegenerative disorders. Deep understanding of the BDNF-activated molecular cascade may thus help to find new biomarkers and therapeutic targets. One interesting direction is related to the early phase of BDNF-dependent gene expression regulation, which is responsible for the activation of selective gene programs that lead to stable functional and structural remodeling of neurons. Immediate-early coding genes activated by BDNF are under investigation, but the involvement of the non-coding RNAs is largely unexplored, especially the long non-coding RNAs (lncRNAs). lncRNAs are emerging as key regulators that can orchestrate different aspects of nervous system development, homeostasis, and plasticity, making them attractive candidate markers and therapeutic targets for brain diseases. We used microarray technology to identify differentially expressed lncRNAs in the immediate response phase of BDNF stimulation in a neuronal cell model. Our observations on the putative functional role of lncRNAs provide clues to their involvement as master regulators of gene expression cascade triggered by BDNF.

  14. Early detection of oil-induced stress in crops using spectral and thermal responses

    Science.gov (United States)

    Emengini, Ebele Josephine; Blackburn, George Alan; Theobald, Julian Charles

    2013-01-01

    Oil pollution is a major source of environmental degradation, and requires accurate monitoring and timely detection for an effective control of its occurrence. This paper examines the potential of a remote sensing approach using the spectral and thermal responses of crops for the early detection of stress caused by oil pollution. In a glasshouse, pot-grown maize was treated with oil at sublethal and lethal applications. Thereafter, leaf thermal, spectral and physiological measurements were taken every two to three days to monitor the development of stress responses. Our results indicate that absolute leaf temperature was a poor indicator of developing stress. However, a derived thermal index (IG) responded consistently in the early stages of physiological damage. Various spectral reflectance features were highly sensitive to oil-induced stress. A narrow-band index using wavelengths in the near-infrared and red-edge region, (R755-R716)/(R755+R716), was optimal for previsual detection of oil-induced stress. This index had a strong linear relationship with photosynthetic rate. This indicates that by detecting vegetation stress, thermal and hyperspectral remote sensing has considerable potential for the timely detection of oil pollution in the environment.

  15. YopH inhibits early pro-inflammatory cytokine responses during plague pneumonia

    Directory of Open Access Journals (Sweden)

    Bubeck Sarah S

    2010-06-01

    Full Text Available Abstract Background Yersinia pestis is the causative agent of pneumonic plague; recently, we and others reported that during the first 24-36 hours after pulmonary infection with Y. pestis pro-inflammatory cytokine expression is undetectable in lung tissues. Results Here, we report that, intranasal infection of mice with CO92 delta yopH mutant results in an early pro-inflammatory response in the lungs characterized by an increase in the pro-inflammatory cytokines Tumor Necrosis Factor-alpha and Interleukin one-beta 24 hours post-infection. CO92 delta yopH colonizes the lung but does not disseminate to the liver or spleen and is cleared from the host within 72 hours post-infection. This is different from what is observed in a wild-type CO92 infection, where pro-inflammatory cytokine expression and immune cell infiltration into the lungs is not detectable until 36-48 h post-infection. CO92 rapidly disseminates to the liver and spleen resulting in high bacterial burdens in these tissues ultimately cumulating in death 72-94 h post-infection. Mice deficient in TNF-alpha are more susceptible to CO92 delta yopH infection with 40% of the mice succumbing to infection. Conclusions Altogether, our results suggest that YopH can inhibit an early pro-inflammatory response in the lungs of mice and that this is an important step in the pathogenesis of infection.

  16. Do Young and Old Preschoolers Exhibit Response Bias Due to Different Mechanisms? Investigating Children's Response Time

    Science.gov (United States)

    Okanda, Mako; Itakura, Shoji

    2011-01-01

    Previous studies have suggested that younger preschoolers exhibit a yes bias due to underdeveloped cognitive abilities, whereas older preschoolers exhibit a response bias due to other factors. To test this hypothesis, we investigated the response latency to yes-no questions pertaining to familiar and unfamiliar objects in 3- to 6-year-olds. The…

  17. Associative conditioning with leg cycling and inspiratory resistance enhances the early exercise ventilatory response in humans.

    Science.gov (United States)

    Turner, Duncan; Stewart, Jamie D

    2004-12-01

    Repeated trials of hypercapnic exercise [deltaPET CO2 = 7 (1) mmHg] augment the increase in inspired minute ventilation and tidal volume (V(T)) in the early phase of subsequent trials of unencumbered exercise alone. The increase in V(T) in the first 20 s of exercise was correlated to the increase in V(T) evoked during hypercapnic exercise trials, suggesting that the evoked increase in V(T) during conditioning may be a factor in mediating associative conditioning. To test this hypothesis, inspiratory resistive loading (IRL) was employed to evoke an increase in V(T) [deltaV(T) = 0.4 (0.1) I(BTPS)] during conditioning exercise trials [IRL + EX; deltaP(ET)CO2 = 2 (l) mmHg]. IRL + EX associative conditioning elicited a significant augmentation of the early minute ventilation (+46%) and V(T) (+100%) responses to subsequent unencumbered exercise. The latter was correlated to the evoked increase in V(T) during associative conditioning with IRL + EX. The results support the hypothesis that an evoked increase in V(T) during associative conditioning could be a factor in eliciting long-term modulation of minute ventilation in subsequent unencumbered exercise. The results further indicated that the modulation of ventilation early in exercise is not due to sensitisation to repeated trials of either IRL or exercise alone. Associative conditioning may shape the ventilatory response to exercise through a process of motor learning. Data are presented as mean (SEM) unless otherwise stated.

  18. Mechanical changes in human dental pulp stem cells during early odontogenic differentiation.

    Science.gov (United States)

    Jones, Taneka D; Naimipour, Hamed; Sun, Shan; Cho, Michael; Alapati, Satish B

    2015-01-01

    Cell adhesion and migration in bioactive scaffolds require actin cytoskeleton remodeling and focal adhesion formation. Additionally, human dental pulp stem cells (hDPSCs) undergo several changes in their mechanical properties during odontogenic differentiation. The effect of factors essential for odontogenesis on actin stress fiber elasticity and focal adhesion formation is not known. Live hDPSCs cultured in odontogenic media were imaged for cytoskeleton changes using an atomic force microscope. The Young's modulus (kPa) of the cytoskeleton was recorded as a function of culture medium for 10 days. Focal adhesion formation was assessed using immunofluorescence. Cultured hDPSCs were incubated with a monoclonal vinculin antibody, and filamentous actins were visualized using 0.5 μmol/L phalloidin. Cytoskeletal elasticity significantly increased in response to odontogenic media. Both the number and physical size of focal adhesions in hDPSCs also increased. Up-regulation of vinculin expression was evident. The increase in the formation of focal adhesions was consistent with actin remodeling to stress fibers. Our findings suggest that hDPSCs firmly attach to the glass substrate in response to odontogenic media. Successful regeneration of pulp-dentin tissue using biomimetic scaffolds will likely require cell-extracellular matrix interactions influenced by biochemical induction factors. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  19. Hormesis, cellular stress response and neuroinflammation in schizophrenia: Early onset versus late onset state.

    Science.gov (United States)

    Calabrese, Vittorio; Giordano, James; Crupi, Rosalia; Di Paola, Rosanna; Ruggieri, Martino; Bianchini, Rio; Ontario, Maria Laura; Cuzzocrea, Salvatore; Calabrese, Edward J

    2017-05-01

    Abnormal redox homeostasis and oxidative stress have been proposed to play a role in the etiology of several neuropsychiatric spectrum disorders. Emerging interest has recently focused on markers of oxidative stress and neuroinflammation in schizophrenic spectrum disorders, at least in particular subgroups of patients. Altered expression of genes related to oxidative stress, oxidative damage to DNA, protein and lipids, as well as reduced glutathione levels in central and peripheral tissues could act synergistically, and contribute to the course of the disease.  Herein, we discuss cellular mechanisms that may be operative in neuroinflammation and contributory to schizophrenia. We address modulation of endogenous cellular defense mechanisms as a potentially innovative approach to therapeutics for schizophrenia, and other neuropsychiatric conditions that are associated with neuroinflammation. Specifically, we discuss the emerging role of heme oxygenase as prominent member of neuroprotective network in redox stress responsive mechanisms, as well as the importance of glutathione relevant in schizophrenia pathophysiology. Finally we introduce the hormetic dose response concept as relevant and important to neuroprotection, and review hormetic mechanisms as possible approaches to manipulation of neuroinflammatory targets that may be viable for treating schizophrenia spectrum disorders. © 2016 Wiley Periodicals, Inc.

  20. Hepatitis C virus reveals a novel early control in acute immune response.

    Directory of Open Access Journals (Sweden)

    Noëlla Arnaud

    2011-10-01

    Full Text Available Recognition of viral RNA structures by the intracytosolic RNA helicase RIG-I triggers induction of innate immunity. Efficient induction requires RIG-I ubiquitination by the E3 ligase TRIM25, its interaction with the mitochondria-bound MAVS protein, recruitment of TRAF3, IRF3- and NF-κB-kinases and transcription of Interferon (IFN. In addition, IRF3 alone induces some of the Interferon-Stimulated Genes (ISGs, referred to as early ISGs. Infection of hepatocytes with Hepatitis C virus (HCV results in poor production of IFN despite recognition of the viral RNA by RIG-I but can lead to induction of early ISGs. HCV was shown to inhibit IFN production by cleaving MAVS through its NS3/4A protease and by controlling cellular translation through activation of PKR, an eIF2α-kinase containing dsRNA-binding domains (DRBD. Here, we have identified a third mode of control of IFN induction by HCV. Using HCVcc and the Huh7.25.CD81 cells, we found that HCV controls RIG-I ubiquitination through the di-ubiquitine-like protein ISG15, one of the early ISGs. A transcriptome analysis performed on Huh7.25.CD81 cells silenced or not for PKR and infected with JFH1 revealed that HCV infection leads to induction of 49 PKR-dependent genes, including ISG15 and several early ISGs. Silencing experiments revealed that this novel PKR-dependent pathway involves MAVS, TRAF3 and IRF3 but not RIG-I, and that it does not induce IFN. Use of PKR inhibitors showed that this pathway requires the DRBD but not the kinase activity of PKR. We then demonstrated that PKR interacts with HCV RNA and MAVS prior to RIG-I. In conclusion, HCV recruits PKR early in infection as a sensor to trigger induction of several IRF3-dependent genes. Among those, ISG15 acts to negatively control the RIG-I/MAVS pathway, at the level of RIG-I ubiquitination.These data give novel insights in the machinery involved in the early events of innate immune response.

  1. Broad CTL Response in Early HIV Infection Drives Multiple Concurrent CTL Escapes.

    Science.gov (United States)

    Leviyang, Sivan; Ganusov, Vitaly V

    2015-10-01

    Recent studies have highlighted the ability of HIV to escape from cytotoxic T lymphocyte (CTL) responses that concurrently target multiple viral epitopes. Yet, the viral dynamics involved in such escape are incompletely understood. Previous analyses have made several strong assumptions regarding HIV escape from CTL responses such as independent or non-concurrent escape from individual CTL responses. Using experimental data from evolution of HIV half genomes in four patients we observe concurrent viral escape from multiple CTL responses during early infection (first 100 days of infection), providing confirmation of a recent result found in a study of one HIV-infected patient. We show that current methods of estimating CTL escape rates, based on the assumption of independent escapes, are biased and perform poorly when CTL escape proceeds concurrently at multiple epitopes. We propose a new method for analyzing longitudinal sequence data to estimate the rate of CTL escape across multiple epitopes; this method involves few parameters and performs well in simulation studies. By applying our novel method to experimental data, we find that concurrent multiple escapes occur at rates between 0.03 and 0.4 day(-1), a relatively broad range that reflects uncertainty due to sparse sampling and wide ranges of parameter values. However, we show that concurrent escape at rates 0.1-0.2 day(-1) across multiple epitopes is consistent with our patient datasets.

  2. Topological dependence of mechanical responses of solidification microstructures in aluminum brazed joints

    Institute of Scientific and Technical Information of China (English)

    GAO Feng(高峰); QIAN Yi-yu(钱乙余); D.P.Sekulic; MA Xin(马鑫); F.Yoshida

    2003-01-01

    The main objective is to provide an evidence of spatial dependence of mechanical responses of a heterogeneous aluminum brazed joint re-solidified clad,and to confirm a sufficient sensitivity of a nano-indentation--load curve method for identifying the dependence.Topological features of a network of solidification microstructures(αphase and eutectic),formed during quench in a brazing process of aluminum alloy,influence significantly dynamic mechanical responses of resulting heterogeneous material.Nano/micro indentation depth vs load characteristics of differing phases suggest a spatially sensitive mechanical response of a re-solidified fillet in the joint zone.Hence,a spatial distribution,pattern formations and other morphological characteristics of microstructures have a direct impact on an ultimate joint integrity.Topology-induced variations of indentation-load curves was presented.A hypothesis involving microstructures'spatial distribution vs mechanical response was formulated.

