Shape control of an adaptive wing for transonic drag reduction

NASA Astrophysics Data System (ADS)

Austin, Fred; Van Nostrand, William C.

1995-05-01

Theory and experiments to control the static shape of flexible structures by employing internal translational actuators are summarized and plants to extend the work to adaptive wings are presented. Significant reductions in the shock-induced drag are achievable during transonic- cruise by small adaptive modifications to the wing cross-sectional profile. Actuators are employed as truss elements of active ribs to deform the wing cross section. An adaptive-rib model was constructed, and experiments validated the shape-control theory. Plans for future development under an ARPA/AFWAL contract include payoff assessments of the method on an actual aircraft, the development of inchworm TERFENOL-D actuators, and the development of a method to optimize the wing cross-sectional shapes by direct-drag measurements.

Multigenerational epigenetic adaptation of the hepatic wound-healing response.

PubMed

Zeybel, Müjdat; Hardy, Timothy; Wong, Yi K; Mathers, John C; Fox, Christopher R; Gackowska, Agata; Oakley, Fiona; Burt, Alastair D; Wilson, Caroline L; Anstee, Quentin M; Barter, Matt J; Masson, Steven; Elsharkawy, Ahmed M; Mann, Derek A; Mann, Jelena

2012-09-01

We investigated whether ancestral liver damage leads to heritable reprogramming of hepatic wound healing in male rats. We found that a history of liver damage corresponds with transmission of an epigenetic suppressive adaptation of the fibrogenic component of wound healing to the male F1 and F2 generations. Underlying this adaptation was less generation of liver myofibroblasts, higher hepatic expression of the antifibrogenic factor peroxisome proliferator-activated receptor γ (PPAR-γ) and lower expression of the profibrogenic factor transforming growth factor β1 (TGF-β1) compared to rats without this adaptation. Remodeling of DNA methylation and histone acetylation underpinned these alterations in gene expression. Sperm from rats with liver fibrosis were enriched for the histone variant H2A.Z and trimethylation of histone H3 at Lys27 (H3K27me3) at PPAR-γ chromatin. These modifications to the sperm chromatin were transmittable by adaptive serum transfer from fibrotic rats to naive rats and similar modifications were induced in mesenchymal stem cells exposed to conditioned media from cultured rat or human myofibroblasts. Thus, it is probable that a myofibroblast-secreted soluble factor stimulates heritable epigenetic signatures in sperm so that the resulting offspring better adapt to future fibrogenic hepatic insults. Adding possible relevance to humans, we found that people with mild liver fibrosis have hypomethylation of the PPARG promoter compared to others with severe fibrosis.

Methods for evaluating the Caenorhabditis elegans dauer state: standard dauer-formation assay using synthetic daumones and proteomic analysis of O-GlcNAc modifications.

PubMed

Lee, Jeeyong; Kim, Kwang-Youl; Joo, Hyoe-Jin; Kim, Heekyeong; Jeong, Pan-Young; Paik, Young-Ki

2011-01-01

The dauer state is a non-feeding, alternative L3 state characterized by a number of distinctive metabolic and morphological changes. There are many naturally occurring dauer-inducing pheromones, termed daumones, that have been suggested by some to exhibit differences in dauer-inducing activity. Here, we have established a standard dauer-formation assay that uses synthetic daumones 1, 2, and 3, the three major daumones. To analyze the proteome of Caenorhabditis elegans in the dauer state, we focused on O-GlcNAc modification, a cytosolic modification of proteins that is known to interact either competitively or synergistically with protein phosphorylation. Protein O-GlcNAc modification is an important biological process in cells that can ensure the timely response to extracellular stimuli, such as daumone, and maintain cellular homeostasis. Establishing a standard method for assaying dauer formation using different synthetic daumones, and using differences in O-GlcNAcylated proteins during the dauer state to analyze the dauer proteome will lead to a better understanding of dauer biology of C. elegans in the context of animal longevity and adaptation under harsh environments. Copyright © 2011 Elsevier Inc. All rights reserved.

Expected treatment dose construction and adaptive inverse planning optimization: Implementation for offline head and neck cancer adaptive radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan Di; Liang Jian

Purpose: To construct expected treatment dose for adaptive inverse planning optimization, and evaluate it on head and neck (h and n) cancer adaptive treatment modification. Methods: Adaptive inverse planning engine was developed and integrated in our in-house adaptive treatment control system. The adaptive inverse planning engine includes an expected treatment dose constructed using the daily cone beam (CB) CT images in its objective and constrains. Feasibility of the adaptive inverse planning optimization was evaluated retrospectively using daily CBCT images obtained from the image guided IMRT treatment of 19 h and n cancer patients. Adaptive treatment modification strategies with respect tomore » the time and the number of adaptive inverse planning optimization during the treatment course were evaluated using the cumulative treatment dose in organs of interest constructed using all daily CBCT images. Results: Expected treatment dose was constructed to include both the delivered dose, to date, and the estimated dose for the remaining treatment during the adaptive treatment course. It was used in treatment evaluation, as well as in constructing the objective and constraints for adaptive inverse planning optimization. The optimization engine is feasible to perform planning optimization based on preassigned treatment modification schedule. Compared to the conventional IMRT, the adaptive treatment for h and n cancer illustrated clear dose-volume improvement for all critical normal organs. The dose-volume reductions of right and left parotid glands, spine cord, brain stem and mandible were (17 {+-} 6)%, (14 {+-} 6)%, (11 {+-} 6)%, (12 {+-} 8)%, and (5 {+-} 3)% respectively with the single adaptive modification performed after the second treatment week; (24 {+-} 6)%, (22 {+-} 8)%, (21 {+-} 5)%, (19 {+-} 8)%, and (10 {+-} 6)% with three weekly modifications; and (28 {+-} 5)%, (25 {+-} 9)%, (26 {+-} 5)%, (24 {+-} 8)%, and (15 {+-} 9)% with five weekly modifications. Conclusions: Adaptive treatment modification can be implemented including the expected treatment dose in the adaptive inverse planning optimization. The retrospective evaluation results demonstrate that utilizing the weekly adaptive inverse planning optimization, the dose distribution of h and n cancer treatment can be largely improved.« less

Investigation of light-induced conformation changes in spiropyran-modified succinylated poly(L-lysine).

PubMed

Cooper, T M; Stone, M O; Natarajan, L V; Crane, R L

1995-08-01

To determine the maximum range of coupling between side-chain photochromism and polypeptide conformation change, we modified the carboxylate side chains of succinylated poly(L-lysine) with a spiropyran to form polypeptide I. The extent of modification was determined to be 35.5%. The spacer group length between the polypeptide alpha-carbon and the dye was 12 atoms, providing minimum polypeptide-dye interaction. Conformation changes were monitored by circular dichroism as a function of light adaptation and solvent composition (hexafluoroisopropanol [HFIP] vs trifluoroethanol [TFE]). Under all solvent compositions, the dark-adapted dye was in the merocyanine form. Light adaptation by visible light converted the dye to the spiropyran form. When dissolved in TFE, I adopted a helical conformation insensitive to light adaptation. With increasing percentage HFIP, a solvent-induced helix-to-coil transition was observed around 80% (vol/vol) HFIP. At 100% HFIP, both light- and dark-adapted forms of I were in the coil state. Near the midpoint of the solvent-induced helix-to-coil transition, light adaptation caused conformation changes. Applying helix-to-coil transition theory, we measured a statistically significant difference in coil segment-HFIP binding constant for light- vs dark-adapted solutions (6.38 +/- 0.03 M-1 vs 6.56 +/- 0.03 M-1), but not for the nucleation parameter sigma (1.2 +/- 0.4 10(-3) vs 1.3 +/- 0.3 x 10(-3). The small binding constant difference translated to a light-induced binding energy difference of 17 cal/mol/monomer. Near the midpoint of the helix-to-coil transition, collective interactions between monomer units made possible the translation of a small energy difference (less than RT) into large macromolecular conformation changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Epigenetic Regulation in Plant Responses to the Environment

PubMed Central

Baulcombe, David C.; Dean, Caroline

2014-01-01

In this article, we review environmentally mediated epigenetic regulation in plants using two case histories. One of these, vernalization, mediates adaptation of plants to different environments and it exemplifies processes that are reset in each generation. The other, virus-induced silencing, involves transgenerationally inherited epigenetic modifications. Heritable epigenetic marks may result in heritable phenotypic variation, influencing fitness, and so be subject to natural selection. However, unlike genetic inheritance, the epigenetic modifications show instability and are influenced by the environment. These two case histories are then compared with other phenomena in plant biology that are likely to represent epigenetic regulation in response to the environment. PMID:25183832

A cell biologist's perspective on physiological adaptation to opiate drugs.

PubMed

von Zastrow, Mark

2004-01-01

Opiate drugs such as morphine and heroin are among the most effective analgesics known but are also highly addictive. The clinical utility of opiates is limited by adaptive changes in the nervous system occurring after prolonged or repeated drug administration. These adaptations are believed to play an important role in the development of physiological tolerance and dependence to opiates, and to contribute to additional changes underlying the complex neurobehavioral syndrome of drug addiction. All of these adaptive changes are initiated by the binding of opiate drugs to a subfamily of G protein-coupled receptors that are also activated by endogenously produced opioid neuropeptides. It is increasingly evident that opiate-induced adaptations occur at multiple levels in the nervous system, beginning with regulation of opioid receptors themselves and extending to a complex network of direct and indirect modifications of "downstream" signaling machinery. Efforts in my laboratory are directed at understanding the biochemical and cell biological basis of opiate adaptations. So far, we have focused primarily on adaptations occurring at the level of opioid receptors themselves. These studies have contributed to defining a set of membrane trafficking mechanisms by which the number and functional activity of opioid receptors are controlled. The role of these mechanisms in affecting adaptation of "downstream" neurobiological substrates, and in mediating opiate-induced changes in whole-animal physiology and behavior, are exciting questions that are only beginning to be explored.

Asymptotic Linearity of Optimal Control Modification Adaptive Law with Analytical Stability Margins

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.

2010-01-01

Optimal control modification has been developed to improve robustness to model-reference adaptive control. For systems with linear matched uncertainty, optimal control modification adaptive law can be shown by a singular perturbation argument to possess an outer solution that exhibits a linear asymptotic property. Analytical expressions of phase and time delay margins for the outer solution can be obtained. Using the gradient projection operator, a free design parameter of the adaptive law can be selected to satisfy stability margins.

Adaptation of human adipose tissue to hypocaloric diet.

PubMed

Rossmeislová, L; Mališová, L; Kračmerová, J; Štich, V

2013-05-01

Hypocaloric diet is a key component of the weight-reducing treatment of obesity and obesity-related disorders. Hypocaloric diets and the associated weight reduction promote improvement of metabolic profile of obese individuals. Among the mechanisms that underlie this beneficial metabolic outcome, the diet-induced modifications of morphological and functional characteristics of human adipose tissue (AT) are believed to have an important role. Prospective studies of hypocaloric weight-reducing dietary intervention demonstrate effects on adipocyte metabolism, namely lipolysis and lipogenesis, and associated changes of the adipocyte size. The endocrine function of AT, which involves cytokine and adipokine production by adipocytes, as well as by cells of stromavascular fraction, is also regulated by dietary intervention. Related inflammatory status of AT is modulated also as a consequence of the changes in recruitment of immune cells, mainly macrophages, in AT. Here, we give an overview of metabolic and endocrine modifications in human AT induced by a variety of hypocaloric diets.

Static shape control for adaptive wings

NASA Astrophysics Data System (ADS)

Austin, Fred; Rossi, Michael J.; van Nostrand, William; Knowles, Gareth; Jameson, Antony

1994-09-01

A theoretical method was developed and experimentally validated, to control the static shape of flexible structures by employing internal translational actuators. A finite element model of the structure, without the actuators present, is employed to obtain the multiple-input, multiple-output control-system gain matrices for actuator-load control as well as actuator-displacement control. The method is applied to the quasistatic problem of maintaining an optimum-wing cross section during various transonic-cruise flight conditions to obtain significant reductions in the shock-induced drag. Only small, potentially achievable, adaptive modifications to the profile are required. The adaptive-wing concept employs actuators as truss elements of active ribs to reshape the wing cross section by deforming the structure. Finite element analyses of an adaptive-rib model verify the controlled-structure theory. Experiments on the model were conducted, and arbitrarily selected deformed shapes were accurately achieved.

Empirical Examinations of Modifications and Adaptations to Evidence-Based Psychotherapies: Methodologies, Impact, and Future Directions.

PubMed

Stirman, Shannon Wiltsey; Gamarra, Jennifer; Bartlett, Brooke; Calloway, Amber; Gutner, Cassidy

2017-12-01

This review describes methods used to examine the modifications and adaptations to evidence-based psychological treatments (EBPTs), assesses what is known about the impact of modifications and adaptations to EBPTs, and makes recommendations for future research and clinical care. One hundred eight primary studies and three meta-analyses were identified. All studies examined planned adaptations, and many simultaneously investigated multiple types of adaptations. With the exception of studies on adding or removing specific EBPT elements, few studies compared adapted EBPTs to the original protocols. There was little evidence that adaptations in the studies were detrimental, but there was also limited consistent evidence that adapted protocols outperformed the original protocols, with the exception of adding components to EBPTs. Implications for EBPT delivery and future research are discussed.

Sequential Actions of SIRT1-RELB-SIRT3 Coordinate Nuclear-Mitochondrial Communication during Immunometabolic Adaptation to Acute Inflammation and Sepsis*

PubMed Central

Liu, Tie Fu; Vachharajani, Vidula; Millet, Patrick; Bharadwaj, Manish S.; Molina, Anthony J.; McCall, Charles E.

2015-01-01

We reported that NAD+-dependent SIRT1, RELB, and SIRT6 nuclear proteins in monocytes regulate a switch from the glycolysis-dependent acute inflammatory response to fatty acid oxidation-dependent sepsis adaptation. We also found that disrupting SIRT1 activity during adaptation restores immunometabolic homeostasis and rescues septic mice from death. Here, we show that nuclear SIRT1 guides RELB to differentially induce SIRT3 expression and also increases mitochondrial biogenesis, which alters bioenergetics during sepsis adaptation. We constructed this concept using TLR4-stimulated THP1 human promonocytes, a model that mimics the initiation and adaptation stages of sepsis. Following increased expression, mitochondrial SIRT3 deacetylase activates the rate-limiting tricarboxylic acid cycle (TCA) isocitrate dehydrogenase 2 and superoxide dismutase 2, concomitant with increases in citrate synthase activity. Mitochondrial oxygen consumption rate increases early and decreases during adaptation, parallel with modifications to membrane depolarization, ATP generation, and production of mitochondrial superoxide and whole cell hydrogen peroxide. Evidence of SIRT1-RELB induction of mitochondrial biogenesis included increases in mitochondrial mass, mitochondrial-to-nuclear DNA ratios, and both nuclear and mitochondrial encoded proteins. We confirmed the SIRT-RELB-SIRT3 adaptation link to mitochondrial bioenergetics in both TLR4-stimulated normal and sepsis-adapted human blood monocytes and mouse splenocytes. We also found that SIRT1 inhibition ex vivo reversed the sepsis-induced changes in bioenergetics. PMID:25404738

Reverse Induced Fit-Driven MAS-Downstream Transduction: Looking for Metabotropic Agonists.

PubMed

Pernomian, Larissa; Gomes, Mayara S; de Paula da Silva, Carlos H Tomich; Rosa, Joaquin M C

2017-01-01

Protective effects of MAS activation have spurred clinical interests in developing MAS agonists. However, current bases that drive this process preclude that physiological concentrations of peptide MAS agonists induce an atypical signaling that does not reach the metabotropic efficacy of constitutive activation. Canonical activation of MAS-coupled G proteins is only achieved by supraphysiological concentrations of peptide MAS agonists or physiological concentrations of chemically modified analogues. These pleiotropic differences are because of two overlapped binding domains: one non-metabotropic site that recognizes peptide agonists and one metabotropic domain that recognizes modified analogues. It is feasible that supraphysiological concentrations of peptide MAS agonists undergo to chemical modifications required for binding to metabotropic domain. Receptor oligomerization enhances pharmacological parameters coupled to metabotropic signaling. The formation of receptor-signalosome complex makes the transduction of agonists more adaptive. Considering the recent identification of MAS-signalosome, we aimed to postulate the reverse induced fit hypothesis in which MAS-signalosome would trigger chemical modifications required for agonists bind to MAS metabotropic domain. Here we cover rational perspectives for developing novel metabotropic MAS agonists in the view of the reverse induced-fit hypothesis. Predicting a 3D model of MAS metabotropic domain may guide the screening of chemical modifications required for metabotropic efficacy. Pharmacophore-based virtual screening would select potential metabotropic MAS agonists from virtual libraries from human proteome. Rational perspectives that consider reverse induced fit hypothesis during MAS activation for developing metabotropic MAS agonists represents the best approach in providing MAS ligands with constitutive efficacy at physiological concentrations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Whole-body cryotherapy in athletes.

PubMed

Banfi, Giuseppe; Lombardi, Giovanni; Colombini, Alessandra; Melegati, Gianluca

2010-06-01

Cold therapy is commonly used as a procedure to relieve pain symptoms, particularly in inflammatory diseases, injuries and overuse symptoms. A peculiar form of cold therapy (or stimulation) was proposed 30 years ago for the treatment of rheumatic diseases. The therapy, called whole-body cryotherapy (WBC), consists of exposure to very cold air that is maintained at -110 degrees C to -140 degrees C in special temperature-controlled cryochambers, generally for 2 minutes. WBC is used to relieve pain and inflammatory symptoms caused by numerous disorders, particularly those associated with rheumatic conditions, and is recommended for the treatment of arthritis, fibromyalgia and ankylosing spondylitis. In sports medicine, WBC has gained wider acceptance as a method to improve recovery from muscle injury. Unfortunately, there are few papers concerning the application of the treatment on athletes. The study of possible enhancement of recovery from injuries and possible modification of physiological parameters, taking into consideration the limits imposed by antidoping rules, is crucial for athletes and sports physicians for judging the real benefits and/or limits of WBC. According to the available literature, WBC is not harmful or detrimental in healthy subjects. The treatment does not enhance bone marrow production and could reduce the sport-induced haemolysis. WBC induces oxidative stress, but at a low level. Repeated treatments are apparently not able to induce cumulative effects; on the contrary, adaptive changes on antioxidant status are elicited--the adaptation is evident where WBC precedes or accompanies intense training. WBC is not characterized by modifications of immunological markers and leukocytes, and it seems to not be harmful to the immunological system. The WBC effect is probably linked to the modifications of immunological molecules having paracrine effects, and not to systemic immunological functions. In fact, there is an increase in anti-inflammatory cytokine interleukin (IL)-10, and a decrease in proinflammatory cytokine IL-2 and chemokine IL-8. Moreover, the decrease in intercellular adhesion molecule-1 supported the anti-inflammatory response. Lysosomal membranes are stabilized by WBC, reducing potential negative effects on proteins of lysosomal enzymes. The cold stimulation shows positive effects on the muscular enzymes creatine kinase and lactate dehydrogenase, and it should be considered a procedure that facilitates athletes' recovery. Cardiac markers troponin I and high-sensitivity C-reactive protein, parameters linked to damage and necrosis of cardiac muscular tissue, but also to tissue repair, were unchanged, demonstrating that there was no damage, even minimal, in the heart during the treatment. N-Terminal pro B-type natriuretic peptide (NT-proBNP), a parameter linked to heart failure and ventricular power decrease, showed an increase, due to cold stress. However, the NT-proBNP concentrations observed after WBC were lower than those measured after a heavy training session, suggesting that the treatment limits the increase of the parameter that is typical of physical exercise. WBC did not stimulate the pituitary-adrenal cortex axis: the hormonal modifications are linked mainly to the body's adaptation to the stress, shown by an increase of noradrenaline (norepinephrine). We conclude that WBC is not harmful and does not induce general or specific negative effects in athletes. The treatment does not induce modifications of biochemical and haematological parameters, which could be suspected in athletes who may be cheating. The published data are generally not controversial, but further studies are necessary to confirm the present observations.

Ghosts of thermal past: reef fish exposed to historic high temperatures have heightened stress response to further stressors

NASA Astrophysics Data System (ADS)

Mills, S. C.; Beldade, R.; Chabanet, P.; Bigot, L.; O'Donnell, J. L.; Bernardi, G.

2015-12-01

Individual exposure to stressors can induce changes in physiological stress responses through modulation of the hypothalamic-pituitary-interrenal (HPI) axis. Despite theoretical predictions, little is known about how individuals will respond to unpredictable short-lived stressors, such as thermal events. We examine the primary neuroendocrine response of coral reef fish populations from the Îles Eparses rarely exposed to anthropogenic stress, but that experienced different thermal histories. Skunk anemonefish, Amphiprion akallopisos, showed different cortisol responses to a generic stressor between islands, but not along a latitudinal gradient. Those populations previously exposed to higher maximum temperatures showed greater responses of their HPI axis. Archive data reveal thermal stressor events occur every 1.92-6 yr, suggesting that modifications to the HPI axis could be adaptive. Our results highlight the potential for adaptation of the HPI axis in coral reef fish in response to a climate-induced thermal stressor.

Visuo-Vestibular Interactions

NASA Technical Reports Server (NTRS)

1997-01-01

Session TA3 includes short reports covering: (1) Vestibulo-Oculomotor Interaction in Long-Term Microgravity; (2) Effects of Weightlessness on the Spatial Orientation of Visually Induced Eye Movements; (3) Adaptive Modification of the Three-Dimensional Vestibulo-Ocular Reflex during Prolonged Microgravity; (4) The Dynamic Change of Brain Potential Related to Selective Attention to Visual Signals from Left and Right Visual Fields; (5) Locomotor Errors Caused by Vestibular Suppression; and (6) A Novel, Image-Based Technique for Three-Dimensional Eye Measurement.

Multigenerational Epigenetic Adaptation of the Hepatic Wound-Healing Response

PubMed Central

Zeybel, Müjdat; Hardy, Timothy; Wong, Yi K.; Mathers, John C.; Fox, Christopher R.; Gackowska, Agata; Oakley, Fiona; Burt, Alastair D.; Wilson, Caroline L.; Anstee, Quentin M.; Barter, Matt J.; Masson, Steven; Elsharkawy, Ahmed M.; Mann, Derek A.; Mann, Jelena

2012-01-01

We asked if ancestral liver damage leads to heritable reprogramming of hepatic wound-healing. We discovered that male rats with a history of liver damage transmit epigenetic suppressive adaptation of the fibrogenic component of wound-healing through male F1 and F2 generations. Underlying this adaptation was reduced generation of liver myofibroblasts, increased hepatic expression of antifibrogenic PPAR-γ and decreased expression of profibrogenic TGF-β1. Remodelling of DNA methylation and histone acetylation underpinned these alterations in gene expression. Sperm from rats with liver fibrosis were enriched for H2A.Z and H3K27me3 at PPAR-γ chromatin. These sperm chromatin modifications were transmittable by adaptive serum transfer from fibrotic rats and were induced in stem cells exposed to myofibroblast-conditioned media. A myofibroblast secreted soluble factor therefore stimulates heritable epigenetic signatures to sperm so as to adapt fibrogenesis in offspring. Humans with mild liver fibrosis display PPAR-γ promoter hypomethylation compared with severe fibrotics, thus lending support for epigenetic regulation of fibrosis. PMID:22941276

Adaptation of Lorke's method to determine and compare ED50 values: the cases of two anticonvulsants drugs.

PubMed

Garrido-Acosta, Osvaldo; Meza-Toledo, Sergio Enrique; Anguiano-Robledo, Liliana; Valencia-Hernández, Ignacio; Chamorro-Cevallos, Germán

2014-01-01

We determined the median effective dose (ED50) values for the anticonvulsants phenobarbital and sodium valproate using a modification of Lorke's method. This modification allowed appropriate statistical analysis and the use of a smaller number of mice per compound tested. The anticonvulsant activities of phenobarbital and sodium valproate were evaluated in male CD1 mice by maximal electroshock (MES) and intraperitoneal administration of pentylenetetrazole (PTZ). The anticonvulsant ED50 values were obtained through modifications of Lorke's method that involved changes in the selection of the three first doses in the initial test and the fourth dose in the second test. Furthermore, a test was added to evaluate the ED50 calculated by the modified Lorke's method, allowing statistical analysis of the data and determination of the confidence limits for ED50. The ED50 for phenobarbital against MES- and PTZ-induced seizures was 16.3mg/kg and 12.7mg/kg, respectively. The sodium valproate values were 261.2mg/kg and 159.7mg/kg, respectively. These results are similar to those found using the traditional methods of finding ED50, suggesting that the modifications made to Lorke's method generate equal results using fewer mice while increasing confidence in the statistical analysis. This adaptation of Lorke's method can be used to determine median letal dose (LD50) or ED50 for compounds with other pharmacological activities. Copyright © 2014 Elsevier Inc. All rights reserved.

Alcohol-Induced Histone Acetylation Reveals a Gene Network Involved in Alcohol Tolerance

PubMed Central

Ghezzi, Alfredo; Krishnan, Harish R.; Lew, Linda; Prado, Francisco J.; Ong, Darryl S.; Atkinson, Nigel S.

2013-01-01

Sustained or repeated exposure to sedating drugs, such as alcohol, triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Alcohol-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most of which may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct alcohols. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol. PMID:24348266

Bi-Objective Optimal Control Modification Adaptive Control for Systems with Input Uncertainty

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.

2012-01-01

This paper presents a new model-reference adaptive control method based on a bi-objective optimal control formulation for systems with input uncertainty. A parallel predictor model is constructed to relate the predictor error to the estimation error of the control effectiveness matrix. In this work, we develop an optimal control modification adaptive control approach that seeks to minimize a bi-objective linear quadratic cost function of both the tracking error norm and predictor error norm simultaneously. The resulting adaptive laws for the parametric uncertainty and control effectiveness uncertainty are dependent on both the tracking error and predictor error, while the adaptive laws for the feedback gain and command feedforward gain are only dependent on the tracking error. The optimal control modification term provides robustness to the adaptive laws naturally from the optimal control framework. Simulations demonstrate the effectiveness of the proposed adaptive control approach.

tRNA-mediated codon-biased translation in mycobacterial hypoxic persistence

NASA Astrophysics Data System (ADS)

Chionh, Yok Hian; McBee, Megan; Babu, I. Ramesh; Hia, Fabian; Lin, Wenwei; Zhao, Wei; Cao, Jianshu; Dziergowska, Agnieszka; Malkiewicz, Andrzej; Begley, Thomas J.; Alonso, Sylvie; Dedon, Peter C.

2016-11-01

Microbial pathogens adapt to the stress of infection by regulating transcription, translation and protein modification. We report that changes in gene expression in hypoxia-induced non-replicating persistence in mycobacteria--which models tuberculous granulomas--are partly determined by a mechanism of tRNA reprogramming and codon-biased translation. Mycobacterium bovis BCG responded to each stage of hypoxia and aerobic resuscitation by uniquely reprogramming 40 modified ribonucleosides in tRNA, which correlate with selective translation of mRNAs from families of codon-biased persistence genes. For example, early hypoxia increases wobble cmo5U in tRNAThr(UGU), which parallels translation of transcripts enriched in its cognate codon, ACG, including the DosR master regulator of hypoxic bacteriostasis. Codon re-engineering of dosR exaggerates hypoxia-induced changes in codon-biased DosR translation, with altered dosR expression revealing unanticipated effects on bacterial survival during hypoxia. These results reveal a coordinated system of tRNA modifications and translation of codon-biased transcripts that enhance expression of stress response proteins in mycobacteria.

tRNA-mediated codon-biased translation in mycobacterial hypoxic persistence

PubMed Central

Chionh, Yok Hian; McBee, Megan; Babu, I. Ramesh; Hia, Fabian; Lin, Wenwei; Zhao, Wei; Cao, Jianshu; Dziergowska, Agnieszka; Malkiewicz, Andrzej; Begley, Thomas J.; Alonso, Sylvie; Dedon, Peter C.

2016-01-01

Microbial pathogens adapt to the stress of infection by regulating transcription, translation and protein modification. We report that changes in gene expression in hypoxia-induced non-replicating persistence in mycobacteria—which models tuberculous granulomas—are partly determined by a mechanism of tRNA reprogramming and codon-biased translation. Mycobacterium bovis BCG responded to each stage of hypoxia and aerobic resuscitation by uniquely reprogramming 40 modified ribonucleosides in tRNA, which correlate with selective translation of mRNAs from families of codon-biased persistence genes. For example, early hypoxia increases wobble cmo5U in tRNAThr(UGU), which parallels translation of transcripts enriched in its cognate codon, ACG, including the DosR master regulator of hypoxic bacteriostasis. Codon re-engineering of dosR exaggerates hypoxia-induced changes in codon-biased DosR translation, with altered dosR expression revealing unanticipated effects on bacterial survival during hypoxia. These results reveal a coordinated system of tRNA modifications and translation of codon-biased transcripts that enhance expression of stress response proteins in mycobacteria. PMID:27834374

On Time Delay Margin Estimation for Adaptive Control and Optimal Control Modification

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.

2011-01-01

This paper presents methods for estimating time delay margin for adaptive control of input delay systems with almost linear structured uncertainty. The bounded linear stability analysis method seeks to represent an adaptive law by a locally bounded linear approximation within a small time window. The time delay margin of this input delay system represents a local stability measure and is computed analytically by three methods: Pade approximation, Lyapunov-Krasovskii method, and the matrix measure method. These methods are applied to the standard model-reference adaptive control, s-modification adaptive law, and optimal control modification adaptive law. The windowing analysis results in non-unique estimates of the time delay margin since it is dependent on the length of a time window and parameters which vary from one time window to the next. The optimal control modification adaptive law overcomes this limitation in that, as the adaptive gain tends to infinity and if the matched uncertainty is linear, then the closed-loop input delay system tends to a LTI system. A lower bound of the time delay margin of this system can then be estimated uniquely without the need for the windowing analysis. Simulation results demonstrates the feasibility of the bounded linear stability method for time delay margin estimation.

V1 orientation plasticity is explained by broadly tuned feedforward inputs and intracortical sharpening.

PubMed

Teich, Andrew F; Qian, Ning

2010-03-01

Orientation adaptation and perceptual learning change orientation tuning curves of V1 cells. Adaptation shifts tuning curve peaks away from the adapted orientation, reduces tuning curve slopes near the adapted orientation, and increases the responses on the far flank of tuning curves. Learning an orientation discrimination task increases tuning curve slopes near the trained orientation. These changes have been explained previously in a recurrent model (RM) of orientation selectivity. However, the RM generates only complex cells when they are well tuned, so that there is currently no model of orientation plasticity for simple cells. In addition, some feedforward models, such as the modified feedforward model (MFM), also contain recurrent cortical excitation, and it is unknown whether they can explain plasticity. Here, we compare plasticity in the MFM, which simulates simple cells, and a recent modification of the RM (MRM), which displays a continuum of simple-to-complex characteristics. Both pre- and postsynaptic-based modifications of the recurrent and feedforward connections in the models are investigated. The MRM can account for all the learning- and adaptation-induced plasticity, for both simple and complex cells, while the MFM cannot. The key features from the MRM required for explaining plasticity are broadly tuned feedforward inputs and sharpening by a Mexican hat intracortical interaction profile. The mere presence of recurrent cortical interactions in feedforward models like the MFM is insufficient; such models have more rigid tuning curves. We predict that the plastic properties must be absent for cells whose orientation tuning arises from a feedforward mechanism.

When we should worry more: using cognitive bias modification to drive adaptive health behaviour.

PubMed

Notebaert, Lies; Chrystal, Jessica; Clarke, Patrick J F; Holmes, Emily A; MacLeod, Colin

2014-01-01

A lack of behavioural engagement in health promotion or disease prevention is a problem across many health domains. In these cases where people face a genuine danger, a reduced focus on threat and low levels of anxiety or worry are maladaptive in terms of promoting protection or prevention behaviour. Therefore, it is possible that increasing the processing of threat will increase worry and thereby enhance engagement in adaptive behaviour. Laboratory studies have shown that cognitive bias modification (CBM) can increase or decrease anxiety and worry when increased versus decreased processing of threat is encouraged. In the current study, CBM for interpretation (CBM-I) is used to target engagement in sun protection behaviour. The goal was to investigate whether inducing a negative rather than a positive interpretation bias for physical threat information can enhance worry elicited when viewing a health campaign video (warning against melanoma skin cancer), and consequently lead to more adaptive behaviour (sun protection). Participants were successfully trained to either adopt a positive or negative interpretation bias using physical threat scenarios. However, contrary to expectations results showed that participants in the positive training condition reported higher levels of worry elicited by the melanoma video than participants in the negative training condition. Video elicited worry was, however, positively correlated with a measure of engagement in sun protection behaviour, suggesting that higher levels of worry do promote adaptive behaviour. These findings imply that more research is needed to determine under which conditions increased versus decreased processing of threat can drive adaptive worry. Various potential explanations for the current findings and suggestions for future research are discussed.

Cold adaptation shapes the robustness of metabolic networks in Drosophila melanogaster

PubMed Central

Williams, CM; Watanabe, M; Guarracino, MR; Ferraro, MB; Edison, AS; Morgan, TJ; Boroujerdi, AFB; Hahn, DA

2015-01-01

When ectotherms are exposed to low temperatures, they enter a cold-induced coma (chill coma) that prevents resource acquisition, mating, oviposition, and escape from predation. There is substantial variation in time taken to recover from chill coma both within and among species, and this variation is correlated with habitat temperatures such that insects from cold environments recover more quickly. This suggests an adaptive response, but the mechanisms underlying variation in recovery times are unknown, making it difficult to decisively test adaptive hypotheses. We use replicated lines of Drosophila melanogaster selected in the laboratory for fast (hardy) or slow (susceptible) chill-coma recovery times to investigate modifications to metabolic profiles associated with cold adaptation. We measured metabolite concentrations of flies before, during, and after cold exposure using NMR spectroscopy to test the hypotheses that hardy flies maintain metabolic homeostasis better during cold exposure and recovery, and that their metabolic networks are more robust to cold-induced perturbations. The metabolites of cold-hardy flies were less cold responsive and their metabolic networks during cold exposure were more robust, supporting our hypotheses. Metabolites involved in membrane lipid synthesis, tryptophan metabolism, oxidative stress, energy balance, and proline metabolism were altered by selection on cold tolerance. We discuss the potential significance of these alterations. PMID:25308124

The Role of Adaptation in Body Load-Regulating Mechanisms During Locomotion

NASA Technical Reports Server (NTRS)

Ruttley, Tara; Holt, Christopher; Mulavara, Ajitkumar; Bloomberg, Jacob

2010-01-01

Body loading is a fundamental parameter that modulates motor output during locomotion, and is especially important for controlling the generation of stepping patterns, dynamic balance, and termination of locomotion. Load receptors that regulate and control posture and stance in locomotion include the Golgi tendon organs and muscle spindles at the hip, knee, and ankle joints, and the Ruffini endings and the Pacinian corpuscles in the soles of the feet. Increased body weight support (BWS) during locomotion results in an immediate reorganization of locomotor control, such as a reduction in stance and double support duration and decreased hip, ankle, and knee angles during the gait cycle. Previous studies on the effect during exposure to increased BWS while walking showed a reduction in lower limb joint angles and gait cycle timing that represents a reorganization of locomotor control. Until now, no studies have investigated how locomotor control responds after a period of exposure to adaptive modification in the body load sensing system. The goal of this research was to determine the adaptive properties of body load-regulating mechanisms in locomotor control during locomotion. We hypothesized that body load-regulating mechanisms contribute to locomotor control, and adaptive changes in these load-regulating mechanisms require reorganization to maintain forward locomotion. Head-torso coordination, lower limb movement patterns, and gait cycle timing were evaluated before and after a 30-minute adaptation session during which subjects walked on a treadmill at 5.4 km/hr with 40% body weight support (BWS). Before and after the adaptation period, head-torso and lower limb 3D kinematic data were obtained while performing a goal directed task during locomotion with 0% BWS using a video-based motion analysis system, and gait cycle timing parameters were collected by foot switches positioned under the heel and toe of the subjects shoes. Subjects showed adaptive modification in the body load-regulating mechanisms that included increased head movement amplitude, increased knee and ankle flexion, and increased stance, stride, and double support time, with no change in the performance of the task with respect to that measured before exposure to BWS. These changes in locomotor control are opposite to that reported during 40% BWS exposure and indicative of an after-effect after removal of the adaptive stimulus. Therefore, it is evident that just 30 minutes of 40% BWS during locomotion was sufficient to induce adaptive modifications in the body load sensing systems that contribute to reorganization of sensory contributions to stable locomotor control.

Visually induced self-motion sensation adapts rapidly to left-right reversal of vision

NASA Technical Reports Server (NTRS)

Oman, C. M.; Bock, O. L.

1981-01-01

Three experiments were conducted using 15 adult volunteers with no overt oculomotor or vestibular disorders. In all experiments, left-right vision reversal was achieved using prism goggles, which permitted a binocular field of vision subtending approximately 45 deg horizontally and 28 deg vertically. In all experiments, circularvection (CV) was tested before and immediately after a period of exposure to reversed vision. After one to three hours of active movement while wearing vision-reversing goggles, 10 of 15 (stationary) human subjects viewing a moving stripe display experienced a self-rotation illusion in the same direction as seen stripe motion, rather than in the opposite (normal) direction, demonstrating that the central neural pathways that process visual self-rotation cues can undergo rapid adaptive modification.

Body side-specific control of motor activity during turning in a walking animal

PubMed Central

Gruhn, Matthias; Rosenbaum, Philipp; Bockemühl, Till; Büschges, Ansgar

2016-01-01

Animals and humans need to move deftly and flexibly to adapt to environmental demands. Despite a large body of work on the neural control of walking in invertebrates and vertebrates alike, the mechanisms underlying the motor flexibility that is needed to adjust the motor behavior remain largely unknown. Here, we investigated optomotor-induced turning and the neuronal mechanisms underlying the differences between the leg movements of the two body sides in the stick insect Carausius morosus. We present data to show that the generation of turning kinematics in an insect are the combined result of descending unilateral commands that change the leg motor output via task-specific modifications in the processing of local sensory feedback as well as modification of the activity of local central pattern generating networks in a body-side-specific way. To our knowledge, this is the first study to demonstrate the specificity of such modifications in a defined motor task. DOI: http://dx.doi.org/10.7554/eLife.13799.001 PMID:27130731

Maximum type 1 error rate inflation in multiarmed clinical trials with adaptive interim sample size modifications.

PubMed

Graf, Alexandra C; Bauer, Peter; Glimm, Ekkehard; Koenig, Franz

2014-07-01

Sample size modifications in the interim analyses of an adaptive design can inflate the type 1 error rate, if test statistics and critical boundaries are used in the final analysis as if no modification had been made. While this is already true for designs with an overall change of the sample size in a balanced treatment-control comparison, the inflation can be much larger if in addition a modification of allocation ratios is allowed as well. In this paper, we investigate adaptive designs with several treatment arms compared to a single common control group. Regarding modifications, we consider treatment arm selection as well as modifications of overall sample size and allocation ratios. The inflation is quantified for two approaches: a naive procedure that ignores not only all modifications, but also the multiplicity issue arising from the many-to-one comparison, and a Dunnett procedure that ignores modifications, but adjusts for the initially started multiple treatments. The maximum inflation of the type 1 error rate for such types of design can be calculated by searching for the "worst case" scenarios, that are sample size adaptation rules in the interim analysis that lead to the largest conditional type 1 error rate in any point of the sample space. To show the most extreme inflation, we initially assume unconstrained second stage sample size modifications leading to a large inflation of the type 1 error rate. Furthermore, we investigate the inflation when putting constraints on the second stage sample sizes. It turns out that, for example fixing the sample size of the control group, leads to designs controlling the type 1 error rate. © 2014 The Author. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A study of selected environmental quality remote sensors for free flyer missions launched from the space shuttle

NASA Technical Reports Server (NTRS)

Goldstein, H. W.; Grenda, R. N.

1977-01-01

The sensors were examined for adaptability to shuttle by reviewing pertinent information regarding sensor characteristics as they related to the shuttle and Multimission Modular Spacecraft environments. This included physical and electrical characteristics, data output and command requirements, attitude and orientation requirements, thermal and safety requirements, and adaptability and modification for space. The sensor requirements and characteristics were compared with the corresponding shuttle and Multimission Modular Spacecraft characteristics and capabilities. On this basis the adaptability and necessary modifications for each sensor were determined. A number of the sensors were examined in more detail and estimated cost for the modifications was provided.

Transgenerational effects of insecticides-implications for rapid pest evolution in agroecosystems.

PubMed

Brevik, Kristian; Lindström, Leena; McKay, Stephanie D; Chen, Yolanda H

2018-04-01

Although pesticides are a major selective force in driving the evolution of insect pests, the evolutionary processes that give rise to insecticide resistance remain poorly understood. Insecticide resistance has been widely observed to increase with frequent and intense insecticide exposure, but can be lost following the relaxation of insecticide use. One possible but rarely explored explanation is that insecticide resistance may be associated with epigenetic modifications, which influence the patterning of gene expression without changing underlying DNA sequence. Epigenetic modifications such as DNA methylation, histone modifications, and small RNAs have been observed to be heritable in arthropods, but their role in the context of rapid evolution of insecticide resistance remain poorly understood. Here, we discuss evidence supporting how: firstly, insecticide-induced effects can be transgenerationally inherited; secondly, epigenetic modifications are heritable; and thirdly, epigenetic modifications are responsive to pesticide and xenobiotic stress. Therefore, pesticides may drive the evolution of resistance via epigenetic processes. Moreover, insect pests primed by pesticides may be more tolerant of other stress, further enhancing their success in adapting to agroecosystems. Resolving the role of epigenetic modifications in the rapid evolution of insect pests has the potential to lead to new approaches for integrated pest management as well as improve our understanding of how anthropogenic stress may drive the evolution of insect pests. Copyright © 2018 Elsevier Inc. All rights reserved.

Redox regulation of cGMP-dependent protein kinase Iα in the cardiovascular system

PubMed Central

Prysyazhna, Oleksandra; Eaton, Philip

2015-01-01

Elevated levels of oxidants in biological systems have been historically referred to as “oxidative stress,” a choice of words that perhaps conveys an imbalanced view of reactive oxygen species in cells and tissues. The term stress suggests a harmful role, whereas a contemporary view is that oxidants are also crucial for the maintenance of homeostasis or adaptive signaling that can actually limit injury. This regulatory role for oxidants is achieved in part by them inducing oxidative post-translational modifications of proteins which may alter their function or interactions. Such mechanisms allow changes in cell oxidant levels to be coupled to regulated alterations in enzymatic function (i.e., signal transduction), which enables “redox signaling.” In this review we focus on the role of cGMP-dependent protein kinase (PKG) Ia disulfide dimerisation, an oxidative modification that is induced by oxidants that directly activates the enzyme, discussing how this impacts on the cardiovascular system. Additionally, how this oxidative activation of PKG may coordinate with or differ from classical activation of this kinase by cGMP is also considered. PMID:26236235

Advances in adaptive control theory: Gradient- and derivative-free approaches

NASA Astrophysics Data System (ADS)

Yucelen, Tansel

In this dissertation, we present new approaches to improve standard designs in adaptive control theory, and novel adaptive control architectures. We first present a novel Kalman filter based approach for approximately enforcing a linear constraint in standard adaptive control design. One application is that this leads to alternative forms for well known modification terms such as e-modification. In addition, it leads to smaller tracking errors without incurring significant oscillations in the system response and without requiring high modification gain. We derive alternative forms of e- and adaptive loop recovery (ALR-) modifications. Next, we show how to use Kalman filter optimization to derive a novel adaptation law. This results in an optimization-based time-varying adaptation gain that reduces the need for adaptation gain tuning. A second major contribution of this dissertation is the development of a novel derivative-free, delayed weight update law for adaptive control. The assumption of constant unknown ideal weights is relaxed to the existence of time-varying weights, such that fast and possibly discontinuous variation in weights are allowed. This approach is particulary advantageous for applications to systems that can undergo a sudden change in dynamics, such as might be due to reconfiguration, deployment of a payload, docking, or structural damage, and for rejection of external disturbance processes. As a third and final contribution, we develop a novel approach for extending all the methods developed in this dissertation to the case of output feedback. The approach is developed only for the case of derivative-free adaptive control, and the extension of the other approaches developed previously for the state feedback case to output feedback is left as a future research topic. The proposed approaches of this dissertation are illustrated in both simulation and flight test.

Adaptation of community health worker-delivered behavioral activation for torture survivors in Kurdistan, Iraq.

PubMed

Magidson, J F; Lejuez, C W; Kamal, T; Blevins, E J; Murray, L K; Bass, J K; Bolton, P; Pagoto, S

2015-12-01

Growing evidence supports the use of Western therapies for the treatment of depression, trauma, and stress delivered by community health workers (CHWs) in conflict-affected, resource-limited countries. A recent randomized controlled trial (Bolton et al . 2014 a ) supported the efficacy of two CHW-delivered interventions, cognitive processing therapy (CPT) and brief behavioral activation treatment for depression (BATD), for reducing depressive symptoms and functional impairment among torture survivors in the Kurdish region of Iraq. This study describes the adaptation of the CHW-delivered BATD approach delivered in this trial (Bolton et al .2014 a ), informed by the Assessment-Decision-Administration-Production-Topical experts-Integration-Training-Testing (ADAPT-ITT) framework for intervention adaptation (Wingood & DiClemente, 2008). Cultural modifications, adaptations for low-literacy, and tailored training and supervision for non-specialist CHWs are presented, along with two clinical case examples to illustrate delivery of the adapted intervention in this setting. Eleven CHWs, a study psychiatrist, and the CHW clinical supervisor were trained in BATD. The adaptation process followed the ADAPT-ITT framework and was iterative with significant input from the on-site supervisor and CHWs. Modifications were made to fit Kurdish culture, including culturally relevant analogies, use of stickers for behavior monitoring, cultural modifications to behavioral contracts, and including telephone-delivered sessions to enhance feasibility. BATD was delivered by CHWs in a resource-poor, conflict-affected area in Kurdistan, Iraq, with some important modifications, including low-literacy adaptations, increased cultural relevancy of clinical materials, and tailored training and supervision for CHWs. Barriers to implementation, lessons learned, and recommendations for future efforts to adapt behavioral therapies for resource-limited, conflict-affected areas are discussed.

A Hypothetical Perspective on the Relative Contributions of Strategic and Adaptive Control Mechanisms in Plastic Recalibration of Locomotor Heading Direction

NASA Technical Reports Server (NTRS)

Richards, J. T.; Mulavara, A. P.; Ruttley, T.; Peters, B. T.; Warren, L. E.; Bloomberg, J. J.

2006-01-01

We have previously shown that viewing simulated rotary self-motion during treadmill locomotion causes adaptive modification of the control of position and trajectory during over-ground locomotion, which functionally reflects adaptive changes in the sensorimotor integration of visual, vestibular, and proprioceptive cues (Mulavara et al., 2005). The objective of this study was to investigate how strategic changes in torso control during exposure to simulated rotary self-motion during treadmill walking influences adaptive modification of locomotor heading direction during over-ground stepping.

Dioxin induces Ahr-dependent robust DNA demethylation of the Cyp1a1 promoter via Tdg in the mouse liver.

PubMed

Amenya, Hesbon Z; Tohyama, Chiharu; Ohsako, Seiichiroh

2016-10-07

The aryl hydrocarbon receptor (Ahr) is a highly conserved nuclear receptor that plays an important role in the manifestation of toxicity induced by polycyclic aromatic hydrocarbons. As a xenobiotic sensor, Ahr is involved in chemical biotransformation through activation of drug metabolizing enzymes. The activated Ahr cooperates with coactivator complexes to induce epigenetic modifications at target genes. Thus, it is conceivable that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent Ahr ligand, may elicit robust epigenetic changes in vivo at the Ahr target gene cytochrome P450 1a1 (Cyp1a1). A single dose of TCDD administered to adult mice induced Ahr-dependent CpG hypomethylation, changes in histone modifications, and thymine DNA glycosylase (Tdg) recruitment at the Cyp1a1 promoter in the liver within 24 hrs. These epigenetic changes persisted until 40 days post-TCDD treatment and there was Cyp1a1 mRNA hyperinduction upon repeat administration of TCDD at this time-point. Our demethylation assay using siRNA knockdown and an in vitro methylated plasmid showed that Ahr, Tdg, and the ten-eleven translocation methyldioxygenases Tet2 and Tet3 are required for the TCDD-induced DNA demethylation. These results provide novel evidence of Ahr-driven active DNA demethylation and epigenetic memory. The epigenetic alterations influence response to subsequent chemical exposure and imply an adaptive mechanism to xenobiotic stress.

Dioxin induces Ahr-dependent robust DNA demethylation of the Cyp1a1 promoter via Tdg in the mouse liver

NASA Astrophysics Data System (ADS)

Amenya, Hesbon Z.; Tohyama, Chiharu; Ohsako, Seiichiroh

2016-10-01

The aryl hydrocarbon receptor (Ahr) is a highly conserved nuclear receptor that plays an important role in the manifestation of toxicity induced by polycyclic aromatic hydrocarbons. As a xenobiotic sensor, Ahr is involved in chemical biotransformation through activation of drug metabolizing enzymes. The activated Ahr cooperates with coactivator complexes to induce epigenetic modifications at target genes. Thus, it is conceivable that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent Ahr ligand, may elicit robust epigenetic changes in vivo at the Ahr target gene cytochrome P450 1a1 (Cyp1a1). A single dose of TCDD administered to adult mice induced Ahr-dependent CpG hypomethylation, changes in histone modifications, and thymine DNA glycosylase (Tdg) recruitment at the Cyp1a1 promoter in the liver within 24 hrs. These epigenetic changes persisted until 40 days post-TCDD treatment and there was Cyp1a1 mRNA hyperinduction upon repeat administration of TCDD at this time-point. Our demethylation assay using siRNA knockdown and an in vitro methylated plasmid showed that Ahr, Tdg, and the ten-eleven translocation methyldioxygenases Tet2 and Tet3 are required for the TCDD-induced DNA demethylation. These results provide novel evidence of Ahr-driven active DNA demethylation and epigenetic memory. The epigenetic alterations influence response to subsequent chemical exposure and imply an adaptive mechanism to xenobiotic stress.

Trial-by-trial adaptation of movements during mental practice under force field.

PubMed

Anwar, Muhammad Nabeel; Khan, Salman Hameed

2013-01-01

Human nervous system tries to minimize the effect of any external perturbing force by bringing modifications in the internal model. These modifications affect the subsequent motor commands generated by the nervous system. Adaptive compensation along with the appropriate modifications of internal model helps in reducing human movement errors. In the current study, we studied how motor imagery influences trial-to-trial learning in a robot-based adaptation task. Two groups of subjects performed reaching movements with or without motor imagery in a velocity-dependent force field. The results show that reaching movements performed with motor imagery have relatively a more focused generalization pattern and a higher learning rate in training direction.

Acid Response of Bifidobacterium longum subsp. longum BBMN68 Is Accompanied by Modification of the Cell Membrane Fatty Acid Composition.

PubMed

Liu, Songling; Ren, Fazheng; Jiang, Jingli; Zhao, Liang

2016-07-28

The acid response of Bifidobacterium longum subsp. longum BBMN68 has been studied in our previous study. The fab gene, which is supposed to be involved in membrane fatty acid biosynthesis, was demonstrated to be induced in acid response. In order to investigate the relationship between acid response and cell membrane fatty acid composition, the acid adaptation of BBMN68 was assessed and the membrane fatty acid composition at different adaptation conditions was identified. Indeed, the fatty acid composition was influenced by acid adaptation. Our results showed that the effective acid adaptations were accompanied with decrease in the unsaturated to saturated fatty acids ratio (UFA/SFA) and increase in cyclopropane fatty acid (CFA) content, which corresponded to previous studies. Moreover, both effective and non-effective acid adaptation conditions resulted in decrease in the C18:1 cis-9/C18:1 trans-9 ratio, indicating that the C18:1 cis-9/C18:1 trans-9 ratio is associated with acid tolerance response but not with acid adaptation response. Taken together, this study indicated that the UFA/SFA and CFA content of BBMN68 were involved in acid adaptation and the C18:1 cis-9/C18:1 trans-9 ratio was involved in acid tolerance response.

Providing the Support Services Needed by Students Who Are Deaf or Hard of Hearing.

ERIC Educational Resources Information Center

Luetke-Stahlman, Barbara

1998-01-01

Discusses programmatic and curricular modifications often needed for students included in public school settings who are deaf or hard of hearing, such as adapting the mode/flow of classroom communication, linguistic-level changes, and adapting the listening and physical environment. Possible curricular modifications are suggested for…

FLEXWAL: A computer program for predicting the wall modifications for two-dimensional, solid, adaptive-wall tunnels

NASA Technical Reports Server (NTRS)

Everhart, J. L.

1983-01-01

A program called FLEXWAL for calculating wall modifications for solid, adaptive-wall wind tunnels is presented. The method used is the iterative technique of NASA TP-2081 and is applicable to subsonic and transonic test conditions. The program usage, program listing, and a sample case are given.

The Interplay Between Strategic And Adaptive Control Mechanisms In Plastic Recalibration Of Locomotor Function

NASA Technical Reports Server (NTRS)

Richards, J. T.; Mulavara, A. P.; Bloomberg, J. J.

2006-01-01

We have previously shown that viewing simulated rotary self-motion during treadmill locomotion causes immediate strategic modifications (Richards et al. 2004) as well as an after effect reflecting adaptive modification of the control of position and trajectory during over-ground locomotion (Mulavara et al. 2005). The process of sensorimotor adaptation is comprised of both strategic and adaptive control mechanisms. Strategic control involves cognitive, on-line corrections to limb movements once one is aware of a sensory discordance. Over an extended period of exposure to the sensory discordance, new strategic sensorimotor coordination patterns are reinforced until they become more automatic, and therefore adaptive, in nature. The objective of this study was to investigate how strategic changes in trunk control during exposure to simulated rotary self-motion during treadmill walking influences adaptive modification of locomotor heading direction during over-ground stepping. Subjects (n = 10) walked on a motorized linear treadmill while viewing a wide field-of-view virtual scene for 24 minutes. The scene was static for the first 4 minutes and then, for the last 20 minutes, depicted constant rate self-motion equivalent to walking in a counter-clockwise, circular path around the perimeter of a room. Subjects performed five stepping trials both before and after the exposure period to assess after effects. Results from our previous study showed a significant change in heading direction (HD) during post-exposure step tests that was opposite the direction in which the scene rotated during the adaptation period. For the present study, we quantified strategic modifications in trunk movement control during scene exposure using normalized root mean square (R(sub p)) variation of the subject's 3D trunk positions and normalized sum of standard deviations (R(sub o)) variation of 3D trunk orientations during scene rotation relative to that during static scene presentation. Associated 95% confidence intervals, CI(sub P) and CI(sub O), were calculated to investigate the variation of strategic modifications during scene exposure. Repeated measures ANOVA and individual subject regression analyses showed that R(sub P) and R(sub O) (i.e. strategic modifications) for trunk fore/aft (X) and yaw movements, respectively, decreased significantly over the exposure period. Furthermore, we found a significant correlation between the magnitude change in HD and the rate at which the variation of strategic modifications in trunk X decreased. We also found evidence of a correlation between HD and the rate at which strategic modifications in trunk yaw decreased (p = .06). We infer that adaptive recalibration of locomotor trajectory using optic flow stimuli depends on the rate at which strategic intervention is reduced.

Phase and amplitude beam shaping with two deformable mirrors implementing input plane and Fourier plane phase modifications.

PubMed

Wu, Chensheng; Ko, Jonathan; Rzasa, John R; Paulson, Daniel A; Davis, Christopher C

2018-03-20

We find that ideas in optical image encryption can be very useful for adaptive optics in achieving simultaneous phase and amplitude shaping of a laser beam. An adaptive optics system with simultaneous phase and amplitude shaping ability is very desirable for atmospheric turbulence compensation. Atmospheric turbulence-induced beam distortions can jeopardize the effectiveness of optical power delivery for directed-energy systems and optical information delivery for free-space optical communication systems. In this paper, a prototype adaptive optics system is proposed based on a famous image encryption structure. The major change is to replace the two random phase plates at the input plane and Fourier plane of the encryption system, respectively, with two deformable mirrors that perform on-demand phase modulations. A Gaussian beam is used as an input to replace the conventional image input. We show through theory, simulation, and experiments that the slightly modified image encryption system can be used to achieve arbitrary phase and amplitude beam shaping within the limits of stroke range and influence function of the deformable mirrors. In application, the proposed technique can be used to perform mode conversion between optical beams, generate structured light signals for imaging and scanning, and compensate atmospheric turbulence-induced phase and amplitude beam distortions.

Proteomics of Skeletal Muscle: Focus on Insulin Resistance and Exercise Biology

PubMed Central

Deshmukh, Atul S.

2016-01-01

Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence, of altered protein expressions profiles and/or their posttranslational modifications (PTMs). Mass spectrometry (MS)-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle proteomics are challenging. This review describes the technical limitations of skeletal muscle proteomics as well as emerging developments in proteomics workflow with respect to samples preparation, liquid chromatography (LC), MS and computational analysis. These technologies have not yet been fully exploited in the field of skeletal muscle proteomics. Future studies that involve state-of-the-art proteomics technology will broaden our understanding of exercise-induced adaptations as well as molecular pathogenesis of insulin resistance. This could lead to the identification of new therapeutic targets. PMID:28248217

Output Feedback Adaptive Control of Non-Minimum Phase Systems Using Optimal Control Modification

NASA Technical Reports Server (NTRS)

Nguyen, Nhan; Hashemi, Kelley E.; Yucelen, Tansel; Arabi, Ehsan

2018-01-01

This paper describes output feedback adaptive control approaches for non-minimum phase SISO systems with relative degree 1 and non-strictly positive real (SPR) MIMO systems with uniform relative degree 1 using the optimal control modification method. It is well-known that the standard model-reference adaptive control (MRAC) cannot be used to control non-SPR plants to track an ideal SPR reference model. Due to the ideal property of asymptotic tracking, MRAC attempts an unstable pole-zero cancellation which results in unbounded signals for non-minimum phase SISO systems. The optimal control modification can be used to prevent the unstable pole-zero cancellation which results in a stable adaptation of non-minimum phase SISO systems. However, the tracking performance using this approach could suffer if the unstable zero is located far away from the imaginary axis. The tracking performance can be recovered by using an observer-based output feedback adaptive control approach which uses a Luenberger observer design to estimate the state information of the plant. Instead of explicitly specifying an ideal SPR reference model, the reference model is established from the linear quadratic optimal control to account for the non-minimum phase behavior of the plant. With this non-minimum phase reference model, the observer-based output feedback adaptive control can maintain stability as well as tracking performance. However, in the presence of the mismatch between the SPR reference model and the non-minimum phase plant, the standard MRAC results in unbounded signals, whereas a stable adaptation can be achieved with the optimal control modification. An application of output feedback adaptive control for a flexible wing aircraft illustrates the approaches.

Mechanotransduction as an Adaptation to Gravity

PubMed Central

Najrana, Tanbir; Sanchez-Esteban, Juan

2016-01-01

Gravity has played a critical role in the development of terrestrial life. A key event in evolution has been the development of mechanisms to sense and transduce gravitational force into biological signals. The objective of this manuscript is to review how living organisms on Earth use mechanotransduction as an adaptation to gravity. Certain cells have evolved specialized structures, such as otoliths in hair cells of the inner ear and statoliths in plants, to respond directly to the force of gravity. By conducting studies in the reduced gravity of spaceflight (microgravity) or simulating microgravity in the laboratory, we have gained insights into how gravity might have changed life on Earth. We review how microgravity affects prokaryotic and eukaryotic cells at the cellular and molecular levels. Genomic studies in yeast have identified changes in genes involved in budding, cell polarity, and cell separation regulated by Ras, PI3K, and TOR signaling pathways. Moreover, transcriptomic analysis of late pregnant rats have revealed that microgravity affects genes that regulate circadian clocks, activate mechanotransduction pathways, and induce changes in immune response, metabolism, and cells proliferation. Importantly, these studies identified genes that modify chromatin structure and methylation, suggesting that long-term adaptation to gravity may be mediated by epigenetic modifications. Given that gravity represents a modification in mechanical stresses encounter by the cells, the tensegrity model of cytoskeletal architecture provides an excellent paradigm to explain how changes in the balance of forces, which are transmitted across transmembrane receptors and cytoskeleton, can influence intracellular signaling pathways and gene expression. PMID:28083527

Mechanotransduction as an Adaptation to Gravity.

PubMed

Najrana, Tanbir; Sanchez-Esteban, Juan

2016-01-01

Gravity has played a critical role in the development of terrestrial life. A key event in evolution has been the development of mechanisms to sense and transduce gravitational force into biological signals. The objective of this manuscript is to review how living organisms on Earth use mechanotransduction as an adaptation to gravity. Certain cells have evolved specialized structures, such as otoliths in hair cells of the inner ear and statoliths in plants, to respond directly to the force of gravity. By conducting studies in the reduced gravity of spaceflight (microgravity) or simulating microgravity in the laboratory, we have gained insights into how gravity might have changed life on Earth. We review how microgravity affects prokaryotic and eukaryotic cells at the cellular and molecular levels. Genomic studies in yeast have identified changes in genes involved in budding, cell polarity, and cell separation regulated by Ras, PI3K, and TOR signaling pathways. Moreover, transcriptomic analysis of late pregnant rats have revealed that microgravity affects genes that regulate circadian clocks, activate mechanotransduction pathways, and induce changes in immune response, metabolism, and cells proliferation. Importantly, these studies identified genes that modify chromatin structure and methylation, suggesting that long-term adaptation to gravity may be mediated by epigenetic modifications. Given that gravity represents a modification in mechanical stresses encounter by the cells, the tensegrity model of cytoskeletal architecture provides an excellent paradigm to explain how changes in the balance of forces, which are transmitted across transmembrane receptors and cytoskeleton, can influence intracellular signaling pathways and gene expression.

Targeting the adaptive molecular landscape of castration-resistant prostate cancer

PubMed Central

Wyatt, Alexander W; Gleave, Martin E

2015-01-01

Castration and androgen receptor (AR) pathway inhibitors induce profound and sustained responses in advanced prostate cancer. However, the inevitable recurrence is associated with reactivation of the AR and progression to a more aggressive phenotype termed castration-resistant prostate cancer (CRPC). AR reactivation can occur directly through genomic modification of the AR gene, or indirectly via co-factor and co-chaperone deregulation. This mechanistic heterogeneity is further complicated by the stress-driven induction of a myriad of overlapping cellular survival pathways. In this review, we describe the heterogeneous and evolvable molecular landscape of CRPC and explore recent successes and failures of therapeutic strategies designed to target AR reactivation and adaptive survival pathways. We also discuss exciting areas of burgeoning anti-tumour research, and their potential to improve the survival and management of patients with CRPC. PMID:25896606

A systematic review of recommended modifications of CBT for people with cognitive impairments following brain injury.

PubMed

Gallagher, Melanie; McLeod, Hamish J; McMillan, Thomas M

2016-11-22

Due to diverse cognitive, emotional and interpersonal changes that can follow brain injury, psychological therapies often need to be adapted to suit the complex needs of this population. The aims of the study were to synthesise published recommendations for therapy modifications following brain injury from non-progressive traumatic, vascular, or metabolic causes and to determine how often such modifications have been applied to cognitive behavioural therapy (CBT) for post-injury emotional adjustment problems. A systematic review and narrative synthesis of therapy modifications recommended in review articles and reported in intervention studies was undertaken. Database and manual searches identified 688 unique papers of which eight review articles and 16 intervention studies met inclusion criteria. The review articles were thematically analysed and a checklist of commonly recommended modifications composed. The checklist items clustered under themes of: therapeutic education and formulation; attention; communication; memory; and executive functioning. When this checklist was applied to the intervention studies, memory aids and an emphasis on socialising patients to the CBT model were most frequently reported as adaptations. It was concluded that the inconsistent reporting of psychological therapy adaptations for people with brain injury is a barrier to developing effective and replicable therapies. We present a comprehensive account of potential modifications that should be used to guide future research and practice.

An Analysis of the Optimal Control Modification Method Applied to Flutter Suppression

NASA Technical Reports Server (NTRS)

Drew, Michael; Nguyen, Nhan T.; Hashemi, Kelley E.; Ting, Eric; Chaparro, Daniel

2017-01-01

Unlike basic Model Reference Adaptive Control (MRAC)l, Optimal Control Modification (OCM) has been shown to be a promising MRAC modification with robustness and analytical properties not present in other adaptive control methods. This paper presents an analysis of the OCM method, and how the asymptotic property of OCM is useful for analyzing and tuning the controller. We begin with a Lyapunov stability proof of an OCM controller having two adaptive gain terms, then the less conservative and easily analyzed OCM asymptotic property is presented. Two numerical examples are used to show how this property can accurately predict steady state stability and quantitative robustness in the presence of time delay, and relative to linear plant perturbations, and nominal Loop Transfer Recovery (LTR) tuning. The asymptotic property of the OCM controller is then used as an aid in tuning the controller applied to a large scale aeroservoelastic longitudinal aircraft model for flutter suppression. Control with OCM adaptive augmentation is shown to improve performance over that of the nominal non-adaptive controller when significant disparities exist between the controller/observer model and the true plant model.

Adaptive Control with Reference Model Modification

NASA Technical Reports Server (NTRS)

Stepanyan, Vahram; Krishnakumar, Kalmanje

2012-01-01

This paper presents a modification of the conventional model reference adaptive control (MRAC) architecture in order to improve transient performance of the input and output signals of uncertain systems. A simple modification of the reference model is proposed by feeding back the tracking error signal. It is shown that the proposed approach guarantees tracking of the given reference command and the reference control signal (one that would be designed if the system were known) not only asymptotically but also in transient. Moreover, it prevents generation of high frequency oscillations, which are unavoidable in conventional MRAC systems for large adaptation rates. The provided design guideline makes it possible to track a reference commands of any magnitude from any initial position without re-tuning. The benefits of the method are demonstrated with a simulation example

Parameter Estimation for a Hybrid Adaptive Flight Controller

NASA Technical Reports Server (NTRS)

Campbell, Stefan F.; Nguyen, Nhan T.; Kaneshige, John; Krishnakumar, Kalmanje

2009-01-01

This paper expands on the hybrid control architecture developed at the NASA Ames Research Center by addressing issues related to indirect adaptation using the recursive least squares (RLS) algorithm. Specifically, the hybrid control architecture is an adaptive flight controller that features both direct and indirect adaptation techniques. This paper will focus almost exclusively on the modifications necessary to achieve quality indirect adaptive control. Additionally this paper will present results that, using a full non -linear aircraft model, demonstrate the effectiveness of the hybrid control architecture given drastic changes in an aircraft s dynamics. Throughout the development of this topic, a thorough discussion of the RLS algorithm as a system identification technique will be provided along with results from seven well-known modifications to the popular RLS algorithm.

PHOTONICS AND NANOTECHNOLOGY Laser-induced modification of transparent crystals and glasses

NASA Astrophysics Data System (ADS)

Bulgakova, N. M.; Stoian, Razvan; Rosenfeld, A.

2010-12-01

We analyse the processes taking place in transparent crystals and glasses irradiated by ultrashort laser pulses in the regimes typical of various applications in optoelectronics and photonics. We consider some phenomena, which have been previously described by the authors within the different model representations: charging of the dielectric surface due to electron photoemission resulting in a Coulomb explosion; crater shaping by using an adaptive control of the laser pulse shape; optimisation of the waveguide writing in materials strongly resistant to laser-induced compaction under ordinary irradiation conditions. The developed models and analysis of the processes relying on these models include the elements of the solid-state physics, plasma physics, thermodynamics, theory of elasticity and plasticity. Some important experimental observations which require explanations and adequate description are summarised.

Control Systems with Normalized and Covariance Adaptation by Optimal Control Modification

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T. (Inventor); Burken, John J. (Inventor); Hanson, Curtis E. (Inventor)

2016-01-01

Disclosed is a novel adaptive control method and system called optimal control modification with normalization and covariance adjustment. The invention addresses specifically to current challenges with adaptive control in these areas: 1) persistent excitation, 2) complex nonlinear input-output mapping, 3) large inputs and persistent learning, and 4) the lack of stability analysis tools for certification. The invention has been subject to many simulations and flight testing. The results substantiate the effectiveness of the invention and demonstrate the technical feasibility for use in modern aircraft flight control systems.

Adaptation and Cultural Diffusion.

ERIC Educational Resources Information Center

Ormrod, Richard K.

1992-01-01

Explores the role of adaptation in cultural diffusion. Explains that adaptation theory recognizes the lack of independence between innovations and their environmental settings. Discusses testing and selection, modification, motivation, and cognition. Suggests that adaptation effects are pervasive in cultural diffusion but require a broader, more…

Software evolution. What kind of evolution?

NASA Astrophysics Data System (ADS)

Torres-Carbonell, J. J.; Parets-Llorca, J.

2001-06-01

Most Software Systems capable of adapting to the environment or of performing some kind of adaptive activity (such as pattern learning, behavior simulations and the like) use concepts and models from Biology. Nevertheless, such approaches are based on the Modern Synthesis, i.e., Darwinism plus Mendelism, and this implies preadaptive mutations in, and subsequent selection of the better adapted individuals. These pre-adaptive changes usually do not produce the desired effect, are virtually useless and require some kind of backtracking for the system to obtain profit from adaptation. It is our contention that an evolutionary approach in Software Systems development cannot be based on pre-adaptive mutations, but rather on post-adaptive ones, that is, anticipatory mutations and modifications (Lamarkism). A novel way of understanding evolution in Software Systems based on applied Lamarkism is presented and a framework that allows the incorporation of modifications according to the necessities of the system and the will of the modeller is proposed.

Advances in Adaptive Control Methods

NASA Technical Reports Server (NTRS)

Nguyen, Nhan

2009-01-01

This poster presentation describes recent advances in adaptive control technology developed by NASA. Optimal Control Modification is a novel adaptive law that can improve performance and robustness of adaptive control systems. A new technique has been developed to provide an analytical method for computing time delay stability margin for adaptive control systems.

The Listeria monocytogenes Bile Stimulon under Acidic Conditions Is Characterized by Strain-Specific Patterns and the Upregulation of Motility, Cell Wall Modification Functions, and the PrfA Regulon

PubMed Central

Guariglia-Oropeza, Veronica; Orsi, Renato H.; Guldimann, Claudia; Wiedmann, Martin; Boor, Kathryn J.

