Greater level of physical activity associated with better cognitive function in hemodialysis in end stage renal disease

Patients with chronic kidney disease (CKD) have a lower exercise tolerance and poor functional capacity, carry on a sedentary lifestyle. Another important change found in patients with CKD is cognitive dysfunction. Physical inactivity has been associated with cognitive dysfunction in the general population, but few studies have evaluated this association in CKD. To assess the association between physical activity and cognitive function in patients with CKD on hemodialysis (HD). We evaluated 102 patients undergoing HD. The participants completed the International Physical Activity Questionnaire, which assesses the level of physical activity and the Mini Mental State Examination, used for cognitive screening. Patients were divided into three groups according to their level of physical activity (GI: active/GII: irregularly active/GIII: sedentary). It was applied logistic regression analysis and adopted as outcome variable the presence of cognitive impairment and preserving as independent variables those with a probability of statistical difference between groups of less than 0.1. It was considered statistically significant when p less than 0.05. The groups were similar in age, duration of HD, and smoking. Statistically significant difference regarding race, body mass index, diabetes mellitus, underlying disease and degree of cognitive impairment. Regarding laboratory data, the groups differed in terms of creatinine, glucose, hemoglobin and hematocrit. There was significant association with better physical activity and cognitive function, even adjusting for confounding variables. the highest level of physical activity was associated with better cognitive function in CKD patients undergoing HD.

STUDIES OF DISULFOTON TOLERANCE IN RATS

Disulfoton (O,O, diethyl S-2-(ethylthio)ethyl phosphorodithioate) and other organophosphorus ester compounds are insecticides which inhibit acetylcholinesterase. Chemicals of this class cause signs of toxicity in mammals which are referable to acculmulation of acetylcholine at neuroeffector sites. A tolerance to this toxic action can be induced in experimental animals by giving multiple, sublethal doses of the compounds. There is strong evidence that disulfoton tolerance occurs because of a reduction in the sensitivity of tissues in the affected animals to acetylcholine.^ Experiments were designed to test the possibility that a decrease in the number of muscarinic cholinergic receptors could be downmodulating the sensitivity of tissues to acetylcholine. It was found that, concomitant with the onset of disulfoton tolerance, there was a decrease relative to control values in the specific binding of {('3)H} quinuclidinyl benzilate ({('3)H}QNB, a compound which selectively labels muscarinic cholinergic receptors) to homogenates of rat brain and ileal muscle. The decrease in {('3)H}QNB binding was due to a reduction in the density of muscarinic receptors. There was, however, no alteration in the binding of {('3)H} QNB, or the muscarinic agonists {('3)H} oxotremorine-M and oxotremorine to atria from disulfoton-tolerant rats. The possibility that cardiac tissue was not subsensitive to cholinergic agonists was ruled out in experiments testing the effect of the muscarinic agonist carbachol on heart rate in vivo, and the negative chronotropic effect of oxotremorine on atria from disulfoton-tolerant rats: a clear reduction in the sensitivity to cholinergic agonists was seen in each case. It was, therefore concluded that the specificity and temporal correlation of {('3)H}QNB binding decreases suggested that the loss of muscarinic receptors might play a role in modulating the sensitivity of several tissues to acetylcholine, but that other mechanisms also contribute to the tolerance phenomenon.^ Other experiments revealed that disulfoton tolerance, as measured by resistance to the lethal effects of carbachol, could be induced by feeding rats low levels of the organophosphorus ester in the diet. The concentration of disulfoton used inhibited acetylcholinesterase, but not to the extent that overt signs of toxicity were observed. These results suggested that tolerance to organophosphorus ester insecticides could be induced in rodents with a dosing scheme which more closely modeled the sort of low level exposures which would be expected in humans environmentally or occupationally in contact with these compounds. ^

Determinants of political tolerance : a literature review

This paper reviews the current literature on political tolerance with particular reference to its individual- and aggregate-level determinants. Individual-level determinants such as authoritarianism, education, contact, and threat perception are found to have robust effects on tolerance. What are less known are the mediating factors that enhance or reduce these effects. In recent years, increasing attention has been directed toward the impact of contextual factors on threat and contact effects.

