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The most pathogenic transthyretin variant, L55P, forms amyloid fibrils under acidic conditions and protofilaments under physiological conditions.

The L55P transthyretin (TTR) familial amyloid polyneuropathy-associated variant is distinct from the other TTR variants studied to date and the wild-type protein in that the L55P tetramer can dissociate to the monomeric amyloidogenic intermediate and form fibril precursors under physiological conditions (pH 7.0, 37 degrees C). The activation barrier associated with L55P-TTR tetramer dissociation is lower than the barrier for wild-type transthyretin dissociation, which does not form fibrils under physiological conditions. The L55P-TTR tetramer is also very sensitive to acidic conditions, readily dissociating to form the monomeric amyloidogenic intermediate between pH 5.5-5.0 where the wild-type TTR adopts a nonamyloidogenic tetrameric structure. The formation of the L55P monomeric amyloidogenic intermediate involves subtle tertiary structural changes within the beta-sheet rich subunit as discerned from Trp fluorescence, circular dichroism analysis, and ANS binding studies. The assembly of the L55P-TTR amyloidogenic intermediate at physiological pH (pH 7.5) affords protofilaments that elongate with time. TEM studies suggest that the entropic barrier associated with filament assembly (amyloid fibril formation) is high in vitro, amyloid being defined by the laterally assembled four filament structure observed by Blake upon isolation of "fibrils" from the eye of a FAP patient. The L55P-TTR protofilaments formed in vitro bind Congo red and thioflavin T (albeit more weakly than the fibrils produced at acidic pH), suggesting that the structure observed probably represents an amyloid precursor. The structural continuum from misfolded monomer through protofilaments, filaments, and ultimately fibrils must be considered as a possible source of pathology associated with these diseases.

Amyloid↗

Conditionals and conditional probability.

The authors report 3 experiments in which participants were invited to judge the probability of statements of the form if p then q given frequency information about the cases pq, p not q, not pq, and not p not q (where not = not). Three hypotheses were compared: (a) that people equate the probability with that of the material conditional, 1 - P(p not q); (b) that people assign the conditional probability, P(q/p); and (c) that people assign the conjunctive probability P(pq). The experimental evidence allowed rejection of the 1st hypothesis but provided some support for the 2nd and 3rd hypotheses. Individual difference analyses showed that half of the participants used conditional probability and that most of the remaining participants used conjunctive probability as the basis of their judgments.

Color Perception↗

Postponed reproduction as an adaptation to winter conditions in Drosophila melanogaster: evidence for clinal variation under semi-natural conditions.

Patterns of climatic adaptation in drosophila and other insects have largely been inferred from laboratory comparisons of traits that vary clinally. Here, we extend this research to comparisons under semi-natural conditions. To test for clinal variation in reproductive patterns and survival over winter, Drosophila melanogaster populations were initiated from seven collection sites along the eastern coast of Australia, ranging from tropical to temperate regions. The fecundity and survival of these populations were monitored in field cages at a temperate location until all adults had died more than 5 months later. Total fecundity showed a curvilinear relationship with latitude, due to higher egg production by high- and low-latitude populations. Adults from temperate locations survived winter conditions better than those from subtropical populations but not tropical ones. There was a linear cline in the timing of egg production: temperate populations produced eggs later than populations from lower latitudes. This cline is likely to be adaptive because egg-to-adult viability experiments indicated that only eggs laid in spring developed successfully to the adult stage. There was no evidence for climatic adaptation in the immature stages. The adult mortality rate increased gradually over winter, and in some populations was also correlated with the minimum ambient temperature. These results indicate that adaptation to winter conditions in D. melanogaster has involved shifts in reproductive patterns.

Acclimatization↗

Principles and design of a novel magnetic force mechanical conditioning bioreactor for tissue engineering, stem cell conditioning, and dynamic in vitro screening.

Mechanical conditioning of cells and tissue constructs in bioreactors is an important factor in determining the properties of tissue being produced. Mechanical conditioning within a bioreactor environment, however, has proven difficult. This paper presents the theoretical basis, design, and initial results of a mechanical conditioning system for cell and tissue culture which is based on biocompatible magnetic micro- and nanoparticles acting as a remote stress mechanism without invasion of the sterile bioreactor environment.