  3. Demographic and occupational predictors of early response to a mailed invitation to enroll in a longitudinal health study

    Directory of Open Access Journals (Sweden)

    Smith Besa

    2007-01-01

    Full Text Available Abstract Background Often in survey research, subsets of the population invited to complete the survey do not respond in a timely manner and valuable resources are expended in recontact efforts. Various methods of improving response have been offered, such as reducing questionnaire length, offering incentives, and utilizing reminders; however, these methods can be costly. Utilizing characteristics of early responders (refusal or consent in enrollment and recontact efforts may be a unique and cost-effective approach for improving the quality of epidemiologic research. Methods To better understand early responders of any kind, we compared the characteristics of individuals who explicitly refused, consented, or did not respond within 2 months from the start of enrollment into a large cohort study of US military personnel. A multivariate polychotomous logistic regression model was used to estimate the effect of each covariate on the odds of early refusal and on the odds of early consent versus late/non-response, while simultaneously adjusting for all other variables in the model. Results From regression analyses, we found many similarities between early refusers and early consenters. Factors associated with both early refusal and early consent included older age, higher education, White race/ethnicity, Reserve/Guard affiliation, and certain information technology and support occupations. Conclusion These data suggest that early refusers may differ from late/non-responders, and that certain characteristics are associated with both early refusal and early consent to participate. Structured recruitment efforts that utilize these differences may achieve early response, thereby reducing mail costs and the use of valuable resources in subsequent contact efforts.

  4. Early cytokine and antibody responses against Coxiella burnetii in aerosol infection of BALB/c mice

    Science.gov (United States)

    Schoffelen, Teske; Self, Joshua S.; Fitzpatrick, Kelly A.; Netea, Mihai G.; van Deuren, Marcel; Joosten, Leo A. B.; Kersh, Gilbert J.

    2016-01-01

    Coxiella burnetii, a Gram-negative intracellular bacterium, can give rise to Q fever in humans and is transmitted mainly by inhalation of infected aerosols from animal reservoirs. Serology is commonly used to diagnose Q fever, but the early cellular immune response –i.e. C. burnetii-specific interferon(IFN)-γ production in response to antigen challenge– might be an additional diagnostic. Detection of IFN-γ responses has been used to identify past and chronic Q fever infections, but the IFN-γ response in acute Q fever has not been described. By challenging immunocompetent BALB/c mice with aerosols containing phase I C. burnetii, the timing and extent of IFN-γ recall responses was evaluated in an acute C. burnetii infection. Other cytokines were also measured in an effort to identify other potential diagnostic markers. The data show that after initial expansion of bacteria first in lungs and then in other tissues, the infection was cleared from day 10 onwards as reflected by the decreasing number of bacteria. The antigen-induced IFN-γ production by splenocytes coincided with emergence of IgM phase II-antibodies at day 10 post-infection, and preceded appearance of IgG-antibodies. This was accompanied by the production of pro-inflammatory cytokines including IL-6, KC and IP-10, followed by MCP-1, but not by IL-1β and TNF-α, and only very low production of the anti-inflammatory cytokine IL-10. These data suggest that analysis of antigen-specific IFN-γ responses could be a useful tool for diagnosis of acute Q-fever. Moreover, the current model of C.burnetii infection could be used to give new insights into immunological factors that predispose to development of persistent infection. PMID:25618420

  5. Analysis of gene expression during parabolic flights reveals distinct early gravity responses in Arabidopsis roots.

    Science.gov (United States)

    Aubry-Hivet, D; Nziengui, H; Rapp, K; Oliveira, O; Paponov, I A; Li, Y; Hauslage, J; Vagt, N; Braun, M; Ditengou, F A; Dovzhenko, A; Palme, K

    2014-01-01

    Plant roots are among most intensively studied biological systems in gravity research. Altered gravity induces asymmetric cell growth leading to root bending. Differential distribution of the phytohormone auxin underlies root responses to gravity, being coordinated by auxin efflux transporters from the PIN family. The objective of this study was to compare early transcriptomic changes in roots of Arabidopsis thaliana wild type, and pin2 and pin3 mutants under parabolic flight conditions and to correlate these changes to auxin distribution. Parabolic flights allow comparison of transient 1-g, hypergravity and microgravity effects in living organisms in parallel. We found common and mutation-related genes differentially expressed in response to transient microgravity phases. Gene ontology analysis of common genes revealed lipid metabolism, response to stress factors and light categories as primarily involved in response to transient microgravity phases, suggesting that fundamental reorganisation of metabolic pathways functions upstream of a further signal mediating hormonal network. Gene expression changes in roots lacking the columella-located PIN3 were stronger than in those deprived of the epidermis and cortex cell-specific PIN2. Moreover, repetitive exposure to microgravity/hypergravity and gravity/hypergravity flight phases induced an up-regulation of auxin responsive genes in wild type and pin2 roots, but not in pin3 roots, suggesting a critical function of PIN3 in mediating auxin fluxes in response to transient microgravity phases. Our study provides important insights towards understanding signal transduction processes in transient microgravity conditions by combining for the first time the parabolic flight platform with the transcriptome analysis of different genetic mutants in the model plant, Arabidopsis. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

  6. Hormonal induction of an immediate-early gene response in myogenic cell lines--a paradigm for heart growth.

    Science.gov (United States)

    Maass, A; Grohé, C; Kubisch, C; Wollnik, B; Vetter, H; Neyses, L

    1995-05-01

    Cardiac hypertrophy is characterized by growth of myocardial cells without proliferation. Many endo- paracrine stimuli such as angiotensin II, endothelin, alpha 1-adrenergic agonists, and insulin have been shown to be able to induce cardiac hypertrophy either in vivo or in vitro. We have used the myoblast model of differentiation and proliferation to determine nuclear signal transduction mechanisms in muscle and (by analogy) cardiac growth. The first nuclear event known to occur when a growth stimulus acts upon a cell is induction of a family of immediate-early genes. Our group focused on the role of one of these genes, the early growth response gene-1 (Egr-1). We have shown that this gene is induced in isolated adult cardiac myocytes in the presence of endothelin. An anti-sense oligonucleotide complementary to the first six codons of the Egr-1 mRNA abolishes the stimulation of protein synthesis induced by endothelin. In the present study we further characterized paracrine growth stimuli in the myogenic cell line Sol8, which was used as a paradigm to further investigate mechanisms of paracrine growth induction. We demonstrated that a variety of candidate endo- paracrine stimuli for the induction of cardiac hypertrophy induced the Egr-1 messenger RNA in the myogenic cell line Sol8. Among these are endothelin, insulin, basic fibroblast growth factor, and platelet-derived growth factor BB (PDGF BB). We conclude: (1) In analogy to the myocardium, these growth factors act upon myoblasts. (2) This line appears to be a suitable model for the molecular characterization of Egr-1 target genes.

  7. Metabolic induction and early responses of mouse blastocyst developmental programming following maternal low protein diet affecting life-long health.

    Directory of Open Access Journals (Sweden)

    Judith J Eckert

    Full Text Available Previously, we have shown that a maternal low protein diet, fed exclusively during the preimplantation period of mouse development (Emb-LPD, is sufficient to induce by the blastocyst stage a compensatory growth phenotype in late gestation and postnatally, correlating with increased risk of adult onset cardiovascular disease and behavioural dysfunction. Here, we examine mechanisms of induction of maternal Emb-LPD programming and early compensatory responses by the embryo. Emb-LPD induced changes in maternal serum metabolites at the time of blastocyst formation (E3.5, notably reduced insulin and increased glucose, together with reduced levels of free amino acids (AAs including branched chain AAs leucine, isoleucine and valine. Emb-LPD also caused reduction in the branched chain AAs within uterine fluid at the blastocyst stage. These maternal changes coincided with an altered content of blastocyst AAs and reduced mTORC1 signalling within blastocysts evident in reduced phosphorylation of effector S6 ribosomal protein and its ratio to total S6 protein but no change in effector 4E-BP1 phosphorylated and total pools. These changes were accompanied by increased proliferation of blastocyst trophectoderm and total cells and subsequent increased spreading of trophoblast cells in blastocyst outgrowths. We propose that induction of metabolic programming following Emb-LPD is achieved through mTORC1signalling which acts as a sensor for preimplantation embryos to detect maternal nutrient levels via branched chain AAs and/or insulin availability. Moreover, this induction step associates with changes in extra-embryonic trophectoderm behaviour occurring as early compensatory responses leading to later nutrient recovery.

  8. The relationship between early ego strength and adolescent responses to the threat of nuclear war

    Energy Technology Data Exchange (ETDEWEB)

    Andrekus, N.J.

    1989-01-01

    Ego resiliency and ego control, measured when subjects were 3 or 4 years old, were related to expectation of war, concern for the future, and activism in response to the threat of nuclear war, measured when subjects were 18 years old. Data from 92 participants in a longitudinal study of ego and cognitive development conducted by Jeanne and Jack Block at the University of California, Berkeley were used to test hypotheses. Assessments with the California Child Q-set, composited across multiple independent observers, provide measures of ego resiliency and ego control. Adolescent interviews regarding the perception of likelihood of nuclear war, how this affects their future, and their antinuclear and general political activism were scaled and rated. Early ego resiliency and ego under control were hypothesized to account for the variance in adolescent nuclear responses and activism. The only significant longitudinal relationships were in the female sample, where ego under control was found to be a significant predictor of both general political activism (p<.01) and ideas of the future being affected by the nuclear threat (p<.05). Among males, the relationship between early ego resiliency and adolescent antinuclear activism approached significance (p<.10). Adolescent personality was significantly related to several measures of nuclear response. In girls, adolescent ego under control related to perception of likelihood of nuclear war (p<.05) and antinuclear activism (p<.05), and the interaction of ego resiliency and ego under control predicted general political activism (p<.0005). In boys, adolescent ego resiliency correlated with antinuclear activism (p<.05). These findings were discussed in terms of antecedent parenting styles, and conceptual links were drawn between children's ego resiliency and security of attachment, perspective taking, and moral development.

  9. RNA-seq Analysis of Clinical-Grade Osteochondral Allografts Reveals Activation of Early Response Genes

    Science.gov (United States)

    Lin, Yang; Lewallen, Eric A.; Camilleri, Emily T.; Bonin, Carolina A.; Jones, Dakota L.; Dudakovic, Amel; Galeano-Garces, Catalina; Wang, Wei; Karperien, Marcel J.; Larson, Annalise N.; Dahm, Diane L.; Stuart, Michael J.; Levy, Bruce A.; Smith, Jay; Ryssman, Daniel B.; Westendorf, Jennifer J.; Im, Hee-Jeong; van Wijnen, Andre J.; Riester, Scott M.; Krych, Aaron J.

    2016-01-01

    Preservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA-seq) and real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) to assess genome-wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of “early response genes” that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of “early response genes” and reduced levels of ECM-related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. PMID:26909883

  10. Phenological behaviour of early spring flowering trees in Spain in response to recent climate changes

    Science.gov (United States)

    Hidalgo-Galvez, M. D.; García-Mozo, H.; Oteros, J.; Mestre, A.; Botey, R.; Galán, C.

    2017-03-01

    This research reports the phenological trends of four early spring and late winter flowering trees in Spain (south Europe) from a recent period (1986-2012). The studied species were deciduous trees growing in different climatic areas: hazel (Corylus avellana L.), willow (Salix alba L.), ash (Fraxinus angustifolia Vahl.) and white mulberry (Morus alba L.). We analysed the response to climate and the trends of the following phenophases observed at the field: budburst, leaf unfolding, flowering, fruit ripening, fruit harvesting, leaf colour change and leaf-fall. The study was carried out in 17 sampling sites in the country with the aim of detecting the recent phenological response to the climate of these species, and the possible effect of climate change. We have observed differences in the phenological response to climate depending on each species. Sixty-one percent of studied sites suffered an advance of early spring phenophases, especially budburst on average by -0.67 days and flowering on average by -0.15 days during the studied period, and also in the subsequent fruit ripening and harvesting phases on average by -1.06 days. By contrast, it has been detected that 63% of sampling sites showed a delay in autumn vegetative phases, especially leaf-fall events on average by +1.15 days. The statistic correlation analysis shows in the 55% of the studied localities that phenological advances are the consequence of the increasing trend detected for temperature—being minimum temperature the most influential factor—and in the 52% of them, phenological advances occurred by rainfall variations. In general, leaf unfolding and flowering from these species showed negative correlations in relation to temperature and rainfall, whereas that leaf colour change and leaf-fall presented positive correlations. The results obtained have a great relevance due to the fact that they can be considered as reliable bio-indicators of the impact of the recent climate changes in southern

  11. Invasive species information networks: Collaboration at multiple scales for prevention, early detection, and rapid response to invasive alien species

    Science.gov (United States)

    Simpson, Annie; Jarnevich, Catherine S.; Madsen, John; Westbrooks, Randy G.; Fournier, Christine; Mehrhoff, Les; Browne, Michael; Graham, Jim; Sellers, Elizabeth A.