Molecular basis of salt tolerance in Physcomitrella Patens model plant: potassium homeostasis and physiological roles of chx transporters

El suelo salino impone un estrés abiótico importante que causa graves problemas en la agricultura ya que la mayoría de los cultivos se ven afectados por la salinidad debido a efectos osmóticos y tóxicos. Por ello, la contaminación y la escasez de agua dulce, la salinización progresiva de tierras y el aumento exponencial de la población humana representan un grave problema que amenaza la seguridad alimentaria mundial para las generaciones futuras. Por lo tanto, aumentar la tolerancia a la salinidad de los cultivos es un objetivo estratégico e ineludible para garantizar el suministro de alimentos en el futuro. Mantener una óptima homeostasis de K+ en plantas que sufren estrés salino es un objetivo importante en el proceso de obtención de plantas tolerantes a la salinidad. Aunque el modelo de la homeostasis de K+ en las plantas está razonablemente bien descrito en términos de entrada de K+, muy poco se sabe acerca de los genes implicados en la salida de K+ o de su liberación desde la vacuola. En este trabajo se pretende aclarar algunos de los mecanismos implicados en la homeostasis de K+ en plantas. Para ello se eligió la briofita Physcomitrella patens, una planta no vascular de estructura simple y de fase haploide dominante que, entre muchas otras cualidades, hacen que sea un modelo ideal. Lo más importante es que no sólo P. patens es muy tolerante a altas concentraciones de Na+, sino que también su posición filogenética en la evolución de las plantas abre la posibilidad de estudiar los cambios claves que, durante el curso de la evolución, se produjeron en las diversas familias de los transportadores de K+. Se han propuesto varios transportadores de cationes como candidatos que podrían tener un papel en la salida de K+ o su liberación desde la vacuola, especialmente miembros de la familia CPA2 que contienen las familias de transportadores KEA y CHX. En este estudio se intenta aumentar nuestra comprensión de las funciones de los transportadores de CHX en las células de las plantas usando P. patens, como ya se ha dicho. En esta especie, se han identificado cuatro genes CHX, PpCHX1-4. Dos de estos genes, PpCHX1 y PpCHX2, se expresan aproximadamente al mismo nivel que el gen PpACT5, y los otros dos genes muestran una expresión muy baja. La expresión de PpCHX1 y PpCHX2 en mutantes de Escherichia coli defectivos en el transporte de K+ restauraron el crecimiento de esta cepa en medios con bajo contenido de K+, lo que viii sugiere que la entrada de K+ es energizada por un mecanismo de simporte con H+. Por otra parte, estos transportadores suprimieron el defecto asociado a la mutación kha1 en Saccharomyces cerevisiae, lo que sugiere que podrían mediar un antiporte en K+/H+. La proteína PpCHX1-GFP expresada transitoriamente en protoplastos de P. patens co-localizó con un marcador de Golgi. En experimentos similares, la proteína PpCHX2-GFP localizó aparentemente en la membrana plasmática y tonoplasto. Se construyeron las líneas mutantes simples de P. patens ΔPpchx1 y ΔPpchx2, y también el mutante doble ΔPpchx2 ΔPphak1. Los mutantes simples crecieron normalmente en todas las condiciones ensayadas y mostraron flujos de entrada normales de K+ y Rb+; la mutación ΔPpchx2 no aumentó el defecto de las plantas ΔPphak1. En experimentos a largo plazo, las plantas ΔPpchx2 mostraron una retención de Rb+ ligeramente superior que las plantas silvestres, lo que sugiere que PpCHX2 promueve la transferencia de Rb+ desde la vacuola al citosol o desde el citosol al medio externo, actuando en paralelo con otros transportadores. Sugerimos que transportadores de K+ de varias familias están involucrados en la homeostasis de pH de orgánulos ya sea mediante antiporte K+/H+ o simporte K+-H+.ix ABSTRACT Soil salinity is a major abiotic stress causing serious problems in agriculture as most crops are affected by it. Moreover, the contamination and shortage of freshwater, progressive land salinization and exponential increase of human population aggravates the problem implying that world food security may not be ensured for the next generations. Thus, a strategic and an unavoidable goal would be increasing salinity tolerance of plant crops to secure future food supply. Maintaining an optimum K+ homeostasis in plants under salinity stress is an important trait to pursue in the process of engineering salt tolerant plants. Although the model of K+ homeostasis in plants is reasonably well described in terms of K+ influx, very little is known about the genes implicated in K+ efflux or release from the vacuole. In this work, we aim to clarify some of the mechanisms involved in K+ homeostasis in plants. For this purpose, we chose the bryophyte plant Physcomitrella patens, a nonvascular plant of simple structure and dominant haploid phase that, among many other characteristics, makes it an ideal model. Most importantly, not only P. patens is very tolerant to high concentrations of Na+, but also its phylogenetic position in land plant evolution opens the possibility to study the key changes that occurred in K+ transporter families during the course of evolution. Several cation transporter candidates have been proposed to have a role in K+ efflux or release from the vacuole especially members of the CPA2 family which contains the KEA and CHX transporter families. We intended in this study to increase our understanding of the functions of CHX transporters in plant cells using P. patens, in which four CHX genes have been identified, PpCHX1-4. Two of these genes, PpCHX1 and PpCHX2, are expressed at approximately the same level as the PpACT5 gene, but the other two genes show an extremely low expression. PpCHX1 and PpCHX2 restored growth of Escherichia coli mutants on low K+-containing media, suggesting they mediated K+ uptake that may be energized by symport with H+. In contrast, these genes suppressed the defect associated to the kha1 mutation in Saccharomyces cerevisiae, which suggest that they might mediate K+/H+ antiport. PpCHX1-GFP protein transiently expressed in P. patens protoplasts co-localized with a Golgi marker. In similar experiments, the PpCHX2-GFP protein appeared to localize to tonoplast and plasma x membrane. We constructed the ΔPpchx1 and ΔPpchx2 single mutant lines, and the ΔPpchx2 ΔPphak1 double mutant. Single mutant plants grew normally under all the conditions tested and exhibited normal K+ and Rb+ influxes; the ΔPpchx2 mutation did not increase the defect of ΔPphak1 plants. In long-term experiments, ΔPpchx2 plants showed a slightly higher Rb+ retention than wild type plants, which suggests that PpCHX2 mediates the transfer of Rb+ from either the vacuole to the cytosol or from the cytosol to the external medium in parallel with other transporters. We suggest that K+ transporters of several families are involved in the pH homeostasis of organelles by mediating either K+/H+ antiport or K+-H+ symport.