2018-01-01

Listeria monocytogenes uses a variety of transcriptional regulation strategies to adapt to the extra-host environment, the gastrointestinal tract, and the intracellular host environment. While the alternative sigma factor SigB has been proposed to be a key transcriptional regulator that facilitates L. monocytogenes adaptation to the gastrointestinal environment, the L. monocytogenes' transcriptional response to bile exposure is not well-understood. RNA-seq characterization of the bile stimulon was performed in two L. monocytogenes strains representing lineages I and II. Exposure to bile at pH 5.5 elicited a large transcriptomic response with ~16 and 23% of genes showing differential transcription in 10403S and H7858, respectively. The bile stimulon includes genes involved in motility and cell wall modification mechanisms, as well as genes in the PrfA regulon, which likely facilitate survival during the gastrointestinal stages of infection that follow bile exposure. The fact that bile exposure induced the PrfA regulon, but did not induce further upregulation of the SigB regulon (beyond that expected by exposure to pH 5.5), suggests a model where at the earlier stages of gastrointestinal infection (e.g., acid exposure in the stomach), SigB-dependent gene expression plays an important role. Subsequent exposure to bile induces the PrfA regulon, potentially priming L. monocytogenes for subsequent intracellular infection stages. Some members of the bile stimulon showed lineage- or strain-specific distribution when 27 Listeria genomes were analyzed. Even though sigB null mutants showed increased sensitivity to bile, the SigB regulon was not found to be upregulated in response to bile beyond levels expected by exposure to pH 5.5. Comparison of wildtype and corresponding ΔsigB strains newly identified 26 SigB-dependent genes, all with upstream putative SigB-dependent promoters. PMID:29467736

Crystal structure of laser-induced subsurface modifications in Si

NASA Astrophysics Data System (ADS)

Verburg, P. C.; Smillie, L. A.; Römer, G. R. B. E.; Haberl, B.; Bradby, J. E.; Williams, J. S.; Huis in't Veld, A. J.

2015-08-01

Laser-induced subsurface modification of dielectric materials is a well-known technology. Applications include the production of optical components and selective etching. In addition to dielectric materials, the subsurface modification technology can be applied to silicon, by employing near to mid-infrared radiation. An application of subsurface modifications in silicon is laser-induced subsurface separation, which is a method to separate wafers into individual dies. Other applications for which proofs of concept exist are the formation of waveguides and resistivity tuning. However, limited knowledge is available about the crystal structure of subsurface modifications in silicon. In this work, we investigate the geometry and crystal structure of laser-induced subsurface modifications in monocrystalline silicon wafers. In addition to the generation of lattice defects, we found that transformations to amorphous silicon and Si -iii/Si -xii occur as a result of the laser irradiation.

Verifiable Adaptive Control with Analytical Stability Margins by Optimal Control Modification

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.

2010-01-01

This paper presents a verifiable model-reference adaptive control method based on an optimal control formulation for linear uncertain systems. A predictor model is formulated to enable a parameter estimation of the system parametric uncertainty. The adaptation is based on both the tracking error and predictor error. Using a singular perturbation argument, it can be shown that the closed-loop system tends to a linear time invariant model asymptotically under an assumption of fast adaptation. A stability margin analysis is given to estimate a lower bound of the time delay margin using a matrix measure method. Using this analytical method, the free design parameter n of the optimal control modification adaptive law can be determined to meet a specification of stability margin for verification purposes.

Crystal structure of laser-induced subsurface modifications in Si

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verburg, P. C.; Smillie, L. A.; Römer, G. R. B. E.

2015-06-04

Laser-induced subsurface modification of dielectric materials is a well-known technology. Applications include the production of optical components and selective etching. In addition to dielectric materials, the subsurface modification technology can be applied to silicon, by employing near to mid-infrared radiation. An application of subsurface modifications in silicon is laser-induced subsurface separation, which is a method to separate wafers into individual dies. Other applications for which proofs of concept exist are the formation of waveguides and resistivity tuning. However, limited knowledge is available about the crystal structure of subsurface modifications in silicon. In this paper, we investigate the geometry and crystalmore » structure of laser-induced subsurface modifications in monocrystalline silicon wafers. Finally, in addition to the generation of lattice defects, we found that transformations to amorphous silicon and Si-iii/Si-xii occur as a result of the laser irradiation.« less

Epigenetic and chromatin-based mechanisms in environmental stress adaptation and stress memory in plants.

PubMed

Lämke, Jörn; Bäurle, Isabel

2017-06-27

Plants frequently have to weather both biotic and abiotic stressors, and have evolved sophisticated adaptation and defense mechanisms. In recent years, chromatin modifications, nucleosome positioning, and DNA methylation have been recognized as important components in these adaptations. Given their potential epigenetic nature, such modifications may provide a mechanistic basis for a stress memory, enabling plants to respond more efficiently to recurring stress or even to prepare their offspring for potential future assaults. In this review, we discuss both the involvement of chromatin in stress responses and the current evidence on somatic, intergenerational, and transgenerational stress memory.

50 CFR 217.88 - Renewal of Letters of Authorization and adaptive management.

Code of Federal Regulations, 2014 CFR

2014-10-01

... to the adaptive management component of these regulations, provided that: (1) NMFS is notified that... that modifications are appropriate pursuant to the adaptive management component of these regulations...) Adaptive Management—NMFS may modify or augment the existing mitigation or monitoring measures (after...

50 CFR 217.88 - Renewal of Letters of Authorization and adaptive management.

Code of Federal Regulations, 2012 CFR

2012-10-01

... to the adaptive management component of these regulations, provided that: (1) NMFS is notified that... that modifications are appropriate pursuant to the adaptive management component of these regulations...) Adaptive Management—NMFS may modify or augment the existing mitigation or monitoring measures (after...

50 CFR 217.88 - Renewal of Letters of Authorization and adaptive management.

Code of Federal Regulations, 2013 CFR

2013-10-01

... to the adaptive management component of these regulations, provided that: (1) NMFS is notified that... that modifications are appropriate pursuant to the adaptive management component of these regulations...) Adaptive Management—NMFS may modify or augment the existing mitigation or monitoring measures (after...

Exposure Control Using Adaptive Multi-Stage Item Bundles.

ERIC Educational Resources Information Center

Luecht, Richard M.

This paper presents a multistage adaptive testing test development paradigm that promises to handle content balancing and other test development needs, psychometric reliability concerns, and item exposure. The bundled multistage adaptive testing (BMAT) framework is a modification of the computer-adaptive sequential testing framework introduced by…

Endoplasmic Reticulum Stress and Type 2 Diabetes

PubMed Central

Back, Sung Hoon; Kaufman, Randal J.

2013-01-01

Given the functional importance of the endoplasmic reticulum (ER), an organelle that performs folding, modification, and trafficking of secretory and membrane proteins to the Golgi compartment, the maintenance of ER homeostasis in insulin-secreting β-cells is very important. When ER homeostasis is disrupted, the ER generates adaptive signaling pathways, called the unfolded protein response (UPR), to maintain homeostasis of this organelle. However, if homeostasis fails to be restored, the ER initiates death signaling pathways. New observations suggest that both chronic hyperglycemia and hyperlipidemia, known as important causative factors of type 2 diabetes (T2D), disrupt ER homeostasis to induce unresolvable UPR activation and β-cell death. This review examines how the UPR pathways, induced by high glucose and free fatty acids (FFAs), interact to disrupt ER function and cause β-cell dysfunction and death. PMID:22443930

The Evolutionary Origin of Female Orgasm.

PubMed

Pavličev, Mihaela; Wagner, Günter

2016-09-01

The evolutionary explanation of female orgasm has been difficult to come by. The orgasm in women does not obviously contribute to the reproductive success, and surprisingly unreliably accompanies heterosexual intercourse. Two types of explanations have been proposed: one insisting on extant adaptive roles in reproduction, another explaining female orgasm as a byproduct of selection on male orgasm, which is crucial for sperm transfer. We emphasize that these explanations tend to focus on evidence from human biology and thus address the modification of a trait rather than its evolutionary origin. To trace the trait through evolution requires identifying its homologue in other species, which may have limited similarity with the human trait. Human female orgasm is associated with an endocrine surge similar to the copulatory surges in species with induced ovulation. We suggest that the homolog of human orgasm is the reflex that, ancestrally, induced ovulation. This reflex became superfluous with the evolution of spontaneous ovulation, potentially freeing female orgasm for other roles. This is supported by phylogenetic evidence showing that induced ovulation is ancestral, while spontaneous ovulation is derived within eutherians. In addition, the comparative anatomy of female reproductive tract shows that evolution of spontaneous ovulation is correlated with increasing distance of clitoris from the copulatory canal. In summary, we suggest that the female orgasm-like trait may have been adaptive, however for a different role, namely for inducing ovulation. With the evolution of spontaneous ovulation, orgasm was freed to gain secondary roles, which may explain its maintenance, but not its origin. © 2016 Wiley Periodicals, Inc.

Rapid response to changing environments during biological invasions: DNA methylation perspectives.

PubMed

Huang, Xuena; Li, Shiguo; Ni, Ping; Gao, Yangchun; Jiang, Bei; Zhou, Zunchun; Zhan, Aibin

2017-12-01

Dissecting complex interactions between species and their environments has long been a research hot spot in the fields of ecology and evolutionary biology. The well-recognized Darwinian evolution has well-explained long-term adaptation scenarios; however, "rapid" processes of biological responses to environmental changes remain largely unexplored, particularly molecular mechanisms such as DNA methylation that have recently been proposed to play crucial roles in rapid environmental adaptation. Invasive species, which have capacities to successfully survive rapidly changing environments during biological invasions, provide great opportunities to study molecular mechanisms of rapid environmental adaptation. Here, we used the methylation-sensitive amplified polymorphism (MSAP) technique in an invasive model ascidian, Ciona savignyi, to investigate how species interact with rapidly changing environments at the whole-genome level. We detected quite rapid DNA methylation response: significant changes of DNA methylation frequency and epigenetic differentiation between treatment and control groups occurred only after 1 hr of high-temperature exposure or after 3 hr of low-salinity challenge. In addition, we detected time-dependent hemimethylation changes and increased intragroup epigenetic divergence induced by environmental stresses. Interestingly, we found evidence of DNA methylation resilience, as most stress-induced DNA methylation variation maintained shortly (~48 hr) and quickly returned back to the control levels. Our findings clearly showed that invasive species could rapidly respond to acute environmental changes through DNA methylation modifications, and rapid environmental changes left significant epigenetic signatures at the whole-genome level. All these results provide fundamental background to deeply investigate the contribution of DNA methylation mechanisms to rapid contemporary environmental adaptation. © 2017 John Wiley & Sons Ltd.

Performance Optimizing Adaptive Control with Time-Varying Reference Model Modification

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.; Hashemi, Kelley E.

2017-01-01

This paper presents a new adaptive control approach that involves a performance optimization objective. The control synthesis involves the design of a performance optimizing adaptive controller from a subset of control inputs. The resulting effect of the performance optimizing adaptive controller is to modify the initial reference model into a time-varying reference model which satisfies the performance optimization requirement obtained from an optimal control problem. The time-varying reference model modification is accomplished by the real-time solutions of the time-varying Riccati and Sylvester equations coupled with the least-squares parameter estimation of the sensitivities of the performance metric. The effectiveness of the proposed method is demonstrated by an application of maneuver load alleviation control for a flexible aircraft.

Stereoscopic Viewing Can Induce Changes in the CA/C Ratio.

PubMed

Neveu, Pascaline; Roumes, Corinne; Philippe, Matthieu; Fuchs, Philippe; Priot, Anne-Emmanuelle

2016-08-01

Stereoscopic displays challenge the neural cross-coupling between accommodation and vergence by inducing a constant accommodative demand and a varying vergence demand. Stereoscopic viewing calls for a decrease in the gain of vergence accommodation, which is the accommodation caused by vergence, quantified by using the convergence-accommodation to convergence (CA/C) ratio. However, its adaptability is still a subject of debate. Cross-coupling (CA/C and AC/A ratios) and tonic components of vergence and accommodation were assessed in 12 participants (27.5 ± 5 years, stereoacuity better than 60 arc seconds, 6/6 acuity with corrected refractive error) before and after a 20-minute exposure to stereoscopic viewing. During stimulation, vergence demand oscillated from 1 to 3 meter angles along a virtual sagittal line in sinusoidal movements, while accommodative demand was fixed at 1.5 diopters. Results showed a decreased CA/C ratio (-10.36%, df = 10, t = 2.835, P = 0.018), with no change in the AC/A ratio (P = 0.090), tonic vergence (P = 0.708), and tonic accommodation (P = 0.493). These findings demonstrated that the CA/C ratio can exhibit adaptive adjustments. The observed nature and amount of the oculomotor modification failed to compensate for the stereoscopic constraint.

Adapting HIV prevention evidence-based interventions in practice settings: an interview study

PubMed Central

2009-01-01

Background Evidence-based interventions that are being delivered in real-world settings are adapted to enhance the external validity of these interventions. The purpose of this study was to examine multiple intervention adaptations made during pre-implementation, implementation, maintenance, and evolution phases of human immunodeficiency virus HIV prevention technology transfer. We examined two important categories of adaptations -- modifications to key characteristics, such as activities or delivery methods of interventions and reinvention of the interventions including addition and deletion of core elements. Methods Study participants were thirty-four community-based organization staff who were implementing evidence-based interventions in Los Angeles, California. Participants were interviewed twice and interviews were professionally transcribed. Transcriptions were coded by two coders with good inter-rater reliability (kappa coefficient = 0.73). Sixty-two open-ended codes for adaptation activities, which were linked to 229 transcript segments, were categorized as modifications of key characteristics or reinvention. Results Participants described activities considered modifications to key characteristics and reinvention of evidence-based interventions during pre-implementation, implementation, and maintenance phases. None of the participants reported accessing technical assistance or guidance when reinventing their interventions. Staff executed many of the recommended steps for sound adaptation of these interventions for new populations and settings. Conclusion Staff reported modifying and reinventing interventions when translating HIV prevention programs into practice. Targeted technical assistance for formative evaluation should be focused on the pre-implementation phase during which frequent modifications occur. Continuous or repeated measurements of fidelity are recommended. Increased technical assistance and guidance are needed to ensure that reinventions are evaluated and consistent with the aims of the original interventions. Providing strategic technical assistance and written guidance can facilitate effective HIV prevention technology transfer of evidence-based interventions. PMID:19930653

Transposon-mediated epigenetic regulation contributes to phenotypic diversity and environmental adaptation in rice.

PubMed

Song, Xianwei; Cao, Xiaofeng

2017-04-01

Transposable elements (TEs) have long been regarded as 'selfish DNA', and are generally silenced by epigenetic mechanisms. However, work in the past decade has identified positive roles for TEs in generating genomic novelty and diversity in plants. In particular, recent studies suggested that TE-induced epigenetic alterations and modification of gene expression contribute to phenotypic variation and adaptation to geography or stress. These findings have led many to regard TEs, not as junk DNA, but as sources of control elements and genomic diversity. As a staple food crop and model system for genomic research on monocot plants, rice (Oryza sativa) has a modest-sized genome that harbors massive numbers of DNA transposons (class II transposable elements) scattered across the genome, which may make TE regulation of genes more prevalent. In this review, we summarize recent progress in research on the functions of rice TEs in modulating gene expression and creating new genes. We also examine the contributions of TEs to phenotypic diversity and adaptation to environmental conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Locomotor Dysfunction after Long-duration Space Flight and Development of Countermeasures to Facilitate Faster Recovery

NASA Astrophysics Data System (ADS)

Mulavara, Ajitkumar; Wood, Scott; Cohen, Helen; Bloomberg, Jacob

2012-07-01

Exposure to the microgravity conditions of space flight induces adaptive modification in sensorimotor function allowing astronauts to operate in this unique environment. This adaptive state, however, is inappropriate for a 1-g environment. Consequently astronauts must spend time readapting to Earth's gravity following their return to Earth. During this readaptation period, alterations in sensorimotor function cause various disturbances in astronaut gait during postflight walking. They often rely more on vision for postural and gait stability and many report the need for greater cognitive supervision of motor actions that previous to space flight were fully automated. Over the last several years our laboratory has investigated postflight astronaut locomotion with the aim of better understanding how adaptive changes in underlying sensorimotor mechanisms contribute to postflight gait dysfunction. Exposure to the microgravity conditions of space flight induces adaptive modification in the control of vestibularly-mediated reflexive head movement during locomotion after space flight. Furthermore, during motor learning, adaptive transitions are composed of two main mechanisms: strategic and plastic. Strategic mechanisms represent immediate and transitory modifications in control to deal with changes in the prevailing environment that, if prolonged, induce plastic mechanisms designed to automate new behavioral responses. The goal of the present study was to examine the contributions of sensorimotor subsystems such as the vestibular and body load sensing (BLS) somatosensory influences on head movement control during locomotion after long-duration space flight. Further we present data on the two motor learning processes during readaptation of locomotor function after long-duration space flight. Eighteen astronauts performed two tests of locomotion before and after 6 months of space flight: a treadmill walking test to examine vestibular reflexive mechanisms controlling head movement control and a functional mobility test to investigate overall functional locomotor ability. Postflight sessions were given on days 1, 2, 4, 7 after their return. Subjects walked on a treadmill driven at 1.8 m/s while performing a visual task. Motion data from head and trunk segmental motion data were obtained to calculate the angular head pitch (HP) movements during walking trials while subjects performed the visual task, to estimate the contributions of vestibular reflexive mechanisms in HP movements. Astronauts showed a heterogeneous response pattern of both increases and decreases in the amplitude of HP movement. We investigated the underlying mechanisms of this heterogeneity in postflight responses in head movement control by examining data obtained using the same experimental test paradigm on a vestibular clinical population (VC) and in normal subjects undergoing adaptation to acute body load support unloading. Results showed that exposure to unloaded locomotion caused a significant increase in HP movements, whereas in the VC patients the HP movements were significantly decreased. We infer that BLS-mediated somatosensory input centrally modulates vestibular input and can adaptively modify head-movement control during locomotion. Thus, space flight may cause a central adaptation of the converging vestibular and body load-sensing somatosensory systems. To investigate changes in functional mobility astronaut subjects walked at their preferred pace around an obstacle course consisting of several pylons and obstacles set up on a foam floor, which provided an unstable walking surface. Subjects were instructed to walk around the course as fast as possible without touching any of the objects on the course for a total of six individual trials per test session. One of the dependent measures was time to complete the course (TCC, sec). The learning rate over the six trials performed on preflight and the first day after landing (micro curve) was used to characterize the immediate compensatory strategic response. The learning rate over the six trials of the postflight test days (macro curve) was used to characterize the longer-term plastic response. Adaptation to space flight led to a 52% increase in TCC one day after landing. Recovery to pre-flight scores took an average of two weeks after landing. Subjects showed both strategic and plastic recovery patterns based on the slopes obtained from the micro and macro curves compared to preflight. A regression analysis revealed a significant correlation between the slope values of the macro and micro curves indicating a relationship between strategic and plastic recovery processes. Results showed that both strategic and plastic motor learning processes play a role in postflight restoration of functional mobility and showed a dynamic interplay between these two mechanisms during postflight recovery. These results suggest that gait adaptability training programs which are being developed to facilitate adaptive transition to planetary environments, coupled with low levels of electrical stimulation of the vestibular system, can be optimized to engage both strategic and plastic processes to facilitate rapid restoration of postflight functional mobility.

Space flight and neurovestibular adaptation

NASA Technical Reports Server (NTRS)

Reschke, M. F.; Bloomberg, J. J.; Harm, D. L.; Paloski, W. H.

1994-01-01

Space flight represents a form of sensory stimulus rearrangement requiring modification of established terrestrial response patterns through central reinterpretation. Evidence of sensory reinterpretation is manifested as postflight modifications of eye/head coordination, locomotor patterns, postural control strategies, and illusory perceptions of self or surround motion in conjunction with head movements. Under normal preflight conditions, the head is stabilized during locomotion, but immediately postflight reduced head stability, coupled with inappropriate eye/head coordination, results in modifications of gait. Postflight postural control exhibits increased dependence on vision which compensates for inappropriate interpretation of otolith and proprioceptive inputs. Eye movements compensatory for perceived self motion, rather than actual head movements have been observed postflight. Overall, the in-flight adaptive modification of head stabilization strategies, changes in head/eye coordination, illusionary motion, and postural control are maladaptive for a return to the terrestrial environment.

Electronic properties of solids excited with intermediate laser power densities

NASA Astrophysics Data System (ADS)

Sirotti, Fausto; Tempo Beamline Team

Intermediate laser power density up to about 100 GW/cm2 is below the surface damage threshold is currently used to induce modification in the physical properties on short time scales. The absorption of a short laser pulse induces non-equilibrium electronic distributions followed by lattice-mediated equilibrium taking place only in the picosecond range. The role of the hot electrons is particularly important in several domains as for example fast magnetization and demagnetization processes, laser induced phase transitions, charge density waves. Angular resolved photoelectron spectroscopy measuring directly energy and momentum of electrons is the most adapted tool to study the electronic excitations at short time scales during and after fast laser excitations. The main technical problem is the space charge created by the pumping laser pulse. I will present angular resolved multiphoton photoemission results obtained with 800 nm laser pulses showing how space charge electrons emitted during fast demagnetization processes can be measured. Unable enter Affiliation: CNRS-SOLEIL Synchrotron L'Orme des Merisiers , Saint Aubin 91192 Gif sur Yvette France.

Induced mutation and epigenetics modification in plants for crop improvement by targeting CRISPR/Cas9 technology.

PubMed

Khan, Muhammad Hafeez Ullah; Khan, Shahid U; Muhammad, Ali; Hu, Limin; Yang, Yang; Fan, Chuchuan

2018-06-01

Clustered regularly interspaced palindromic repeats associated protein Cas9 (CRISPR-Cas9), originally an adaptive immunity system of prokaryotes, is revolutionizing genome editing technologies with minimal off-targets in the present era. The CRISPR/Cas9 is now highly emergent, advanced, and highly specific tool for genome engineering. The technology is widely used to animal and plant genomes to achieve desirable results. The present review will encompass how CRISPR-Cas9 is revealing its beneficial role in characterizing plant genetic functions, genomic rearrangement, how it advances the site-specific mutagenesis, and epigenetics modification in plants to improve the yield of field crops with minimal side-effects. The possible pitfalls of using and designing CRISPR-Cas9 for plant genome editing are also discussed for its more appropriate applications in plant biology. Therefore, CRISPR/Cas9 system has multiple benefits that mostly scientists select for genome editing in several biological systems. © 2017 Wiley Periodicals, Inc.

An adaptive approach to the dynamic allocation of buffer storage. M.S. Thesis

NASA Technical Reports Server (NTRS)

Crooke, S. C.

1970-01-01

Several strategies for the dynamic allocation of buffer storage are simulated and compared. The basic algorithms investigated, using actual statistics observed in the Univac 1108 EXEC 8 System, include the buddy method and the first-fit method. Modifications are made to the basic methods in an effort to improve and to measure allocation performance. A simulation model of an adaptive strategy is developed which permits interchanging the two different methods, the buddy and the first-fit methods with some modifications. Using an adaptive strategy, each method may be employed in the statistical environment in which its performance is superior to the other method.

A modified theoretical framework to assess implementation fidelity of adaptive public health interventions.

PubMed

Pérez, Dennis; Van der Stuyft, Patrick; Zabala, Maríadel Carmen; Castro, Marta; Lefèvre, Pierre

2016-07-08

One of the major debates in implementation research turns around fidelity and adaptation. Fidelity is the degree to which an intervention is implemented as intended by its developers. It is meant to ensure that the intervention maintains its intended effects. Adaptation is the process of implementers or users bringing changes to the original design of an intervention. Depending on the nature of the modifications brought, adaptation could either be potentially positive or could carry the risk of threatening the theoretical basis of the intervention, resulting in a negative effect on expected outcomes. Adaptive interventions are those for which adaptation is allowed or even encouraged. Classical fidelity dimensions and conceptual frameworks do not address the issue of how to adapt an intervention while still maintaining its effectiveness. We support the idea that fidelity and adaptation co-exist and that adaptations can impact either positively or negatively on the intervention's effectiveness. For adaptive interventions, research should answer the question how an adequate fidelity-adaptation balance can be reached. One way to address this issue is by looking systematically at the aspects of an intervention that are being adapted. We conducted fidelity research on the implementation of an empowerment strategy for dengue prevention in Cuba. In view of the adaptive nature of the strategy, we anticipated that the classical fidelity dimensions would be of limited use for assessing adaptations. The typology we used in the assessment-implemented, not-implemented, modified, or added components of the strategy-also had limitations. It did not allow us to answer the question which of the modifications introduced in the strategy contributed to or distracted from outcomes. We confronted our empirical research with existing literature on fidelity, and as a result, considered that the framework for implementation fidelity proposed by Carroll et al. in 2007 could potentially meet our concerns. We propose modifications to the framework to assess both fidelity and adaptation. The modified Carroll et al.'s framework we propose may permit a comprehensive assessment of the implementation fidelity-adaptation balance required when implementing adaptive interventions, but more empirical research is needed to validate it.

Transgenerational, Dynamic Methylation of Stomata Genes in Response to Low Relative Humidity

PubMed Central

Tricker, Penny J.; Rodríguez López, Carlos M.; Gibbings, George; Hadley, Paul; Wilkinson, Mike J.

2013-01-01

Transgenerational inheritance of abiotic stress-induced epigenetic modifications in plants has potential adaptive significance and might condition the offspring to improve the response to the same stress, but this is at least partly dependent on the potency, penetrance and persistence of the transmitted epigenetic marks. We examined transgenerational inheritance of low Relative Humidity-induced DNA methylation for two gene loci in the stomatal developmental pathway in Arabidopsis thaliana and the abundance of associated short-interfering RNAs (siRNAs). Heritability of low humidity-induced methylation was more predictable and penetrative at one locus (SPEECHLESS, entropy ≤ 0.02; χ2 < 0.001) than the other (FAMA, entropy ≤ 0.17; χ2 ns). Methylation at SPEECHLESS correlated positively with the continued presence of local siRNAs (r2 = 0.87; p = 0.013) which, however, could be disrupted globally in the progeny under repeated stress. Transgenerational methylation and a parental low humidity-induced stomatal phenotype were heritable, but this was reversed in the progeny under repeated treatment in a previously unsuspected manner. PMID:23531533

Non-specific protein modifications by a phytochemical induce heat shock response for self-defense.

PubMed

Ohnishi, Kohta; Ohkura, Shinya; Nakahata, Erina; Ishisaka, Akari; Kawai, Yoshichika; Terao, Junji; Mori, Taiki; Ishii, Takeshi; Nakayama, Tsutomu; Kioka, Noriyuki; Matsumoto, Shinya; Ikeda, Yasutaka; Akiyama, Minoru; Irie, Kazuhiro; Murakami, Akira

2013-01-01

Accumulated evidence shows that some phytochemicals provide beneficial effects for human health. Recently, a number of mechanistic studies have revealed that direct interactions between phytochemicals and functional proteins play significant roles in exhibiting their bioactivities. However, their binding selectivities to biological molecules are considered to be lower due to their small and simple structures. In this study, we found that zerumbone, a bioactive sesquiterpene, binds to numerous proteins with little selectivity. Similar to heat-denatured proteins, zerumbone-modified proteins were recognized by heat shock protein 90, a constitutive molecular chaperone, leading to heat shock factor 1-dependent heat shock protein induction in hepa1c1c7 mouse hepatoma cells. Furthermore, oral administration of this phytochemical up-regulated heat shock protein expressions in the livers of Sprague-Dawley rats. Interestingly, pretreatment with zerumbone conferred a thermoresistant phenotype to hepa1c1c7 cells as well as to the nematode Caenorhabditis elegans. It is also important to note that several phytochemicals with higher hydrophobicity or electrophilicity, including phenethyl isothiocyanate and curcumin, markedly induced heat shock proteins, whereas most of the tested nutrients did not. These results suggest that non-specific protein modifications by xenobiotic phytochemicals cause mild proteostress, thereby inducing heat shock response and leading to potentiation of protein quality control systems. We considered these bioactivities to be xenohormesis, an adaptation mechanism against xenobiotic chemical stresses. Heat shock response by phytochemicals may be a fundamental mechanism underlying their various bioactivities.

Non-Specific Protein Modifications by a Phytochemical Induce Heat Shock Response for Self-Defense

PubMed Central

Ohnishi, Kohta; Ohkura, Shinya; Nakahata, Erina; Ishisaka, Akari; Kawai, Yoshichika; Terao, Junji; Mori, Taiki; Ishii, Takeshi; Nakayama, Tsutomu; Kioka, Noriyuki; Matsumoto, Shinya; Ikeda, Yasutaka; Akiyama, Minoru; Irie, Kazuhiro; Murakami, Akira

2013-01-01

Accumulated evidence shows that some phytochemicals provide beneficial effects for human health. Recently, a number of mechanistic studies have revealed that direct interactions between phytochemicals and functional proteins play significant roles in exhibiting their bioactivities. However, their binding selectivities to biological molecules are considered to be lower due to their small and simple structures. In this study, we found that zerumbone, a bioactive sesquiterpene, binds to numerous proteins with little selectivity. Similar to heat-denatured proteins, zerumbone-modified proteins were recognized by heat shock protein 90, a constitutive molecular chaperone, leading to heat shock factor 1-dependent heat shock protein induction in hepa1c1c7 mouse hepatoma cells. Furthermore, oral administration of this phytochemical up-regulated heat shock protein expressions in the livers of Sprague-Dawley rats. Interestingly, pretreatment with zerumbone conferred a thermoresistant phenotype to hepa1c1c7 cells as well as to the nematode Caenorhabditis elegans. It is also important to note that several phytochemicals with higher hydrophobicity or electrophilicity, including phenethyl isothiocyanate and curcumin, markedly induced heat shock proteins, whereas most of the tested nutrients did not. These results suggest that non-specific protein modifications by xenobiotic phytochemicals cause mild proteostress, thereby inducing heat shock response and leading to potentiation of protein quality control systems. We considered these bioactivities to be xenohormesis, an adaptation mechanism against xenobiotic chemical stresses. Heat shock response by phytochemicals may be a fundamental mechanism underlying their various bioactivities. PMID:23536805

Host-driven diversification of gall-inducing Acacia thrips and the aridification of Australia

PubMed Central

McLeish, Michael J; Chapman, Thomas W; Schwarz, Michael P

2007-01-01

Background Insects that feed on plants contribute greatly to the generation of biodiversity. Hypotheses explaining rate increases in phytophagous insect diversification and mechanisms driving speciation in such specialists remain vexing despite considerable attention. The proliferation of plant-feeding insects and their hosts are expected to broadly parallel one another where climate change over geological timescales imposes consequences for the diversification of flora and fauna via habitat modification. This work uses a phylogenetic approach to investigate the premise that the aridification of Australia, and subsequent expansion and modification of arid-adapted host flora, has implications for the diversification of insects that specialise on them. Results Likelihood ratio tests indicated the possibility of hard molecular polytomies within two co-radiating gall-inducing species complexes specialising on the same set of host species. Significant tree asymmetry is indicated at a branch adjacent to an inferred transition to a Plurinerves ancestral host species. Lineage by time diversification plots indicate gall-thrips that specialise on Plurinerves hosts differentially experienced an explosive period of speciation contemporaneous with climatic cycling during the Quaternary period. Chronological analyses indicated that the approximate age of origin of gall-inducing thrips on Acacia might be as recent as 10 million years ago during the Miocene, as truly arid landscapes first developed in Australia. Conclusion Host-plant diversification and spatial heterogeneity of hosts have increased the potential for specialisation, resource partitioning, and unoccupied ecological niche availability for gall-thrips on Australian Acacia. PMID:17257412

Infection and body odours: evolutionary and medical perspectives.

PubMed

Prugnolle, Franck; Lefèvre, Thierry; Renaud, François; Møller, Anders Pape; Missé, Dorothée; Thomas, Frédéric

2009-09-01

Infections are often followed by a change in body odours. For a long time, these changes were considered as non-specific (with no adaptive value) but recent evidences suggest that this may not always be true. Odour modifications due to an infection may either be of adaptive value for the parasite or the host. Here, we describe the observations in support of this idea, discuss the potential roles these modifications may play for the parasite and the host and propose a set of future directions that we think should allow to better understand the mechanisms at the origin of these modifications and how they may be used by both parasites and their human hosts.

Modified Method of Adaptive Artificial Viscosity for Solution of Gas Dynamics Problems on Parallel Computer Systems

NASA Astrophysics Data System (ADS)

Popov, Igor; Sukov, Sergey

2018-02-01

A modification of the adaptive artificial viscosity (AAV) method is considered. This modification is based on one stage time approximation and is adopted to calculation of gasdynamics problems on unstructured grids with an arbitrary type of grid elements. The proposed numerical method has simplified logic, better performance and parallel efficiency compared to the implementation of the original AAV method. Computer experiments evidence the robustness and convergence of the method to difference solution.

Space flight and changes in spatial orientation

NASA Technical Reports Server (NTRS)

Reschke, Millard F.; Bloomberg, Jacob J.; Harm, Deborah L.; Paloski, William H.

1992-01-01

From a sensory point of view, space flight represents a form of stimulus rearrangement requiring modification of established terrestrial response patterns through central reinterpretation. Evidence of sensory reinterpretation is manifested as postflight modifications of eye/head coordination, locomotor patterns, postural control strategies, and illusory perceptions of self or surround motion in conjunction with head movements. Under normal preflight conditions, the head is stabilized during locomotion, but immediately postflight reduced head stability, coupled with inappropriate eye/head coordination, results in modifications of gait. Postflight postural control exhibits increased dependence on vision which compensates for inappropriate interpretation of otolith and proprioceptive inputs. Eye movements compensatory for perceived self motion, rather than actual head movements have been observed postflight. Overall, the in-flight adaptive modification of head stabilization strategies, changes in head/eye coordination, illusionary motion, and postural control are maladaptive for a return to the terrestrial environment. Appropriate countermeasures for long-duration flights will rely on preflight adaptation and in-flight training.

Glutamatergic synaptic plasticity in the mesocorticolimbic system in addiction

PubMed Central

van Huijstee, Aile N.; Mansvelder, Huibert D.

2015-01-01

Addictive drugs remodel the brain’s reward circuitry, the mesocorticolimbic dopamine (DA) system, by inducing widespread adaptations of glutamatergic synapses. This drug-induced synaptic plasticity is thought to contribute to both the development and the persistence of addiction. This review highlights the synaptic modifications that are induced by in vivo exposure to addictive drugs and describes how these drug-induced synaptic changes may contribute to the different components of addictive behavior, such as compulsive drug use despite negative consequences and relapse. Initially, exposure to an addictive drug induces synaptic changes in the ventral tegmental area (VTA). This drug-induced synaptic potentiation in the VTA subsequently triggers synaptic changes in downstream areas of the mesocorticolimbic system, such as the nucleus accumbens (NAc) and the prefrontal cortex (PFC), with further drug exposure. These glutamatergic synaptic alterations are then thought to mediate many of the behavioral symptoms that characterize addiction. The later stages of glutamatergic synaptic plasticity in the NAc and in particular in the PFC play a role in maintaining addiction and drive relapse to drug-taking induced by drug-associated cues. Remodeling of PFC glutamatergic circuits can persist into adulthood, causing a lasting vulnerability to relapse. We will discuss how these neurobiological changes produced by drugs of abuse may provide novel targets for potential treatment strategies for addiction. PMID:25653591

Differential behavioural and endocrine responses of common voles (Microtus arvalis) to nest predators and resource competitors.

PubMed

Liesenjohann, Monique; Liesenjohann, Thilo; Palme, Rupert; Eccard, Jana Anja

2013-09-08

Adaptive behavioural strategies promoting co-occurrence of competing species are known to result from a sympatric evolutionary past. Strategies should be different for indirect resource competition (exploitation, e.g., foraging and avoidance behaviour) than for direct interspecific interference (e.g., aggression, vigilance, and nest guarding). We studied the effects of resource competition and nest predation in sympatric small mammal species using semi-fossorial voles and shrews, which prey on vole offspring during their sensitive nestling phase. Experiments were conducted in caged outdoor enclosures. Focus common vole mothers (Microtus arvalis) were either caged with a greater white-toothed shrew (Crocidura russula) as a potential nest predator, with an herbivorous field vole (Microtus agrestis) as a heterospecific resource competitor, or with a conspecific resource competitor. We studied behavioural adaptations of vole mothers during pregnancy, parturition, and early lactation, specifically modifications of the burrow architecture and activity at burrow entrances. Further, we measured pre- and postpartum faecal corticosterone metabolites (FCMs) of mothers to test for elevated stress hormone levels. Only in the presence of the nest predator were prepartum FCMs elevated, but we found no loss of vole nestlings and no differences in nestling body weight in the presence of the nest predator or the heterospecific resource competitor. Although the presence of both the shrew and the field vole induced prepartum modifications to the burrow architecture, only nest predators caused an increase in vigilance time at burrow entrances during the sensitive nestling phase. Voles displayed an adequate behavioural response for both resource competitors and nest predators. They modified burrow architecture to improve nest guarding and increased their vigilance at burrow entrances to enhance offspring survival chances. Our study revealed differential behavioural adaptations to resource competitors and nest predators.

Differential behavioural and endocrine responses of common voles (Microtus arvalis) to nest predators and resource competitors

PubMed Central

2013-01-01

Background Adaptive behavioural strategies promoting co-occurrence of competing species are known to result from a sympatric evolutionary past. Strategies should be different for indirect resource competition (exploitation, e.g., foraging and avoidance behaviour) than for direct interspecific interference (e.g., aggression, vigilance, and nest guarding). We studied the effects of resource competition and nest predation in sympatric small mammal species using semi-fossorial voles and shrews, which prey on vole offspring during their sensitive nestling phase. Experiments were conducted in caged outdoor enclosures. Focus common vole mothers (Microtus arvalis) were either caged with a greater white-toothed shrew (Crocidura russula) as a potential nest predator, with an herbivorous field vole (Microtus agrestis) as a heterospecific resource competitor, or with a conspecific resource competitor. Results We studied behavioural adaptations of vole mothers during pregnancy, parturition, and early lactation, specifically modifications of the burrow architecture and activity at burrow entrances. Further, we measured pre- and postpartum faecal corticosterone metabolites (FCMs) of mothers to test for elevated stress hormone levels. Only in the presence of the nest predator were prepartum FCMs elevated, but we found no loss of vole nestlings and no differences in nestling body weight in the presence of the nest predator or the heterospecific resource competitor. Although the presence of both the shrew and the field vole induced prepartum modifications to the burrow architecture, only nest predators caused an increase in vigilance time at burrow entrances during the sensitive nestling phase. Conclusion Voles displayed an adequate behavioural response for both resource competitors and nest predators. They modified burrow architecture to improve nest guarding and increased their vigilance at burrow entrances to enhance offspring survival chances. Our study revealed differential behavioural adaptations to resource competitors and nest predators. PMID:24010574

Dietary modification of brain function: effects on neuroendocrine and psychological determinants of mental health- and stress-related disorders.

PubMed

Waladkhani, A R; Hellhammer, J

2008-01-01

Stress is associated with both psychological and biological adaptation. Chronic stress, however, impairs adaptation, and may finally lead to illness, in part through unhealthy changes in nutritional behavior. This chapter shows how physiological and psychological stress responses are affected by different food ingredients, and how stress affects health behavior, for example food choice. It becomes obvious that nutrition is closely linked to food choice and that food ingredients affect a broad range of neuroendocrine and related psychological processes, which regulate adaptation to chronic stress. Thus, dietary modification may become a valuable tool to modify the susceptibility to stress and stress-related disorders.

Length adaptation of airway smooth muscle.

PubMed

Bossé, Ynuk; Sobieszek, Apolinary; Paré, Peter D; Seow, Chun Y

2008-01-01

Many types of smooth muscle, including airway smooth muscle (ASM), are capable of generating maximal force over a large length range due to length adaptation, which is a relatively rapid process in which smooth muscle regains contractility after experiencing a force decrease induced by length fluctuation. Although the underlying mechanism is unclear, it is believed that structural malleability of smooth muscle cells is essential for the adaptation to occur. The process is triggered by strain on the cell cytoskeleton that results in a series of yet undefined biochemical and biophysical events leading to restructuring of the cytoskeleton and contractile apparatus and consequently optimization of the overlap between the myosin and actin filaments. Although length adaptability is an intrinsic property of smooth muscle, maladaptation of ASM could result in excessive constriction of the airways and the inability of deep inspirations to dilate them. In this article, we describe the phenomenon of length adaptation in ASM and some possible underlying mechanisms that involve the myosin filament assembly and disassembly. We discuss a possible role of maladaptation of ASM in the pathogenesis of asthma. We believe that length adaptation in ASM is mediated by specific proteins and their posttranslational regulations involving covalent modifications, such as phosphorylation. The discovery of these molecules and the processes that regulate their activity will greatly enhance our understanding of the basic mechanisms of ASM contraction and will suggest molecular targets to alleviate asthma exacerbation related to excessive constriction of the airways.

Sequence adaptations during growth of rescued classical swine fever viruses in cell culture and within infected pigs.

PubMed

Hadsbjerg, Johanne; Friis, Martin B; Fahnøe, Ulrik; Nielsen, Jens; Belsham, Graham J; Rasmussen, Thomas Bruun

2016-08-30

Classical swine fever virus (CSFV) causes an economically important disease of swine. Four different viruses were rescued from full-length cloned cDNAs derived from the Paderborn strain of CSFV. Three of these viruses had been modified by mutagenesis (with 7 or 8 nt changes) within stem 2 of the subdomain IIIf of the internal ribosome entry site (IRES) that directs the initiation of protein synthesis. Rescued viruses were inoculated into pigs. The rescued vPader10 virus, without modifications in the IRES, induced clinical disease in pigs that was very similar to that observed previously with the parental field strain and transmission to in-contact pigs occurred. Two sequence reversions, in the NS2 and NS5B coding regions, became dominant within the virus populations in these infected pigs. Rescued viruses, with mutant IRES elements, did not induce disease and only very limited circulation of viral RNA could be detected. However, the animals inoculated with these mutant viruses seroconverted against CSFV. Thus, these mutant viruses were highly attenuated in vivo. All 4 rescued viruses were also passaged up to 20 times in cell culture. Using full genome sequencing, the same two adaptations within each of four independent virus populations were observed that restored the coding sequence to that of the parental field strain. These adaptations occurred with different kinetics. The combination of reverse genetics and in depth, full genome sequencing provides a powerful approach to analyse virus adaptation and to identify key determinants of viral replication efficiency in cells and within host animals. Copyright © 2016 Elsevier B.V. All rights reserved.

Creating Online Training for Procedures in Global Health with PEARLS (Procedural Education for Adaptation to Resource-Limited Settings).

PubMed

Bensman, Rachel S; Slusher, Tina M; Butteris, Sabrina M; Pitt, Michael B; On Behalf Of The Sugar Pearls Investigators; Becker, Amanda; Desai, Brinda; George, Alisha; Hagen, Scott; Kiragu, Andrew; Johannsen, Ron; Miller, Kathleen; Rule, Amy; Webber, Sarah

2017-11-01

The authors describe a multiinstitutional collaborative project to address a gap in global health training by creating a free online platform to share a curriculum for performing procedures in resource-limited settings. This curriculum called PEARLS (Procedural Education for Adaptation to Resource-Limited Settings) consists of peer-reviewed instructional and demonstration videos describing modifications for performing common pediatric procedures in resource-limited settings. Adaptations range from the creation of a low-cost spacer for inhaled medications to a suction chamber for continued evacuation of a chest tube. By describing the collaborative process, we provide a model for educators in other fields to collate and disseminate procedural modifications adapted for their own specialty and location, ideally expanding this crowd-sourced curriculum to reach a wide audience of trainees and providers in global health.

Adaptations and Access to Assessment of Common Core Content

ERIC Educational Resources Information Center

Kettler, Ryan J.

2015-01-01

This chapter introduces theory that undergirds the role of testing adaptations in assessment, provides examples of item modifications and testing accommodations, reviews research relevant to each, and introduces a new paradigm that incorporates opportunity to learn (OTL), academic enablers, testing adaptations, and inferences that can be made from…

Improved Innate and Adaptive Immunostimulation by Genetically Modified HIV-1 Protein Expressing NYVAC Vectors

PubMed Central

Quakkelaar, Esther D.; Redeker, Anke; Haddad, Elias K.; Harari, Alexandre; McCaughey, Stella Mayo; Duhen, Thomas; Filali-Mouhim, Abdelali; Goulet, Jean-Philippe; Loof, Nikki M.; Ossendorp, Ferry; Perdiguero, Beatriz; Heinen, Paul; Gomez, Carmen E.; Kibler, Karen V.; Koelle, David M.; Sékaly, Rafick P.; Sallusto, Federica; Lanzavecchia, Antonio; Pantaleo, Giuseppe; Esteban, Mariano; Tartaglia, Jim; Jacobs, Bertram L.; Melief, Cornelis J. M.

2011-01-01

Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses in vitro from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells in vitro. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines. PMID:21347234

Head-group acylation of monogalactosyldiacylglycerol is a common stress response, but the acyl-galactose acyl composition varies with the plant species and applied stress

USDA-ARS?s Scientific Manuscript database

Head group acylation of monogalactosyldiacylglycerol is a plant lipid modification occurring during bacterial infection. Little is known about the range of stresses that induce this lipid modification, the molecular species induced, and the function of the modification. Lipidomic analysis using trip...

Bacterial Adaptation to Antibiotics through Regulatory RNAs.

PubMed

Felden, Brice; Cattoir, Vincent

2018-05-01

The extensive use of antibiotics has resulted in a situation where multidrug-resistant pathogens have become a severe menace to human health worldwide. A deeper understanding of the principles used by pathogens to adapt to, respond to, and resist antibiotics would pave the road to the discovery of drugs with novel mechanisms. For bacteria, antibiotics represent clinically relevant stresses that induce protective responses. The recent implication of regulatory RNAs (small RNAs [sRNAs]) in antibiotic response and resistance in several bacterial pathogens suggests that they should be considered innovative drug targets. This minireview discusses sRNA-mediated mechanisms exploited by bacterial pathogens to fight against antibiotics. A critical discussion of the newest findings in the field is provided, with emphasis on the implication of sRNAs in major mechanisms leading to antibiotic resistance, including drug uptake, active drug efflux, drug target modifications, biofilms, cell walls, and lipopolysaccharide (LPS) biosynthesis. Of interest is the lack of knowledge about sRNAs implicated in Gram-positive compared to Gram-negative bacterial resistance. Copyright © 2018 American Society for Microbiology.

Experience-Dependent Rewiring of Specific Inhibitory Connections in Adult Neocortex

PubMed Central

Kätzel, Dennis; Miesenböck, Gero

2014-01-01

Although neocortical connectivity is remarkably stereotyped, the abundance of some wiring motifs varies greatly between cortical areas. To examine if regional wiring differences represent functional adaptations, we have used optogenetic raster stimulation to map the laminar distribution of GABAergic interneurons providing inhibition to pyramidal cells in layer 2/3 (L2/3) of adult mouse barrel cortex during sensory deprivation and recovery. Whisker trimming caused large, motif-specific changes in inhibitory synaptic connectivity: ascending inhibition from deep layers 4 and 5 was attenuated to 20%–45% of baseline, whereas inhibition from superficial layers remained stable (L2/3) or increased moderately (L1). The principal mechanism of deprivation-induced plasticity was motif-specific changes in inhibitory-to-excitatory connection probabilities; the strengths of extant connections were left unaltered. Whisker regrowth restored the original balance of inhibition from deep and superficial layers. Targeted, reversible modifications of specific inhibitory wiring motifs thus contribute to the adaptive remodeling of cortical circuits. PMID:24586113

Mechanism of covalent modification of glyceraldehyde-3-phosphate dehydrogenase at its active site thiol by nitric oxide, peroxynitrite and related nitrosating agents.

PubMed

Mohr, S; Stamler, J S; Brüne, B

1994-07-18

Previous studies have suggested that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) undergoes covalent modification of an active site thiol by a NO.-induced [32P]NAD(+)-dependent mechanism. However, the efficacy of GAPDH modification induced by various NO donors was found to be independent of spontaneous rates of NO. release. To further test the validity of this mechanism, we studied the effects of nitrosonium tertrafluoroborate (BF4NO), a strong NO+ donor. BF4NO potently induces GAPDH labeling by the radioactive nucleotide. In this case, the addition of thiol significantly attenuates enzyme modification by competing for the NO moiety in the formation of RS-NO. Peroxynitrite (ONOO-) also induces GAPDH modification in the presence of thiol, consistent with the notion that this species can transfer NO+ (or NO2+) through the intermediacy of RS-NO. However, the efficiency of this reaction is limited by ONOO- -induced oxidation of protein SH groups at the active site. ONOO- generation appears to account for the modification of GAPDH by SIN-1. Thus, S-nitrosylation of the active site thiol is a prequisite for subsequent post-translational modification with NAD+, and emphasizes the role of NO+ transfer in the initial step of this pathway. Our findings thus provide a uniform mechanism by which nitric oxide and related NO donors initiate non-enzymatic ADP-ribosylation (like) reactions. In biological systems, endogenous RS-NO are likely to support the NO group transfer to thiol-containing proteins.

Plant natriuretic peptides induce proteins diagnostic for an adaptive response to stress.

PubMed

Turek, Ilona; Marondedze, Claudius; Wheeler, Janet I; Gehring, Chris; Irving, Helen R

2014-01-01

In plants, structural and physiological evidence has suggested the presence of biologically active natriuretic peptides (PNPs). PNPs are secreted into the apoplast, are systemically mobile and elicit a range of responses signaling via cGMP. The PNP-dependent responses include tissue specific modifications of cation transport and changes in stomatal conductance and the photosynthetic rate. PNP also has a critical role in host defense responses. Surprisingly, PNP-homologs are produced by several plant pathogens during host colonization suppressing host defense responses. Here we show that a synthetic peptide representing the biologically active fragment of the Arabidopsis thaliana PNP (AtPNP-A) induces the production of reactive oxygen species in suspension-cultured A. thaliana (Col-0) cells. To identify proteins whose expression changes in an AtPNP-A dependent manner, we undertook a quantitative proteomic approach, employing tandem mass tag (TMT) labeling, to reveal temporal responses of suspension-cultured cells to 1 nM and 10 pM PNP at two different time-points post-treatment. Both concentrations yield a distinct differential proteome signature. Since only the higher (1 nM) concentration induces a ROS response, we conclude that the proteome response at the lower concentration reflects a ROS independent response. Furthermore, treatment with 1 nM PNP results in an over-representation of the gene ontology (GO) terms "oxidation-reduction process," "translation" and "response to salt stress" and this is consistent with a role of AtPNP-A in the adaptation to environmental stress conditions.

Plant natriuretic peptides induce proteins diagnostic for an adaptive response to stress

PubMed Central

Turek, Ilona; Marondedze, Claudius; Wheeler, Janet I.; Gehring, Chris; Irving, Helen R.

2014-01-01

In plants, structural and physiological evidence has suggested the presence of biologically active natriuretic peptides (PNPs). PNPs are secreted into the apoplast, are systemically mobile and elicit a range of responses signaling via cGMP. The PNP-dependent responses include tissue specific modifications of cation transport and changes in stomatal conductance and the photosynthetic rate. PNP also has a critical role in host defense responses. Surprisingly, PNP-homologs are produced by several plant pathogens during host colonization suppressing host defense responses. Here we show that a synthetic peptide representing the biologically active fragment of the Arabidopsis thaliana PNP (AtPNP-A) induces the production of reactive oxygen species in suspension-cultured A. thaliana (Col-0) cells. To identify proteins whose expression changes in an AtPNP-A dependent manner, we undertook a quantitative proteomic approach, employing tandem mass tag (TMT) labeling, to reveal temporal responses of suspension-cultured cells to 1 nM and 10 pM PNP at two different time-points post-treatment. Both concentrations yield a distinct differential proteome signature. Since only the higher (1 nM) concentration induces a ROS response, we conclude that the proteome response at the lower concentration reflects a ROS independent response. Furthermore, treatment with 1 nM PNP results in an over-representation of the gene ontology (GO) terms “oxidation-reduction process,” “translation” and “response to salt stress” and this is consistent with a role of AtPNP-A in the adaptation to environmental stress conditions. PMID:25505478

Pilot Evaluation of Adaptive Control in Motion-Based Flight Simulator

NASA Technical Reports Server (NTRS)

Kaneshige, John T.; Campbell, Stefan Forrest

2009-01-01

The objective of this work is to assess the strengths, weaknesses, and robustness characteristics of several MRAC (Model-Reference Adaptive Control) based adaptive control technologies garnering interest from the community as a whole. To facilitate this, a control study using piloted and unpiloted simulations to evaluate sensitivities and handling qualities was conducted. The adaptive control technologies under consideration were ALR (Adaptive Loop Recovery), BLS (Bounded Linear Stability), Hybrid Adaptive Control, L1, OCM (Optimal Control Modification), PMRAC (Predictor-based MRAC), and traditional MRAC

Fatiguing contractions increase protein S-glutathionylation occupancy in mouse skeletal muscle.

PubMed

Kramer, Philip A; Duan, Jicheng; Gaffrey, Matthew J; Shukla, Anil K; Wang, Lu; Bammler, Theo K; Qian, Wei-Jun; Marcinek, David J

2018-05-23

Protein S-glutathionylation is an important reversible post-translational modification implicated in redox signaling. Oxidative modifications to protein thiols can alter the activity of metabolic enzymes, transcription factors, kinases, phosphatases, and the function of contractile proteins. However, the extent to which muscle contraction induces oxidative modifications in redox sensitive thiols is not known. The purpose of this study was to determine the targets of S-glutathionylation redox signaling following fatiguing contractions. Anesthetized adult male CB6F1 (BALB/cBy × C57BL/6) mice were subjected to acute fatiguing contractions for 15 min using in vivo stimulations. The right (stimulated) and left (unstimulated) gastrocnemius muscleswere collected 60 min after the last stimulation and processed for redox proteomics assay of S-glutathionylation. Using selective reduction with a glutaredoxin enzyme cocktail and resin-assisted enrichment technique, we quantified the levels of site-specific protein S-glutathionylation at rest and following fatiguing contractions. Redox proteomics revealed over 2200 sites of S-glutathionylation modifications, of which 1290 were significantly increased after fatiguing contractions. Muscle contraction leads to the greatest increase in S-glutathionylation in the mitochondria (1.03%) and the smallest increase in the nucleus (0.47%). Regulatory cysteines were significantly S-glutathionylated on mitochondrial complex I and II, GAPDH, MDH1, ACO2, and mitochondrial complex V among others. Similarly, S-glutathionylation of RYR1, SERCA1, titin, and troponin I2 are known to regulate muscle contractility and were significantly S-glutathionylated after just 15 min of fatiguing contractions. The largest fold changes (> 1.6) in the S-glutathionylated proteome after fatigue occurred on signaling proteins such as 14-3-3 protein gamma and MAP2K4, as well as proteins like SERCA1, and NDUV2 of mitochondrial complex I, at previously unknown glutathionylation sites. These findings highlight the important role of redox control over muscle physiology, metabolism, and the exercise adaptive response. This study lays the groundwork for future investigation into the altered exercise adaptation associated with chronic conditions, such as sarcopenia. Copyright © 2018. Published by Elsevier B.V.

Xenopus laevis - A success story in biological research in Space

NASA Astrophysics Data System (ADS)

Horn, E.

A feature of sensory, neuronal and motor systems is the existence of a critical period during their development. Environmental modifications, in particular stimulus depri-vation, during this period of life affects development in a long-term manner. For gravity sensory systems, space flights offer the only opportunity for deprivation conditions. Studies in the amphibian Xenopus laevis presented the most complete picture. The presentation demonstrates the importance of Xenopus laevis as an ex-perimental model animal in the past and even for future research in Space. Studies are presented which range from fertilization in Space and anatomical studies during early development under weightlessness up to post-flight studies on the anatomy of the peripheral sense organ, the spinal motor activity and behavior. Gravity depriva-tion induces anatomical as well as behavioral and neurophysiological modifications, which are normalized either during flight (thickening of the blastocoel roof) or after reentry in 1g-conditions (swimming and reflex behavior, spinal motor activity). The physiological changes can be explained by mechanisms of physiological adaptation. However, the studies also revealed stages which were insensitive to gravity depriva-tion; they point to the existence of a critical period. Observations on morphological mal-formations are described which are reversible after termination of microgravity and which are linked to a depression of vestibular reflex behavior. They might be caused by a competition between dorsalization and ventralization inducing growth factors. This observation offers the possibility for a genetic approach in finding ba-sics for microgravity effects on the development of Xenopus, and in a general frame, on the development of vertebrates including men. At the present stage of research, it remains open whether adaptive processes during exposure to altered gravity or the existence of a critical period in vestibular development are responsible for develop-mental modifications observed during and after exposure to altered gravity. Also extensive hypergravity studies on the vestibuloocular reflex didn't contribute to a clarification between these alternatives. Thus both deprivation and augmentation studies have to be extended to older tadpole stages and longer exposure periods. The necessary hardware was developed recently. However, the most important depriva-tion approach is limited due to the too low number of space flights. Supported by DLR, grants 01QV89250-5, 50WB9553-7, 50WB0140 and by DFG, grants Ho664/16-1

Cell-type-specific profiling of protein-DNA interactions without cell isolation using targeted DamID with next-generation sequencing.

PubMed

Marshall, Owen J; Southall, Tony D; Cheetham, Seth W; Brand, Andrea H

2016-09-01

This protocol is an extension to: Nat. Protoc. 2, 1467-1478 (2007); doi:10.1038/nprot.2007.148; published online 7 June 2007The ability to profile transcription and chromatin binding in a cell-type-specific manner is a powerful aid to understanding cell-fate specification and cellular function in multicellular organisms. We recently developed targeted DamID (TaDa) to enable genome-wide, cell-type-specific profiling of DNA- and chromatin-binding proteins in vivo without cell isolation. As a protocol extension, this article describes substantial modifications to an existing protocol, and it offers additional applications. TaDa builds upon DamID, a technique for detecting genome-wide DNA-binding profiles of proteins, by coupling it with the GAL4 system in Drosophila to enable both temporal and spatial resolution. TaDa ensures that Dam-fusion proteins are expressed at very low levels, thus avoiding toxicity and potential artifacts from overexpression. The modifications to the core DamID technique presented here also increase the speed of sample processing and throughput, and adapt the method to next-generation sequencing technology. TaDa is robust, reproducible and highly sensitive. Compared with other methods for cell-type-specific profiling, the technique requires no cell-sorting, cross-linking or antisera, and binding profiles can be generated from as few as 10,000 total induced cells. By profiling the genome-wide binding of RNA polymerase II (Pol II), TaDa can also identify transcribed genes in a cell-type-specific manner. Here we describe a detailed protocol for carrying out TaDa experiments and preparing the material for next-generation sequencing. Although we developed TaDa in Drosophila, it should be easily adapted to other organisms with an inducible expression system. Once transgenic animals are obtained, the entire experimental procedure-from collecting tissue samples to generating sequencing libraries-can be accomplished within 5 d.

Quantitative-phase microscopy of nanosecond laser-induced micro-modifications inside silicon.

PubMed

Li, Q; Chambonneau, M; Chanal, M; Grojo, D

2016-11-20

Laser-induced permanent modification inside silicon has been recently demonstrated by using tightly focused nanosecond sources at a 1550 nm wavelength. We have developed a quantitative-phase microscope operating in the near-infrared domain to characterize the laser-induced modifications deep into silicon. By varying the number of applied laser pulses and the energy, we observe porous and densified regions in the focal region. The observed changes are associated with refractive index variations |Δn| exceeding 10^-3, enough to envision the laser writing of optical functionalities inside silicon.

Methylphenidate administration determines enduring changes in neuroglial network in rats.

PubMed

Cavaliere, Carlo; Cirillo, Giovanni; Bianco, Maria Rosaria; Adriani, Walter; De Simone, Antonietta; Leo, Damiana; Perrone-Capano, Carla; Papa, Michele

2012-01-01

Repeated exposure to psychostimulant drugs induces complex molecular and structural modifications in discrete brain regions of the meso-cortico-limbic system. This structural remodeling is thought to underlie neurobehavioral adaptive responses. Administration to adolescent rats of methylphenidate (MPH), commonly used in attention deficit and hyperactivity disorder (ADHD), triggers alterations of reward-based behavior paralleled by persistent and plastic synaptic changes of neuronal and glial markers within key areas of the reward circuits. By immunohistochemistry, we observe a marked increase of glial fibrillary acidic protein (GFAP) and neuronal nitric oxide synthase (nNOS) expression and a down-regulation of glial glutamate transporter GLAST in dorso-lateral and ventro-medial striatum. Using electron microscopy, we find in the prefrontal cortex a significant reduction of the synaptic active zone length, paralleled by an increase of dendritic spines. We demonstrate that in limbic areas the MPH-induced reactive astrocytosis affects the glial glutamatergic uptake system that in turn could determine glutamate receptor sensitization. These processes could be sustained by NO production and synaptic rearrangement and contribute to MPH neuroglial induced rewiring. Copyright © 2011. Published by Elsevier B.V.

A quick and efficient method to generate mammalian stable cell lines based on a novel inducible alphavirus DNA/RNA layered system.

PubMed

Aranda, Alejandro; Bezunartea, Jaione; Casales, Erkuden; Rodriguez-Madoz, Juan R; Larrea, Esther; Prieto, Jesus; Smerdou, Cristian

2014-12-01

We report a new method to generate high-expressing mammalian cell lines in a quick and efficient way. For that purpose, we developed a master cell line (MCL) containing an inducible alphavirus vector expressing GFP integrated into the genome. In the MCL, recombinant RNA levels increased >4,600-fold after induction, due to a doxycycline-dependent RNA amplification loop. The MCL maintained inducibility and expression during 50 passages, being more efficient for protein expression than a conventional cell line. To generate new cell lines, mutant LoxP sites were inserted into the MCL, allowing transgene and selection gene exchange by Cre-directed recombination, leading to quick generation of inducible cell lines expressing proteins of therapeutic interest, like human cardiotrophin-1 and oncostatin-M at several mg/l/24 h. These proteins contained posttranslational modifications, showed bioactivity, and were efficiently purified. Remarkably, this system allowed production of toxic proteins, like oncostatin-M, since cells able to express it could be grown to the desired amount before induction. These cell lines were easily adapted to growth in suspension, making this methodology very attractive for therapeutic protein production.

The Best of Practical Pointers.

ERIC Educational Resources Information Center

Association for Research, Administration, Professional Councils & Societies, Reston, VA.

This publication is a compilation of monographs offering practical suggestions for teachers of adapted physical education. It contains numerous suggestions on teaching techniques, activity adaptations, equipment modifications, programming information, coaching hints, skill development strategies, and curriculum data. The five sections offer…

Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. IV. Responses after spectacle-induced adaptation

NASA Technical Reports Server (NTRS)

Clendaniel, R. A.; Lasker, D. M.; Minor, L. B.; Shelhamer, M. J. (Principal Investigator)

2001-01-01

The horizontal angular vestibuloocular reflex (VOR) evoked by sinusoidal rotations from 0.5 to 15 Hz and acceleration steps up to 3,000 degrees /s(2) to 150 degrees /s was studied in six squirrel monkeys following adaptation with x2.2 magnifying and x0.45 minimizing spectacles. For sinusoidal rotations with peak velocities of 20 degrees /s, there were significant changes in gain at all frequencies; however, the greatest gain changes occurred at the lower frequencies. The frequency- and velocity-dependent gain enhancement seen in normal monkeys was accentuated following adaptation to magnifying spectacles and diminished with adaptation to minimizing spectacles. A differential increase in gain for the steps of acceleration was noted after adaptation to the magnifying spectacles. The gain during the acceleration portion, G(A), of a step of acceleration (3,000 degrees /s(2) to 150 degrees /s) increased from preadaptation values of 1.05 +/- 0.08 to 1.96 +/- 0.16, while the gain during the velocity plateau, G(V), only increased from 0.93 +/- 0.04 to 1.36 +/- 0.08. Polynomial fits to the trajectory of the response during the acceleration step revealed a greater increase in the cubic than the linear term following adaptation with the magnifying lenses. Following adaptation to the minimizing lenses, the value of G(A) decreased to 0.61 +/- 0.08, and the value of G(V) decreased to 0.59 +/- 0.09 for the 3,000 degrees /s(2) steps of acceleration. Polynomial fits to the trajectory of the response during the acceleration step revealed that there was a significantly greater reduction in the cubic term than in the linear term following adaptation with the minimizing lenses. These findings indicate that there is greater modification of the nonlinear as compared with the linear component of the VOR with spectacle-induced adaptation. In addition, the latency to the onset of the adapted response varied with the dynamics of the stimulus. The findings were modeled with a bilateral model of the VOR containing linear and nonlinear pathways that describe the normal behavior and adaptive processes. Adaptation for the linear pathway is described by a transfer function that shows the dependence of adaptation on the frequency of the head movement. The adaptive process for the nonlinear pathway is a gain enhancement element that provides for the accentuated gain with rising head velocity and the increased cubic component of the responses to steps of acceleration. While this model is substantially different from earlier models of VOR adaptation, it accounts for the data in the present experiments and also predicts the findings observed in the earlier studies.

Therapeutic home adaptations for older adults with disabilities.

PubMed

Unwin, Brian K; Andrews, Christopher M; Andrews, Patrick M; Hanson, Janice L

2009-11-01

Family physicians commonly care for older patients with disabilities. Many of these patients need help maintaining a therapeutic home environment to preserve their comfort and independence. Patients often have little time to decide how to address the limitations of newly-acquired disabilities. Physicians can provide patients with general recommendations in home modification after careful history and assessment. Universal design features, such as one-story living, no-step entries, and wide hallways and doors, are key adaptations for patients with physical disabilities. Home adaptations for patients with dementia include general safety measures such as grab bars and door alarms, and securing potentially hazardous items, such as cleaning supplies and medications. Improved lighting and color contrast, enlarged print materials, and vision aids can assist patients with limited vision. Patients with hearing impairments may benefit from interventions that provide supplemental visual and vibratory cues and alarms. Although funding sources are available, home modification is often a nonreimbursed expense. However, sufficient home modifications may allow the patient and caregivers to safely remain in the home without transitioning to a long-term care facility.

Alteration of human serum albumin binding properties induced by modifications: A review

NASA Astrophysics Data System (ADS)

Maciążek-Jurczyk, Małgorzata; Szkudlarek, Agnieszka; Chudzik, Mariola; Pożycka, Jadwiga; Sułkowska, Anna

2018-01-01

Albumin, a major transporting protein in the blood, is the main target of modification that affects the binding of drugs to Sudlow's site I and II. These modification of serum protein moderates its physiological function, and works as a biomarker of some diseases. The main goal of the paper was to explain the possible alteration of human serum albumin binding properties induced by modifications such as glycation, oxidation and ageing, their origin, methods of evaluation and positive and negative meaning described by significant researchers.

Metabolic markers in sports medicine.

PubMed

Banfi, Giuseppe; Colombini, Alessandra; Lombardi, Giovanni; Lubkowska, Anna

2012-01-01

Physical exercise induces adaptations in metabolism considered beneficial for health. Athletic performance is linked to adaptations, training, and correct nutrition in individuals with genetic traits that can facilitate such adaptations. Intense and continuous exercise, training, and competitions, however, can induce changes in the serum concentrations of numerous laboratory parameters. When these modifications, especially elevated laboratory levels, result outside the reference range, further examinations are ordered or participation in training and competition is discontinued or sports practice loses its appeal. In order to correctly interpret commonly used laboratory data, laboratory professionals and sport physicians need to know the behavior of laboratory parameters during and after practice and competition. We reviewed the literature on liver, kidney, muscle, heart, energy, and bone parameters in athletes with a view to increase the knowledge about clinical chemistry applied to sport and to stimulate studies in this field. In liver metabolism, the interpretation of serum aminotransferases concentration in athletes should consider the release of aspartate aminotransferase (AST) from muscle and of alanine aminotransferase (ALT) mainly from the liver, when bilirubin can be elevated because of continuous hemolysis, which is typical of exercise. Muscle metabolism parameters such as creatine kinase (CK) are typically increased after exercise. This parameter can be used to interpret the physiological release of CK from muscle, its altered release due to rhabdomyolysis, or incomplete recovery due to overreaching or trauma. Cardiac markers are released during exercise, and especially endurance training. Increases in these markers should not simply be interpreted as a signal of cardiac damage or wall stress but rather as a sign of regulation of myocardial adaptation. Renal function can be followed in athletes by measuring serum creatinine concentration, but it should be interpreted considering the athlete's body-mass index (BMI) and phase of the competitive season; use of cystatin C could be a reliable alternative to creatinine. Exercise and training induce adaptations in glucose metabolism which improve glucose utilization in athletes and are beneficial for reducing insulin insensitivity in nonathletes. Glucose metabolism differs slightly for different sports disciplines, as revealed in laboratory levels. Sport activities induce a blood lipid profile superior to that of sedentary subjects. There are few reports for a definitive conclusion, however. The differences between athletes and sedentary subjects are mainly due to high-density lipoprotein cholesterol (HDLC) concentrations in physically active individuals, although some differences among sport disciplines exist. The effect of sports on serum and urinary markers for bone metabolism is not univocal; further studies are needed to establish the real and effective influence of sport on bone turnover and especially to establish its beneficial effect.

Reducing the oxygen concentration of gases delivered from anaesthetic machines unadapted for medical air

PubMed Central

Clutton, R. E.; Schoeffmann, G.; Chesnil, M.; Gregson, R.; Reed, F.; Lawson, H.; Eddleston, M.

2014-01-01

High fractional concentrations of inspired oxygen (FiO2) delivered over prolonged periods produce characteristic histological changes in the lungs and airway of exposed animals. Modern medical anaesthetic machines are adapted to deliver medical air (FiO2=0.21) for the purpose of reducing FiO2; anaesthetic machines designed for the veterinary market have not been so adapted. Two inexpensive modifications that allow medical air to be added to the gas flow from veterinary anaesthetic machines are described. The advantages and disadvantages of each modification are discussed. PMID:21862470

Direct model reference adaptive control with application to flexible robots

NASA Technical Reports Server (NTRS)

Steinvorth, Rodrigo; Kaufman, Howard; Neat, Gregory W.

1992-01-01

A modification to a direct command generator tracker-based model reference adaptive control (MRAC) system is suggested in this paper. This modification incorporates a feedforward into the reference model's output as well as the plant's output. Its purpose is to eliminate the bounded model following error present in steady state when previous MRAC systems were used. The algorithm was evaluated using the dynamics for a single-link flexible-joint arm. The results of these simulations show a response with zero steady state model following error. These results encourage further use of MRAC for various types of nonlinear plants.

MRAC Revisited: Guaranteed Performance with Reference Model Modification

NASA Technical Reports Server (NTRS)

Stepanyan, Vahram; Krishnakumar, Kalmaje

2010-01-01

This paper presents modification of the conventional model reference adaptive control (MRAC) architecture in order to achieve guaranteed transient performance both in the output and input signals of an uncertain system. The proposed modification is based on the tracking error feedback to the reference model. It is shown that approach guarantees tracking of a given command and the ideal control signal (one that would be designed if the system were known) not only asymptotically but also in transient by a proper selection of the error feedback gain. The method prevents generation of high frequency oscillations that are unavoidable in conventional MRAC systems for large adaptation rates. The provided design guideline makes it possible to track a reference command of any magnitude form any initial position without re-tuning. The benefits of the method are demonstrated in simulations.

tRNA wobble modifications and protein homeostasis

PubMed Central

Ranjan, Namit; Rodnina, Marina V.