    2009-01-01

    Accurate analysis of present distributions and effective modeling of future distributions of invasive alien species (IAS) are both highly dependent on the availability and accessibility of occurrence data and natural history information about the species. Invasive alien species monitoring and detection networks (such as the Invasive Plant Atlas of New England and the Invasive Plant Atlas of the MidSouth) generate occurrence data at local and regional levels within the United States, which are shared through the US National Institute of Invasive Species Science. The Inter-American Biodiversity Information Network's Invasives Information Network (I3N), facilitates cooperation on sharing invasive species occurrence data throughout the Western Hemisphere. The I3N and other national and regional networks expose their data globally via the Global Invasive Species Information Network (GISIN). International and interdisciplinary cooperation on data sharing strengthens cooperation on strategies and responses to invasions. However, limitations to effective collaboration among invasive species networks leading to successful early detection and rapid response to invasive species include: lack of interoperability; data accessibility; funding; and technical expertise. This paper proposes various solutions to these obstacles at different geographic levels and briefly describes success stories from the invasive species information networks mentioned above. Using biological informatics to facilitate global information sharing is especially critical in invasive species science, as research has shown that one of the best indicators of the invasiveness of a species is whether it has been invasive elsewhere. Data must also be shared across disciplines because natural history information (e.g. diet, predators, habitat requirements, etc.) about a species in its native range is vital for effective prevention, detection, and rapid response to an invasion. Finally, it has been our

  12. Explanations, mechanisms, and developmental models: Why the nativist account of early perceptual learning is not a proper mechanistic model

    Directory of Open Access Journals (Sweden)

    Radenović Ljiljana

    2013-01-01

    Full Text Available In the last several decades a number of studies on perceptual learning in early infancy have suggested that even infants seem to be sensitive to the way objects move and interact in the world. In order to explain the early emergence of infants’ sensitivity to causal patterns in the world some psychologists have proposed that core knowledge of objects and causal relations is innate (Leslie & Keeble 1987, Carey & Spelke, 1994; Keil, 1995; Spelke et al., 1994. The goal of this paper is to examine the nativist developmental model by investigating the criteria that a mechanistic model needs to fulfill if it is to be explanatory. Craver (2006 put forth a number of such criteria and developed a few very useful distinctions between explanation sketches and proper mechanistic explanations. By applying these criteria to the nativist developmental model I aim to show, firstly, that nativists only partially characterize the phenomenon at stake without giving us the details of when and under which conditions perception and attention in early infancy take place. Secondly, nativist start off with a description of the phenomena to be explained (even if it is only a partial description but import into it a particular theory of perception that requires further empirical evidence and further defense on its own. Furthermore, I argue that innate knowledge is a good candidate for a filler term (a term that is used to name the still unknown processes and parts of the mechanism and is likely to become redundant. Recent extensive research on early intermodal perception indicates that the mechanism enabling the perception of regularities and causal patterns in early infancy is grounded in our neurophysiology. However, this mechanism is fairly basic and does not involve highly sophisticated cognitive structures or innate core knowledge. I conclude with a remark that a closer examination of the mechanisms involved in early perceptual learning indicates that the nativism

  13. Hepatic and Nephric NRF2 Pathway Up-Regulation, an Early Antioxidant Response, in Acute Arsenic-Exposed Mice

    Directory of Open Access Journals (Sweden)

    Jinlong Li

    2015-10-01

    Full Text Available Inorganic arsenic (iAs, a proven human carcinogen, damages biological systems through multiple mechanisms, one of them being reactive oxygen species (ROS production. NRF2 is a redox-sensitive transcription factor that positively regulates the genes of encoding antioxidant and detoxification enzymes to neutralize ROS. Although NRF2 pathway activation by iAs has been reported in various cell types, however, the experimental data in vivo are very limited and not fully elucidated in humans. The present investigation aimed to explore the hepatic and nephric NRF2 pathway upregulation in acute arsenic-exposed mice in vivo. Our results showed 10 mg/kg NaAsO2 elevated the NRF2 protein and increased the transcription of Nrf2 mRNA, as well as up-regulated NRF2 downstream targets HO-1, GST and GCLC time- and dose-dependently both in the liver and kidney. Acute NaAsO2 exposure also resulted in obvious imbalance of oxidative redox status represented by the increase of GSH and MDA, and the decrease of T-AOC. The present investigation reveals that hepatic and nephric NRF2 pathway expression is an early antioxidant defensive response upon iAs exposure. A better knowledge about the NRF2 pathway involvment in the cellular response against arsenic could help improve the strategies for reducing the cellular toxicity related to this metalloid.

  14. Isolation and characterization of a spotted leaf 32 mutant with early leaf senescence and enhanced defense response in rice

    Science.gov (United States)

    Sun, Liting; Wang, Yihua; Liu, Ling-long; Wang, Chunming; Gan, Ting; Zhang, Zhengyao; Wang, Yunlong; Wang, Di; Niu, Mei; Long, Wuhua; Li, Xiaohui; Zheng, Ming; Jiang, Ling; Wan, Jianmin

    2017-01-01

    Leaf senescence is a complex biological process and defense responses play vital role for rice development, their molecular mechanisms, however, remain elusive in rice. We herein reported a rice mutant spotted leaf 32 (spl32) derived from a rice cultivar 9311 by radiation. The spl32 plants displayed early leaf senescence, identified by disintegration of chloroplasts as cellular evidence, dramatically decreased contents of chlorophyll, up-regulation of superoxide dismutase enzyme activity and malondialdehyde, as physiological characteristic, and both up-regulation of senescence-induced STAY GREEN gene and senescence-associated transcription factors, and down-regulation of photosynthesis-associated genes, as molecular indicators. Positional cloning revealed that SPL32 encodes a ferredoxin-dependent glutamate synthase (Fd-GOGAT). Compared to wild type, enzyme activity of GOGAT was significantly decreased, and free amino acid contents, particularly for glutamate and glutamine, were altered in spl32 leaves. Moreover, the mutant was subjected to uncontrolled oxidative stress due to over-produced reactive oxygen species and damaged scavenging pathways, in accordance with decreased photorespiration rate. Besides, the mutant showed higher resistance to Xanthomonas oryzae pv. Oryzae than its wild type, coupled with up-regulation of four pathogenesis-related marker genes. Taken together, our results highlight Fd-GOGAT is associated with the regulation of leaf senescence and defense responses in rice. PMID:28139777

  15. Thermo-mechanical loading response of hardened and tempered iron-carbon based alloys

    NARCIS (Netherlands)

    Morra, P.V.

    2004-01-01

    The mechanisms causing long term changes of materials at mild operating conditions, i.e. relatively low temperatures and loads, has not received as much attention as that for high temperature operating conditions because small strains are involved. Nevertheless the thermo-mechanical loading response

  16. Thermo-mechanical loading response of hardened and tempered iron-carbon based alloys

    NARCIS (Netherlands)

    Morra, P.V.

    2004-01-01

    The mechanisms causing long term changes of materials at mild operating conditions, i.e. relatively low temperatures and loads, has not received as much attention as that for high temperature operating conditions because small strains are involved. Nevertheless the thermo-mechanical loading response

  17. High-strain-rate tensile mechanical response of a polyurethane elastomeric material

    NARCIS (Netherlands)

    Fan, J.T.; Weerheijm, J.; Sluys, L.J.

    2015-01-01

    The dynamic tensile mechanical response of a soft polymer material (Clear Flex 75) is investigated using a split Hopkinson tension bar (SHTB). Stress-strain relations are derived to reveal the mechanical properties at moderate and high strain rates. These relations appear to be rate dependent. Under

  18. Early perturbation in mitochondria redox homeostasis in response to environmental stress predicts cell fate in diatoms.

    Science.gov (United States)

    van Creveld, Shiri Graff; Rosenwasser, Shilo; Schatz, Daniella; Koren, Ilan; Vardi, Assaf

    2015-02-01

    Diatoms are ubiquitous marine photosynthetic eukaryotes that are responsible for about 20% of global photosynthesis. Nevertheless, little is known about the redox-based mechanisms that mediate diatom sensing and acclimation to environmental stress. Here we used a redox-sensitive green fluorescent protein sensor targeted to various subcellular organelles in the marine diatom Phaeodactylum tricornutum, to map the spatial and temporal oxidation patterns in response to environmental stresses. Specific organelle oxidation patterns were found in response to various stress conditions such as oxidative stress, nutrient limitation and exposure to diatom-derived infochemicals. We found a strong correlation between the mitochondrial glutathione (GSH) redox potential (EGSH) and subsequent induction of cell death in response to the diatom-derived unsaturated aldehyde 2E,4E/Z-decadienal (DD), and a volatile halocarbon (BrCN) that mediate trophic-level interactions in marine diatoms. Induction of cell death in response to DD was mediated by oxidation of mitochondrial EGSH and was reversible by application of GSH only within a narrow time frame. We found that cell fate can be accurately predicted by a distinct life-death threshold of mitochondrial EGSH (-335 mV). We propose that compartmentalized redox-based signaling can integrate the input of diverse environmental cues and will determine cell fate decisions as part of algal acclimation to stress conditions.

  19. Early immune responses in rainbow trout liver upon viral hemorrhagic septicemia virus (VHSV) infection.

    Science.gov (United States)

    Castro, Rosario; Abós, Beatriz; Pignatelli, Jaime; von Gersdorff Jørgensen, Louise; González Granja, Aitor; Buchmann, Kurt; Tafalla, Carolina

    2014-01-01

    Among the essential metabolic functions of the liver, in mammals, a role as mediator of systemic and local innate immunity has also been reported. Although the presence of an important leukocyte population in mammalian liver is well documented, the characterization of leukocyte populations in the teleost liver has been only scarcely addressed. In the current work, we have confirmed the presence of IgM+, IgD+, IgT+, CD8α+, CD3+ cells, and cells expressing major histocompatibility complex (MHC-II) in rainbow trout (Oncorhynchus mykiss) liver by flow cytometry and/or immunohistochemistry analysis. Additionally, the effect of viral hemorrhagic septicemia virus (VHSV) on the liver immune response was assessed. First, we studied the effect of viral intraperitoneal injection on the transcription of a wide selection of immune genes at days 1, 2 and 5 post-infection. These included a group of leukocyte markers genes, pattern recognition receptors (PRRs), chemokines, chemokine receptor genes, and other genes involved in the early immune response and in acute phase reaction. Our results indicate that T lymphocytes play a key role in the initial response to VHSV in the liver, since CD3, CD8, CD4, perforin, Mx and interferon (IFN) transcription levels were up-regulated in response to VHSV. Consequently, flow cytometry analysis of CD8α+ cells in liver and spleen at day 5 post-infection revealed a decrease in the number of CD8α+ cells in the spleen and an increased population in the liver. No differences were found however in the percentages of B lymphocyte (IgM+ or IgD+) populations. In addition, a strong up-regulation in the transcription levels of several PRRs and chemokines was observed from the second day of infection, indicating an important role of these factors in the response of the liver to viral infections.

  20. Early immune responses in rainbow trout liver upon viral hemorrhagic septicemia virus (VHSV infection.

    Directory of Open Access Journals (Sweden)

    Rosario Castro

    Full Text Available Among the essential metabolic functions of the liver, in mammals, a role as mediator of systemic and local innate immunity has also been reported. Although the presence of an important leukocyte population in mammalian liver is well documented, the characterization of leukocyte populations in the teleost liver has been only scarcely addressed. In the current work, we have confirmed the presence of IgM+, IgD+, IgT+, CD8α+, CD3+ cells, and cells expressing major histocompatibility complex (MHC-II in rainbow trout (Oncorhynchus mykiss liver by flow cytometry and/or immunohistochemistry analysis. Additionally, the effect of viral hemorrhagic septicemia virus (VHSV on the liver immune response was assessed. First, we studied the effect of viral intraperitoneal injection on the transcription of a wide selection of immune genes at days 1, 2 and 5 post-infection. These included a group of leukocyte markers genes, pattern recognition receptors (PRRs, chemokines, chemokine receptor genes, and other genes involved in the early immune response and in acute phase reaction. Our results indicate that T lymphocytes play a key role in the initial response to VHSV in the liver, since CD3, CD8, CD4, perforin, Mx and interferon (IFN transcription levels were up-regulated in response to VHSV. Consequently, flow cytometry analysis of CD8α+ cells in liver and spleen at day 5 post-infection revealed a decrease in the number of CD8α+ cells in the spleen and an increased population in the liver. No differences were found however in the percentages of B lymphocyte (IgM+ or IgD+ populations. In addition, a strong up-regulation in the transcription levels of several PRRs and chemokines was observed from the second day of infection, indicating an important role of these factors in the response of the liver to viral infections.

  1. Genetics of mechanisms controlling responses to two major pathogens in broiler and layer chickens

    DEFF Research Database (Denmark)

    Hamzic, Edin

    The objective of this thesis was to improve the understanding of molecular mechanisms controlling the response to two major pathogens, Eimeria maxima (coccidiosis) and infectious bronchitis virus (IBV), in broiler and layer chickens, respectively. Breeding for the improved response to the two pat...

  2. A quantum-mechanical perspective on linear response theory within polarizable embedding

    DEFF Research Database (Denmark)

    List, Nanna Holmgaard; Norman, Patrick; Kongsted, Jacob

    2017-01-01

    We present a derivation of linear response theory within polarizable embedding starting from a rigorous quantum-mechanical treatment of a composite system. To this aim, two different subsystem decompositions (symmetric and nonsymmetric) of the linear response function are introduced and the pole...

  3. Developmental trajectory from early responses to transgressions to future antisocial behavior: evidence for the role of the parent-child relationship from two longitudinal studies.