Unifying theory of hypoxia tolerance: molecular/metabolic defense and rescue mechanisms for surviving oxygen lack.

We develop a unifying theory of hypoxia tolerance based on information from two cell level models (brain cortical cells and isolated hepatocytes) from the highly anoxia tolerant aquatic turtle and from other more hypoxia sensitive systems. We propose that the response of hypoxia tolerant systems to oxygen lack occurs in two phases (defense and rescue). The first lines of defense against hypoxia include a balanced suppression of ATP-demand and ATP-supply pathways; this regulation stabilizes (adenylates) at new steady-state levels even while ATP turnover rates greatly decline. The ATP demands of ion pumping are down-regulated by generalized "channel" arrest in hepatocytes and by "spike" arrest in neurons. Hypoxic ATP demands of protein synthesis are down-regulated probably by translational arrest. In hypoxia sensitive cells this translational arrest seems irreversible, but hypoxia-tolerant systems activate "rescue" mechanisms if the period of oxygen lack is extended by preferentially regulating the expression of several proteins. In these cells, a cascade of processes underpinning hypoxia rescue and defense begins with an oxygen sensor (a heme protein) and a signal-transduction pathway, which leads to significant gene-based metabolic reprogramming-the rescue process-with maintained down-regulation of energy-demand and energy-supply pathways in metabolism throughout the hypoxic period. This recent work begins to clarify how normoxic maintenance ATP turnover rates can be drastically (10-fold) down-regulated to a new hypometabolic steady state, which is prerequisite for surviving prolonged hypoxia or anoxia. The implications of these developments are extensive in biology and medicine.