2016-01-01

Abstract tRNA is a central component of the protein synthesis machinery in the cell. In living cells, tRNAs undergo numerous post-transcriptional modifications. In particular, modifications at the anticodon loop play an important role in ensuring efficient protein synthesis, maintaining protein homeostasis, and helping cell adaptation and survival. Hypo-modification of the wobble position of the tRNA anticodon loop is of particular relevance for translation regulation and is implicated in various human diseases. In this review we summarize recent evidence of how methyl and thiol modifications in eukaryotic tRNA at position 34 affect cellular fitness and modulate regulatory circuits at normal conditions and under stress. PMID:27335723

Mediational Modification of Creative Behaviors.

ERIC Educational Resources Information Center

Russell, Crawford L.

1981-01-01

Adapting the cognitive behavior modification work of Bandura and Mahoney, the author suggests a "mediational approach" to teaching creativity in the art classroom; here the desired behavior is modeled, guided experience is offered for practice, then reward in the form of approval is given for successful completion of the event. (Editor/SJL)

Mainstreaming: Sharing Ideas, Strategies, Materials, Techniques.

ERIC Educational Resources Information Center

Hillside School, Cushing, OK.

The manual provides teaching approaches based on a model of least to highest modification of instruction, which may be used for a continuum of special education placements ranging from regular classroom through hospital settings. The first section on adaptive techniques (requiring the least modification) includes suggestions to adjust time for…

Modification of plasma membrane proton pumps in cucumber roots as an adaptation mechanism to salt stress.

PubMed

Janicka-Russak, Małgorzata; Kabała, Katarzyna; Wdowikowska, Anna; Kłobus, Grażyna

2013-07-01

The effect of salt stress (50mM NaCl) on modification of plasma membrane (PM) H(+)-ATPase (EC 3.6.3.14) activity in cucumber roots was studied. Plants were grown under salt stress for 1, 3 or 6 days. In salt-stressed plants, weak stimulation of ATP hydrolytic activity of PM H(+)-ATPase and significant stimulation of proton transport through the plasma membrane were observed. The H(+)/ATP coupling ratio in the plasma membrane of plants subjected to salt stress significantly increased. The greatest stimulation of PM H(+)-ATPase was in 6-day stressed plants. Increased H2O2 accumulation under salt stress conditions in cucumber roots was also observed, with the greatest accumulation observed in 6-day stressed plants. Additionally, during the sixth day of salinity, there appeared heat shock proteins (HSPs) 17.7 and 101, suggesting that repair processes and adaptation to stress occurred in plants. Under salt stress conditions, fast post-translational modifications took place. Protein blot analysis with antibody against phosphothreonine and 14-3-3 proteins showed that, under salinity, the level of those elements increased. Additionally, under salt stress, activity changes of PM H(+)-ATPase can partly result from changes in the pattern of expression of PM H(+)-ATPase genes. In cucumber seedlings, there was increased expression of CsHA10 under salt stress and the transcript of a new PM H(+)-ATPase gene isoform, CsHA1, also appeared. Accumulation of the CsHA1 transcript was induced by NaCl exposure, and was not expressed at detectable levels in roots of control plants. The appearance of a new PM H(+)-ATPase transcript, in addition to the increase in enzyme activity, indicates the important role of the enzyme in maintaining ion homeostasis in plants under salt stress. Copyright © 2013 Elsevier GmbH. All rights reserved.

Personal cooling air filtering device

DOEpatents

Klett, James [Knoxville, TN; Conway, Bret [Denver, NC

2002-08-13

A temperature modification system for modifying the temperature of fluids includes at least one thermally conductive carbon foam element, the carbon foam element having at least one flow channel for the passage of fluids. At least one temperature modification device is provided, the temperature modification device thermally connected to the carbon foam element and adapted to modify the temperature of the carbon foam to modify the temperature of fluids flowing through the flow channels. Thermoelectric and/or thermoionic elements can preferably be used as the temperature modification device. A method for the reversible temperature modification of fluids includes the steps of providing a temperature modification system including at least one thermally conductive carbon foam element having flow channels and at least one temperature modification device, and flowing a fluid through the flow channels.

Mass spectrometry-based carboxyl footprinting of proteins: Method evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Hao; Wen, Jianzhong; Huang, Richard Y-C.

2012-02-01

Protein structure determines function in biology, and a variety of approaches have been employed to obtain structural information about proteins. Mass spectrometry-based protein footprinting is one fast-growing approach. One labeling-based footprinting approach is the use of a water-soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and glycine ethyl ester (GEE) to modify solvent-accessible carboxyl groups on glutamate (E) and aspartate (D). This paper describes method development of carboxyl-group modification in protein footprinting. The modification protocol was evaluated by using the protein calmodulin as a model. Because carboxyl-group modification is a slow reaction relative to protein folding and unfolding, there is an issue that modificationsmore » at certain sites may induce protein unfolding and lead to additional modification at sites that are not solvent-accessible in the wild-type protein. We investigated this possibility by using hydrogen deuterium amide exchange (H/DX). The study demonstrated that application of carboxyl group modification in probing conformational changes in calmodulin induced by Ca{sup 2+} binding provides useful information that is not compromised by modification-induced protein unfolding.« less

Adaptive arrays for satellite communications

NASA Technical Reports Server (NTRS)

Gupta, I. J.; Ksienski, A. A.

1984-01-01

The suppression of interfering signals in a satellite communication system was studied. Adaptive arrays are used to suppress interference at the reception site. It is required that the interference be suppressed to very low levels and a modified adaptive circuit is used which accomplishes the desired objective. Techniques for the modification of the transmit patterns to minimize interference with neighboring communication links are explored.

Ph.D. and Ed.D. Program Adaptations for College Teachers.

ERIC Educational Resources Information Center

Dressel, Paul L.; Guiste, Evelyn B.

The extent to which the Ph.D. and/or Ed.D. programs have been adapted to assist in preparing students for college teaching was surveyed. Of 309 universities, 122 responded, and of these, 72 had no adaptations. However, 50 universities indicated the availability, in at least one discipline or field, of modifications in the Ph.D. and/or Ed.D.…

Mudskippers and Their Genetic Adaptations to an Amphibious Lifestyle

PubMed Central

You, Xinxin; Sun, Min; Li, Jia; Bian, Chao; Chen, Jieming; Yu, Hui; Shi, Qiong

2018-01-01

Simple Summary Mudskippers are an interesting group of goggle-eyed amphibious fish that can live both in water and on land. They are a useful model for obtaining insights into the genetic mechanisms underlying the terrestrial adaptations of amphibious fish. This review summarizes the morphological and physiological modifications of representative mudskippers, and focuses on the recent advancement of genomic studies on their genetic adaptations to the amphibious lifestyle. Abstract Mudskippers are the largest group of amphibious teleost fish that are uniquely adapted to live on mudflats. During their successful transition from aqueous life to terrestrial living, these fish have evolved morphological and physiological modifications of aerial vision and olfaction, higher ammonia tolerance, aerial respiration, improved immunological defense against terrestrial pathogens, and terrestrial locomotion using protruded pectoral fins. Comparative genomic and transcriptomic data have been accumulated and analyzed for understanding molecular mechanisms of the terrestrial adaptations. Our current review provides a general introduction to mudskippers and recent research advances of their genetic adaptations to the amphibious lifestyle, which will be helpful for understanding the evolutionary transition of vertebrates from water to land. Our insights into the genomes and transcriptomes will also support molecular breeding, functional identification, and natural compound screening. PMID:29414871

Concise review: managing genotoxicity in the therapeutic modification of stem cells.

PubMed

Baum, Christopher; Modlich, Ute; Göhring, Gudrun; Schlegelberger, Brigitte

2011-10-01

The therapeutic use of procedures for genetic stem cell modification is limited by potential adverse events related to uncontrolled mutagenesis. Prominent findings have been made in hematopoietic gene therapy, demonstrating the risk of clonal, potentially malignant outgrowth on the basis of mutations acquired during or after therapeutic genome modification. The incidence and the growth rate of insertional mutants have been linked to the "stemness" of the target cells and vector-related features such as the integration pattern, the architecture, and the exact content of transgene cassettes. Milieu factors supporting the survival and expansion of mutants may eventually allow oncogenic progression. Similar concerns apply for medicinal products based on pluripotent stem cells. Focusing on the genetic stress induced by insertional mutagenesis and culture adaptation, we propose four conclusions. (a) Mutations occurring in the production of stem cell-based medicines may be unavoidable and need to be classified according to their risk to trigger the formation of clones that are sufficiently long-lived and mitotically active to acquire secondary transforming mutations. (b) The development of rational prevention strategies depends upon the identification of the specific mutations forming such "dominant clones" (which can also be addressed as cancer stem cell precursors) and a better knowledge of the mechanisms underlying their creation, expansion, and homeostatic control. (c) Quantitative assay systems are required to assess the practical value of preventive actions. (d) Improved approaches for the genetic modification of stem cells can address all critical steps in the origin and growth control of mutants. Copyright © 2011 AlphaMed Press.

Environmental chemical exposures and human epigenetics

PubMed Central

Hou, Lifang; Zhang, Xiao; Wang, Dong; Baccarelli, Andrea

2012-01-01

Every year more than 13 million deaths worldwide are due to environmental pollutants, and approximately 24% of diseases are caused by environmental exposures that might be averted through preventive measures. Rapidly growing evidence has linked environmental pollutants with epigenetic variations, including changes in DNA methylation, histone modifications and microRNAs. Environ mental chemicals and epigenetic changes All of these mechanisms are likely to play important roles in disease aetiology, and their modifications due to environmental pollutants might provide further understanding of disease aetiology, as well as biomarkers reflecting exposures to environmental pollutants and/or predicting the risk of future disease. We summarize the findings on epigenetic alterations related to environmental chemical exposures, and propose mechanisms of action by means of which the exposures may cause such epigenetic changes. We discuss opportunities, challenges and future directions for future epidemiology research in environmental epigenomics. Future investigations are needed to solve methodological and practical challenges, including uncertainties about stability over time of epigenomic changes induced by the environment, tissue specificity of epigenetic alterations, validation of laboratory methods, and adaptation of bioinformatic and biostatistical methods to high-throughput epigenomics. In addition, there are numerous reports of epigenetic modifications arising following exposure to environmental toxicants, but most have not been directly linked to disease endpoints. To complete our discussion, we also briefly summarize the diseases that have been linked to environmental chemicals-related epigenetic changes. PMID:22253299

Long-term exposure of rapeseed (Brassica napus L.) to ZnO nanoparticles: anatomical and ultrastructural responses.

PubMed

Mousavi Kouhi, Seyed Mousa; Lahouti, Mehrdad; Ganjeali, Ali; Entezari, Mohammad H

2015-07-01

Rapid development of nanotechnology in recent years has raised concerns about nanoparticle (NPs) release into the environment and its adverse effects on living organisms. The present study is the first comprehensive report on the anatomical and ultrastructural changes of a variety of cells after long-term exposure of plant to NPs or bulk material particles (BPs). Light and electron microscopy revealed some anatomical and ultrastructural modifications of the different types of cell in the root and leaf, induced by both types of treatment. Zinc oxide (ZnO) BPs-induced modifications were surprisingly more than those induced by ZnO NPs. The modifications induced by ZnO BPs or ZnO NPs were almost similar to those induced by excess Zn. Zn content of the root and leaf of both ZnO NPs- and ZnO BPs-treated plants was severely increased, where the increase was greater in the plants treated with ZnO BPs. Overall, these results indicate that the modifications induced by ZnO particles can be attributed, at least partly, to the Zn(2+) dissolution by ZnO particles rather than their absorption by root and their subsequent effects.

An Unorthodox Sensory Adaptation Site in the Escherichia coli Serine Chemoreceptor

PubMed Central

Han, Xue-Sheng

2014-01-01

The serine chemoreceptor of Escherichia coli contains four canonical methylation sites for sensory adaptation that lie near intersubunit helix interfaces of the Tsr homodimer. An unexplored fifth methylation site, E502, lies at an intrasubunit helix interface closest to the HAMP domain that controls input-output signaling in methyl-accepting chemotaxis proteins. We analyzed, with in vivo Förster resonance energy transfer (FRET) kinase assays, the serine thresholds and response cooperativities of Tsr receptors with different mutationally imposed modifications at sites 1 to 4 and/or at site 5. Tsr variants carrying E or Q at residue 502, in combination with unmodifiable D and N replacements at adaptation sites 1 to 4, underwent both methylation and demethylation/deamidation, although detection of the latter modifications required elevated intracellular levels of CheB. These Tsr variants could not mediate a chemotactic response to serine spatial gradients, demonstrating that adaptational modifications at E502 alone are not sufficient for Tsr function. Moreover, E502 is not critical for Tsr function, because only two amino acid replacements at this residue abrogated serine chemotaxis: Tsr-E502P had extreme kinase-off output and Tsr-E502I had extreme kinase-on output. These large threshold shifts are probably due to the unique HAMP-proximal location of methylation site 5. However, a methylation-mimicking glutamine at any Tsr modification site raised the serine response threshold, suggesting that all sites influence signaling by the same general mechanism, presumably through changes in packing stability of the methylation helix bundle. These findings are consistent with control of input-output signaling in Tsr through dynamic interplay of the structural stabilities of the HAMP and methylation bundles. PMID:24272777

Cognitive Control and Conflict Adaptation in Youth with High-Functioning Autism

ERIC Educational Resources Information Center

Larson, Michael J.; South, Mikle; Clayson, Peter E.; Clawson, Ann

2012-01-01

Background: Youth diagnosed with autism spectrum disorders (ASD) often show deficits in cognitive control processes, potentially contributing to characteristic difficulties monitoring and regulating behavior. Modification of performance following conflict can be measured by examining conflict adaptation, the adjustment of cognitive resources based…

Electric-field-induced modification in Curie temperature of Co monolayer on Pt(111)

NASA Astrophysics Data System (ADS)

Nakamura, Kohji; Oba, Mikito; Akiyama, Toru; Ito, Tomonori; Weinert, Michael

2015-03-01

Magnetism induced by an external electric field (E-field) has received much attention as a potential approach for controlling magnetism at the nano-scale with the promise of ultra-low energy power consumption. Here, the E-field-induced modification of the Curie temperature for a prototypical transition-metal thin layer of a Co monolayer on Pt(111) is investigated by first-principles calculations by using the full-potential linearized augmented plane wave method that treats spin-spiral structures in an E-field. An applied E-field modifies the magnon (spin-spiral formation) energies by a few meV, which leads to a modification of the exchange pair interaction parameters within the classical Heisenberg model. With inclusion of the spin-orbit coupling (SOC), the magnetocrystalline anisotropy and the Dzyaloshinskii-Morita interaction are obtained by the second variation SOC method. An E-field-induced modification of the Curie temperature is demonstrated by Monte Carlo simulations, in which a change in the exchange interaction is found to play a key role.

Final Environmental Impact Statement Establishment and Operation of an Intelligence, Surveillance, Reconnaissance, and Strike Capability Andersen Air Force Base, Guam

DTIC Science & Technology

2007-01-01

Mariana Fruit Bat Pup Recruitment at Pati Point Colony; • Brown Tree Snake Interdiction and Control; and • Adaptive Management and Ground Track...establishment of a mitigation monitoring plan and adaptive management program. FUTURE ACTIONS As discussed in the Final EIS, the Air Force recognizes that...would initiate modifications to aircraft ground tracks and profiles over sensitive areas through an adaptive management strategy. This adaptive

Modification of the Nominal Group Activity for On-Line Instruction.

ERIC Educational Resources Information Center

Maulding, Wanda S.

This paper discusses how the Nominal Group Technique (NGT) can be adapted for use in online instruction. The four basic stages of the NGT (listing, recording, collating, and prioritizing) are described, and modifications for online delivery are detailed, including: (1) the instructor posts the Socratic question or problem to be posed; (2) students…

Older Adults' Opinions on Fall Prevention in Relation to Physical Activity Level.

PubMed

Tuvemo Johnson, Susanna; Martin, Cathrin; Anens, Elisabeth; Johansson, Ann-Christin; Hellström, Karin

2018-01-01

The purpose of this study was to explore and describe older adults' opinions regarding actions to prevent falls and to analyze differences in the opinions of highly versus less physically active older adults. An open-ended question was answered by 262 individuals aged 75 to 98 years living in the community. The answers were analyzed using qualitative content analysis, and differences in the categories were compared between highly and less physically active persons. Physical activity was measured according to a five-level scale. The content analysis resulted in eight categories: assistive devices, avoiding hazards, behavioral adaptive strategies, being physically active, healthy lifestyle, indoor modifications, outdoor modifications, and seeking assistance. Behavioral adaptive strategies were mentioned to a greater extent by highly active people, and indoor modifications were more often mentioned by less active older adults. Support for active self-directed behavioral strategies might be important for fall prevention among less physically active older adults.

Synergistic Modification Induced Specific Recognition between Histone and TRIM24 via Fluctuation Correlation Network Analysis

NASA Astrophysics Data System (ADS)

Zhang, Jinmai; Luo, Huajie; Liu, Hao; Ye, Wei; Luo, Ray; Chen, Hai-Feng

2016-04-01

Histone modification plays a key role in gene regulation and gene expression. TRIM24 as a histone reader can recognize histone modification. However the specific recognition mechanism between TRIM24 and histone modification is unsolved. Here, systems biology method of dynamics correlation network based on molecular dynamics simulation was used to answer the question. Our network analysis shows that the dynamics correlation network of H3K23ac is distinctly different from that of wild type and other modifications. A hypothesis of “synergistic modification induced recognition” is then proposed to link histone modification and TRIM24 binding. These observations were further confirmed from community analysis of networks with mutation and network perturbation. Finally, a possible recognition pathway is also identified based on the shortest path search for H3K23ac. Significant difference of recognition pathway was found among different systems due to methylation and acetylation modifications. The analysis presented here and other studies show that the dynamic network-based analysis might be a useful general strategy to study the biology of protein post-translational modification and associated recognition.

The role of brassinosteroids in the regulation of the plasma membrane H+-ATPase and NADPH oxidase under cadmium stress.

PubMed

Jakubowska, Dagmara; Janicka, Małgorzata

2017-11-01

The present research aim was to define the role of brassinosteroids (BRs) in plant adaptation to cadmium stress. We observed a stimulating effect of exogenous BR on the activity of two plasma membrane enzymes which play a key role in plants adaptation to cadmium stress, H + -ATPase (EC 3.6.3.14) and NADPH oxidase (EC 1.6.3.1). Using anti-phosphothreonine antibody we showed that modification of PM H + -ATPase activity under BR action could result from phosphorylation of the enzyme protein. Also the relative expression of genes encoding both PM H + -ATPase and NADPH oxidase was affected by BR. To confirm the role of BR in the cadmium stimulating effect on activity of both studied plasma membrane enzymes, an assay in the presence of a BR biosynthesis inhibitor (propiconazole) was performed. Moreover, as a tool in our work we used commercially available plant mutants unable to BR biosynthesis or with dysfunctional BR signaling pathway, to further confirm participation of BR in plant adaptation to heavy metal stress. Presented results demonstrate some elements of the brassinosteroid-induced pathway activated under cadmium stress, wherein H + -ATPase and NADPH oxidase are key factors. Copyright © 2017 Elsevier B.V. All rights reserved.

Hypoxia-induced oxidative base modifications in the VEGF hypoxia-response element are associated with transcriptionally active nucleosomes.

PubMed

Ruchko, Mykhaylo V; Gorodnya, Olena M; Pastukh, Viktor M; Swiger, Brad M; Middleton, Natavia S; Wilson, Glenn L; Gillespie, Mark N

2009-02-01

Reactive oxygen species (ROS) generated in hypoxic pulmonary artery endothelial cells cause transient oxidative base modifications in the hypoxia-response element (HRE) of the VEGF gene that bear a conspicuous relationship to induction of VEGF mRNA expression (K.A. Ziel et al., FASEB J. 19, 387-394, 2005). If such base modifications are indeed linked to transcriptional regulation, then they should be detected in HRE sequences associated with transcriptionally active nucleosomes. Southern blot analysis of the VEGF HRE associated with nucleosome fractions prepared by micrococcal nuclease digestion indicated that hypoxia redistributed some HRE sequences from multinucleosomes to transcriptionally active mono- and dinucleosome fractions. A simple PCR method revealed that VEGF HRE sequences harboring oxidative base modifications were found exclusively in mononucleosomes. Inhibition of hypoxia-induced ROS generation with myxathiozol prevented formation of oxidative base modifications but not the redistribution of HRE sequences into mono- and dinucleosome fractions. The histone deacetylase inhibitor trichostatin A caused retention of HRE sequences in compacted nucleosome fractions and prevented formation of oxidative base modifications. These findings suggest that the hypoxia-induced oxidant stress directed at the VEGF HRE requires the sequence to be repositioned into mononucleosomes and support the prospect that oxidative modifications in this sequence are an important step in transcriptional activation.

Generation of induced pluripotent stem cells from the pig

USDA-ARS?s Scientific Manuscript database

The value of stem cells has become increasingly evident in recent years with the advent of genetic engineering tools that allow site-specific modifications to the genome. The use of stem cells to induce modifications has several potential benefits for the livestock industry including improving anim...

Parity modifies endocrine hormones in urine and problem-solving strategies of captive owl monkeys (Aotus spp.).

PubMed

Bardi, Massimo; Eckles, Meredith; Kirk, Emily; Landis, Timothy; Evans, Sian; Lambert, Kelly G

2014-12-01

Parental behavior modifies neural, physiologic, and behavioral characteristics of both maternal and paternal mammals. These parenting-induced modifications extend to brain regions not typically associated with parental responses themselves but that enhance ancillary responses, such as foraging efficiency and predator avoidance. Here we hypothesized that male and female owl monkeys (Aotus spp.) with reproductive experience (RE) would demonstrate more adaptive ancillary behavioral and neuroendocrine responses than those of their nonRE counterparts. To assess cognitive skills and coping flexibility, we introduced a foraging strategy task, including a set of novel objects (coin holders) marked with different symbols representing different food rewards, to the animals. To assess endocrine responses, urine samples were assayed for cortisol and dehydroepiandrosterone (DHEA) levels and their ratios to determine physiologic measures of emotional regulation in RE and nonRE owl monkeys. Compared with nonRE monkeys, experienced parents had higher DHEA:cortisol ratios after exposure to habituation training and on the first day of testing in the foraging task. Both hormones play critical roles in the stress response and coping mechanisms, and a high DHEA:cortisol ratio usually indicates increased coping skills. In addition, RE monkeys exhibited more efficient foraging responses (by 4-fold) than did the nonRE mating pairs. We conclude that RE modifies relevant behavioral and hormonal responses of both maternal and paternal owl monkeys exposed to a challenging cognitive paradigm. Corroborating previous research demonstrating adaptive modifications in foraging efficiency and emotional responses in reproductively experienced rodents, the current results extend these findings to a monogamous primate species.

Parity Modifies Endocrine Hormones in Urine and Problem-Solving Strategies of Captive Owl Monkeys (Aotus spp.)

PubMed Central

Eckles, Meredith; Kirk, Emily; Landis, Timothy; Evans, Sian; Lambert, Kelly G

2014-01-01

Parental behavior modifies neural, physiologic, and behavioral characteristics of both maternal and paternal mammals. These parenting-induced modifications extend to brain regions not typically associated with parental responses themselves but that enhance ancillary responses, such as foraging efficiency and predator avoidance. Here we hypothesized that male and female owl monkeys (Aotus spp.) with reproductive experience (RE) would demonstrate more adaptive ancillary behavioral and neuroendocrine responses than those of their nonRE counterparts. To assess cognitive skills and coping flexibility, we introduced a foraging strategy task, including a set of novel objects (coin holders) marked with different symbols representing different food rewards, to the animals. To assess endocrine responses, urine samples were assayed for cortisol and dehydroepiandrosterone (DHEA) levels and their ratios to determine physiologic measures of emotional regulation in RE and nonRE owl monkeys. Compared with nonRE monkeys, experienced parents had higher DHEA:cortisol ratios after exposure to habituation training and on the first day of testing in the foraging task. Both hormones play critical roles in the stress response and coping mechanisms, and a high DHEA:cortisol ratio usually indicates increased coping skills. In addition, RE monkeys exhibited more efficient foraging responses (by 4-fold) than did the nonRE mating pairs. We conclude that RE modifies relevant behavioral and hormonal responses of both maternal and paternal owl monkeys exposed to a challenging cognitive paradigm. Corroborating previous research demonstrating adaptive modifications in foraging efficiency and emotional responses in reproductively experienced rodents, the current results extend these findings to a monogamous primate species. PMID:25527030

The UPR reduces glucose metabolism via IRE1 signaling.

PubMed

van der Harg, Judith M; van Heest, Jessica C; Bangel, Fabian N; Patiwael, Sanne; van Weering, Jan R T; Scheper, Wiep

2017-04-01

Neurons are highly dependent on glucose. A disturbance in glucose homeostasis therefore poses a severe risk that is counteracted by activation of stress responses to limit damage and restore the energy balance. A major stress response that is activated under conditions of glucose deprivation is the unfolded protein response (UPR) that is aimed to restore proteostasis in the endoplasmic reticulum. The key signaling of the UPR involves the transient activation of a transcriptional program and an overall reduction of protein synthesis. Since the UPR is strategically positioned to sense and integrate metabolic stress signals, it is likely that - apart from its adaptive response to restore proteostasis - it also directly affects metabolic pathways. Here we investigate the direct role of the UPR in glucose homeostasis. O-GlcNAc is a post-translational modification that is highly responsive to glucose fluctuations. We find that UPR activation results in decreased O-GlcNAc modification, in line with reduced glucose metabolism. Our data indicate that UPR activation has no direct impact on the upstream processes in glucose metabolism; glucose transporter expression, glucose uptake and hexokinase activity. In contrast, prolonged UPR activation decreases glycolysis and mitochondrial metabolism. Decreased mitochondrial respiration is not accompanied by apoptosis or a structural change in mitochondria indicating that the reduction in metabolic rate upon UPR activation is a physiological non-apoptotic response. Metabolic decrease is prevented if the IRE1 pathway of the UPR is inhibited. This indicates that activation of IRE1 signaling induces a reduction in glucose metabolism, as part of an adaptive response. Copyright © 2017 Elsevier B.V. All rights reserved.

Most Colorful Example of Genetic Assimilation? Exploring the Evolutionary Destiny of Recurrent Phenotypic Accommodation.

PubMed

Badyaev, Alexander V; Potticary, Ahva L; Morrison, Erin S

2017-08-01

Evolution of adaptation requires both generation of novel phenotypic variation and retention of a locally beneficial subset of this variation. Such retention can be facilitated by genetic assimilation, the accumulation of genetic and molecular mechanisms that stabilize induced phenotypes and assume progressively greater control over their reliable production. A particularly strong inference into genetic assimilation as an evolutionary process requires a system where it is possible to directly evaluate the extent to which an induced phenotype is progressively incorporated into preexisting developmental pathways. Evolution of diet-dependent pigmentation in birds-where external carotenoids are coopted into internal metabolism to a variable degree before being integrated with a feather's developmental processes-provides such an opportunity. Here we combine a metabolic network view of carotenoid evolution with detailed empirical study of feather modifications to show that the effect of physical properties of carotenoids on feather structure depends on their metabolic modification, their environmental recurrence, and biochemical redundancy, as predicted by the genetic assimilation hypothesis. Metabolized carotenoids caused less stochastic variation in feather structure and were more closely integrated with feather growth than were dietary carotenoids of the same molecular weight. These patterns were driven by the recurrence of organism-carotenoid associations: commonly used dietary carotenoids and biochemically redundant derived carotenoids caused less stochastic variation in feather structure than did rarely used or biochemically unique compounds. We discuss implications of genetic assimilation processes for the evolutionary diversification of diet-dependent animal coloration.

Activity-induced dental modification in holocene siberian hunter-fisher-gatherers.

PubMed

Waters-Rist, Andrea; Bazaliiskii, Vladimir I; Weber, Andrzej; Goriunova, Olga I; Katzenberg, M Anne

2010-10-01

The use of teeth as tools provides clues to past subsistence patterns and cultural practices. Five Holocene period hunter-fisher-gatherer mortuary sites from the south-western region of Lake Baikal, Siberia, Russian Federation, are observed for activity-induced dental modification (AIDM) to further characterize their adaptive regimes. Grooves on the occlusal surfaces of teeth are observed in 25 out of 123 individuals (20.3%) and were most likely produced during the processing of fibers from plants and animals, for making items such as nets and cordage. Regional variation in the frequency of individuals with occlusal grooves is found in riverine versus lakeshore sites. This variation suggests that production of material culture items differed, perhaps in relation to different fishing practices. There is also variation in the distribution of grooves by sex: grooves are found predominately in females, except at the Late Neolithic-Bronze Age river site of Ust'-Ida I where grooves are found exclusively in males. Occlusal grooves were cast using polyvinylsiloxane and maxillary canine impressions were examined by scanning electron microscopy (SEM) to determine striation patterns. Variation in striae orientation suggests that a variety of activities, and/or different manufacturing techniques, were involved in groove production. Overall, the variability in occlusal groove frequency, sex and regional distribution, and microscopic striae patterns, points to the multiplicity of activities and ways in which people used their mouths and teeth in cultural activities. © 2010 Wiley-Liss, Inc.

Electric-field-induced modification of the magnon energy, exchange interaction, and curie temperature of transition-metal thin films.

PubMed

Oba, M; Nakamura, K; Akiyama, T; Ito, T; Weinert, M; Freeman, A J

2015-03-13

The electric-field-induced modification in the Curie temperature of prototypical transition-metal thin films with the perpendicular magnetic easy axis, a freestanding Fe(001) monolayer and a Co monolayer on Pt(111), is investigated by first-principles calculations of spin-spiral structures in an external electric field (E field). An applied E field is found to modify the magnon (spin-spiral formation) energy; the change arises from the E-field-induced screening charge density in the spin-spiral states due to p-d hybridizations. The Heisenberg exchange parameters obtained from the magnon energy suggest an E-field-induced modification of the Curie temperature, which is demonstrated via Monte Carlo simulations that take the magnetocrystalline anisotropy into account.

Sarcomeric protein modification during adrenergic stress enhances cross-bridge kinetics and cardiac output

PubMed Central

Gresham, Kenneth S.; Mamidi, Ranganath; Li, Jiayang; Kwak, Hyerin

2017-01-01

Molecular adaptations to chronic neurohormonal stress, including sarcomeric protein cleavage and phosphorylation, provide a mechanism to increase ventricular contractility and enhance cardiac output, yet the link between sarcomeric protein modifications and changes in myocardial function remains unclear. To examine the effects of neurohormonal stress on posttranslational modifications of sarcomeric proteins, mice were administered combined α- and β-adrenergic receptor agonists (isoproterenol and phenylephrine, IPE) for 14 days using implantable osmotic pumps. In addition to significant cardiac hypertrophy and increased maximal ventricular pressure, IPE treatment accelerated pressure development and relaxation (74% increase in dP/dtmax and 14% decrease in τ), resulting in a 52% increase in cardiac output compared with saline (SAL)-treated mice. Accelerated pressure development was maintained when accounting for changes in heart rate and preload, suggesting that myocardial adaptations contribute to enhanced ventricular contractility. Ventricular myocardium isolated from IPE-treated mice displayed a significant reduction in troponin I (TnI) and myosin-binding protein C (MyBP-C) expression and a concomitant increase in the phosphorylation levels of the remaining TnI and MyBP-C protein compared with myocardium isolated from saline-treated control mice. Skinned myocardium isolated from IPE-treated mice displayed a significant acceleration in the rate of cross-bridge (XB) detachment (46% increase) and an enhanced magnitude of XB recruitment (43% increase) at submaximal Ca2+ activation compared with SAL-treated mice but unaltered myofilament Ca2+ sensitivity of force generation. These findings demonstrate that sarcomeric protein modifications during neurohormonal stress are molecular adaptations that enhance in vivo ventricular contractility through accelerated XB kinetics to increase cardiac output. NEW & NOTEWORTHY Posttranslational modifications to sarcomeric regulatory proteins provide a mechanism to modulate cardiac function in response to stress. In this study, we demonstrate that neurohormonal stress produces modifications to myosin-binding protein C and troponin I, including a reduction in protein expression within the sarcomere and increased phosphorylation of the remaining protein, which serve to enhance cross-bridge kinetics and increase cardiac output. These findings highlight the importance of sarcomeric regulatory protein modifications in modulating ventricular function during cardiac stress. PMID:27909224

Sarcomeric protein modification during adrenergic stress enhances cross-bridge kinetics and cardiac output.

PubMed

Gresham, Kenneth S; Mamidi, Ranganath; Li, Jiayang; Kwak, Hyerin; Stelzer, Julian E

2017-03-01

Molecular adaptations to chronic neurohormonal stress, including sarcomeric protein cleavage and phosphorylation, provide a mechanism to increase ventricular contractility and enhance cardiac output, yet the link between sarcomeric protein modifications and changes in myocardial function remains unclear. To examine the effects of neurohormonal stress on posttranslational modifications of sarcomeric proteins, mice were administered combined α- and β-adrenergic receptor agonists (isoproterenol and phenylephrine, IPE) for 14 days using implantable osmotic pumps. In addition to significant cardiac hypertrophy and increased maximal ventricular pressure, IPE treatment accelerated pressure development and relaxation (74% increase in dP/d t max and 14% decrease in τ), resulting in a 52% increase in cardiac output compared with saline (SAL)-treated mice. Accelerated pressure development was maintained when accounting for changes in heart rate and preload, suggesting that myocardial adaptations contribute to enhanced ventricular contractility. Ventricular myocardium isolated from IPE-treated mice displayed a significant reduction in troponin I (TnI) and myosin-binding protein C (MyBP-C) expression and a concomitant increase in the phosphorylation levels of the remaining TnI and MyBP-C protein compared with myocardium isolated from saline-treated control mice. Skinned myocardium isolated from IPE-treated mice displayed a significant acceleration in the rate of cross-bridge (XB) detachment (46% increase) and an enhanced magnitude of XB recruitment (43% increase) at submaximal Ca 2+ activation compared with SAL-treated mice but unaltered myofilament Ca 2+ sensitivity of force generation. These findings demonstrate that sarcomeric protein modifications during neurohormonal stress are molecular adaptations that enhance in vivo ventricular contractility through accelerated XB kinetics to increase cardiac output. NEW & NOTEWORTHY Posttranslational modifications to sarcomeric regulatory proteins provide a mechanism to modulate cardiac function in response to stress. In this study, we demonstrate that neurohormonal stress produces modifications to myosin-binding protein C and troponin I, including a reduction in protein expression within the sarcomere and increased phosphorylation of the remaining protein, which serve to enhance cross-bridge kinetics and increase cardiac output. These findings highlight the importance of sarcomeric regulatory protein modifications in modulating ventricular function during cardiac stress. Copyright © 2017 the American Physiological Society.

A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration.

PubMed

Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

2016-03-01

Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

Identification, modification, and implementation of an evidence-based psychotherapy for children in a low-income country: the use of TF-CBT in Zambia

PubMed Central

2013-01-01

Background The need to address the treatment gap in mental health services in low- and middle-income countries (LMIC) is well recognized and particularly neglected among children and adolescents. Recent literature with adult populations suggests that evidence-based mental health treatments are effective, feasible, and cross-culturally modifiable for use in LMIC. This paper addresses a gap in the literature documenting pre-trial processes. We describe the process of selecting an intervention to meet the needs of a particular population and the process of cross-cultural adaptation. Methods Community-based participatory research principles were implemented for intervention selection, including joint meetings with stakeholders, review of qualitative research, and review of the literature. Trauma-focused Cognitive Behavioral Therapy (TF-CBT) was chosen as the evidence-based practice for modification and feasibility testing. The TF-CBT adaptation process, rooted within an apprenticeship model of training and supervision, is presented. Clinical case notes were reviewed to document modifications. Results Choosing an intervention can work as a collaborative process with community involvement. Results also show that modifications were focused primarily on implementation techniques rather than changes in TF-CBT core elements. Conclusions Studies documenting implementation processes are critical to understanding why intervention choices are made and how the adaptations are generated in global mental health. More articles are needed on how to implement evidence-based treatments in LMIC. PMID:24148551

Central gene expression changes associated with enhanced neuroendocrine and autonomic response habituation to repeated noise stress after voluntary wheel running in rats

PubMed Central

Sasse, Sarah K.; Nyhuis, Tara J.; Masini, Cher V.; Day, Heidi E. W.; Campeau, Serge

2013-01-01

Accumulating evidence indicates that regular physical exercise benefits health in part by counteracting some of the negative physiological impacts of stress. While some studies identified reductions in some measures of acute stress responses with prior exercise, limited data were available concerning effects on cardiovascular function, and reported effects on hypothalamic-pituitary-adrenocortical (HPA) axis responses were largely inconsistent. Given that exposure to repeated or prolonged stress is strongly implicated in the precipitation and exacerbation of illness, we proposed the novel hypothesis that physical exercise might facilitate adaptation to repeated stress, and subsequently demonstrated significant enhancement of both HPA axis (glucocorticoid) and cardiovascular (tachycardia) response habituation to repeated noise stress in rats with long-term access to running wheels compared to sedentary controls. Stress habituation has been attributed to modifications of brain circuits, but the specific sites of adaptation and the molecular changes driving its expression remain unclear. Here, in situ hybridization histochemistry was used to examine regulation of select stress-associated signaling systems in brain regions representing likely candidates to underlie exercise-enhanced stress habituation. Analyzed brains were collected from active (6 weeks of wheel running) and sedentary rats following control, acute, or repeated noise exposures that induced a significantly faster rate of glucocorticoid response habituation in active animals but preserved acute noise responsiveness. Nearly identical experimental manipulations also induce a faster rate of cardiovascular response habituation in exercised, repeatedly stressed rats. The observed regulation of the corticotropin-releasing factor and brain-derived neurotrophic factor systems across several brain regions suggests widespread effects of voluntary exercise on central functions and related adaptations to stress across multiple response modalities. PMID:24324441

Cereal Crop Proteomics: Systemic Analysis of Crop Drought Stress Responses Towards Marker-Assisted Selection Breeding

PubMed Central

Ghatak, Arindam; Chaturvedi, Palak; Weckwerth, Wolfram

2017-01-01

Sustainable crop production is the major challenge in the current global climate change scenario. Drought stress is one of the most critical abiotic factors which negatively impact crop productivity. In recent years, knowledge about molecular regulation has been generated to understand drought stress responses. For example, information obtained by transcriptome analysis has enhanced our knowledge and facilitated the identification of candidate genes which can be utilized for plant breeding. On the other hand, it becomes more and more evident that the translational and post-translational machinery plays a major role in stress adaptation, especially for immediate molecular processes during stress adaptation. Therefore, it is essential to measure protein levels and post-translational protein modifications to reveal information about stress inducible signal perception and transduction, translational activity and induced protein levels. This information cannot be revealed by genomic or transcriptomic analysis. Eventually, these processes will provide more direct insight into stress perception then genetic markers and might build a complementary basis for future marker-assisted selection of drought resistance. In this review, we survey the role of proteomic studies to illustrate their applications in crop stress adaptation analysis with respect to productivity. Cereal crops such as wheat, rice, maize, barley, sorghum and pearl millet are discussed in detail. We provide a comprehensive and comparative overview of all detected protein changes involved in drought stress in these crops and have summarized existing knowledge into a proposed scheme of drought response. Based on a recent proteome study of pearl millet under drought stress we compare our findings with wheat proteomes and another recent study which defined genetic marker in pearl millet. PMID:28626463

Back to Basics: Working with Young Children with Autism in Inclusive Classrooms

ERIC Educational Resources Information Center

Deris, Aaron R.; Di Carlo, Cynthia F.

2013-01-01

Young children with autism benefit from various adaptations made to an early childhood classroom. This article includes modifications for both teacher-directed and child-initiated activities. Adaptations are given for the classroom environment, daily schedule, sensory needs, transitions and general teaching strategies. The techniques described are…

Failing Tests: Commentary on "Adapting Educational Measurement to the Demands of Test-Based Accountability"

ERIC Educational Resources Information Center

Thissen, David

2015-01-01

In "Adapting Educational Measurement to the Demands of Test-Based Accountability" Koretz takes the time-honored engineering approach to educational measurement, identifying specific problems with current practice and proposing minimal modifications of the system to alleviate those problems. In response to that article, David Thissen…

A Continuum of Paraeducator Support for Utilization in Adapted Physical Education

ERIC Educational Resources Information Center

Haegele, Justin A.; Kozub, Francis M.

2010-01-01

This article describes three different ways of using paraeducators during adapted physical education. (1.) Having paraeducators read a portion of the lesson plan that describes the desired support towards lesson objectives. Paraeducators then assist all students when needed. (2.) Assigning specific modifications for paraeducators through the IEP…

Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma.

PubMed

Kreycy, Nele; Gotzian, Christiane; Fleming, Thomas; Flechtenmacher, Christa; Grabe, Niels; Plinkert, Peter; Hess, Jochen; Zaoui, Karim

2017-05-26

Glyoxalase 1 is a key enzyme in the detoxification of reactive metabolites such as methylglyoxal and induced Glyoxalase 1 expression has been demonstrated for several human malignancies. However, the regulation and clinical relevance of Glyoxalase 1 in the context of head and neck squamous cell carcinoma has not been addressed so far. Argpyrimidine modification as a surrogate for methylglyoxal accumulation and Glyoxalase 1 expression in tumor cells was assessed by immunohistochemical staining of tissue microarrays with specimens from oropharyngeal squamous cell carcinoma patients (n = 154). Prognostic values of distinct Glyoxalase 1 staining patterns were demonstrated by Kaplan-Meier, univariate and multivariate Cox proportional hazard model analysis. The impact of exogenous methylglyoxal or a Glyoxalase 1 inhibitor on the viability of two established tumor cell lines was monitored by a colony-forming assay in vitro. Glyoxalase 1 expression in tumor cells of oropharyngeal squamous cell carcinoma patients was positively correlated with the presence of Argpyrimidine modification and administration of exogenous methylglyoxal induced Glyoxalase 1 protein levels in FaDu and Cal27 cells in vitro. Cal27 cells with lower basal and methylglyoxal-induced Glyoxalase 1 expression were more sensitive to the cytotoxic effect at high methylgyoxal concentrations and both cell lines showed a decrease in colony formation with increasing amounts of a Glyoxalase 1 inhibitor. A high and nuclear Glyoxalase 1 staining was significantly correlated with shorter progression-free and disease-specific survival, and served as an independent risk factor for an unfavorable prognosis of oropharyngeal squamous cell carcinoma patients. Induced Glyoxalase 1 expression is a common feature in the pathogenesis of oropharyngeal squamous cell carcinoma and most likely represents an adaptive response to the accumulation of cytotoxic metabolites. Oropharyngeal squamous cell carcinoma patients with a high and nuclear Glyoxalase 1 staining pattern have a high risk for treatment failure, but might benefit from pharmacological targeting Glyoxalase 1 activity.

Panic disorder among Vietnamese refugees attending a psychiatric clinic: Prevalence and subtypes

PubMed Central

Hinton, Devon; Chau, Ha; Nguyen, Lim; Nguyen, Mai; Pham, Thang; Quinn, Sarah; Tran, Minh

2009-01-01

This study surveys Vietnamese refugees attending two psychiatric clinics to determine both the prevalence of panic disorder (PD) as well as panic attack subtypes in those suffering PD. A culturally valid adaptation of the SCID-panic module (the Vietnamese Panic Disorder Survey or VPDS) was administered to 100 Vietnamese refugees attending two psychiatric clinics. Utilizing culturally sensitive panic probes, the VPDS provides information regarding both the presence of PD and panic attack subtypes during the month prior to interview. Of 100 patients surveyed, 50 (50%) currently suffered PD. Among the 50 patients suffering PD, the most common panic attack subtypes during the previous month were the following: “orthostatic dizziness” (74% of the 50 panic disorder patients [PDPs]), headache (50% of PDPs), wind-induced/temperature-shift-induced (24% of PDPs), effort-induced (18% of PDPs), gastro-intestinal (16% of PDPs), micturition-induced (8% of PDPs), out-of-the-blue palpitations (24% of PDPs), and out-of-the-blue shortness of breath (16% of PDPs). Five mechanisms are adduced to account for this high PD prevalence as well as the specific profile of subtypes: 1) a trauma-caused panic attack diathesis; 2) trauma-event cues; 3) ethnic differences in physiology; 4) catastrophic cognitions generated by cultural syndromes; and 5) a modification of Clark’s spiral of panic. PMID:11738465

Surface Modification of Biomaterials: A Quest for Blood Compatibility

PubMed Central

de Mel, Achala; Cousins, Brian G.; Seifalian, Alexander M.

2012-01-01

Cardiovascular implants must resist thrombosis and intimal hyperplasia to maintain patency. These implants when in contact with blood face a challenge to oppose the natural coagulation process that becomes activated. Surface protein adsorption and their relevant 3D confirmation greatly determine the degree of blood compatibility. A great deal of research efforts are attributed towards realising such a surface, which comprise of a range of methods on surface modification. Surface modification methods can be broadly categorized as physicochemical modifications and biological modifications. These modifications aim to modulate platelet responses directly through modulation of thrombogenic proteins or by inducing antithrombogenic biomolecules that can be biofunctionalised onto surfaces or through inducing an active endothelium. Nanotechnology is recognising a great role in such surface modification of cardiovascular implants through biofunctionalisation of polymers and peptides in nanocomposites and through nanofabrication of polymers which will pave the way for finding a closer blood match through haemostasis when developing cardiovascular implants with a greater degree of patency. PMID:22693509

Rat reaction to hypokinesia after prior adaptation to hypoxia

NASA Technical Reports Server (NTRS)

Barashova, Z. I.; Tarakanova, O. I.

1980-01-01

The effect of prior hypoxia adaptation on body tolerance to hypokinesia was investigated. Rats trained to a 50 day period of hypokinesia and hypoxia with a preliminary month of adaptation to hypoxia showed less weight loss, higher indices for red blood content, heightened reactivity of the overall organism and the central nervous system to acute hypoxia, and decreased modification of the skeletal muscles compared to rats subjected to hypokinesia alone.

Locally adaptive vector quantization: Data compression with feature preservation

NASA Technical Reports Server (NTRS)

Cheung, K. M.; Sayano, M.

1992-01-01

A study of a locally adaptive vector quantization (LAVQ) algorithm for data compression is presented. This algorithm provides high-speed one-pass compression and is fully adaptable to any data source and does not require a priori knowledge of the source statistics. Therefore, LAVQ is a universal data compression algorithm. The basic algorithm and several modifications to improve performance are discussed. These modifications are nonlinear quantization, coarse quantization of the codebook, and lossless compression of the output. Performance of LAVQ on various images using irreversible (lossy) coding is comparable to that of the Linde-Buzo-Gray algorithm, but LAVQ has a much higher speed; thus this algorithm has potential for real-time video compression. Unlike most other image compression algorithms, LAVQ preserves fine detail in images. LAVQ's performance as a lossless data compression algorithm is comparable to that of Lempel-Ziv-based algorithms, but LAVQ uses far less memory during the coding process.

Gradual adaptation of bone structure to aquatic lifestyle in extinct sloths from Peru

PubMed Central

Amson, Eli; de Muizon, Christian; Laurin, Michel; Argot, Christine; de Buffrénil, Vivian

2014-01-01

Non-pathological densification (osteosclerosis) and swelling (pachyostosis) of bones are the main modifications affecting the skeleton of land vertebrates (tetrapods) that returned to water. However, a precise temporal calibration of the acquisition of such adaptations is still wanting. Here, we assess the timing of such acquisition using the aquatic sloth Thalassocnus, from the Neogene of the Pisco Formation, Peru. This genus is represented by five species occurring in successive vertebrate-bearing horizons of distinct ages. It yields the most detailed data about the gradual acquisition of aquatic adaptations among tetrapods, in displaying increasing osteosclerosis and pachyostosis through time. Such modifications, reflecting a shift in the habitat from terrestrial to aquatic, occurred over a short geological time span (ca 4 Myr). Otherwise, the bones of terrestrial pilosans (sloths and anteaters) are much more compact than the mean mammalian condition, which suggests that the osteosclerosis of Thalassocnus may represent an exaptation. PMID:24621950

Modification of motivational interviewing for use with people with mild intellectual disability and challenging behaviour.

PubMed

Frielink, Noud; Embregts, Petri

2013-12-01

Motivational interviewing is a promising method to increase treatment motivation for people with mild intellectual disability and challenging behaviour. The purpose of the present study was to identify how professionals could adapt motivational interviewing techniques for use with clients. We conducted semistructured qualitative interviews and focus groups with 26 clients, parents, and professionals. A general inductive approach led to the identification of multiple core themes. The authors recommend several modifications to accommodate motivational interviewing for use with clients: adapt to language level, adjust to cognitive abilities, and control for social desirability of responding. In addition, certain characteristics of professionals were also found to be critical for effective motivational interviewing: trustworthiness, engagement, acceptance, empathy, and honesty. Concrete recommendations for the adaptation of the motivational interviewing techniques for use with people with mild intellectual disability and challenging behaviour are identified. Certain characteristics of professionals are also critical for maximising the treatment motivation of clients.

An A-T linker adapter polymerase chain reaction method for chromosome walking without restriction site cloning bias.

PubMed

Trinh, Quoclinh; Xu, Wentao; Shi, Hui; Luo, Yunbo; Huang, Kunlun

2012-06-01

A-T linker adapter polymerase chain reaction (PCR) was modified and employed for the isolation of genomic fragments adjacent to a known DNA sequence. The improvements in the method focus on two points. The first is the modification of the PO(4) and NH(2) groups in the adapter to inhibit the self-ligation of the adapter or the generation of nonspecific products. The second improvement is the use of the capacity of rTaq DNA polymerase to add an adenosine overhang at the 3' ends of digested DNA to suppress self-ligation in the digested DNA and simultaneously resolve restriction site clone bias. The combination of modifications in the adapter and in the digested DNA leads to T/A-specific ligation, which enhances the flexibility of this method and makes it feasible to use many different restriction enzymes with a single adapter. This novel A-T linker adapter PCR overcomes the inherent limitations of the original ligation-mediated PCR method such as low specificity and a lack of restriction enzyme choice. Moreover, this method also offers higher amplification efficiency, greater flexibility, and easier manipulation compared with other PCR methods for chromosome walking. Experimental results from 143 Arabidopsis mutants illustrate that this method is reliable and efficient in high-throughput experiments. Copyright © 2012 Elsevier Inc. All rights reserved.

Long noncoding RNA in hematopoiesis and immunity.

PubMed

Satpathy, Ansuman T; Chang, Howard Y

2015-05-19

Dynamic gene expression during cellular differentiation is tightly coordinated by transcriptional and post-transcriptional mechanisms. An emerging theme is the central role of long noncoding RNAs (lncRNAs) in the regulation of this specificity. Recent advances demonstrate that lncRNAs are expressed in a lineage-specific manner and control the development of several cell types in the hematopoietic system. Moreover, specific lncRNAs are induced to modulate innate and adaptive immune responses. lncRNAs can function via RNA-DNA, RNA-RNA, and RNA-protein target interactions. As a result, they affect several stages of gene regulation, including chromatin modification, mRNA biogenesis, and protein signaling. We discuss recent advances, future prospects, and challenges in understanding the roles of lncRNAs in immunity and immune-mediated diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Stress-induced O-GlcNAcylation: an adaptive process of injured cells.

PubMed

Martinez, Marissa R; Dias, Thiago Braido; Natov, Peter S; Zachara, Natasha E

2017-02-08

In the 30 years, since the discovery of nucleocytoplasmic glycosylation, O -GlcNAc has been implicated in regulating cellular processes as diverse as protein folding, localization, degradation, activity, post-translational modifications, and interactions. The cell co-ordinates these molecular events, on thousands of cellular proteins, in concert with environmental and physiological cues to fine-tune epigenetics, transcription, translation, signal transduction, cell cycle, and metabolism. The cellular stress response is no exception: diverse forms of injury result in dynamic changes to the O -GlcNAc subproteome that promote survival. In this review, we discuss the biosynthesis of O -GlcNAc, the mechanisms by which O -GlcNAc promotes cytoprotection, and the clinical significance of these data. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Orexin signaling mediates the antidepressant-like effect of calorie restriction.

PubMed

Lutter, Michael; Krishnan, Vaishnav; Russo, Scott J; Jung, Saendy; McClung, Colleen A; Nestler, Eric J

2008-03-19

During periods of reduced food availability, animals must respond with behavioral adaptations that promote survival. Despite the fact that many psychiatric syndromes include disordered eating patterns as a component of the illness, little is known about the neurobiology underlying behavioral changes induced by short-term calorie restriction. Presently, we demonstrate that 10 d of calorie restriction, corresponding to a 20-25% weight loss, causes a marked antidepressant-like response in two rodent models of depression and that this response is dependent on the hypothalamic neuropeptide orexin (hypocretin). Wild-type mice, but not mice lacking orexin, show longer latency to immobility and less total immobility in the forced swim test after calorie restriction. In the social defeat model of chronic stress, calorie restriction reverses the behavioral deficits seen in wild-type mice but not in orexin knock-out mice. Additionally, chronic social defeat stress induces a prolonged reduction in the expression of prepro-orexin mRNA via epigenetic modification of the orexin gene promoter, whereas calorie restriction enhances the activation of orexin cells after social defeat. Together, these data indicate that orexin plays an essential role in mediating reduced depression-like symptoms induced by calorie restriction.

Optic Flow Dominates Visual Scene Polarity in Causing Adaptive Modification of Locomotor Trajectory

NASA Technical Reports Server (NTRS)

Nomura, Y.; Mulavara, A. P.; Richards, J. T.; Brady, R.; Bloomberg, Jacob J.

2005-01-01

Locomotion and posture are influenced and controlled by vestibular, visual and somatosensory information. Optic flow and scene polarity are two characteristics of a visual scene that have been identified as being critical in how they affect perceived body orientation and self-motion. The goal of this study was to determine the role of optic flow and visual scene polarity on adaptive modification in locomotor trajectory. Two computer-generated virtual reality scenes were shown to subjects during 20 minutes of treadmill walking. One scene was a highly polarized scene while the other was composed of objects displayed in a non-polarized fashion. Both virtual scenes depicted constant rate self-motion equivalent to walking counterclockwise around the perimeter of a room. Subjects performed Stepping Tests blindfolded before and after scene exposure to assess adaptive changes in locomotor trajectory. Subjects showed a significant difference in heading direction, between pre and post adaptation stepping tests, when exposed to either scene during treadmill walking. However, there was no significant difference in the subjects heading direction between the two visual scene polarity conditions. Therefore, it was inferred from these data that optic flow has a greater role than visual polarity in influencing adaptive locomotor function.

Efficiency of plasma actuator ionization in shock wave modification in a rarefied supersonic flow over a flat plate

NASA Astrophysics Data System (ADS)

Joussot, Romain; Lago, Viviana; Parisse, Jean-Denis

2014-12-01

This paper describes experimental and numerical investigations focused on the shock wave modification, induced by a dc glow discharge, of a Mach 2 flow under rarefied regime. The model under investigation is a flat plate equipped with a plasma actuator composed of two electrodes. The glow discharge is generated by applying a negative potential to the upstream electrode, enabling the creation of a weakly ionized plasma. The natural flow (i.e. without the plasma) exhibits a thick laminar boundary layer and a shock wave with a hyperbolic shape. Images of the flow obtained with an ICCD camera revealed that the plasma discharge induces an increase in the shock wave angle. Thermal effects (volumetric, and at the surface) and plasma effects (ionization, and thermal non-equilibrium) are the most relevant processes explaining the observed modifications. The effect induced by the heating of the flat plate surface is studied experimentally by replacing the upstream electrode by a heating element, and numerically by modifying the thermal boundary condition of the model surface. The results show that for a similar temperature distribution over the plate surface, modifications induced by the heating element are lower than those produced by the plasma. This difference shows that other effects than purely thermal effects are involved with the plasma actuator. Measurements of the electron density with a Langmuir probe highlight the fact that the ionization degree plays an important role into the modification of the flow. The gas properties, especially the isentropic exponent, are indeed modified by the plasma above the actuator and upstream the flat plate. This leads to a local modification of the flow conditions, inducing an increase in the shock wave angle.

Glutathione-S-transferase pi 1(GSTP1) gene silencing in prostate cancer cells is reversed by the histone deacetylase inhibitor depsipeptide.

PubMed

Hauptstock, Vera; Kuriakose, Sapuna; Schmidt, Doris; Düster, Robert; Müller, Stefan C; von Ruecker, Alexander; Ellinger, Jörg

2011-09-09

Gene silencing by epigenetic mechanisms is frequent in prostate cancer (PCA). The link between DNA hypermethylation and histone modifications is not completely understood. We chose the GSTP1 gene which is silenced by hypermethylation to analyze the effect of the histone deacetylase inhibitor depsipeptide on DNA methylation and histone modifications at the GSTP1 promoter site. Prostate cell lines (PC-3, LNCaP, and BPH-1) were treated with depsipeptide; apoptosis (FACS analysis), GSTP1 mRNA levels (quantitative real-time PCR), DNA hypermethylation (methylation-specific PCR), and histone modifications (chromatin immunoprecipitation) were studied. Depsipeptide induced apoptosis in PCA cells, but not a cell cycle arrest. Depispeptide reversed DNA hypermethylation and repressive histone modifications (reduction of H3K9me2/3 and H3K27me2/3; increase of H3K18Ac), thereby inducing GSTP1 mRNA re-expression. Successful therapy requires both, DNA demethylation and activating histone modifications, to induce complete gene expression of epigenetically silenced genes and depsipeptide fulfils both criteria. Copyright © 2011 Elsevier Inc. All rights reserved.

An animal model of functional electrical stimulation: evidence that the central nervous system modulates the consequences of training

PubMed Central

Hook, MA; Grau, JW

2011-01-01

Study Design Review of how spinal neurons can modulate the consequences of functional electrical stimulation (FES) in an animal model. Methods Spinal effects of FES are examined in male Sprague–Dawley rats transected at the second thoracic vertebra. The rats are exposed to FES training 24–48 h after surgery. Experimental manipulations of stimulation parameters, combined with physiological and pharmacological procedures, are used to examine the potential role of spinal neurons. Results The isolated spinal cord is inherently capable of learning the response–outcome relations imposed in FES training contingencies. Adaptive behavioral modifications are observed when an outcome (electrical stimulation) is contingent on a behavioral response. In contrast, a lack of correlation between the response and outcome in training produces a learning deficit in the spinal cord, rendering it incapable of adaptive learning for up to 48 h. The N-methyl-D-aspartic acid receptor appears to mediate both the adaptive plasticity and loss of plasticity, seen in this spinal model. Conclusion The behavioral effects observed with FES therapies are not simply due to the direct (motor) consequences of stimulation elicited by the activation of efferent motor neurons and/or selected muscles. FES training has the capacity to shape inherent spinal circuits and to produce a long-lasting behavioral modification. Further understanding of the spinal mechanisms underlying adaptive behavioral modification will be integral for establishing functional neural connections in a regenerating spinal system. PMID:17700514

GSK-3 mediates the okadaic acid-induced modification of collapsin response mediator protein-2 in human SK-N-SH neuroblastoma cells.

PubMed

Ni, Mei-Hui; Wu, Chih-Ching; Chan, Wen-Hsiung; Chien, Kun-Yi; Yu, Jau-Song

2008-04-15

Collapsin response mediator protein-2 (CRMP-2), a phosphoprotein involved in axonal outgrowth and microtubule dynamics, is aberrantly phosphorylated in Alzheimer's disease (AD) brain. Alteration of glycogen synthase kinase-3 (GSK-3) activity is associated with the pathogenesis of AD. Here, we show that CRMP-2 is one of the major substrates for GSK-3 in pig brain extracts. Both GSK-3alpha and 3beta phosphorylate purified pig brain CRMP-2 and significantly alter its mobility in SDS-gels, resembling the CRMP-2 modification observed in AD brain. Interestingly, this modification can be detected in SK-N-SH neuroblastoma cells treated with a phosphatase inhibitor, okadaic acid (OA), and GSK-3 inhibitors completely block this OA-induced event. Knockdown of both GSK-3alpha and 3beta, but not either kinase alone, impairs OA-induced modification of CRMP-2. Mutation of Ser-518 or Ser-522 of CRMP-2, which are highly phosphorylated in AD brain, to Ala blocks the OA-induced modification of CRMP-2 in SK-N-SH cells. Ser-522 prephosphorylated by Cdk5 is required for subsequent GSK-3alpha-mediated phosphorylation of CRMP-2 in vitro. Collectively, our results demonstrate for the first time that OA can induce phosphorylation of CRMP-2 in SK-N-SH cells at sites aberrantly phosphorylated in AD brain, and both GSK-3alpha and 3beta and Ser-522 kinase(s) are involved in this process.

Tungstate-induced color-pattern modifications of butterfly wings are independent of stress response and ecdysteroid effect.

PubMed

Otaki, Joji M; Ogasawara, Tsuyoshi; Yamamoto, Haruhiko

2005-06-01

Systemic injections of sodium tungstate, a protein-tyrosine phosphatase (PTPase) inhibitor, to pupae immediately after pupation have been shown to efficiently produce characteristic color-pattern modifications on the wings of many species of butterflies. Here we demonstrated that the tungstate-induced modification pattern was entirely different from other chemically-induced ones in a species of nymphalid butterfly Junonia (Precis) orithya. In this species, the systemic injections of tungstate produced characteristic expansion of black area and shrinkage of white area together with the move of parafocal elements toward the wing base. Overall, pattern boundaries became obscure. In contrast, an entirely different modification pattern, overall darkening of wings, was observed by the injections of stress-inducing chemicals, thapsigargin, ionomycin, or geldanamycin, to pupae under the rearing conditions for the adult summer form. On the ventral wings, this darkening was due to an increase of the proportion of peppered dark scales, which was reminiscent of the natural fall form of this species. Under the same rearing conditions, the injections of ecdysteroid, which is a well-known hormone being responsible for the seasonal polyphenism of nymphalid butterflies, yielded overall expansion of orange area especially around eyespots. Taken together, we conclude that the tungstate-induced modifications are clearly distinguishable from those of stress response and ecdysteroid effect. This conclusion then suggests that the putative PTPase signaling pathway that is sensitive to tungstate uniquely contributes to the wing-wide color-pattern development in butterflies.

The combined use of analytical tools for exploring tetanus toxin and tetanus toxoid structures.

PubMed

Bayart, Caroline; Peronin, Sébastien; Jean, Elisa; Paladino, Joseph; Talaga, Philippe; Borgne, Marc Le

2017-06-01

Aldehyde detoxification is a process used to convert toxin into toxoid for vaccine applications. In the case of tetanus toxin (TT), formaldehyde is used to obtain the tetanus toxoid (TTd), which is used either for the tetanus vaccine or as carrier protein in conjugate vaccines. Several studies have already been conducted to better understand the exact mechanism of this detoxification. Those studies led to the identification of a number of formaldehyde-induced modifications on lab scale TTd samples. To obtain greater insights of the changes induced by formaldehyde, we used three industrial TTd batches to identify repeatable modifications in the detoxification process. Our strategy was to combine seven analytical tools to map these changes. Mass spectrometry (MS), colorimetric test and amino acid analysis (AAA) were used to study modifications on amino acids. SDS-PAGE, asymmetric flow field flow fractionation (AF4), fluorescence spectroscopy and circular dichroism (CD) were used to study formaldehyde modifications on the whole protein structure. We identified 41 formaldehyde-induced modifications across the 1315 amino acid primary sequence of TT. Of these, five modifications on lysine residues were repeatable across TTd batches. Changes in protein conformation were also observed using SDS-PAGE, AF4 and CD techniques. Each analytical tool brought a piece of information regarding formaldehyde induced-modifications, and all together, these methods provided a comprehensive overview of the structural changes that occurred with detoxification. These results could be the first step leading to site-directed TT mutagenesis studies that may enable the production of a non-toxic equivalent protein without using formaldehyde. Copyright © 2017 Elsevier B.V. All rights reserved.

50 CFR 218.128 - Renewal of Letters of Authorization and adaptive management.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Temporary Maritime Activities Area (GoA TMAA) § 218.128 Renewal of Letters of Authorization and adaptive... activity identified in § 218.120(c) will be renewed upon: (1) Notification to NMFS that the activity... substantial modification to the desired work, mitigation, or monitoring undertaken during the upcoming period...

Adaptive Physical Education and Aquatics for Students with Disabilities: A Teacher's Unique Experience

ERIC Educational Resources Information Center

Blassingame, Jennifer Cheryl

2011-01-01

Students with the most severe disabilities have special needs that cannot be addressed with general education curriculum modifications in a traditional prekindergarten-12th grade environment (Heward, 2006). It is essential that expert teachers with specialized educational background and training are prepared to adapt daily lessons to accommodate…

Conflict Adaptation and Congruency Sequence Effects to Social-Emotional Stimuli in Individuals with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Worsham, Whitney; Gray, Whitney E.; Larson, Michael J.; South, Mikle

2015-01-01

Background: The modification of performance following conflict can be measured using conflict adaptation tasks thought to measure the change in the allocation of cognitive resources in order to reduce conflict interference and improve performance. While previous studies have suggested atypical processing during nonsocial cognitive control tasks,…

Including Exceptional Students in Your Instrumental Music Program

ERIC Educational Resources Information Center

Mixon, Kevin

2005-01-01

This article describes the method and adaptations used by the author in including students with special needs in an instrumental music program. To ensure success in the program, the author shares the method he uses to include exceptional students and enumerates some possible adaptations. There are certainly other methods and modifications that…

An Adaptive Approach to Teaching the Use of the Sonicguide with Modifications for Orthopedic Involvement.

ERIC Educational Resources Information Center

Kitzhoffer, Gerald J.

1983-01-01

Use of the Sonicguide, a binaural sensory aid, by a quadraplegic, totally blind 18-year-old student is described. The rationale for training, device adaptations, and the eventual use of the device as a primary mobility aid in areas familiar to the student are explained. (Author/MC)

Assessment of Postflight Locomotor Performance Utilizing a Test of Functional Mobility: Strategic and Adaptive Responses

NASA Technical Reports Server (NTRS)

Warren, L. E.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Ruttley, T. M.; Bloomberg, J. J.

2006-01-01

Space flight induces adaptive modification in sensorimotor function, allowing crewmembers to operate in the unique microgravity environment. This adaptive state, however, is inappropriate for a terrestrial environment. During a re-adaptation period upon their return to Earth, crewmembers experience alterations in sensorimotor function, causing various disturbances in perception, spatial orientation, posture, gait, and eye-head coordination. Following long duration space flight, sensorimotor dysfunction would prevent or extend the time required to make an emergency egress from the vehicle; compromising crew safety and mission objectives. We are investigating two types of motor learning that may interact with each other and influence a crewmember's ability to re-adapt to Earth's gravity environment. In strategic learning, crewmembers make rapid modifications in their motor control strategy emphasizing error reduction. This type of learning may be critical during the first minutes and hours after landing. In adaptive learning, long-term plastic transformations occur, involving morphological changes and synaptic modification. In recent literature these two behavioral components have been associated with separate brain structures that control the execution of motor strategies: the strategic component was linked to the posterior parietal cortex and the adaptive component was linked to the cerebellum (Pisella, et al. 2004). The goal of this paper was to demonstrate the relative contributions of the strategic and adaptive components to the re-adaptation process in locomotor control after long duration space flight missions on the International Space Station (ISS). The Functional Mobility Test (FMT) was developed to assess crewmember s ability to ambulate postflight from an operational and functional perspective. Sixteen crewmembers were tested preflight (3 sessions) and postflight (days 1, 2, 4, 7, 25) following a long duration space flight (approx 6 months) on the ISS. We have further analyzed the FMT data to characterize strategic and adaptive components during the postflight readaptation period. Crewmembers walked at a preferred pace through an obstacle course set up on a base of 10 cm thick medium density foam (Sunmate Foam, Dynamic Systems, Inc., Leicester, NC). The 6.0m X 4.0m course consisted of several pylons made of foam; a Styrofoam barrier 46.0cm high that crewmembers stepped over; and a portal constructed of two Styrofoam blocks, each 31cm high, with a horizontal bar covered by foam and suspended from the ceiling which was adjusted to the height of the crewmember s shoulder. The portal required crewmembers to bend at the waist and step over a barrier simultaneously. All obstacles were lightweight, soft and easily knocked over. Crewmembers were instructed to walk through the course as quickly and as safely as possible without touching any of the objects on the course. This task was performed three times in the clockwise direction and three times in the counterclockwise direction that was randomly chosen. The dependent measures for each trial were: time to complete the course (seconds) and the number of obstacles touched or knocked down. For each crewmember, the time to complete each FMT trial from postflight days 1, 2, 4, 7 and 25 were further analyzed. A single logarithmic curve using a least squares calculation was fit through these data to produce a single comprehensive curve (macro). This macro curve composed of data spanning 25 days, illustrates the re-adaptive learning function over the longer time scale term. Additionally, logarithmic curves were fit to the 6 data trials within each individual post flight test day to produce 5 separate daily curves. These micro curves, produced from data obtained over the course of minutes, illustrates the strategic learning function exhibited over a relative shorter time scale. The macro curve for all subjects exhibited adaptive motor learning patterns over the 25 day period. Howev, 9/16 crewmembers exhibited significant strategic motor learning patterns in their micro curves, as defined by m > 1 in the equation of the line y=m*LN(x) +b. These data indicate that postflight recovery in locomotor function involves both strategic and adaptive mechanisms. Future countermeasures will be designed to enhance both recovery processes.

Transcriptomic Analysis of the Adaptation of Listeria monocytogenes to Lagoon and Soil Matrices Associated with a Piggery Environment: Comparison of Expression Profiles

PubMed Central

Vivant, Anne-Laure; Desneux, Jeremy; Pourcher, Anne-Marie; Piveteau, Pascal

2017-01-01

Understanding how Listeria monocytogenes, the causative agent of listeriosis, adapts to the environment is crucial. Adaptation to new matrices requires regulation of gene expression. To determine how the pathogen adapts to lagoon effluent and soil, two matrices where L. monocytogenes has been isolated, we compared the transcriptomes of L. monocytogenes CIP 110868 20 min and 24 h after its transfer to effluent and soil extract. Results showed major variations in the transcriptome of L. monocytogenes in the lagoon effluent but only minor modifications in the soil. In both the lagoon effluent and in the soil, genes involved in mobility and chemotaxis and in the transport of carbohydrates were the most frequently represented in the set of genes with higher transcript levels, and genes with phage-related functions were the most represented in the set of genes with lower transcript levels. A modification of the cell envelop was only found in the lagoon environment. Finally, the differential analysis included a large proportion of regulators, regulons, and ncRNAs. PMID:29018416

Transcriptomic Analysis of the Adaptation of Listeria monocytogenes to Lagoon and Soil Matrices Associated with a Piggery Environment: Comparison of Expression Profiles.