Bioreactors↗

Oral conditions and aptitude to receive implants in patients with removable partial dentures: a cross-sectional study. part I. oral conditions.

The relationship between a removable partial denture (RPD) and damage caused to residual oral structures is the subject of on-going research. A group of patients wearing RPD, treated in the same way in the same department, were recalled to evaluate their oral hygiene and to compare the clinical condition of abutment teeth with that of non-abutment teeth. The study shows that most patients were unable to maintain high standards of oral hygiene. In the group of patients with non-optimal hygiene the clinical condition of abutment teeth was worse than that of non-abutment teeth. In the group of patients with optimal oral hygiene the condition of abutment teeth and non-abutment teeth was almost identical. To increase the standards of oral hygiene it is strongly advisable to recall and follow up patients on a regular basis.

Aged↗

Conditioning of extrasystoles in humans with respiratory maneuvers as conditional stimulus.

Extrasystoles are known to occur in some healthy individuals during common respiratory maneuvers such as holding the breath. Evidence is presented which shows that under controlled laboratory conditions this kind of extrasystole can be conditioned. Conditional stimuli signaling inspiration and expiration acquired the properties of the respiratory maneuvers by inducing extrasystoles during normal breathing.

Biological Phenomena↗

Effects of experimental conditions on mycorrhizal relationships between Pinus sylvestris and Lactarius deliciosus and unprecedented fruit-body formation of the Saffron milk cap under controlled soilless conditions.

The mycorrhizal relationships between pines and two edible species of Lactarius sect. Dapetes were investigated by optimizing the experimental conditions of mycelial growth and of mycorrhizal colonization of pine seedlings. In vitro mycelial growth of Lactarius deliciosus and L. sanguifluus was improved on a buffered medium containing glucose, amino acids, and vitamins. Two methods of mycorrhization of pines with Lactarius deliciosus were tested. The mycorrhizal colonization was rapid and intense under non-aseptic conditions with a low nutrient supply and without exogenous glucose. A positive influence of mycorrhizal colonization on Pinus sylvestris growth was subsequently observed. Under axenic conditions and with a high nutrient supply, mycorrhization was stimulated at 10 g/L of exogenous glucose, irrespective of the phosphorus concentration. At high phosphorus level (1 mM) and 0.1, 1.0, or 10.0 g/L glucose, growth of Pinus sylvestris was reduced by inoculation. Stability and development of Pinus spp./Lactarius deliciosus symbioses were assayed in a climatic chamber using containers filled with a synthetic substrate. Over a 2-year culture period, the root systems of the pine seedlings were heavily colonized by Lactarius deliciosus. One year following inoculation, Lactarius deliciosus fruit-body primordia appeared associated with Pinus sylvestris seedlings. Six months later, two mature basidiomata were obtained. This is the first report of soilless fruit-body formation of this edible mushroom.

Basidiomycota↗

Isolation of bacteria degrading carbazole under microaerobic conditions, i.e. nitrogen gas substituted conditions.

Microorganisms degrading carbazole (CA), a model substrate of heterocyclic nitrogen compounds in crude petroleum oil, were screened under microaerobic conditions, i.e. nitrogen gas substituted conditions. Eight bacteria were isolated and identified. For example, Bacillus sp. KUKK-4 degraded 31% of CA when cultivated for 28 days in a medium initially containing CA at 1000 mg/l with shaking under the microaerobic conditions.

Aerobiosis↗

Characterization of conditionally expressed mutants affecting age-specific survival in inbred lines of Drosophila melanogaster: lethal conditions and temperature-sensitive periods.

The specific genetic basis of inbreeding depression is poorly understood. To address this question, two conditionally expressed lethal effects that were found to cause line-specific life span reductions in two separate inbred lines of Drosophila melanogaster were characterized phenotypically and genetically in terms of whether the accelerated mortality effects are dominant or recessive. The mortality effect in one line (I4) is potentially a temperature-sensitive semilethal that expresses in adult males only and is partially dominant. The other line (I10) responds as one would expect for a recessive lethal. It requires a cold shock for expression and is cold sensitive. Flies exhibiting this lethal condition responded as pupae and freshly eclosed imagoes. The effect is recessive in both males and females. The expression of the lethal effects in both lines is highly dependent upon environmental conditions. These results will serve as a basis for more detailed and mechanistic genetic research on inbreeding depression and are relevant to sex- and environment-specific effects on life span observed in quantitative trait loci studies using inbred lines.