    Science.gov (United States)

    Kim, Sanghag; Kochanska, Grazyna; Boldt, Lea J; Nordling, Jamie Koenig; O'Bleness, Jessica J

    2014-02-01

    Parent-child relationships are critical in development, but much remains to be learned about the mechanisms of their impact. We examined the early parent-child relationship as a moderator of the developmental trajectory from children's affective and behavioral responses to transgressions to future antisocial, externalizing behavior problems in the Family Study (102 community mothers, fathers, and infants, followed through age 8) and the Play Study (186 low-income, diverse mothers and toddlers, followed for 10 months). The relationship quality was indexed by attachment security in the Family Study and maternal responsiveness in the Play Study. Responses to transgressions (tense discomfort and reparation) were observed in laboratory mishaps wherein children believed they had damaged a valued object. Antisocial outcomes were rated by parents. In both studies, early relationships moderated the future developmental trajectory: diminished tense discomfort predicted more antisocial outcomes, but only in insecure or unresponsive relationships. That risk was defused in secure or responsive relationships. Moderated mediation analyses in the Family Study indicated that the links between diminished tense discomfort and future antisocial behavior in insecure parent-child dyads were mediated by stronger discipline pressure from parents. By indirectly influencing future developmental sequelae, early relationships may increase or decrease the probability that the parent-child dyad will embark on a path toward antisocial outcomes.

  4. Early response to medical treatment of trigeminal neuralgia in a Nigerian population

    Directory of Open Access Journals (Sweden)

    Osawe Felix Omoregie

    2015-01-01

    Full Text Available Background: This study evaluates the clinical profile of patients suffering from trigeminal neuralgia (TN and correlates the findings with early response of the patients to medical treatment. Patients and Methods: A 4-year prospective study in which patients diagnosed of TN were treated medically and followed up weekly for 8 weeks to determine early treatment outcome, in the University of Benin Teaching Hospital, Benin City, Nigeria. Results: Of the 287 patients seen during the study period, a total of 14 (4.9% patients were diagnosed of TN. Thirteen (4.5% of the cases were selected based on compliance to the 8-week follow-up visits, consisting of 8 (61.5% males and 5 (38.5% females, giving a ratio of 1.6:1. The mean age of the patients was 50±1.5 years. The mandibular (n = 6, 46.2% and maxillary (n = 5, 38.5% divisions of the trigeminal nerve were mostly affected. The lesion was slightly more common on the right side of the face (n = 7, 53.8% than the left side (n = 6, 46.2%. Talking (n=4, 30.8% and chewing (n = 3, 23.1% were the most frequent trigger factors. The patients mostly described the pain as severe, spontaneous, and sharp (n = 5, 38.2%. Most patients became stable on tablets carbamazepine 200 mg 12 hourly, folic acid 5 mg daily, and phenytoin 100 mg daily. Good response was observed in most patients within 2 weeks (n = 6, 46.2% of medical treatment, especially in patients at the seventh decade of age (n = 3, 23.1% and those with lesions involving the mandibular division of the trigeminal nerve (n = 3, 23.1%. Conclusion: This study shows early response of TN to medical treatment. We recommend combination therapy of carbamazepine and folic acid in the treatment of patients, especially elderly patients with lesions involving the mandibular division of the trigeminal nerve.

  5. Characterization of early cortical population response to thalamocortical input in vitro

    Directory of Open Access Journals (Sweden)

    Michael Raymond Heliodor Hill

    2014-01-01

    Full Text Available The in vitro thalamocortical slice preparation of mouse barrel cortex allows for stimulation of the cortex through its natural afferent thalamocortical pathway. This preparation was used here to investigate the first stage of cortical processing in the large postsynaptic dendritic networks as revealed by voltage sensitive dye imaging. We identified the precise location and dimensions of two clearly distinguishable dendritic networks, one in the granular layer IV and one in the infragranular layer V and VI and showed that they have different physiological properties. DiI fluorescent staining further revealed that thalamocortical axons project on to these two networks in the typical barrel like form, not only in the granular but also in the infragranular layer. Finally we investigated the short term dynamics of both the voltage sensitive dye imaging signal and the local field potential in response to a train of eight-pulses at various frequencies in both these layers. We found evidence of differences in the plasticity between the first two response peaks compared to the remaining six peaks as well as differences in short term plasticity between the voltage sensitive dye imaging response and the local field potential. Our findings suggest, that at least early cortical processing takes place in two separate dendritic networks that may stand at the beginning of further parallel computation. The detailed characterization of the parameters of these networks may provide tools for further research into the complex dynamics of large dendritic networks and their role in cortical computation.

  6. Single Pulse Electrical Stimulation to identify epileptogenic cortex: Clinical information obtained from early evoked responses.

    Science.gov (United States)

    Mouthaan, B E; van 't Klooster, M A; Keizer, D; Hebbink, G J; Leijten, F S S; Ferrier, C H; van Putten, M J A M; Zijlmans, M; Huiskamp, G J M

    2016-02-01

    Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, 80 Hz, in the SOZ and seizure propagation areas. We used data from 12 refractory epilepsy patients. SPES consisted of 10 pulses of 1 ms, 4-8 mA and 5s interval on adjacent electrodes pairs. Data were available at 2048 samples/s for six and 512 samples/s (22 bits) for eight patients and analyzed in the time-frequency (TF) and time-domain (TD). Electrodes with ERs were stronger associated with SOZ than non-SOZ electrodes. ERs with frequency content >80 Hz exist and are specific for SOZ channels. ERs evoked by stimulation of seizure onset electrodes were associated with electrodes involved in seizure propagation. Analysis of ERs can reveal aspects of pathology, manifested by association with seizure propagation and areas with high ER numbers that coincide with the SOZ. Not only DRs, but also ERs could have clinical value for mapping epileptogenic cortex and help to unravel aspects of the epileptic network. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Characterization of early cortical population response to thalamocortical input in vitro.

    Science.gov (United States)

    Hill, Michael R H; Greenfield, Susan A

    2013-01-01

    The in vitro thalamocortical slice preparation of mouse barrel cortex allows for stimulation of the cortex through its natural afferent thalamocortical pathway. This preparation was used here to investigate the first stage of cortical processing in the large postsynaptic dendritic networks as revealed by voltage sensitive dye imaging (VSDI). We identified the precise location and dimensions of two clearly distinguishable dendritic networks, one in the granular layer (GL) IV and one in the infragranular layer (IGL) V and VI and showed that they have different physiological properties. DiI fluorescent staining further revealed that thalamocortical axons project on to these two networks in the typical barrel like form, not only in the granular but also in the IGL. Finally we investigated the short-term dynamics of both the VSDI signal and the local field potential (LFP) in response to a train of eight-pulses at various frequencies in both these layers. We found evidence of differences in the plasticity between the first two response peaks compared to the remaining six peaks as well as differences in short-term plasticity between the VSDI response and the LFP. Our findings suggest, that at least early cortical processing takes place in two separate dendritic networks that may stand at the beginning of further parallel computation. The detailed characterization of the parameters of these networks may provide tools for further research into the complex dynamics of large dendritic networks and their role in cortical computation.

  8. Impaired Early-Response Inhibition in Overweight Females with and without Binge Eating Disorder.

    Directory of Open Access Journals (Sweden)

    Jennifer Svaldi

    Full Text Available Several studies report increased reward sensitivity towards food in overweight individuals. By contrast, data is inconclusive with respect to response inhibition in overweight individuals without binge eating disorder (BED. Hence, the latter was addressed in the present study in a group of overweight/obese females with and without BED and a normal-weight control group without eating disorders.A group of women with BED (n = 29, a group of overweight women without BED (n = 33 and normal-weight females (n = 30 participated in a pictorial priming paradigm, with food items (relevant primes and office utensils (neutral primes and color blobs (neutral primes as stimuli. Increased response priming effects (i.e. priming with switches between stimulus categories were taken as indicators of deficient behavioral inhibition.Priming effects for neutral primes were moderate and comparable across all groups. However, primes associated with the food task set lead to increased priming effects in both overweight groups. But, effects were comparable for overweight/obese participants with and without BED.Results suggest that early response inhibition in the context of food is impaired in overweight individuals compared to normal-weight individuals.

  9. The Interaction of Early Maternal Responsiveness and Children's Cognitive Abilities on Later Decoding and Reading Comprehension Skills

    Science.gov (United States)

    Taylor, Heather B.; Anthony, Jason L.; Aghara, Rachel; Smith, Karen E.; Landry, Susan H.

    2008-01-01

    This longitudinal study evaluated the extent to which maternal responsiveness across early childhood and children's cognitive skills predicted children's 8-year decoding and reading comprehension skills for children who varied in biological risk (term, n = 83; preterm, n = 155). Patterns of maternal responsiveness during infancy (6, 12, and 24…

  10. Strategic down-regulation of attentional resources as a mechanism of proactive response inhibition.

    Science.gov (United States)

    Langford, Zachary D; Krebs, Ruth M; Talsma, Durk; Woldorff, Marty G; Boehler, C N

    2016-08-01

    Efficiently avoiding inappropriate actions in a changing environment is central to cognitive control. One mechanism contributing to this ability is the deliberate slowing down of responses in contexts where full response cancellation might occasionally be required, referred to as proactive response inhibition. The present electroencephalographic (EEG) study investigated the role of attentional processes in proactive response inhibition in humans. To this end, we compared data from a standard stop-signal task, in which stop signals required response cancellation ('stop-relevant'), to data where possible stop signals were task-irrelevant ('stop-irrelevant'). Behavioral data clearly indicated the presence of proactive slowing in the standard stop-signal task. A novel single-trial analysis was used to directly model the relationship between response time and the EEG data of the go-trials in both contexts within a multilevel linear models framework. We found a relationship between response time and amplitude of the attention-related N1 component in stop-relevant blocks, a characteristic that was fully absent in stop-irrelevant blocks. Specifically, N1 amplitudes were lower the slower the response time, suggesting that attentional resources were being strategically down-regulated to control response speed. Drift diffusion modeling of the behavioral data indicated that multiple parameters differed across the two contexts, likely suggesting the contribution from independent brain mechanisms to proactive slowing. Hence, the attentional mechanism of proactive response control we report here might coexist with known mechanisms that are more directly tied to motoric response inhibition. As such, our study opens up new research avenues also concerning clinical conditions that feature deficits in proactive response inhibition.

  11. Qualitative differences in the early immune response to live and killed Leishmania major: Implications for vaccination strategies against Leishmaniasis.

    Science.gov (United States)

    Okwor, Ifeoma; Liu, Dong; Uzonna, Jude

    2009-04-28

    Recovery from natural or deliberate infection with Leishmania major leads to the development of lifelong immunity against rechallenge infections. In contrast, vaccination with killed parasites or defined leishmanial antigens generally induces only short-term protection. The reasons for this difference are currently not known but may be related to differences in the quality of the early immune responses to live and killed parasites. Here, we report that live and killed L. major parasites elicit comparable early inflammatory response as evidenced by influx and/or proliferation of cells in the draining lymph nodes (dLNs). In contrast, the early cytokine responses were qualitatively different. Cells from mice inoculated with killed parasites produced significantly more antigen-specific IL-4 and less IFN-gamma than those from mice injected with live parasites. Inclusion of CpG ODN into killed parasite preparations changed the early response to killed parasites from IL-4 to a predominantly IFN-gamma response, resulting in better protection following secondary high dose virulent L. major challenge. Interestingly, CpG-mediated enhancement of killed parasites-induced protection was short-lived and waned after 12 weeks. Taken together, these results suggest that the nature of primary immunity induced by killed and live parasites are qualitatively different and that these differences may account for the differential protection seen in mice following vaccination with live and killed parasites. They further suggest that modulating the early response with an appropriate adjuvant could enhance efficacy of killed parasite vaccines.

  12. Biophysical response of living cells to boron nitride nanoparticles: uptake mechanism and bio-mechanical characterization

    Science.gov (United States)

    Rasel, Md. Alim Iftekhar; Li, Tong; Nguyen, Trung Dung; Singh, Sanjleena; Zhou, Yinghong; Xiao, Yin; Gu, YuanTong

    2015-11-01

    Boron nitride nanomaterials have attracted significant interest due to their superior chemical and physical properties. Despite these novel properties, investigation on the interaction between boron nitride nanoparticle (BN NP) and living systems has been limited. In this study, BN NP (100-250 nm) is assessed as a promising biomaterial for medical applications. The toxicity of BN NP is evaluated by assessing the cells behaviours both biologically (MTT assay, ROS detection etc.) and physically (atomic force microscopy). The uptake mechanism of BN NP is studied by analysing the alternations in cellular morphology based on cell imaging techniques. The results demonstrate in vitro cytocompatibility of BN NP with immense potential for use as an effective nanoparticle for various bio-medical applications.

  13. Biophysical response of living cells to boron nitride nanoparticles: uptake mechanism and bio-mechanical characterization

    Energy Technology Data Exchange (ETDEWEB)

    Rasel, Md. Alim Iftekhar; Li, Tong; Nguyen, Trung Dung; Singh, Sanjleena [Queensland University of Technology (QUT), School of Chemistry, Physics and Mechanical Engineering (Australia); Zhou, Yinghong; Xiao, Yin [Queensland University of Technology (QUT), Institute of Health and Biomedical Innovation (Australia); Gu, YuanTong, E-mail: yuantong.gu@qut.edu.au [Queensland University of Technology (QUT), School of Chemistry, Physics and Mechanical Engineering (Australia)

    2015-11-15

    Boron nitride nanomaterials have attracted significant interest due to their superior chemical and physical properties. Despite these novel properties, investigation on the interaction between boron nitride nanoparticle (BN NP) and living systems has been limited. In this study, BN NP (100–250 nm) is assessed as a promising biomaterial for medical applications. The toxicity of BN NP is evaluated by assessing the cells behaviours both biologically (MTT assay, ROS detection etc.) and physically (atomic force microscopy). The uptake mechanism of BN NP is studied by analysing the alternations in cellular morphology based on cell imaging techniques. The results demonstrate in vitro cytocompatibility of BN NP with immense potential for use as an effective nanoparticle for various bio-medical applications.