PubMed

Vivant, Anne-Laure; Desneux, Jeremy; Pourcher, Anne-Marie; Piveteau, Pascal

2017-01-01

Understanding how Listeria monocytogenes , the causative agent of listeriosis, adapts to the environment is crucial. Adaptation to new matrices requires regulation of gene expression. To determine how the pathogen adapts to lagoon effluent and soil, two matrices where L. monocytogenes has been isolated, we compared the transcriptomes of L. monocytogenes CIP 110868 20 min and 24 h after its transfer to effluent and soil extract. Results showed major variations in the transcriptome of L. monocytogenes in the lagoon effluent but only minor modifications in the soil. In both the lagoon effluent and in the soil, genes involved in mobility and chemotaxis and in the transport of carbohydrates were the most frequently represented in the set of genes with higher transcript levels, and genes with phage-related functions were the most represented in the set of genes with lower transcript levels. A modification of the cell envelop was only found in the lagoon environment. Finally, the differential analysis included a large proportion of regulators, regulons, and ncRNAs.

On-line compensation for perturbations of a reaching movement is cerebellar dependent: support for the task dependency hypothesis.

PubMed

Shimansky, Yury; Wang, Jian-Jun; Bauer, Richard A; Bracha, Vlastislav; Bloedel, James R

2004-03-01

Although the cerebellum has been shown to be critical for the acquisition and retention of adaptive modifications in certain reflex behaviors, this structure's role in the learning of motor skills required to execute complex voluntary goal-directed movements still is unclear. This study explores this issue by analyzing the effects of inactivating the interposed and dentate cerebellar nuclei on the adaptation required to compensate for an external elastic load applied during a reaching movement. We show that cats with these nuclei inactivated can adapt to predictable perturbations of the forelimb during a goal-directed reach by including a compensatory component in the motor plan prior to movement initiation. In contrast, when comparable compensatory modifications must be triggered on-line because the perturbations are applied in randomized trials (i.e., unpredictably), such adaptive responses cannot be executed or reacquired after the interposed and dentate nuclei are inactivated. These findings provide the first demonstration of the condition-dependent nature of the cerebellum's contribution to the learning of a specific volitional task.

An oxidative DNA “damage” and repair mechanism localized in the VEGF promoter is important for hypoxia-induced VEGF mRNA expression

PubMed Central

Pastukh, Viktor; Roberts, Justin T.; Clark, David W.; Bardwell, Gina C.; Patel, Mita; Al-Mehdi, Abu-Bakr; Borchert, Glen M.

2015-01-01

In hypoxia, mitochondria-generated reactive oxygen species not only stimulate accumulation of the transcriptional regulator of hypoxic gene expression, hypoxia inducible factor-1 (Hif-1), but also cause oxidative base modifications in hypoxic response elements (HREs) of hypoxia-inducible genes. When the hypoxia-induced base modifications are suppressed, Hif-1 fails to associate with the HRE of the VEGF promoter, and VEGF mRNA accumulation is blunted. The mechanism linking base modifications to transcription is unknown. Here we determined whether recruitment of base excision DNA repair (BER) enzymes in response to hypoxia-induced promoter modifications was required for transcription complex assembly and VEGF mRNA expression. Using chromatin immunoprecipitation analyses in pulmonary artery endothelial cells, we found that hypoxia-mediated formation of the base oxidation product 8-oxoguanine (8-oxoG) in VEGF HREs was temporally associated with binding of Hif-1α and the BER enzymes 8-oxoguanine glycosylase 1 (Ogg1) and redox effector factor-1 (Ref-1)/apurinic/apyrimidinic endonuclease 1 (Ape1) and introduction of DNA strand breaks. Hif-1α colocalized with HRE sequences harboring Ref-1/Ape1, but not Ogg1. Inhibition of BER by small interfering RNA-mediated reduction in Ogg1 augmented hypoxia-induced 8-oxoG accumulation and attenuated Hif-1α and Ref-1/Ape1 binding to VEGF HRE sequences and blunted VEGF mRNA expression. Chromatin immunoprecipitation-sequence analysis of 8-oxoG distribution in hypoxic pulmonary artery endothelial cells showed that most of the oxidized base was localized to promoters with virtually no overlap between normoxic and hypoxic data sets. Transcription of genes whose promoters lost 8-oxoG during hypoxia was reduced, while those gaining 8-oxoG was elevated. Collectively, these findings suggest that the BER pathway links hypoxia-induced introduction of oxidative DNA modifications in promoters of hypoxia-inducible genes to transcriptional activation. PMID:26432868

Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell death☆

PubMed Central

Okabe, Akishi; Urano, Yasuomi; Itoh, Sayoko; Suda, Naoto; Kotani, Rina; Nishimura, Yuki; Saito, Yoshiro; Noguchi, Noriko

2013-01-01

Lipid peroxidation products have been known to induce cellular adaptive responses and enhance tolerance against subsequent oxidative stress through up-regulation of antioxidant compounds and enzymes. 24S-hydroxycholesterol (24SOHC) which is endogenously produced oxysterol in the brain plays an important role in maintaining brain cholesterol homeostasis. In this study, we evaluated adaptive responses induced by brain-specific oxysterol 24SOHC in human neuroblastoma SH-SY5Y cells. Cells treated with 24SOHC at sub-lethal concentrations showed significant reduction in cell death induced by subsequent treatment with 7-ketocholesterol (7KC) in both undifferentiated and retinoic acid-differentiated SH-SY5Y cells. These adaptive responses were also induced by other oxysterols such as 25-hydroxycholesterol and 27-hydroxycholesterol which are known to be ligands of liver X receptor (LXR). Co-treatment of 24SOHC with 9-cis retinoic acid, a retinoid X receptor ligand, enhanced the adaptive responses. Knockdown of LXRβ by siRNA diminished the adaptive responses induced by 24SOHC almost completely. The treatment with 24SOHC induced the expression of LXR target genes, such as ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1). The 24SOHC-induced adaptive responses were significantly attenuated by siRNA for ABCG1 but not by siRNA for ABCA1. Taken together, these results strongly suggest that 24SOHC at sub-lethal concentrations induces adaptive responses via transcriptional activation of LXR signaling pathway, thereby protecting neuronal cells from subsequent 7KC-induced cytotoxicity. PMID:24371802

A risk-mitigation approach to the management of induced seismicity

NASA Astrophysics Data System (ADS)

Bommer, Julian J.; Crowley, Helen; Pinho, Rui

2015-04-01

Earthquakes may be induced by a wide range of anthropogenic activities such as mining, fluid injection and extraction, and hydraulic fracturing. In recent years, the increased occurrence of induced seismicity and the impact of some of these earthquakes on the built environment have heightened both public concern and regulatory scrutiny, motivating the need for a framework for the management of induced seismicity. Efforts to develop systems to enable control of seismicity have not yet resulted in solutions that can be applied with confidence in most cases. The more rational approach proposed herein is based on applying the same risk quantification and mitigation measures that are applied to the hazard from natural seismicity. This framework allows informed decision-making regarding the conduct of anthropogenic activities that may cause earthquakes. The consequent risk, if related to non-structural damage (when re-location is not an option), can be addressed by appropriate financial compensation. If the risk poses a threat to life and limb, then it may be reduced through the application of strengthening measures in the built environment—the cost of which can be balanced against the economic benefits of the activity in question—rather than attempting to ensure that some threshold on earthquake magnitude or ground-shaking amplitude is not exceeded. However, because of the specific characteristics of induced earthquakes—which may occur in regions with little or no natural seismicity—the procedures used in standard earthquake engineering need adaptation and modification for application to induced seismicity.

A risk-mitigation approach to the management of induced seismicity.

PubMed

Bommer, Julian J; Crowley, Helen; Pinho, Rui

2015-01-01

Earthquakes may be induced by a wide range of anthropogenic activities such as mining, fluid injection and extraction, and hydraulic fracturing. In recent years, the increased occurrence of induced seismicity and the impact of some of these earthquakes on the built environment have heightened both public concern and regulatory scrutiny, motivating the need for a framework for the management of induced seismicity. Efforts to develop systems to enable control of seismicity have not yet resulted in solutions that can be applied with confidence in most cases. The more rational approach proposed herein is based on applying the same risk quantification and mitigation measures that are applied to the hazard from natural seismicity. This framework allows informed decision-making regarding the conduct of anthropogenic activities that may cause earthquakes. The consequent risk, if related to non-structural damage (when re-location is not an option), can be addressed by appropriate financial compensation. If the risk poses a threat to life and limb, then it may be reduced through the application of strengthening measures in the built environment-the cost of which can be balanced against the economic benefits of the activity in question-rather than attempting to ensure that some threshold on earthquake magnitude or ground-shaking amplitude is not exceeded. However, because of the specific characteristics of induced earthquakes-which may occur in regions with little or no natural seismicity-the procedures used in standard earthquake engineering need adaptation and modification for application to induced seismicity.

Principles and methodology for translation and cross-cultural adaptation of the Nordic Occupational Skin Questionnaire (NOSQ-2002) to Spanish and Catalan.

PubMed

Sala-Sastre, Nohemi; Herdman, Mike; Navarro, Lidia; de la Prada, Miriam; Pujol, Ramón M; Serra, Consol; Alonso, Jordi; Flyvholm, Mari-Ann; Giménez-Arnau, Ana M

2009-08-01

Occupational skin diseases are among the most frequent work-related diseases in industrialized countries. The Nordic Occupational Skin Questionnaire (NOSQ-2002), developed in English, is a useful tool for screening of occupational skin diseases. To culturally adapt the NOSQ-2002 to Spanish and Catalan and to assess the clarity, comprehension, cultural relevance and appropriateness of the translated versions. The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) principles of good practice for the translation and cultural adaptation of patient-reported outcomes were followed. After translation into the target language, a first consensus version of the questionnaire was evaluated in multiple cognitive debriefing interviews. The expert panel introduced some modifications in 39 (68%) and 27 (47%) items in the Spanish and Catalan version, respectively (e.g. addition of examples and definitions, reformulation of instructions and use of direct question format). This version was back translated and submitted to the original authors, who suggested a further seven and two modifications in the Spanish and Catalan versions, respectively. A second set of cognitive interviews were performed. A consensus version of both questionnaires was obtained after final modifications based on comments by the patients. The final versions of the Spanish and Catalan NOSQ-2002 questionnaires are now available at www.NRCWE.dk/NOSQ.

Low-temperature diffusion assisted by femtosecond laser-induced modifications at Ni/SiC interface

NASA Astrophysics Data System (ADS)

Okada, Tatsuya; Tomita, Takuro; Ueki, Tomoyuki; Hashimoto, Takuya; Kawakami, Hiroki; Fuchikami, Yuki; Hisazawa, Hiromu; Tanaka, Yasuhiro

2018-01-01

We investigated low-temperature diffusion at the Ni/SiC interface with the assistance of femtosecond laser-induced modifications. Cross sections of the laser-irradiated lines of two different pulse energies — 0.84 and 0.60 J/cm2 in laser fluence — were compared before and after annealing at 673 K. At the laser fluence of 0.60 J/cm2, a single flat Ni-based particle was formed at the interface after annealing. The SiC crystal under the particle was defect-free. The present results suggest the potential application of femtosecond laser-induced modifications to the low-temperature fabrication of contacts at the interface without introducing crystal defects, e.g., dislocations and stacking faults, in SiC.

Modifications to the NIST reference measurement procedure (RMP) for the determination of serum glucose by isotope dilution gas chromatography/mass spectrometry.

PubMed

Prendergast, Jocelyn L; Sniegoski, Lorna T; Welch, Michael J; Phinney, Karen W

2010-07-01

The definitive method (DM), now known as the reference measurement procedure (RMP), for the analysis of glucose in serum was originally published in 1982 by the National Institute of Standards and Technology (NIST). Over the years the method has been subject to a number of modifications to adapt to newer technologies and simplify sample preparation. We discuss here an adaptation of the method associated with serum glucose measurements using a modified isotope dilution gas chromatography/mass spectrometry (ID-GC/MS) method. NIST has used this modified method to certify the concentrations of glucose in SRM 965b, Glucose in Frozen Human Serum, and SRM 1950, Metabolites in Human Plasma. Comparison of results from the revised method with certified values for existing Standard Reference Materials (SRMs) demonstrated that these modifications have not affected the quality of the measurements, giving both good precision and accuracy, while reducing the sample preparation time by a day and a half.

Enterobacter gergoviae membrane modifications are involved in the adaptive response to preservatives used in cosmetic industry.

PubMed

Périamé, Marina; Pagès, Jean-Marie; Davin-Regli, Anne

2015-01-01

The objective of this study was to understand the adaptive mechanisms in Enterobacter gergoviae which are involved in recurrent contaminations in cosmetic products that are incorporated with preservatives. Bacterial strains from two backgrounds were examined for a profound understanding of the mechanisms of adaptation against preservatives. It included a series of Ent. gergoviae strain-ATCC 33028 derivatives, isolated using increasing methylisothiazolinone-chloromethylisothiazolinone (MIT-CMIT) and triclosan concentrations. The other series was of Ent. gergoviae isolates from cosmetic products exhibiting MIT-CMIT and triclosan resistance. We evaluated the outer membrane protein modifications and efflux mechanisms activities responsible for the resistant trait via immunoblotting assays. Additionally, for understanding the efflux activity real-time efflux, experiments were performed. A cross-insusceptibility between preservatives and some disinfectants was observed in MIT-CMIT-resistant derivative isolates, but antibiotics susceptibility was not altered. Resistance to EDTA was significant in all preservatives insusceptible derivative strains, indicating modifications in the LPS layer. Furthermore, an array of real-time efflux assays indicated different activity levels while no variations were detected in porins and AcrAB-TolC pumps production. Overexpression of a specific flagellin-type protein was observed in one of the MIT-CMIT- and triclosan-resistant strains. Another candidate, a 25-kDa peroxiredoxin enzyme involved in oxidative detoxification, was identified to be overexpressed in MIT-CMIT derivative. A similar profile was also observed among strains isolated from cosmetic products. Our study highlights the existence of adaptive mechanisms such as overexpression of detoxifying enzymes, flagellin, modification of membrane structure/function in Ent. gergoviae. They might be involved in recurrent episodes of contaminations occurring in the cosmetic production lines. No cross-resistance could be observed with antibiotics when MICs to preservatives were increased; however, a decrease in the disinfectants bactericidal effects was confirmed in preservative-tolerant strains. This will impact industry disinfection strategies treatment against bacteria. © 2014 The Society for Applied Microbiology.

Disorder induced semiconductor to metal transition and modifications of grain boundaries in nanocrystalline zinc oxide thin film

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Fouran; Kumar, Vinod; Chaudhary, Babloo

2012-10-01

This paper report on the disorder induced semiconductor to metal transition (SMT) and modifications of grain boundaries in nanocrystalline zinc oxide thin film. Disorder is induced using energetic ion irradiation. It eliminates the possibility of impurities induced transition. However, it is revealed that some critical concentration of defects is needed for inducing such kind of SMT at certain critical temperature. Above room temperature, the current-voltage characteristics in reverse bias attributes some interesting phenomenon, such as electric field induced charge transfer, charge trapping, and diffusion of defects. The transition is explained by the defects induced disorder and strain in ZnO crystallitesmore » created by high density of electronic excitations.« less

Using an electrohydraulic ankle foot orthosis to study modifications in feedforward control during locomotor adaptation to force fields applied in stance

PubMed Central

Noel, Martin; Fortin, Karine; Bouyer, Laurent J

2009-01-01

Background Adapting to external forces during walking has been proposed as a tool to improve locomotion after central nervous system injury. However, sensorimotor integration during walking varies according to the timing in the gait cycle, suggesting that adaptation may also depend on gait phases. In this study, an ElectroHydraulic AFO (EHO) was used to apply forces specifically during mid-stance and push-off to evaluate if feedforward movement control can be adapted in these 2 gait phases. Methods Eleven healthy subjects walked on a treadmill before (3 min), during (5 min) and after (5 min) exposure to 2 force fields applied by the EHO (mid-stance/push-off; ~10 Nm, towards dorsiflexion). To evaluate modifications in feedforward control, strides with no force field ('catch strides') were unexpectedly inserted during the force field walking period. Results When initially exposed to a mid-stance force field (FF20%), subjects showed a significant increase in ankle dorsiflexion velocity. Catches applied early into the FF20% were similar to baseline (P > 0.99). Subjects gradually adapted by returning ankle velocity to baseline over ~50 strides. Catches applied thereafter showed decreased ankle velocity where the force field was normally applied, indicating the presence of feedforward adaptation. When initially exposed to a push-off force field (FF50%), plantarflexion velocity was reduced in the zone of force field application. No adaptation occurred over the 5 min exposure. Catch strides kinematics remained similar to control at all times, suggesting no feedforward adaptation. As a control, force fields assisting plantarflexion (-3.5 to -9.5 Nm) were applied and increased ankle plantarflexion during push-off, confirming that the lack of kinematic changes during FF50% catch strides were not simply due to a large ankle impedance. Conclusion Together these results show that ankle exoskeletons such as the EHO can be used to study phase-specific adaptive control of the ankle during locomotion. Our data suggest that, for short duration exposure, a feedforward modification in torque output occurs during mid-stance but not during push-off. These findings are important for the design of novel rehabilitation methods, as they suggest that the ability to use resistive force fields for training may depend on targeted gait phases. PMID:19493356

Using an electrohydraulic ankle foot orthosis to study modifications in feedforward control during locomotor adaptation to force fields applied in stance.

PubMed

Noel, Martin; Fortin, Karine; Bouyer, Laurent J

2009-06-03

Adapting to external forces during walking has been proposed as a tool to improve locomotion after central nervous system injury. However, sensorimotor integration during walking varies according to the timing in the gait cycle, suggesting that adaptation may also depend on gait phases. In this study, an ElectroHydraulic AFO (EHO) was used to apply forces specifically during mid-stance and push-off to evaluate if feedforward movement control can be adapted in these 2 gait phases. Eleven healthy subjects walked on a treadmill before (3 min), during (5 min) and after (5 min) exposure to 2 force fields applied by the EHO (mid-stance/push-off; approximately 10 Nm, towards dorsiflexion). To evaluate modifications in feedforward control, strides with no force field ('catch strides') were unexpectedly inserted during the force field walking period. When initially exposed to a mid-stance force field (FF 20%), subjects showed a significant increase in ankle dorsiflexion velocity. Catches applied early into the FF 20% were similar to baseline (P > 0.99). Subjects gradually adapted by returning ankle velocity to baseline over approximately 50 strides. Catches applied thereafter showed decreased ankle velocity where the force field was normally applied, indicating the presence of feedforward adaptation. When initially exposed to a push-off force field (FF 50%), plantarflexion velocity was reduced in the zone of force field application. No adaptation occurred over the 5 min exposure. Catch strides kinematics remained similar to control at all times, suggesting no feedforward adaptation. As a control, force fields assisting plantarflexion (-3.5 to -9.5 Nm) were applied and increased ankle plantarflexion during push-off, confirming that the lack of kinematic changes during FF 50% catch strides were not simply due to a large ankle impedance. Together these results show that ankle exoskeletons such as the EHO can be used to study phase-specific adaptive control of the ankle during locomotion. Our data suggest that, for short duration exposure, a feedforward modification in torque output occurs during mid-stance but not during push-off. These findings are important for the design of novel rehabilitation methods, as they suggest that the ability to use resistive force fields for training may depend on targeted gait phases.

Sunlight irradiance and habituation of visual evoked potentials in migraine: The environment makes its mark.

PubMed

Lisicki, Marco; D'Ostilio, Kevin; Erpicum, Michel; Schoenen, Jean; Magis, Delphine

2017-01-01

Background Migraine is a complex multifactorial disease that arises from the interaction between a genetic predisposition and an enabling environment. Habituation is considered as a fundamental adaptive behaviour of the nervous system that is often impaired in migraine populations. Given that migraineurs are hypersensitive to light, and that light deprivation is able to induce functional changes in the visual cortex recognizable through visual evoked potentials habituation testing, we hypothesized that regional sunlight irradiance levels could influence the results of visual evoked potentials habituation studies performed in different locations worldwide. Methods We searched the literature for visual evoked potentials habituation studies comparing healthy volunteers and episodic migraine patients and correlated their results with levels of local solar radiation. Results After reviewing the literature, 26 studies involving 1291 participants matched our inclusion criteria. Deficient visual evoked potentials habituation in episodic migraine patients was reported in 19 studies. Mean yearly sunlight irradiance was significantly higher in locations of studies reporting deficient habituation. Correlation analyses suggested that visual evoked potentials habituation decreases with increasing sunlight irradiance in migraine without aura patients. Conclusion Results from this hypothesis generating analysis suggest that variations in sunlight irradiance may induce adaptive modifications in visual processing systems that could be reflected in visual evoked potentials habituation, and thus partially account for the difference in results between studies performed in geographically distant centers. Other causal factors such as genetic differences could also play a role, and therefore well-designed prospective trials are warranted.

Source term evaluation for combustion modeling

NASA Technical Reports Server (NTRS)

Sussman, Myles A.

1993-01-01

A modification is developed for application to the source terms used in combustion modeling. The modification accounts for the error of the finite difference scheme in regions where chain-branching chemical reactions produce exponential growth of species densities. The modification is first applied to a one-dimensional scalar model problem. It is then generalized to multiple chemical species, and used in quasi-one-dimensional computations of shock-induced combustion in a channel. Grid refinement studies demonstrate the improved accuracy of the method using this modification. The algorithm is applied in two spatial dimensions and used in simulations of steady and unsteady shock-induced combustion. Comparisons with ballistic range experiments give confidence in the numerical technique and the 9-species hydrogen-air chemistry model.

Epigenetic and Genetic Contributions to Adaptation in Chlamydomonas.

PubMed

Kronholm, Ilkka; Bassett, Andrew; Baulcombe, David; Collins, Sinéad

2017-09-01

Epigenetic modifications, such as DNA methylation or histone modifications, can be transmitted between cellular or organismal generations. However, there are no experiments measuring their role in adaptation, so here we use experimental evolution to investigate how epigenetic variation can contribute to adaptation. We manipulated DNA methylation and histone acetylation in the unicellular green alga Chlamydomonas reinhardtii both genetically and chemically to change the amount of epigenetic variation generated or transmitted in adapting populations in three different environments (salt stress, phosphate starvation, and high CO2) for two hundred asexual generations. We find that reducing the amount of epigenetic variation available to populations can reduce adaptation in environments where it otherwise happens. From genomic and epigenomic sequences from a subset of the populations, we see changes in methylation patterns between the evolved populations over-represented in some functional categories of genes, which is consistent with some of these differences being adaptive. Based on whole genome sequencing of evolved clones, the majority of DNA methylation changes do not appear to be linked to cis-acting genetic mutations. Our results show that transgenerational epigenetic effects play a role in adaptive evolution, and suggest that the relationship between changes in methylation patterns and differences in evolutionary outcomes, at least for quantitative traits such as cell division rates, is complex. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Tropical cyclone perceptions, impacts and adaptation in the Southwest Pacific: an urban perspective from Fiji, Vanuatu and Tonga

NASA Astrophysics Data System (ADS)

Magee, Andrew D.; Verdon-Kidd, Danielle C.; Kiem, Anthony S.; Royle, Stephen A.

2016-05-01

The destruction caused by tropical cyclone (TC) Pam in March 2015 is considered one of the worst natural disasters in the history of Vanuatu. It has highlighted the need for a better understanding of TC impacts and adaptation in the Southwest Pacific (SWP) region. Therefore, the key aims of this study are to (i) understand local perceptions of TC activity, (ii) investigate impacts of TC activity and (iii) uncover adaptation strategies used to offset the impacts of TCs. To address these aims, a survey (with 130 participants from urban areas) was conducted across three SWP small island states (SISs): Fiji, Vanuatu and Tonga (FVT). It was found that respondents generally had a high level of risk perception and awareness of TCs and the associated physical impacts, but lacked an understanding of the underlying weather conditions. Responses highlighted that current methods of adaptation generally occur at the local level, immediately prior to a TC event (preparation of property, gathering of food, finding a safe place to shelter). However higher level adaptation measures (such as the modification to building structures) may reduce vulnerability further. Finally, we discuss the potential of utilising weather-related traditional knowledge and non-traditional knowledge of empirical and climate-model-based weather forecasts to improve TC outlooks, which would ultimately reduce vulnerability and increase adaptive capacity. Importantly, lessons learned from this study may result in the modification and/or development of existing adaptation strategies.

Complex Changes in the Innate and Adaptive Immunity Accompany Progressive Degeneration of the Nigrostriatal Pathway Induced by Intrastriatal Injection of 6-Hydroxydopamine in the Rat.

PubMed

Ambrosi, Giulia; Kustrimovic, Natasa; Siani, Francesca; Rasini, Emanuela; Cerri, Silvia; Ghezzi, Cristina; Dicorato, Giuseppe; Caputo, Sofia; Marino, Franca; Cosentino, Marco; Blandini, Fabio

2017-07-01

We investigated changes in innate and adaptive immunity paralleling the progressive nigrostriatal damage occurring in a neurotoxic model of Parkinson's disease (PD) based on unilateral infusion of 6-hydroxydopamine (6-OHDA) into the rat striatum. A time-course analysis was conducted to assess changes in morphology (activation) and cell density of microglia and astrocytes, microglia polarization (M1 vs. M2 phenotype), lymphocyte infiltration in the lesioned substantia nigra pars compacta (SNc), and modifications of CD8+ and subsets of CD4+ T cell in peripheral blood accompanying nigrostriatal degeneration. Confirming previous results, we observed slightly different profiles of activation for astrocytes and microglia paralleling nigral neuronal loss. For astrocytes, morphological changes and cell density increases were mostly evident at the latest time points (14 and 28 days post-surgery), while moderate microglia activation was present since the earliest time point. For the first time, in this model, we described the time-dependent profile of microglia polarization. Activated microglia clearly expressed the M2 phenotype in the earlier phase of the experiment, before cell death became manifest, gradually shifting to the M1 phenotype as SNc cell death started. In parallel, a reduction in the percentage of circulating CD4+ T regulatory (Treg) cells, starting as early as day 3 post-6-OHDA injection, was detected in 6-OHDA-injected rats. Our data show that nigrostriatal degeneration is associated with complex changes in central and peripheral immunity. Microglia activation and polarization, Treg cells, and the factors involved in their cross-talk should be further investigated as targets for the development of therapeutic strategies for disease modification in PD.

Nutrient-induced modifications of wood anatomical traits of Alchornea lojaensis (Euphorbiaceae)

NASA Astrophysics Data System (ADS)

Spannl, Susanne; Homeier, Jürgen; Bräuning, Achim

2016-05-01

Regarding woody plant responses on higher atmospheric inputs of the macronutrients nitrogen (N) and phosphorous (P) on tropical forests in the future, an adaptive modification of wood anatomical traits on the cellular level of woody plants is expected. As part of an interdisciplinary nutrient manipulation experiment (NUMEX) carried out in Southern Ecuador, we present here the first descriptive and quantitative wood anatomical analysis of the tropical evergreen tree species Alchornea lojaensis (Euphorbiaceae). We sampled branch wood of nine individual trees belonging to treatments with N fertilization, N+P fertilization, and a control group, respectively. Quantitative evaluations of eleven different vessel parameters were conducted. The results showed that this endemic tree species will be able to adapt well to the future effects of climate change and higher nutrient deposition. This was firstly implied by an increase in vessel diameter and consequently a higher theo. area-specific hydraulic conductivity with higher nutrient availability. Secondly, the percentage of small vessels (0-20µm diameter) strongly increased with fertilization. Thirdly, the vessel arrangement (solitary vessels vs. multiple vessel groupings) changed towards a lower percentage of solitary vessel fraction (VS), and concurrently towards a higher total vessel grouping index (VG) and a higher mean group size of non-solitary vessels (VM) after N and N+P addition. We conclude that higher nutrient availability of N and N+P triggered higher foliage amount and water demand, leading to higher cavitation risk in larger vessels. This is counteracted by a stronger grouping of vessels with smaller risk of cavitation to ensure water supply during drier periods that are expected to occur in higher frequency in the near future.

Activity-induced histone modifications govern Neurexin-1 mRNA splicing and memory preservation.

PubMed

Ding, Xinlu; Liu, Sanxiong; Tian, Miaomiao; Zhang, Wenhao; Zhu, Tao; Li, Dongdong; Wu, Jiawei; Deng, HaiTeng; Jia, Yichang; Xie, Wei; Xie, Hong; Guan, Ji-Song

2017-05-01

Epigenetic mechanisms regulate the formation, consolidation and reconsolidation of memories. However, the signaling path from neuronal activation to epigenetic modifications within the memory-related brain circuit remains unknown. We report that learning induces long-lasting histone modifications in hippocampal memory-activated neurons to regulate memory stability. Neuronal activity triggers a late-onset shift in Nrxn1 splice isoform choice at splicing site 4 by accumulating a repressive histone marker, H3K9me3, to modulate the splicing process. Activity-dependent phosphorylation of p66α via AMP-activated protein kinase recruits HDAC2 and Suv39h1 to establish repressive histone markers and changes the connectivity of the activated neurons. Removal of Suv39h1 abolished the activity-dependent shift in Nrxn1 splice isoform choice and reduced the stability of established memories. We uncover a cell-autonomous process for memory preservation in which memory-related neurons initiate a late-onset reduction of their rewiring capacities through activity-induced histone modifications.

Implementing Sympson-Hetter Item-Exposure Control in a Shadow-Test Approach to Constrained Adaptive Testing

ERIC Educational Resources Information Center

Veldkamp, Bernard P.; van der Linden, Wim J.

2008-01-01

In most operational computerized adaptive testing (CAT) programs, the Sympson-Hetter (SH) method is used to control the exposure of the items. Several modifications and improvements of the original method have been proposed. The Stocking and Lewis (1998) version of the method uses a multinomial experiment to select items. For severely constrained…

Modification of transparent materials with ultrashort laser pulses: What is energetically and mechanically meaningful?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bulgakova, Nadezhda M., E-mail: nadezhda.bulgakova@hilase.cz; Institute of Thermophysics SB RAS, 1 Lavrentyev Ave., 630090 Novosibirsk; Zhukov, Vladimir P.

A comprehensive analysis of laser-induced modification of bulk glass by single ultrashort laser pulses is presented which is based on combination of optical Maxwell-based modeling with thermoelastoplastic simulations of post-irradiation behavior of matter. A controversial question on free electron density generated inside bulk glass by ultrashort laser pulses in modification regimes is addressed on energy balance grounds. Spatiotemporal dynamics of laser beam propagation in fused silica have been elucidated for the regimes used for direct laser writing in bulk glass. 3D thermoelastoplastic modeling of material relocation dynamics under laser-induced stresses has been performed up to the microsecond timescale when allmore » motions in the material decay. The final modification structure is found to be imprinted into material matrix already at sub-nanosecond timescale. Modeling results agree well with available experimental data on laser light transmission through the sample and the final modification structure.« less

Salt stress induces the formation of a novel type of 'pressure wood' in two Populus species.

PubMed

Janz, Dennis; Lautner, Silke; Wildhagen, Henning; Behnke, Katja; Schnitzler, Jörg-Peter; Rennenberg, Heinz; Fromm, Jörg; Polle, Andrea

2012-04-01

• Salinity causes osmotic stress and limits biomass production of plants. The goal of this study was to investigate mechanisms underlying hydraulic adaptation to salinity. • Anatomical, ecophysiological and transcriptional responses to salinity were investigated in the xylem of a salt-sensitive (Populus × canescens) and a salt-tolerant species (Populus euphratica). • Moderate salt stress, which suppressed but did not abolish photosynthesis and radial growth in P. × canescens, resulted in hydraulic adaptation by increased vessel frequencies and decreased vessel lumina. Transcript abundances of a suite of genes (FLA, COB-like, BAM, XET, etc.) previously shown to be activated during tension wood formation, were collectively suppressed in developing xylem, whereas those for stress and defense-related genes increased. A subset of cell wall-related genes was also suppressed in salt-exposed P. euphratica, although this species largely excluded sodium and showed no anatomical alterations. Salt exposure influenced cell wall composition involving increases in the lignin : carbohydrate ratio in both species. • In conclusion, hydraulic stress adaptation involves cell wall modifications reciprocal to tension wood formation that result in the formation of a novel type of reaction wood in upright stems named 'pressure wood'. Our data suggest that transcriptional co-regulation of a core set of genes determines reaction wood composition. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

[The high pressure life of piezophiles].

PubMed

Oger, Philippe; Cario, Anaïs

2014-01-01

The deep biosphere is composed of very different biotopes located in the depth of the oceans, the ocean crust or the lithosphere. Although very different, deep biosphere biotopes share one common feature, high hydrostatic pressure. The deep biosphere is colonized by specific organisms, called piezophiles, that are able to grow under high hydrostatic pressure. Bacterial piezophiles are mainly psychrophiles belonging to five genera of γ-proteobacteria, Photobacterium, Shewanella, Colwellia, Psychromonas and Moritella, while piezophilic Archaea are mostly (hyper)thermophiles from the Thermococcales. None of these genera are specific for the deep biosphere. High pressure deeply impacts the activity of cells and cellular components, and reduces the activity of numerous key processes, eventually leading to cell death of piezosensitive organisms. Biochemical and genomic studies yield a fragmented view on the adaptive mechanisms in piezophiles. It is yet unclear whether piezophilic adaptation requires the modification of a few genes, or metabolic pathways, or a more profound reorganization of the genome, the fine tuning of gene expression to compensate the pressure-induced loss of activity of the proteins most affected by high pressure, or a stress-like physiological cell response. In contrast to what has been seen for thermophily or halophily, the adaptation to high pressure is diffuse in the genome and may concern only a small fraction of the genes. © Société de Biologie, 2014.

Modeling of silicon in femtosecond laser-induced modification regimes: accounting for ambipolar diffusion

NASA Astrophysics Data System (ADS)

Derrien, Thibault J.-Y.; Bulgakova, Nadezhda M.

2017-05-01

During the last decades, femtosecond laser irradiation of materials has led to the emergence of various applications based on functionalization of surfaces at the nano- and microscale. Via inducing a periodic modification on material surfaces (band gap modification, nanostructure formation, crystallization or amorphization), optical and mechanical properties can be tailored, thus turning femtosecond laser to a key technology for development of nanophotonics, bionanoengineering, and nanomechanics. Although modification of semiconductor surfaces with femtosecond laser pulses has been studied for more than two decades, the dynamics of coupling of intense laser light with excited matter remains incompletely understood. In particular, swift formation of a transient overdense electron-hole plasma dynamically modifies optical properties in the material surface layer and induces large gradients of hot charge carriers, resulting in ultrafast charge-transport phenomena. In this work, the dynamics of ultrafast laser excitation of a semiconductor material is studied theoretically on the example of silicon. A special attention is paid to the electron-hole pair dynamics, taking into account ambipolar diffusion effects. The results are compared with previously developed simulation models, and a discussion of the role of charge-carrier dynamics in localization of material modification is provided.

A shared mechanism of defense against predators and parasites: chitin regulation and its implications for life-history theory.

PubMed

Beckerman, Andrew P; de Roij, Job; Dennis, Stuart R; Little, Tom J

2013-12-01

Defenses against predators and parasites offer excellent illustrations of adaptive phenotypic plasticity. Despite vast knowledge about such induced defenses, they have been studied largely in isolation, which is surprising, given that predation and parasitism are ubiquitous and act simultaneously in the wild. This raises the possibility that victims must trade-off responses to predation versus parasitism. Here, we propose that arthropod responses to predators and parasites will commonly be based on the endocrine regulation of chitin synthesis and degradation. The proposal is compelling because many inducible defenses are centered on temporal or spatial modifications of chitin-rich structures. Moreover, we show how the chitin synthesis pathway ends in a split to carapace or gut chitin, and how this form of molecular regulation can be incorporated into theory on life-history trade-offs, specifically the Y-model. Our hypothesis thus spans several biological scales to address advice from Stearns that "Endocrine mechanisms may prove to be only the tip of an iceberg of physiological mechanisms that modulate the expression of genetic covariance".

Shakeout: A New Approach to Regularized Deep Neural Network Training.

PubMed

Kang, Guoliang; Li, Jun; Tao, Dacheng

2018-05-01

Recent years have witnessed the success of deep neural networks in dealing with a plenty of practical problems. Dropout has played an essential role in many successful deep neural networks, by inducing regularization in the model training. In this paper, we present a new regularized training approach: Shakeout. Instead of randomly discarding units as Dropout does at the training stage, Shakeout randomly chooses to enhance or reverse each unit's contribution to the next layer. This minor modification of Dropout has the statistical trait: the regularizer induced by Shakeout adaptively combines , and regularization terms. Our classification experiments with representative deep architectures on image datasets MNIST, CIFAR-10 and ImageNet show that Shakeout deals with over-fitting effectively and outperforms Dropout. We empirically demonstrate that Shakeout leads to sparser weights under both unsupervised and supervised settings. Shakeout also leads to the grouping effect of the input units in a layer. Considering the weights in reflecting the importance of connections, Shakeout is superior to Dropout, which is valuable for the deep model compression. Moreover, we demonstrate that Shakeout can effectively reduce the instability of the training process of the deep architecture.

Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis.

PubMed

Brown, Marishka K; Chan, May T; Zimmerman, John E; Pack, Allan I; Jackson, Nicholas E; Naidoo, Nirinjini

2014-06-01

Alterations in the quality, quantity, and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response. The effectiveness of the adaptive unfolded protein response is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of X-box binding protein 1 and upregulation of phosphorylated elongation initiation factor 2 α, in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged or sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep or sleep debt discharge. Copyright © 2014 Elsevier Inc. All rights reserved.

Aging induced ER stress alters sleep and sleep homeostasis

PubMed Central

Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

2014-01-01

Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of x-box binding protein 1 (XBP1) and upregulation of phosphorylated elongation initiation factor 2 α (p-eIF2α), in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged/sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep/ sleep debt discharge. PMID:24444805

SU-8 based microdevices to study self-induced chemotaxis in 3D microenvironments

NASA Astrophysics Data System (ADS)

Ayuso, Jose; Monge, Rosa; Llamazares, Guillermo; Moreno, Marco; Agirregabiria, Maria; Berganzo, Javier; Doblaré, Manuel; Ochoa, Iñaki; Fernandez, Luis

2015-05-01

Tissues are complex three-dimensional structures in which cell behaviour is frequently guided by chemotactic signals. Although starvation and nutrient restriction induce many different chemotactic processes, the recreation of such conditions in vitro remains difficult when using standard cell culture equipment. Recently, microfluidic techniques have arisen as powerful tools to mimic such physiological conditions. In this context, microfluidic three-dimensional cell culture systems require precise control of cell/hydrogel location because samples need to be placed within a microchamber without obstruction of surrounding elements. In this article, SU-8 is studied as structural material for the fabrication of complex cell culture devices due to its good mechanical properties, low gas permeability and sensor integration capacity. In particular, this manuscript presents a SU-8 based microdevice designed to create “self-induced” medium starvation, based on the combination of nutrient restriction and natural cell metabolism. Results show a natural migratory response towards nutrient source, showing how cells adapt to their own microenvironment modifications. The presented results demonstrate the SU-8 potential for microdevice fabrication applied to cell culture.

Conceptual design study of a Harrier V/STOL research aircraft

NASA Technical Reports Server (NTRS)

Bode, W. E.; Berger, R. L.; Elmore, G. A.; Lacey, T. R.

1978-01-01

MCAIR recently completed a conceptual design study to define modification approaches to, and derive planning prices for the conversion of a two place Harrier to a V/STOL control, display and guidance research aircraft. Control concepts such as rate damping, attitude stabilization, velocity command, and cockpit controllers are to be demonstrated. Display formats will also be investigated, and landing, navigation and guidance systems flight tested. The rear cockpit is modified such that it can be quickly adapted to faithfully simulate the controls, displays and handling qualities of a Type A or Type B V/STOL. The safety pilot always has take command capability. The modifications studied fall into two categories: basic modifications and optional modifications. Technical descriptions of the basic modifications and of the optional modifications are presented. The modification plan and schedule as well as the test plan and schedule are presented. The failure mode and effects analysis, aircraft performance, aircraft weight, and aircraft support are discussed.

The evolutionary implications of epigenetic inheritance.

PubMed

Jablonka, Eva

2017-10-06

The Modern Evolutionary Synthesis (MS) forged in the mid-twentieth century was built on a notion of heredity that excluded soft inheritance, the inheritance of the effects of developmental modifications. However, the discovery of molecular mechanisms that generate random and developmentally induced epigenetic variations is leading to a broadening of the notion of biological heredity that has consequences for ideas about evolution. After presenting some old challenges to the MS that were raised, among others, by Karl Popper, I discuss recent research on epigenetic inheritance, which provides experimental and theoretical support for these challenges. There is now good evidence that epigenetic inheritance is ubiquitous and is involved in adaptive evolution and macroevolution. I argue that the many evolutionary consequences of epigenetic inheritance open up new research areas and require the extension of the evolutionary synthesis beyond the current neo-Darwinian model.

DNA Methylation and Demethylation in Plant Immunity.

PubMed

Deleris, A; Halter, T; Navarro, L

2016-08-04

Detection of plant and animal pathogens triggers a massive transcriptional reprogramming, which is directed by chromatin-based processes, and ultimately results in antimicrobial immunity. Although the implication of histone modifications in orchestrating biotic stress-induced transcriptional reprogramming has been well characterized, very little was known, until recently, about the role of DNA methylation and demethylation in this process. In this review, we summarize recent findings on the dynamics and biological relevance of DNA methylation and demethylation in plant immunity against nonviral pathogens. In particular, we report the implications of these epigenetic regulatory processes in the transcriptional and co-transcriptional control of immune-responsive genes and discuss their relevance in fine-tuning antimicrobial immune responses. Finally, we discuss the possible yet elusive role of DNA methylation and demethylation in systemic immune responses, transgenerational immune priming, and de novo epiallelism, which could be adaptive.

Space Station requirements for in-flight exercise countermeasures

NASA Technical Reports Server (NTRS)

Hayes, Judith C.; Harris, Bernard A.

1990-01-01

In an effort to retard the deleterious effects of space adaptation, NASA has defined requirements for an Exercise Countermeasure Facility (ECF) within the Space Station Crew Health Care System (CHeCS). The application of exercise as a countermeasure to spaceflight-induced deconditioning has been utilized in the past by both the United States and the Soviet space programs. The ECF will provide exercise hardware, physiological monitoring capabilities, and an interactive motivational display system. ECF operations and data will be coupled through the Space Station Freedom Data Management System for monitoring of inflight training and testing from ground control, thus allowing for real-time evaluation of crewmember performance and modification of exercise prescriptions. Finally, the objective of the ECF is to monitor and control the exercise of crewmembers for the maintenance of an operational level of fitness to ensure mission success.

Backstepping Design of Adaptive Neural Fault-Tolerant Control for MIMO Nonlinear Systems.

PubMed

Gao, Hui; Song, Yongduan; Wen, Changyun

In this paper, an adaptive controller is developed for a class of multi-input and multioutput nonlinear systems with neural networks (NNs) used as a modeling tool. It is shown that all the signals in the closed-loop system with the proposed adaptive neural controller are globally uniformly bounded for any external input in . In our control design, the upper bound of the NN modeling error and the gains of external disturbance are characterized by unknown upper bounds, which is more rational to establish the stability in the adaptive NN control. Filter-based modification terms are used in the update laws of unknown parameters to improve the transient performance. Finally, fault-tolerant control is developed to accommodate actuator failure. An illustrative example applying the adaptive controller to control a rigid robot arm shows the validation of the proposed controller.In this paper, an adaptive controller is developed for a class of multi-input and multioutput nonlinear systems with neural networks (NNs) used as a modeling tool. It is shown that all the signals in the closed-loop system with the proposed adaptive neural controller are globally uniformly bounded for any external input in . In our control design, the upper bound of the NN modeling error and the gains of external disturbance are characterized by unknown upper bounds, which is more rational to establish the stability in the adaptive NN control. Filter-based modification terms are used in the update laws of unknown parameters to improve the transient performance. Finally, fault-tolerant control is developed to accommodate actuator failure. An illustrative example applying the adaptive controller to control a rigid robot arm shows the validation of the proposed controller.

A Pilot Study of an Adaptive, Idiographic, and Multi-Component Attention Bias Modification Program for Social Anxiety Disorder

PubMed Central

Amir, Nader; Kuckertz, Jennie M.; Strege, Marlene V.

2016-01-01

An attentional bias toward threat may be one mechanism underlying clinical anxiety. Attention bias modification (ABM) aims to reduce symptoms of anxiety disorders by directly modifying this deficit. However, existing ABM training programs have not consistently modified attentional bias and may not reflect optimal learning needs of participants (i.e., lack of explicit instruction, training goal unclear to participants, lack of feedback, non-adaptive, inability to differentiate or target different components of attentional bias). In the current study, we introduce a new adaptive ABM program (AABM) and test its feasibility in individuals with social anxiety disorder. We report task characteristics and preliminary evidence that this task consistently modifies attentional bias and that changes in attentional bias (but not number of trials) correlate with the level of symptom reduction. These results suggest that AABM may be a targeted method for the next generation of studies examining the utility of attention training. PMID:27795598

Induction of Fatty Acid Composition Modifications and Tolerance to Biocides in Salmonella enterica Serovar Typhimurium by Plant-Derived Terpenes▿

PubMed Central

Dubois-Brissonnet, Florence; Naïtali, Murielle; Mafu, Akier Assanta; Briandet, Romain

2011-01-01

To enhance food safety and stability, the food industry tends to use natural antimicrobials such as plant-derived compounds as an attractive alternative to chemical preservatives. Nonetheless, caution must be exercised in light of the potential for bacterial adaptation to these molecules, a phenomenon previously observed with other antimicrobials. The aim of this study was to characterize the adaptation of Salmonella enterica serovar Typhimurium to sublethal concentrations of four terpenes extracted from aromatic plants: thymol, carvacrol, citral, and eugenol, or combinations thereof. Bacterial adaptation in these conditions was demonstrated by changes in membrane fatty acid composition showing (i) limitation of the cyclization of unsaturated fatty acids to cyclopropane fatty acids when cells entered the stationary phase and (ii) bacterial membrane saturation. Furthermore, we demonstrated an increased cell resistance to the bactericidal activity of two biocides (peracetic acid and didecyl dimethyl ammonium bromide). The implications of membrane modifications in terms of hindering the penetration of antimicrobials through the bacterial membrane are discussed. PMID:21131520

Adaptation of commercial microscopes for advanced imaging applications

NASA Astrophysics Data System (ADS)

Brideau, Craig; Poon, Kelvin; Stys, Peter

2015-03-01

Today's commercially available microscopes offer a wide array of options to accommodate common imaging experiments. Occasionally, an experimental goal will require an unusual light source, filter, or even irregular sample that is not compatible with existing equipment. In these situations the ability to modify an existing microscopy platform with custom accessories can greatly extend its utility and allow for experiments not possible with stock equipment. Light source conditioning/manipulation such as polarization, beam diameter or even custom source filtering can easily be added with bulk components. Custom and after-market detectors can be added to external ports using optical construction hardware and adapters. This paper will present various examples of modifications carried out on commercial microscopes to address both atypical imaging modalities and research needs. Violet and near-ultraviolet source adaptation, custom detection filtering, and laser beam conditioning and control modifications will be demonstrated. The availability of basic `building block' parts will be discussed with respect to user safety, construction strategies, and ease of use.

Epigenetics of Peripheral B-Cell Differentiation and the Antibody Response

PubMed Central

Zan, Hong; Casali, Paolo

2015-01-01

Epigenetic modifications, such as histone post-translational modifications, DNA methylation, and alteration of gene expression by non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are heritable changes that are independent from the genomic DNA sequence. These regulate gene activities and, therefore, cellular functions. Epigenetic modifications act in concert with transcription factors and play critical roles in B cell development and differentiation, thereby modulating antibody responses to foreign- and self-antigens. Upon antigen encounter by mature B cells in the periphery, alterations of these lymphocytes epigenetic landscape are induced by the same stimuli that drive the antibody response. Such alterations instruct B cells to undergo immunoglobulin (Ig) class switch DNA recombination (CSR) and somatic hypermutation (SHM), as well as differentiation to memory B cells or long-lived plasma cells for the immune memory. Inducible histone modifications, together with DNA methylation and miRNAs modulate the transcriptome, particularly the expression of activation-induced cytidine deaminase, which is essential for CSR and SHM, and factors central to plasma cell differentiation, such as B lymphocyte-induced maturation protein-1. These inducible B cell-intrinsic epigenetic marks guide the maturation of antibody responses. Combinatorial histone modifications also function as histone codes to target CSR and, possibly, SHM machinery to the Ig loci by recruiting specific adaptors that can stabilize CSR/SHM factors. In addition, lncRNAs, such as recently reported lncRNA-CSR and an lncRNA generated through transcription of the S region that form G-quadruplex structures, are also important for CSR targeting. Epigenetic dysregulation in B cells, including the aberrant expression of non-coding RNAs and alterations of histone modifications and DNA methylation, can result in aberrant antibody responses to foreign antigens, such as those on microbial pathogens, and generation of pathogenic autoantibodies, IgE in allergic reactions, as well as B cell neoplasia. Epigenetic marks would be attractive targets for new therapeutics for autoimmune and allergic diseases, and B cell malignancies. PMID:26697022

Vestibular-Somatosensory Convergence in Head Movement Control During Locomotion after Long-Duration Space Flight

NASA Technical Reports Server (NTRS)

Mulavara, Ajitkumar; Ruttley, Tara; Cohen, Helen; Peters, Brian; Miller, Chris; Brady, Rachel; Merkle, Lauren; Bloomberg, Jacob

2010-01-01

Exposure to the microgravity conditions of space flight induces adaptive modification in the control of vestibular-mediated reflexive head movement during locomotion after space flight. Space flight causes astronauts to be exposed to somatosensory adaptation in both the vestibular and body load-sensing (BLS) systems. The goal of these studies was to examine the contributions of vestibular and BLS-mediated somatosensory influences on head movement control during locomotion after long-duration space flight. Subjects were asked to walk on a treadmill driven at 1.8 m/s while performing a visual acuity task. Data were collected using the same testing protocol from three independent subject groups; 1) normal subjects before and after exposure to 30 minutes of 40% bodyweight unloaded treadmill walking, 2) bilateral labyrinthine deficient (LD) patients and 3) astronauts who performed the protocol before and after long duration space flight. Motion data from head and trunk segmental motion data were obtained to calculate the angular head pitch (HP) movements during walking trials while subjects performed the visual task, to estimate the contributions of vestibular reflexive mechanisms in HP movements. Results showed that exposure to unloaded locomotion caused a significant increase in HP movements, whereas in the LD patients the HP movements were significantly decreased. Astronaut subjects results showed a heterogeneous response of both increases and decreases in the amplitude of HP movement. We infer that BLS-mediated somatosensory input centrally modulates vestibular input and can adaptively modify head-movement control during locomotion. Thus, space flight may cause a central adaptation mediated by the converging vestibular and body load-sensing somatosensory systems.

Electrochemical impedance spectroscopy investigation on the clinical lifetime of ProTaper rotary file system.

PubMed

Penta, Virgil; Pirvu, Cristian; Demetrescu, Ioana

2014-01-01

The main objective of the current paper is to show that electrochemical impedance spectroscopy (EIS) could be a method for evaluating and predicting of ProTaper rotary file system clinical lifespan. This particular aspect of everyday use of the endodontic files is of great importance in each dental practice and has profound clinical implications. The method used for quantification resides in the electrochemical impedance spectroscopy theory and has in its main focus the characteristics of the surface titanium oxide layer. This electrochemical technique has been adapted successfully to identify the quality of the Ni-Ti files oxide layer. The modification of this protective layer induces changes in corrosion behavior of the alloy modifying the impedance value of the file. In order to assess the method, 14 ProTaper sets utilized on different patients in a dental clinic have been submitted for testing using EIS. The information obtained in regard to the surface oxide layer has offered an indication of use and proves that the said layer evolves with each clinical application. The novelty of this research is related to an electrochemical technique successfully adapted for Ni-Ti file investigation and correlation with surface and clinical aspects.

Performance Optimizing Multi-Objective Adaptive Control with Time-Varying Model Reference Modification

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.; Hashemi, Kelley E.; Yucelen, Tansel; Arabi, Ehsan

2017-01-01

This paper presents a new adaptive control approach that involves a performance optimization objective. The problem is cast as a multi-objective optimal control. The control synthesis involves the design of a performance optimizing controller from a subset of control inputs. The effect of the performance optimizing controller is to introduce an uncertainty into the system that can degrade tracking of the reference model. An adaptive controller from the remaining control inputs is designed to reduce the effect of the uncertainty while maintaining a notion of performance optimization in the adaptive control system.

Adaptation of the membrane in Archaea.

PubMed

Oger, Philippe M; Cario, Anaïs

2013-12-15

Microbes often face contrasted and fluctuating environmental conditions, to which they need to adapt or die. Because membranes play a central role in regulating fluxes inward and outward from the cells, maintaining the appropriate structure of the membrane is crucial to maintain cellular integrity and functions. This is achieved in bacteria and eucarya by a modification of the membrane lipid compositions, a strategy termed homeoviscous adaptation. We review here evidence for homeoviscous adaptation in Archaea, and discuss the limits of this strategy and our knowledge in this very peculiar domain of life. © 2013 Elsevier B.V. All rights reserved.

38 CFR 21.216 - Special equipment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... aids to closed-circuit TV systems which amplify reading material for veterans with severe visual impairments. (3) Modifications to improve access. This category includes adaptations of environment not...

Enduring stereoscopic motion aftereffects induced by prolonged adaptation.

PubMed

Bowd, C; Rose, D; Phinney, R E; Patterson, R

1996-11-01

This study investigated the effects of prolonged adaptation on the recovery of the stereoscopic motion aftereffect (adaptation induced by moving binocular disparity information). The adapting and test stimuli were stereoscopic grating patterns created from disparity, embedded in dynamic random-dot stereograms. Motion aftereffects induced by luminance stimuli were included in the study for comparison. Adaptation duration was either 1, 2, 4, 8, 16, 32 or 64 min and the duration of the ensuing aftereffect was the variable of interest. The results showed that aftereffect duration was proportional to the square root of adaptation duration for both stereoscopic and luminance stimuli; on log-log axes, the relation between aftereffect duration and adaptation duration was a power law with the slope near 0.5 in both cases. For both kinds of stimuli, there was no sign of adaptation saturation even at the longest adaptation duration.

Acoustics of Clear and Noise-Adapted Speech in Children, Young, and Older Adults

ERIC Educational Resources Information Center

Smiljanic, Rajka; Gilbert, Rachael C.

2017-01-01

Purpose: This study investigated acoustic-phonetic modifications produced in noise-adapted speech (NAS) and clear speech (CS) by children, young adults, and older adults. Method: Ten children (11-13 years of age), 10 young adults (18-29 years of age), and 10 older adults (60-84 years of age) read sentences in conversational and clear speaking…

Adaptive Driving Equipment: Selection and Major Considerations [and] Battery Powered Scooters and 3-Wheelers. Information Support Packets #1 and #2.

ERIC Educational Resources Information Center

Stevens, John H.

Two brief guides offer suggestions for persons with physical disabilities who are considering the purchase of adaptive driving equipment, battery-powered scooters, or three wheelers. The first guide offers guidelines for individuals considering purchase of special hand controls or other modifications or a van lift to enhance their independence in…

The progressive adaptation of a georgian isolate of African swine fever virus to vero cells leads to a gradual attenuation of virulence in swine corresponding to major modifications of the viral genome.

PubMed

Krug, Peter W; Holinka, Lauren G; O'Donnell, Vivian; Reese, Bo; Sanford, Brenton; Fernandez-Sainz, Ignacio; Gladue, Douglas P; Arzt, Jonathan; Rodriguez, Luis; Risatti, Guillermo R; Borca, Manuel V

2015-02-01

African swine fever virus (ASFV) causes a contagious and often lethal disease of feral and domestic swine. Experimental vaccines derived from naturally occurring, genetically modified, or cell culture-adapted ASFV have been evaluated, but no commercial vaccine is available to control African swine fever (ASF). We report here the genotypic and phenotypic analysis of viruses obtained at different passages during the process of adaptation of a virulent ASFV field isolate from the Republic of Georgia (ASFV-G) to grow in cultured cell lines. ASFV-G was successively passaged 110 times in Vero cells. Viruses obtained at passages 30, 60, 80, and 110 were evaluated in vitro for the ability to replicate in Vero cells and primary swine macrophages cultures and in vivo for assessing virulence in swine. Replication of ASFV-G in Vero cells increased with successive passages, corresponding to a decreased replication in primary swine macrophages cultures. In vivo, progressive loss of virus virulence was observed with increased passages in Vero cells, and complete attenuation of ASFV-G was observed at passage 110. Infection of swine with the fully attenuated virus did not confer protection against challenge with virulent parental ASFV-G. Full-length sequence analysis of each of these viruses revealed significant deletions that gradually accumulated in specific areas at the right and left variable ends of the genome. Mutations that result in amino acid substitutions and frameshift mutations were also observed, though in a rather limited number of genes. The potential importance of these genetic changes in virus adaptation/attenuation is discussed. The main problem in controlling ASF is the lack of vaccines. Attempts to produce vaccines by adaptation of ASFV to cultured cell lines have been made. These attempts led to the production of attenuated viruses that conferred only homologous protection. Specifics regarding adaptation of these isolates to cell cultures have been insufficiently described. Details like the numbers of passages required to obtain attenuated viruses, genetic modifications introduced into the virus genomes along passages, and the extent of attenuation and induced protective efficacy are not readily available. In this study, we assessed the changes that lead to decreased growth in swine macrophages and to attenuation in swine. Loss of virulence, probably associated with limited replication in vivo, may lead to the lack of protective immunity in swine observed after challenge. This report provides valuable information that can be used to further the understanding of ASFV gene function, virus attenuation, and protection against infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The Progressive Adaptation of a Georgian Isolate of African Swine Fever Virus to Vero Cells Leads to a Gradual Attenuation of Virulence in Swine Corresponding to Major Modifications of the Viral Genome

PubMed Central

Krug, Peter W.; Holinka, Lauren G.; O'Donnell, Vivian; Reese, Bo; Sanford, Brenton; Fernandez-Sainz, Ignacio; Gladue, Douglas P.; Arzt, Jonathan; Rodriguez, Luis; Risatti, Guillermo R.

2014-01-01

ABSTRACT African swine fever virus (ASFV) causes a contagious and often lethal disease of feral and domestic swine. Experimental vaccines derived from naturally occurring, genetically modified, or cell culture-adapted ASFV have been evaluated, but no commercial vaccine is available to control African swine fever (ASF). We report here the genotypic and phenotypic analysis of viruses obtained at different passages during the process of adaptation of a virulent ASFV field isolate from the Republic of Georgia (ASFV-G) to grow in cultured cell lines. ASFV-G was successively passaged 110 times in Vero cells. Viruses obtained at passages 30, 60, 80, and 110 were evaluated in vitro for the ability to replicate in Vero cells and primary swine macrophages cultures and in vivo for assessing virulence in swine. Replication of ASFV-G in Vero cells increased with successive passages, corresponding to a decreased replication in primary swine macrophages cultures. In vivo, progressive loss of virus virulence was observed with increased passages in Vero cells, and complete attenuation of ASFV-G was observed at passage 110. Infection of swine with the fully attenuated virus did not confer protection against challenge with virulent parental ASFV-G. Full-length sequence analysis of each of these viruses revealed significant deletions that gradually accumulated in specific areas at the right and left variable ends of the genome. Mutations that result in amino acid substitutions and frameshift mutations were also observed, though in a rather limited number of genes. The potential importance of these genetic changes in virus adaptation/attenuation is discussed. IMPORTANCE The main problem in controlling ASF is the lack of vaccines. Attempts to produce vaccines by adaptation of ASFV to cultured cell lines have been made. These attempts led to the production of attenuated viruses that conferred only homologous protection. Specifics regarding adaptation of these isolates to cell cultures have been insufficiently described. Details like the numbers of passages required to obtain attenuated viruses, genetic modifications introduced into the virus genomes along passages, and the extent of attenuation and induced protective efficacy are not readily available. In this study, we assessed the changes that lead to decreased growth in swine macrophages and to attenuation in swine. Loss of virulence, probably associated with limited replication in vivo, may lead to the lack of protective immunity in swine observed after challenge. This report provides valuable information that can be used to further the understanding of ASFV gene function, virus attenuation, and protection against infection. PMID:25505073

Ultrafast laser-induced modifications of energy bands of non-metal crystals

NASA Astrophysics Data System (ADS)

Gruzdev, Vitaly

2009-10-01

Ultrafast laser-induced variations of electron energy bands of transparent solids significantly influence ionization and conduction-band electron absorption driving the initial stage of laser-induced damage (LID). The mechanisms of the variations are attributed to changing electron functions from bonding to anti-bonding configuration via laser-induced ionization; laser-driven electron oscillations in quasi-momentum space; and direct distortion of the inter-atomic potential by electric field of laser radiation. The ionization results in the band-structure modification via accumulation of broken chemical bonds between atoms and provides significant contribution to the overall modification only when enough excited electrons are accumulated in the conduction band. The oscillations are associated with modification of electron energy by pondermotive potential of the oscillations. The direct action of radiation's electric field leads to specific high-frequency Franz-Keldysh effect (FKE) spreading the allowed electron states into the bands of forbidden energy. Those processes determine the effective band gap that is a laser-driven energy gap between the modified electron energy bands. Among those mechanisms, the latter two provide reversible band-structure modification that takes place from the beginning of the ionization and are, therefore, of special interest due to their strong influence on the initial stage of the ionization. The pondermotive potential results either in monotonous increase or oscillatory variations of the effective band gap that has been taken into account in some ionization models. The classical FKE provides decrease of the band gap. We analyzing the competition between those two opposite trends of the effective-band-gap variations and discuss applications of those effects for considerations of the laser-induced damage and its threshold in transparent solids.

Process for derivatizing carbon nanotubes with diazonium species

NASA Technical Reports Server (NTRS)

Tour, James M. (Inventor); Bahr, Jeffrey L. (Inventor); Yang, Jiping (Inventor)

2007-01-01

The invention incorporates new processes for the chemical modification of carbon nanotubes. Such processes involve the derivatization of multi- and single-wall carbon nanotubes, including small diameter (ca. 0.7 nm) single-wall carbon nanotubes, with diazonium species. The method allows the chemical attachment of a variety of organic compounds to the side and ends of carbon nanotubes. These chemically modified nanotubes have applications in polymer composite materials, molecular electronic applications and sensor devices. The methods of derivatization include electrochemical induced reactions thermally induced reactions (via in-situ generation of diazonium compounds or pre-formed diazonium compounds), and photochemically induced reactions. The derivatization causes significant changes in the spectroscopic properties of the nanotubes. The estimated degree of functionality is ca. 1 out of every 20 to 30 carbons in a nanotube bearing a functionality moiety. Such electrochemical reduction processes can be adapted to apply site-selective chemical functionalization of nanotubes. Moreover, when modified with suitable chemical groups, the derivatized nanotubes are chemically compatible with a polymer matrix, allowing transfer of the properties of the nanotubes (such as, mechanical strength or electrical conductivity) to the properties of the composite material as a whole. Furthermore, when modified with suitable chemical groups, the groups can be polymerized to form a polymer that includes carbon nanotubes ##STR00001##.

High throughput atmospheric pressure plasma-induced graft polymerization for identifying protein-resistant surfaces.

PubMed

Gu, Minghao; Kilduff, James E; Belfort, Georges

2012-02-01

Three critical aspects of searching for and understanding how to find highly resistant surfaces to protein adhesion are addressed here with specific application to synthetic membrane filtration. They include the (i) discovery of a series of previously unreported monomers from a large library of monomers with high protein resistance and subsequent low fouling characteristics for membrane ultrafiltration of protein-containing fluids, (ii) development of a new approach to investigate protein-resistant mechanisms from structure-property relationships, and (iii) adaptation of a new surface modification method, called atmospheric pressure plasma-induced graft polymerization (APP), together with a high throughput platform (HTP), for low cost vacuum-free synthesis of anti-fouling membranes. Several new high-performing chemistries comprising two polyethylene glycol (PEG), two amines and one zwitterionic monomers were identified from a library (44 commercial monomers) of five different classes of monomers as strong protein-resistant monomers. Combining our analysis here, using the Hansen solubility parameters (HSP) approach, and data from the literature, we conclude that strong interactions with water (hydrogen bonding) and surface flexibility are necessary for producing the highest protein resistance. Superior protein-resistant surfaces and subsequent anti-fouling performance was obtained with the HTP-APP as compared with our earlier HTP-photo graft-induced polymerization (PGP). Copyright © 2011 Elsevier Ltd. All rights reserved.

Fuzhuan tea consumption imparts hepatoprotective effects and alters intestinal microbiota in high saturated fat diet-fed rats.

PubMed

Foster, Michelle T; Gentile, Christopher L; Cox-York, Kimberly; Wei, Yuren; Wang, Dong; Estrada, Andrea L; Reese, Lauren; Miller, Tirrel; Pagliassotti, Michael J; Weir, Tiffany L

2016-05-01

Nonalcoholic fatty liver disease is an obesity-related disorder characterized by lipid infiltration of the liver. Management is limited to lifestyle modifications, highlighting the need for alternative therapeutic options. The objective of this study was to examine if fermented Fuzhuan tea prevents metabolic impairments associated with development of hepatic steatosis. Rats consumed control (CON) or high saturated fat (SAT) diets with or without Fuzhuan tea for 8 weeks. Outcomes included enzymatic and gene expression measures of metabolic dysregulation in liver and adipose tissue. Pyrosequencing was used to assess intestinal microbiota adaptations. Fuzhuan tea prevented diet-induced inflammation in the liver. Liver triglycerides of ∼18 mg/g were observed in SAT-fed animals, but remained similar to CON diet levels (∼12 mg/g) when supplemented with Fuzhuan tea. In adipose tissue, tea treatment prevented SAT-induced inflammation and reduced plasma leptin approximately twofold. Fuzhuan tea also altered intestinal function and was associated with a threefold increase in two Lactobacillus spp. These data suggest that Fuzhuan tea protects against liver and adipose tissue stress induced by a high SAT diet and positively influences intestinal function. Further investigation of the molecular targets of Fuzhuan tea is warranted. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An Optimal Control Modification to Model-Reference Adaptive Control for Fast Adaptation

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.; Krishnakumar, Kalmanje; Boskovic, Jovan

2008-01-01

This paper presents a method that can achieve fast adaptation for a class of model-reference adaptive control. It is well-known that standard model-reference adaptive control exhibits high-gain control behaviors when a large adaptive gain is used to achieve fast adaptation in order to reduce tracking error rapidly. High gain control creates high-frequency oscillations that can excite unmodeled dynamics and can lead to instability. The fast adaptation approach is based on the minimization of the squares of the tracking error, which is formulated as an optimal control problem. The necessary condition of optimality is used to derive an adaptive law using the gradient method. This adaptive law is shown to result in uniform boundedness of the tracking error by means of the Lyapunov s direct method. Furthermore, this adaptive law allows a large adaptive gain to be used without causing undesired high-gain control effects. The method is shown to be more robust than standard model-reference adaptive control. Simulations demonstrate the effectiveness of the proposed method.

Investigations of respiratory control systems simulation

NASA Technical Reports Server (NTRS)

Gallagher, R. R.

1973-01-01

The Grodins' respiratory control model was investigated and it was determined that the following modifications were necessary before the model would be adaptable for current research efforts: (1) the controller equation must be modified to allow for integration of the respiratory system model with other physiological systems; (2) the system must be more closely correlated to the salient physiological functionings; (3) the respiratory frequency and the heart rate should be expanded to illustrate other physiological relationships and dependencies; and (4) the model should be adapted to particular individuals through a better defined set of initial parameter values in addition to relating these parameter values to the desired environmental conditions. Several of Milhorn's respiratory control models were also investigated in hopes of using some of their features as modifications for Grodins' model.

Growth and cell wall changes in stem organs under microgravity and hypergravity conditions

NASA Astrophysics Data System (ADS)

Hoson, Takayuki; Soga, Kouichi; Wakabayashi, Kazuyuki; Kamisaka, Seiichiro

Gravity strongly influences plant growth and development, which is fundamentally brought about by modifications to the properties of the cell wall. We have examined the changes in growth and cell wall properties in seedling organs under hypergravity conditions produced by centrifugation and under microgravity conditions in space. Hypergravity stimuli have been shown to decrease the growth rate of various seedling organs. When hypergravity suppressed elongation growth, a decrease in cell wall extensibility (an increase in cell wall rigidity) was induced. Hypergravity has also been shown to increase cell wall thickness in various mate-rials. In addition, a polymerization of certain matrix polysaccharides was brought about by hypergravity: in dicotyledons hypergravity increased the molecular size of xyloglucans, whereas hypergravity increased that of 1,3,1,4-β-glucans in monocotyledonous Gramineae. These mod-ifications to cell wall metabolism may be responsible for a decrease in cell wall extensibility, leading to growth suppression under hypergravity conditions. How then does microgravity in-fluence growth and cell wall properties? Here, there was a possibility that microgravity might induce changes similar to those by hypergravity, because plants have evolved and adapted to 1 g condition for more than 400 million years. However, the changes observed under microgravity conditions in space were just opposite to those induced by hypergravity: stimulation of elonga-tion growth, an increase in cell wall extensibility, and a decrease in cell wall thickness as well as depolymerization of cell wall polysaccharides were brought about in space. Furthermore, growth and cell wall properties varied in proportion to the logarithm of the magnitude of grav-ity in the range from microgravity to hypergravity, as shown in the dose-response relation in light and hormonal responses. Thus, microgravity may be a `stress-less' environment for plant seedlings to grow and develop. Preliminary results obtained by recent Space Seed experiment in the Kibo Module on the International Space Station (PI: S. Kamisaka) suggest that this hypothesis is also applicable to mature Arabidopsis plants.

Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance

PubMed Central

Lehotský, Ján; Tothová, Barbara; Kovalská, Maria; Dobrota, Dušan; Beňová, Anna; Kalenská, Dagmar; Kaplán, Peter

2016-01-01

Homocysteine (Hcy) is a toxic, sulfur-containing intermediate of methionine metabolism. Hyperhomocysteinemia (hHcy), as a consequence of impaired Hcy metabolism or defects in crucial co-factors that participate in its recycling, is assumed as an independent human stroke risk factor. Neural cells are sensitive to prolonged hHcy treatment, because Hcy cannot be metabolized either by the transsulfuration pathway or by the folate/vitamin B12 independent remethylation pathway. Its detrimental effect after ischemia-induced damage includes accumulation of reactive oxygen species (ROS) and posttranslational modifications of proteins via homocysteinylation and thiolation. Ischemic preconditioning (IPC) is an adaptive response of the CNS to sub-lethal ischemia, which elevates tissues tolerance to subsequent ischemia. The main focus of this review is on the recent data on homocysteine metabolism and mechanisms of its neurotoxicity. In this context, the review documents an increased oxidative stress and functional modification of enzymes involved in redox balance in experimentally induced hyperhomocysteinemia. It also gives an interpretation whether hyperhomocysteinemia alone or in combination with IPC affects the ischemia-induced neurodegenerative changes as well as intracellular signaling. Studies document that hHcy alone significantly increased Fluoro-Jade C- and TUNEL-positive cell neurodegeneration in the rat hippocampus as well as in the cortex. IPC, even if combined with hHcy, could still preserve the neuronal tissue from the lethal ischemic effects. This review also describes the changes in the mitogen-activated protein kinase (MAPK) protein pathways following ischemic injury and IPC. These studies provide evidence for the interplay and tight integration between ERK and p38 MAPK signaling mechanisms in response to the hHcy and also in association of hHcy with ischemia/IPC challenge in the rat brain. Further investigations of the protective factors leading to ischemic tolerance and recognition of the co-morbid risk factors would result in development of new avenues for exploration of novel therapeutics against ischemia and stroke. PMID:27932944

Heritability of targeted gene modifications induced by plant-optimized CRISPR systems.