Oxygen sensors and energy sensors act synergistically to achieve a graded alteration in gene expression: Consequences for assessing the level of neuroprotection in response to stressors

Changes in gene expression are associated with switching to an autoprotected phenotype in response to environmental and physiological stress. Ubiquitous molecular chaperones from the heat shock protein (HSP) superfamily confer neuronal protection that can be blocked by antibodies. Recent research has focused on the interactions between the molecular sensors that affect the increased expression of neuroprotective HSPs above constitutive levels. An examination of the conditions under which the expression of heat shock protein 70 (Hsp70) was up regulated in a hypoxia and anoxia tolerant tropical species, the epaulette shark (Hemiscyllium ocellatum), revealed that up-regulation was dependent on exceeding a stimulus threshold for an oxidative stressor. While hypoxic-preconditioning confers neuroprotective changes, there was no increase in the level of Hsp70 indicating that its increased expression was not associated with achieving a neuroprotected state in response to hypoxia in the epaulette shark. Conversely, there was a significant increase in Hsp70 in response to anoxic-preconditioning, highlighting the presence of a stimulus threshold barrier and raising the possibility that, in this species, Hsp70 contributes to the neuroprotective response to extreme crises, such as oxidative stress. Interestingly, there was a synergistic effect of coincident stressors on Hsp70 expression, which was revealed when metabolic stress was superimposed upon oxidative stress. Brain energy charge was significantly lower when adenosine receptor blockade, provided by treatment with aminophylline, was present prior to the final anoxic episode, under these circumstances, the level of Hsp70 induced was significantly higher than in the pair-matched saline treated controls. An understanding of the molecular and metabolic basis for neuroprotective switches, which result in an up-regulation of neuroprotective Hsp70 expression in the brain, is needed so that intervention strategies can be devised to manage CNS pathologies and minimise damage caused by ischemia and trauma. In addition, the current findings indicate that measurements of HSP expression per se may provide a useful correlate of the level of neuroprotection achieved in the switch to an autoprotected phenotype.

Central-tapped node linked modular fault-tolerance topology for SRM applications

Electric vehicles (EVs) and hybrid electric vehicles (HEVs) can reduce greenhouse gas emissions while switched reluctance motor (SRM) is one of the promising motor for such applications. This paper presents a novel SRM fault-diagnosis and fault-tolerance operation solution. Based on the traditional asymmetric half-bridge topology for the SRM driving, the central tapped winding of the SRM in modular half-bridge configuration are introduced to provide fault-diagnosis and fault-tolerance functions, which are set idle in normal conditions. The fault diagnosis can be achieved by detecting the characteristic of the excitation and demagnetization currents. An SRM fault-tolerance operation strategy is also realized by the proposed topology, which compensates for the missing phase torque under the open-circuit fault, and reduces the unbalanced phase current under the short-circuit fault due to the uncontrolled faulty phase. Furthermore, the current sensor placement strategy is also discussed to give two placement methods for low cost or modular structure. Simulation results in MATLAB/Simulink and experiments on a 750-W SRM validate the effectiveness of the proposed strategy, which may have significant implications and improve the reliability of EVs/HEVs.

Shopping Cart System: Load Balancing and Fault Tolerance in the OSGi Service Platform

The main purpose of this paper was to find a simple solution for load balancing and fault tolerance in OSGi. The challenge was to implement a highly available web application such as a shopping cart system with load balancing and fault tolerance, without having to change the core of OSGi.

Early analysis of fault-attack effects for cryptographic hardware

International audience

Fault tolerance logging-based model for deterministic systems

Fault tolerance allows a system to remain operational to some degree when some of its components fail. One of the most common fault tolerance mechanisms consists on logging the system state periodically, and recovering the system to a consistent state in the event of a failure. This paper describes a general fault tolerance logging-based mechanism, which can be layered over deterministic systems. Our proposal describes how a logging mechanism can recover the underlying system to a consistent state, even if an action or set of actions were interrupted mid-way, due to a server crash. We also propose different methods of storing the logging information, and describe how to deploy a fault tolerant master-slave cluster for information replication. We adapt our model to a previously proposed framework, which provided common relational features, like transactions with atomic, consistent, isolated and durable properties, to NoSQL database management systems.