Animals↗

A preliminary analysis of the effects of prior classroom conditions on performance under analogue analysis conditions.

We systematically manipulated two prior classroom conditions to explore their effects on performance under analogue assessments for a 7-year-old girl with severe intellectual disabilities who exhibited aggressive behavior. Results demonstrated consistently higher levels of aggression during demand analogue conditions when they were preceded by one of the classroom conditions.

Aggression↗

Positive conditioned suppression: conditioned suppression using positive reinforcers as the unconditioned stimuli.

Research has revealed the phenomenon of conditioned suppression in which the rate of responding is reduced during a stimulus that is paired with noncontingent shock. The present study replicated this procedure, but used noncontingent positive reinforcers instead of the aversive shock. The lever-pressing responses of rats were reinforced with food or water. While the rats were responding, a stimulus was occasionally presented and paired with the delivery of a noncontingent positive reinforcer, which was either food, water, or brain stimulation for different rats. The result was a reduction in the rate of responding during the conditioned stimulus. This finding shows that conditioned suppression occurs during a signal for reinforcing as well as aversive stimuli.

Journal Article↗

Measurements of the air conditioning capacity of the nose during normal and pathological conditions and pharmacological influence.

A simple method is introduced for measuring the air conditioning capacity of the nose. A flow of 8 1/min dry air is introduced by a catheter into the nasopharynx, while 5 1/min is sucked out from the investigated nasal cavity through a psychrometer. The additional 3 1/min passes down into the pharynx, thus reducing the intermingling with expiratory air. By using CO2 as a tracer, this error was found to be maximally 15% and often about 1%. The three different enthalpy factors: increase in enthalpy of dry air, vaporization, and increase in enthalpy of water vapour, were calculated separately and the vaporization was found to be the dominant factor. The calculated total supply of humidity showed that the method presented causes at least a slight stress on the humidifying capacity. Pharmacological studies have shown that subcutaneously injected atropine decreased the total enthalpy and that of water vapour, while nasal administration of oximetazoline also decreased the total enthalpy. Nasal administration of homatropine or pilocarpine had no effect on the air conditioning. In comparison with normal subjects, those with vasomotor rhinitis had an increased enthalpy of the air, while the same enthalpy factor was reduced in cases with atrophic rhinitis. Laryngectomized patients had no significant difference in the air conditioning capacity of the nose in relation to normal subjects, while patients operated with partial maxillectomy had a considerable reduction in vaporization and total enthalpy.

Atropine↗

Nondiseased dentinal root surface following citric acid or tetracycline hydrochloride conditioning: a scanning electron microscopic study on the effects of ultrasonic irrigation before and after root conditioning.

The scanning electron microscope was used to evaluate the effects of ultrasonic irrigation before and after root conditioning. Six groups of five specimens each received saline irrigation; ultrasonic irrigation; saline irrigation followed by root conditioning with either citric acid or tetracycline hydrochloride; or ultrasonic irrigation followed by root conditioning with either citric acid or tetracycline hydrochloride. After immersion in citric acid or tetracycline hydrochloride solutions, root dentin was rinsed again with saline or irrigated ultrasonically. Control specimens exhibited an amorphous, irregular surface smear layer. Ultrasonic irrigation, citric acid, and tetracycline hydrochloride were effective in removing the smear layer. Use of ultrasonic irrigation before and after acid application improved the exposure of dentinal fibrils.

Acid Etching, Dental↗

Effect of melatonin on the isolated heart in the standard perfusion conditions and in the conditions of calcium paradox.