PubMed

Mao, Yanfei; Botella, Jose Ramon; Zhu, Jian-Kang

2017-03-01

The Streptococcus-derived CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 (CRISPR-associated protein 9) system has emerged as a very powerful tool for targeted gene modifications in many living organisms including plants. Since the first application of this system for plant gene modification in 2013, this RNA-guided DNA endonuclease system has been extensively engineered to meet the requirements of functional genomics and crop trait improvement in a number of plant species. Given its short history, the emphasis of many studies has been the optimization of the technology to improve its reliability and efficiency to generate heritable gene modifications in plants. Here we review and analyze the features of customized CRISPR/Cas9 systems developed for plant genetic studies and crop breeding. We focus on two essential aspects: the heritability of gene modifications induced by CRISPR/Cas9 and the factors affecting its efficiency, and we provide strategies for future design of systems with improved activity and heritability in plants.

Exercise reverses metabolic syndrome in high-fat diet-induced obese rats.

PubMed

Touati, Sabeur; Meziri, Fayçal; Devaux, Sylvie; Berthelot, Alain; Touyz, Rhian M; Laurant, Pascal

2011-03-01

Chronic consumption of a high-fat diet induces obesity. We investigated whether exercise would reverse the cardiometabolic disorders associated with obesity without it being necessary to change from a high- to normal-fat diet. Sprague-Dawley rats were placed on a high-fat (HFD) or control diet (CD) for 12 wk. HFD rats were then divided into four groups: sedentary HFD (HFD-S), exercise trained (motor treadmill for 12 wk) HFD (HFD-Ex), modified diet (HFD to CD; HF/CD-S), and exercise trained with modified diet (HF/CD-Ex). Cardiovascular risk parameters associated with metabolic syndrome were measured, and contents of aortic Akt, phospho-Akt at Ser (473), total endothelial nitric oxide synthase (eNOS), and phospho-eNOS at Ser (1177) were determined by Western blotting. Chronic consumption of HFD induced a metabolic syndrome. Exercise and dietary modifications reduced adiposity, improved glucose and insulin levels and plasma lipid profile, and exerted an antihypertensive effect. Exercise was more effective than dietary modification in improving plasma levels of thiobarbituric acid-reacting substance and in correcting the endothelium-dependent relaxation to acetylcholine and insulin. Furthermore, independent of the diet used, exercise increased Akt and eNOS phosphorylation. Metabolic syndrome induced by HFD is reversed by exercise and diet modification. It is demonstrated that exercise training induces these beneficial effects without the requirement for dietary modification, and these beneficial effects may be mediated by shear stress-induced Akt/eNOS pathway activation. Thus, exercise may be an effective strategy to reverse almost all the atherosclerotic risk factors linked to obesity, particularly in the vasculature.

Cardiovascular Adaptations Induced by Resistance Training in Animal Models.

PubMed

Melo, S F S; da Silva Júnior, N D; Barauna, V G; Oliveira, E M

2018-01-01

In the last 10 years the number of studies showing the benefits of resistance training (RT) to the cardiovascular system, have grown. In comparison to aerobic training, RT-induced favorable adaptations to the cardiovascular system have been ignored for many years, thus the mechanisms of the RT-induced cardiovascular adaptations are still uncovered. The lack of animal models with comparable protocols to the RT performed by humans hampers the knowledge. We have used squat-exercise model, which is widely used by many others laboratories. However, to a lesser extent, other models are also employed to investigate the cardiovascular adaptations. In the subsequent sections we will review the information regarding cardiac morphological adaptations, signaling pathway of the cardiac cell, cardiac function and the vascular adaptation induced by RT using this animal model developed by Tamaki et al. in 1992. Furthermore, we also describe cardiovascular findings observed using other animal models of RT.

The Cell Nucleus in Physiological and Experimentally Induced Hypometabolism

NASA Astrophysics Data System (ADS)

Malatesta, M.

The main problem for manned space mission is, at present, represented by the mass penalty associated to the human presence. An efficient approach could be the induction of a hypometabolic stasis in the astronauts, thus drastically reducing the physical and psychological requirements of the crew. On the other hand, in the wild, a reduction in resource consumptions physiologi- cally occurs in certain animals which periodically enter hibernation, a hypometabolic state in which both the energy need and energy offer are kept at a minimum. During the last twelve years, we have been studying different tissues of hibernating dormice, with the aim of analyzing their features during the euthermia -hibernation-arousal cycle as well as getting insight into the mechanisms allowing adaptation to hypometabolism. We paid particular attention to the cell nucleus, as it is the site of chief metabolic functions, such as DNA replication and RNA transcription. Our observations revealed no significant modification in the basic features of cell nuclei during hibernation; however, the cell nuclei of hibernating dormice showed unusual nuclear bodies containing molecules involved in RNA pathways. Therefore, we supposed that they could represent storage/assembly sites of several factors for processing some RNA which could be slowly synthesised during hibernation and rapidly and abundantly released in early arousal in order to meet the increased metabolic needs of the cell. The nucleolus also underwent structural and molecular modifications during hibernation, maybe to continue important nucleolar functions, or, alternatively, permit a most efficient reactivation upon arousal. On the basis of the observations made in vivo , we recently tried to experimentally induce a reversible hypometabolic state in in vitro models, using cell lines derived from hibernating and non-hibernating species. By administering the synthetic opioid DADLE, we could significantly reduce both RNA transcrip- tion and export to cytoplasm, protein synthesis and cell proliferation. In addition, we induced the formation of some nuclear bodies similar to those found in natural hibernators. The total reversibility of DADLE effects and the absence of cytotoxicity make this molecule an interesting candidate to induce a controlled hypometabolic state, at least in in vitro systems.

Profiling Changes in Histone Post-translational Modifications by Top-Down Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Mowei; Wu, Si; Stenoien, David L.

Top-down mass spectrometry is a valuable tool for charactering post-translational modifications on histones for understanding of gene control and expression. In this protocol, we describe a top-down workflow using liquid chromatography coupled to mass spectrometry for fast global profiling of changes in histone proteoforms between a wild-type and a mutant of a fungal species. The proteoforms exhibiting different abundances can be subjected to further targeted studies by other mass spectrometric or biochemical assays. This method can be generally adapted for preliminary screening for changes in histone modifications between samples such as wild-type vs. mutant, and control vs. disease.

Developmental aspects of a life course approach to healthy ageing

PubMed Central

Cooper, C.; Aihie Sayer, A.; Eendebak, R. J.; Clough, G. F.; Beard, J. R.

2016-01-01

Abstract We examine the mechanistic basis and wider implications of adopting a developmental perspective on human ageing. Previous models of ageing have concentrated on its genetic basis, or the detrimental effects of accumulated damage, but also have raised issues about whether ageing can be viewed as adaptive itself, or is a consequence of other adaptive processes, for example if maintenance and repair processes in the period up to reproduction are traded off against later decline in function. A life course model places ageing in the context of the attainment of peak capacity for a body system, starting in early development when plasticity permits changes in structure and function induced by a range of environmental stimuli, followed by a period of decline, the rate of which depends on the peak attained as well as the later life conditions. Such path dependency in the rate of ageing may offer new insights into its modification. Focusing on musculoskeletal and cardiovascular function, we discuss this model and the possible underlying mechanisms, including endothelial function, oxidative stress, stem cells and nutritional factors such as vitamin D status. Epigenetic changes induced during developmental plasticity, and immune function may provide a common mechanistic process underlying a life course model of ageing. The life course trajectory differs in high and low resource settings. New insights into the developmental components of the life course model of ageing may lead to the design of biomarkers of later chronic disease risk and to new interventions to promote healthy ageing, with important implications for public health. PMID:26518329

Developmental aspects of a life course approach to healthy ageing.

PubMed

Hanson, M A; Cooper, C; Aihie Sayer, A; Eendebak, R J; Clough, G F; Beard, J R

2016-04-15

We examine the mechanistic basis and wider implications of adopting a developmental perspective on human ageing. Previous models of ageing have concentrated on its genetic basis, or the detrimental effects of accumulated damage, but also have raised issues about whether ageing can be viewed as adaptive itself, or is a consequence of other adaptive processes, for example if maintenance and repair processes in the period up to reproduction are traded off against later decline in function. A life course model places ageing in the context of the attainment of peak capacity for a body system, starting in early development when plasticity permits changes in structure and function induced by a range of environmental stimuli, followed by a period of decline, the rate of which depends on the peak attained as well as the later life conditions. Such path dependency in the rate of ageing may offer new insights into its modification. Focusing on musculoskeletal and cardiovascular function, we discuss this model and the possible underlying mechanisms, including endothelial function, oxidative stress, stem cells and nutritional factors such as vitamin D status. Epigenetic changes induced during developmental plasticity, and immune function may provide a common mechanistic process underlying a life course model of ageing. The life course trajectory differs in high and low resource settings. New insights into the developmental components of the life course model of ageing may lead to the design of biomarkers of later chronic disease risk and to new interventions to promote healthy ageing, with important implications for public health. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Genetic signatures of natural selection in response to air pollution in red spruce (Picea rubens, Pinaceae).

PubMed

Bashalkhanov, Stanislav; Eckert, Andrew J; Rajora, Om P

2013-12-01

One of the most important drivers of local adaptation for forest trees is climate. Coupled to these patterns, however, are human-induced disturbances through habitat modification and pollution. The confounded effects of climate and disturbance have rarely been investigated with regard to selective pressure on forest trees. Here, we have developed and used a population genetic approach to search for signals of selection within a set of 36 candidate genes chosen for their putative effects on adaptation to climate and human-induced air pollution within five populations of red spruce (Picea rubens Sarg.), distributed across its natural range and air pollution gradient in eastern North America. Specifically, we used FST outlier and environmental correlation analyses to highlight a set of seven single nucleotide polymorphisms (SNPs) that were overly correlated with climate and levels of sulphate pollution after correcting for the confounding effects of population history. Use of three age cohorts within each population allowed the effects of climate and pollution to be separated temporally, as climate-related SNPs (n = 7) showed the strongest signals in the oldest cohort, while pollution-related SNPs (n = 3) showed the strongest signals in the youngest cohorts. These results highlight the usefulness of population genetic scans for the identification of putatively nonneutral evolution within genomes of nonmodel forest tree species, but also highlight the need for the development and application of robust methodologies to deal with the inherent multivariate nature of the genetic and ecological data used in these types of analyses. © 2013 John Wiley & Sons Ltd.

Salt modulates gravity signaling pathway to regulate growth direction of primary roots in Arabidopsis.

PubMed

Sun, Feifei; Zhang, Wensheng; Hu, Haizhou; Li, Bao; Wang, Youning; Zhao, Yankun; Li, Kexue; Liu, Mengyu; Li, Xia

2008-01-01

Plant root architecture is highly plastic during development and can adapt to many environmental stresses. The proper distribution of roots within the soil under various conditions such as salinity, water deficit, and nutrient deficiency greatly affects plant survival. Salinity profoundly affects the root system architecture of Arabidopsis (Arabidopsis thaliana). However, despite the inhibitory effects of salinity on root length and the number of roots, very little is known concerning influence of salinity on root growth direction and the underlying mechanisms. Here we show that salt modulates root growth direction by reducing the gravity response. Exposure to salt stress causes rapid degradation of amyloplasts in root columella cells of Arabidopsis. The altered root growth direction in response to salt was found to be correlated with PIN-FORMED2 (PIN2) messenger RNA abundance and expression and localization of the protein. Furthermore, responsiveness to gravity of salt overly sensitive (sos) mutants is substantially reduced, indicating that salt-induced altered gravitropism of root growth is mediated by ion disequilibrium. Mutation of SOS genes also leads to reduced amyloplast degradation in root tip columella cells and the defects in PIN2 gene expression in response to salt stress. These results indicate that the SOS pathway may mediate the decrease of PIN2 messenger RNA in salinity-induced modification of gravitropic response in Arabidopsis roots. Our findings provide new insights into the development of a root system necessary for plant adaptation to high salinity and implicate an important role of the SOS signaling pathway in this process.

Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics.

PubMed

Rosenbaum, David; Mattina, Alessandro; Koch, Edouard; Rossant, Florence; Gallo, Antonio; Kachenoura, Nadjia; Paques, Michel; Redheuil, Alban; Girerd, Xavier

2016-06-01

In humans, adaptive optics camera enables precise large-scale noninvasive retinal microcirculation evaluation to assess ageing, blood pressure and antihypertensive treatments respective roles on retinal arterioles anatomy. We used adaptive optics camera rtx1 (Imagine-Eyes, Orsay, France) to measure wall thickness, internal diameter and to calculate wall-to-lumen ratio (WLR) and wall cross-sectional area of retinal arterioles. This assessment was repeated within a short period in two subgroups of hypertensive individuals without or with a drug-induced blood pressure drop. In 1000 individuals, mean wall thickness, lumen diameter and WLR were 23.2 ± 3.9, 78.0 ± 10.9 and 0.300 ± 0.054 μm, respectively. Blood pressure and age both independently increased WLR by thickening arterial wall. In opposite, hypertension narrowed lumen in younger as compared to older individuals (73.2 ± 9.0 vs. 81.7 ± 10.2 μm; P < 0.001), whereas age exerted no influence on lumen diameter. Short-term blood pressure drop (-29.3 ± 17.3/-14.4 ± 10.0 mmHg) induced a WLR decrease (-6.0 ± 8.0%) because of lumen dilatation (+4.4 ± 5.9%) without wall thickness changes. By contrast, no modifications were observed in individuals with stable blood pressure. In treated and controlled hypertensives under monotherapy WLR normalization was observed because of combined wall decrease and lumen dilatation independently of antihypertensive pharmacological classes. In multivariate analysis, hypertension drug regimen was not an independent predictor of any retinal anatomical indices. Retinal arteriolar remodeling comprised blood pressure and age-driven wall thickening as well as blood pressure-triggered lumen narrowing in younger individuals. Remodeling reversal observed in controlled hypertensives seems to include short-term functional and long-term structural changes.

Experimental Investigation of Laser-sustained Plasma in Supersonic Argon Flow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sperber, David; Eckel, Hans-Albert; Moessinger, Peter

Laser-induced energy deposition is widely discussed as a flow control technique in supersonic transportation. In case of thermal laser-plasma upstream of a blunt body, a substantial adaptation of shock wave geometry and magnitude of wave drag is predicted. Related to the research on laser supported detonation, the paper describes the implementation of laser-sustained plasma in a supersonic Argon jet. The stable plasma state is generated by the intersection of a Q-switched Nd:YAG-laser and a continuous wave CO{sub 2}-laser beams, for ignition and maintenance of the plasma respectively. A miniature supersonic Ludwieg tube test facility generates a supersonic jet at velocitiesmore » of Mach 2.1. Modifications of the flow and plasma conditions are investigated and characterized by Schlieren flow visualisation, laser energy transmission and plasma radiation measurements. The results include the discussions of the flow field as well as the required laser and gas parameters.« less

An MRM-based workflow for absolute quantitation of lysine-acetylated metabolic enzymes in mouse liver.

PubMed

Xu, Leilei; Wang, Fang; Xu, Ying; Wang, Yi; Zhang, Cuiping; Qin, Xue; Yu, Hongxiu; Yang, Pengyuan

2015-12-07

As a key post-translational modification mechanism, protein acetylation plays critical roles in regulating and/or coordinating cell metabolism. Acetylation is a prevalent modification process in enzymes. Protein acetylation modification occurs in sub-stoichiometric amounts; therefore extracting biologically meaningful information from these acetylation sites requires an adaptable, sensitive, specific, and robust method for their quantification. In this work, we combine immunoassays and multiple reaction monitoring-mass spectrometry (MRM-MS) technology to develop an absolute quantification for acetylation modification. With this hybrid method, we quantified the acetylation level of metabolic enzymes, which could demonstrate the regulatory mechanisms of the studied enzymes. The development of this quantitative workflow is a pivotal step for advancing our knowledge and understanding of the regulatory effects of protein acetylation in physiology and pathophysiology.

Targeted Modification of Mitochondrial ROS Production Converts High Glucose-Induced Cytotoxicity to Cytoprotection: Effects on Anesthetic Preconditioning.

PubMed

Sedlic, Filip; Muravyeva, Maria Y; Sepac, Ana; Sedlic, Marija; Williams, Anna Marie; Yang, Meiying; Bai, Xiaowen; Bosnjak, Zeljko J

2017-01-01

Contradictory reports on the effects of diabetes and hyperglycemia on myocardial infarction range from cytotoxicity to cytoprotection. The study was designed to investigate acute effects of high glucose-driven changes in mitochondrial metabolism and osmolarity on adaptive mechanisms and resistance to oxidative stress of isolated rat cardiomyocytes. We examined the effects of high glucose on several parameters of mitochondrial bioenergetics, including changes in oxygen consumption, mitochondrial membrane potential, and NAD(P)H fluorometry. Effects of high glucose on the endogenous cytoprotective mechanisms elicited by anesthetic preconditioning (APC) and the mediators of cell injury were also tested. These experiments included real-time measurements of reactive oxygen species (ROS) production and mitochondrial permeability transition pore (mPTP) opening in single cells by laser scanning fluorescence confocal microscopy, and cell survival assay. High glucose rapidly enhanced mitochondrial energy metabolism, observed by increase in NAD(P)H fluorescence intensity, oxygen consumption, and mitochondrial membrane potential. This substantially elevated production of ROS, accelerated opening of the mPTP, and decreased survival of cells exposed to oxidative stress. Abrogation of high glucose-induced mitochondrial hyperpolarization with 2,4 dinitrophenol (DNP) significantly, but not completely, attenuated ROS production to a level similar to hyperosmotic mannitol control. DNP treatment reversed high glucose-induced cytotoxicity to cytoprotection. Hyperosmotic mannitol treatment also induced cytoprotection. High glucose abrogated APC-induced mitochondrial depolarization, delay in mPTP opening and cytoprotection. In conclusion, high glucose-induced mitochondrial hyperpolarization abolishes APC and augments cell injury. Attenuation of high glucose-induced ROS production by eliminating mitochondrial hyperpolarization protects cardiomyocytes. J. Cell. Physiol. 232: 216-224, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

LIF and fast imaging plasma jet characterization relevant for NTP biomedical applications

NASA Astrophysics Data System (ADS)

Riès, D.; Dilecce, G.; Robert, E.; Ambrico, P. F.; Dozias, S.; Pouvesle, J.-M.

2014-07-01

In the field of biomedical application, many publications report on non-thermal plasma jet potentialities for cell behaviour modifications in cancer treatment, wound healing or sterilization. However most previous plasma jet characterizations were performed when jets expend freely in air. Only recently has the influence of the targeted surface been properly considered. In this work, modifications induced by various types of targets, mimicking the biological samples, in the plasma propagation and production of hydroxyl radicals are evidenced through time-resolved intensified charge-coupled device imaging and laser-induced fluorescence (LIF) measurements. A LIF model, also specifically dedicated to estimate air and water penetration inside the jet, is used and proves to be well adapted to characterize the plasma jet under biomedical application conditions. It is shown that the plasma produced by the plasma gun counter-propagates after impinging the surface which, for the same operating parameters, leads to an increase of almost one order of magnitude in the maximum OH density (from ˜2 × 1013 cm-3 for open-air propagation to ˜1 × 1014 cm-3 for a grounded metal target). The nature of the target, especially its electrical conductivity, as well as gas flow rate and voltage amplitude are playing a key role in the production of hydroxyl radicals. The strong interplay between gas flow dynamics and plasma propagation is here confirmed by air and water distribution measurements. The need for a multi-diagnostic approach, as well as great care in setting up the in situ characterization of plasma jets, is here emphasized. Special attention must not only be paid to voltage amplitude and gas flow rate but also to the nature, humidity and conductivity of the target.

Cold acclimation alters DNA methylation patterns and confers tolerance to heat and increases growth rate in Brassica rapa

PubMed Central

Liu, Tongkun; Li, Ying; Duan, Weike; Huang, Feiyi

2017-01-01

Abstract Epigenetic modifications are implicated in plant adaptations to abiotic stresses. Exposure of plants to one stress can induce resistance to other stresses, a process termed cross-adaptation, which is not well understood. In this study, we aimed to unravel the epigenetic basis of elevated heat-tolerance in cold-acclimated Brassica rapa by conducting a genome-wide DNA methylation analysis of leaves from control (CK) and cold-acclimated (CA) plants. We found that both methylation and demethylation occurred during cold acclimation. Two significantly altered pathways, malate dehydrogenase activity and carbon fixation, and 1562 differentially methylated genes, including BramMDH1, BraKAT2, BraSHM4, and Bra4CL2, were identified in CA plants. Genetic validation and treatment of B. rapa with 5-aza-2-deoxycytidine (Aza) suggested that promoter demethylation of four candidate genes increased their transcriptional activities. Physiological analysis suggested that elevated heat-tolerance and high growth rate were closely related to increases in organic acids and photosynthesis, respectively. Functional analyses demonstrated that the candidate gene BramMDH1 (mMDH: mitochondrial malate dehydrogenase) directly enhances organic acids and photosynthesis to increase heat-tolerance and growth rate in Arabidopsis. However, Aza-treated B. rapa, which also has elevated BramMDH1 levels, did not exhibit enhanced heat-tolerance. We therefore suggest that DNA demethylation alone is not sufficient to increase heat-tolerance. This study demonstrates that altered DNA methylation contributes to cross-adaptation. PMID:28158841

Changes related to gender, geographic population and habitat in the antennal phenotype of Triatoma patagonica Del Ponte, 1929 (Hemiptera: Reduviidae).

PubMed

Rodríguez, Claudia S; Crocco, Liliana; Altamirano, Alejandra; Catalá, Silvia

2013-02-01

Triatomines undergo morphological changes as an adaptive response to different habitats (wild, peridomestic, domestic, laboratory). The characterization of the antennal phenotype provides information on intraspecific variation caused by geographical origin and/or habitat. Triatoma patagonica Del Ponte, 1929 is known to occur in peridomiciles of rural areas in Argentina, where it also invades non-colonized dwellings. Here we describe and compare the antennal phenotype of T. patagonica in populations of different geographic origin, and explore possible modifications induced by laboratory rearing with the aim of investigating the range of phenotypic variation of the species for the first time. Sixty antennas of adult males and females of T. patagonica belonging to two peridomiciliary populations of different geographical origin were analyzed. Four types of sensilla were observed in three antennal segments, showing sexual dimorphism in the species. The multivariate analysis separated the populations of similar habitat (peridomicile) but different geographical origin, without showing differences between the peridomiciliary and laboratory populations of the same geographical origin. These results suggest phenotypic plasticity in T. patagonica, which would allow the species to adapt to a wide range of habitats without having a close association with a given host and its environment. The range of antennal phenotypic variation of T. patagonica would also be an indicator of its current stage of adaptation to the human environment. Copyright © 2012 Elsevier B.V. All rights reserved.

Mass Spectrometric Analysis of Glyoxal and Methylglyoxal-Induced Modifications in Human Hemoglobin from Poorly Controlled Type 2 Diabetes Mellitus Patients.

PubMed

Chen, Hauh-Jyun Candy; Chen, Yu-Chin; Hsiao, Chiung-Fong; Chen, Pin-Fan

2015-12-21

Glyoxal and methylglyoxal are oxoaldehydes derived from the degradation of glucose-protein conjugates and from lipid peroxidation, and they are also present in the environment. This study investigated the site-specific reaction of glyoxal and methylglyoxal with the amino acid residues on human hemoglobin using a shot-gun proteomic approach with nanoflow liquid chromatography/nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS). In human hemoglobin incubated with glyoxal, modification on 8 different sites, including lysine residues at α-Lys-11, α-Lys-16, α-Lys-56, β-Lys-17, β-Lys-66, β-Lys-144, and arginine residues at α-Arg-92 and β-Arg-30, was observed using a data-dependent scan. In methylglyoxal-treated hemoglobin, there were specific residues, namely, α-Arg-92, β-Lys-66, β-Arg-30, and β-Lys-144, forming carboxyethylation as well as the dehydrated product hydroimidazolone at α-Arg-92 and β-Arg-30. These lysine and arginine modifications were confirmed by accurate mass measurement and the MS(2) and MS(3) spectra. The most intensive signal of each modified peptide was used as the precursor ion to perform the product ion scan. The relative extent of modifications was semiquantified simultaneously relative to the native reference peptide by nanoLC-NSI/MS/MS under the selected reaction monitoring (SRM) mode. The extent of these modifications increased dose-dependently with increasing concentrations of glyoxal or methylglyoxal. Six out of the eight modifications induced by glyoxal and three out of the six modifications induced by methylglyoxal were detected in hemoglobin freshly isolated from human blood samples. The relative extent of modification of these post-translational modifications was quantified in poorly controlled type 2 diabetes mellitus patients (n = 20) and in nondiabetic control subjects (n = 21). The results show that the carboxymethylated peptides at α-Lys-16, α-Arg-92, β-Lys-17, β-Lys-66, and the peptide at α-Arg-92 with methylglyoxal-derived hydroimidazolone are significantly higher in diabetic patients than in normal individuals (p value <0.05). This report identified and quantified glyoxal- and methylglyoxal-modified hemoglobin peptides in humans and revealed the association of the extent of modifications at specific sites with T2DM. Only one drop (10 μL) of fresh blood is needed for this assay, and only an equivalent of 1 μg of hemoglobin was analyzed by the nanoLC-NSI/MS/MS-SRM system. These results suggest the potential use of these specific post-translational modifications in hemoglobin as feasible biomarker candidates to assess protein damage induced by glyoxal and methylglyoxal.

Computer program documentation modified version of the JA70 aerodynamic heating computer program H800 (MINIVER with a DISSPLA plot package

NASA Technical Reports Server (NTRS)

Olmedo, L.

1980-01-01

The changes, modifications, and inclusions which were adapted to the current version of the MINIVER program are discussed. Extensive modifications were made to various subroutines, and a new plot package added. This plot package is the Johnson Space Center DISSPLA Graphics System currently driven under an 1110 EXEC 8 configuration. User instructions on executing the MINIVER program are provided and the plot package is described.

General and inducible hypermutation facilitate parallel adaptation in Pseudomonas aeruginosa despite divergent mutation spectra.

PubMed

Weigand, Michael R; Sundin, George W

2012-08-21

The successful growth of hypermutator strains of bacteria contradicts a clear preference for lower mutation rates observed in the microbial world. Whether by general DNA repair deficiency or the inducible action of low-fidelity DNA polymerases, the evolutionary strategies of bacteria include methods of hypermutation. Although both raise mutation rate, general and inducible hypermutation operate through distinct molecular mechanisms and therefore likely impart unique adaptive consequences. Here we compare the influence of general and inducible hypermutation on adaptation in the model organism Pseudomonas aeruginosa PAO1 through experimental evolution. We observed divergent spectra of single base substitutions derived from general and inducible hypermutation by sequencing rpoB in spontaneous rifampicin-resistant (Rif(R)) mutants. Likewise, the pattern of mutation in a draft genome sequence of a derived inducible hypermutator isolate differed from those of general hypermutators reported in the literature. However, following experimental evolution, populations of both mutator types exhibited comparable improvements in fitness across varied conditions that differed from the highly specific adaptation of nonmutators. Our results suggest that despite their unique mutation spectra, general and inducible hypermutation can analogously influence the ecology and adaptation of bacteria, significantly shaping pathogenic populations where hypermutation has been most widely observed.

Statistically qualified neuro-analytic failure detection method and system

DOEpatents

Vilim, Richard B.; Garcia, Humberto E.; Chen, Frederick W.

2002-03-02

An apparatus and method for monitoring a process involve development and application of a statistically qualified neuro-analytic (SQNA) model to accurately and reliably identify process change. The development of the SQNA model is accomplished in two stages: deterministic model adaption and stochastic model modification of the deterministic model adaptation. Deterministic model adaption involves formulating an analytic model of the process representing known process characteristics, augmenting the analytic model with a neural network that captures unknown process characteristics, and training the resulting neuro-analytic model by adjusting the neural network weights according to a unique scaled equation error minimization technique. Stochastic model modification involves qualifying any remaining uncertainty in the trained neuro-analytic model by formulating a likelihood function, given an error propagation equation, for computing the probability that the neuro-analytic model generates measured process output. Preferably, the developed SQNA model is validated using known sequential probability ratio tests and applied to the process as an on-line monitoring system. Illustrative of the method and apparatus, the method is applied to a peristaltic pump system.

Paradoxical enhancement of chemoreceptor detection sensitivity by a sensory adaptation enzyme

PubMed Central

Han, Xue-Sheng; Dahlquist, Frederick W.; Parkinson, John S.

2017-01-01

A sensory adaptation system that tunes chemoreceptor sensitivity enables motile Escherichia coli cells to track chemical gradients with high sensitivity over a wide dynamic range. Sensory adaptation involves feedback control of covalent receptor modifications by two enzymes: CheR, a methyltransferase, and CheB, a methylesterase. This study describes a CheR function that opposes the signaling consequences of its catalytic activity. In the presence of CheR, a variety of mutant serine chemoreceptors displayed up to 40-fold enhanced detection sensitivity to chemoeffector stimuli. This response enhancement effect did not require the known catalytic activity of CheR, but did involve a binding interaction between CheR and receptor molecules. Response enhancement was maximal at low CheR:receptor stoichiometry and quantitative analyses argued against a reversible binding interaction that simply shifts the ON–OFF equilibrium of receptor signaling complexes. Rather, a short-lived CheR binding interaction appears to promote a long-lasting change in receptor molecules, either a covalent modification or conformation that enhances their response to attractant ligands. PMID:28827352

Characterization of Tyrosine Nitration and Cysteine Nitrosylation Modifications by Metastable Atom-Activation Dissociation Mass Spectrometry

NASA Astrophysics Data System (ADS)

Cook, Shannon L.; Jackson, Glen P.

2011-02-01

The fragmentation behavior of nitrated and S-nitrosylated peptides were studied using collision induced dissociation (CID) and metastable atom-activated dissociation mass spectrometry (MAD-MS). Various charge states, such as 1+, 2+, 3+, 2-, of modified and unmodified peptides were exposed to a beam of high kinetic energy helium (He) metastable atoms resulting in extensive backbone fragmentation with significant retention of the post-translation modifications (PTMs). Whereas the high electron affinity of the nitrotyrosine moiety quenches radical chemistry and fragmentation in electron capture dissociation (ECD) and electron transfer dissociation (ETD), MAD does produce numerous backbone cleavages in the vicinity of the modification. Fragment ions of nitrosylated cysteine modifications typically exhibit more abundant neutral losses than nitrated tyrosine modifications because of the extremely labile nature of the nitrosylated cysteine residues. However, compared with CID, MAD produced between 66% and 86% more fragment ions, which preserved the labile -NO modification. MAD was also able to differentiate I/L residues in the modified peptides. MAD is able to induce radical ion chemistry even in the presence of strong radical traps and therefore offers unique advantages to ECD, ETD, and CID for determination of PTMs such as nitrated and S-nitrosylated peptides.

How visual short-term memory maintenance modulates subsequent visual aftereffects.

PubMed

Saad, Elyana; Silvanto, Juha

2013-05-01

Prolonged viewing of a visual stimulus can result in sensory adaptation, giving rise to perceptual phenomena such as the tilt aftereffect (TAE). However, it is not known if short-term memory maintenance induces such effects. We examined how visual short-term memory (VSTM) maintenance modulates the strength of the TAE induced by subsequent visual adaptation. We reasoned that if VSTM maintenance induces aftereffects on subsequent encoding of visual information, then it should either enhance or reduce the TAE induced by a subsequent visual adapter, depending on the congruency of the memory cue and the adapter. Our results were consistent with this hypothesis and thus indicate that the effects of VSTM maintenance can outlast the maintenance period.

From Feline Idiopathic Ulcerative Dermatitis to Feline Behavioral Ulcerative Dermatitis: Grooming Repetitive Behaviors Indicators of Poor Welfare in Cats

PubMed Central

Titeux, Emmanuelle; Gilbert, Caroline; Briand, Amaury; Cochet-Faivre, Noëlle

2018-01-01

Feline idiopathic head-and-neck dermatitis—also named feline idiopathic ulcerative dermatitis (IUD)—is considered as a rare skin disease of unknown origin. It is usually associated with a crusted, non-healing, self-induced ulcer occurring most commonly on the dorsal or lateral neck or between the scapula where self-grooming by scratching occurs. Usually, IUD is diagnosed after exclusion of other causes of pruritus. In feline medicine, self-induced alopecia is recognized as a behavioral disorder (abnormal repetitive behavior) due to excessive licking, which is an amplification of a normal maintenance behavior. Such repetitive behaviors, like self-induced alopecia or self-induced wounds, are named stereotypies and considered as indicators of poor welfare. The objectives of our study were to determine, first, if the repetitive behavior associated with self-induced wounds was related to a poor welfare, and, second, if improving the welfare in the cat’s environment would lead to healing, thanks to environmental enrichment. We recruited 13 cats diagnosed with IUD by a dermatologist. These cats were referred to a behaviorist for welfare evaluation. A welfare score was attributed using a new 21-point welfare scale. The median score of the 13 IUD cats was 16, while the median score of 35 healthy cats was 7 (significant difference, p < 0.001). Major modifications of the cat’s environment and the human–cat relationship were then recommended for IUD cats. Within 15 days after environment modifications, ulcerative lesions were healed and welfare scores improved significantly (median score of 6, significantly different from the score before environmental modifications), being similar to healthy cats (no significant differences). Only one cat was treated with a psychotropic drug, owners being reluctant to improve environmental modifications. These results suggest that feline IUD is a behavioral disorder indicative of poor welfare and that it requires management by behavior specialists, proposing environmental modifications. We hence propose to rename this affection to “behavioral ulcerative dermatitis,” given that welfare scores were significantly different from healthy cats, and that environmental modifications modified welfare scores and lead to successful healing in all cases. PMID:29713639

Carbachol-induced volume adaptation in mouse bladder and length adaptation via rhythmic contraction in rabbit detrusor.

PubMed

Speich, John E; Wilson, Cameron W; Almasri, Atheer M; Southern, Jordan B; Klausner, Adam P; Ratz, Paul H

2012-10-01

The length-tension (L-T) relationships in rabbit detrusor smooth muscle (DSM) are similar to those in vascular and airway smooth muscles and exhibit short-term length adaptation characterized by L-T curves that shift along the length axis as a function of activation and strain history. In contrast to skeletal muscle, the length-active tension (L-T(a)) curve for rabbit DSM strips does not have a unique peak tension value with a single ascending and descending limb. Instead, DSM can exhibit multiple ascending and descending limbs, and repeated KCl-induced contractions at a particular muscle length on an ascending or descending limb display increasingly greater tension. In the present study, mouse bladder strips with and without urothelium exhibited KCl-induced and carbachol-induced length adaptation, and the pressure-volume relationship in mouse whole bladder displayed short-term volume adaptation. Finally, prostaglandin-E(2)-induced low-level rhythmic contraction produced length adaptation in rabbit DSM strips. A likely role of length adaptation during bladder filling is to prepare DSM cells to contract efficiently over a broad range of volumes. Mammalian bladders exhibit spontaneous rhythmic contraction (SRC) during the filling phase and SRC is elevated in humans with overactive bladder (OAB). The present data identify a potential physiological role for SRC in bladder adaptation and motivate the investigation of a potential link between short-term volume adaptation and OAB with impaired contractility.

Development of an Autonomous Broadband Acoustic Scattering System for Remote Characterization of Zooplankton

DTIC Science & Technology

2008-01-01

backscatter at a single narrowband frequency, and some AUVs carry single-frequency sidescan sonars (and this technology has been adapted for gliders), the...broadband acoustic scattering system by adapting existing technology that has been recently developed at WHOI for a monostatic Doppler sonar module...broadband acoustic backscattering system: 1) Modifications to the monostatic Doppler sonar module, recently developed at WHOI for turbulence studies

Assessment of protein modifications in liver of rats under chronic treatment with paracetamol (acetaminophen) using two complementary mass spectrometry-based metabolomic approaches.

PubMed

Mast, Carole; Lyan, Bernard; Joly, Charlotte; Centeno, Delphine; Giacomoni, Franck; Martin, Jean-François; Mosoni, Laurent; Dardevet, Dominique; Pujos-Guillot, Estelle; Papet, Isabelle

2015-04-29

Liver protein can be altered under paracetamol (APAP) treatment. APAP-protein adducts and other protein modifications (oxidation/nitration, expression) play a role in hepatotoxicity induced by acute overdoses, but it is unknown whether liver protein modifications occur during long-term treatment with non-toxic doses of APAP. We quantified APAP-protein adducts and assessed other protein modifications in the liver from rats under chronic (17 days) treatment with two APAP doses (0.5% or 1% of APAP in the diet w/w). A targeted metabolomic method was validated and used to quantify APAP-protein adducts as APAP-cysteine adducts following proteolytic hydrolysis. The limit of detection was found to be 7ng APAP-cysteine/mL hydrolysate i.e. an APAP-Cys to tyrosine ratio of 0.016‰. Other protein modifications were assessed on the same protein hydrolysate by untargeted metabolomics including a new strategy to process the data and identify discriminant molecules. These two complementary mass spectrometry (MS)-based metabolic approaches enabled the assessment of a wide range of protein modifications induced by chronic treatment with APAP. APAP-protein adducts were detected even in the absence of glutathione depletion and hepatotoxicity, i.e. in the 0.5% APAP group, and increased by 218% in the 1% APAP group compared to the 0.5% APAP group. At the same time, the untargeted metabolomic method revealed a decrease in the binding of cysteine, cysteinyl-glycine and GSH to thiol groups of protein cysteine residues, an increase in the oxidation of tryptophan and proline residues and a modification in protein expression. This wide range of modifications in liver proteins occurred in rats under chronic treatment with APAP that did not induce hepatotoxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Modification of splenic stiffness on acoustic radiation force impulse parallels the variation of portal pressure induced by transjugular intrahepatic portosystemic shunt.

PubMed

De Santis, Adriano; Nardelli, Silvia; Bassanelli, Chiara; Lupo, Marinella; Iegri, Claudia; Di Ciesco, Carmela Anna; Forlino, Mariana; Farcomeni, Alessio; Riggio, Oliviero

2018-03-01

Spleen and liver stiffness (LS) measured by acoustic radiation force impulse (ARFI) imaging has been shown to be useful in identifying patients with portal hypertension. The study aims to establish if the modification of portal pressure induced by a transjugular intrahepatic portosystemic shunt (TIPS) parallels the modification of spleen or LS measured by ARFI in order to understand if ARFI may be used to monitor the modification of portal pressure in patients with cirrhosis. Thirty-eight patients with severe portal hypertension underwent LS and spleen stiffness (SS) before TIPS and 1 week after TIPS. Portal atrial gradient (PAG) was measured before and after the shunt opening. Portal atrial gradient decreased significantly from 19.5 to 6 mmHg (P < 0.001). SS decreased significantly after TIPS (pre-TIPS 3.7 m/s vs post-TIPS 3. 1 m/s; P < 0.001), and LS was also significantly modified by TIPS (pre-TIPS 2.8 m/s vs post-TIPS 2.4 m/s; P = 0.003). PAG and SS values measured before and after TIPS were significantly correlated (r = 0.56; P < 0.001); on the other hand, PAG and LS were not (r = 0.19; P = 0.27). Two patients developed a persistent hepatic encephalopathy refractory to medical treatment and were submitted to the reduction of the stent diameter. The modification of SS was parallel to the modification of PAG. Spleen stiffness is superior to LS in detecting the modification of portal pressure induced by TIPS. This makes SS a potential non-invasive method to monitor the modification of portal hypertension. Further investigations are needed to establish applicability and clinical utility of this promising tool in the treatment of portal hypertension. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

EPAS1 variants in high altitude Tibetan wolves were selectively introgressed into highland dogs.

PubMed

vonHoldt, Bridgett; Fan, Zhenxin; Ortega-Del Vecchyo, Diego; Wayne, Robert K

2017-01-01

Admixture can facilitate adaptation. For example, black wolves have obtained the variant causing black coat color through past hybridization with domestic dogs and have higher fitness than gray colored wolves. Another recent example of the transfer of adaptive variation between the two species has been suggested by the similarity between high altitude Tibetan mastiffs and wolves at the EPAS1 gene, a transcription factor induced in low oxygen environments. Here, we investigate the directionality of admixture in EPAS1 between 28 reference highland gray wolves, 15 reference domestic dogs, and 21 putatively admixed highland wolves. This experimental design represents an expanded sample of Asian dogs and wolves from previous studies. Admixture was inferred using 17,709 publicly available SNP genotypes on canine chromosome 10. We additionally conducted a scan for positive selection in the highland dog genome. We find an excess of highland gray wolf ancestry at the EPAS1 locus in highland domestic dogs, suggesting adaptive introgression from wolves to dogs. The signal of admixture is limited in genomic extent to a small region on chromosome 10, indicating that it is the focus of selection in an oxygen-limited environment. Our results suggest that an adaptive variant of EPAS1 in highland wolves was transferred to highland dogs, carrying linked variants that potentially function in hypoxia response at high elevation. The intertwined history of dogs and wolves ensures a unique evolutionary dynamic where variants that have appeared in the history of either species can be tested for their effects on fitness under natural and artificial selection. Such coupled evolutionary histories may be key to the persistence of wild canines and their domesticated kin given the increasing anthropogenic modifications that characterize the future of both species.

Bacillus cereus cell response upon exposure to acid environment: toward the identification of potential biomarkers

PubMed Central

Desriac, Noémie; Broussolle, Véronique; Postollec, Florence; Mathot, Anne-Gabrielle; Sohier, Danièle; Coroller, Louis; Leguerinel, Ivan

2013-01-01

Microorganisms are able to adapt to different environments and evolve rapidly, allowing them to cope with their new environments. Such adaptive response and associated protections toward other lethal stresses, is a crucial survival strategy for a wide spectrum of microorganisms, including food spoilage bacteria, pathogens, and organisms used in functional food applications. The growing demand for minimal processed food yields to an increasing use of combination of hurdles or mild preservation factors in the food industry. A commonly used hurdle is low pH which allows the decrease in bacterial growth rate but also the inactivation of pathogens or spoilage microorganisms. Bacillus cereus is a well-known food-borne pathogen leading to economical and safety issues in food industry. Because survival mechanisms implemented will allow bacteria to cope with environmental changes, it is important to provide understanding of B. cereus stress response. Thus this review deals with the adaptive traits of B. cereus cells facing to acid stress conditions. The acid stress response of B. cereus could be divided into four groups (i) general stress response (ii) pH homeostasis, (iii) metabolic modifications and alkali production and (iv) secondary oxidative stress response. This current knowledge may be useful to understand how B. cereus cells may cope to acid environment such as encountered in food products and thus to find some molecular biomarkers of the bacterial behavior. These biomarkers could be furthermore used to develop new microbial behavior prediction tools which can provide insights into underlying molecular physiological states which govern the behavior of microorganisms and thus opening the avenue toward the detection of stress adaptive behavior at an early stage and the control of stress-induced resistance throughout the food chain. PMID:24106490

Enteric neuroplasticity in seawater-adapted European eel (Anguilla anguilla).

PubMed

Sorteni, C; Clavenzani, P; De Giorgio, R; Portnoy, O; Sirri, R; Mordenti, O; Di Biase, A; Parmeggiani, A; Menconi, V; Chiocchetti, R

2014-02-01

European eels live most of their lives in freshwater until spawning migration to the Sargasso Sea. During seawater adaptation, eels modify their physiology, and their digestive system adapts to the new environment, drinking salt water to compensate for the continuous water loss. In that period, eels stop feeding until spawning. Thus, the eel represents a unique model to understand the adaptive changes of the enteric nervous system (ENS) to modified salinity and starvation. To this purpose, we assessed and compared the enteric neuronal density in the cranial portion of the intestine of freshwater eels (control), lagoon eels captured in brackish water before their migration to the Sargasso Sea (T0), and starved seawater eels hormonally induced to sexual maturity (T18; 18 weeks of starvation and treatment with standardized carp pituitary extract). Furthermore, we analyzed the modification of intestinal neuronal density of hormonally untreated eels during prolonged starvation (10 weeks) in seawater and freshwater. The density of myenteric (MP) and submucosal plexus (SMP) HuC/D-immunoreactive (Hu-IR) neurons was assessed in wholemount preparations and cryosections. The number of MP and SMP HuC/D-IR neurons progressively increased from the freshwater to the salty water habitat (control > T0 > T18; P < 0.05). Compared with freshwater eels, the number of MP and SMP HuC/D-IR neurons significantly increased (P < 0.05) in the intestine of starved untreated salt water eels. In conclusion, high salinity evokes enteric neuroplasticity as indicated by the increasing number of HuC/D-IR MP and SMP neurons, a mechanism likely contributing to maintaining the body homeostasis of this fish in extreme conditions. © 2013 Anatomical Society.

Genomic and proteomic analysis of the Alkali-Tolerance Response (AlTR) in Listeria monocytogenes 10403S

PubMed Central

Giotis, Efstathios S; Muthaiyan, Arunachalam; Blair, Ian S; Wilkinson, Brian J; McDowell, David A

2008-01-01

Background Information regarding the Alkali-Tolerance Response (AlTR) in Listeria monocytogenes is very limited. Treatment of alkali-adapted cells with the protein synthesis inhibitor chloramphenicol has revealed that the AlTR is at least partially protein-dependent. In order to gain a more comprehensive perspective on the physiology and regulation of the AlTR, we compared differential gene expression and protein content of cells adapted at pH 9.5 and un-adapted cells (pH 7.0) using complementary DNA (cDNA) microarray and two-dimensional (2D) gel electrophoresis, (combined with mass spectrometry) respectively. Results In this study, L. monocytogenes was shown to exhibit a significant AlTR following a 1-h exposure to mild alkali (pH 9.5), which is capable of protecting cells from subsequent lethal alkali stress (pH 12.0). Adaptive intracellular gene expression involved genes that are associated with virulence, the general stress response, cell division, and changes in cell wall structure and included many genes with unknown functions. The observed variability between results of cDNA arrays and 2D gel electrophoresis may be accounted for by posttranslational modifications. Interestingly, several alkali induced genes/proteins can provide a cross protective overlap to other types of stresses. Conclusion Alkali pH provides therefore L. monocytogenes with nonspecific multiple-stress resistance that may be vital for survival in the human gastrointestinal tract as well as within food processing systems where alkali conditions prevail. This study showed strong evidence that the AlTR in L. monocytogenes functions as to minimize excess alkalisation and energy expenditures while mobilizing available carbon sources. PMID:18577215

Enteric neuroplasticity in seawater-adapted European eel (Anguilla anguilla)

PubMed Central

Sorteni, C; Clavenzani, P; De Giorgio, R; Portnoy, O; Sirri, R; Mordenti, O; Di Biase, A; Parmeggiani, A; Menconi, V; Chiocchetti, R

2014-01-01

European eels live most of their lives in freshwater until spawning migration to the Sargasso Sea. During seawater adaptation, eels modify their physiology, and their digestive system adapts to the new environment, drinking salt water to compensate for the continuous water loss. In that period, eels stop feeding until spawning. Thus, the eel represents a unique model to understand the adaptive changes of the enteric nervous system (ENS) to modified salinity and starvation. To this purpose, we assessed and compared the enteric neuronal density in the cranial portion of the intestine of freshwater eels (control), lagoon eels captured in brackish water before their migration to the Sargasso Sea (T0), and starved seawater eels hormonally induced to sexual maturity (T18; 18 weeks of starvation and treatment with standardized carp pituitary extract). Furthermore, we analyzed the modification of intestinal neuronal density of hormonally untreated eels during prolonged starvation (10 weeks) in seawater and freshwater. The density of myenteric (MP) and submucosal plexus (SMP) HuC/D-immunoreactive (Hu-IR) neurons was assessed in wholemount preparations and cryosections. The number of MP and SMP HuC/D-IR neurons progressively increased from the freshwater to the salty water habitat (control > T0 > T18; P < 0.05). Compared with freshwater eels, the number of MP and SMP HuC/D-IR neurons significantly increased (P < 0.05) in the intestine of starved untreated salt water eels. In conclusion, high salinity evokes enteric neuroplasticity as indicated by the increasing number of HuC/D-IR MP and SMP neurons, a mechanism likely contributing to maintaining the body homeostasis of this fish in extreme conditions. PMID:24433383

Thermo-elasto-plastic simulations of femtosecond laser-induced structural modifications: Application to cavity formation in fused silica

NASA Astrophysics Data System (ADS)

Beuton, Romain; Chimier, Benoît; Breil, Jérôme; Hébert, David; Maire, Pierre-Henri; Duchateau, Guillaume

2017-11-01

The absorbed laser energy of a femtosecond laser pulse in a transparent material induces a warm dense matter region relaxation of which may lead to structural modifications in the surrounding cold matter. The modeling of the thermo-elasto-plastic material response is addressed to predict such modifications. It has been developed in a 2D plane geometry and implemented in a hydrodynamic Lagrangian code. The particular case of a tightly focused laser beam in the bulk of fused silica is considered as a first application of the proposed general model. It is shown that the warm dense matter relaxation, influenced by the elasto-plastic behavior of the surrounding cold matter, generates both strong shock and rarefaction waves. Permanent deformations appear in the surrounding solid matter if the induced stress becomes larger than the yield strength. This interaction results in the formation of a sub-micrometric cavity surrounded by an overdense area. This approach also allows one to predict regions where cracks may form. The present modeling can be used to design nanostructures induced by short laser pulses.

Adaptation of Arabidopsis to nitrogen limitation involves induction of anthocyanin synthesis which is controlled by the NLA gene

PubMed Central

Peng, Mingsheng; Hudson, Darryl; Schofield, Andrew; Tsao, Rong; Yang, Raymond; Gu, Honglan; Bi, Yong-Mei; Rothstein, Steven. J.

2008-01-01

Plants can survive a limiting nitrogen (N) supply by developing a set of N limitation adaptive responses. However, the Arabidopsis nla (nitrogen limitation adaptation) mutant fails to produce such responses, and cannot adapt to N limitation. In this study, the nla mutant was utilized to understand further the effect of NLA on Arabidopsis adaptation to N limitation. Grown with limiting N, the nla mutant could not accumulate anthocyanins and instead produced an N limitation-induced early senescence phenotype. In contrast, when supplied with limiting N and limiting phosphorus (Pi), the nla mutants accumulated abundant anthocyanins and did not show the N limitation-induced early senescence phenotype. These results support the hypothesis that Arabidopsis has a specific pathway to control N limitation-induced anthocyanin synthesis, and the nla mutation disrupts this pathway. However, the nla mutation does not affect the Pi limitation-induced anthocyanin synthesis pathway. Therefore, Pi limitation induced the nla mutant to accumulate anthocyanins under N limitation and allowed this mutant to adapt to N limitation. Under N limitation, the nla mutant had a significantly down-regulated expression of many genes functioning in anthocyanin synthesis, and an enhanced expression of genes involved in lignin production. Correspondingly, the nla mutant grown with limiting N showed a significantly lower production of anthocyanins (particularly cyanidins) and an increase in lignin contents compared with wild-type plants. These data suggest that NLA controls Arabidopsis adaptability to N limitation by channelling the phenylpropanoid metabolic flux to the induced anthocyanin synthesis, which is important for Arabidopsis to adapt to N limitation. PMID:18552353

Low-frequency stimulation cancels the high-frequency-induced long-lasting effects in the rat medial vestibular nuclei.

PubMed

Grassi, S; Pettorossi, V E; Zampolini, M

1996-05-15

In rat brainstem slices, we investigated the effects of low-frequency stimulation (LFS) of the primary vestibular afferents on the amplitude of the field potentials evoked in the medial vestibular nuclei (MVN). LFS induced long-term effects, the sign of which depended on whether the vestibular neurons were previously conditioned by HFS. In unconditioned slices, LFS evoked modifications of the responses that were similar to those observed after HFS but had a smaller extension. In fact, LFS caused long-lasting potentiation of the N1 wave in the MVN ventral portion (Vp) and long-lasting depression of the N2 wave in the MVN dorsal portion (Dp), whereas it provoked small and variable effects on the N1 wave. By contrast, when the synaptic transmission was already conditioned, LFS influenced the synaptic responses oppositely, reducing or annulling the HFS long-term effects. This phenomenon was specifically induced by LFS, because HFS was not able to cause it. The involvement of NMDA receptors in mediating the LFS long-term effects was supported by the fact that AP-5 prevented their induction. In addition, the annulment of HFS long-term effects by LFS was also demonstrated by the shift in the latency of the evoked unitary potentials after LFS. In conclusion, we suggest that the reduction of the previously induced conditioning could represent a cancellation mechanism, useful to quickly adapt the vestibular system to continuous different needs and to avoid saturation.

c-Jun and Hypoxia-Inducible Factor 1 Functionally Cooperate in Hypoxia-Induced Gene Transcription

PubMed Central

Alfranca, Arántzazu; Gutiérrez, M. Dolores; Vara, Alicia; Aragonés, Julián; Vidal, Felipe; Landázuri, Manuel O.

2002-01-01

Under low-oxygen conditions, cells develop an adaptive program that leads to the induction of several genes, which are transcriptionally regulated by hypoxia-inducible factor 1 (HIF-1). On the other hand, there are other factors which modulate the HIF-1-mediated induction of some genes by binding to cis-acting motifs present in their promoters. Here, we show that c-Jun functionally cooperates with HIF-1 transcriptional activity in different cell types. Interestingly, a dominant-negative mutant of c-Jun which lacks its transactivation domain partially inhibits HIF-1-mediated transcription. This cooperative effect is not due to an increase in the nuclear amount of the HIF-1α subunit, nor does it require direct binding of c-Jun to DNA. c-Jun and HIF-1α are able to associate in vivo but not in vitro, suggesting that this interaction involves the participation of additional proteins and/or a posttranslational modification of these factors. In this context, hypoxia induces phosphorylation of c-Jun at Ser63 in endothelial cells. This process is involved in its cooperative effect, since specific blockade of the JNK pathway and mutation of c-Jun at Ser63 and Ser73 impair its functional cooperation with HIF-1. The functional interplay between c-Jun and HIF-1 provides a novel insight into the regulation of some genes, such as the one for VEGF, which is a key regulator of tumor angiogenesis. PMID:11739718

Estrogen Receptor β Agonist Attenuates Endoplasmic Reticulum Stress-Induced Changes in Social Behavior and Brain Connectivity in Mice.

PubMed

Crider, Amanda; Nelson, Tyler; Davis, Talisha; Fagan, Kiley; Vaibhav, Kumar; Luo, Matthew; Kamalasanan, Sunay; Terry, Alvin V; Pillai, Anilkumar

2018-02-12

Impaired social interaction is a key feature of several major psychiatric disorders including depression, autism, and schizophrenia. While, anatomically, the prefrontal cortex (PFC) is known as a key regulator of social behavior, little is known about the cellular mechanisms that underlie impairments of social interaction. One etiological mechanism implicated in the pathophysiology of the aforementioned psychiatric disorders is cellular stress and consequent adaptive responses in the endoplasmic reticulum (ER) that can result from a variety of environmental and physical factors. The ER is an organelle that serves essential roles in protein modification, folding, and maturation of proteins; however, the specific role of ER stress in altered social behavior is unknown. In this study, treatment with tunicamycin, an ER stress inducer, enhanced the phosphorylation level of inositol-requiring ER-to-nucleus signal kinase 1 (IRE1) and increased X-box-binding protein 1 (XBP1) mRNA splicing activity in the mouse PFC, whereas inhibition of IRE1/XBP1 pathway in PFC by a viral particle approach attenuated social behavioral deficits caused by tunicamycin treatment. Reduced estrogen receptor beta (ERβ) protein levels were found in the PFC of male mice following tunicamycin treatment. Pretreatment with an ERβ specific agonist, ERB-041 significantly attenuated tunicamycin-induced deficits in social behavior, and activation of IRE1/XBP1 pathway in mouse PFC. Moreover, ERB-041 inhibited tunicamycin-induced increases in functional connectivity between PFC and hippocampus in male mice. Together, these results show that ERβ agonist attenuates ER stress-induced deficits in social behavior through the IRE-1/XBP1 pathway.

Virus-induced gene silencing in Rauwolfia species.

PubMed

Corbin, Cyrielle; Lafontaine, Florent; Sepúlveda, Liuda Johana; Carqueijeiro, Ines; Courtois, Martine; Lanoue, Arnaud; Dugé de Bernonville, Thomas; Besseau, Sébastien; Glévarec, Gaëlle; Papon, Nicolas; Atehortúa, Lucia; Giglioli-Guivarc'h, Nathalie; Clastre, Marc; St-Pierre, Benoit; Oudin, Audrey; Courdavault, Vincent

2017-07-01

Elucidation of the monoterpene indole alkaloid biosynthesis has recently progressed in Apocynaceae through the concomitant development of transcriptomic analyses and reverse genetic approaches performed by virus-induced gene silencing (VIGS). While most of these tools have been primarily adapted for the Madagascar periwinkle (Catharanthus roseus), the VIGS procedure has scarcely been used on other Apocynaceae species. For instance, Rauwolfia sp. constitutes a unique source of specific and valuable monoterpene indole alkaloids such as the hypertensive reserpine but are also well recognized models for studying alkaloid metabolism, and as such would benefit from an efficient VIGS procedure. By taking advantage of a recent modification in the inoculation method of the Tobacco rattle virus vectors via particle bombardment, we demonstrated that the biolistic-mediated VIGS approach can be readily used to silence genes in both Rauwolfia tetraphylla and Rauwolfia serpentina. After establishing the bombardment conditions minimizing injuries to the transformed plantlets, gene downregulation efficiency was evaluated at approximately a 70% expression decrease in both species by silencing the phytoene desaturase encoding gene. Such a gene silencing approach will thus constitute a critical tool to identify and characterize genes involved in alkaloid biosynthesis in both of these prominent Rauwolfia species.

Development, epigenetics and metabolic programming

PubMed Central

Godfrey, Keith M; Costello, Paula; Lillycrop, Karen

2016-01-01

It is now widely recognised that the environment in early life can have important effects on human growth and development, including the “programming” of far reaching effects on the risk of developing common metabolic and other non-communicable diseases in later life. We have shown that greater childhood adiposity is associated with higher maternal adiposity, low maternal vitamin D status, excessive gestational weight gain, and short duration of breastfeeding; maternal dietary patterns in pregnancy and vitamin D status have been linked with childhood bone mineral content and muscle function. Human studies have identified fetal liver blood flow adaptations and epigenetic changes as potential mechanisms that could link maternal influences with offspring body composition. In experimental studies there is now substantial evidence that the environment during early life induces altered phenotypes through epigenetic mechanisms. Epigenetic processes such as DNA methylation, covalent modifications of histones and non-coding RNAs can induce changes in gene expression without a change in DNA base sequence. Such processes are involved in cell differentiation and genomic imprinting, as well as the phenomenon of developmental plasticity in response to environmental influences. Elucidation of such epigenetic processes may enable early intervention strategies to improve early development and growth. PMID:27088334

Dynamic Sumoylation of a Conserved Transcription Corepressor Prevents Persistent Inclusion Formation during Hyperosmotic Stress

PubMed Central

Oeser, Michelle L.; Amen, Triana; Nadel, Cory M.; Bradley, Amanda I.; Reed, Benjamin J.; Jones, Ramon D.; Gopalan, Janani; Kaganovich, Daniel; Gardner, Richard G.

2016-01-01

Cells are often exposed to physical or chemical stresses that can damage the structures of essential biomolecules. Stress-induced cellular damage can become deleterious if not managed appropriately. Rapid and adaptive responses to stresses are therefore crucial for cell survival. In eukaryotic cells, different stresses trigger post-translational modification of proteins with the small ubiquitin-like modifier SUMO. However, the specific regulatory roles of sumoylation in each stress response are not well understood. Here, we examined the sumoylation events that occur in budding yeast after exposure to hyperosmotic stress. We discovered by proteomic and biochemical analyses that hyperosmotic stress incurs the rapid and transient sumoylation of Cyc8 and Tup1, which together form a conserved transcription corepressor complex that regulates hundreds of genes. Gene expression and cell biological analyses revealed that sumoylation of each protein directs distinct outcomes. In particular, we discovered that Cyc8 sumoylation prevents the persistence of hyperosmotic stress-induced Cyc8-Tup1 inclusions, which involves a glutamine-rich prion domain in Cyc8. We propose that sumoylation protects against persistent inclusion formation during hyperosmotic stress, allowing optimal transcriptional function of the Cyc8-Tup1 complex. PMID:26800527

Some challenges with statistical inference in adaptive designs.

PubMed

Hung, H M James; Wang, Sue-Jane; Yang, Peiling

2014-01-01

Adaptive designs have generated a great deal of attention to clinical trial communities. The literature contains many statistical methods to deal with added statistical uncertainties concerning the adaptations. Increasingly encountered in regulatory applications are adaptive statistical information designs that allow modification of sample size or related statistical information and adaptive selection designs that allow selection of doses or patient populations during the course of a clinical trial. For adaptive statistical information designs, a few statistical testing methods are mathematically equivalent, as a number of articles have stipulated, but arguably there are large differences in their practical ramifications. We pinpoint some undesirable features of these methods in this work. For adaptive selection designs, the selection based on biomarker data for testing the correlated clinical endpoints may increase statistical uncertainty in terms of type I error probability, and most importantly the increased statistical uncertainty may be impossible to assess.

Aflatoxin B1-induced epigenetic alterations: An overview.

PubMed

Dai, Yaqi; Huang, Kunlun; Zhang, Boyang; Zhu, Liye; Xu, Wentao

2017-11-01

Aflatoxin B1 (AFB1) is widely distributed in nature, especially in a variety of food commodities. It is confirmed to be the most toxic of all the aflatoxins. The toxicity of AFB1 has been well investigated, and it may result in severe health problems including carcinogenesis, mutagenesis, growth retardation, and immune suppression. Epigenetic modifications including DNA methylation, histone modifications and regulation of non-coding RNA play an important role in AFB1-induced disease and carcinogenesis. To better understand the evidence for AFB1-induced epigenetic alterations and the potential mechanisms of the toxicity of AFB1, we conducted a review of published studies of AFB1-induced epigenetic alterations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Post-transcriptional modifications in development and stem cells.

PubMed

Frye, Michaela; Blanco, Sandra

2016-11-01

Cells adapt to their environment by linking external stimuli to an intricate network of transcriptional, post-transcriptional and translational processes. Among these, mechanisms that couple environmental cues to the regulation of protein translation are not well understood. Chemical modifications of RNA allow rapid cellular responses to external stimuli by modulating a wide range of fundamental biochemical properties and processes, including the stability, splicing and translation of messenger RNA. In this Review, we focus on the occurrence of N 6 -methyladenosine (m 6 A), 5-methylcytosine (m 5 C) and pseudouridine (Ψ) in RNA, and describe how these RNA modifications are implicated in regulating pluripotency, stem cell self-renewal and fate specification. Both post-transcriptional modifications and the enzymes that catalyse them modulate stem cell differentiation pathways and are essential for normal development. © 2016. Published by The Company of Biologists Ltd.

Surface modification of porous titanium with rice husk as space holder

NASA Astrophysics Data System (ADS)

Wang, Xinsheng; Hou, Junjian; Liu, Yanpei

2018-06-01

Porous titanium was characterized after its surface modification by acid and alkali solution immersion. The results show that the acid surface treatment caused the emergence of flocculent sodium titanate and induced apatite formation. The surface modification of porous titanium promotes biological activation, and the application of porous titanium is also improved as an implant material because of the existence of C and Si.

The Formative Method for Adapting Psychotherapy (FMAP): A community-based developmental approach to culturally adapting therapy

PubMed Central

Hwang, Wei-Chin

2010-01-01

How do we culturally adapt psychotherapy for ethnic minorities? Although there has been growing interest in doing so, few therapy adaptation frameworks have been developed. The majority of these frameworks take a top-down theoretical approach to adapting psychotherapy. The purpose of this paper is to introduce a community-based developmental approach to modifying psychotherapy for ethnic minorities. The Formative Method for Adapting Psychotherapy (FMAP) is a bottom-up approach that involves collaborating with consumers to generate and support ideas for therapy adaptation. It involves 5-phases that target developing, testing, and reformulating therapy modifications. These phases include: (a) generating knowledge and collaborating with stakeholders (b) integrating generated information with theory and empirical and clinical knowledge, (c) reviewing the initial culturally adapted clinical intervention with stakeholders and revising the culturally adapted intervention, (d) testing the culturally adapted intervention, and (e) finalizing the culturally adapted intervention. Application of the FMAP is illustrated using examples from a study adapting psychotherapy for Chinese Americans, but can also be readily applied to modify therapy for other ethnic groups. PMID:20625458

Robust high-performance control for robotic manipulators

NASA Technical Reports Server (NTRS)

Seraji, H.

1989-01-01

A robust control scheme to accomplish accurate trajectory tracking for an integrated system of manipulator-plus-actuators is proposed. The control scheme comprises a feedforward and a feedback controller. The feedforward controller contains any known part of the manipulator dynamics that can be used for online control. The feedback controller consists of adaptive position and velocity feedback gains and an auxiliary signal which is simply generated by a fixed-gain proportional/integral/derivative controller. The feedback controller is updated by very simple adaptation laws which contain both proportional and integral adaptation terms. By introduction of a simple sigma modification to the adaptation laws, robustness is guaranteed in the presence of unmodeled dynamics and disturbances.

Challenge to Aviation: Hatching a Leaner Pterosauer. [Improving Commercial Aircraft Design for Greater Fuel Efficiency

NASA Technical Reports Server (NTRS)

Moss, F. E.

1975-01-01

Modifications in commercial aircraft design, particularly the development of lighter aircraft, are discussed as effective means of reducing aviation fuel consumption. The modifications outlined include: (1) use of the supercritical wing; (2) generation of the winglet; (3) production and flight testing of composite materials; and, (4) implementation of fly-by-wire control systems. Attention is also given to engineering laminar air flow control, improving cargo payloads, and adapting hydrogen fuels for aircraft use.

The Redox Proteome*

PubMed Central

Go, Young-Mi; Jones, Dean P.

2013-01-01

The redox proteome consists of reversible and irreversible covalent modifications that link redox metabolism to biologic structure and function. These modifications, especially of Cys, function at the molecular level in protein folding and maturation, catalytic activity, signaling, and macromolecular interactions and at the macroscopic level in control of secretion and cell shape. Interaction of the redox proteome with redox-active chemicals is central to macromolecular structure, regulation, and signaling during the life cycle and has a central role in the tolerance and adaptability to diet and environmental challenges. PMID:23861437

Interleukin 1 β-induced SMAD2/3 linker modifications are TAK1 dependent and delay TGFβ signaling in primary human mesenchymal stem cells.

PubMed

van den Akker, Guus G; van Beuningen, Henk M; Vitters, Elly L; Koenders, Marije I; van de Loo, Fons A; van Lent, Peter L; Blaney Davidson, Esmeralda N; van der Kraan, Peter M

2017-12-01

Chondrogenic differentiation of mesenchymal stem cells (MSC) requires transforming growth factor beta (TGFβ) signaling. TGFβ binds to the type I receptor activin-like kinase (ALK)5 and results in C-terminal SMAD2/3 phosphorylation (pSMAD2/3C). In turn pSMAD2/3C translocates to the nucleus and regulates target gene expression. Inflammatory mediators are known to exert an inhibitory effect on MSC differentiation. In this study we investigated the effect of interleukin 1 β (IL1β) on SMAD2/3 signaling dynamics and post-translational modifications. Co-stimulation of MSC with TGFβ and IL1β did not affect peak pSMAD2C levels at 1h post-stimulation. Surprisingly, SMAD3 transcriptional activity, as determined by the CAGA 12 -luciferase reporter construct, was enhanced by co-stimulation of TGFβ and IL1β compared to TGFβ alone. Furthermore, IL1β stimulation induced CAGA 12 -luciferase activity in a SMAD dependent way. As SMAD function can be modulated independent of canonical TGFβ signaling through the SMAD linker domain, we studied SMAD2 linker phosphorylation at specific threonine and serine residues. SMAD2 linker threonine and serine modifications were observed within 1h following TGFβ, IL1β or TGFβ and IL1β stimulation. Upon co-stimulation linker modified SMAD2 accumulated in the cytoplasm and SMAD2/3 target gene transcription (ID1, JUNB) at 2-4h was inhibited. A detailed time course analysis of IL1β-induced SMAD2 linker modifications revealed a distinct temperospatial pattern compared to TGFβ. Co-stimulation with both factors resulted in a similar kinetic profile as TGFβ alone. Nevertheless, IL1β did subtly alter TGFβ-induced pSMAD2C levels between 8 and 24h post-stimulation, which was reflected by TGFβ target gene expression (PAI1, JUNB). Direct evidence for the importance of SMAD3 linker modifications for the effect of IL1β on TGFβ signaling was obtained by over-expression of SMAD3 or a SMAD3 linker phospho-mutant. Finally, an inhibitor screening was performed to identify kinases involved in SMAD2/3 linker modifications. We identified TAK1 kinase activity as crucial for IL1β-induced SMAD2 linker modifications and CAGA 12 -luciferase activity. TGFβ and IL1β signaling interact at the SMAD2/3 level in human primary MSC. Down-stream TGFβ target genes were repressed by IL1β independent of C-terminal SMAD2 phosphorylation. We demonstrate that SMAD2/3 linker modifications are required for this interplay and identified TAK1 as a crucial mediator of IL1β-induced TGFβ signal modulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Electronic modification of Cu-based chalcopyrite semiconductors induced by lattice deformation and composition alchemy

NASA Astrophysics Data System (ADS)

Jiang, F. D.; Feng, J. Y.

2008-02-01

Using first principles calculation, we systematically investigate the electronic modification of Cu-based chalcopyrite semiconductors induced by lattice deformation and composition alchemy. It is shown that the optical band gap Eg is remarkably sensitive to the anion displacement μ, resulting from the opposite shifts of conduction band minimum and valence band maximum. Meanwhile, the dependence of structural parameters of alloyed compounds on alloy composition x is demonstrated for both cation and anion alloying. The d orbitals of group-III cations are found to be of great importance in the calculation. Abnormal changes in the optical band gap Eg induced by anion alloying are addressed.

Cell wall modifications of two Arabidopsis thaliana ecotypes, Col and Sha, in response to sub-optimal growth conditions: An integrative study.