Plasmodium vivax: Induction of CD4(+)CD25(+)FoxP3(+) Regulatory T Cells during Infection Are Directly Associated with Level of Circulating Parasites

Circulation CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) have been associated with the delicate balancing between control of overwhelming acute malaria infection and prevention of immune pathology due to disproportionate inflammatory responses to erythrocytic stage of the parasite. While the role of Tregs has been well-documented in murine models and P. falciparum infection, the phenotype and function of Tregs in P. vivax infection is still poorly characterized. In the current study, we demonstrated that patients with acute P. vivax infection presented a significant augmentation of circulating Tregs producing anti-inflammatory (IL-10 and TGF-beta) as well as pro-inflammatory (IFN-gamma, IL-17) cytokines, which was further positively correlated with parasite burden. Surface expression of GITR molecule and intracellular expression of CTLA-4 were significantly upregulated in Tregs from infected donors, presenting also a positive association between either absolute numbers of CD4(+)CD25(+)FoxP3(+)GITR(+) or CD4(+)CD25(+)FoxP3(+)CTLA-4(+) and parasite load. Finally, we demonstrate a suppressive effect of Treg cells in specific T cell proliferative responses of P. vivax infected subjects after antigen stimulation with Pv-AMA-1. Our findings indicate that malaria vivax infection lead to an increased number of activated Treg cells that are highly associated with parasite load, which probably exert an important contribution to the modulation of immune responses during P. vivax infection.

Predictive factors of non-deterioration of glucose tolerance following a 2-year behavioral intervention

Aim: To identify predictive factors associated with non-deterioration of glucose metabolism following a 2-year behavioral intervention in Japanese-Brazilians. Methods: 295 adults (59.7% women) without diabetes completed 2-year intervention program. Characteristics of those who maintained/improved glucose tolerance status (non-progressors) were compared with those who worsened (progressors) after the intervention. In logistic regression analysis, the condition of non-progressor was used as dependent variable. Results: Baseline characteristics of non-progressors (71.7%) and progressors were similar, except for the former being younger and having higher frequency of disturbed glucose tolerance and lower C-reactive protein (CRP). In logistic regression, non-deterioration of glucose metabolism was associated with disturbed glucose tolerance impaired fasting glucose or impaired glucose tolerance - (p < 0.001) and CRP levels <= 0.04 mg/dL (p = 0.01), adjusted for age and anthropometric variables. Changes in anthropometry and physical activity and achievement of weight and dietary goals after intervention were similar in subsets that worsened or not the glucose tolerance status. Conclusion: The whole sample presented a homogeneous behavior during the intervention. Lower CRP levels and diagnosis of glucose intolerance at baseline were predictors of non-deterioration of the glucose metabolism after a relatively simple intervention, independent of body adiposity.

Evaluation of aluminium tolerance in grapevine rootstocks

Aluminum (Al) toxicity is a major worldwide agricultural problem. At low pH, Al speciates into the soluble and phyto-toxic form Al(3+), inhibiting the root growth and affecting plant development. In Brazil, agriculture in acidic soils with elevated concentration of Al has significantly increased in the last decades. Therefore, in order to achieve efficient agriculture practices, the selection of plant cultivars with improved Al resistance has become crucial in this type of soils. In this work we have evaluated the Al resistance of six genotypes of grapevine rootstocks. The grapevine hardwood cuttings were grown in nutrient solution in the absence and presence of 250 and 500 mu M Al at pH 4.2. The phenotypic indexes of relative root growth, fresh and dry root weight, root area, hematoxylin staining profile, and Al content were evaluated for all six genotypes. These phenotypic indexes allowed us to identify the `Kober 5BB`, `Gravesac`, `Paulsen 1103`, and `IAC 766` grapevine rootstocks genotypes as the ones with the highest resistance to Al. Likewise, `IAC 572` and `R110` genotypes were the most Al-sensitive cultivars. We evaluated the root organic acid exudation profile in the most Al-resistant (`Kober 5BB`) and most Al-sensitive (`R110`) in plantlets cultivated in vitro in the absence and presence of 100, 200, and 400 mu M of Al. Among several compounds detected, citrate was the only organic acid related to the Al resistance phenotype observed in the `Kober 5BB` genotype. The high constitutive citrate exudation observed in `Kober 5BB` strongly suggests that exudation of this particular organic acid may impart Al-resistance/a melioration in grapevine.