UNLABELLED: The effect of melatonin (MLT) on the isolated rat heart was studied using the standard perfusion conditions (Langendorff preparation) and model of calcium paradox (Ca(2+)-paradox). Ca(2+)-paradox was induced by 1 minute perfusion with Ca(2+)-free Krebs-Henseleit (KH) solution and subsequent 20 minutes perfusion with a normal Ca(2+)-containing KH solution. In MLT group, MLT (10 micromol/l) was in the perfusion solution throughout the experiment. In controls, there was no MLT. VARIABLES: heart rate, coronary flow, systolic and diastolic pressure, +dP/dt max (index of contractility) and -dP/dt max (index of relaxation) were measured at the end of stabilization, i.e. after 30 minutes of standard perfusion and then in the 5th, 10th, 15th, 20th minute after perfusion with Ca(2+)-free KH solution. RESULTS: There was no difference between MLT group and controls in the standard perfusion conditions at the end of stabilization. After perfusion with Ca(2+)-free KH solution, systolic-diastolic difference (in the 10th, 15th, 20th minute), +dP/dt max (in the 5th, l0th, 15th, 20th minute) and -dP/dt max (in the 15th minute) were significantly decreased in MLT group in comparison to controls. CONCLUSION: Melatonin didn't influence rat isolated heart in standard perfusion conditions but it made the heart more susceptible to Ca(2+)-paradox.

Animals↗

Oral diseases and conditions throughout the lifespan. I. Diseases and conditions directly associated with tooth loss.

This is the first of two articles providing an overall view of oral diseases and conditions, taking the oral cavity and its organs and tissues as integrated parts of the human body. This article provides an overview of three oral diseases and conditions that are associated directly with loss of tooth structure or loss of teeth and reviews their risk factors and preventive and treatment interventions. Two of these conditions, dental caries and periodontal diseases (or their sequelae), remain the main cause of tooth loss in the U.S. Prevention, treatment, and control of these diseases require many hours of training during dental education and many hours of treatment in dental practice. The profession has fragmented into specialties based on diseases; as a result, many dentists fail to see them as integral elements of the human experience. As primary care specialists, dentists must be reminded that they need to make prevention the first choice, provide the best treatment possible based on available scientific evidence, and keep informed of new advances in research while always remembering that the oral cavity is an integral part of the human body. The changes and trends observed in the epidemiology of oral diseases will demand new skills in our dental graduates. Future dental graduates may achieve a solid understanding of oral diseases at both the biological and population level by using oral tissues and saliva to diagnose systemic diseases, relying on medical facilities to order laboratory tests, and diagnosing and treating patients in close collaboration with their medical colleagues.

Dental Caries↗

Disrupted retention of the classically conditioned nictitating membrane response in the aluminum-intoxicated rabbit using electrical stimulation of the brain as a conditioned stimulus.

Rabbits were classically conditioned to emit an eyeblink conditioned response (CR) to electrical stimulation (ESB) of the medial geniculate nucleus (MGN) paired with a corneal air puff until they attained a criterion of two consecutive days of greater than 90% CRs. They then received intraventricular injections of 1% AlCl3, HCL, or normal saline. Ten days postinjection, each animal underwent a retention test consisting of 50 ESB alone presentations. Whereas all saline and HCL animals gave at least 90% CRs during retention, no aluminum rabbit emitted more than 30% CRs. Considered with the results of previous work, these data suggest that aluminum-induced neurofibrillary degeneration disrupts retention of the CR by affecting central associative processes.

Albinism↗

Olfactory conditioning experiments in a food-searching passerine bird in semi-natural conditions.

Because passerine birds have a very small relative olfactory bulb size, they have been considered to have weak olfactory capacities for decades. Recent investigations however suggest that breeding female blue tits (Parus caeruleus) are sensitive to lavender odour in the reproductive context of building and maintaining the nest. Here, we present results of an olfactory conditioning experiment in blue tits held in semi-natural conditions during the breeding season. We show that captive male blue tits, trained to associate lavender odour with a food reward, are more attracted to an empty feeder box emitting lavender odour than an odourless empty feeder box. Females did not distinguish significantly between empty feeders with and without lavender odour during the test phase, although they responded positively at the end of the training phase. These results suggest that male blue tits can use olfaction in a context not related to nest building. Additional experiments will be required to better understand the observed sex differences in response to the experimental set up, and in what context free-ranging individuals use olfaction.

Animals↗

Effects of differential rearing condition on heart rate conditioning and response suppression.

Rats were reared in either an enriched or isolated environment for 60 days following weaning. Neither rearing environment nor sex affected heart rate conditioning. However, when the CS used during conditioning was subsequently presented in a drinking situation, males reared in isolation showed a greater degree of response suppression than did similarly reared females. Males and females reared in the enriched environment did not differ in degree of response suppression.

Acoustic Stimulation↗