  14. Regenerated Spider Silk Possess Mechanical Properties of Super- and Cyclic Contraction in Response to Environmental Humidity

    Science.gov (United States)

    Lu, Shan; Swaminathan, Ganesh; Evans, Samuel; Blackledge, Todd

    2013-06-01

    Major Ampullate (MA) spider silk is among the most impressive biomaterials due to its unparalleled mechanical properties, such as super-contraction and cyclic response to changes in humidity. Electro-spinning enables the generation of engineered silk fibers with controlled parameters and dimentions for various medical and commercial applications. However, their applications hinge on the ability to reproduce the mechanical properties such as a precise expansion-contraction response existed in natural silk fibers. Here, we successfully reproduced MA spider-silk fibers from solutions of natural MA silk proteins via electrospinning, which exhibit the super-contraction and cyclic response to humidity change in a manner mirroring the natural fibers.

  15. Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

    Energy Technology Data Exchange (ETDEWEB)

    Van der Meeren, A.; Tourdes, F.; Gremy, O.; Grillon, G.; Abram, M.C.; Poncy, J.L.; Griffiths, N. [CEA, DSV, DRR, SRCA, Centre DAM Ile de France, F-91297 Bruyeres Le Chatel, Arpajon (France)

    2008-07-01

    Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO{sub 2} or different isotopic compositions (70% or 97% {sup 239}Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multi-nucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1 beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO{sub 2}-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% {sup 239}Pu than for 70% {sup 239}Pu. (authors)

  16. Early changes in shoot transcriptome of rice in response to Rhodotorula mucilaginosa JGTA-S1

    Directory of Open Access Journals (Sweden)

    Chinmay Saha

    2015-12-01

    Full Text Available Yeasts of Rhodotorula genus have been reported to show endophytic colonization in different plants. Some of the Rhodotorula species are found to exhibit plant growth promoting activities and also have been reported to protect plants against invading pathogens. A yeast strain closely related to Rhodotorula mucilaginosa was isolated from the endosphere of Typha angustifolia collected from a Uranium mine. A microarray analysis was performed to investigate the early changes in rice shoot transcripts in response to this yeast (R. mucilaginosa JGTA-S1. Transcriptional changes were monitored in 6 h and 24 h treated rice plant shoots as compared to 0 h control. The microarray data has been submitted to the NCBI GEO repository under the accession number of GSE64321.

  17. Beyond Contact Tracing: Community-Based Early Detection for Ebola Response

    CERN Document Server

    Cooney, Daniel; Bar-Yam, Yaneer

    2015-01-01

    The 2014 Ebola outbreak in west Africa raised many questions about the control of infectious disease in an increasingly connected global society. Limited availability of contact information has made contact tracing difficult or impractical in combating the outbreak. We consider the development of multi-scale public health strategies and simulate policies for community-level response aimed at early screening of communities rather than individuals, as well as travel restrictions to prevent community cross-contamination. Our analysis shows community screening to be effective even at a relatively low level of compliance. In our simulations, 40% of individuals conforming to this policy is enough to stop the outbreak. Simulations with a 50% compliance rate are consistent with the case counts in Liberia during the period of rapid decline after mid September, 2014. We also find the travel restriction policies to be effective at reducing the risks associated with compliance substantially below the 40% level, shortenin...

  18. Radiolabeled Apoptosis Imaging Agents for Early Detection of Response to Therapy

    Directory of Open Access Journals (Sweden)

    Kazuma Ogawa

    2014-01-01

    Full Text Available Since apoptosis plays an important role in maintaining homeostasis and is associated with responses to therapy, molecular imaging of apoptotic cells could be useful for early detection of therapeutic effects, particularly in oncology. Radiolabeled annexin V compounds are the hallmark in apoptosis imaging in vivo. These compounds are reviewed from the genesis of apoptosis (cell death imaging agents up to recent years. They have some disadvantages, including slow clearance and immunogenicity, because they are protein-based imaging agents. For this reason, several studies have been conducted in recent years to develop low molecule apoptosis imaging agents. In this review, radiolabeled phosphatidylserine targeted peptides, radiolabeled bis(zinc(II-dipicolylamine complex, radiolabeled 5-fluoropentyl-2-methyl-malonic acid (ML-10, caspase-3 activity imaging agents, radiolabeled duramycin, and radiolabeled phosphonium cation are reviewed as promising low-molecular-weight apoptosis imaging agents.

  19. Early life history and habitat ecology of estuarine fishes: responses to natural and human induced change

    Directory of Open Access Journals (Sweden)

    Kenneth Able

    2015-12-01

    Full Text Available Our understanding of the early life history of fishes and their habitats has proceeded from basic natural history to ecology, but we often need to return to natural history to address deficiencies in conceptual and quantitative models of ecosystems. This understanding is further limited by the complex life history of fishes and the lack of appreciation of shifting baselines in estuaries. These inadequacies are especially evident when we try to address the effects of human influences, e.g. fishing, urbanization, and climate change. Often our baselines are inadequate or inaccurate. Our work has detected these along the coasts of the U.S. in extensive time series of larval fish ingress into estuaries, studies of the effects of urbanization, and responses to catastrophes such as the BP oil spill. Long-term monitoring, especially, continues to provide critical insights

  20. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas; Forestier, Erik; Frandsen, Thomas L; Harila-Saari, Arja; Heyman, Mats; Jonsson, Olafur G; Lähteenmäki, Päivi M; Lausen, Birgitte; Vaitkevičienė, Goda; Asberg, Ann; Schmiegelow, Kjeld

    2014-08-01

    Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744 patients on Nordic-Baltic trials. CNS status was classified as CNS1 (no CSF blasts), CNS2 ( 0.15). The 12-year event-free survival for patients with leukemic mass on neuroimaging did not differ from patients with negative or no scan (0.50 vs. 0.60; P = 0.7) or between patients with symptoms or signs suggestive of CNS leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia. © 2014 Wiley Periodicals, Inc.

  1. Lung function and bronchial responsiveness after Mycoplasma pneumoniae infection in early childhood

    DEFF Research Database (Denmark)

    Boysen, Birgitte Kjær; Jensen, Jørgen S; Nielsen, Kim G

    2008-01-01

    follow-up examination including lung function testing (28 PCR-positive and 37 PCR-negative). In addition to the PCR-test for M. pneumoniae all respiratory tract specimens were additionally tested for other atypical bacteria and for viruses by PCR. Lung function was measured as specific airway resistance...... by whole-body plethysmography and bronchial hyperresponsiveness was assessed by cold, dry air hyperventilation. Neither baseline lung function nor bronchial response to cold dry air hyperventilation differed between M. pneumoniae-positive and -negative children: mean baseline lung function were 1.17 versus...... 1.21 (kPa sec), P = 0.45; and mean change in specific resistance was 13% versus 9%, P = 0.42. In conclusion, M. pneumoniae infection in early childhood was not associated with long-term effects on lung function and bronchial hyperresponsiveness 2 years after infection....

  2. A Case Report on Juvenile Neuromyelitis Optica: Early Onset, Long Remission Period, and Atypical Treatment Response.

    Science.gov (United States)

    Elpers, Christiane; Gross, Catharina C; Fiedler, Barbara; Meuth, Sven G; Kurlemann, Gerhard

    2015-08-01

    Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease of the central nervous system and preferentially targets the optic nerves and spinal cord. NMO is rare in children and clinical course of the disease is highly variable as described in studies. Here, we present a case report of a young girl presenting with a rare course of pediatric NMO with an early disease onset at the age of 12 years, a relapse free interval of 4 years, evidence of NMO immunoglobulin G (IgG) and an unusual response against immunosuppressive therapy. The aim of this report is to highlight the potentially long remission period between relapses complicating proper diagnosis despite well defined diagnostic criteria. In addition, we want to encourage the use of rituximab in pediatric NMO, although larger cohorts are warranted to establish B cell depleting therapies in juvenile NMO.

  3. Phonemic versus allophonic status modulates early brain responses to language sounds: an MEG/ERF study

    DEFF Research Database (Denmark)

    Nielsen, Andreas Højlund; Gebauer, Line; Mcgregor, William

    Objective: An early component of the auditory event-related potential (ERP), the mismatch negativity (MMN/MMNm), has been shown to be sensitive to native versus non-native language sounds (Brandmeyer et al., 2012; Kazanina et al., 2006; Näätänen et al., 1997); i.e. sensitive to phonemic versus...... allophonic sound contrasts. So far this has only been attested between languages. In the present study we wished to investigate this effect within the same language: Does the same sound contrast that is phonemic in one environment, but allophonic in another, elicit different MMNm responses in native......] thus as deviants, respectively. Data were preprocessed using Elekta’s MaxFilter software and SPM8, all statistical analyses were conducted in sensor-space using SPM8. Results: Focusing on the 150-300 ms time period after stimulus onset (typical MMNm time range for language sound contrasts), only...

  4. Early human bone response to laser metal sintering surface topography: a histologic report.

    Science.gov (United States)

    Mangano, Carlo; Piattelli, Adriano; d'Avila, Susana; Iezzi, Giovanna; Mangano, Francesco; Onuma, Tatiana; Shibli, Jamil Awad

    2010-01-01

    This histologic report evaluated the early human bone response to a direct laser metal sintering implant surface retrieved after a short period of healing. A selective laser sintering procedure using a Ti-6Al-4V alloy powder with a particle size of 25-45 microm prepared this surface topography. One experimental microimplant was inserted into the anterior mandible of a patient during conventional implant surgery of the jaw. The microimplant and surrounding tissues were removed after 2 months of unloaded healing and were prepared for histomorphometric analysis. Histologically, the peri-implant bone appeared in close contact with the implant surface, whereas marrow spaces could be detected in other areas along with prominently stained cement lines. The mean of bone-to-implant contact was 69.51%. The results of this histologic report suggest that the laser metal sintering surface could be a promising alternative to conventional implant surface topographies.

  5. Wisconsin Twin Research: early development, childhood psychopathology, autism, and sensory over-responsivity.

    Science.gov (United States)

    Schmidt, Nicole L; Van Hulle, Carol A; Brooker, Rebecca J; Meyer, Lauren R; Lemery-Chalfant, Kathryn; Goldsmith, H Hill

    2013-02-01

    The Wisconsin Twin Research Program comprises multiple longitudinal studies that utilize a panel recruited from statewide birth records for the years 1989 through 2004. Our research foci are the etiology and developmental course of early emotions, temperament, childhood anxiety and impulsivity, autism, sensory over-responsivity, and related topics. A signature feature of this research program is the breadth and depth of assessment during key periods of development. The assessments include extensive home- and laboratory-based behavioral batteries, recorded sibling and caregiver interactions, structured psychiatric interviews with caregivers and adolescents, observer ratings of child behavior, child self-report, cognitive testing, neuroendocrine measures, medical records, dermatoglyphics, genotyping, and neuroimaging. Across the various studies, testing occasions occurred between 3 months and 18 years of age. Data collection for some aspects of the research program has concluded and, for other aspects, longitudinal follow-ups are in progress.

  6. Potentiation of the early visual response to learned danger signals in adults and adolescents.

    Science.gov (United States)

    Levita, Liat; Howsley, Philippa; Jordan, Jeff; Johnston, Pat

    2015-02-01

    The reinforcing effects of aversive outcomes on avoidance behaviour are well established. However, their influence on perceptual processes is less well explored, especially during the transition from adolescence to adulthood. Using electroencephalography, we examined whether learning to actively or passively avoid harm can modulate early visual responses in adolescents and adults. The task included two avoidance conditions, active and passive, where two different warning stimuli predicted the imminent, but avoidable, presentation of an aversive tone. To avoid the aversive outcome, participants had to learn to emit an action (active avoidance) for one of the warning stimuli and omit an action for the other (passive avoidance). Both adults and adolescents performed the task with a high degree of accuracy. For both adolescents and adults, increased N170 event-related potential amplitudes were found for both the active and the passive warning stimuli compared with control conditions. Moreover, the potentiation of the N170 to the warning stimuli was stable and long lasting. Developmental differences were also observed; adolescents showed greater potentiation of the N170 component to danger signals. These findings demonstrate, for the first time, that learned danger signals in an instrumental avoidance task can influence early visual sensory processes in both adults and adolescents.