PubMed

Duruflé, Harold; Hervé, Vincent; Ranocha, Philippe; Balliau, Thierry; Zivy, Michel; Chourré, Josiane; San Clemente, Hélène; Burlat, Vincent; Albenne, Cécile; Déjean, Sébastien; Jamet, Elisabeth; Dunand, Christophe

2017-10-01

With the global temperature change, plant adaptations are predicted, but little is known about the molecular mechanisms underlying them. Arabidopsis thaliana is a model plant adapted to various environmental conditions, in particular able to develop along an altitudinal gradient. Two ecotypes, Columbia (Col) growing at low altitude, and Shahdara (Sha) growing at 3400m, have been studied at optimal and sub-optimal growth temperature (22°C vs 15°C). Macro- and micro-phenotyping, cell wall monosaccharides analyses, cell wall proteomics, and transcriptomics have been performed in order to accomplish an integrative analysis. The analysis has been focused on cell walls (CWs) which are assumed to play roles in response to environmental changes. At 15°C, both ecotypes presented characteristic morphological traits of low temperature growth acclimation such as reduced rosette diameter, increased number of leaves, modifications of their CW composition and cuticle reinforcement. Altogether, the integrative analysis has allowed identifying several candidate genes/proteins possibly involved in the cell wall modifications observed during the temperature acclimation response. Copyright © 2017 Elsevier B.V. All rights reserved.

Maternal programming of sex-specific responses to predator odor stress in adult rats.

PubMed

St-Cyr, Sophie; Abuaish, Sameera; Sivanathan, Shathveekan; McGowan, Patrick O

2017-08-01

Prenatal stress mediated through the mother can lead to long-term adaptations in stress-related phenotypes in offspring. This study tested the long-lasting effect of prenatal exposure to predator odor, an ethologically relevant and psychogenic stressor, in the second half of pregnancy. As adults, the offspring of predator odor-exposed mothers showed increased anxiety-like behaviors in commonly used laboratory tasks assessing novelty-induced anxiety, increased defensive behavior in males and increased ACTH stress reactivity in females in response to predator odor. Female offspring from predator odor-exposed dams showed increased transcript abundance of glucocorticoid receptor (NR3C1) on the day of birth and FK506 binding protein 5 (FKBP5) in adulthood in the amygdala. The increase in FKBP5 expression was associated with decreased DNA methylation in Fkbp5 intron V. These results indicate a sex-specific response to maternal programming by prenatal predator odor exposure and a potential epigenetic mechanism linking these responses with modifications of the stress axis in females. These results are in accordance with the mismatch hypothesis stating that an animal's response to cues within its life history reflects environmental conditions anticipated during important developmental periods and should be adaptive when these conditions are concurring. Copyright © 2017 Elsevier Inc. All rights reserved.

De Novo Transcriptome Assembly and Identification of Gene Candidates for Rapid Evolution of Soil Al Tolerance in Anthoxanthum odoratum at the Long-Term Park Grass Experiment

PubMed Central

Gould, Billie; McCouch, Susan; Geber, Monica

2015-01-01

Studies of adaptation in the wild grass Anthoxanthum odoratum at the Park Grass Experiment (PGE) provided one of the earliest examples of rapid evolution in plants. Anthoxanthum has become locally adapted to differences in soil Al toxicity, which have developed there due to soil acidification from long-term experimental fertilizer treatments. In this study, we used transcriptome sequencing to identify Al stress responsive genes in Anthoxanhum and identify candidates among them for further molecular study of rapid Al tolerance evolution at the PGE. We examined the Al content of Anthoxanthum tissues and conducted RNA-sequencing of root tips, the primary site of Al induced damage. We found that despite its high tolerance Anthoxanthum is not an Al accumulating species. Genes similar to those involved in organic acid exudation (TaALMT1, ZmMATE), cell wall modification (OsSTAR1), and internal Al detoxification (OsNRAT1) in cultivated grasses were responsive to Al exposure. Expression of a large suite of novel loci was also triggered by early exposure to Al stress in roots. Three-hundred forty five transcripts were significantly more up- or down-regulated in tolerant vs. sensitive Anthoxanthum genotypes, providing important targets for future study of rapid evolution at the PGE. PMID:26148203

De Novo Transcriptome Assembly and Identification of Gene Candidates for Rapid Evolution of Soil Al Tolerance in Anthoxanthum odoratum at the Long-Term Park Grass Experiment.

PubMed

Gould, Billie; McCouch, Susan; Geber, Monica

2015-01-01

Studies of adaptation in the wild grass Anthoxanthum odoratum at the Park Grass Experiment (PGE) provided one of the earliest examples of rapid evolution in plants. Anthoxanthum has become locally adapted to differences in soil Al toxicity, which have developed there due to soil acidification from long-term experimental fertilizer treatments. In this study, we used transcriptome sequencing to identify Al stress responsive genes in Anthoxanhum and identify candidates among them for further molecular study of rapid Al tolerance evolution at the PGE. We examined the Al content of Anthoxanthum tissues and conducted RNA-sequencing of root tips, the primary site of Al induced damage. We found that despite its high tolerance Anthoxanthum is not an Al accumulating species. Genes similar to those involved in organic acid exudation (TaALMT1, ZmMATE), cell wall modification (OsSTAR1), and internal Al detoxification (OsNRAT1) in cultivated grasses were responsive to Al exposure. Expression of a large suite of novel loci was also triggered by early exposure to Al stress in roots. Three-hundred forty five transcripts were significantly more up- or down-regulated in tolerant vs. sensitive Anthoxanthum genotypes, providing important targets for future study of rapid evolution at the PGE.

Evaluation of novel synthetic TLR7/8 agonists as vaccine adjuvants

PubMed Central

Smith, Alyson J.; Li, Yufeng; Bazin, Hélène G.; St-Jean, Julien R.; Larocque, Daniel; Evans, Jay T.; Baldridge, Jory R.

2016-01-01

Small-molecule adjuvants that boost and direct adaptive immunity provide a powerful means to increase the effectiveness of vaccines. Through rational design several novel imidazoquinoline and oxoadenine TLR7/8 agonists, each with unique molecular modifications, were synthesized and assessed for their ability to augment adaptive immunity. All agonists bound human TLR7 and TLR8 and induced maturation of both human mDCs and pDCs. All agonists prompted production of type I interferon and/or proinflammatory cytokines, albeit with varying potencies. In most in vitro assays, the oxoadenine class of agonists proved more potent than the imidazoquinolines. Therefore, an optimized oxoadenine TLR7/8 agonist that demonstrated maximal activity in the in vitro assays was further assessed in a vaccine study with the CRM197 antigen in a porcine model. Antigen-specific antibody production was greatly enhanced in a dose dependent manner, with antibody titers increased 800-fold compared to titers from pigs vaccinated with the non-adjuvanted vaccine. Moreover, pigs vaccinated with antigen containing the highest dose of adjuvant promoted a 13-fold increase in the percentage of antigen-specific CD3+/CD8+ T cells over pigs vaccinated with antigen alone. Together this work demonstrates the promise of these novel TLR7/8 agonists as effective human vaccine adjuvants. PMID:27402566

[Supposed role of "metabolic memory" in formation of response reaction to stress-factors in young and adult organisms].

PubMed

Bozhkov, A I; Dlubovskaia, V L; Dmitriev, Iu V; Meshaĭkina, N I; Maleev, V A; Klimova, E M

2009-01-01

The influence of the combined long-lasted influences of sulfur sulfate and diet restriction in young (3 month age) and adult (21 month age) Vistar rats on activity of glucose-6-phospatase, alaninaminotranspherase (ALT), aspartataminotranspherase (AST), and on phosphorilating activity of liver mitochondria was studied to investigate the role of metabolic memory on the peculiarities of response reaction. The young animals not differed from adult ones in the possibility of inducing activity of glucose-6-phospatase, ALT, and on phosphorilating activity after the influence of sulfur sulfate and diet restriction. The age-related differences in glucose-6-phospatase and transpherases and phosphorilating activity existing in control disappeared after the long-lasted action of sulfur sulfate and diet restriction. The answer reaction in enzyme activity to stress factors applied many times depends upon the metabolic memory formed in the process of adaptation, and the age of animals have no influence on it. In some relation the ontogenesis may be considered as a result of adaptation genesis. The metabolic memory can change the answer of the system to the stress influence. There are three types of modification of the answer to stress factors: the answer remains unchanged (metabolic memory), "paradox answer" formation, and super activation of the metabolic system.

Epigenetics: Beyond Chromatin Modifications and Complex Genetic Regulation1

PubMed Central

Eichten, Steven R.; Schmitz, Robert J.; Springer, Nathan M.

2014-01-01

Chromatin modifications and epigenetics may play important roles in many plant processes, including developmental regulation, responses to environmental stimuli, and local adaptation. Chromatin modifications describe biochemical changes to chromatin state, such as alterations in the specific type or placement of histones, modifications of DNA or histones, or changes in the specific proteins or RNAs that associate with a genomic region. The term epigenetic is often used to describe a variety of unexpected patterns of gene regulation or inheritance. Here, we specifically define epigenetics to include the key aspects of heritability (stable transmission of gene expression states through mitotic or meiotic cell divisions) and independence from DNA sequence changes. We argue against generically equating chromatin and epigenetics; although many examples of epigenetics involve chromatin changes, those chromatin changes are not always heritable or may be influenced by genetic changes. Careful use of the terms chromatin modifications and epigenetics can help separate the biochemical mechanisms of regulation from the inheritance patterns of altered chromatin states. Here, we also highlight examples in which chromatin modifications and epigenetics affect important plant processes. PMID:24872382

Laser-induced transient grating setup with continuously tunable period

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vega-Flick, A.; Applied Physics Department, CINVESTAV-Unidad Mérida, Carretera Antigua a Progreso Km 6, Cordemex, Mérida, Yucatán 97310 Mexico; Eliason, J. K.

2015-12-15

We present a modification of the laser-induced transient grating setup enabling continuous tuning of the transient grating period. The fine control of the period is accomplished by varying the angle of the diffraction grating used to split excitation and probe beams. The setup has been tested by measuring dispersion of bulk and surface acoustic waves in both transmission and reflection geometries. The presented modification is fully compatible with optical heterodyne detection and can be easily implemented in any transient grating setup.

Inexact adaptive Newton methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bertiger, W.I.; Kelsey, F.J.

1985-02-01

The Inexact Adaptive Newton method (IAN) is a modification of the Adaptive Implicit Method/sup 1/ (AIM) with improved Newton convergence. Both methods simplify the Jacobian at each time step by zeroing coefficients in regions where saturations are changing slowly. The methods differ in how the diagonal block terms are treated. On test problems with up to 3,000 cells, IAN consistently saves approximately 30% of the CPU time when compared to the fully implicit method. AIM shows similar savings on some problems, but takes as much CPU time as fully implicit on other test problems due to poor Newton convergence.

Bacillus subtilis alters the proportion of major membrane phospholipids in response to surfactin exposure.

PubMed

Uttlová, Petra; Pinkas, Dominik; Bechyňková, Olga; Fišer, Radovan; Svobodová, Jaroslava; Seydlová, Gabriela

2016-12-01

Surfactin, an anionic lipopeptide produced by Bacillus subtilis, is an antimicrobial that targets the cytoplasmic membrane. Nowadays it appears increasingly apparent that the mechanism of resistance against these types of antibiotics consists of target site modification. This prompted us to investigate whether the surfactin non-producing strain B. subtilis 168 changes its membrane composition in response to a sublethal surfactin concentration. Here we show that the exposure of B. subtilis to surfactin at concentrations of 350 and 650 μg/ml (designated as SF350 and SF650, respectively) leads to a concentration-dependent growth arrest followed by regrowth with an altered growth rate. Analysis of the membrane lipid composition revealed modifications both in the polar head group and the fatty acid region. The presence of either surfactin concentration resulted in a reduction in the content of the major membrane phospholipid phosphatidylglycerol (PG) and increase in phosphatidylethanolamine (PE), which was accompanied by elevated levels of phosphatidic acid (PA) in SF350 cultures. The fatty acid analysis of SF350 cells showed a marked increase in non-branched high-melting fatty acids, which lowered the fluidity of the membrane interior measured as the steady-state fluorescence anisotropy of DPH. The liposome leakage of carboxyfluorescein-loaded vesicles resembling the phospholipid composition of surfactin-adapted cells showed that the susceptibility to surfactin-induced leakage is strongly reduced when the PG/PE ratio decreases and/or PA is included in the target bilayer. We concluded that the modifications of the phospholipid content of B. subtilis cells might provide a self-tolerance of the membrane active surfactin. Copyright © 2016 Elsevier B.V. All rights reserved.

Sequential ChIP Protocol for Profiling Bivalent Epigenetic Modifications (ReChIP).

PubMed

Desvoyes, Bénédicte; Sequeira-Mendes, Joana; Vergara, Zaida; Madeira, Sofia; Gutierrez, Crisanto

2018-01-01

Identification of chromatin modifications, e.g., histone acetylation and methylation, among others, is widely carried out by using a chromatin immunoprecipitation (ChIP) strategy. The information obtained with these procedures is useful to gain an overall picture of modifications present in all cells of the population under study. It also serves as a basis to figure out the mechanisms of chromatin organization and gene regulation at the population level. However, the ultimate goal is to understand gene regulation at the level of single chromatin fibers. This requires the identification of chromatin modifications that occur at a given genomic location and within the same chromatin fiber. This is achieved by following a sequential ChIP strategy using two antibodies to distinguish different chromatin modifications. Here, we describe a sequential ChIP protocol (Re-ChIP), paying special attention to the controls needed and the required steps to obtain meaningful and reproducible results. The protocol is developed for young Arabidopsis seedlings but could be adapted to other plant materials.

Cell Wall Structure in Cells Adapted to Growth on the Cellulose-Synthesis Inhibitor 2,6-Dichlorobenzonitrile 1

PubMed Central

Shedletzky, Esther; Shmuel, Miri; Trainin, Tali; Kalman, Sara; Delmer, Deborah

1992-01-01

Our previous work (E. Shedletzky, M. Shmuel, D.P. Delmer, D.T.A. Lamport [1990] Plant Physiol 94:980-987) showed that suspension-cultured tomato cells adapted to growth on the cellulose synthesis inhibitor 2,6-dichlorobenzonitrile (DCB) have a markedly altered cell wall composition, most notably a markedly reduced level of the cellulose-xyloglucan network. This study compares the adaptation to DCB of two cell lines from dicots (tomato [Lycopersicon esculentum] and tobacco [Nicotiana tabacum]) and a Graminaceous monocot (barley [Hordeum bulbosum] endosperm). The difference in wall structures between the dicots and the monocot is reflected in the very different types of wall modifications induced by growth on DCB. The dicots, having reduced levels of cellulose and xyloglucan, possess walls the major integrity of which is provided by Ca2+-bridged pectates because protoplasts can be prepared from these cells simply by treatment with divalent cation chelator and a purified endopolygalacturonase. The tensile strength of these walls is considerably less than walls from nonadapted cells, but wall porosity is not altered. In contrast, walls from adapted barley cells contain very little pectic material and normal to elevated levels of noncellulosic polysaccharides compared with walls from nonadapted cells. Surprisingly, they have tensile strengths higher than their nonadapted counterpart, although cellulose levels are reduced by 70%. Evidence is presented that these walls obtain their additional strength by an altered pattern of cross-linking of polymers involving phenolic components. Such cross-linking may also explain the observation that the porosity of these walls is also considerably reduced. Cells of adapted lines of both the dicots and barley are resistant to plasmolysis, suggesting that they possess very strong connections between the wall and the plasma membrane. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:16652933

45 CFR 162.940 - Exceptions from standards to permit testing of proposed modifications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... consistent with the other standards adopted under this part and, as appropriate, with other private and.... (x) Incorporate flexibility to adapt more easily to changes in the health care infrastructure (such...

45 CFR 162.940 - Exceptions from standards to permit testing of proposed modifications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... consistent with the other standards adopted under this part and, as appropriate, with other private and.... (x) Incorporate flexibility to adapt more easily to changes in the health care infrastructure (such...

Biological considerations in the delineation of critical habitat

USGS Publications Warehouse

Knight, Richard R.

1980-01-01

Grizzly bears (Ursus arctos) require large areas to satisfy their needs for food, cover, and space. They thrive best where disturbance by man is minimal. It is not a coincidence that the two major grizzly bear populations in the lower 48 states exist in large wilderness systems closely associated with two large national parks and a relatively large game preserve. If management objectives for these areas do not change, and man-bear interactions can be kept low, viable grizzly bear populations can be maintained. Outside of parks and wilderness areas, the picture is less clear. Grizzly bears adapt to some habitat modifications. the extent of their adaptability to habitat modification or human interaction is largely unknown. Answers to many pertinent questions will be slow in coming. In the meantime, management policies based on common sense rather than on adversary reactions among agencies are the best insurance of the grizzlies' survival.

Femtosecond laser-induced refractive index modification in multicomponent glasses

NASA Astrophysics Data System (ADS)

Bhardwaj, V. R.; Simova, E.; Corkum, P. B.; Rayner, D. M.; Hnatovsky, C.; Taylor, R. S.; Schreder, B.; Kluge, M.; Zimmer, J.

2005-04-01

We present a comprehensive study on femtosecond laser-induced refractive index modification in a wide variety of multicomponent glasses grouped as borosilicate, aluminum-silicate, and heavy-metal oxide glasses along with lanthanum-borate and sodium-phosphate glasses. By using high-spatial resolution refractive index profiling techniques, we demonstrate that under a wide range of writing conditions the refractive index modification in multicomponent glasses can be positive, negative, or nonuniform, and exhibits a strong dependence on the glass composition. With the exception of some aluminum-silicate glasses all other glasses exhibited a negative/nonuniform index change. We also demonstrate direct writing of waveguides in photosensitive Foturan® glass with a femtosecond laser without initiating crystallization by thermal treatment. Upon ceramization of lithium-aluminum-silicate glasses such as Foturan®, Zerodur®, and Robax® we observe switching of laser-induced refractive index change from being positive to negative. The measured transmission losses in the waveguides at 1550nm agree with the index profile measurements in alkali-free aluminum-silicate glasses.

The Role of Stress-Induced O-GlcNAc Protein Modification in the Regulation of Membrane Transport

PubMed Central

Fisi, Viktória; Miseta, Attila

2017-01-01

O-linked N-acetylglucosamine (O-GlcNAc) is a posttranslational modification that is increasingly recognized as a signal transduction mechanism. Unlike other glycans, O-GlcNAc is a highly dynamic and reversible process that involves the addition and removal of a single N-acetylglucosamine molecule to Ser/Thr residues of proteins. UDP-GlcNAc—the direct substrate for O-GlcNAc modification—is controlled by the rate of cellular metabolism, and thus O-GlcNAc is dependent on substrate availability. Serving as a feedback mechanism, O-GlcNAc influences the regulation of insulin signaling and glucose transport. Besides nutrient sensing, O-GlcNAc was also implicated in the regulation of various physiological and pathophysiological processes. Due to improvements of mass spectrometry techniques, more than one thousand proteins were detected to carry the O-GlcNAc moiety; many of them are known to participate in the regulation of metabolites, ions, or protein transport across biological membranes. Recent studies also indicated that O-GlcNAc is involved in stress adaptation; overwhelming evidences suggest that O-GlcNAc levels increase upon stress. O-GlcNAc elevation is generally considered to be beneficial during stress, although the exact nature of its protective effect is not understood. In this review, we summarize the current data regarding the oxidative stress-related changes of O-GlcNAc levels and discuss the implications related to membrane trafficking. PMID:29456783

A review of cultural adaptations of screening tools for autism spectrum disorders.

PubMed

Soto, Sandra; Linas, Keri; Jacobstein, Diane; Biel, Matthew; Migdal, Talia; Anthony, Bruno J

2015-08-01

Screening children to determine risk for Autism Spectrum Disorders has become more common, although some question the advisability of such a strategy. The purpose of this systematic review is to identify autism screening tools that have been adapted for use in cultures different from that in which they were developed, evaluate the cultural adaptation process, report on the psychometric properties of the adapted instruments, and describe the implications for further research and clinical practice. A total of 21 articles met criteria for inclusion, reporting on the cultural adaptation of autism screening in 19 countries and in 10 languages. The cultural adaptation process was not always clearly outlined and often did not include the recommended guidelines. Cultural/linguistic modifications to the translated tools tended to increase with the rigor of the adaptation process. Differences between the psychometric properties of the original and adapted versions were common, indicating the need to obtain normative data on populations to increase the utility of the translated tool. © The Author(s) 2014.

[Stress-induced cellular adaptive mutagenesis].

PubMed

Zhu, Linjiang; Li, Qi

2014-04-01

The adaptive mutations exist widely in the evolution of cells, such as antibiotic resistance mutations of pathogenic bacteria, adaptive evolution of industrial strains, and cancerization of human somatic cells. However, how these adaptive mutations are generated is still controversial. Based on the mutational analysis models under the nonlethal selection conditions, stress-induced cellular adaptive mutagenesis is proposed as a new evolutionary viewpoint. The hypothetic pathway of stress-induced mutagenesis involves several intracellular physiological responses, including DNA damages caused by accumulation of intracellular toxic chemicals, limitation of DNA MMR (mismatch repair) activity, upregulation of general stress response and activation of SOS response. These responses directly affect the accuracy of DNA replication from a high-fidelity manner to an error-prone one. The state changes of cell physiology significantly increase intracellular mutation rate and recombination activity. In addition, gene transcription under stress condition increases the instability of genome in response to DNA damage, resulting in transcription-associated DNA mutagenesis. In this review, we summarize these two molecular mechanisms of stress-induced mutagenesis and transcription-associated DNA mutagenesis to help better understand the mechanisms of adaptive mutagenesis.

Modified diadenosine tetraphosphates with dual specificity for P2Y1 and P2Y12 are potent antagonists of ADP-induced platelet activation

PubMed Central

CHANG, H.; YANACHKOV, I. B.; DIX, E. J.; LI, Y. F.; BARNARD, M. R.; WRIGHT, G. E.; MICHELSON, A. D.; FRELINGER, A. L.

2017-01-01

Summary Background Diadenosine 5′,5‴-P1,P4-tetraphosphate (Ap4A), a natural compound stored in platelet dense granules, inhibits ADP-induced platelet aggregation. Ap4A inhibits the platelet ADP receptors P2Y1 and P2Y12, is a partial agonist of P2Y12, and is a full agonist of the platelet ATP-gated ion channel P2X1. Modification of the Ap4A tetraphosphate backbone enhances inhibition of ADP-induced platelet aggregation. However, the effects of these Ap4A analogs on human platelet P2Y1, P2Y12 and P2X1 are unclear. Objective To determine the agonist and antagonist activities of diadenosine tetraphosphate analogs towards P2Y1, P2Y12, and P2X1. Methods We synthesized the following Ap4A analogs: P1,P4-dithiotetraphosphate; P2,P3-chloromethylenetetraphosphate; P1-thio-P2,P3-chloromethylenetetraphosphate; and P1,P4-dithio-P2,P3-chloromethylenetetraphosphate. We then measured the effects of these analogs on: (i) ADP-induced platelet aggregation; (ii) P2Y1-mediated changes in cytosolic Ca2+; (iii) P2Y12-mediated changes in vasodilator-stimulated phosphoprotein phosphorylation; and (iv) P2X1-mediated entry of extracellular Ca2+. Results Ap4A analogs with modifications in the phosphate backbone inhibited both P2Y1 and P2Y12, and showed no agonist activity towards these receptors. The dithio modification increased inhibition of P2Y1, P2Y12, and platelet aggregation, whereas the chloromethylene modification increased inhibition of P2Y12 and platelet aggregation, but decreased P2Y1 inhibition. Combining the dithio and chloromethylene modifications increased P2Y1 and P2Y12 inhibition. As compared with Ap4A, each modification decreased agonist activity towards P2X1, and the dual modification completely eliminated P2X1 agonist activity. Conclusions As compared with Ap4A, tetraphosphate backbone analogs of Ap4A have diminished activity towards P2X1 but inhibit both P2Y1 and P2Y12 and, with greater potency, inhibit ADP-induced platelet aggregation. Thus, diadenosine tetraphosphate analogs with dual receptor selectivity may have potential as antiplatelet drugs. PMID:23083103

Structure, chaperone-like activity and allergenicity profile of bovine caseins upon peroxynitrite modification: New evidences underlying mastitis pathomechanisms.

PubMed

Sadeghian, Tanaz; Tavaf, Zohreh; Oryan, Ahmad; Shokouhi, Raheleh; Pourpak, Zahra; Moosavi-Movahedi, Ali Akbar; Yousefi, Reza

2018-01-01

Mastitis, an inflammatory reaction frequently develops in response to intra-mammary bacterial infection‌‌, may induce the generation of peroxynitrite (PON)‌ which is a highly potent reactive oxygen and nitrogen species. Caseins as the intrinsically unfolded proteins seem feasible substrates to react with PON. Therefore, in the current study, structural and functional aspects of both β-casein (β-CN) and whole casein fraction (WCF) were evaluated after PON modification, using a variety of techniques. Modification of the bovine caseins with PON results in an important enhancement in the carbonyl, nitrotryptophan, nitrotyrosine and dityrosine content of these proteins‌. The results of fluorescence and far UV-CD assessments suggested significant structural alteration of caseins upon PON-modification. The chaperone-like activity of β-casein was significantly altered after PON modification. The results of scanning electron microscopy suggest that bovine caseins display unique morphological features after treatment with PON. Also, the PON-modified caseins preserved their allergenicity profile and displayed partial resistance against digestion by the pancreatic proteases. Ascorbic acid, an important antioxidant component of milk, was also capable to significantly prevent the PON-induced structural damages in bovine milk caseins. In conclusion, our results suggest that PON may have significant role in the structural and functional alteration of milk caseins. Also, the PON-induced structural damaging effects of caseins might be effectively prevented by a sufficient level of milk antioxidant components particularly by ascorbic acid. Copyright © 2017 Elsevier B.V. All rights reserved.

A Novel Post-translational Modification of Nucleolin, SUMOylation at Lys-294, Mediates Arsenite-induced Cell Death by Regulating gadd45α mRNA Stability*

PubMed Central

Zhang, Dongyun; Liang, Yuguang; Xie, Qipeng; Gao, Guangxun; Wei, Jinlong; Huang, Haishan; Li, Jingxia; Gao, Jimin; Huang, Chuanshu

2015-01-01

Nucleolin is a ubiquitously expressed protein and participates in many important biological processes, such as cell cycle regulation and ribosomal biogenesis. The activity of nucleolin is regulated by intracellular localization and post-translational modifications, including phosphorylation, methylation, and ADP-ribosylation. Small ubiquitin-like modifier (SUMO) is a category of recently verified forms of post-translational modifications and exerts various effects on the target proteins. In the studies reported here, we discovered SUMOylational modification of human nucleolin protein at Lys-294, which facilitated the mRNA binding property of nucleolin by maintaining its nuclear localization. In response to arsenic exposure, nucleolin-SUMO was induced and promoted its binding with gadd45α mRNA, which increased gadd45α mRNA stability and protein expression, subsequently causing GADD45α-mediated cell death. On the other hand, ectopic expression of Mn-SOD attenuated the arsenite-generated superoxide radical level, abrogated nucleolin-SUMO, and in turn inhibited arsenite-induced apoptosis by reducing GADD45α expression. Collectively, our results for the first time demonstrate that nucleolin-SUMO at K294R plays a critical role in its nucleus sequestration and gadd45α mRNA binding activity. This novel biological function of nucleolin is distinct from its conventional role as a proto-oncogene. Therefore, our findings here not only reveal a new modification of nucleolin protein and its novel functional paradigm in mRNA metabolism but also expand our understanding of the dichotomous roles of nucleolin in terms of cancer development, which are dependent on multiple intracellular conditions and consequently the appropriate regulations of its modifications, including SUMOylation. PMID:25561743

TET1 and TET3 are essential in induction of Th2-type immunity partly through regulation of IL-4/13A expression in zebrafish model.

PubMed

Yang, Chao; Li, Zhuo; Kang, Wei; Tian, Yu; Yan, Yuzhu; Chen, Wei

2016-10-10

It has been considered that epigenetic modulation can affect a diverse array of cellular activities, in which ten eleven translocation (TET) methylcytosine dioxygenase family members refer to a group of fundamental components involved in catalyzation of 5-hydroxymethylcytosine and modification of gene expression. Even though the function of TET proteins has been gradually revealed, their roles in immune regulation are still largely unknown. Recent studies provided clues that TET2 could regulate several innate immune-related inflammatory mediators in mammals. This study sought to explore the function of TET family members in potential T-helper (Th) cell differentiation involved in adaptive immunity by utilizing a zebrafish model. As shown by results, soluble antigens could induce expression of zebrafish IL-4/13A (i.e. a pivotal Th2-type cytokine essential in Th2 cell differentiation and functions), and further trigger the expression of Th1- and Th2-related genes. It is noteworthy that this response was accompanied by the up-regulation of two TET family members (TET1 and TET3) both in immune organs (spleen and kidney) and cells (peripheral lymphocytes). Knocking-down of TET1 and TET3 will give rise to the decreased responses of IL-4/13A induction against exogenous soluble antigen stimulation, and further restrain the expression of Th2-related genes, which indicates a restrained Th2 cell differentiation. Nonetheless, TET2 did not exhibit effect on the modification of Th1/Th2 related gene expression. Hence, these data showed that TET1 and TET3 might be two significant epigenetic regulators involved in Th2 differentiation through regulation of IL-4/13A expression. This is the first report to show that TET family members play indispensable roles in Th2-type immunity, indicating an epigenetic modulation manner involved in adaptive immune regulations and responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Evolutionary changes of Hox genes and relevant regulatory factors provide novel insights into mammalian morphological modifications.

PubMed

Li, Kui; Sun, Xiaohui; Chen, Meixiu; Sun, Yingying; Tian, Ran; Wang, Zhengfei; Xu, Shixia; Yang, Guang

2018-01-01

The diversity of body plans of mammals accelerates the innovation of lifestyles and the extensive adaptation to different habitats, including terrestrial, aerial and aquatic habitats. However, the genetic basis of those phenotypic modifications, which have occurred during mammalian evolution, remains poorly explored. In the present study, we synthetically surveyed the evolutionary pattern of Hox clusters that played a powerful role in the morphogenesis along the head-tail axis of animal embryos and the main regulatory factors (Mll, Bmi1 and E2f6) that control the expression of Hox genes. A deflected density of repetitive elements and lineage-specific radical mutations of Mll have been determined in marine mammals with morphological changes, suggesting that evolutionary changes may alter Hox gene expression in these lineages, leading to the morphological modification of these lineages. Although no positive selection was detected at certain ancestor nodes of lineages, the increased ω values of Hox genes implied the relaxation of functional constraints of these genes during the mammalian evolutionary process. More importantly, 49 positively-selected sites were identified in mammalian lineages with phenotypic modifications, indicating adaptive evolution acting on Hox genes and regulatory factors. In addition, 3 parallel amino acid substitutions in some Hox genes were examined in marine mammals, which might be responsible for their streamlined body. © 2017 The Authors. Integrative Zoology published by International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Mobile application to induce lifestyle modifications in type 2 diabetic patients: prototype based on international guidelines

NASA Astrophysics Data System (ADS)

García-Jaramillo, M.; Delgado, J. S.; León-Vargas, F.

2015-12-01

This paper describes a prototype app to induce lifestyle modifications in newly diagnosed type 2 diabetic patients. The app design is based on International Diabetes Federation guidelines and recommendations from clinical studies related to diabetes health-care. Two main approaches, lifestyle modification and self-management education are used owing to significant benefits reported. The method used is based on setting goals under medical support related to physical activity, nutritional habits and weight loss, in addition to educational messages. This is specially implemented to address the main challenges that have limited the success of similar mobile applications already validated on diabetic patients. A traffic light is used to show the overall state of the goals compliance. This state could be understood as excellent (green), there are aspects to improve (yellow), or some individual goals are not carrying out (red). An example of how works this method is presented in results. Furthermore, the app provides recommendations to the user in case the overall state was in yellow or red. The recommendations pretend to induce the user to make changes in their eating habits and physical activity. According to international guidelines and clinical studies, a prototype of mobile application to induce a lifestyle modification in order to prevent adverse risk factors related to diabetes was presented. The resulting application is apparently consistent with clinical judgments, but a formal clinical validation is required. The effectiveness of this app is currently under consideration for the Colombian population with type 2 diabetes.

The link between UHC reforms and health system governance: lessons from Asia.

PubMed

Hort, Krishna; Jayasuriya, Rohan; Dayal, Prarthna

2017-05-15

Purpose The purpose of this paper is to examine how and to what extent the design and implementation of universal health coverage (UHC) reforms have been influenced by the governance arrangements of health systems in low- and middle-income countries (LMIC); and how governments in these countries have or have not responded to the challenges of governance for UHC. Design/methodology/approach Comparative case study analysis of three Asian countries with substantial experience of UHC reforms (Thailand, Vietnam and China) was undertaken using data from published studies and grey literature. Studies included were those which described the modifications and adaptations that occurred during design and implementation of the UHC programme, the actors and institutions involved and how these changes related to the governance of the health system. Findings Each country adapted the design of their UHC programmes to accommodate their specific institutional arrangements, and then made further modifications in response to issues arising during implementation. The authors found that these modifications were often related to the impacts on governance of the institutional changes inherent in UHC reforms. Governments varied in their response to these governance impacts, with Thailand prepared to adopt new governance modes (which the authors termed as an "adaptive" response), while China and Vietnam have tended to persist with traditional hierarchical governance modes ("reactive" responses). Originality/value This study addresses a gap in current knowledge on UHC reform, and finds evidence of a complex interaction between substantive health sector reform and governance reform in the LMIC context in Asia, confirming recent similar observations on health reforms in high-income countries.

Stability of sublethal acid stress adaptaion and induced cross protection against lauric arginate in Listeria monocytogenes

USDA-ARS?s Scientific Manuscript database

The stability of acid stress adaptation in Listeria monocytogenes and its induced cross protection effect against GRAS (generally recognized as safe) antimicrobial compounds has never been investigated before. In the present study, the acid stress adaptation in L. monocytogenes was initially induced...

Workstations for people with disabilities: an example of a virtual reality approach

PubMed Central

Budziszewski, Paweł; Grabowski, Andrzej; Milanowicz, Marcin; Jankowski, Jarosław

2016-01-01

This article describes a method of adapting workstations for workers with motion disability using computer simulation and virtual reality (VR) techniques. A workstation for grinding spring faces was used as an example. It was adjusted for two people with a disabled right upper extremity. The study had two stages. In the first, a computer human model with a visualization of maximal arm reach and preferred workspace was used to develop a preliminary modification of a virtual workstation. In the second stage, an immersive VR environment was used to assess the virtual workstation and to add further modifications. All modifications were assessed by measuring the efficiency of work and the number of movements involved. The results of the study showed that a computer simulation could be used to determine whether a worker with a disability could access all important areas of a workstation and to propose necessary modifications. PMID:26651540

An adaptive and generalizable closed-loop system for control of medically induced coma and other states of anesthesia

NASA Astrophysics Data System (ADS)

Yang, Yuxiao; Shanechi, Maryam M.

2016-12-01

Objective. Design of closed-loop anesthetic delivery (CLAD) systems is an important topic, particularly for medically induced coma, which needs to be maintained for long periods. Current CLADs for medically induced coma require a separate offline experiment for model parameter estimation, which causes interruption in treatment and is difficult to perform. Also, CLADs may exhibit bias due to inherent time-variation and non-stationarity, and may have large infusion rate variations at steady state. Finally, current CLADs lack theoretical performance guarantees. We develop the first adaptive CLAD for medically induced coma, which addresses these limitations. Further, we extend our adaptive system to be generalizable to other states of anesthesia. Approach. We designed general parametric pharmacodynamic, pharmacokinetic and neural observation models with associated guidelines, and derived a novel adaptive controller. We further penalized large steady-state drug infusion rate variations in the controller. We derived theoretical guarantees that the adaptive system has zero steady-state bias. Using simulations that resembled real time-varying and noisy environments, we tested the closed-loop system for control of two different anesthetic states, burst suppression in medically induced coma and unconsciousness in general anesthesia. Main results. In 1200 simulations, the adaptive system achieved precise control of both anesthetic states despite non-stationarity, time-variation, noise, and no initial parameter knowledge. In both cases, the adaptive system performed close to a baseline system that knew the parameters exactly. In contrast, a non-adaptive system resulted in large steady-state bias and error. The adaptive system also resulted in significantly smaller steady-state infusion rate variations compared to prior systems. Significance. These results have significant implications for clinically viable CLAD design for a wide range of anesthetic states, with potential cost-saving and therapeutic benefits.

An adaptive and generalizable closed-loop system for control of medically induced coma and other states of anesthesia.

PubMed

Yang, Yuxiao; Shanechi, Maryam M

2016-12-01

Design of closed-loop anesthetic delivery (CLAD) systems is an important topic, particularly for medically induced coma, which needs to be maintained for long periods. Current CLADs for medically induced coma require a separate offline experiment for model parameter estimation, which causes interruption in treatment and is difficult to perform. Also, CLADs may exhibit bias due to inherent time-variation and non-stationarity, and may have large infusion rate variations at steady state. Finally, current CLADs lack theoretical performance guarantees. We develop the first adaptive CLAD for medically induced coma, which addresses these limitations. Further, we extend our adaptive system to be generalizable to other states of anesthesia. We designed general parametric pharmacodynamic, pharmacokinetic and neural observation models with associated guidelines, and derived a novel adaptive controller. We further penalized large steady-state drug infusion rate variations in the controller. We derived theoretical guarantees that the adaptive system has zero steady-state bias. Using simulations that resembled real time-varying and noisy environments, we tested the closed-loop system for control of two different anesthetic states, burst suppression in medically induced coma and unconsciousness in general anesthesia. In 1200 simulations, the adaptive system achieved precise control of both anesthetic states despite non-stationarity, time-variation, noise, and no initial parameter knowledge. In both cases, the adaptive system performed close to a baseline system that knew the parameters exactly. In contrast, a non-adaptive system resulted in large steady-state bias and error. The adaptive system also resulted in significantly smaller steady-state infusion rate variations compared to prior systems. These results have significant implications for clinically viable CLAD design for a wide range of anesthetic states, with potential cost-saving and therapeutic benefits.

The Altered Hepatic Tubulin Code in Alcoholic Liver Disease

PubMed Central

Groebner, Jennifer L.; Tuma, Pamela L.

2015-01-01

The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the “tubulin code” are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease. PMID:26393662

The Altered Hepatic Tubulin Code in Alcoholic Liver Disease.

PubMed

Groebner, Jennifer L; Tuma, Pamela L

2015-09-18

The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the "tubulin code" are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease.

Heat-induced Irreversible Denaturation of the Camelid Single Domain VHH Antibody Is Governed by Chemical Modifications

PubMed Central

Akazawa-Ogawa, Yoko; Takashima, Mizuki; Lee, Young-Ho; Ikegami, Takahisa; Goto, Yuji; Uegaki, Koichi; Hagihara, Yoshihisa

2014-01-01

The variable domain of camelid heavy chain antibody (VHH) is highly heat-resistant and is therefore ideal for many applications. Although understanding the process of heat-induced irreversible denaturation is essential to improve the efficacy of VHH, its inactivation mechanism remains unclear. Here, we showed that chemical modifications predominantly governed the irreversible denaturation of VHH at high temperatures. After heat treatment, the activity of VHH was dependent only on the incubation time at 90 °C and was insensitive to the number of heating (90 °C)-cooling (20 °C) cycles, indicating a negligible role for folding/unfolding intermediates on permanent denaturation. The residual activity was independent of concentration; therefore, VHH lost its activity in a unimolecular manner, not by aggregation. A VHH mutant lacking Asn, which is susceptible to chemical modifications, had significantly higher heat resistance than did the wild-type protein, indicating the importance of chemical modifications to VHH denaturation. PMID:24739391

Adapting a Navier-Stokes code to the ICL-DAP

NASA Technical Reports Server (NTRS)

Grosch, C. E.

1985-01-01

The results of an experiment are reported, i.c., to adapt a Navier-Stokes code, originally developed on a serial computer, to concurrent processing on the CL Distributed Array Processor (DAP). The algorithm used in solving the Navier-Stokes equations is briefly described. The architecture of the DAP and DAP FORTRAN are also described. The modifications of the algorithm so as to fit the DAP are given and discussed. Finally, performance results are given and conclusions are drawn.

Simple and versatile modifications allowing time gated spectral acquisition, imaging and lifetime profiling on conventional wide-field microscopes

NASA Astrophysics Data System (ADS)

Pal, Robert; Beeby, Andrew

2014-09-01

An inverted microscope has been adapted to allow time-gated imaging and spectroscopy to be carried out on samples containing responsive lanthanide probes. The adaptation employs readily available components, including a pulsed light source, time-gated camera, spectrometer and photon counting detector, allowing imaging, emission spectroscopy and lifetime measurements. Each component is controlled by a suite of software written in LabVIEW and is powered via conventional USB ports.

33 CFR 332.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... following terms are defined: Adaptive management means the development of a management strategy that... guides modification of those projects to optimize performance. It includes the selection of appropriate... monitoring results to identify potential problems of a compensatory mitigation project and the identification...

Meiosis evolves: adaptation to external and internal environments.

PubMed

Bomblies, Kirsten; Higgins, James D; Yant, Levi

2015-10-01

306 I. 306 II. 307 III. 312 IV. 317 V. 318 319 References 319 SUMMARY: Meiosis is essential for the fertility of most eukaryotes and its structures and progression are conserved across kingdoms. Yet many of its core proteins show evidence of rapid or adaptive evolution. What drives the evolution of meiosis proteins? How can constrained meiotic processes be modified in response to challenges without compromising their essential functions? In surveying the literature, we found evidence of two especially potent challenges to meiotic chromosome segregation that probably necessitate adaptive evolutionary responses: whole-genome duplication and abiotic environment, especially temperature. Evolutionary solutions to both kinds of challenge are likely to involve modification of homologous recombination and synapsis, probably via adjustments of core structural components important in meiosis I. Synthesizing these findings with broader patterns of meiosis gene evolution suggests that the structural components of meiosis coevolve as adaptive modules that may change in primary sequence and function while maintaining three-dimensional structures and protein interactions. The often sharp divergence of these genes among species probably reflects periodic modification of entire multiprotein complexes driven by genomic or environmental changes. We suggest that the pressures that cause meiosis to evolve to maintain fertility may cause pleiotropic alterations of global crossover rates. We highlight several important areas for future research. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Design for a region-wide adaptive search for the ivorybilled woodpecker with the objective of estimating occupancy and related parameters

USGS Publications Warehouse

Cooper, R.J.; Mordecai, Rua S.; Mattsson, B.G.; Conroy, M.J.; Pacifici, K.; Peterson, J.T.; Moore, C.T.

2008-01-01

We describe a survey design and field protocol for the Ivory-billed Woodpecker (Campephilus principalis) search effort that will: (1) allow estimation of occupancy, use, and detection probability for habitats at two spatial scales within the bird?s former range, (2) assess relationships between occupancy, use, and habitat characteristics at those scales, (3) eventually allow the development of a population viability model that depends on patch occupancy instead of difficult-to-measure demographic parameters, and (4) be adaptive, allowing newly collected information to update the above models and search locations. The approach features random selection of patches to be searched from a sampling frame stratified and weighted by patch quality, and requires multiple visits per patch. It is adaptive within a season in that increased search activity is allowed in and around locations of strong visual and/or aural evidence, and adaptive among seasons in that habitat associations allow modification of stratum weights. This statistically rigorous approach is an improvement over simply visiting the ?best? habitat in an ad hoc fashion because we can learn from prior effort and modify the search accordingly. Results from the 2006-07 search season indicate weak relationships between occupancy and habitat (although we suggest modifications of habitat measurement protocols), and a very low detection probability, suggesting more visits per patch are required. Sample size requirements will be discussed.

Post-Synthetic Defucosylation of AGP by Aspergillus nidulans α-1,2-Fucosidase Expressed in Arabidopsis Apoplast Induces Compensatory Upregulation of α-1,2-Fucosyltransferases.

PubMed

Pogorelko, Gennady V; Reem, Nathan T; Young, Zachary T; Chambers, Lauran; Zabotina, Olga A

2016-01-01

Cell walls are essential components of plant cells which perform a variety of important functions for the different cell types, tissues and organs of a plant. Besides mechanical function providing cell shape, cell walls participate in intercellular communication, defense during plant-microbe interactions, and plant growth. The plant cell wall consists predominantly of polysaccharides with the addition of structural glycoproteins, phenolic esters, minerals, lignin, and associated enzymes. Alterations in the cell wall composition created through either changes in biosynthesis of specific constituents or their post-synthetic modifications in the apoplast compromise cell wall integrity and frequently induce plant compensatory responses as a result of these alterations. Here we report that post-synthetic removal of fucose residues specifically from arabinogalactan proteins in the Arabidopsis plant cell wall induces differential expression of fucosyltransferases and leads to the root and hypocotyl elongation changes. These results demonstrate that the post-synthetic modification of cell wall components presents a valuable approach to investigate the potential signaling pathways induced during plant responses to such modifications that usually occur during plant development and stress responses.

Cyclosporin A inhibits UV-radiation-induced membrane damage but is unable to inhibit carboxyatractyloside-induced permeability transition.

PubMed

García, Noemí; Zazueta, Cecilia; El-Hafidi, Mohammed; Pavón, Natalia; Martínez-Abundis, Eduardo; Hernández-Esquivel, Luz; Chávez, Edmundo

2009-11-01

This work was undertaken to gain further information on the chemical characteristics of the membrane entity involved in the formation of the nonspecific pore. Mitochondria were subjected to oxidative stress by exposure to UV radiation. The results indicate that ultraviolet C radiation induces structural modifications in the adenine nucleotide translocase that lead to membrane permeability transition. Membrane leakage was assessed by measuring mitochondrial Ca2+ transport, the transmembrane electric gradient, and mitochondrial swelling. UV-irradiated mitochondria were unable to retain matrix Ca2+ or to maintain a high level of membrane potential when Ca2+ was added; furthermore, UV-irradiated mitochondria underwent large amplitude swelling. Release of cytochrome c and formation of malondialdehyde, owing to lipid peroxidation, were also seen. Structural modifications of the translocase were revealed by an increase in the binding of the fluorescent probe eosin-5-maleimide to thiol residues of the ADP/ATP carrier. These modifications, taken together with findings indicating that cyclosporin resulted unable to inhibit carboxyatractyloside-induced permeability transition, prompted us to conclude that the translocase could constitute the nonspecific pore or at least be an important modulator of it.

Understanding the dynamics of the Seguro Popular de Salud policy implementation in Mexico from a complex adaptive systems perspective.

PubMed

Nigenda, Gustavo; González-Robledo, Luz María; Juárez-Ramírez, Clara; Adam, Taghreed

2016-05-13

In 2003, Mexico's Seguro Popular de Salud (SPS), was launched as an innovative financial mechanism implemented to channel new funds to provide health insurance to 50 million Mexicans and to reduce systemic financial inequities. The objective of this article is to understand the complexity and dynamics that contributed to the adaptation of the policy in the implementation stage, how these changes occurred, and why, from a complex and adaptive systems perspective. A complex adaptive systems (CAS) framework was used to carry out a secondary analysis of data obtained from four SPS's implementation evaluations. We first identified key actors, their roles, incentives and power, and their responses to the policy and guidelines. We then developed a causal loop diagram to disentangle the feedback dynamics associated with the modifications of the policy implementation which we then analyzed using a CAS perspective. Implementation variations were identified in seven core design features during the first 10 years of implementation period, and in each case, the SPS's central coordination introduced modifications in response to the reactions of the different actors. We identified several CAS phenomena associated with these changes including phase transitions, network emergence, resistance to change, history dependence, and feedback loops. Our findings generate valuable lessons to policy implementation processes, especially those involving a monetary component, where the emergence of coping mechanisms and other CAS phenomena inevitably lead to modifications of policies and their interpretation by those who implement them. These include the difficulty of implementing strategies that aim to pool funds through solidarity among beneficiaries where the rich support the poor when there are no incentives for the rich to do so. Also, how resistance to change and history dependence can pose significant challenges to implementing changes, where the local actors use their significant power to oppose or modify these changes.

Fatigue-induced early onset of anticipatory postural adjustments in non-fatigued muscles: support for a centrally mediated adaptation.

PubMed

Strang, Adam J; Berg, William P; Hieronymus, Mathias

2009-08-01

Muscle fatigue has been shown to result in early onset of anticipatory postural adjustments (APAs) relative to those produced in a non-fatigued state. This adaptation is thought to reflect an attempt to preserve postural stability during a focal movement performed in a fatigued state. It remains unclear, however, whether this adaptation is of central (e.g., central nervous system motor command) or peripheral (e.g., muscle contractile properties), origin. One way to confirm that this adaptation is centrally driven is to identify fatigued-induced early APA onsets in non-fatigued muscles. In this study, APAs were obtained using a rapid bilateral reaching maneuver and recorded via surface electromyography before and after conditions of rest (n = 25) or fatigue (n = 25). Fatigue was generated using isokinetic exercise of the right leg. Results showed that fatigue-induced early APA onsets occurred in fatigued and non-fatigued muscles, confirming that fatigue-induced early APA onset is a centrally mediated adaptation.

Profiling Changes in Histone Post-translational Modifications by Top-Down Mass Spectrometry.

PubMed

Zhou, Mowei; Wu, Si; Stenoien, David L; Zhang, Zhaorui; Connolly, Lanelle; Freitag, Michael; Paša-Tolić, Ljiljana

2017-01-01

Top-down mass spectrometry is a valuable tool for understanding gene expression through characterization of combinatorial histone post-translational modifications (i.e., histone code). In this protocol, we describe a top-down workflow that employs liquid chromatography (LC) coupled to mass spectrometry (MS), for fast global profiling of changes in histone proteoforms, and apply LCMS top-down approach for comparative analysis of a wild-type and a mutant fungal species. The proteoforms exhibiting differential abundances can be subjected to further targeted studies by other MS or orthogonal (e.g., biochemical) assays. This method can be generally adapted for screening of changes in histone modifications between samples such as wild type vs. mutant or healthy vs. diseased.

Virtual Reality to Maximize Function for Hand and Arm Rehabilitation: Exploration of Neural Mechanisms

PubMed Central

MERIANS, Alma S.; TUNIK, Eugene; ADAMOVICH, Sergei V.

2015-01-01

Stroke patients report hand function as the most disabling motor deficit. Current evidence shows that learning new motor skills is essential for inducing functional neuroplasticity and functional recovery. Adaptive training paradigms that continually and interactively move a motor outcome closer to the targeted skill are important to motor recovery. Computerized virtual reality simulations when interfaced with robots, movement tracking and sensing glove systems are particularly adaptable, allowing for online and offline modifications of task based activities using the participant’s current performance and success rate. We have developed a second generation system that can exercise the hand and the arm together or in isolation and provides for both unilateral and bilateral hand and arm activities in three-dimensional space. We demonstrate that by providing haptic assistance for the hand and arm and adaptive anti-gravity support, the system can accommodate patients with lower level impairments. We hypothesize that combining training in VE with observation of motor actions can bring additional benefits. We present a proof of concept of a novel system that integrates interactive VE with functional neuroimaging to address this issue. Three components of this system are synchronized, the presentation of the visual display of the virtual hands, the collection of fMRI images and the collection of hand joint angles from the instrumented gloves. We show that interactive VEs can facilitate activation of brain areas during training by providing appropriately modified visual feedback. We predict that visual augmentation can become a tool to facilitate functional neuroplasticity. PMID:19592790

Epigenetic patterns newly established after interspecific hybridization in natural populations of Solanum

PubMed Central

Cara, Nicolás; Marfil, Carlos F; Masuelli, Ricardo W

2013-01-01

Interspecific hybridization is known for triggering genetic and epigenetic changes, such as modifications on DNA methylation patterns and impact on phenotypic plasticity and ecological adaptation. Wild potatoes (Solanum, section Petota) are adapted to multiple habitats along the Andes, and natural hybridizations have proven to be a common feature among species of this group. Solanum × rechei, a recently formed hybrid that grows sympatrically with the parental species S. kurtzianum and S. microdontum, represents an ideal model for studying the ecologically and evolutionary importance of hybridization in generating of epigenetic variability. Genetic and epigenetic variability and their correlation with morphological variation were investigated in wild and ex situ conserved populations of these three wild potato species using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified polymorphism (MSAP) techniques. We observed that novel methylation patterns doubled the number of novel genetic patterns in the hybrid and that the morphological variability measured on 30 characters had a higher correlation with the epigenetic than with the genetic variability. Statistical comparison of methylation levels suggested that the interspecific hybridization induces genome demethylation in the hybrids. A Bayesian analysis of the genetic data reveled the hybrid nature of S. × rechei, with genotypes displaying high levels of admixture with the parental species, while the epigenetic information assigned S. × rechei to its own cluster with low admixture. These findings suggested that after the hybridization event, a novel epigenetic pattern was rapidly established, which might influence the phenotypic plasticity and adaptation of the hybrid to new environments. PMID:24198938

Identification of Maillard reaction induced chemical modifications on Ara h 1

USDA-ARS?s Scientific Manuscript database

The Maillard reaction is a non-enzymatic glycation reaction between proteins and reducing sugars that can modify nut allergens during thermal processing. These modifications can alter the structural and immunological properties of these allergens, and may result in increased IgE binding. Here, we ...

Specific histone modification responds to arsenic-induced oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Lu

To explore whether specific histone modifications are associated with arsenic-induced oxidative damage, we recruited 138 arsenic-exposed and arsenicosis subjects from Jiaole Village, Xinren County of Guizhou province, China where the residents were exposed to arsenic from indoor coal burning. 77 villagers from Shang Batian Village that were not exposed to high arsenic coal served as the control group. The concentrations of urine and hair arsenic in the arsenic-exposure group were 2.4-fold and 2.1-fold (all P < 0.001) higher, respectively, than those of the control group. Global histone modifications in human peripheral lymphocytes (PBLCs) were examined by ELISA. The results showedmore » that altered global levels of H3K18ac, H3K9me2, and H3K36me3 correlated with both urinary and hair-arsenic levels of the subjects. Notably, H3K36me3 and H3K18ac modifications were associated with urinary 8-OHdG (H3K36me3: β = 0.16; P = 0.042, H3K18ac: β = − 0.24; P = 0.001). We also found that the modifications of H3K18ac and H3K36me3 were enriched in the promoters of oxidative stress response (OSR) genes in human embryonic kidney (HEK) cells and HaCaT cells, providing evidence that H3K18ac and H3K36me3 modifications mediate transcriptional regulation of OSR genes in response to NaAsO{sub 2} treatment. Particularly, we found that reduced H3K18ac modification correlated with suppressed expression of OSR genes in HEK cells with long term arsenic treatment and in PBLCs of all the subjects. Taken together, we reveal a critical role for specific histone modification in response to arsenic-induced oxidative damage. - Highlights: • H3K18ac, H3K9me2 and H3K36me3 were associated with arsenic exposed levels. • H3K18ac and H3K36me3 were correlated with oxidative damage induced by arsenic. • H3K18ac and H3K36me3 might involve in transcriptional regulation of OSR genes. • Dysregulation of H3K18ac and H3K36me3 might be biomarkers of arsenic toxicity.« less

Salient Distractors Can Induce Saccade Adaptation

PubMed Central

Khan, Afsheen; McFadden, Sally A.; Wallman, Josh

2014-01-01

When saccadic eye movements consistently fail to land on their intended target, saccade accuracy is maintained by gradually adapting the movement size of successive saccades. The proposed error signal for saccade adaptation has been based on the distance between where the eye lands and the visual target (retinal error). We studied whether the error signal could alternatively be based on the distance between the predicted and actual locus of attention after the saccade. Unlike conventional adaptation experiments that surreptitiously displace the target once a saccade is initiated towards it, we instead attempted to draw attention away from the target by briefly presenting salient distractor images on one side of the target after the saccade. To test whether less salient, more predictable distractors would induce less adaptation, we separately used fixed random noise distractors. We found that both visual attention distractors were able to induce a small degree of downward saccade adaptation but significantly more to the more salient distractors. As in conventional adaptation experiments, upward adaptation was less effective and salient distractors did not significantly increase amplitudes. We conclude that the locus of attention after the saccade can act as an error signal for saccade adaptation. PMID:24876947

Design and Validation of CRISPR/Cas9 Systems for Targeted Gene Modification in Induced Pluripotent Stem Cells.

PubMed

Lee, Ciaran M; Zhu, Haibao; Davis, Timothy H; Deshmukh, Harshahardhan; Bao, Gang

2017-01-01

The CRISPR/Cas9 system is a powerful tool for precision genome editing. The ability to accurately modify genomic DNA in situ with single nucleotide precision opens up new possibilities for not only basic research but also biotechnology applications and clinical translation. In this chapter, we outline the procedures for design, screening, and validation of CRISPR/Cas9 systems for targeted modification of coding sequences in the human genome and how to perform genome editing in induced pluripotent stem cells with high efficiency and specificity.

Capture, Unfolding, and Detection of Individual tRNA Molecules Using a Nanopore Device

PubMed Central

Smith, Andrew M.; Abu-Shumays, Robin; Akeson, Mark; Bernick, David L.

2015-01-01

Transfer RNAs (tRNA) are the most common RNA molecules in cells and have critical roles as both translators of the genetic code and regulators of protein synthesis. As such, numerous methods have focused on studying tRNA abundance and regulation, with the most widely used methods being RNA-seq and microarrays. Though revolutionary to transcriptomics, these assays are limited by an inability to encode tRNA modifications in the requisite cDNA. These modifications are abundant in tRNA and critical to their function. Here, we describe proof-of-concept experiments where individual tRNA molecules are examined as linear strands using a biological nanopore. This method utilizes an enzymatically ligated synthetic DNA adapter to concentrate tRNA at the lipid bilayer of the nanopore device and efficiently denature individual tRNA molecules, as they are pulled through the α-hemolysin (α-HL) nanopore. Additionally, the DNA adapter provides a loading site for ϕ29 DNA polymerase (ϕ29 DNAP), which acts as a brake on the translocating tRNA. This increases the dwell time of adapted tRNA in the nanopore, allowing us to identify the region of the nanopore signal that is produced by the translocating tRNA itself. Using adapter-modified Escherichia coli tRNAfMet and tRNALys, we show that the nanopore signal during controlled translocation is dependent on the identity of the tRNA. This confirms that adapter-modified tRNA can translocate end-to-end through nanopores and provide the foundation for future work in direct sequencing of individual transfer RNA with a nanopore-based device. PMID:26157798

Adaptation to sensory-motor reflex perturbations is blind to the source of errors.

PubMed

Hudson, Todd E; Landy, Michael S

2012-01-06

In the study of visual-motor control, perhaps the most familiar findings involve adaptation to externally imposed movement errors. Theories of visual-motor adaptation based on optimal information processing suppose that the nervous system identifies the sources of errors to effect the most efficient adaptive response. We report two experiments using a novel perturbation based on stimulating a visually induced reflex in the reaching arm. Unlike adaptation to an external force, our method induces a perturbing reflex within the motor system itself, i.e., perturbing forces are self-generated. This novel method allows a test of the theory that error source information is used to generate an optimal adaptive response. If the self-generated source of the visually induced reflex perturbation is identified, the optimal response will be via reflex gain control. If the source is not identified, a compensatory force should be generated to counteract the reflex. Gain control is the optimal response to reflex perturbation, both because energy cost and movement errors are minimized. Energy is conserved because neither reflex-induced nor compensatory forces are generated. Precision is maximized because endpoint variance is proportional to force production. We find evidence against source-identified adaptation in both experiments, suggesting that sensory-motor information processing is not always optimal.

Selected photographic techniques, a compilation

NASA Technical Reports Server (NTRS)

1971-01-01

A selection has been made of methods, devices, and techniques developed in the field of photography during implementation of space and nuclear research projects. These items include many adaptations, variations, and modifications to standard hardware and practice, and should prove interesting to both amateur and professional photographers and photographic technicians. This compilation is divided into two sections. The first section presents techniques and devices that have been found useful in making photolab work simpler, more productive, and higher in quality. Section two deals with modifications to and special applications for existing photographic equipment.

Providing the support services needed by students who are deaf or hard of hearing.

PubMed

Luetke-Stahlman, B

1998-12-01

When students who are deaf or hard of hearing are appropriately placed, program-level and curriculum-level adaptations may both need to be discussed to ensure social as well as academic progress. Programmatic modifications may involve communication, linguistic, and grading issues, and both the listening and physical settings. Curricular modifications may involve the classroom structure, rapport and affect, the instructional format and language, the lesson format and materials, comprehension monitoring, activity and assignment completion, and placement choices. Professionals should work cooperatively to make and monitor changes.

New class of control laws for robotic manipulators. I - Nonadaptive case. II - Adaptive case

NASA Technical Reports Server (NTRS)

Wen, John T.; Bayard, David S.

1988-01-01

A new class of exponentially stabilizing control laws for joint level control of robot arms is discussed. Closed-loop exponential stability has been demonstrated for both the set point and tracking control problems by a slight modification of the energy Lyapunov function and the use of a lemma which handles third-order terms in the Lyapunov function derivatives. In the second part, these control laws are adapted in a simple fashion to achieve asymptotically stable adaptive control. The analysis addresses the nonlinear dynamics directly without approximation, linearization, or ad hoc assumptions, and uses a parameterization based on physical (time-invariant) quantities.

An Adaption Tool Kit for Teaching Music

ERIC Educational Resources Information Center

McDowell, Carol

2010-01-01

Music-education majors often struggle when making classroom and curricular modifications for their lesson plans during their university coursework. This article offers behavioral, curricular, environmental, motivational, organizational, and presentational strategies for planning instruction for various disabilities in the music classroom.…

Quick Information Sheets.

ERIC Educational Resources Information Center

Wisconsin Univ., Madison. Trace Center.

This compilation of "Trace Quick Sheets" provides descriptions, prices, and ordering information for products and services that assist with communication, control, and computer access for disabled individuals. Product descriptions or product sources are included for: adaptive toys and toy modifications; head pointers, light pointers, and…

Mitogen- and Stress-Activated Kinase 1 (MSK1) Regulates Cigarette Smoke-Induced Histone Modifications on NF-κB-dependent Genes

PubMed Central

Sundar, Isaac K.; Chung, Sangwoon; Hwang, Jae-woong; Lapek, John D.; Bulger, Michael; Friedman, Alan E.; Yao, Hongwei; Davie, James R.; Rahman, Irfan

2012-01-01

Cigarette smoke (CS) causes sustained lung inflammation, which is an important event in the pathogenesis of chronic obstructive pulmonary disease (COPD). We have previously reported that IKKα (I kappaB kinase alpha) plays a key role in CS-induced pro-inflammatory gene transcription by chromatin modifications; however, the underlying role of downstream signaling kinase is not known. Mitogen- and stress-activated kinase 1 (MSK1) serves as a specific downstream NF-κB RelA/p65 kinase, mediating transcriptional activation of NF-κB-dependent pro-inflammatory genes. The role of MSK1 in nuclear signaling and chromatin modifications is not known, particularly in response to environmental stimuli. We hypothesized that MSK1 regulates chromatin modifications of pro-inflammatory gene promoters in response to CS. Here, we report that CS extract activates MSK1 in human lung epithelial (H292 and BEAS-2B) cell lines, human primary small airway epithelial cells (SAEC), and in mouse lung, resulting in phosphorylation of nuclear MSK1 (Thr581), phospho-acetylation of RelA/p65 at Ser276 and Lys310 respectively. This event was associated with phospho-acetylation of histone H3 (Ser10/Lys9) and acetylation of histone H4 (Lys12). MSK1 N- and C-terminal kinase-dead mutants, MSK1 siRNA-mediated knock-down in transiently transfected H292 cells, and MSK1 stable knock-down mouse embryonic fibroblasts significantly reduced CS extract-induced MSK1, NF-κB RelA/p65 activation, and posttranslational modifications of histones. CS extract/CS promotes the direct interaction of MSK1 with RelA/p65 and p300 in epithelial cells and in mouse lung. Furthermore, CS-mediated recruitment of MSK1 and its substrates to the promoters of NF-κB-dependent pro-inflammatory genes leads to transcriptional activation, as determined by chromatin immunoprecipitation. Thus, MSK1 is an important downstream kinase involved in CS-induced NF-κB activation and chromatin modifications, which have implications in pathogenesis of COPD. PMID:22312446

Melanoma differentiation associated gene-7/interleukin-24 induces caspase-3 denitrosylation to facilitate the activation of cancer cell apoptosis.

PubMed

Tian, Hui; Zhang, De-Fang; Zhang, Bao-Fu; Li, Hui-Zhong; Zhang, Qing; Li, Lian-Tao; Pei, Dong-Sheng; Zheng, Jun-Nian

2015-03-01

Melanoma differentiation-associated gene-7 (mda-7)/interleukin-24 (IL-24) induces caspase-3 cleavage and subsequent activation via the intrinsic or extrinsic pathway to result in cancer cell-selective apoptosis, but whether mda-7/IL-24 may directly regulate caspase-3 through the post-translational modification remains unknown. Here, we reported that tumor-selective replicating adenovirus ZD55-IL-24 led to caspase-3 denitrosylation and subsequent activation, indicating that caspase-3 denitrosylation played a crucial role in ZD55-IL-24-induced cancer cell apoptosis. To confirm the relationship between caspase-3 denitrosylation and its activation in response to ZD55-IL-24, we treated carcinoma cells with the different nitric oxide (NO) regulators to modulate caspase-3 denitrosylation level, then observed the corresponding caspase-3 cleavage. We found that NO inhibitor 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide (PTIO) promoted caspase-3 denitrosylation and caspase-3 cleavage, thereby exacerbating ZD55-IL-24-induced cancer cell apoptosis, whereas NO donor sodium nitroprusside (SNP) showed the opposite effect. Moreover, caspase-3 denitrosylation facilitated its downstream target poly ADP-ribose polymerase (PARP) degradation that further increased the apoptotic susceptibility. Although caspase-3 activation controlled by denitrosylation modification has emerged as an important regulator of programmed cell death, the detailed molecular mechanism by which caspase-3 exerts its denitrosylation modification in response to ZD55-IL-24 still needs to be elucidated. Thus, our results demonstrated that ZD55-IL-24 increased Fas expression to enhance thioredoxin reductase 2 (TrxR2), which was responsible for caspase-3 denitrosylation. Collectively, these findings elucidate that ZD55-IL-24 induces caspase-3 denitrosylation through Fas-mediated TrxR2 enhancement, thereby facilitating caspase-3 cleavage and the downstream caspase signaling pathway activation, which provides a novel insight into ZD55-IL-24-induced cancer-specific apoptosis by post-translational modification of the apoptotic executor caspase-3.

Methods used in adaptation of health-related guidelines: A systematic survey.

PubMed

Abdul-Khalek, Rima A; Darzi, Andrea J; Godah, Mohammad W; Kilzar, Lama; Lakis, Chantal; Agarwal, Arnav; Abou-Jaoude, Elias; Meerpohl, Joerg J; Wiercioch, Wojtek; Santesso, Nancy; Brax, Hneine; Schünemann, Holger; Akl, Elie A

2017-12-01

Adaptation refers to the systematic approach for considering the endorsement or modification of recommendations produced in one setting for application in another as an alternative to de novo development. To describe and assess the methods used for adapting health-related guidelines published in peer-reviewed journals, and to assess the quality of the resulting adapted guidelines. We searched Medline and Embase up to June 2015. We assessed the method of adaptation, and the quality of included guidelines. Seventy-two papers were eligible. Most adapted guidelines and their source guidelines were published by professional societies (71% and 68% respectively), and in high-income countries (83% and 85% respectively). Of the 57 adapted guidelines that reported any detail about adaptation method, 34 (60%) did not use a published adaptation method. The number (and percentage) of adapted guidelines fulfilling each of the ADAPTE steps ranged between 2 (4%) and 57 (100%). The quality of adapted guidelines was highest for the "scope and purpose" domain and lowest for the "editorial independence" domain (respective mean percentages of the maximum possible scores were 93% and 43%). The mean score for "rigor of development" was 57%. Most adapted guidelines published in peer-reviewed journals do not report using a published adaptation method, and their adaptation quality was variable.

Neuroplastic Changes Induced by Cognitive Rehabilitation in Traumatic Brain Injury: A Review.

PubMed

Galetto, Valentina; Sacco, Katiuscia

2017-09-01

Cognitive deficits are among the most disabling consequences of traumatic brain injury (TBI), leading to long-term outcomes and interfering with the individual's recovery. One of the most effective ways to reduce the impact of cognitive disturbance in everyday life is cognitive rehabilitation, which is based on the principles of brain neuroplasticity and restoration. Although there are many studies in the literature focusing on the effectiveness of cognitive interventions in reducing cognitive deficits following TBI, only a few of them focus on neural modifications induced by cognitive treatment. The use of neuroimaging or neurophysiological measures to evaluate brain changes induced by cognitive rehabilitation may have relevant clinical implications, since they could add individualized elements to cognitive assessment. Nevertheless, there are no review studies in the literature investigating neuroplastic changes induced by cognitive training in TBI individuals. Due to lack of data, the goal of this article is to review what is currently known on the cerebral modifications following rehabilitation programs in chronic TBI. Studies investigating both the functional and structural neural modifications induced by cognitive training in TBI subjects were identified from the results of database searches. Forty-five published articles were initially selected. Of these, 34 were excluded because they did not meet the inclusion criteria. Eleven studies were found that focused solely on the functional and neurophysiological changes induced by cognitive rehabilitation. Outcomes showed that cerebral activation may be significantly modified by cognitive rehabilitation, in spite of the severity of the injury.

Butyrate induced IGF2 activation correlated with distinct chromatin landscapes due to histone modification

USDA-ARS?s Scientific Manuscript database

Histone modification has emerged as a very important mechanism regulating the transcriptional status of the genome. Insulin-like growth factor 2 (IGF2) is a peptide hormone controlling various cellular processes such as proliferation and apoptosis. IGF2 and H19 are reciprocally regulated imprinted ...

Cognitive Bias Modification Training in Adolescents: Effects on Interpretation Biases and Mood

ERIC Educational Resources Information Center

Lothmann, Claudia; Holmes, Emily A.; Chan, Stella W. Y.; Lau, Jennifer Y. F.

2011-01-01

Background: Negative biases in the interpretation of ambiguous material have been linked to anxiety and mood problems. Accumulating data from adults show that positive and negative interpretation styles can be induced through cognitive bias modification (CBM) paradigms with accompanying changes in mood. Despite the therapeutic potential of…

Persistent ERK Activation Maintains Learning-Induced Long-Lasting Modulation of Synaptic Connectivity

ERIC Educational Resources Information Center

Cohen-Matsliah, Sivan Ida; Seroussi, Yaron; Rosenblum, Kobi; Barkai, Edi

2008-01-01

Pyramidal neurons in the piriform cortex from olfactory-discrimination (OD) trained rats undergo synaptic modifications that last for days after learning. A particularly intriguing modification is reduced paired-pulse facilitation (PPF) in the synapses interconnecting these cells; a phenomenon thought to reflect enhanced synaptic release. The…

A Poly(Lactic-co-Glycolic) Acid Nanovaccine Based on Chimeric Peptides from Different Leishmania infantum Proteins Induces Dendritic Cells Maturation and Promotes Peptide-Specific IFNγ-Producing CD8+ T Cells Essential for the Protection against Experimental Visceral Leishmaniasis.