Pre and post-natal exposure to ambient level of air pollution impairs memory of rats: the role of oxidative stress

The aims of this study were to evaluate whether air pollution during pre-natal and post-natal phases change habituation and short-term discriminative memories and if oxidants are involved in this process. As secondary objectives, it was to evaluate if the change of filtered to nonfiltered environment could protect the cortex of rats against oxidative stress as well as to modify the behavior of these animals. Wistar, male rats were divided into four groups (n = 12/group): pre and post-natal exposure until adulthood to filtered air (FA); pre-natal period to nonfiltered air (NFA-FA); until (21st post-natal day) and post-natal to filtered air until adulthood (PND21); prenatal to filtered air until PND21 and post-natal to nonfiltered air until adulthood (FA-NFA); pre and post-natal to nonfiltered air (NFA). After 150 days of air pollution exposure, animals were tested in the spontaneous object recognition test to evaluate short-term discriminative and habituation memories. Rats were euthanized; blood was collected for metal determination; cortex dissected for oxidative stress evaluation. There was a significant increase in malondialdehyde (MDA) levels in the NFA group when compared to other groups (FA: 1.730 +/- 0.217; NFA-FA: 1.101 +/- 0.217; FA-NFA: 1.014 +/- 0.300; NFA: 5.978 +/- 1.920 nmol MDA/mg total proteins; p = 0.007). NFA group presented a significant decrease in short-term discriminative (FA: 0.603 +/- 0.106; NFA-FA: 0.669 +/- 0.0666; FA-NFA: 0.374 +/- 0.178; NFA: -0.00631 +/- 0.106 sec; p = 0.006) and an improvement in habituation memories when compared to other groups. Therefore, exposure to air pollution during both those periods impairs short-term discriminative memory and cortical oxidative stress may mediate this process.

High level of aspartic acid-bond isomerization during the synthesis of an N-linked tau glycopeptide

An increased degree of utilization of the potential N-glycosylation site In the fourth repeat unit of the human tau protein may be involved in the inability of tau to bind to the corresponding tubulin sequence(s) and in the subsequent development of the paired helical filaments of Alzheimer's disease. To model these processes, we synthesized the octadecapeptide spanning this region without sugar, and with the addition of an N-acetyl-glucosamine moiety. The carbohydrate-protected, glycosylated asparagine was incorporated as a building block during conventional Fmoc-solid phase peptide synthesis. While the crude non-glycosylated analog was obtained as a single peptide, two peptides with, the identical, expected masses, in approximately equal amounts, were detected after the cleavage of the peracetylated glycopeptide. Surprisingly, the two glycopeptides switched positions on the reversed-phase high performance liquid chromatogram after removal of the sugar-protecting acetyl groups. Nuclear magnetic resonance spectroscopy and peptide sequencing identified the more hydrophobic deprotected peak as the target peptide, and the more hydrophilic deprotected peak as a peptide analog in which the aspartic acid-bond just preceding the glycosylated asparagine residue was isomerized resulting in the formation of a beta-peptide. The anomalous chromatographic behavior of the acetylated beta-isomer could be explained on the basis of the generation of an extended hydrophobic surface which is not present in any of the other three glycopeptide variants. Repetition of the syntheses, with altered conditions and reagents, revealed reproducibly high levels of aspartic acid-bond isomerization of the glycopeptide as well as lack of isomerization for the non-glycosylated parent analog. If similar increased aspartic acid-bond isomerization occurs in vivo, a protein modification well known to take place for both the amyloid deposits and the neurofibrillary tangles in Alzheimer's disease, this process may explain the aggregation of glycosylated tau into the paired helical filaments in the affected brains. Copyright (C) 1999 European Peptide Society and John Wiley & Sons, Ltd.