  7. Genotypic responses and diallel analysis for an early resistance test to Sclerotinia sclerotiorum in sunflower

    Directory of Open Access Journals (Sweden)

    Castaño Fernando

    2002-11-01

    Full Text Available The evaluation of sunflower genotypic performance against Sclerotinia sclerotiorum infections is important for understanding its usefulness as source of resistance. In the field, artificial and natural resistance tests provide important information that can be used in the selection of the best materials, however the procedures for resistance tests are usually both expensive and laborious. This work describes the performance of sunflower genotypes of broad genetic base at an early stage of plant development using a resistance test carried out under controlled conditions in the greenhouse. Statistical analysis detected highly significant genotypic responses and the combined abilities effects among the evaluated populations and their offspring, obtained by a diallel crossing system method 2 for dead seedlings (% at 25 days after S. sclerotiorum infection on the basal stem. The methodology allowed superior parents to be detected and crosses to be furthered in the selection for S. sclerotiorum resistance. The usefulness of the evaluated genetic materials and the early resistance test in sunflower breeding plans is discussed.

  8. Immediate early response of the circadian polyA ribonuclease nocturnin to two extracellular stimuli.

    Science.gov (United States)

    Garbarino-Pico, Eduardo; Niu, Shuang; Rollag, Mark D; Strayer, Carl A; Besharse, Joseph C; Green, Carla B

    2007-05-01

    Nocturnin (Noc, also called Ccrn4l [carbon catabolite repression 4-like]) is a circadian deadenylase that is rhythmically expressed in multiple tissues in mice with peak mRNA levels in early night. Since several other circadian genes are induced by extracellular stimuli, we tested the hypothesis that Noc is acutely regulated in NIH3T3 cells. A serum shock and the phorbol ester TPA induced Noc transcript levels in quiescent NIH3T3 cultures while dexamethasone and forskolin, which are known to induce other clock genes in culture, were without effect. NOC protein levels also were induced by serum. The half-life of the TPA-induced Noc mRNA is short, and the inhibition of protein synthesis by cycloheximide prevents Noc mRNA degradation and revealed a 30-fold increase in the transcript levels after 4 h of TPA treatment. Since this acute induction is not dependent on protein synthesis, Noc behaves like other immediate early genes. Remarkably, these acute effects are specific to Noc as the mRNAs encoding other known mouse deadenylases, CCR4, CAF1, PAN2, and PARN, were not induced in the same paradigm. Our data show that in addition to its robust circadian regulation, Noc expression can be regulated acutely, and imply that it can respond directly and specifically to physiological cues. NOC may act in turning off the expression of genes that are required to be silenced as a response to these extracellular signals.

  9. Computation of the effective nonlinear mechanical response of lattice materials considering geometrical nonlinearities

    Science.gov (United States)

    ElNady, Khaled; Goda, Ibrahim; Ganghoffer, Jean-François

    2016-09-01

    The asymptotic homogenization technique is presently developed in the framework of geometrical nonlinearities to derive the large strains effective elastic response of network materials viewed as repetitive beam networks. This works extends the small strains homogenization method developed with special emphasis on textile structures in Goda et al. (J Mech Phys Solids 61(12):2537-2565, 2013). A systematic methodology is established, allowing the prediction of the overall mechanical properties of these structures in the nonlinear regime, reflecting the influence of the geometrical and mechanical micro-parameters of the network structure on the overall response of the chosen equivalent continuum. Internal scale effects of the initially discrete structure are captured by the consideration of a micropolar effective continuum model. Applications to the large strain response of 3D hexagonal lattices and dry textiles exemplify the powerfulness of the proposed method. The effective mechanical responses obtained for different loadings are validated by FE simulations performed over a representative unit cell.

  10. Ecologically Relevant Cooling Early in Life Alters Prefledging Adrenocortical Response in Free-Living Songbirds.

    Science.gov (United States)

    Lynn, Sharon E; Kern, Michael D

    In vertebrates, exposure to stressful stimuli early in development may alter the activity of the hypothalamo-pituitary-adrenal (HPA) axis, with the potential for fitness consequences later in life. For altricial species, whose young rely on their parents for food, warmth, and protection from predators, adult behavior can modify the impact of some stressors on their offspring after birth or hatching. We have shown that single bouts of cooling that normally occur when brooding females leave the nest elevate corticosterone secretion in very young free-living eastern bluebird (Sialia sialis) chicks. Thus, natural variation in maternal brooding patterns can result in differential exposure of offspring to cooling, and also to glucocorticoids, very early in development. We tested the hypothesis that exposure to repeated bouts of cooling (mimicking those that occur normally when females leave the nest) would alter the activity of the chicks' HPA axis later in life. We exposed free-living chicks to either four 18-min bouts of cooling or brooding temperatures (control) during the first week after hatching. Then, just before fledging (i.e., at least 7 d after the cooling treatments had ceased), we assessed their corticosterone responses to restraint. Repeatedly cooled chicks had a significantly lower corticosterone response to restraint than did control chicks but did not differ from controls in other measures of growth and development. Our data suggest that natural variation in maternal brooding patterns, and hence natural variation in the chicks' body temperature, can alter the activity of the HPA axis well beyond the brooding period.

  11. Psychometric Evaluation of the Ford Insomnia Response to Stress Test (FIRST) in Early Pregnancy.

    Science.gov (United States)

    Gelaye, Bizu; Zhong, Qiu-Yue; Barrios, Yasmin V; Redline, Susan; Drake, Christopher L; Williams, Michelle A

    2016-04-15

    To evaluate the construct validity and factor structure of the Spanish-language version of the Ford Insomnia Response to Stress Test questionnaire (FIRST-S) when used in early pregnancy. A cohort of 647 women were interviewed at ≤ 16 weeks of gestation to collect information regarding lifestyle, demographic, and sleep characteristics. The factorial structure of the FIRST-S was tested through exploratory and confirmatory factor analyses (EFA and CFA). Internal consistency and construct validity were also assessed by evaluating the association between the FIRST-S with symptoms of depression, anxiety, and sleep quality. Item response theory (IRT) analyses were conducted to complement classical test theory (CTT) analytic approaches. The mean score of the FIRST-S was 13.8 (range: 9-33). The results of the EFA showed that the FIRST-S contained a one-factor solution that accounted for 69.8% of the variance. The FIRST-S items showed good internal consistency (Cronbach α = 0.81). CFA results corroborated the one-factor structure finding from the EFA; and yielded measures indicating goodness of fit (comparative fit index of 0.902) and accuracy (root mean square error of approximation of 0.057). The FIRST-S had good construct validity as demonstrated by statistically significant associations of FIRST-S scores with sleep quality, antepartum depression and anxiety symptoms. Finally, results from IRT analyses suggested excellent item infit and outfit measures. The FIRST-S was found to have good construct validity and internal consistency for assessing vulnerability to insomnia during early pregnancy. © 2016 American Academy of Sleep Medicine.

  12. Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection.

    Directory of Open Access Journals (Sweden)

    Thomas J Hannan

    Full Text Available Chronic infections are an increasing problem due to the aging population and the increase in antibiotic resistant organisms. Therefore, understanding the host-pathogen interactions that result in chronic infection is of great importance. Here, we investigate the molecular basis of chronic bacterial cystitis. We establish that introduction of uropathogenic E. coli (UPEC into the bladders of C3H mice results in two distinct disease outcomes: resolution of acute infection or development of chronic cystitis lasting months. The incidence of chronic cystitis is both host strain and infectious dose-dependent. Further, development of chronic cystitis is preceded by biomarkers of local and systemic acute inflammation at 24 hours post-infection, including severe pyuria and bladder inflammation with mucosal injury, and a distinct serum cytokine signature consisting of elevated IL-5, IL-6, G-CSF, and the IL-8 analog KC. Mice deficient in TLR4 signaling or lymphocytes lack these innate responses and are resistant, to varying degrees, to developing chronic cystitis. Treatment of C3H mice with the glucocorticoid anti-inflammatory drug dexamethasone prior to UPEC infection also suppresses the development of chronic cystitis. Finally, individuals with a history of chronic cystitis, lasting at least 14 days, are significantly more susceptible to redeveloping severe, chronic cystitis upon bacterial challenge. Thus, we have discovered that the development of chronic cystitis in C3H mice by UPEC is facilitated by severe acute inflammatory responses early in infection, which subsequently are predisposing to recurrent cystitis, an insidious problem in women. Overall, these results have significant implications for our understanding of how early host-pathogen interactions at the mucosal surface determines the fate of disease.

  13. Macrophages are essential for the early wound healing response and the formation of a fibrovascular scar.

    Science.gov (United States)

    He, Lizhi; Marneros, Alexander G

    2013-06-01

    After wounding, multiple cell types interact to form a fibrovascular scar; the formation and cellular origins of these scars are incompletely understood. We used a laser-injury wound model of choroidal neovascularization in the eye to determine the spatiotemporal cellular events that lead to formation of a fibrovascular scar. After laser injury, F4/80(+) myeloid cells infiltrate the wound site and induce smooth muscle actin (SMA) expression in adjacent retinal pigment epithelial cells, with subsequent formation of a SMA(+)NG2(+) myofibroblastic scaffold, into which endothelial cells then infiltrate to form a fibrovascular lesion. Cells of the fibrovascular scaffold express the proangiogenic factor IL-1β strongly, whereas retinal pigment epithelial cells are the main source of VEGF-A. Subsequent choroidal neovascularization is limited to the area demarcated by this myofibroblastic scaffold and occurs independently of epithelial- or myeloid-derived VEGF-A. The SMA(+)NG2(+) myofibroblastic cells, F4/80(+) macrophages, and adjacent epithelial cells actively proliferate in the early phase of the wound healing response. Cell-lineage tracing experiments suggest that the SMA(+)NG2(+) myofibroblastic scaffold originates from choroidal pericyte-like cells. Targeted ablation of macrophages inhibits the formation of this fibrovascular scaffold, and expression analysis reveals that these macrophages are Arg1(+)YM1(+)F4/80(+) alternatively activated M2-like macrophages, which do not require IL-4/STAT6 or IL-10 signaling for their activation. Thus, macrophages are essential for the early wound healing response and the formation of a fibrovascular scar.

  14. APRI as a predictor of early viral response in chronic hepatitis C patients

    Institute of Scientific and Technical Information of China (English)

    José A Mata-Marín; José L Fuentes-Allen; Jesús Gaytán-Martínez; Bulmaro Manjarrez-Téllez; Alberto Chaparro-Sánchez; Carla I Arroyo-Anduiza

    2009-01-01

    AIM: To evaluate the aspartate aminotransferase (AST) to platelet ratio index (APRI) as a predictive factor of early viral response in chronic hepatitis C naive patients.METHODS: We performed an ambispective casecontrol study. We enrolled chronic hepatitis C naive patients who were evaluated to start therapy with PEGylated interferon a-2b (1.5 mg/kg per week) and ribavirin (> 75 kg: 1200 mg and < 75 kg: 1000 mg). Patients were allocated into two groups, group 1: Hepatitis C patients with early viral response (EVR), group 2: Patients without EVR. Odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the relationship between each risk factor and the EVR in both groups.RESULTS: During the study, 80 patients were analyzed, 45 retrospectively and 35 prospectively. The mean ± SD age of our subjects was 42.9 ± 12 years; weight 70 kg (± 11.19), AST 64.6 IU/mL (± 48.74), alanine aminotransferase (ALT) 76.3 IU/mL (± 63.08) and platelets 209 000 mill/mm3 (± 84 429). Fifty-five (68.8%) were genotype 1 and 25 (31.3%) were genotype 2 or 3; the mean hepatitis C virus RNA viral load was 2 269 061 IU/mL (± 7 220 266). In the univariate analysis, APRI was not associated with EVR [OR 0.61 (95% CI 0.229-1.655, P = 0.33)], and the absence of EVR was only associated with genotype 1 [OR 0.28 (95% CI 0.08-0.94, P = 0.034)]. After adjustment in a logistic regression model, genotype 1 remains significant.CONCLUSION: APRI was not a predictor of EVR in chronic hepatitis C; Genotype 1 was the only predictive factor associated with the absence of EVR in our patients.

  15. Early suppression of immune response in Heliothis virescens larvae by the endophagous

    Directory of Open Access Journals (Sweden)

    R Ferrarese

    2005-04-01

    Full Text Available Toxoneuron nigriceps is an endophagous parasitoid of larval stages of the noctuid moth Heliothisvirescens. As all parasitoids, this wasp avoid host immune reaction by a combination of several passiveand active mechanisms. Secretions injected by ovipositing females, which contain venom, calyx fluid andpolydnaviruses, are the most probably factors actively disrupting Heliothis virescens immune system. Thispaper describes the main alterations of the host immune response observed shortly after oviposition by T.nigriceps. A transient block of prophenoloxidase activity is registered along with changes in hemocytenumber, adhesion and structure, which suggest the occurrence of apoptosis. In contrast, the hostplasmatocytes appear structurally unaltered, but unable to produce a capsule in vitro.

  16. Molecular mechanisms of early-life stress in 5-Htt deficient mice: Gene x environment interactions and epigenetic programming

    OpenAIRE

    2012-01-01

    Early-life stress has been shown to influence the development of the brain and to increase the risk for psychiatric disorders later in life. Furthermore, variation in the human serotonin transporter (5-HTT, SLC6A4) gene is suggested to exert a modulating effect on the association between early-life stress and the risk for depression. At the basis of these gene x environment (G x E) interactions, epigenetic mechanisms, such as DNA-methylation, seem to represent the primary biological processes...