PubMed

Athanasiou, Evita; Agallou, Maria; Tastsoglou, Spyros; Kammona, Olga; Hatzigeorgiou, Artemis; Kiparissides, Costas; Karagouni, Evdokia

2017-01-01

Visceral leishmaniasis, caused by Leishmania ( L .) donovani and L. infantum protozoan parasites, can provoke overwhelming and protracted epidemics, with high case-fatality rates. An effective vaccine against the disease must rely on the generation of a strong and long-lasting T cell immunity, mediated by CD4 + T H1 and CD8 + T cells. Multi-epitope peptide-based vaccine development is manifesting as the new era of vaccination strategies against Leishmania infection. In this study, we designed chimeric peptides containing HLA-restricted epitopes from three immunogenic L. infantum proteins (cysteine peptidase A, histone H1, and kinetoplastid membrane protein 11), in order to be encapsulated in poly(lactic- co -glycolic) acid nanoparticles with or without the adjuvant monophosphoryl lipid A (MPLA) or surface modification with an octapeptide targeting the tumor necrosis factor receptor II. We aimed to construct differentially functionalized peptide-based nanovaccine candidates and investigate their capacity to stimulate the immunomodulatory properties of dendritic cells (DCs), which are critical regulators of adaptive immunity generated upon vaccination. According to our results, DCs stimulation with the peptide-based nanovaccine candidates with MPLA incorporation or surface modification induced an enhanced maturation profile with prominent IL-12 production, promoting allogeneic T cell proliferation and intracellular production of IFNγ by CD4 + and CD8 + T cell subsets. In addition, DCs stimulated with the peptide-based nanovaccine candidate with MPLA incorporation exhibited a robust transcriptional activation, characterized by upregulated genes indicative of vaccine-driven DCs differentiation toward type 1 phenotype. Immunization of HLA A2.1 transgenic mice with this peptide-based nanovaccine candidate induced peptide-specific IFNγ-producing CD8 + T cells and conferred significant protection against L. infantum infection. Concluding, our findings supported that encapsulation of more than one chimeric multi-epitope peptides from different immunogenic L. infantum proteins in a proper biocompatible delivery system with the right adjuvant is considered as an improved promising approach for the development of a vaccine against VL.

A Poly(Lactic-co-Glycolic) Acid Nanovaccine Based on Chimeric Peptides from Different Leishmania infantum Proteins Induces Dendritic Cells Maturation and Promotes Peptide-Specific IFNγ-Producing CD8+ T Cells Essential for the Protection against Experimental Visceral Leishmaniasis

PubMed Central

Athanasiou, Evita; Agallou, Maria; Tastsoglou, Spyros; Kammona, Olga; Hatzigeorgiou, Artemis; Kiparissides, Costas; Karagouni, Evdokia

2017-01-01

Visceral leishmaniasis, caused by Leishmania (L.) donovani and L. infantum protozoan parasites, can provoke overwhelming and protracted epidemics, with high case-fatality rates. An effective vaccine against the disease must rely on the generation of a strong and long-lasting T cell immunity, mediated by CD4+ TH1 and CD8+ T cells. Multi-epitope peptide-based vaccine development is manifesting as the new era of vaccination strategies against Leishmania infection. In this study, we designed chimeric peptides containing HLA-restricted epitopes from three immunogenic L. infantum proteins (cysteine peptidase A, histone H1, and kinetoplastid membrane protein 11), in order to be encapsulated in poly(lactic-co-glycolic) acid nanoparticles with or without the adjuvant monophosphoryl lipid A (MPLA) or surface modification with an octapeptide targeting the tumor necrosis factor receptor II. We aimed to construct differentially functionalized peptide-based nanovaccine candidates and investigate their capacity to stimulate the immunomodulatory properties of dendritic cells (DCs), which are critical regulators of adaptive immunity generated upon vaccination. According to our results, DCs stimulation with the peptide-based nanovaccine candidates with MPLA incorporation or surface modification induced an enhanced maturation profile with prominent IL-12 production, promoting allogeneic T cell proliferation and intracellular production of IFNγ by CD4+ and CD8+ T cell subsets. In addition, DCs stimulated with the peptide-based nanovaccine candidate with MPLA incorporation exhibited a robust transcriptional activation, characterized by upregulated genes indicative of vaccine-driven DCs differentiation toward type 1 phenotype. Immunization of HLA A2.1 transgenic mice with this peptide-based nanovaccine candidate induced peptide-specific IFNγ-producing CD8+ T cells and conferred significant protection against L. infantum infection. Concluding, our findings supported that encapsulation of more than one chimeric multi-epitope peptides from different immunogenic L. infantum proteins in a proper biocompatible delivery system with the right adjuvant is considered as an improved promising approach for the development of a vaccine against VL. PMID:28659922

Flexible architecture of inducible morphological plasticity.

PubMed

Kishida, Osamu; Nishimura, Kinya

2006-05-01

1. Predator-induced morphological defences are produced in response to an emergent predator regime. In natural systems, prey organisms usually experience temporal shifting of the composition of the predator assemblage and of the intensity of predation risk from each predator species. Although, a repetitive morphological change in response to a sequential shift of the predator regime such as alteration of the predator species or diminution of the predation risk may be adaptive, such flexible inducible morphological defences are not ubiquitous. 2. We experimentally addressed whether a flexible inducible morphological defence is accomplished in response to serial changes in the predation regime, using a model prey species which adopt different defensive morphological phenotypes in response to different predator species. Rana pirica (Matsui) tadpoles increased body depth and tail depth against the predatory larval salamander Hynobius retardatus (Dunn); on the other hand, they only increased tail depth against the predatory larval dragonfly Aeshna nigroflava (Martin). 3. Rana pirica tadpoles with the predator-specific phenotypes were subjected to removal or exchange of the predator species. After removal of the predator species, tadpoles with each predator-specific phenotype changed their phenotype to the nondefensive basic one, suggesting that both predator-specific phenotypes are costly to maintain. After an exchange of the predator species, tadpoles with each predator-specific phenotype reciprocally, flexibly shifted their phenotype to the now more suitable predator-specific one only by modifying their body part. The partial modification can effectively reduce time and energy expenditures involved in repetitive morphological changes, and therefore suggest that the costs of the flexible morphological changes are reduced.

Microgravity-induced modifications of the vestibuloocular reflex in Xenopus laevis tadpoles are related to development and the occurrence of tail lordosis.

PubMed

Horn, Eberhard R

2006-08-01

During space flights, tadpoles of the clawed toad Xenopus laevis occasionally develop upward bended tails (tail lordosis). The tail lordosis disappears after re-entry to 1g within a couple of days. The mechanisms responsible for the induction of the tail lordosis are unknown; physical conditions such as weight de-loading or physiological factors such as decreased vestibular activity in microgravity might contribute. Microgravity (microg) also exerts significant effects on the roll-induced vestibuloocular reflex (rVOR). The rVOR was used to clarify whether tail lordosis is caused by physiological factors, by correlating the occurrence of microg-induced tail lordosis with the extent of microg-induced rVOR modifications. Post-flight recordings from three space flights (D-2 Spacelab mission, STS-55 in 1993; Shuttle-to-Mir mission SMM-06, STS-84 in 1997; French Soyuz taxi flight Andromède to ISS in 2001) were analyzed in these experiments. At onset of microgravity, tadpoles were at stages 25-28, 33-36 or 45. Parameters tested were rVOR gain (ratio between the angular eye movement and the lateral 30 degrees roll) and rVOR amplitude (maximal angular postural change of the eyes during a 360 degrees lateral roll). A ratio of 22-84% of tadpoles developed lordotic tails, depending on the space flight. The overall observation was that the rVOR of tadpoles with normal tails was either not affected by microgravity, or it was enhanced. In contrast, the rVOR of lordotic animals always revealed a depression. In particular, during post-flight days 1-11, tadpoles with lordotic tails from all three groups (25-28, 33-36 and 45) showed a lower rVOR gain and amplitude than the 1g-controls. The rVOR gain and amplitude of tadpoles from the groups 25-28 and 33-36 that developed normal tails was not affected by microgravity while the rVOR of microg-tadpoles from the stage-45 group with normal tails revealed a significant rVOR augmentation. (1) the vestibular system of tadpoles with lordotic tails is developmentally retarded by microgravity; (2) after a critical status of vestibular maturation obtained during the appearance of first swimming, microgravity activates an adaptation mechanism that causes a sensitization of the vestibular system.

Direction-Specific Adaptation in Neuronal and Behavioral Responses of an Insect Mechanosensory System.

PubMed

Ogawa, Hiroto; Oka, Kotaro

2015-08-19

Stimulus-specific adaptation (SSA) is considered to be the neural underpinning of habituation to frequent stimuli and novelty detection. However, neither the cellular mechanism underlying SSA nor the link between SSA-like neuronal plasticity and behavioral modulation is well understood. The wind-detection system in crickets is one of the best models for investigating the neural basis of SSA. We found that crickets exhibit stimulus-direction-specific adaptation in wind-elicited avoidance behavior. Repetitive air currents inducing this behavioral adaptation reduced firings to the stimulus and the amplitude of excitatory synaptic potentials in wind-sensitive giant interneurons (GIs) related to the avoidance behavior. Injection of a Ca(2+) chelator into GIs diminished both the attenuation of firings and the synaptic depression induced by the repetitive stimulation, suggesting that adaptation of GIs induced by this stimulation results in Ca(2+)-mediated modulation of postsynaptic responses, including postsynaptic short-term depression. Some types of GIs showed specific adaptation to the direction of repetitive stimuli, resulting in an alteration of their directional tuning curves. The types of GIs for which directional tuning was altered displayed heterogeneous direction selectivity in their Ca(2+) dynamics that was restricted to a specific area of dendrites. In contrast, other types of GIs with constant directionality exhibited direction-independent global Ca(2+) elevation throughout the dendritic arbor. These results suggest that depression induced by local Ca(2+) accumulation at repetitively activated synapses of key neurons underlies direction-specific behavioral adaptation. This input-selective depression mediated by heterogeneous Ca(2+) dynamics could confer the ability to detect novelty at the earliest stages of sensory processing in crickets. Stimulus-specific adaptation (SSA) is considered to be the neural underpinning of habituation and novelty detection. We found that crickets exhibit stimulus-direction-specific adaptation in wind-elicited avoidance behavior. Repetitive air currents inducing this behavioral adaptation altered the directional selectivity of wind-sensitive giant interneurons (GIs) via direction-specific adaptation mediated by dendritic Ca(2+) elevation. The GIs for which directional tuning was altered displayed heterogeneous direction selectivity in their Ca(2+) dynamics and the transient increase in Ca(2+) evoked by the repeated puffs was restricted to a specific area of dendrites. These results suggest that depression induced by local Ca(2+) accumulation at repetitively activated synapses of key neurons underlies direction-specific behavioral adaptation. Our findings elucidate the subcellular mechanism underlying SSA-like neuronal plasticity related to behavioral adaptation. Copyright © 2015 the authors 0270-6474/15/3511644-12$15.00/0.

COX-2 expression induced by diesel particles involves chromatin modification and degradation of HDAC1

EPA Science Inventory

Cyclooxygenase-2 (COX-2) plays an important role in the inflammatory response induced by physiologic and stress stimuli. Exposure to diesel exhaust particulate matter (DEP) has been shown to induce pulmonary inflammation and exacerbate asthma and chronic obstructive pulmonary dis...

Adaptation of a Simple Microfluidic Platform for High-Dimensional Quantitative Morphological Analysis of Human Mesenchymal Stromal Cells on Polystyrene-Based Substrates.

PubMed

Lam, Johnny; Marklein, Ross A; Jimenez-Torres, Jose A; Beebe, David J; Bauer, Steven R; Sung, Kyung E

2017-12-01

Multipotent stromal cells (MSCs, often called mesenchymal stem cells) have garnered significant attention within the field of regenerative medicine because of their purported ability to differentiate down musculoskeletal lineages. Given the inherent heterogeneity of MSC populations, recent studies have suggested that cell morphology may be indicative of MSC differentiation potential. Toward improving current methods and developing simple yet effective approaches for the morphological evaluation of MSCs, we combined passive pumping microfluidic technology with high-dimensional morphological characterization to produce robust tools for standardized high-throughput analysis. Using ultraviolet (UV) light as a modality for reproducible polystyrene substrate modification, we show that MSCs seeded on microfluidic straight channel devices incorporating UV-exposed substrates exhibited morphological changes that responded accordingly to the degree of substrate modification. Substrate modification also effected greater morphological changes in MSCs seeded at a lower rather than higher density within microfluidic channels. Despite largely comparable trends in morphology, MSCs seeded in microscale as opposed to traditional macroscale platforms displayed much higher sensitivity to changes in substrate properties. In summary, we adapted and qualified microfluidic cell culture platforms comprising simple straight channel arrays as a viable and robust tool for high-throughput quantitative morphological analysis to study cell-material interactions.

Experimental modification of interpretation bias about animal fear in young children: effects on cognition, avoidance behavior, anxiety vulnerability, and physiological responding.

PubMed

Lester, Kathryn J; Field, Andy P; Muris, Peter

2011-01-01

This study investigated the effects of experimentally modifying interpretation biases for children's cognitions, avoidance behavior, anxiety vulnerability, and physiological responding. Sixty-seven children (6-11 years) were randomly assigned to receive a positive or negative interpretation bias modification procedure to induce interpretation biases toward or away from threat about ambiguous situations involving Australian marsupials. Children rapidly learned to select outcomes of ambiguous situations, which were congruent with their assigned condition. Furthermore, following positive modification, children's threat biases about novel ambiguous situations significantly decreased, whereas threat biases significantly increased after negative modification. In response to a stress-evoking behavioral avoidance test, positive modification attenuated behavioral avoidance compared to negative modification. However, no significant effects of bias modification on anxiety vulnerability or physiological responses to this stress-evoking Behavioral Avoidance Task were observed.

Vibration control in statically indeterminate adaptive truss structures

NASA Technical Reports Server (NTRS)

Baycan, C. M.; Utku, Senol; Wada, Ben K.

1993-01-01

In this work vibration control of statically indeterminate adaptive truss structures is investigated. Here, the actuators (i.e., length adjusting devices) that are used for vibration control, work against the axial forces caused by the inertial forces. In statically determinate adaptive trusses no axial force is induced by the actuation. The control problem in statically indeterminate trusses may be dominated by the actuation-induced axial element forces. The creation of actuation-induced axial forces puts the system to a higher energy state, thus aggravates the controls. It is shown that by the usage of sufficient number of slave actuators in addition to the actual control actuators, the actuation-induced axial element forces can be nullified, and the control problem of the statically indeterminate adaptive truss problem is reduced to that of a statically determinate one. It is also shown that the usage of slave actuators saves a great amount of control energy and provides robustness for the controls.

DNA repair factor XPC is modified by SUMO-1 and ubiquitin following UV irradiation

PubMed Central

Wang, Qi-En; Zhu, Qianzheng; Wani, Gulzar; El-Mahdy, Mohamed A.; Li, Jinyou; Wani, Altaf A.

2005-01-01

Nucleotide excision repair (NER) is the major DNA repair process that removes diverse DNA lesions including UV-induced photoproducts. There are more than 20 proteins involved in NER. Among them, XPC is thought to be one of the first proteins to recognize DNA damage during global genomic repair (GGR), a sub-pathway of NER. In order to study the mechanism through which XPC participates in GGR, we investigated the possible modifications of XPC protein upon UV irradiation in mammalian cells. Western blot analysis of cell lysates from UV-irradiated normal human fibroblast, prepared by direct boiling in an SDS lysis buffer, showed several anti-XPC antibody-reactive bands with molecular weight higher than the original XPC protein. The reciprocal immunoprecipitation and siRNA transfection analysis demonstrated that XPC protein is modified by SUMO-1 and ubiquitin. By using several NER-deficient cell lines, we found that DDB2 and XPA are required for UV-induced XPC modifications. Interestingly, both the inactivation of ubiquitylation and the treatment of proteasome inhibitors quantitatively inhibited the UV-induced XPC modifications. Furthermore, XPC protein is degraded significantly following UV irradiation in XP-A cells in which sumoylation of XPC does not occur. Taken together, we conclude that XPC protein is modified by SUMO-1 and ubiquitin following UV irradiation and these modifications require the functions of DDB2 and XPA, as well as the ubiquitin–proteasome system. Our results also suggest that at least one function of UV-induced XPC sumoylation is related to the stabilization of XPC protein. PMID:16030353

Inducible SUMO modification of TANK alleviates its repression of TLR7 signalling.

PubMed

Renner, Florian; Saul, Vera V; Pagenstecher, Axel; Wittwer, Tobias; Schmitz, Michael Lienhard

2011-02-01

Adaptor proteins allow temporal and spatial coordination of signalling. In this study, we show SUMOylation of the adaptor protein TANK and its interacting kinase TANK-binding kinase 1 (TBK1). Modification of TANK by the small ubiquitin-related modifier (SUMO) at the evolutionarily conserved Lys 282 is triggered by the kinase activities of IκB kinase ɛ (IKKɛ) and TBK1. Stimulation of TLR7 leads to inducible SUMOylation of TANK, which in turn weakens the interaction with IKKɛ and thus relieves the negative function of TANK on signal propagation. Reconstitution experiments show that an absence of TANK SUMOylation impairs inducible expression of distinct TLR7-dependent target genes, providing a molecular mechanism that allows the control of TANK function.

Manipulating Semicrystalline Polymers in Confinement.

PubMed

Shingne, Nitin; Geuss, Markus; Thurn-Albrecht, Thomas; Schmidt, Hans-Werner; Mijangos, Carmen; Steinhart, Martin; Martín, Jaime

2017-08-17

Because final properties of nanoscale polymeric structures are largely determined by the solid-state microstructure of the confined polymer, it is imperative not only to understand how the microstructure of polymers develops under nanoscale confinement but also to establish means to manipulate it. Here we present a series of processing strategies, adapted from methods used in bulk polymer processing, that allow us to control the solidification of polymer nanostructures. First, we show that supramolecular nucleating agents can be readily used to modify the crystallization kinetics of confined poly(vinylidene fluoride) (PVDF). In addition, we demonstrate that microstructural features that are not traditionally affected by nucleating agents, such as the orientation of crystals, can be tuned with the crystallization temperature applied. Interestingly, we also show that high crystallization temperatures and long annealing periods induce the formation of the γ modification of PVDF, hence enabling the simple production of ferro/piezoelectric nanostructures. We anticipate that the approaches presented here can open up a plethora of new possibilities for the processing of polymer-based nanostructures with tailored properties and functionalities.

Global Proteomics Analysis of the Response to Starvation in C. elegans*

PubMed Central

Larance, Mark; Pourkarimi, Ehsan; Wang, Bin; Brenes Murillo, Alejandro; Kent, Robert; Lamond, Angus I.; Gartner, Anton

2015-01-01

Periodic starvation of animals induces large shifts in metabolism but may also influence many other cellular systems and can lead to adaption to prolonged starvation conditions. To date, there is limited understanding of how starvation affects gene expression, particularly at the protein level. Here, we have used mass-spectrometry-based quantitative proteomics to identify global changes in the Caenorhabditis elegans proteome due to acute starvation of young adult animals. Measuring changes in the abundance of over 5,000 proteins, we show that acute starvation rapidly alters the levels of hundreds of proteins, many involved in central metabolic pathways, highlighting key regulatory responses. Surprisingly, we also detect changes in the abundance of chromatin-associated proteins, including specific linker histones, histone variants, and histone posttranslational modifications associated with the epigenetic control of gene expression. To maximize community access to these data, they are presented in an online searchable database, the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd/). PMID:25963834

A controlled double-duration inducible gene expression system for cartilage tissue engineering.

PubMed

Ma, Ying; Li, Junxiang; Yao, Yi; Wei, Daixu; Wang, Rui; Wu, Qiong

2016-05-25

Cartilage engineering that combines competent seeding cells and a compatible scaffold is increasingly gaining popularity and is potentially useful for the treatment of various bone and cartilage diseases. Intensive efforts have been made by researchers to improve the viability and functionality of seeding cells of engineered constructs that are implanted into damaged cartilage. Here, we designed an integrative system combining gene engineering and the controlled-release concept to solve the problems of both seeding cell viability and functionality through precisely regulating the anti-apoptotic gene bcl-2 in the short-term and the chondrogenic master regulator Sox9 in the long-term. Both in vitro and in vivo experiments demonstrated that our system enhances the cell viability and chondrogenic effects of the engineered scaffold after introduction of the system while restricting anti-apoptotic gene expression to only the early stage, thereby preventing potential oncogenic and overdose effects. Our system was designed to be modular and can also be readily adapted to other tissue engineering applications with minor modification.

Poly(ethylene oxide) surfactant polymers.

PubMed

Vacheethasanee, Katanchalee; Wang, Shuwu; Qiu, Yongxing; Marchant, Roger E

2004-01-01

We report on a series of structurally well-defined surfactant polymers that undergo surface-induced self-assembly on hydrophobic biomaterial surfaces. The surfactant polymers consist of a poly(vinyl amine) backbone with poly(ethylene oxide) and hexanal pendant groups. The poly(vinyl amine) (PVAm) was synthesized by hydrolysis of poly(N-vinyl formamide) following free radical polymerization of N-vinyl formamide. Hexanal and aldehyde-terminated poly(ethylene oxide) (PEO) were simultaneously attached to PVAm via reductive amination. Surfactant polymers with different PEO:hexanal ratios and hydrophilic/hydrophobic balances were prepared, and characterized by FT-IR, 1H-NMR and XPS spectroscopies. Surface active properties at the air/water interface were determined by surface tension measurements. Surface activity at a solid surface/water interface was demonstrated by atomic force microscopy, showing epitaxially molecular alignment for surfactant polymers adsorbed on highly oriented pyrolytic graphite. The surfactant polymers described in this report can be adapted for simple non-covalent surface modification of biomaterials and hydrophobic surfaces to provide highly hydrated interfaces.

Chimeric Antigen Receptor-Engineered T Cells for Immunotherapy of Cancer

PubMed Central

Cartellieri, Marc; Bachmann, Michael; Feldmann, Anja; Bippes, Claudia; Stamova, Slava; Wehner, Rebekka; Temme, Achim; Schmitz, Marc

2010-01-01

CD4+ and CD8+ T lymphocytes are powerful components of adaptive immunity, which essentially contribute to the elimination of tumors. Due to their cytotoxic capacity, T cells emerged as attractive candidates for specific immunotherapy of cancer. A promising approach is the genetic modification of T cells with chimeric antigen receptors (CARs). First generation CARs consist of a binding moiety specifically recognizing a tumor cell surface antigen and a lymphocyte activating signaling chain. The CAR-mediated recognition induces cytokine production and tumor-directed cytotoxicity of T cells. Second and third generation CARs include signal sequences from various costimulatory molecules resulting in enhanced T-cell persistence and sustained antitumor reaction. Clinical trials revealed that the adoptive transfer of T cells engineered with first generation CARs represents a feasible concept for the induction of clinical responses in some tumor patients. However, further improvement is required, which may be achieved by second or third generation CAR-engrafted T cells. PMID:20467460

The role of intra-domain disulfide bonds in heat-induced irreversible denaturation of camelid single domain VHH antibodies

PubMed Central

Akazawa-Ogawa, Yoko; Uegaki, Koichi; Hagihara, Yoshihisa

2016-01-01

Camelid-derived single domain VHH antibodies are highly heat resistant, and the mechanism of heat-induced VHH denaturation predominantly relies on the chemical modification of amino acids. Although chemical modification of disulfide bonds has been recognized as a cause for heat-induced denaturation of many proteins, there have been no mutagenesis studies, in which the number of disulfide bonds was controlled. In this article, we examined a series of mutants of two different VHHs with single, double or no disulfide bonds, and scrutinized the effects of these disulfide bond modifications on VHH denaturation. With the exception of one mutant, the heat resistance of VHHs decreased when the number of disulfide bonds increased. The effect of disulfide bonds on heat denaturation was more striking if the VHH had a second disulfide bond, suggesting that the contribution of disulfide shuffling is significant in proteins with multiple disulfide bonds. Furthermore, our results directly indicate that removal of a disulfide bond can indeed increase the heat resistance of a protein, irrespective of the negative impact on equilibrium thermodynamic stability. PMID:26289739

Mudskippers and Their Genetic Adaptations to an Amphibious Lifestyle.

PubMed

You, Xinxin; Sun, Min; Li, Jia; Bian, Chao; Chen, Jieming; Yi, Yunhai; Yu, Hui; Shi, Qiong

2018-02-07

Mudskippers are the largest group of amphibious teleost fish that are uniquely adapted to live on mudflats. During their successful transition from aqueous life to terrestrial living, these fish have evolved morphological and physiological modifications of aerial vision and olfaction, higher ammonia tolerance, aerial respiration, improved immunological defense against terrestrial pathogens, and terrestrial locomotion using protruded pectoral fins. Comparative genomic and transcriptomic data have been accumulated and analyzed for understanding molecular mechanisms of the terrestrial adaptations. Our current review provides a general introduction to mudskippers and recent research advances of their genetic adaptations to the amphibious lifestyle, which will be helpful for understanding the evolutionary transition of vertebrates from water to land. Our insights into the genomes and transcriptomes will also support molecular breeding, functional identification, and natural compound screening.

Parallel implementation of an adaptive scheme for 3D unstructured grids on the SP2

NASA Technical Reports Server (NTRS)

Strawn, Roger C.; Oliker, Leonid; Biswas, Rupak

1996-01-01

Dynamic mesh adaption on unstructured grids is a powerful tool for computing unsteady flows that require local grid modifications to efficiently resolve solution features. For this work, we consider an edge-based adaption scheme that has shown good single-processor performance on the C90. We report on our experience parallelizing this code for the SP2. Results show a 47.0X speedup on 64 processors when 10 percent of the mesh is randomly refined. Performance deteriorates to 7.7X when the same number of edges are refined in a highly-localized region. This is because almost all the mesh adaption is confined to a single processor. However, this problem can be remedied by repartitioning the mesh immediately after targeting edges for refinement but before the actual adaption takes place. With this change, the speedup improves dramatically to 43.6X.

Parallel Implementation of an Adaptive Scheme for 3D Unstructured Grids on the SP2

NASA Technical Reports Server (NTRS)

Oliker, Leonid; Biswas, Rupak; Strawn, Roger C.

1996-01-01

Dynamic mesh adaption on unstructured grids is a powerful tool for computing unsteady flows that require local grid modifications to efficiently resolve solution features. For this work, we consider an edge-based adaption scheme that has shown good single-processor performance on the C90. We report on our experience parallelizing this code for the SP2. Results show a 47.OX speedup on 64 processors when 10% of the mesh is randomly refined. Performance deteriorates to 7.7X when the same number of edges are refined in a highly-localized region. This is because almost all mesh adaption is confined to a single processor. However, this problem can be remedied by repartitioning the mesh immediately after targeting edges for refinement but before the actual adaption takes place. With this change, the speedup improves dramatically to 43.6X.

Mechanisms of β-cell functional adaptation to changes in workload

PubMed Central

Wortham, Matthew; Sander, Maike

2016-01-01

Insulin secretion must be tightly coupled to nutritional state to maintain blood glucose homeostasis. To this end, pancreatic β-cells sense and respond to changes in metabolic conditions, thereby anticipating insulin demands for a given physiological context. This is achieved in part through adjustments of nutrient metabolism, which is controlled at several levels including allosteric regulation, posttranslational modifications, and altered expression of metabolic enzymes. In this review, we discuss mechanisms of β-cell metabolic and functional adaptation in the context of two physiological states that alter glucose-stimulated insulin secretion: fasting and insulin resistance. We review current knowledge of metabolic changes that occur in the β-cell during adaptation and specifically discuss transcriptional mechanisms that underlie β-cell adaptation. A more comprehensive understanding of how β-cells adapt to changes in nutrient state could identify mechanisms to be co-opted for therapeutically modulating insulin secretion in metabolic disease. PMID:27615135

Attractive manifold-based adaptive solar attitude control of satellites in elliptic orbits

NASA Astrophysics Data System (ADS)

Lee, Keum W.; Singh, Sahjendra N.

2011-01-01

The paper presents a novel noncertainty-equivalent adaptive (NCEA) control system for the pitch attitude control of satellites in elliptic orbits using solar radiation pressure (SRP). The satellite is equipped with two identical solar flaps to produce control moments. The adaptive law is based on the attractive manifold design using filtered signals for synthesis, which is a modification of the immersion and invariance (I&I) method. The control system has a modular controller-estimator structure and has separate tunable gains. A special feature of this NCEA law is that the trajectories of the satellite converge to a manifold in an extended state space, and the adaptive law recovers the performance of a deterministic controller. This recovery of performance cannot be obtained with certainty-equivalent adaptive (CEA) laws. Simulation results are presented which show that the NCEA law accomplishes precise attitude control of the satellite in an elliptic orbit, despite large parameter uncertainties.

An adaptive two-stage sequential design for sampling rare and clustered populations

USGS Publications Warehouse

Brown, J.A.; Salehi, M.M.; Moradi, M.; Bell, G.; Smith, D.R.

2008-01-01

How to design an efficient large-area survey continues to be an interesting question for ecologists. In sampling large areas, as is common in environmental studies, adaptive sampling can be efficient because it ensures survey effort is targeted to subareas of high interest. In two-stage sampling, higher density primary sample units are usually of more interest than lower density primary units when populations are rare and clustered. Two-stage sequential sampling has been suggested as a method for allocating second stage sample effort among primary units. Here, we suggest a modification: adaptive two-stage sequential sampling. In this method, the adaptive part of the allocation process means the design is more flexible in how much extra effort can be directed to higher-abundance primary units. We discuss how best to design an adaptive two-stage sequential sample. ?? 2008 The Society of Population Ecology and Springer.

Environmental Impact on DNA Methylation in the Germline: State of the Art and Gaps of Knowledge

PubMed Central

Pacchierotti, Francesca; Spanò, Marcello

2015-01-01

The epigenome consists of chemical changes in DNA and chromatin that without modifying the DNA sequence modulate gene expression and cellular phenotype. The epigenome is highly plastic and reacts to changing external conditions with modifications that can be inherited to daughter cells and across generations. Whereas this innate plasticity allows for adaptation to a changing environment, it also implies the potential of epigenetic derailment leading to so-called epimutations. DNA methylation is the most studied epigenetic mark. DNA methylation changes have been associated with cancer, infertility, cardiovascular, respiratory, metabolic, immunologic, and neurodegenerative pathologies. Experiments in rodents demonstrate that exposure to a variety of chemical stressors, occurring during the prenatal or the adult life, may induce DNA methylation changes in germ cells, which may be transmitted across generations with phenotypic consequences. An increasing number of human biomonitoring studies show environmentally related DNA methylation changes mainly in blood leukocytes, whereas very few data have been so far collected on possible epigenetic changes induced in the germline, even by the analysis of easily accessible sperm. In this paper, we review the state of the art on factors impinging on DNA methylation in the germline, highlight gaps of knowledge, and propose priorities for future studies. PMID:26339587

Boron Tolerance in Aspergillus nidulans Is Sustained by the SltA Pathway Through the SLC-Family Transporters SbtA and SbtB

PubMed Central

Villarino, María; Mendizabal, Gorka; Garzia, Aitor; Ugalde, Unai

2017-01-01

Microbial cells interact with the environment by adapting to external changes. Signal transduction pathways participate in both sensing and responding in the form of modification of gene expression patterns, enabling cell survival. The filamentous fungal-specific SltA pathway regulates tolerance to alkalinity, elevated cation concentrations and, as shown in this work, also stress conditions induced by borates. Growth of sltA− mutants is inhibited by increasing millimolar concentrations of boric acid or borax (sodium tetraborate). In an attempt to identify genes required for boron-stress response, we determined the boric acid or borax-dependent expression of sbtA and sbtB, orthologs of Saccharomyces cerevisiae bor1, and a reduction in their transcript levels in a ΔsltA mutant. Deletion of sbtA, but mainly that of sbtB, decreased the tolerance to boric acid or borax. In contrast, null mutants of genes coding for additional transporters of the Solute Carrier (SLC) family, sB, sbtD or sbtE, showed an unaltered growth pattern under the same stress conditions. Taken together, our results suggest that the SltA pathway induces, through SbtA and SbtB, the export of toxic concentrations of borates, which have largely recognized antimicrobial properties. PMID:28753996

Early T Cell Signalling Is Reversibly Altered in PD-1+ T Lymphocytes Infiltrating Human Tumors

PubMed Central

Wang, Shu-Fang; Fouquet, Stéphane; Chapon, Maxime; Salmon, Hélène; Regnier, Fabienne; Labroquère, Karine; Badoual, Cécile; Damotte, Diane; Validire, Pierre; Maubec, Eve; Delongchamps, Nicolas B.; Cazes, Aurélie; Gibault, Laure; Garcette, Marylène; Dieu-Nosjean, Marie-Caroline; Zerbib, Marc; Avril, Marie-Françoise; Prévost-Blondel, Armelle; Randriamampita, Clotilde; Trautmann, Alain; Bercovici, Nadège

2011-01-01

To improve cancer immunotherapy, a better understanding of the weak efficiency of tumor-infiltrating T lymphocytes (TIL) is necessary. We have analyzed the functional state of human TIL immediately after resection of three types of tumors (NSCLC, melanoma and RCC). Several signalling pathways (calcium, phosphorylation of ERK and Akt) and cytokine secretion are affected to different extents in TIL, and show a partial spontaneous recovery within a few hours in culture. The global result is an anergy that is quite distinct from clonal anergy induced in vitro, and closer to adaptive tolerance in mice. PD-1 (programmed death -1) is systematically expressed by TIL and may contribute to their anergy by its mere expression, and not only when it interacts with its ligands PD-L1 or PD-L2, which are not expressed by every tumor. Indeed, the TCR-induced calcium and ERK responses were reduced in peripheral blood T cells transfected with PD-1. Inhibition by sodium stibogluconate of the SHP-1 and SHP-2 phosphatases that associate with several inhibitory receptors including PD-1, relieves part of the anergy apparent in TIL or in PD-1-transfected T cells. This work highlights some of the molecular modifications contributing to functional defects of human TIL. PMID:21408177

Attractor Structures of Signaling Networks: Consequences of Different Conformational Barcode Dynamics and Their Relations to Network-Based Drug Design.

PubMed

Szalay, Kristóf Z; Nussinov, Ruth; Csermely, Peter

2014-06-01

Conformational barcodes tag functional sites of proteins and are decoded by interacting molecules transmitting the incoming signal. Conformational barcodes are modified by all co-occurring allosteric events induced by post-translational modifications, pathogen, drug binding, etc. We argue that fuzziness (plasticity) of conformational barcodes may be increased by disordered protein structures, by integrative plasticity of multi-phosphorylation events, by increased intracellular water content (decreased molecular crowding) and by increased action of molecular chaperones. This leads to increased plasticity of signaling and cellular networks. Increased plasticity is both substantiated by and inducing an increased noise level. Using the versatile network dynamics tool, Turbine (www.turbine.linkgroup.hu), here we show that the 10 % noise level expected in cellular systems shifts a cancer-related signaling network of human cells from its proliferative attractors to its largest, apoptotic attractor representing their health-preserving response in the carcinogen containing and tumor suppressor deficient environment modeled in our study. Thus, fuzzy conformational barcodes may not only make the cellular system more plastic, and therefore more adaptable, but may also stabilize the complex system allowing better access to its largest attractor. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conversion of cis unsaturated fatty acids to trans, a possible mechanism for the protection of phenol-degrading Pseudomonas putida P8 from substrate toxicity.

PubMed Central

Heipieper, H J; Diefenbach, R; Keweloh, H

1992-01-01

A trans unsaturated fatty acid was found as a major constituent in the lipids of Pseudomonas putida P8. The fatty acid was identified as 9-trans-hexadecenoic acid by gas chromatography, argentation thin-layer chromatography, and infrared absorption spectrometry. Growing cells of P. putida P8 reacted to the presence of sublethal concentrations of phenol in the medium with changes in the fatty acid composition of the lipids, thereby increasing the degree of saturation. At phenol concentrations which completely inhibited the growth of P. putida, the cells were still able to increase the content of the trans unsaturated fatty acid and simultaneously to decrease the proportion of the corresponding 9-cis-hexadecenoic acid. This conversion of fatty acids was also induced by 4-chlorophenol in nongrowing cells in which the de novo synthesis of lipids had stopped, as shown by incorporation experiments with labeled acetate. The isomerization of the double bond in the presence of chloramphenicol indicates a constitutively operating enzyme system. The cis-to-trans modification of the fatty acids studied here apparently is a new way of adapting the membrane fluidity to the presence of phenols, thereby compensating for the elevation of membrane permeability induced by these toxic substances. PMID:1622260

H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition

PubMed Central

Nancy, Patrice; Siewiera, Johan; Tagliani, Elisa; Osokine, Ivan; Manandhar, Priyanka; Clementi, Caterina

2017-01-01

Uncovering the causes of pregnancy complications such as preterm labor requires greater insight into how the uterus remains in a noncontractile state until term and then surmounts this state to enter labor. Here, we show that dynamic generation and erasure of the repressive histone modification tri-methyl histone H3 lysine 27 (H3K27me3) in decidual stromal cells dictate both elements of pregnancy success in mice. In early gestation, H3K27me3-induced transcriptional silencing of select gene targets ensured uterine quiescence by preventing the decidua from expressing parturition-inducing hormone receptors, manifesting type 1 immunity, and most unexpectedly, generating myofibroblasts and associated wound-healing responses. In late gestation, genome-wide H3K27 demethylation allowed for target gene upregulation, decidual activation, and labor entry. Pharmacological inhibition of H3K27 demethylation in late gestation not only prevented term parturition, but also inhibited delivery while maintaining pup viability in a noninflammatory model of preterm parturition. Immunofluorescence analysis of human specimens suggested that similar regulatory events might occur in the human decidua. Together, these results reveal the centrality of regulated gene silencing in the uterine adaptation to pregnancy and suggest new areas in the study and treatment of pregnancy disorders. PMID:29202469

Neuronal adaptation to simulated and optically-induced astigmatic defocus.

PubMed

Ohlendorf, Arne; Tabernero, Juan; Schaeffel, Frank

2011-03-25

It is well established that spatial adaptation can improve visual acuity over time in the presence of spherical defocus. It is less well known how far adaptation to astigmatic defocus can enhance visual acuity. We adapted subjects to "simulated" and optically-induced "real" astigmatic defocus, and studied how much they adapt and how selective adaptation was for the axis of astigmatism. Ten subjects with a mean age of 26.7±2.4years (range 23-30) were enrolled in the study, three of them myopic (average spherical equivalent (SE)±SD: -3.08±1.42D) and seven emmetropic (average SE±SD: -0.11±0.18D). All had a corrected minimum visual acuity (VA) of logVA 0.0. For adaptation, subjects watched a movie at 4m distance for 10min that was convolved frame-by-frame with an astigmatic point spread function, equivalent to +3D defocus, or they watched an unfiltered movie but with spectacle frames with a 0/+3D astigmatic trial lenses. Subsequently, visual acuity was determined at the same distance, using high contrast letter acuity charts. Four experiments were performed. In experiment (1), simulated astigmatic defocus was presented both for adaptation and testing, in experiment (2) optically-induced astigmatic defocus was presented both for adaptation and testing of visual acuity. In all these cases, the +3D power meridian was at 0°. In experiments (3) and (4), the +3D power meridian was at 0° during adaptation but rotated to 90° during testing. Astigmatic defocus was simulated in experiment (3) but optically-induced in experiment (4). Experiments 1 and 2: adaptation to either simulated or real astigmatic defocus increased visual acuity in both test paradigms, simulated (change in VA 0.086±0.069 log units; p<0.01) and lens-induced astigmatic defocus (change in VA 0.068±0.031 log units; p<0.001). Experiments 3 and 4: when the axis was rotated, the improvement in visual acuity failed to reach significance, both for simulated (change in VA 0.042±0.079 log units; p=0.13) and lens-induced astigmatic defocus (change in VA 0.038±0.086 log units; p=0.19). Adaptation to astigmatic defocus occurs for both simulated and real defocus, and the effects of adaptation seem to be selective for the axis of astigmatism. These observations suggest that adaptation involves a re-adjustment of the spatial filters selectively for astigmatic meridians, although the underlying mechanism must be more complicated than just changes in shapes of the receptive fields of retinal or cortical neurons. Copyright © 2011 Elsevier Ltd. All rights reserved.

Direct Adaptive Rejection of Vortex-Induced Disturbances for a Powered SPAR Platform

NASA Technical Reports Server (NTRS)

VanZwieten, Tannen S.; Balas, Mark J.; VanZwieten, James H.; Driscoll, Frederick R.

2009-01-01

The Rapidly Deployable Stable Platform (RDSP) is a novel vessel designed to be a reconfigurable, stable at-sea platform. It consists of a detachable catamaran and spar, performing missions with the spar extending vertically below the catamaran and hoisting it completely out of the water. Multiple thrusters located along the spar allow it to be actively controlled in this configuration. A controller is presented in this work that uses an adaptive feedback algorithm in conjunction with Direct Adaptive Disturbance Rejection (DADR) to mitigate persistent, vortex-induced disturbances. Given the frequency of a disturbance, the nominal DADR scheme adaptively compensates for its unknown amplitude and phase. This algorithm is extended to adapt to a disturbance frequency that is only coarsely known by including a Phase Locked Loop (PLL). The PLL improves the frequency estimate on-line, allowing the modified controller to reduce vortex-induced motions by more than 95% using achievable thrust inputs.

Modification of feeding circuits in the evolution of social behavior.

PubMed

Fischer, Eva K; O'Connell, Lauren A

2017-01-01

Adaptive trade-offs between foraging and social behavior intuitively explain many aspects of individual decision-making. Given the intimate connection between social behavior and feeding/foraging at the behavioral level, we propose that social behaviors are linked to foraging on a mechanistic level, and that modifications of feeding circuits are crucial in the evolution of complex social behaviors. In this Review, we first highlight the overlap between mechanisms underlying foraging and parental care and then expand this argument to consider the manipulation of feeding-related pathways in the evolution of other complex social behaviors. We include examples from diverse taxa to highlight that the independent evolution of complex social behaviors is a variation on the theme of feeding circuit modification. © 2017. Published by The Company of Biologists Ltd.

A “Spike-Based” Grammar Underlies Directional Modification in Network Connectivity: Effect on Bursting Activity and Implications for Bio-Hybrids Systems

PubMed Central

Zullo, Letizia; Chiappalone, Michela; Martinoia, Sergio; Benfenati, Fabio

2012-01-01

Developed biological systems are endowed with the ability of interacting with the environment; they sense the external state and react to it by changing their own internal state. Many attempts have been made to build ‘hybrids’ with the ability of perceiving, modifying and reacting to external modifications. Investigation of the rules that govern network changes in a hybrid system may lead to finding effective methods for ‘programming’ the neural tissue toward a desired task. Here we show a new perspective in the use of cortical neuronal cultures from embryonic mouse as a working platform to study targeted synaptic modifications. Differently from the common timing-based methods applied in bio-hybrids robotics, here we evaluated the importance of endogenous spike timing in the information processing. We characterized the influence of a spike-patterned stimulus in determining changes in neuronal synchronization (connectivity strength and precision) of the evoked spiking and bursting activity in the network. We show that tailoring the stimulation pattern upon a neuronal spike timing induces the network to respond stronger and more precisely to the stimulation. Interestingly, the induced modifications are conveyed more consistently in the burst timing. This increase in strength and precision may be a key in the interaction of the network with the external world and may be used to induce directional changes in bio-hybrid systems. PMID:23145147

Favorable 2'-substitution in the loop region of a thrombin-binding DNA aptamer.

PubMed

Awachat, Ragini; Wagh, Atish A; Aher, Manisha; Fernandes, Moneesha; Kumar, Vaijayanti A

2018-06-01

Simple 2'-OMe-chemical modification in the loop region of the 15mer G-rich DNA sequence GGTTGGTGTGGTTGG is reported. The G-quadruplex structure of this thrombin-binding aptamer (TBA), is stabilized by single modifications (T → 2'-OMe-U), depending on the position of the modification. The structural stability also renders significantly increased inhibition of thrombin-induced fibrin polymerization, a process closely associated with blood-clotting. Copyright © 2018 Elsevier Ltd. All rights reserved.

Do pH and flavonoids influence hypochlorous acid-induced catalase inhibition and heme modification?

PubMed

Krych-Madej, Justyna; Gebicka, Lidia

2015-09-01

Hypochlorous acid (HOCl), highly reactive oxidizing and chlorinating species, is formed in the immune response to invading pathogens by the reaction of hydrogen peroxide with chloride catalyzed by the enzyme myeloperoxidase. Catalase, an important antioxidant enzyme, catalyzing decomposition of hydrogen peroxide to water and molecular oxygen, hampers in vitro HOCl formation, but is also one of the main targets for HOCl. In this work we have investigated HOCl-induced catalase inhibition at different pH, and the influence of flavonoids (catechin, epigallocatechin gallate and quercetin) on this process. It has been shown that HOCl-induced catalase inhibition is independent on pH in the range 6.0-7.4. Preincubation of catalase with epigallocatechin gallate and quercetin before HOCl treatment enhances the degree of catalase inhibition, whereas catechin does not affect this process. Our rapid kinetic measurements of absorption changes around the heme group have revealed that heme modification by HOCl is mainly due to secondary, intramolecular processes. The presence of flavonoids, which reduce active catalase intermediate, Compound I to inactive Compound II have not influenced the kinetics of HOCl-induced heme modification. Possible mechanisms of the reaction of hypochlorous acid with catalase are proposed and the biological consequences are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Electronic excitation induced modifications in elongated iron nanoparticle encapsulated multiwalled carbon nanotubes under ion irradiation

NASA Astrophysics Data System (ADS)

Saikiran, V.; Bazylewski, P.; Sameera, I.; Bhatia, Ravi; Pathak, A. P.; Prasad, V.; Chang, G. S.

2018-05-01

Multi-wall carbon nanotubes (MWCNT) filled with Fe nanorods were shown to have contracted and deformed under heavy ion irradiation. In this study, 120 MeV Ag and 80 MeV Ni ion irradiation was performed to study the deformation and defects induced in iron filled MWCNT under heavy ion irradiation. The structural modifications induced due to electronic excitation by ion irradiation were investigated employing high-resolution transmission electron microscopy, micro-Raman scattering experiments, and synchrotron-based X-ray absorption and emission spectroscopy. We understand that the ion irradiation causes modifications in the Fe nanorods which result in compressions and expansions of the nanotubes, and in turn leads to the buckling of MWCNT. The G band of the Raman spectra shifts slightly towards higher wavenumber and the shoulder G‧ band enhances with the increase of ion irradiation fluence, where the buckling wavelength depends on the radius 'r' of the nanotubes as exp[(r)0.5]. The intensity ratio of the D to G Raman modes initially decreases at the lowest fluence, and then it increases with the increase in ion fluence. The electron diffraction pattern and the high resolution images clearly show the presence of ion induced defects on the walls of the tube and encapsulated iron nanorods.

Enhancement of Oscillatory Flap Propulsors for Low Speed Flows in Water

DTIC Science & Technology

2010-07-13

in efficiency results from a reduction in the induced drag created by the lifting surface. Many of these modifications such as winglets , tip bulbs...one of the many terms that account for the total power loss. Thus, winglet -type tip modifications for the OFD are expected to lead to an

Identification of histone modifications in biomedical text for supporting epigenomic research

PubMed Central

Kolářik, Corinna; Klinger, Roman; Hofmann-Apitius, Martin

2009-01-01

Background Posttranslational modifications of histones influence the structure of chromatine and in such a way take part in the regulation of gene expression. Certain histone modification patterns, distributed over the genome, are connected to cell as well as tissue differentiation and to the adaption of organisms to their environment. Abnormal changes instead influence the development of disease states like cancer. The regulation mechanisms for modifying histones and its functionalities are the subject of epigenomics investigation and are still not completely understood. Text provides a rich resource of knowledge on epigenomics and modifications of histones in particular. It contains information about experimental studies, the conditions used, and results. To our knowledge, no approach has been published so far for identifying histone modifications in text. Results We have developed an approach for identifying histone modifications in biomedical literature with Conditional Random Fields (CRF) and for resolving the recognized histone modification term variants by term standardization. For the term identification F1 measures of 0.84 by 10-fold cross-validation on the training corpus and 0.81 on an independent test corpus have been obtained. The standardization enabled the correct transformation of 96% of the terms from training and 98% from test the corpus. Due to the lack of terminologies exhaustively covering specific histone modification types, we developed a histone modification term hierarchy for use in a semantic text retrieval system. Conclusion The developed approach highly improves the retrieval of articles describing histone modifications. Since text contains context information about performed studies and experiments, the identification of histone modifications is the basis for supporting literature-based knowledge discovery and hypothesis generation to accelerate epigenomic research. PMID:19208128

Identification of histone modifications in biomedical text for supporting epigenomic research.

PubMed

Kolárik, Corinna; Klinger, Roman; Hofmann-Apitius, Martin

2009-01-30

Posttranslational modifications of histones influence the structure of chromatine and in such a way take part in the regulation of gene expression. Certain histone modification patterns, distributed over the genome, are connected to cell as well as tissue differentiation and to the adaption of organisms to their environment. Abnormal changes instead influence the development of disease states like cancer. The regulation mechanisms for modifying histones and its functionalities are the subject of epigenomics investigation and are still not completely understood. Text provides a rich resource of knowledge on epigenomics and modifications of histones in particular. It contains information about experimental studies, the conditions used, and results. To our knowledge, no approach has been published so far for identifying histone modifications in text. We have developed an approach for identifying histone modifications in biomedical literature with Conditional Random Fields (CRF) and for resolving the recognized histone modification term variants by term standardization. For the term identification F1 measures of 0.84 by 10-fold cross-validation on the training corpus and 0.81 on an independent test corpus have been obtained. The standardization enabled the correct transformation of 96% of the terms from training and 98% from test the corpus. Due to the lack of terminologies exhaustively covering specific histone modification types, we developed a histone modification term hierarchy for use in a semantic text retrieval system. The developed approach highly improves the retrieval of articles describing histone modifications. Since text contains context information about performed studies and experiments, the identification of histone modifications is the basis for supporting literature-based knowledge discovery and hypothesis generation to accelerate epigenomic research.

Predator-induced larval cloning in the sand dollar Dendraster excentricus: might mothers matter?

PubMed

Vaughn, Dawn

2009-10-01

Predator-induced cloning in echinoid larvae, with reduced size a consequence of cloning, is a dramatic modification of development and a novel response to risks associated with prolonged planktonic development. Recent laboratory studies demonstrate that exposure to stimuli from predators (i.e., fish mucus) induces cloning in the pluteus larvae (plutei) of Dendraster excentricus. However, the timing and incidence of cloning and size reduction of unrelated conspecific plutei differed across experiments. A variable cloning response suggests the effects of such factors as cue quality, egg provisioning, maternal experience, and genetic background, indicating that the potential advantages of cloning as an adaptive response to predators are not available to all larvae. This study tested the hypothesis that cloning in D. excentricus plutei is maternally influenced. Plutei from three half-sibling larval families (different mothers, same father) were exposed to fish mucus for 9 days during early development. Cloning was inferred in a percentage of plutei from each family; however, the rate and success of cloning differed significantly among the larval half-siblings. Unexpectedly, all mucus-treated plutei were smaller and developmentally delayed when compared to all plutei reared in the absence of a mucus stimulus. Thus, while the results from this study support the hypothesis of an influence of mothers on cloning of larval offspring, reduced larval size was a uniform response to fish mucus and did not indicate an effect of mothers. Hypotheses of the developmental effects of fish mucus on larval size with or without successful cloning are discussed.

Influence of physical exercise on traumatic brain injury deficits: scaffolding effect.

PubMed

Archer, Trevor

2012-05-01

Traumatic brain injury (TBI) may be due to a bump, blow, or jolt to the head or a penetrating head injury that disrupts normal brain function; it presents an ever-growing, serious public health problem that causes a considerable number of fatalities and cases of permanent disability annually. Physical exercise restores the healthy homeostatic regulation of stress, affect and the regulation of hypothalamic-pituitary-adrenal axis. Physical activity attenuates or reverses the performance deficits observed in neurocognitive tasks. It induces anti-apoptotic effects and buttresses blood-brain barrier intactness. Exercise offers a unique non-pharmacologic, non-invasive intervention that incorporates different regimes, whether dynamic or static, endurance, or resistance. Exercise intervention protects against vascular risk factors that include hypertension, diabetes, cellular inflammation, and aortic rigidity. It induces direct changes in cerebrovasculature that produce beneficial changes in cerebral blood flow, angiogenesis and vascular disease improvement. The improvements induced by physical exercise regimes in brain plasticity and neurocognitive performance are evident both in healthy individuals and in those afflicted by TBI. The overlap and inter-relations between TBI effects on brain and cognition as related to physical exercise and cognition may provide lasting therapeutic benefits for recovery from TBI. It seems likely that some modification of the notion of scaffolding would postulate that physical exercise reinforces the adaptive processes of the brain that has undergone TBI thereby facilitating the development of existing networks, albeit possibly less efficient, that compensate for those lost through damage. © Springer Science+Business Media, LLC 2011

The repetition timing of high frequency afferent stimulation drives the bidirectional plasticity at central synapses in the rat medial vestibular nuclei.

PubMed

Scarduzio, M; Panichi, R; Pettorossi, V E; Grassi, S

2012-10-25

In this study we show that high frequency stimulation (HFS, 100Hz) of afferent fibers to the medial vestibular nucleus (MVN) can induce opposite long-term modifications of synaptic responses in the type B neurons depending upon the stimulation pattern. Long burst stimulation (LBS: 2s) and short burst stimulation (SBS: 0.55s) were applied with different burst number (BN) and inter-burst intervals (IBI). It results that both LBS and SBS can induce either N-methyl-d aspartate receptors (NMDARs)-mediated long-term potentiation (LTP) or long-term depression (LTD), depending on temporal organization of repetitive bursts. In particular, the IBI plays a relevant role in guiding the shift from LTP to LTD since by using both LBS and SBS LTP is induced by shorter IBI than LTD. By contrast, the sign of long-term effect does not depend on the mean impulse frequency evaluated within the entire stimulation period. Therefore, the patterns of repetitive vestibular activation with different ratios between periods of increased activity and periods of basal activity may lead to LTP or LTD probably causing different levels of postsynaptic Ca(2+). On the whole, this study demonstrates that glutamatergic vestibular synapse in the MVN can undergo NMDAR-dependent bidirectional plasticity and puts forward a new aspect for understanding the adaptive and compensatory plasticity of the oculomotor responses. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Does a single gait training session performed either overground or on a treadmill induce specific short-term effects on gait parameters in patients with hemiparesis? A randomized controlled study.

PubMed

Bonnyaud, Céline; Pradon, Didier; Zory, Raphael; Bensmail, Djamel; Vuillerme, Nicolas; Roche, Nicolas

2013-01-01

Gait training for patients with hemiparesis is carried out independently overground or on a treadmill. Several studies have shown differences in hemiparetic gait parameters during overground versus treadmill walking. However, few studies have compared the effects of these 2 gait training conditions on gait parameters, and no study has compared the short-term effects of these techniques on all biomechanical gait parameters. To determine whether a gait training session performed overground or on a treadmill induces specific short-term effects on biomechanical gait parameters in patients with hemiparesis. Twenty-six subjects with hemiparesis were randomly assigned to a single session of either overground or treadmill gait training. The short-term effects on spatiotemporal, kinematic, and kinetic gait parameters were assessed using gait analysis before and immediately after the training and after a 20-minute rest. Speed, cadence, percentage of single support phase, peak knee extension, peak propulsion, and braking on the paretic side were significantly increased after the gait training session. However, there were no specific changes dependent on the type of gait training performed (overground or on a treadmill). A gait training session performed by subjects with hemiparesis overground or on a treadmill did not induce specific short-term effects on biomechanical gait parameters. The increase in gait velocity that followed a gait training session seemed to reflect specific modifications of the paretic lower limb and adaptation of the nonparetic lower limb.

Supramolecular engineering through temperature-induced chemical modification of 2H-tetraphenylporphyrin on Ag(111): flat phenyl conformation and possible dehydrogenation reactions.

PubMed

Di Santo, Giovanni; Blankenburg, Stephan; Castellarin-Cudia, Carla; Fanetti, Mattia; Borghetti, Patrizia; Sangaletti, Luigi; Floreano, Luca; Verdini, Alberto; Magnano, Elena; Bondino, Federica; Pignedoli, Carlo A; Nguyen, Manh-Thuong; Gaspari, Roberto; Passerone, Daniele; Goldoni, Andrea

2011-12-16

Scratching the surface: Formation of a monolayer of 2H-tetraphenylporphyrins (2H-TPP) on Ag(111), either by sublimation of a multilayer in the range 525-600 K or by annealing (at the same temperature) a monolayer deposited at room temperature, induces a chemical modification of the molecules. Rotation of the phenyl rings into a flat conformation is observed and tentatively explained, by using DFT calculations, as a peculiar reaction due to molecular dehydrogenation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of novel synthetic TLR7/8 agonists as vaccine adjuvants.

PubMed

Smith, Alyson J; Li, Yufeng; Bazin, Hélène G; St-Jean, Julien R; Larocque, Daniel; Evans, Jay T; Baldridge, Jory R

2016-08-05

Small-molecule adjuvants that boost and direct adaptive immunity provide a powerful means to increase the effectiveness of vaccines. Through rational design several novel imidazoquinoline and oxoadenine TLR7/8 agonists, each with unique molecular modifications, were synthesized and assessed for their ability to augment adaptive immunity. All agonists bound human TLR7 and TLR8 and induced maturation of both human mDCs and pDCs. All agonists prompted production of type I interferon and/or proinflammatory cytokines, albeit with varying potencies. In most in vitro assays, the oxoadenine class of agonists proved more potent than the imidazoquinolines. Therefore, an optimized oxoadenine TLR7/8 agonist that demonstrated maximal activity in the in vitro assays was further assessed in a vaccine study with the CRM197 antigen in a porcine model. Antigen-specific antibody production was greatly enhanced in a dose dependent manner, with antibody titers increased 800-fold compared to titers from pigs vaccinated with the non-adjuvanted vaccine. Moreover, pigs vaccinated with antigen containing the highest dose of adjuvant promoted a 13-fold increase in the percentage of antigen-specific CD3(+)/CD8(+) T cells over pigs vaccinated with antigen alone. Together this work demonstrates the promise of these novel TLR7/8 agonists as effective human vaccine adjuvants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Robust adaptive control modeling of human arm movements subject to altered gravity and mechanical loads

NASA Astrophysics Data System (ADS)

Tryfonidis, Michail

It has been observed that during orbital spaceflight the absence of gravitation related sensory inputs causes incongruence between the expected and the actual sensory feedback resulting from voluntary movements. This incongruence results in a reinterpretation or neglect of gravity-induced sensory input signals. Over time, new internal models develop, gradually compensating for the loss of spatial reference. The study of adaptation of goal-directed movements is the main focus of this thesis. The hypothesis is that during the adaptive learning process the neural connections behave in ways that can be described by an adaptive control method. The investigation presented in this thesis includes two different sets of experiments. A series of dart throwing experiments took place onboard the space station Mir. Experiments also took place at the Biomechanics lab at MIT, where the subjects performed a series of continuous trajectory tracking movements while a planar robotic manipulandum exerted external torques on the subjects' moving arms. The experimental hypothesis for both experiments is that during the first few trials the subjects will perform poorly trying to follow a prescribed trajectory, or trying to hit a target. A theoretical framework is developed that is a modification of the sliding control method used in robotics. The new control framework is an attempt to explain the adaptive behavior of the subjects. Numerical simulations of the proposed framework are compared with experimental results and predictions from competitive models. The proposed control methodology extends the results of the sliding mode theory to human motor control. The resulting adaptive control model of the motor system is robust to external dynamics, even those of negative gain, uses only position and velocity feedback, and achieves bounded steady-state error without explicit knowledge of the system's nonlinearities. In addition, the experimental and modeling results demonstrate that visuomotor learning is important not only for error correction through internal model adaptation on ground or in microgravity, but also for the minimization of the total mean-square error in the presence of random variability. Thus human intelligent decision displays certain attributes that seem to conform to Bayesian statistical games. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)

Assessment and Evaluation in Adapted Physical Education.

ERIC Educational Resources Information Center

Kennedy, Charlotte I.; Bundschuh, Ernie

Intended for physical education teachers, the booklet describes informal and formal methods for evaluating handicapped children to determine whether they can participate in a regular physical education program with nonhandicapped students, in a regular physical education program with modification, or in a specially designed physical education…

Volleyball: Special Olympics Sports Skills Instructional Program.

ERIC Educational Resources Information Center

Special Olympics, Inc., Washington, DC.

One of seven booklets on Special Olympics Sports Skills Instructional Programs, this guide presents an instructional program for volleyball coaches working with mentally retarded persons. The instructional program presents information on the following topics: long term goals; short term objectives; modifications and adaptations of equipment, sport…

Adaptation to vestibular disorientation. X, Modification of vestibular nystagmus and "vertigo" by means of visual stimulation.

DOT National Transportation Integrated Search

1968-10-01

A conflict among sensory signals frequently underlies problems of disorientation, vertigo, and motion sickness. In this study, visual information in conflict with vestibular signals was presented to groups of subjects by illuminating the test room fo...

A Review & Critique of Trainee-Oriented Training Programs.

ERIC Educational Resources Information Center

Klein-Konz, Ann; Todd-Mancillas, William R.

This paper reviews literature on trainee-oriented training programs, which assign to individual employees predominant responsibility for diagnosing organizational problems requiring changes in employees' behaviors. A Self-Change, Adaption, and Modification (SCAM) Model is developed. The literature support for the model is written in similar…

Micro-masonry for 3D additive micromanufacturing.

PubMed

Keum, Hohyun; Kim, Seok

2014-08-01

Transfer printing is a method to transfer solid micro/nanoscale materials (herein called 'inks') from a substrate where they are generated to a different substrate by utilizing elastomeric stamps. Transfer printing enables the integration of heterogeneous materials to fabricate unexampled structures or functional systems that are found in recent advanced devices such as flexible and stretchable solar cells and LED arrays. While transfer printing exhibits unique features in material assembly capability, the use of adhesive layers or the surface modification such as deposition of self-assembled monolayer (SAM) on substrates for enhancing printing processes hinders its wide adaptation in microassembly of microelectromechanical system (MEMS) structures and devices. To overcome this shortcoming, we developed an advanced mode of transfer printing which deterministically assembles individual microscale objects solely through controlling surface contact area without any surface alteration. The absence of an adhesive layer or other modification and the subsequent material bonding processes ensure not only mechanical bonding, but also thermal and electrical connection between assembled materials, which further opens various applications in adaptation in building unusual MEMS devices.

Plasma-induced polymerization for enhancing paper hydrophobicity.

PubMed

Song, Zhaoping; Tang, Jiebin; Li, Junrong; Xiao, Huining

2013-01-30

Hydrophobic modification of cellulose fibers was conducted via plasma-induced polymerization in an attempt to graft the hydrophobic polymer chains on paper surface, this increasing the hydrophobicity of paper. Two hydrophobic monomers, butyl acrylate (BA) and 2-ethylhexyl acrylate (2-EHA), were grafted on cellulose fibers, induced by atmospheric cold plasma. Various influencing factors associated with the plasma-induced grafting were investigated. Contact-angle measurement, Fourier Transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM) were used to ascertain the occurrence of the grafting and characterized the changes of the cellulose fiber after modification. The results showed that the hydrophobicity of the modified paper sheet was improved significantly after the plasma-induced grafting. The water contact angle on the paper surface reached up to 130°. The morphological differences between modified and unmodified samples were also revealed by SEM observation. The resulting paper is promising as a green-based packaging material. Copyright © 2012 Elsevier Ltd. All rights reserved.

Characterization of thiol-based redox modifications of Brassica napusSNF1-related protein kinase 2.6-2C.

PubMed

Ma, Tianyi; Yoo, Mi-Jeong; Zhang, Tong; Liu, Lihong; Koh, Jin; Song, Wen-Yuan; Harmon, Alice C; Sha, Wei; Chen, Sixue

2018-04-01

Sucrose nonfermenting 1-related protein kinase 2.6 (SnRK2.6), also known as Open Stomata 1 (OST1) in Arabidopsis thaliana , plays a pivotal role in abscisic acid (ABA)-mediated stomatal closure. Four SnRK2.6 paralogs were identified in the Brassica napus genome in our previous work. Here we studied one of the paralogs, BnSnRK2.6-2C , which was transcriptionally induced by ABA in guard cells. Recombinant BnSnRK2.6-2C exhibited autophosphorylation activity and its phosphorylation sites were mapped. The autophosphorylation activity was inhibited by S-nitrosoglutathione (GSNO) and by oxidized glutathione (GSSG), and the inhibition was reversed by reductants. Using monobromobimane (mBBr) labeling, we demonstrated a dose-dependent modification of BnSnRK2.6-2C by GSNO. Furthermore, mass spectrometry analysis revealed previously uncharacterized thiol-based modifications including glutathionylation and sulfonic acid formation. Of the six cysteine residues in BnSnRK2.6-2C, C159 was found to have different types of thiol modifications, suggesting its high redox sensitivity and versatility. In addition, mBBr labeling on tyrosine residues was identified. Collectively, these data provide detailed biochemical characterization of redox-induced modifications and changes of the BnSnRK2.6-2C activity.

Small RNA Library Preparation Method for Next-Generation Sequencing Using Chemical Modifications to Prevent Adapter Dimer Formation.

PubMed

Shore, Sabrina; Henderson, Jordana M; Lebedev, Alexandre; Salcedo, Michelle P; Zon, Gerald; McCaffrey, Anton P; Paul, Natasha; Hogrefe, Richard I

2016-01-01

For most sample types, the automation of RNA and DNA sample preparation workflows enables high throughput next-generation sequencing (NGS) library preparation. Greater adoption of small RNA (sRNA) sequencing has been hindered by high sample input requirements and inherent ligation side products formed during library preparation. These side products, known as adapter dimer, are very similar in size to the tagged library. Most sRNA library preparation strategies thus employ a gel purification step to isolate tagged library from adapter dimer contaminants. At very low sample inputs, adapter dimer side products dominate the reaction and limit the sensitivity of this technique. Here we address the need for improved specificity of sRNA library preparation workflows with a novel library preparation approach that uses modified adapters to suppress adapter dimer formation. This workflow allows for lower sample inputs and elimination of the gel purification step, which in turn allows for an automatable sRNA library preparation protocol.

Grid adaption based on modified anisotropic diffusion equations formulated in the parametic domain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hagmeijer, R.

1994-11-01

A new grid-adaption algorithm for problems in computational fluid dynamics is presented. The basic equations are derived from a variational problem formulated in the parametric domain of the mapping that defines the existing grid. Modification of the basic equations provides desirable properties in boundary layers. The resulting modified anisotropic diffusion equations are solved for the computational coordinates as functions of the parametric coordinates and these functions are numerically inverted. Numerical examples show that the algorithm is robust, that shocks and boundary layers are well-resolved on the adapted grid, and that the flow solution becomes a globally smooth function of themore » computational coordinates.« less

Electron-beam irradiation induced transformation of Cu2(OH)3NO3 nanoflakes into nanocrystalline CuO

NASA Astrophysics Data System (ADS)

Padhi, S. K.; Gottapu, S. N.; Krishna, M. Ghanashyam

2016-05-01

The transmission electron microscope electron-beam (TEM e-beam) as a material modification tool has been demonstrated. The material modification is realised in the high-resolution TEM mode (largest condenser aperture, 150 μm, and 200 nm spot size) at a 200 keV beam energy. The Cu2(OH)3NO3 (CHN) nanoflakes used in this study were microwave solution processed that were layered single crystals and radiation sensitive. The single domain CHN flakes disintegrate into a large number of individual CuO crystallites within a 90 s span of time. The sequential bright-field, dark-field, and selected area electron diffraction modes were employed to record the evolved morphology, microstructural changes, and structural transformation that validate CHN modification. High-resolution transmission electron microscopy imaging of e-beam irradiated regions unambiguously supports the growth of CuO nanoparticles (11.8(3.2) nm in diameter). This study demonstrates e-beam irradiation induced CHN depletion, subsequent nucleation and growth of nanocrystalline CuO regions well embedded in the parent burnt porous matrix which can be useful for miniaturized sensing applications. NaBH4 induced room temperature reduction of CHN to elemental Cu and its printability on paper was also demonstrated.The transmission electron microscope electron-beam (TEM e-beam) as a material modification tool has been demonstrated. The material modification is realised in the high-resolution TEM mode (largest condenser aperture, 150 μm, and 200 nm spot size) at a 200 keV beam energy. The Cu2(OH)3NO3 (CHN) nanoflakes used in this study were microwave solution processed that were layered single crystals and radiation sensitive. The single domain CHN flakes disintegrate into a large number of individual CuO crystallites within a 90 s span of time. The sequential bright-field, dark-field, and selected area electron diffraction modes were employed to record the evolved morphology, microstructural changes, and structural transformation that validate CHN modification. High-resolution transmission electron microscopy imaging of e-beam irradiated regions unambiguously supports the growth of CuO nanoparticles (11.8(3.2) nm in diameter). This study demonstrates e-beam irradiation induced CHN depletion, subsequent nucleation and growth of nanocrystalline CuO regions well embedded in the parent burnt porous matrix which can be useful for miniaturized sensing applications. NaBH4 induced room temperature reduction of CHN to elemental Cu and its printability on paper was also demonstrated. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02572b

Cultural adaptation of evidence-based practice utilizing an iterative stakeholder process and theoretical framework: problem solving therapy for Chinese older adults

PubMed Central

Chu, Joyce P.; Huynh, Loanie; Areán, Patricia

2011-01-01

Objectives Main objectives were to familiarize the reader with a theoretical framework for modifying evidence-based interventions for cultural groups, and to provide an example of one method, Formative Method for Adapting Psychotherapies (FMAP), in the adaptation of an evidence-based intervention for a cultural group notorious for refusing mental health treatment. Methods Provider and client stakeholder input combined with an iterative testing process within the FMAP framework was utilized to create the Problem Solving Therapy—Chinese Older Adult (PST-COA) manual for depression. Data from pilot-testing the intervention with a clinically depressed Chinese elderly woman are reported. Results PST-COA is categorized as a ‘culturally-adapted’ treatment, where core mediating mechanisms of PST were preserved, but cultural themes of measurement methodology, stigma, hierarchical provider-client relationship expectations, and acculturation enhanced core components to make PST more understandable and relevant for Chinese elderly. Modifications also encompassed therapeutic framework and peripheral elements affecting engagement and retention. PST-COA applied with a depressed Chinese older adult indicated remission of clinical depression and improvement in mood. Fidelity with and acceptability of the treatment was sufficient as the client completed and reported high satisfaction with PST-COA. Conclusions PST, as a non-emotion-focused, evidence-based intervention, is a good fit for depressed Chinese elderly. Through an iterative stakeholder process of cultural adaptation, several culturally-specific modifications were applied to PST to create the PST-COA manual. PST-COA preserves core therapeutic PST elements but includes cultural adaptations in therapeutic framework and key administration and content areas that ensure greater applicability and effectiveness for the Chinese elderly community. PMID:21500283

Specific Sensory Techniques and Sensory Environmental Modifications for Children and Youth With Sensory Integration Difficulties: A Systematic Review.

PubMed

Bodison, Stefanie C; Parham, L Diane

This systematic review examined the effectiveness of specific sensory techniques and sensory environmental modifications to improve participation of children with sensory integration (SI) difficulties. Abstracts of 11,436 articles published between January 2007 and May 2015 were examined. Studies were included if designs reflected high levels of evidence, participants demonstrated SI difficulties, and outcome measures addressed function or participation. Eight studies met inclusion criteria. Seven studies evaluated effects of specific sensory techniques for children with autism spectrum disorder (ASD) or attention deficit hyperactivity disorder: Qigong massage, weighted vests, slow swinging, and incorporation of multisensory activities into preschool routines. One study of sensory environmental modifications examined adaptations to a dental clinic for children with ASD. Strong evidence supported Qigong massage, moderate evidence supported sensory modifications to the dental care environment, and limited evidence supported weighted vests. The evidence is insufficient to draw conclusions regarding slow linear swinging and incorporation of multisensory activities into preschool settings. Copyright © 2018 by the American Occupational Therapy Association, Inc.

Can they dig it? Functional morphology and semifossoriality among small-eared shrews, genus Cryptotis (Mammalia, Soricidae)

USGS Publications Warehouse

Woodman, Neal; Gaffney, Sarah A.

2014-01-01

Small-eared shrews (Mammalia: Soricidae: Cryptotis), exhibit modifications of the forelimb skeleton that have been interpreted as adaptations for semifossoriality. Most species inhabit remote regions, however, and their locomotory and foraging behaviors remain mostly speculative. To better understand the morphological modifications in the absence of direct observations, we quantified variation in these species by measuring 151 individuals representing 18 species and populations of Cryptotis and two species of moles (Talpidae) for comparison. From our measurements, we calculated 22 indices, most of which have been used previously to characterize substrate use among rodents and other taxa. We analyzed the indices using 1) average percentile ranks, 2) principal components analysis, and 3) cluster analysis. From these analyses, we determined that three basic modes of substrate adaptation are present within Cryptotis: 1) a primarily terrestrial mode, with species that are capable of burrowing, but lack adaptations to increase digging efficiency, 2) a semifossorial mode, with species whose forelimbs bones show strong muscle attachment areas and increased mechanical advantage, and 3) an intermediate mode. In addition to identifying new morphological characters and contributing to our understanding of the functional morphology of soricids, these analyses provide additional insight into the ecology of the species of interest.

To what extent may changes in the root system architecture of Arabidopsis thaliana grown under contrasted homogenous nitrogen regimes be explained by changes in carbon supply? A modelling approach.

PubMed

Brun, François; Richard-Molard, Céline; Pagès, Loïc; Chelle, Michaël; Ney, Bertrand

2010-05-01

Root system architecture adapts to low nitrogen (N) nutrition. Some adaptations may be mediated by modifications of carbon (C) fluxes. The objective of this study was to test the hypothesis that changes in root system architecture under different N regimes may be accounted for by using simple hypotheses of C allocation within the root system of Arabidopsis thaliana. With that purpose, a model during vegetative growth was developed that predicted the main traits of root system architecture (total root length, lateral root number, and specific root length). Different experimental data sets crossing three C levels and two N homogenous nutrition levels were generated. Parameters were estimated from an experiment carried out under medium C and high N conditions. They were then checked under other CxN conditions. It was found that the model was able to simulate correctly C effects on root architecture in both high and low N nutrition conditions, with the same parameter values. It was concluded that C flux modifications explained the major part of root system adaptation to N supply, even if they were not sufficient to simulate some changes, such as specific root length.

Mass Spectrometry Profiles Superoxide-Induced Intra-molecular Disulfide in the FMN-binding Subunit of Mitochondrial Complex I

PubMed Central

Zhang, Liwen; Xu, Hua; Chen, Chwen-Lih; Green-Church, Kari B.; Freitas, Michael A.; Chen, Yeong-Renn

2008-01-01

Protein thiols with regulatory functions play a critical role in maintaining the homeostasis of the redox state in mitochondria. One major host of regulatory cysteines in mitochondria is complex I, with the thiols primarily located on its 51 kDa FMN-binding subunit. In response to oxidative stress, these thiols are expected to form intra-molecular disulfide bridges as one of their oxidative post-translational modifications. Here, to test this hypothesis and gain insights into the molecular pattern of disulfide in complex I, the isolated bovine complex I was prepared. Superoxide (O2•−) is generated by complex I under the conditions of enzyme turnover. O2•−-induced intra-molecular disulfide formation at the 51 kDa subunit was determined by tandem mass spectrometry and database searching, with the latter accomplished by adaptation of the in-house developed database search engine, MassMatrix [Xu H., et. al J. Proteome Res. (2008) 7, 138–44]. LC/MS/MS analysis of tryptic/chymotryptic digests of the 51 kDa subunit from alkylated complex I revealed that four specific cysteines (C125, C142, C187, and C206) of the 51 kDa subunit were involved in the formation of mixed intra-molecular disulfide linkages. In all, three cysteine pairs were observed: C125/C142, C187/C206, and C142/C206. The formation of disulfide bond was subsequently inhibited by superoxide dismutase, indicating the involvement of O2•−. These results elucidated by mass spectrometry indicates that the residues of C125, C142, C187, and C206 are the specific regulatory cysteines of complex I, and they participate in the oxidative modification with disulfide formation under the physiological or pathophysiological conditions of oxidative stress. PMID:18789718

Neurobiological Signatures of Alcohol Dependence Revealed by Protein Profiling

PubMed Central

Gorini, Giorgio; Roberts, Amanda J.; Mayfield, R. Dayne

2013-01-01

Alcohol abuse causes dramatic neuroadaptations in the brain, which contribute to tolerance, dependence, and behavioral modifications. Previous proteomic studies in human alcoholics and animal models have identified candidate alcoholism-related proteins. However, recent evidences suggest that alcohol dependence is caused by changes in co-regulation that are invisible to single protein-based analysis. Here, we analyze global proteomics data to integrate differential expression, co-expression networks, and gene annotations to unveil key neurobiological rearrangements associated with the transition to alcohol dependence modeled by a Chronic Intermittent Ethanol (CIE), two-bottle choice (2BC) paradigm. We analyzed cerebral cortices (CTX) and midbrains (MB) from male C57BL/6J mice subjected to a CIE, 2BC paradigm, which induces heavy drinking and represents one of the best available animal models for alcohol dependence and relapse drinking. CIE induced significant changes in protein levels in dependent mice compared with their non-dependent controls. Multiple protein isoforms showed region-specific differential regulation as a result of post-translational modifications. Our integrative analysis identified modules of co-expressed proteins that were highly correlated with CIE treatment. We found that modules most related to the effects of CIE treatment coordinate molecular imbalances in endocytic- and energy-related pathways, with specific proteins involved, such as dynamin-1. The qRT-PCR experiments validated both differential and co-expression analyses, and the correspondence among our data and previous genomic and proteomic studies in humans and rodents substantiates our findings. The changes identified above may play a key role in the escalation of ethanol consumption associated with dependence. Our approach to alcohol addiction will advance knowledge of brain remodeling mechanisms and adaptive changes in response to drug abuse, contribute to understanding of organizational principles of CTX and MB proteomes, and define potential new molecular targets for treating alcohol addiction. The integrative analysis employed here highlight the advantages of systems approaches in studying the neurobiology of alcohol addiction. PMID:24358215

Crickets in space: morphological, physiological and behavioral alterations induced by space flight and hypergravity

NASA Astrophysics Data System (ADS)

Horn, E.; Agricola, H.; Böser, S.; Förster, S.; Kämper, G.; Riewe, P.; Sebastian, C.

"Crickets in Space" was a Neurolab experiment by which the balance between genetic programs and the gravitational environment for the development of a gravity sensitive neuronal system was studied. The model character of crickets was justified by their external gravity receptors, identified position-sensitive interneurons (PSI) and gravity-related compensatory head response, and by the specific relation of this behavior to neuronal arousal systems activated by locomotion. These advantages allowed to study the impact of modified gravity on cellular processes in a complex organism. Eggs, 1st, 4th and 6th stage larvae of Acheta domesticus were used. Post-flight experiments revealed a low susceptibility of the behavior to micro- and hypergravity while the physiology of the PSI was significantly affected. Immunocytological investigations revealed a stage-dependent sensitivity of thoracic GABAergic motoneurons to 3g-conditions concerning their soma sizes but not their topographical arrangement. The morphology of neuromuscular junctions was not affected by 3g-hypergravity. Peptidergic neurons from cerebral sensorimotor centers revealed no significant modifications by microgravity (μg). The contrary physiological and behavioral results indicate a facilitation of 1g-readaptation originating from accessory gravity, proprioceptive and visual sense organs. Absence of anatomical modifications point to an effective time window of μg- or 3g-expo-sure related to the period of neuronal proliferation. The analysis of basic mechanisms of how animals and man adapt to altered gravitational conditions will profit from a continuation of the project "Crickets in Space".

Arginine and Polyamines Fate in Leishmania Infection

PubMed Central

Muxel, Sandra M.; Aoki, Juliana I.; Fernandes, Juliane C. R.; Laranjeira-Silva, Maria F.; Zampieri, Ricardo A.; Acuña, Stephanie M.; Müller, Karl E.; Vanderlinde, Rubia H.; Floeter-Winter, Lucile M.

2018-01-01

Leishmania is a protozoan parasite that alternates its life cycle between the sand fly and the mammalian host macrophages, involving several environmental changes. The parasite responds to these changes by promoting a rapid metabolic adaptation through cellular signaling modifications that lead to transcriptional and post-transcriptional gene expression regulation and morphological modifications. Molecular approaches such as gene expression regulation, next-generation sequencing (NGS), microRNA (miRNA) expression profiling, in cell Western blot analyses and enzymatic activity profiling, have been used to characterize the infection of murine BALB/c and C57BL/6 macrophages, as well as the human monocytic cell-lineage THP-1, with Leishmania amazonensis wild type (La-WT) or arginase knockout (La-arg-). These models are being used to elucidate physiological roles of arginine and polyamines pathways and the importance of arginase for the establishment of the infection. In this review, we will describe the main aspects of Leishmania-host interaction, focusing on the arginine and polyamines pathways and pointing to possible targets to be used for prognosis and/or in the control of the infection. The parasite enzymes, arginase and nitric oxide synthase-like, have essential roles in the parasite survival and in the maintenance of infection. On the other hand, in mammalian macrophages, defense mechanisms are activated inducing alterations in the mRNA, miRNA and enzymatic profiles that lead to the control of infection. Furthermore, the genetic background of both parasite and host are also important to define the fate of infection. PMID:29379478

Gene expression profiles in promoted-growth rice seedlings that germinated from the seeds implanted by low-energy N+ beam

PubMed Central

Ya, Huiyuan; Chen, Qiufang; Wang, Weidong; Chen, Wanguang; Qin, Guangyong; Jiao, Zhen

2012-01-01

The stimulation effect that some beneficial agronomic qualities have exhibited in present-generation plants have also been observed due to ion implantation on plants. However, there is relatively little knowledge regarding the molecular mechanism of the stimulation effects of ion-beam implantation. In order to extend our current knowledge about the functional genes related to this stimulation effect, we have reported a comprehensive microarray analysis of the transcriptome features of the promoted-growth rice seedlings germinating from seeds implanted by a low-energy N+ beam. The results showed that 351 up-regulated transcripts and 470 down-regulated transcripts, including signaling proteins, kinases, plant hormones, transposable elements, transcription factors, non-coding protein RNA (including miRNA), secondary metabolites, resistance proteins, peroxidase and chromatin modification, are all involved in the stimulating effects of ion-beam implantation. The divergences of the functional catalog between the vacuum and ion implantation suggest that ion implantation is the principle cause of the ion-beam implantation biological effects, and revealed the complex molecular networks required to adapt to ion-beam implantation stress in plants, including enhanced transposition of transposable elements, promoted ABA biosynthesis and changes in chromatin modification. Our data will extend the current understanding of the molecular mechanisms and gene regulation of stimulation effects. Further research on the candidates reported in this study should provide new insights into the molecular mechanisms of biological effects induced by ion-beam implantation. PMID:22843621

Development of neuronal and sensorimotor systems in the absence of gravity: Neurobiological research on four soyuz taxi flights to the international space station

NASA Astrophysics Data System (ADS)

Horn, Eberhard R.; Dournon, Christian; Frippiat, Jean-Pol; Marco, Roberto; Böser, Sybille; Kirschnick, Uta

2007-09-01

Neurobiological experiments on 4 animal species (Xenopus laevis, Pleurodeles waltl, Drosophila melanogaster, Acheta domesticus) were performed to study effects of microgravity on development and aging of neuronal, sensory and motor systems. Animal models were selected according to their suitability to answer questions concerning μg-effects on neuroanatomy, neuronal activity, and behaviour. The studies were performed on the Soyuz Taxi flights Andromède, Cervantes, Eneide and LDM-TMA8/TMA7. Observations from these flights include: (1) In tadpoles and cricket larvae, morphological features of sensory cells and neurons are rarely affected by microgravity. (2) In crickets, in-flight fertilization was successful; after landing, flight larvae hatched earlier than ground reared siblings. (3) In crickets, proliferation of peptidergic neurons and their projection patterns within the nervous system were not affected by microgravity. (4) During aging, the impact of microgravity on peptidergic neurons of male Drosophila was limited to the size of cell body. (5) In Xenopus, neurophysiological features of the spinal motor system during fictive swimming were partially modified. (6) In Xenopus tadpoles, the vestibuloocular reflex was affected in an age-related manner. Modifications were also related to the occurrence of a tail lordosis induced by microgravity. It is concluded that adaptation to microgravity during development and aging is mainly based on physiological mechanisms within the central nervous system while structural modifications of the sensory and neuronal system contribute less.

Laser hardening techniques on steam turbine blade and application

NASA Astrophysics Data System (ADS)

Yao, Jianhua; Zhang, Qunli; Kong, Fanzhi; Ding, Qingming

Different laser surface hardening techniques, such as laser alloying and laser solution strengthening were adopted to perform modification treatment on the local region of inset edge for 2Cr13 and 17-4PH steam turbine blades to prolong the life of the blades. The microstructures, microhardness and anti-cavitation properties were investigated on the blades after laser treatment. The hardening mechanism and technique adaptability were researched. Large scale installation practices confirmed that the laser surface modification techniques are safe and reliable, which can improve the properties of blades greatly with advantages of high automation, high quality, little distortion and simple procedure.

The effects of metal ions on the DNA damage induced by hydrogen peroxide.

PubMed

Kobayashi, S; Ueda, K; Komano, T

1990-01-01

The effects of metal ions on DNA damage induced by hydrogen peroxide were investigated using two methods, agarose-gel electrophoretic analysis of supercoiled DNA and sequencing-gel analysis of single end-labeled DNA fragments of defined sequences. Hydrogen peroxide induced DNA damage when iron or copper ion was present. At least two classes of DNA damage were induced, one being direct DNA-strand cleavage, and the other being base modification labile to hot piperidine. The investigation of the damaged sites and the inhibitory effects of radical scavengers revealed that hydroxyl radical was the species which attacked DNA in the reaction of H2O2/Fe(II). On the other hand, two types of DNA damage were induced by H2O2/Cu(II). Type I damage was predominant and inhibited by potassium iodide, but type II was not. The sites of the base-modification induced by type I damage were similar to those by lipid peroxidation products and by ascorbate in the presence of Cu(II), suggesting the involvement of radical species other than free hydroxyl radical in the damaging reactions.

The influence of approach-avoidance motivational orientation on conflict adaptation.

PubMed

Hengstler, Maikel; Holland, Rob W; van Steenbergen, Henk; van Knippenberg, Ad

2014-06-01

To deal effectively with a continuously changing environment, our cognitive system adaptively regulates resource allocation. Earlier findings showed that an avoidance orientation (induced by arm extension), relative to an approach orientation (induced by arm flexion), enhanced sustained cognitive control. In avoidance conditions, performance on a cognitive control task was enhanced, as indicated by a reduced congruency effect, relative to approach conditions. Extending these findings, in the present behavioral studies we investigated dynamic adaptations in cognitive control-that is, conflict adaptation. We proposed that an avoidance state recruits more resources in response to conflicting signals, and thereby increases conflict adaptation. Conversely, in an approach state, conflict processing diminishes, which consequently weakens conflict adaptation. As predicted, approach versus avoidance arm movements affected both behavioral congruency effects and conflict adaptation: As compared to approach, avoidance movements elicited reduced congruency effects and increased conflict adaptation. These results are discussed in line with a possible underlying neuropsychological model.

Alcohol and epigenetic changes: Summary of the 2011 Alcohol and Immunology Research Interest Group (AIRIG) meeting

PubMed Central

Zahs, Anita; Curtis, Brenda J.; Waldschmidt, Thomas J.; Brown, Lou Ann S.; Gauthier, Theresa W.; Choudhry, Mashkoor A.; Kovacs, Elizabeth J.; Bird, Melanie D.

2013-01-01

On November 18, 2011, the 16th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at Loyola University Medical Center in Maywood, Illinois. The focus of this year’s meeting was alcohol’s effect on epigenetic changes and possible outcomes induced by these changes. Two sessions, which consisted of talks from invited speakers as well as presentations of selected abstracts, were held in addition to a poster session. Participants presented information on alcohol-induced alterations in histone modifications and gene expression along with immunologic responses to alcohol. Speakers shared new research specifically on histone deacetylase enzyme expression and modifications due to alcohol and the downstream effect of these modifications may have on gene expression and tissue damage. Additional studies suggested that alcohol exacerbates inflammation when combined with other insults such as infection, trauma, inhalation injury, and disease. PMID:22738858

Effects of electrode modification using calcium on the performance of alternating current field-induced polymer electroluminescent devices

NASA Astrophysics Data System (ADS)

Xia, Yingdong; Chen, Yonghua; Smith, Gregory M.; Li, Yuan; Huang, Wenxiao; Carroll, David L.

2013-06-01

In this work, the effects of electrode modification by calcium (Ca) on the performance of AC field induced polymer electroluminescence (FIPEL) devices are studied. The FIPEL device with Ca/Al electrode exhibits 550 cd m-2, which is 27.5 times higher than that of the device with only an Al electrode (20 cd m-2). Both holes and electrons are injected from one electrode in our FIPEL device. We found that the electron injection can be significantly enhanced by a Ca modification on the Al electrode without greatly affecting the hole injection. Therefore, the electrons and holes can be effectively recombined in the emissive layer to form more excitons under the AC voltage, leading to effective light emission. The device emitted much brighter light than other AC-based organic EL devices. This result provides an easy and effective way to improve FIPEL performance.

Role of Carbonyl Modifications on Aging-Associated Protein Aggregation

PubMed Central

Tanase, Maya; Urbanska, Aleksandra M.; Zolla, Valerio; Clement, Cristina C.; Huang, Liling; Morozova, Kateryna; Follo, Carlo; Goldberg, Michael; Roda, Barbara; Reschiglian, Pierluigi; Santambrogio, Laura

2016-01-01

Protein aggregation is a common biological phenomenon, observed in different physiological and pathological conditions. Decreased protein solubility and a tendency to aggregate is also observed during physiological aging but the causes are currently unknown. Herein we performed a biophysical separation of aging-related high molecular weight aggregates, isolated from the bone marrow and splenic cells of aging mice and followed by biochemical and mass spectrometric analysis. The analysis indicated that compared to younger mice an increase in protein post-translational carbonylation was observed. The causative role of these modifications in inducing protein misfolding and aggregation was determined by inducing carbonyl stress in young mice, which recapitulated the increased protein aggregation observed in old mice. Altogether our analysis indicates that oxidative stress-related post-translational modifications accumulate in the aging proteome and are responsible for increased protein aggregation and altered cell proteostasis. PMID:26776680

Investigating the Signature of Aquatic Resource Use within Pleistocene Hominin Dietary Adaptations

PubMed Central

Archer, Will; Braun, David R.

2013-01-01

There is general agreement that the diet of early hominins underwent dramatic changes shortly after the appearance of stone tools in the archaeological record. It is often assumed that this change is associated with dietary expansion to incorporate large mammal resources. Although other aspects of the hominin diet, such as aquatic or vegetal resources, are assumed to be a part of hominin subsistence, identifying evidence of these adaptations has proved difficult. Here we present a series of analyses that provide methodological support for the inclusion of aquatic resources in hominin dietary reconstructions. We suggest that bone surface modifications in aquatic species are morphologically distinguishable from bone surface modifications on terrestrial taxa. We relate these findings to differences that we document in the surface mechanical properties of the two types of bone, as reflected by significant differences in bone surface microhardness values between aquatic and terrestrial species. We hypothesize that the characteristics of bone surface modifications on aquatic taxa inhibit the ability of zooarchaeologists to consistently diagnose them correctly. Contingently, this difficulty influences correspondence levels between zooarchaeologists, and may therefore result in misinterpretation of the taphonomic history of early Pleistocene aquatic faunal assemblages. A blind test using aquatic specimens and a select group of 9 experienced zooarchaeologists as participants was designed to test this hypothesis. Investigation of 4 different possible explanations for blind test results suggest the dominant factors explaining patterning relate to (1) the specific methodologies employed to diagnose modifications on aquatic specimens and (2) the relative experience of participants with modifications on aquatic bone surfaces. Consequently we argue that an important component of early hominin diets may have hitherto been overlooked as a result of (a) the paucity of referential frameworks within which to identify such a component and (b) the inability of applied identification methodologies to consistently do so. PMID:23990891

Adaptations of the vestibular system to short and long-term exposures to altered gravity

NASA Astrophysics Data System (ADS)

Bruce, L.

Long-term space flight creates unique environmental conditions to which the vestibular system must adapt for optimal survival. We are studying two aspects of this vestibular adaptation: (1) How does long-term exposure to microgravity and hypergravity affect the development of vestibular afferents? (2) How does short- term exposure to extremely rapid changes in gravity, such as those that occur during launch and landing, affect the vestibular system. During space flight the gravistatic receptors in the otolith organs are effectively unloaded. In hypergravity conditions they are overloaded. However, the angular acceleration receptors of the semicircular canals receive relatively normal stimulation in both micro- and hypergravity.Rat embryos exposed to microgravity from gestation day 10 (prior to vestibular function) until gestation day 20 (vestibular system is somewhat functional) showed that afferents from the posterior vertical canal projecting to the medial vestibular nucleus developed similarly in microgravity, hypergravity, and in controls . However, afferents from the saccule showed delayed development in microgravity as compared to development in hypergravity and in controls. Cerebellar plasticity is crucial for modification of sensory-motor control and learning. Thus we explored the possibility that strong vestibular stimuli would modify cerebellar motor control (i.e., eye movement, postural control, gut motility) by altering the morphology of cerebellar Purkinje cells. To study the effects of short-term exposures to strong vestibular stimuli we focused on structural changes in the vestibulo-cerebellum that are caused by strong vestibular stimuli. Adult mice were exposed to various combinations of constant and/or rapidly changing angular and linear accelerations for 8.5 min (the time length of shuttle launch). Our data shows that these stimuli cause intense excitation of cerebellar Purkinje cells, inducing up-regulation of clathrin-mediated endocytosis. Different types of stimulation affect Purkinje cells in particular locations of the vestibulo-cerebellum. This system allows us to study how the vestibular environment can modify cerebellar function, allowing animals to adapt to new environments. Supported by NASA grant NAG2-1353.

Identifying Trustworthiness Deficit in Legacy Systems Using the NFR Approach

DTIC Science & Technology

2014-01-01

trustworthy envi- ronment. These adaptations can be stated in terms of design modifications and/or implementation mechanisms (for example, wrappers) that will...extensions to the VHSIC Hardware Description Language ( VHDL -AMS). He has spent the last 10 years leading research in high performance embedded computing

Positive Inclusion Experiences.

ERIC Educational Resources Information Center

Ensign, Arselia, Ed.

1996-01-01

This guide focuses on the use of low-end technology to make education more inclusive for children and adolescents with disabilities. The definition of "assistive technology" is discussed, and low-end technology is defined as simple modification/adaptation of toys and games, design and construction of simple switching devices, and the…

Designing for the Physically Disabled.

ERIC Educational Resources Information Center

Ontario Dept. of Education, Toronto.

This publication provides instructions and visual diagrams both for adapting existing structures and for building new facilities to meet the special needs of the disabled. Each of the two main sections is divided into two parts: "The Site" and "The Building." The first section, "Modification of Existing Schools,"…

Teaching about Vietnamese Culture: Water Puppetry as the Soul of the Rice Fields.

ERIC Educational Resources Information Center

Contreras, Gloria

1995-01-01

Maintains that educators can use Vietnamese history and culture to teach about human-environment interaction, adaptation, and modification. Describes Vietnamese water puppetry and recommends its use in U.S. classrooms. Includes five photographs, a description of water puppetry, and instructional suggestions. (CFR)

Computer Access. Tech Use Guide: Using Computer Technology.

ERIC Educational Resources Information Center

Council for Exceptional Children, Reston, VA. Center for Special Education Technology.

One of nine brief guides for special educators on using computer technology, this guide focuses on access including adaptations in input devices, output devices, and computer interfaces. Low technology devices include "no-technology" devices (usually modifications to existing devices), simple switches, and multiple switches. High technology input…

Adaptations of the Multifaceted Genogram in Counseling, Training, and Supervision.

ERIC Educational Resources Information Center

Magnuson, Sandy; Shaw, Holly E.

2003-01-01

Provides a review of representative literature offering modifications of traditional genogram formats, procedures, and emphases. Topics include counseling techniques and interventions for couples' issues related to sexuality, intimacy, and gender roles. Families and stepfamilies are addressed in areas such as grief and loss, alcoholism, and…

Raman-microscopy investigation of vitrification-induced structural damages in mature bovine oocytes

PubMed Central

De Canditiis, Carolina; Zito, Gianluigi; Rubessa, Marcello; Roca, Maria Serena; Carotenuto, Rosa; Sasso, Antonio; Gasparrini, Bianca

2017-01-01

Although oocyte cryopreservation has great potentials in the field of reproductive technologies, it still is an open challenge in the majority of domestic animals and little is known on the biochemical transformation induced by this process in the different cellular compartments. Raman micro-spectroscopy allows the non-invasive evaluation of the molecular composition of cells, based on the inelastic scattering of laser photons by vibrating molecules. The aim of this work was to assess the biochemical modifications of both the zona pellucida and cytoplasm of vitrified/warmed in vitro matured bovine oocytes at different post-warming times. By taking advantage of Principal Component Analysis, we were able to shed light on the biochemical transformation induced by the cryogenic treatment, also pointing out the specific role of cryoprotective agents (CPs). Our results suggest that vitrification induces a transformation of the protein secondary structure from the α-helices to the β-sheet form, while lipids tend to assume a more packed configuration in the zona pellucida. Both modifications result in a mechanical hardening of this cellular compartment, which could account for the reduced fertility rates of vitrified oocytes. Furthermore, biochemical modifications were observed at the cytoplasmic level in the protein secondary structure, with α-helices loss, suggesting cold protein denaturation. In addition, a decrease of lipid unsaturation was found in vitrified oocytes, suggesting oxidative damages. Interestingly, most modifications were not observed in oocytes exposed to CPs, suggesting that they do not severely affect the biochemical architecture of the oocyte. Nevertheless, in oocytes exposed to CPs decreased developmental competence and increased reactive oxygen species production were observed compared to the control. A more severe reduction of cleavage and blastocyst rates after in vitro fertilization was obtained from vitrified oocytes. Our experimental outcomes also suggest a certain degree of reversibility of the induced transformations, which renders vitrified oocytes more similar to untreated cells after 2 h warming. PMID:28531193

Detecting Chemically Modified DNA Bases Using Surface Enhanced Raman Spectroscopy

PubMed Central

Barhoumi, Aoune; Halas, Naomi J.

2013-01-01

Post-translational modifications of DNA- changes in the chemical structure of individual bases that occur without changes in the DNA sequence- are known to alter gene expression. They are believed to result in frequently deleterious phenotypic changes, such as cancer. Methylation of adenine, methylation and hydroxymethylation of cytosine, and guanine oxidation are the primary DNA base modifications identified to date. Here we show it is possible to use surface enhanced Raman spectroscopy (SERS) to detect these primary DNA base modifications. SERS detection of modified DNA bases is label-free and requires minimal additional sample preparation, reducing the possibility of additional chemical modifications induced prior to measurement. This approach shows the feasibility of DNA base modification assessment as a potentially routine analysis that may be further developed for clinical diagnostics. PMID:24427449

Detecting Chemically Modified DNA Bases Using Surface Enhanced Raman Spectroscopy.

PubMed

Barhoumi, Aoune; Halas, Naomi J

2011-12-15

Post-translational modifications of DNA- changes in the chemical structure of individual bases that occur without changes in the DNA sequence- are known to alter gene expression. They are believed to result in frequently deleterious phenotypic changes, such as cancer. Methylation of adenine, methylation and hydroxymethylation of cytosine, and guanine oxidation are the primary DNA base modifications identified to date. Here we show it is possible to use surface enhanced Raman spectroscopy (SERS) to detect these primary DNA base modifications. SERS detection of modified DNA bases is label-free and requires minimal additional sample preparation, reducing the possibility of additional chemical modifications induced prior to measurement. This approach shows the feasibility of DNA base modification assessment as a potentially routine analysis that may be further developed for clinical diagnostics.

The Climate Adaptation Frontier

DOE Office of Scientific and Technical Information (OSTI.GOV)

Preston, Benjamin L

2013-01-01

Climate adaptation has emerged as a mainstream risk management strategy for assisting in maintaining socio-ecological systems within the boundaries of a safe operating space. Yet, there are limits to the ability of systems to adapt. Here, we introduce the concept of an adaptation frontier , which is defined as a socio-ecological system s transitional adaptive operating space between safe and unsafe domains. A number of driving forces are responsible for determining the sustainability of systems on the frontier. These include path dependence, adaptation/development deficits, values conflicts and discounting of future loss and damage. The cumulative implications of these driving forcesmore » are highly uncertain. Nevertheless, the fact that a broad range of systems already persist at the edge of their frontiers suggests a high likelihood that some limits will eventually be exceeded. The resulting system transformation is likely to manifest as anticipatory modification of management objectives or loss and damage. These outcomes vary significantly with respect to their ethical implications. Successful navigation of the adaptation frontier will necessitate new paradigms of risk governance to elicit knowledge that encourages reflexive reevaluation of societal values that enable or constrain sustainability.« less

Left-Deviating Prism Adaptation in Left Neglect Patient: Reflexions on a Negative Result

PubMed Central

Luauté, Jacques; Jacquin-Courtois, Sophie; O'Shea, Jacinta; Christophe, Laure; Rode, Gilles; Boisson, Dominique; Rossetti, Yves

2012-01-01

Adaptation to right-deviating prisms is a promising intervention for the rehabilitation of patients with left spatial neglect. In order to test the lateral specificity of prism adaptation on left neglect, the present study evaluated the effect of left-deviating prism on straight-ahead pointing movements and on several classical neuropsychological tests in a group of five right brain-damaged patients with left spatial neglect. A group of healthy subjects was also included for comparison purposes. After a single session of exposing simple manual pointing to left-deviating prisms, contrary to healthy controls, none of the patients showed a reliable change of the straight-ahead pointing movement in the dark. No significant modification of attentional paper-and-pencil tasks was either observed immediately or 2 hours after prism adaptation. These results suggest that the therapeutic effect of prism adaptation on left spatial neglect relies on a specific lateralized mechanism. Evidence for a directional effect for prism adaptation both in terms of the side of the visuomanual adaptation and therefore possibly in terms of the side of brain affected by the stimulation is discussed. PMID:23050168

Disassociation between primary motor cortical activity and movement kinematics during adaptation to reach perturbations.

PubMed

Cai, X; Shimansky, Y P; Weber, D J; He, Jiping

2004-01-01

The relationship between movement kinematics and motor cortical activity was studied in monkeys performing a center-out reaching task during their adaptation to force perturbations applied to the wrist. The main feature of adaptive changes in movement kinematics was anticipatory deviation of hand paths in the direction opposite to that of the upcoming perturbation. We identified a group of neurons in the dorsal lateral portion of the primary motor cortex where a gradual buildup of spike activity immediately preceding the actual (in perturbation trials) or the "would-be" (in unperturbed/catch trials) perturbation onset was observed. These neurons were actively involved in the adaptation process, which was evident from the gradual increase in the amplitude of their movement-related modulation of spike activity from virtual zero and development of certain directional tuning pattern (DTP). However, the day-to-day dynamics of the kinematics adaptation was dramatically different from that of the neuronal activity. Hence, the adaptive modification of the motor cortical activity is more likely to reflect the development of the internal model of the perturbation dynamics, rather than motor instructions determining the adaptive behavior.

Structural and physico-chemical properties of insoluble rice bran fiber: effect of acid–base induced modifications

USDA-ARS?s Scientific Manuscript database

The structural modifications of insoluble rice bran fiber (IRBF) by sequential regimes of sulphuric acid (H2SO4) and their effects on the physicochemical attributes were studied. The increment of H2SO4 concentration resulted in decreased water holding capacity that ultimately enhanced the oil bindin...

Oxygen Consumption and Usage During Physical Exercise: The Balance Between Oxidative Stress and ROS-Dependent Adaptive Signaling

PubMed Central

Zhao, Zhongfu; Koltai, Erika; Ohno, Hideki; Atalay, Mustafa

2013-01-01

Abstract The complexity of human DNA has been affected by aerobic metabolism, including endurance exercise and oxygen toxicity. Aerobic endurance exercise could play an important role in the evolution of Homo sapiens, and oxygen was not important just for survival, but it was crucial to redox-mediated adaptation. The metabolic challenge during physical exercise results in an elevated generation of reactive oxygen species (ROS) that are important modulators of muscle contraction, antioxidant protection, and oxidative damage repair, which at moderate levels generate physiological responses. Several factors of mitochondrial biogenesis, such as peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), mitogen-activated protein kinase, and SIRT1, are modulated by exercise-associated changes in the redox milieu. PGC-1α activation could result in decreased oxidative challenge, either by upregulation of antioxidant enzymes and/or by an increased number of mitochondria that allows lower levels of respiratory activity for the same degree of ATP generation. Endogenous thiol antioxidants glutathione and thioredoxin are modulated with high oxygen consumption and ROS generation during physical exercise, controlling cellular function through redox-sensitive signaling and protein–protein interactions. Endurance exercise-related angiogenesis, up to a significant degree, is regulated by ROS-mediated activation of hypoxia-inducible factor 1α. Moreover, the exercise-associated ROS production could be important to DNA methylation and post-translation modifications of histone residues, which create heritable adaptive conditions based on epigenetic features of chromosomes. Accumulating data indicate that exercise with moderate intensity has systemic and complex health-promoting effects, which undoubtedly involve regulation of redox homeostasis and signaling. Antioxid. Redox Signal. 18, 1208–1246. PMID:22978553

Proteomic Profiling Reveals Adaptive Responses to Surgical Myocardial Ischemia Reperfusion in Hibernating Arctic Ground Squirrels Compared to Rats

PubMed Central

Quinones, Quintin J.; Zhang, Zhiquan; Ma, Qing; Smith, Michael P.; Soderblom, Erik; Moseley, M. Arthur; Bain, James; Newgard, Christopher B.; Muehlbauer, Michael J.; Hirschey, Matthew; Drew, Kelly L.; Barnes, Brian M.; Podgoreanu, Mihai V.

2016-01-01

Background Hibernation is an adaptation to extreme environments known to provide organ protection against ischemia-reperfusion (I/R) injury. An unbiased systems approach was utilized to investigate hibernation-induced changes characteristic of the hibernator cardioprotective phenotype, by comparing the myocardial proteome of winter hibernating arctic ground squirrels (HIB AGS), summer active (SA) AGS, and rats subjected to I/R, and further correlating with targeted metabolic changes. Methods In a well-defined rodent model of I/R by deep hypothermic circulatory arrest followed by 3h or 24h of reperfusion or sham, myocardial protein abundance in AGS (HIB, SA) and rats (n=4-5/group) was quantified by label-free proteomics (n=4-5/group), and correlated with metabolic changes. Results Compared to rats, HIB AGS displayed markedly reduced plasma levels of Troponin I, myocardial apoptosis, and left ventricular contractile dysfunction. Of the 1,320 rat and 1,478 AGS proteins identified, 545 were differentially expressed between HIB AGS and rat hearts (47% upregulated, 53% downregulated). Gene ontology analysis revealed downregulation in HIB AGS hearts of most proteins involved in mitochondrial energy transduction, including electron transport chain complexes, acetyl CoA biosynthesis, Krebs cycle, glycolysis and ketogenesis. Conversely, fatty acid oxidation enzymes and Sirtuin-3 were upregulated in HIB AGS, with preserved peroxisome proliferator activated receptor-α activity and reduced tissue levels of acylcarnitines and ceramides following I/R. Conclusions Natural cardioprotective adaptations in hibernators involve extensive metabolic remodeling, featuring increased expression of fatty acid metabolic proteins and reduced levels of toxic lipid metabolites. Robust upregulation of Sirtuin-3 suggests that post-translational modifications may underlie organ protection in hibernating mammals. PMID:27187119

Comparison of Strategies for Climate Change Adaptation of Water Supply and Flood Control Reservoirs

NASA Astrophysics Data System (ADS)

Ng, T. L.; Yang, P.; Bhushan, R.

2016-12-01

With climate change, streamflows are expected to become more fluctuating, with more frequent and intense floods and droughts. This complicates reservoir operation, which is highly sensitive to inflow variability. We make a comparative evaluation of three strategies for adapting reservoirs to climate-induced shifts in streamflow patterns. Specifically, we examine the effectiveness of (i) expanding the capacities of reservoirs by way of new off-stream reservoirs, (ii) introducing wastewater reclamation to augment supplies, and (iii) improving real-time streamflow forecasts for more optimal decision-making. The first two are hard strategies involving major infrastructure modifications, while the third a soft strategy entailing adjusting the system operation. A comprehensive side-by-side comparison of the three strategies is as yet lacking in the literature despite the many past studies investigating the strategies individually. To this end, we developed an adaptive forward-looking linear program that solves to yield the optimal decisions for the current time as a function of an ensemble forecast of future streamflows. Solving the model repeatedly on a rolling basis with regular updating of the streamflow forecast simulates the system behavior over the entire operating horizon. Results are generated for two hypothetical water supply and flood control reservoirs of differing inflows and demands. Preliminary findings suggest that of the three strategies, improving streamflow forecasts to be most effective in mitigating the effects of climate change. We also found that, in average terms, both additional reservoir capacity and wastewater reclamation have potential to reduce water shortage and downstream flooding. However, in the worst case, the potential of the former to reduce water shortage is limited, and similarly so the potential of the latter to reduce downstream flooding.

Polymicrobial sepsis and non-specific immunization induce adaptive immunosuppression to a similar degree.

PubMed

Schmoeckel, Katrin; Mrochen, Daniel M; Hühn, Jochen; Pötschke, Christian; Bröker, Barbara M

2018-01-01

Sepsis is frequently complicated by a state of profound immunosuppression, in its extreme form known as immunoparalysis. We have studied the role of the adaptive immune system in the murine acute peritonitis model. To read out adaptive immunosuppression, we primed post-septic and control animals by immunization with the model antigen TNP-ovalbumin in alum, and measured the specific antibody-responses via ELISA and ELISpot assay as well as T-cell responses in a proliferation assay after restimulation. Specific antibody titers, antibody affinity and plasma cell counts in the bone marrow were reduced in post-septic animals. The antigen-induced splenic proliferation was also impaired. The adaptive immunosuppression was positively correlated with an overwhelming general antibody response to the septic insult. Remarkably, antigen "overload" by non-specific immunization induced a similar degree of adaptive immunosuppression in the absence of sepsis. In both settings, depletion of regulatory T cells before priming reversed some parameters of the immunosuppression. In conclusion, our data show that adaptive immunosuppression occurs independent of profound systemic inflammation and life-threatening illness.

Polymicrobial sepsis and non-specific immunization induce adaptive immunosuppression to a similar degree

PubMed Central

Hühn, Jochen; Pötschke, Christian

2018-01-01

Sepsis is frequently complicated by a state of profound immunosuppression, in its extreme form known as immunoparalysis. We have studied the role of the adaptive immune system in the murine acute peritonitis model. To read out adaptive immunosuppression, we primed post-septic and control animals by immunization with the model antigen TNP-ovalbumin in alum, and measured the specific antibody-responses via ELISA and ELISpot assay as well as T-cell responses in a proliferation assay after restimulation. Specific antibody titers, antibody affinity and plasma cell counts in the bone marrow were reduced in post-septic animals. The antigen-induced splenic proliferation was also impaired. The adaptive immunosuppression was positively correlated with an overwhelming general antibody response to the septic insult. Remarkably, antigen “overload” by non-specific immunization induced a similar degree of adaptive immunosuppression in the absence of sepsis. In both settings, depletion of regulatory T cells before priming reversed some parameters of the immunosuppression. In conclusion, our data show that adaptive immunosuppression occurs independent of profound systemic inflammation and life-threatening illness. PMID:29415028

Transfer of perceptual-motor training and the space adaptation syndrome

NASA Technical Reports Server (NTRS)

Kennedy, R. S.; Berbaum, K. S.; Williams, M. C.; Brannan, J.; Welch, R. B.

1987-01-01

Perceptual cue conflict may be the basis for the symptoms which are experienced by space travelers in microgravity conditions. Recovery has been suggested to take place after perceptual modification or reinterpretation. To elucidate this process, 10 subjects who repeatedly experienced a visual/vestibular conflict over trials and days, were tested in a similar but not identical perceptual situation (pseudo-Coriolis) to determine whether any savings in perceptual adaptation had occurred as compared to an unpracticed control group (N = 40). The practiced subjects experienced lessening dizziness and ataxia within and over sessions.

Adaptive refinement tools for tetrahedral unstructured grids

NASA Technical Reports Server (NTRS)

Pao, S. Paul (Inventor); Abdol-Hamid, Khaled S. (Inventor)

2011-01-01

An exemplary embodiment providing one or more improvements includes software which is robust, efficient, and has a very fast run time for user directed grid enrichment and flow solution adaptive grid refinement. All user selectable options (e.g., the choice of functions, the choice of thresholds, etc.), other than a pre-marked cell list, can be entered on the command line. The ease of application is an asset for flow physics research and preliminary design CFD analysis where fast grid modification is often needed to deal with unanticipated development of flow details.

Adaptive antenna arrays for satellite communication

NASA Technical Reports Server (NTRS)

Gupta, Inder J.

1989-01-01

The feasibility of using adaptive antenna arrays to provide interference protection in satellite communications was studied. The feedback loops as well as the sample matric inversion (SMI) algorithm for weight control were studied. Appropriate modifications in the two were made to achieve the required interference suppression. An experimental system was built to test the modified feedback loops and the modified SMI algorithm. The performance of the experimental system was evaluated using bench generated signals and signals received from TVRO geosynchronous satellites. A summary of results is given. Some suggestions for future work are also presented.

An adaptive method for a model of two-phase reactive flow on overlapping grids

NASA Astrophysics Data System (ADS)

Schwendeman, D. W.

2008-11-01

A two-phase model of heterogeneous explosives is handled computationally by a new numerical approach that is a modification of the standard Godunov scheme. The approach generates well-resolved and accurate solutions using adaptive mesh refinement on overlapping grids, and treats rationally the nozzling terms that render the otherwise hyperbolic model incapable of a conservative representation. The evolution and structure of detonation waves for a variety of one and two-dimensional configurations will be discussed with a focus given to problems of detonation diffraction and failure.

Hydrogen Sulfide: A Signal Molecule in Plant Cross-Adaptation

PubMed Central

Li, Zhong-Guang; Min, Xiong; Zhou, Zhi-Hao

2016-01-01

For a long time, hydrogen sulfide (H2S) has been considered as merely a toxic by product of cell metabolism, but nowadays is emerging as a novel gaseous signal molecule, which participates in seed germination, plant growth and development, as well as the acquisition of stress tolerance including cross-adaptation in plants. Cross-adaptation, widely existing in nature, is the phenomenon in which plants expose to a moderate stress can induce the resistance to other stresses. The mechanism of cross-adaptation is involved in a complex signal network consisting of many second messengers such as Ca2+, abscisic acid, hydrogen peroxide and nitric oxide, as well as their crosstalk. The cross-adaptation signaling is commonly triggered by moderate environmental stress or exogenous application of signal molecules or their donors, which in turn induces cross-adaptation by enhancing antioxidant system activity, accumulating osmolytes, synthesizing heat shock proteins, as well as maintaining ion and nutrient balance. In this review, based on the current knowledge on H2S and cross-adaptation in plant biology, H2S homeostasis in plant cells under normal growth conditions; H2S signaling triggered by abiotic stress; and H2S-induced cross-adaptation to heavy metal, salt, drought, cold, heat, and flooding stress were summarized, and concluded that H2S might be a candidate signal molecule in plant cross-adaptation. In addition, future research direction also has been proposed. PMID:27833636

Nonlinear adaptive control system design with asymptotically stable parameter estimation error

NASA Astrophysics Data System (ADS)

Mishkov, Rumen; Darmonski, Stanislav

2018-01-01

The paper presents a new general method for nonlinear adaptive system design with asymptotic stability of the parameter estimation error. The advantages of the approach include asymptotic unknown parameter estimation without persistent excitation and capability to directly control the estimates transient response time. The method proposed modifies the basic parameter estimation dynamics designed via a known nonlinear adaptive control approach. The modification is based on the generalised prediction error, a priori constraints with a hierarchical parameter projection algorithm, and the stable data accumulation concepts. The data accumulation principle is the main tool for achieving asymptotic unknown parameter estimation. It relies on the parametric identifiability system property introduced. Necessary and sufficient conditions for exponential stability of the data accumulation dynamics are derived. The approach is applied in a nonlinear adaptive speed tracking vector control of a three-phase induction motor.

Guidelines for adapting cognitive stimulation therapy to other cultures

PubMed Central

Aguirre, Elisa; Spector, Aimee; Orrell, Martin

2014-01-01

Cognitive stimulation therapy (CST) has been shown to be an useful and cost effective intervention that increases cognition and quality of life of people with mild to moderate dementia. It is increasing in popularity in the UK and worldwide, and a number of research teams have examined its effectiveness in other contexts and cultures. However, it is necessary to develop clear evidence-based guidelines for cultural modification of the intervention. This article describes a community-based developmental approach to adapt CST to different cultures, following the five phases of the formative method for adapting psychotherapy (FMAP), an approach that involves collaborating with service users as a first step to generate and support ideas for therapy adaptation. Examples based on clinical and practical experience are presented, along with suggestions for applying these changes in different cultural contexts. PMID:25061282

Topologically heterogeneous beta cell adaptation in response to high-fat diet in mice.

PubMed

Ellenbroek, Johanne H; Töns, Hendrica A; de Graaf, Natascha; Loomans, Cindy J; Engelse, Marten A; Vrolijk, Hans; Voshol, Peter J; Rabelink, Ton J; Carlotti, Françoise; de Koning, Eelco J

2013-01-01

Beta cells adapt to an increased insulin demand by enhancing insulin secretion via increased beta cell function and/or increased beta cell number. While morphological and functional heterogeneity between individual islets exists, it is unknown whether regional differences in beta cell adaptation occur. Therefore we investigated beta cell adaptation throughout the pancreas in a model of high-fat diet (HFD)-induced insulin resistance in mice. C57BL/6J mice were fed a HFD to induce insulin resistance, or control diet for 6 weeks. The pancreas was divided in a duodenal (DR), gastric (GR) and splenic (SR) region and taken for either histology or islet isolation. The capacity of untreated islets from the three regions to adapt in an extrapancreatic location was assessed by transplantation under the kidney capsule of streptozotocin-treated mice. SR islets showed 70% increased beta cell proliferation after HFD, whereas no significant increase was found in DR and GR islets. Furthermore, isolated SR islets showed twofold enhanced glucose-induced insulin secretion after HFD, as compared with DR and GR islets. In contrast, transplantation of islets isolated from the three regions to an extrapancreatic location in diabetic mice led to a similar decrease in hyperglycemia and no difference in beta cell proliferation. HFD-induced insulin resistance leads to topologically heterogeneous beta cell adaptation and is most prominent in the splenic region of the pancreas. This topological heterogeneity in beta cell adaptation appears to result from extrinsic factors present in the islet microenvironment.

IKKβ-induced inflammation impacts the kinetics but not the magnitude of the immune response to a viral vector

PubMed Central

Hopewell, Emily L.; Bronk, Crystina C.; Massengill, Michael; Engelman, Robert W.; Beg, Amer A.

2012-01-01

Microbial adjuvants in vaccines activate key transcription factors, including NF-κB and interferon response factors (IRFs). However, the individual role of these transcription factor pathways in promoting adaptive immunity by adjuvants is not clear. It is widely believed that induction of a strong inflammatory response potentiates an adaptive immune response. In this study, we sought to determine whether activation of the pro-inflammatory inhibitor of κB kinase β (IKKβ) canonical NF-κB pathway promoted vaccine-induced immune responses. An adenovirus expressing constitutively-activated IKKβ (AdIKK) induced robust DC maturation and high expression of key cytokines compared to a control virus. In vivo, AdIKK triggered rapid inflammation after pulmonary infection, increased leukocyte entry into draining LNs, and enhanced early antibody and T-cell responses. Notably, AdIKK did not influence the overall magnitude of the adaptive immune response. These results indicate that induction of inflammation by IKKβ/NF-κB in this setting impacts the kinetics but not the magnitude of adaptive immune responses. These findings therefore help define the individual role of a key pathway induced by vaccine adjuvants in promoting adaptive immunity. PMID:22161279

Evolution of adaptation mechanisms: Adaptation energy, stress, and oscillating death.

PubMed

Gorban, Alexander N; Tyukina, Tatiana A; Smirnova, Elena V; Pokidysheva, Lyudmila I

2016-09-21

In 1938, Selye proposed the notion of adaptation energy and published 'Experimental evidence supporting the conception of adaptation energy.' Adaptation of an animal to different factors appears as the spending of one resource. Adaptation energy is a hypothetical extensive quantity spent for adaptation. This term causes much debate when one takes it literally, as a physical quantity, i.e. a sort of energy. The controversial points of view impede the systematic use of the notion of adaptation energy despite experimental evidence. Nevertheless, the response to many harmful factors often has general non-specific form and we suggest that the mechanisms of physiological adaptation admit a very general and nonspecific description. We aim to demonstrate that Selye׳s adaptation energy is the cornerstone of the top-down approach to modelling of non-specific adaptation processes. We analyze Selye׳s axioms of adaptation energy together with Goldstone׳s modifications and propose a series of models for interpretation of these axioms. Adaptation energy is considered as an internal coordinate on the 'dominant path' in the model of adaptation. The phenomena of 'oscillating death' and 'oscillating remission' are predicted on the base of the dynamical models of adaptation. Natural selection plays a key role in the evolution of mechanisms of physiological adaptation. We use the fitness optimization approach to study of the distribution of resources for neutralization of harmful factors, during adaptation to a multifactor environment, and analyze the optimal strategies for different systems of factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Proteomic analysis of the cyanobacterium of the Azolla symbiosis: identity, adaptation, and NifH modification.

PubMed

Ekman, Martin; Tollbäck, Petter; Bergman, Birgitta

2008-01-01

Cyanobacteria are able to form stable nitrogen-fixing symbioses with diverse eukaryotes. To extend our understanding of adaptations imposed by plant hosts, two-dimensional gel electrophoresis and mass spectrometry (MS) were used for comparative protein expression profiling of a cyanobacterium (cyanobiont) dwelling in leaf cavities of the water-fern Azolla filiculoides. Homology-based protein identification using peptide mass fingerprinting [matrix-assisted laser desorption ionization-time of flight (MALDI-TOF-MS)], tandem MS analyses, and sequence homology searches resulted in an identification success rate of 79% of proteins analysed in the unsequenced cyanobiont. Compared with a free-living strain, processes related to energy production, nitrogen and carbon metabolism, and stress-related functions were up-regulated in the cyanobiont while photosynthesis and metabolic turnover rates were down-regulated, stressing a slow heterotrophic mode of growth, as well as high heterocyst frequencies and nitrogen-fixing capacities. The first molecular data set on the nature of the NifH post-translational modification in cyanobacteria was also obtained: peptide mass spectra of the protein demonstrated the presence of a 300-400 Da protein modification localized to a specific 13 amino acid sequence, within the part of the protein that is ADP-ribosylated in other bacteria and close to the active site of nitrogenase. Furthermore, the distribution of the highest scoring database hits for the identified proteins points to the possibility of using proteomic data in taxonomy.

Mitochondria-specific antioxidant supplementation does not influence endurance exercise training-induced adaptations in circulating angiogenic cells, skeletal muscle oxidative capacity or maximal oxygen uptake.

PubMed

Shill, Daniel D; Southern, W Michael; Willingham, T Bradley; Lansford, Kasey A; McCully, Kevin K; Jenkins, Nathan T

2016-12-01

Reducing excessive oxidative stress, through chronic exercise or antioxidants, can decrease the negative effects induced by excessive amounts of oxidative stress. Transient increases in oxidative stress produced during acute exercise facilitate beneficial vascular training adaptations, but the effects of non-specific antioxidants on exercise training-induced vascular adaptations remain elusive. Circulating angiogenic cells (CACs) are an exercise-inducible subset of white blood cells that maintain vascular integrity. We investigated whether mitochondria-specific antioxidant (MitoQ) supplementation would affect the response to 3 weeks of endurance exercise training in CACs, muscle mitochondrial capacity and maximal oxygen uptake in young healthy men. We show that endurance exercise training increases multiple CAC types, an adaptation that is not altered by MitoQ supplementation. Additionally, MitoQ does not affect skeletal muscle or whole-body aerobic adaptations to exercise training. These results indicate that MitoQ supplementation neither enhances nor attenuates endurance training adaptations in young healthy men. Antioxidants have been shown to improve endothelial function and cardiovascular outcomes. However, the effects of antioxidants on exercise training-induced vascular adaptations remain elusive. General acting antioxidants combined with exercise have not impacted circulating angiogenic cells (CACs). We investigated whether mitochondria-specific antioxidant (MitoQ) supplementation would affect the response to 3 weeks of endurance exercise training on CD3 + , CD3 + /CD31 + , CD14 + /CD31 + , CD31 + , CD34 + /VEGFR2 + and CD62E + peripheral blood mononuclear cells (PBMCs), muscle mitochondrial capacity, and maximal oxygen uptake (VO2 max ) in healthy men aged 22.1 ± 0.7 years, with a body mass index of 26.9 ± 0.9 kg m -2 , and 24.8 ± 1.3% body fat. Analysis of main effects revealed that training induced 33, 105 and 285% increases in CD14 + /CD31 + , CD62E + and CD34 + /VEGFR2 + CACs, respectively, and reduced CD3 + /CD31 - PBMCs by 14%. There was no effect of MitoQ on CAC levels. Also independent of MitoQ supplementation, exercise training significantly increased quadriceps muscle mitochondrial capacity by 24% and VO2 max by roughly 7%. In conclusion, endurance exercise training induced increases in multiple CAC types, and this adaptation is not modified by MitoQ supplementation. Furthermore, we demonstrate that a mitochondrial-targeted antioxidant does not influence skeletal muscle or whole-body aerobic adaptations to exercise training. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Mitochondria‐specific antioxidant supplementation does not influence endurance exercise training‐induced adaptations in circulating angiogenic cells, skeletal muscle oxidative capacity or maximal oxygen uptake

PubMed Central

Shill, Daniel D.; Southern, W. Michael; Willingham, T. Bradley; Lansford, Kasey A.; McCully, Kevin K.

2016-01-01

Key points Reducing excessive oxidative stress, through chronic exercise or antioxidants, can decrease the negative effects induced by excessive amounts of oxidative stress. Transient increases in oxidative stress produced during acute exercise facilitate beneficial vascular training adaptations, but the effects of non‐specific antioxidants on exercise training‐induced vascular adaptations remain elusive.Circulating angiogenic cells (CACs) are an exercise‐inducible subset of white blood cells that maintain vascular integrity.We investigated whether mitochondria‐specific antioxidant (MitoQ) supplementation would affect the response to 3 weeks of endurance exercise training in CACs, muscle mitochondrial capacity and maximal oxygen uptake in young healthy men.We show that endurance exercise training increases multiple CAC types, an adaptation that is not altered by MitoQ supplementation. Additionally, MitoQ does not affect skeletal muscle or whole‐body aerobic adaptations to exercise training.These results indicate that MitoQ supplementation neither enhances nor attenuates endurance training adaptations in young healthy men. Abstract Antioxidants have been shown to improve endothelial function and cardiovascular outcomes. However, the effects of antioxidants on exercise training‐induced vascular adaptations remain elusive. General acting antioxidants combined with exercise have not impacted circulating angiogenic cells (CACs). We investigated whether mitochondria‐specific antioxidant (MitoQ) supplementation would affect the response to 3 weeks of endurance exercise training on CD3+, CD3+/CD31+, CD14+/CD31+, CD31+, CD34+/VEGFR2+ and CD62E+ peripheral blood mononuclear cells (PBMCs), muscle mitochondrial capacity, and maximal oxygen uptake (VO2 max ) in healthy men aged 22.1 ± 0.7 years, with a body mass index of 26.9 ± 0.9 kg m–2, and 24.8 ± 1.3% body fat. Analysis of main effects revealed that training induced 33, 105 and 285% increases in CD14+/CD31+, CD62E+ and CD34+/VEGFR2+ CACs, respectively, and reduced CD3+/CD31− PBMCs by 14%. There was no effect of MitoQ on CAC levels. Also independent of MitoQ supplementation, exercise training significantly increased quadriceps muscle mitochondrial capacity by 24% and VO2 max by roughly 7%. In conclusion, endurance exercise training induced increases in multiple CAC types, and this adaptation is not modified by MitoQ supplementation. Furthermore, we demonstrate that a mitochondrial‐targeted antioxidant does not influence skeletal muscle or whole‐body aerobic adaptations to exercise training. PMID:27501153

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Dandan; Perkins, Jordan T.; Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40536

Epigenetic modifications of DNA and histones alter cellular phenotypes without changing genetic codes. Alterations of epigenetic marks can be induced by exposure to environmental pollutants and may contribute to associated disease risks. Here we test the hypothesis that endothelial cell dysfunction induced by exposure to polychlorinated biphenyls (PCBs) is mediated in part though histone modifications. In this study, human vascular endothelial cells were exposed to physiologically relevant concentrations of several PCBs congeners (e.g., PCBs 77, 118, 126 and 153) followed by quantification of inflammatory gene expression and changes of histone methylation. Only exposure to coplanar PCBs 77 and 126 inducedmore » the expression of histone H3K9 trimethyl demethylase jumonji domain-containing protein 2B (JMJD2B) and nuclear factor-kappa B (NF-κB) subunit p65, activated NF-κB signaling as evidenced by nuclear translocation of p65, and up-regulated p65 target inflammatory genes, such as interleukin (IL)-6, C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and IL-1α/β. The increased accumulation of JMJD2B in the p65 promoter led to a depletion of H3K9me3 repression mark, which accounts for the observed up-regulation of p65 and associated inflammatory genes. JMJD2B gene knockdown confirmed a critical role for this histone demethylase in mediating PCB-induced inflammation of the vascular endothelium. Finally, it was determined, via chemical inhibition, that PCB-induced up-regulation of JMJD2B was estrogen receptor-alpha (ER-α) dependent. These data suggest that coplanar PCBs may exert endothelial cell toxicity through changes in histone modifications. - Highlights: • Coplanar PCBs significantly induced histone demethylase JMJD2B expression. • Coplanar PCBs activated NF-κB through p65 up-regulation and nuclear translocation. • Histone H3K4 and K9 modifications were mediated by ER-α/JMJD2B/MLL2 complex. • ER-α may be involved in the regulation of PCB-induced JMJD2B expression.« less

FIBER OPTICS: Role of point defects in the photosensitivity of hydrogen-loaded phosphosilicate glass

NASA Astrophysics Data System (ADS)

Larionov, Yu V.

2010-08-01

It is shown that point defect modifications in hydrogen-loaded phosphosilicate glass (PSG) do not play a central role in determining its photosensitivity. Photochemical reactions that involve a two-step point defect modification and pre-exposure effect are incapable of accounting for photoinduced refractive index changes. It seems likely that a key role in UV-induced refractive index modifications is played by structural changes in the PSG network. Experimental data are presented that demonstrate intricate network rearrangement dynamics during UV exposure of PSG.

Speckle contrast techniques in the study of tissue thermal modification and denaturation

NASA Astrophysics Data System (ADS)

Agafonov, Dmitry N.; Kuznetsova, Liana V.; Zimnyakov, Dmitry A.; Sviridov, Alexander P.; Omelchenko, Alexander I.

2002-05-01

Results of the contrast analysis of time-averaged dynamic speckle patterns in application to monitoring of the structure modification of the thermally treated collagenous tissue such as cartilage are presented. The modification presumably induced by the bound to free water phase transition in the matrix of the treated tissue cause the specific feature of evolution of the time-averaged speckle contrast with the change of the current temperature of modified collagen tissue. This evolution appears as hysteresis associated with irreversible changes in tissue structure.

TiO2 induced structural modifications in Cs containing borosilicate glasses: Raman and infrared studies

NASA Astrophysics Data System (ADS)

Pandey, M.; Banerjee, D.; Sudarsan, V.; Kshirsagar, R. J.

2018-04-01

Effect of TiO2 addition in Cs containing Sodium-borosilicate glasses is studied using Raman and infrared spectroscopic techniques. As revealed from infrared and Raman studies, TiO2 does not form segregated phase, but instead enters into the borosilicate network. It is further observed that TiO2 addition results in modifications of the borate and silicate structural units by transforming into tetraborates and metasilicate structural units. These structural modifications are responsible for Cs immobilization, leach rate and chemical durability of these glasses.

Effect of edge modification on the zigzag BC2N nanoribbons

NASA Astrophysics Data System (ADS)

Xiao, Xiang; Li, Hong; Tie, Jun; Lu, Jing

2016-08-01

We use first principles calculations to investigate the effects of edge modification with nonmetal species on zigzag-edged BC2N nanoribbons (ZBC2NNRs). These ZBC2NNRs show either semiconducting or metallic behaviors depending on the edge modifications and ribbon widths. We find that the O-modification induces a ferromagnetic ground state with a metallic behavior for all the ribbon widths investigated. And when the ribbon width is more than 3.32 nm (NZ ⩾ 16), an antiferromagnetic ground state with a half-metallic behavior is realized in the H-passivated ZBC2NNRs. These versatile electronic properties render the ZBC2NNRs a promising candidate material in nanoelectronics and nanospintronics.

Drug Addiction and DNA Modifications.

PubMed

Brown, Amber N; Feng, Jian

2017-01-01

Drug addiction is a complex disorder which can be influenced by both genetic and environmental factors. Research has shown that epigenetic modifications can translate environmental signals into changes in gene expression, suggesting that epigenetic changes may underlie the causes and possibly treatment of substance use disorders. This chapter will focus on epigenetic modifications to DNA, which include DNA methylation and several recently defined additional DNA epigenetic changes. We will discuss the functions of DNA modifications and methods for detecting them, followed by a description of the research investigating the function and consequences of drug-induced changes in DNA methylation patterns. Understanding these epigenetic changes may provide us translational tools for the diagnosis and treatment of addiction in the future.

Chapter 15: Preparations of entomopathogens and diseased specimens for more detailed study using microscopy

USDA-ARS?s Scientific Manuscript database

The science of Insect Pathology encompasses a diverse assemblage of pathogens from a large and varied group of hosts. Microscopy techniques and protocols for these organisms are complex and varied and often require modifications and adaptations of standard procedures. The objective of this chapter...

49 CFR Appendix E to Part 26 - Individual Determinations of Social and Economic Disadvantage

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Individual Determinations of Social and Economic... Appendix E to Part 26—Individual Determinations of Social and Economic Disadvantage The following guidance is adapted, with minor modifications, from SBA regulations concerning social and economic...

Towards Extended Vantage Theory

ERIC Educational Resources Information Center

Glaz, Adam

2010-01-01

The applicability of Vantage Theory (VT), a model of (colour) categorization, to linguistic data largely depends on the modifications and adaptations of the model for the purpose. An attempt to do so proposed here, called Extended Vantage Theory (EVT), slightly reformulates the VT conception of vantage by capitalizing on some of the entailments of…

Manual Skill Training of Retarded Children.

ERIC Educational Resources Information Center

Pomerantz, David J.

1975-01-01

In an on-going pilot study, training procedures previously found successful with moderately and severely retarded adolescents and adults have been adapted to teaching trainable retarded children (6-, 8-, and 10-years-old) to assemble a 14-piece coaster brake. Modifications in the carefully detailed task analysis approach have included the need for…

The Efficiency of Seminars in Elementary Education

ERIC Educational Resources Information Center

Kocabas, Ibrahim

2006-01-01

Teachers can best process their duties by renewing themselves according to today's context. The modifications in science, technology, culture, and social life change the educational theory and its application. Teachers should have to effectively adapt themselves to these changes. This is possible only by arranging continual in-service training for…

Planning Lessons for Students with Significant Disabilities in High School English Classes

ERIC Educational Resources Information Center

Apitz, Megan; Ruppar, Andrea; Roessler, Karli; Pickett, Kelly J.

2017-01-01

Students with significant disabilities have intellectual disability and require individualized modifications, adaptations, and supports to access grade-level content (National Center on Educational Outcomes, 2013). This group of students presents a unique challenge for literacy instruction, particularly at the high school level. Teachers must…

Script Reforms--Are They Necessary?

ERIC Educational Resources Information Center

James, Gregory

Script reform, the modification of an existing writing system, is often confused with script replacement of one writing system with another. Turkish underwent the replacement of Arabic script by an adaptation of Roman script under Kamel Ataturk, but a similar replacement in Persian was rejected because of the high rate of existing literacy in…

49 CFR Appendix E to Part 26 - Individual Determinations of Social and Economic Disadvantage

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 1 2012-10-01 2012-10-01 false Individual Determinations of Social and Economic... Appendix E to Part 26—Individual Determinations of Social and Economic Disadvantage The following guidance is adapted, with minor modifications, from SBA regulations concerning social and economic...

49 CFR Appendix E to Part 26 - Individual Determinations of Social and Economic Disadvantage

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false Individual Determinations of Social and Economic... Appendix E to Part 26—Individual Determinations of Social and Economic Disadvantage The following guidance is adapted, with minor modifications, from SBA regulations concerning social and economic...

49 CFR Appendix E to Part 26 - Individual Determinations of Social and Economic Disadvantage

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 1 2014-10-01 2014-10-01 false Individual Determinations of Social and Economic... Appendix E to Part 26—Individual Determinations of Social and Economic Disadvantage The following guidance is adapted, with minor modifications, from SBA regulations concerning social and economic...

49 CFR Appendix E to Part 26 - Individual Determinations of Social and Economic Disadvantage

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 1 2011-10-01 2011-10-01 false Individual Determinations of Social and Economic... Appendix E to Part 26—Individual Determinations of Social and Economic Disadvantage The following guidance is adapted, with minor modifications, from SBA regulations concerning social and economic...

Modification and Adaptation of the Program Evaluation Standards in Saudi Arabia

ERIC Educational Resources Information Center

Alyami, Mohammed

2013-01-01

The Joint Committee on Standards for Educational Evaluation's Program Evaluation Standards is probably the most recognized and applied set of evaluation standards globally. The most recent edition of The Program Evaluation Standards includes five categories and 30 standards. The five categories are Utility, Feasibility, Propriety, Accuracy, and…

25 CFR 700.157 - Actual reasonable moving and related expenses-nonresidential moves.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of § 700.151(c) a certified eligible business, farm operation or nonprofit organization is entitled...-moves his business, farm operation, or nonprofit organization, the Commission may approve a payment for... and modifications necessary to adapt such property to the replacement structure or to the utilities or...

27 CFR 24.21 - Modified forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Section 24.21 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... in a net increase in cost to the Government or hinder the effective administration of this part. Except to adapt tax returns for use with data processing equipment, no proposal for modification of a...

49 CFR 595.7 - Requirements for vehicle modifications to accommodate people with disabilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... original equipment manufacturer's controls. (6) S5.3.1 of 49 CFR 571.135, in any case in which the... shaft. (11) S5.2 of 49 CFR 571.203, in any case in which an item of adaptive equipment must be mounted...

49 CFR 595.7 - Requirements for vehicle modifications to accommodate people with disabilities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... original equipment manufacturer's controls. (6) S5.3.1 of 49 CFR 571.135, in any case in which the... shaft. (11) S5.2 of 49 CFR 571.203, in any case in which an item of adaptive equipment must be mounted...

49 CFR 595.7 - Requirements for vehicle modifications to accommodate people with disabilities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... original equipment manufacturer's controls. (6) S5.3.1 of 49 CFR 571.135, in any case in which the... shaft. (11) S5.2 of 49 CFR 571.203, in any case in which an item of adaptive equipment must be mounted...

Conservation and modification of genetic and physiological toolkits underpinning diapause in bumble bee queens

USDA-ARS?s Scientific Manuscript database

Diapause is the key adaptation allowing insects to survive unfavourable conditions and inhabit an array of environments. Physiological changes during diapause are largely conserved across species and are hypothesized to be regulated by a conserved suite of genes (a ‘toolkit’). Furthermore, it is hyp...

Pregnancy as a cardiac stress model

PubMed Central

Chung, Eunhee; Leinwand, Leslie A.

2014-01-01

Cardiac hypertrophy occurs during pregnancy as a consequence of both volume overload and hormonal changes. Both pregnancy- and exercise-induced cardiac hypertrophy are generally thought to be similar and physiological. Despite the fact that there are shared transcriptional responses in both forms of cardiac adaptation, pregnancy results in a distinct signature of gene expression in the heart. In some cases, however, pregnancy can induce adverse cardiac events in previously healthy women without any known cardiovascular disease. Peripartum cardiomyopathy is the leading cause of non-obstetric mortality during pregnancy. To understand how pregnancy can cause heart disease, it is first important to understand cardiac adaptation during normal pregnancy. This review provides an overview of the cardiac consequences of pregnancy, including haemodynamic, functional, structural, and morphological adaptations, as well as molecular phenotypes. In addition, this review describes the signalling pathways responsible for pregnancy-induced cardiac hypertrophy and angiogenesis. We also compare and contrast cardiac adaptation in response to disease, exercise, and pregnancy. The comparisons of these settings of cardiac hypertrophy provide insight into pregnancy-associated cardiac adaptation. PMID:24448313