  17. Early Flood Detection for Rapid Humanitarian Response: Harnessing Near Real-Time Satellite and Twitter Signals

    Directory of Open Access Journals (Sweden)

    Brenden Jongman

    2015-10-01

    Full Text Available Humanitarian organizations have a crucial role in response and relief efforts after floods. The effectiveness of disaster response is contingent on accurate and timely information regarding the location, timing and impacts of the event. Here we show how two near-real-time data sources, satellite observations of water coverage and flood-related social media activity from Twitter, can be used to support rapid disaster response, using case-studies in the Philippines and Pakistan. For these countries we analyze information from disaster response organizations, the Global Flood Detection System (GFDS satellite flood signal, and flood-related Twitter activity analysis. The results demonstrate that these sources of near-real-time information can be used to gain a quicker understanding of the location, the timing, as well as the causes and impacts of floods. In terms of location, we produce daily impact maps based on both satellite information and social media, which can dynamically and rapidly outline the affected area during a disaster. In terms of timing, the results show that GFDS and/or Twitter signals flagging ongoing or upcoming flooding are regularly available one to several days before the event was reported to humanitarian organizations. In terms of event understanding, we show that both GFDS and social media can be used to detect and understand unexpected or controversial flood events, for example due to the sudden opening of hydropower dams or the breaching of flood protection. The performance of the GFDS and Twitter data for early detection and location mapping is mixed, depending on specific hydrological circumstances (GFDS and social media penetration (Twitter. Further research is needed to improve the interpretation of the GFDS signal in different situations, and to improve the pre-processing of social media data for operational use.

  18. Fibronectin Matrix Remodeling in the Regulation of the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression

    Science.gov (United States)

    2011-09-01

    the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression PRINCIPAL INVESTIGATOR: Paula J. McKeown-Longo, Ph.D...2011 4. TITLE AND SUBTITLE Fibronectin Matrix Remodeling in the Regulation of the 5a. CONTRACT NUMBER W81XWH-10-1-0755 Inflammatory Response within...hypothesis that force dependent unfolding of fibronectin in the tumor stroma drives an inflammatory response within the lung tumor microenvironment

  19. ATM-dependent E2F1 accumulation in the nucleolus is an indicator of ribosomal stress in early response to DNA damage.

    Science.gov (United States)

    Jin, Ya-Qiong; An, Guo-Shun; Ni, Ju-Hua; Li, Shu-Yan; Jia, Hong-Ti

    2014-01-01

    The nucleolus plays a major role in ribosome biogenesis. Most genotoxic agents disrupt nucleolar structure and function, which results in the stabilization/activation of p53, inducing cell cycle arrest or apoptosis. Likewise, transcription factor E2F1 as a DNA damage responsive protein also plays roles in cell cycle arrest, DNA repair, or apoptosis in response to DNA damage through transcriptional response and protein-protein interaction. Furthermore, E2F1 is known to be involved in regulating rRNA transcription. However, how E2F1 displays in coordinating DNA damage and nucleolar stress is unclear. In this study, we demonstrate that ATM-dependent E2F1 accumulation in the nucleolus is a characteristic feature of nucleolar stress in early response to DNA damage. We found that at the early stage of DNA damage, E2F1 accumulation in the nucleolus was an ATM-dependent and a common event in p53-suficient and -deficient cells. Increased nucleolar E2F1 was sequestered by the nucleolar protein p14ARF, which repressed E2F1-dependent rRNA transcription initiation, and was coupled with S phase. Our data indicate that early accumulation of E2F1 in the nucleolus is an indicator for nucleolar stress and a component of ATM pathway, which presumably buffers elevation of E2F1 in the nucleoplasm and coordinates the diversifying mechanisms of E2F1 acts in cell cycle progression and apoptosis in early response to DNA damage.

  20. Skeletal muscle adaptation in response to mechanical stress in p130cas-/- mice.

    Science.gov (United States)

    Akimoto, Takayuki; Okuhira, Kanako; Aizawa, Katsuji; Wada, Shogo; Honda, Hiroaki; Fukubayashi, Toru; Ushida, Takashi

    2013-03-01

    Mammalian skeletal muscles undergo adaptation in response to changes in the functional demands upon them, involving mechanical-stress-induced cellular signaling called "mechanotransduction." We hypothesized that p130Cas, which is reported to act as a mechanosensor that transduces mechanical extension into cellular signaling, plays an important role in maintaining and promoting skeletal muscle adaptation in response to mechanical stress via the p38 MAPK signaling pathway. We demonstrate that muscle-specific p130Cas-/- mice express the contractile proteins normally in skeletal muscle. Furthermore, muscle-specific p130Cas-/- mice show normal mechanical-stress-induced muscle adaptation, including exercise-induced IIb-to-IIa muscle fiber type transformation and hypertrophy. Finally, we provide evidence that exercise-induced p38 MAPK signaling is not impaired by the muscle-specific deletion of p130Cas. We conclude that p130Cas plays a limited role in mechanical-stress-induced skeletal muscle adaptation.

  1. Recovery from severe H7N9 disease is associated with diverse response mechanisms dominated by CD8+ T cells

    Science.gov (United States)

    Wang, Zhongfang; Wan, Yanmin; Qiu, Chenli; Quiñones-Parra, Sergio; Zhu, Zhaoqin; Loh, Liyen; Tian, Di; Ren, Yanqin; Hu, Yunwen; Zhang, Xiaoyan; Thomas, Paul G.; Inouye, Michael; Doherty, Peter C.; Kedzierska, Katherine; Xu, Jianqing

    2015-01-01

    The avian origin A/H7N9 influenza virus causes high admission rates (>99%) and mortality (>30%), with ultimately favourable outcomes ranging from rapid recovery to prolonged hospitalization. Using a multicolour assay for monitoring adaptive and innate immunity, here we dissect the kinetic emergence of different effector mechanisms across the spectrum of H7N9 disease and recovery. We find that a diversity of response mechanisms contribute to resolution and survival. Patients discharged within 2–3 weeks have early prominent H7N9-specific CD8+ T-cell responses, while individuals with prolonged hospital stays have late recruitment of CD8+/CD4+ T cells and antibodies simultaneously (recovery by week 4), augmented even later by prominent NK cell responses (recovery >30 days). In contrast, those who succumbed have minimal influenza-specific immunity and little evidence of T-cell activation. Our study illustrates the importance of robust CD8+ T-cell memory for protection against severe influenza disease caused by newly emerging influenza A viruses. PMID:25967273

  2. Herbivore defense responses and associated herbivore defense mechanism as revealed by comparing a resistant wild soybean with a susceptible cultivar

    Directory of Open Access Journals (Sweden)

    Xiaoyi Wang

    2015-12-01

    Full Text Available Plants have evolved sophisticated defense mechanisms against herbivores to help them adapt to the environment. Understanding the defense mechanisms in plants can help us control insects in a more effective manner. In this study, we found that compared with Tianlong 2 (a cultivated soybean with insect susceptibility, ED059 (a wild soybean line with insect resistance contains sharper pubescence tips, as well as lower transcript levels of wound-induced protein kinase (WIPK and salicylic acid-induced protein kinase (SIPK, which are important mitogen-activated protein kinases involved in early defense response to herbivores. The observed lower transcript levels of WIPK and SIPK induced higher levels of jasmonic acid (JA, JA biosynthesis enzymes (AOC3 and some secondary metabolites in ED059. Functional analysis of the KTI1 gene via Agrobacterium-mediated transformation in Arabidopsis thaliana indicated that it plays an important role in herbivore defense in ED059. We further investigated the molecular response of third-instar Helicoverpa armigera (Hübner larvae to Tianlong 2 and ED059. We found apoptotic cells only in the midguts of larvae that fed on ED059. Compared with larvae reared on the susceptible cultivar Tianlong 2, transcript levels of catalase (CAT and glutathione S-transferase (GST were up-regulated, whereas those of CAR, CHSB, and TRY were down-regulated in larvae that fed on the highly resistant variety ED059. We propose that these differences underlie the different herbivore defense responses of ED059 and Tianlong 2.

  3. Imipramine activates glial cell line-derived neurotrophic factor via early growth response gene 1 in astrocytes.

    Science.gov (United States)

    Kim, Yeni; Kim, Se Hyun; Kim, Yong Sik; Lee, Young Han; Ha, Kyooseob; Shin, Soon Young

    2011-06-01

    Recent evidence has suggested that deficits in glial plasticity contribute to the pathophysiology of depressive disorders. The present study explored early growth response 1 (EGR-1) transcriptional regulation of imipramine-induced glial cell line-derived neurotrophic factor (GDNF) expression in astrocytes. After we observed the induction of GDNF mRNA expression in rat astrocytes in response to imipramine, deletion mutant studies showed that the proximal region between -493 and -114 of the GDNF promoter, which contains three binding sites for EGR-1, was essential for maximal imipramine-induced activation of GDNF promoter. The dose-dependent upregulation of EGR-1 by imipramine, the activation of GDNF by the over-expression of EGR-1 without imipramine and the reduction in the imipramine-induced GDNF mRNA expression after silencing of endogenous EGR-1 demonstrated that EGR-1 is upregulated by imipramine to activate the GDNF promoter. Furthermore, imipramine-induced GDNF mRNA expression was strongly attenuated in primary astrocytes from Egr-1(-/-) mice, and the immunoreactivity to an anti-GDNF antibody in glial fibrillary acidic protein-positive cells was lower in imipramine-treated astrocytes from Egr-1(-/-) mice than in those from Egr-1(+/-) mice. To determine whether mitogen-activated protein kinases (MAPKs) were associated with imipramine-induced EGR-1 expression, we examined the induction of MAPK phosphorylation in response to imipramine. Pretreatment of rat primary astrocytes with the MAPK kinase inhibitor U0126 or the JNK inhibitor SP600125 strongly inhibited imipramine-stimulated EGR-1 expression. In conclusion, we found that imipramine induction of EGR-1 upregulated GDNF in astrocytes in a dose-dependent manner. This upregulation may occur through the MEK/ERK and JNK MAPK pathways, which suggests a new therapeutic mechanism of action for depressive disorders.

  4. Experimental studies of the dynamic mechanical response of a single polymer chain

    DEFF Research Database (Denmark)

    Thormann, Esben; Evans, Drew R.; Craig, Vincent S. J.

    2006-01-01

    The high-frequency and low-amplitude dynamic mechanical response from a single poly(vinyl alcohol) chain was investigated. Modification of a commercial atomic force microscope enabled high-frequency and low-amplitude periodic deformations of polymer chains during extension to be performed....... Such an experiment has previously been considered untenable due to hydrodynamic and viscous effects, but we introduce here a method to isolate the response of the polymer from the hydrodynamic response. For periodic deformations with frequencies of 400-2000 Hz and amplitudes of 0.55-16.9 nm, we find that the dynamic...... mechanical response from poly(vinyl alcohol) does not differ from its static response. This result is not unexpected as poly(vinyl alcohol) is a highly flexible polymer with intramolecular relaxation processes taking place on a short time scale. The choice of a polymer with a fast relaxation allows its...

  5. Biochemical response to exposure to six textile dyes in early developmental stages of Xenopus laevis.

    Science.gov (United States)

    Güngördü, Abbas; Birhanli, Ayse; Ozmen, Murat

    2013-01-01

    The present study was undertaken to determine the toxic effect of a lethal concentration of six different commercially used textile dyes on the 46th stage of Xenopus laevis tadpoles. The tadpoles were exposed to Astrazon Red FBL, Astrazon Blue FGRL, Remazol Red RR, Remazol Turquoise Blue G-A, Cibacron Red FN-3G, and Cibacron Blue FN-R for 168 h in static test conditions, and thus, 168-h median lethal concentrations (LC(50)s) of each dye were determined to be 0.35, 0.13, 112, 7, 359, and 15.8 mg/L, respectively. Also, to evaluate the sublethal effects of each dye, tadpoles were exposed to different concentrations of dyes (with respect to 168-h LC(50)s) for 24 h. The alteration of selected enzyme activities was tested. For this aim, glutathione S-transferase (GST), carboxylesterase, and lactate dehydrogenase (LDH) were assayed. After dye exposure, the GST induction or inhibition and LDH induction indicated some possible mechanisms of oxidative stress and deterioration in aerobic respiration processes induced by the tested dyes. Findings of the study suggest that selected biomarker enzymes are useful in understanding the toxic mechanisms of these dyes in X. laevis tadpoles as early warning indicators. Therefore, these selected biomarkers may evaluate the effect of environmental factors, such as textile dye effluents and other industrial pollutants, on amphibians in biomonitoring studies.

  6. [Mechanism of tomato plants enhanced disease resistance against early blight primed by arbuscular mycorrhizal fungus Glomus versiforme].

    Science.gov (United States)

    Song, Yuan-yuan; Wang, Rui-long; Wei, Xiao-chen; Lu, Yong-jian; Tang, Zhao-yang; Wu, Guo-zhao; Su, Yi-juan; Zeng, Ren-sen

    2011-09-01

    Arbuscular mycorrhiza (AM) can not only improve host plants nutrient absorption, but also enhance their disease resistance. Taking the tomato (Lycopersicon esculentum) seedlings preinoculated with axbuscular mycorrhizal fungus (AMF) Glomus versiforme as test materials, this paper studied their protective enzyme activities and defense-related genes expression, and their resistance against a fungal pathogen Alternaria solani Sorauer which causes early blight. The seedlings pre-inoculated with AMF and later inoculated with A. solani showed significantly higher activities of superoxide dismutase (SOD) and peroxidase (POD) in leaves. The leaf SOD activity of the dually inoculated plants reached the maximum 18 h after pathogen inoculation, being 28.6%, 79.2% and 82.8% higher than that of the plants with G. versiforme inoculation alone, pathogen inoculation alone, and non-inoculation, and the Leaf POD activity reached the maximum 65 h after pathogen inoculation, being 762%, 18.3%, and 1710% higher, respectively. Real time RT-PCR analysis showed that dual inoculation with C. versiforme and A. solani strongly induced the expression of three defense-related genes. The transcript levels of pathogen-related protein (PR1), basic type beta-1,3-glucanase (PR-2), and chitinase (PR-3) in leaves were 9.67-, 8.54-, and 13.4-fold higher, as compared with the non-inoculation control, respectively. Bioassay showed that the disease incidence and disease index of the seedlings pre-inoculated with C. versiforme were reduced by 36.3% and 61.4%, respectively, as compared with the non-mycorrhizal control plants. These findings indicated that mycorrhizal colonization could induce stronger and quicker defense responses of host tomato plants, and priming could be an important mechanism of the enhanced disease resistance of mycorrhizal tomato plants.

  7. [Weaning from prolonged mechanical ventilation in neurological weaning units: an evaluation of the German Working Group for early Neurorehabilitation].

    Science.gov (United States)

    Oehmichen, F; Ketter, G; Mertl-Rötzer, M; Platz, T; Puschendorf, W; Rollnik, J D; Schaupp, M; Pohl, M

    2012-10-01

    A significant proportion of patients with long-term mechanical ventilation (MV) and difficult or prolonged weaning suffer from primary or secondary neurological conditions and concomitant functional disorders, in addition to respiratory problems. Therefore, these patients are treated in neurological weaning departments. Using a questionnaire members of the German Working Group for early neurorehabilitation were interviewed with respect to the structure of weaning facilities, weaning strategies, patient characteristics and treatment outcome of patients admitted for weaning in 2009. In the year 2009 a total of 1,486 patients were admitted to 7 participating neurological weaning units. The primary diagnosis was a neurological condition in 97.5% of the patients. In 62.9% of the patients the neurological condition was considered to be primarily responsible for the MV, 22.8% demonstrated pulmonary factors and for 3.0% a cardiac condition was determined to be decisive. In 5.0% of the patients it was not possible to ascertain a single cause or factor. Weaning was successful in 69.8% of all cases, 64.9% (965 patients) were released from the facility without MV, 274 patients (18.4%) were released with MV, 61.3% of these (168 patients) were referred to other rehabilitation facilities or into the care of the family physician and 38.7% (106 patients) were transferred to other hospitals due to special medical problems. The total mortality rate was 16.6% (247 patients deceased). In this first comprehensive evaluation of German neurological weaning centers for patients with long-term MV, structures and treatment outcomes were compared with recent results from the literature.

  8. Chromatic Mechanical Response in 2-D Layered Transition Metal Dichalcogenide (TMDs) based Nanocomposites

    Science.gov (United States)

    Rahneshin, Vahid; Khosravi, Farhad; Ziolkowska, Dominika A.; Jasinski, Jacek B.; Panchapakesan, Balaji

    2016-10-01

    The ability to convert photons of different wavelengths directly into mechanical motion is of significant interest in many energy conversion and reconfigurable technologies. Here, using few layer 2H-MoS2 nanosheets, layer by layer process of nanocomposite fabrication, and strain engineering, we demonstrate a reversible and chromatic mechanical response in MoS2-nanocomposites between 405 nm to 808 nm with large stress release. The chromatic mechanical response originates from the d orbitals and is related to the strength of the direct exciton resonance A and B of the few layer 2H-MoS2 affecting optical absorption and subsequent mechanical response of the nanocomposite. Applying uniaxial tensile strains to the semiconducting few-layer 2H-MoS2 crystals in the nanocomposite resulted in spatially varying energy levels inside the nanocomposite that enhanced the broadband optical absorption up to 2.3 eV and subsequent mechanical response. The unique photomechanical response in 2H-MoS2 based nanocomposites is a result of the rich d electron physics not available to nanocomposites based on sp bonded graphene and carbon nanotubes, as well as nanocomposite based on metallic nanoparticles. The reversible strain dependent optical absorption suggest applications in broad range of energy conversion technologies that is not achievable using conventional thin film semiconductors.

  9. Early biochemical and hematological response to intramuscular cyanocobalamin therapy in vitamin B(12)-deficient patients.

    Science.gov (United States)

    Mansoor, M Azam; Stea, Tonje Holte; Schneede, Jørn; Reine, Andreas

    2013-01-01

    Data on early biochemical and hematological responses to cobalamin therapy in vitamin B12-deficient patients are scarce. Therefore, we investigated whether cobalamin injections would include prompt biochemical and hematological responses in vitamin B12-deficient patients. Seven female patients (mean age: 69.4 years, range: 61-78) with a mean serum cobalamin level of 104 ± 38 pmol/l mean ± SD and 7 male patients (mean age: 67.0 years, range: 53-78) with a mean serum cobalamin level of 84 ± 40 (±SD) participated in the study. They were administered 1 mg i.m. cyanocobalamin per week for 3 weeks. Blood samples were collected before and 1, 3, 7, 14 and 21 days after cobalamin injection. The concentrations of plasma aminothiols and serum methylmalonic acid (MMA) were measured with high-performance liquid chromatography and gas chromatography/mass spectrometry, respectively, and hematological parameters were determined with a hematological analyzer. Already 1 day after intramuscular Cobalamin injections, the concentrations of serum vitamin B12 and plasma total cysteine were significantly increased while the concentrations of serum folate, plasma total homocysteine and serum MMA were decreased. Mean cell volume was also significantly decreased first after 14 days of therapy. Intramuscular cobalamin administration causes swift and significant changes in plasma aminothiols, whereas the first change in hematological parameters was detected only after 14 days. Copyright © 2013 S. Karger AG, Basel.

  10. Social exclusion induces early-stage perceptual and behavioral changes in response to social cues.

    Science.gov (United States)

    Kawamoto, Taishi; Nittono, Hiroshi; Ura, Mitsuhiro

    2014-01-01

    Social exclusion is so aversive that it causes broad cognitive and behavioral changes to regulate the individual's belonging status. The present study examined whether such changes also occur at early neural or automatic behavioral levels in response to social cues. Event-related brain potentials (ERPs) and facial electromyograms (EMGs) were recorded during a task in which participants viewed smiling, disgusted, and neutral faces after experiencing social exclusion or inclusion. Social exclusion was manipulated using a simple ball-tossing game (Cyberball), and need threat was assessed after the game. We found that zygomaticus major muscle activity, which reflects facial mimicry, was larger in response to smiling faces after exclusion than after inclusion. In addition, P1 amplitude, which reflects visual attention, was larger for disgusted faces than for neutral faces following social exclusion. N170 amplitude, which reflects structural encoding of the face, was correlated with heightened need threat. These findings demonstrate that social exclusion induces immediate and rapid changes in attention, perception, and automatic behavior. These findings reflect the rapid and primary regulation of belonging.

  11. Arecoline stimulated early growth response-1 production in human buccal fibroblasts: suppression by epigallocatechin-3-gallate.

    Science.gov (United States)

    Hsieh, Yu-Ping; Chen, Hsin-Ming; Chang, Jenny Zwei-Chieng; Chiang, Chun-Pin; Deng, Yi-Ting; Kuo, Mark Yen-Ping

    2015-04-01

    Early growth response-1 (Egr-1) protein plays an important role in many human fibrotic diseases. Areca nut chewing is the most important risk factor of oral submucous fibrosis (OSF). Egr-1 protein expression in OSF was examined using antibody to Egr-1. Arecoline-induced Egr-1 expression and its signaling pathways were assessed by Western blot analyses in human buccal mucosal fibroblasts (BMFs). Elevated Egr-1 staining was observed in epithelial cells, fibroblast, and inflammatory cells in 7 of 10 OSF cases. Arecoline, a main alkaloid found in the areca nut, stimulated Egr-1 synthesis in BMFs. Pretreatment with antioxidant N-acetyl-L-cysteine, c-Jun NH2-terminal kinase inhibitor SP600125, and extracellular signal-regulated kinase inhibitor PD98059 significantly reduced arecoline-induced Egr-1 synthesis. Epigallocatechin-3-gallate (EGCG) inhibited arecoline-induced Egr-1 synthesis and collagen gel contraction in a dose-responsive manner. Constitutive Egr-1 expression during areca nut chewing may play a role in the pathogenesis of OSF. EGCG could be a good candidate for prevention or treatment of OSF. © 2014 Wiley Periodicals, Inc.

  12. Probing cell structure responses through a shear and stretching mechanical stimulation technique.

    Science.gov (United States)

    Steward, Robert L; Cheng, Chao-Min; Wang, Danny L; LeDuc, Philip R

    2010-04-01

    Cells are complex, dynamic systems that respond to various in vivo stimuli including chemical, mechanical, and scaffolding alterations. The influence of mechanics on cells is especially important in physiological areas that dictate what modes of mechanics exist. Complex, multivariate physiological responses can result from multi-factorial, multi-mode mechanics, including tension, compression, or shear stresses. In this study, we present a novel device based on elastomeric materials that allowed us to stimulate NIH 3T3 fibroblasts through uniaxial strip stretching or shear fluid flow. Cell shape and structural response was observed using conventional approaches such as fluorescent microscopy. Cell orientation and actin cytoskeleton alignment along the direction of applied force were observed to occur after an initial 3 h time period for shear fluid flow and static uniaxial strip stretching experiments although these two directions of alignment were oriented orthogonal relative to each other. This response was then followed by an increasingly pronounced cell and actin cytoskeleton alignment parallel to the direction of force after 6, 12, and 24 h, with 85% of the cells aligned along the direction of force after 24 h. These results indicate that our novel device could be implemented to study the effects of multiple modes of mechanical stimulation on living cells while probing their structural response especially with respect to competing directions of alignment and orientation under these different modes of mechanical stimulation. We believe that this will be important in a diversity of fields including cell mechanotransduction, cell-material interactions, biophysics, and tissue engineering.

  13. Apoptosis-related genes induced in response to ketamine during early life stages of zebrafish.

    Science.gov (United States)

    Félix, Luís M; Serafim, Cindy; Valentim, Ana M; Antunes, Luís M; Matos, Manuela; Coimbra, Ana M

    2017-09-05

    Increasing evidence supports that ketamine, a widely used anaesthetic, potentiates apoptosis during development through the mitochondrial pathway of apoptosis. Defects in the apoptotic machinery can cause or contribute to the developmental abnormalities previously described in ketamine-exposed zebrafish. The involvement of the apoptotic machinery in ketamine-induced teratogenicity was addressed by assessing the apoptotic signals at 8 and 24 hpf following 20min exposure to ketamine at three stages of early zebrafish embryo development (256 cell, 50% epiboly and 1-4 somites stages). Exposure at the 256-cell stage to ketamine induced an up-regulation of casp8 and pcna at 8 hpf while changes in pcna at the mRNA level were observed at 24 hpf. After the 50% epiboly stage exposure, the mRNA levels of casp9 were increased at 8 and 24 hpf while aifm1 was affected at 24 hpf. Both tp53 and pcna expressions were increased at 8 hpf. After exposure during the 1-4 somites stage, no meaningful changes on transcript levels were observed. The distribution of apoptotic cells and the caspase-like enzymatic activities of caspase-3 and -9 were not affected by ketamine exposure. It is proposed that ketamine exposure at the 256-cell stage induced a cooperative mechanism between proliferation and cellular death while following exposure at the 50% epiboly, a p53-dependent and -independent caspase activation may occur. Finally, at the 1-4 somites stage, the defence mechanisms are already fully in place to protect against ketamine-insult. Thus, ketamine teratogenicity seems to be dependent on the functional mechanisms present in each developmental stage. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Breast cancer prevention: lessons to be learned from mechanisms of early pregnancy-mediated breast cancer protection.

    Science.gov (United States)

    Meier-Abt, Fabienne; Bentires-Alj, Mohamed; Rochlitz, Christoph

    2015-03-01

    Pregnancy at early, but not late age, has a strong and life-long protective effect against breast cancer. The expected overall increase in breast cancer incidence demands the development of a pharmaceutical mimicry of early-age pregnancy-mediated protection. Recently, converging results from rodent models and women on molecular and cellular mechanisms underlying the protective effect of early-age pregnancy have opened the door for translational studies on pharmacologic prevention against breast cancer. In particular, alterations in Wnt and TGFβ signaling in mammary stem/progenitor cells reveal new potential targets for preventive interventions, and thus might help to significantly reduce the incidence of breast cancer in the future. ©2015 American Association for Cancer Research.

  15. The influence of social environment in early life on the behavior, stress response, and reproductive system of adult male Norway rats selected for different attitudes to humans.

    Science.gov (United States)

    Gulevich, R G; Shikhevich, S G; Konoshenko, M Yu; Kozhemyakina, R V; Herbeck, Yu E; Prasolova, L A; Oskina, I N; Plyusnina, I Z

    2015-05-15

    The influence of social disturbance in