Increased level of DJ-1 in the cerebrospinal fluids of sporadic Parkinson's disease

DJ-1 is an antioxidant protein whose loss of function by gene mutations has been linked to familial Parkinson's disease (PD). The main objective of the present study was to determine if this molecule was also involved in the pathogenesis of sporadic PD. For this purpose, quantitative immunoblot assays were performed to evaluate DJ-1 in cerebrospinal fluids (CSF) collected from sporadic PD patients (n=40) and non-PD controls (n=38). The results showed that the CSF DJ-1 levels in PD were significantly higher than those in non-PD controls. Especially, upregulation of CSF DJ-1 in the early stage of PD (Yahr I-II) were distinct compared to those in the advanced stage of PD (Yahr III-IV) and non-PD controls (p<0.001 by ANOVA with post hoc Bonferroni's test), suggesting a protective role of DJ-1 against oxidative stress during the early stage. Thus, we propose that CSF DJ-1 could be a possible biomarker for early sporadic PD.     

Taste function in patients with oral burning

Burning mouth syndrome (BMS) is an oral pain disorder occurring primarily in post-menopausal women and is frequently accompanied by taste complaints. This association of symptoms suggests an interaction between the mechanisms of nociception and gustation, two senses with strong hedonic components. Seventy-three patients of the Taste and Smell Clinic at the University of Connecticut Health Center who reported experiencing 'unexplained oral burning' were evaluated for taste function. Both intensity ratings and quality identifications were measured for a concentration series of sucrose ('sweet'), NaCl ('salty'), citric acid ('sour') and quinine-HCl ('bitter'). The 57 women with BMS gave lower intensity ratings to NaCl and sucrose than comparably aged, same sex controls. Concentrations of NaCl and sucrose >0.10 M were most affected; concentrations of sucrose and NaCl <0.10 M were rated similarly by BMS and control women. No intensity differences were found for citric acid or quinine-HCl at any concentration and no differences were evident between the 16 BMS men and the 14 control men for any stimulus. The BMS women also misidentified the quality of 19% of the stimuli that were detected whereas control women misidentified 8%. Both groups detected a similar proportion of stimuli and found lower stimulus concentrations more difficult to identify than higher concentrations. Identification of NaCl as 'salty' and citric acid as 'sour' was particularly difficult for BMS women. The present findings are consistent with the hypothesis that pain pathway activation may affect neural and behavioral taste function.     

Water restriction and fluid temperature alter preference for water and sucrose solutions

The role of diet temperature in ingestive behavior is poorly understood. We examined the importance of stimulus temperature and water-restriction state on the preference for and intake of water and sucrose. Using custom-designed equipment that allows us to monitor and maintain solution temperatures during testing (±0.1 °C), we conducted a series of 2-bottle preference tests (10 °C water vs. sucrose 10-40 °C) and brief access tests (10-40 °C water and sucrose). Water-restricted rats preferred cold water over any sucrose concentration (0.0-1.0 M) if the sucrose was 30 or 40 °C, whereas the same rats preferred sucrose at all concentrations and temperatures when unrestricted suggesting that the water-restriction state interacts with temperature preference. In a series of brief-access tests using a Davis Rig (MS-180), rats reduced licking to cold sucrose compared with 20 °C sucrose, suggesting that unlike water, cold temperature reduced the palatability of sucrose.     

Serum miR-30c-5p is a potential biomarker for multiple system atrophy

Multiple system atrophy (MSA) is a neurodegenerative disease that belongs to the α synucleinopathies. Clinically, there is an overlap between MSA and Parkinson’s disease (PD), especially at the early disease stage. However, these two pathologies differ in terms of disease progression. Currently, no biomarker exists to differentiate MSA from PD. MicroRNAs are non-coding RNAs implicated in gene expression regulation. MiRNAs modulate cellular activity and they control a range of physiological and pathological functions. miRNAs are found in biofluids, such as blood, serum, plasma, saliva, and cerebrospinal fluid. Many groups, including ours, found that circulating miRNAs are differently expressed in blood, plasma, serum and cerebrospinal fluid of PD and MSA patients. In the present study, our primary aim was to determine if serum mir-30-5p and mir-148b-5p can be used as biomarkers for early diagnosis of PD and/or MSA. Our secondary goal was to determine if serum levels of those miRNAs can be correlated with the patients’ clinical profile. Using quantitative PCR (qPCR), we evaluated expression levels of miR-30c-5p and miR148b-5p in serum samples from PD (n?=?56), MSA (n?=?49), and healthy control (n?=?50) subjects. We have found that miR-30c-5p is significantly upregulated in MSA if compared with PD and healthy control subjects. Moreover, serum miR-30c-5p levels correlate with disease duration in both MSA and PD. No significant difference was found in miR-148b-5p among MSA, PD and healthy control subjects. Our results suggest a possible role of serum miR-30-5p as a biomarker for diagnosis and progression of MSA.

     

Binary taste mixture interactions in prop non-tasters, medium-tasters and super-tasters

It is generally assumed that the mutual, but asymmetric, suppression of the components in binary taste mixtures is an invariant property of the human psychophysical response to such mixtures. However, taste intensities have been shown to vary as a function of individual differences in sensitivity, indexed by the perceived bitterness of 6-n-propylthiouracil (PROP). To determine if these variations in taste perception influence taste mixture interactions, groups of PROP super-, medium- and non-tasters assessed four binary taste mixtures: sweet-bitter [sucrose/quinine hydrochloride (QHCl)], sweet-sour (sucrose/citric acid), salty-bitter (NaCl/QHCl) and salty-sour (NaCl/citric acid). In each experiment, subjects received factorial combinations of four levels of each of two tastants and rated individual taste intensities and overall mixture intensity. For each taste quality, super-tasters typically gave higher ratings than either medium- or non-tasters, who tended not to differ. There were also group differences in the interactions of the mixtures' components. Super-tasters rated the overall intensity of the mixtures, most likely reflecting integration of the taste components, as greater than medium- and non-tasters, who again showed few differences. In sweet-bitter mixtures, non-tasters failed to show the suppression of sweetness intensity by the highest QHCl concentration that was evident in super- and medium-tasters. These data show that the perception of both tastes and binary taste mixture interactions varies as a function of PROP taster status, but that this may only be evident when three taster groups are clearly distinguished from one another.     

NaCl detection thresholds: comparison of Fischer 344 and Wistar rats

Adult Fischer 344 (F344) rats fail to display any preference for NaCl solutions at concentrations typically preferred by other rat strains. To determine whether this behavior is due to a strain difference in NaCl detection threshold, a conditioned taste aversion (CTA) was first established to a suprathreshold concentration of NaCl (0.1 M). Then, a series of dilute NaCl solutions, ranging from 0.0 to 0.011 M NaCl, were presented to F344 (n = 16) and Wistar (n = 16) rats. The lowest concentration at which there was a reliable difference in the preference scores of conditioned and control rats was defined as the detection threshold. Results indicate that the detection threshold for NaCl lies between 0.001 and 0.002 M NaCl for both F344 and Wistar rats. The addition of the sodium channel blocker amiloride to the NaCl solutions raised the detection threshold 10-fold to 0.03-0.04 M NaCl for both strains of rats. These results suggest that the NaCl detection thresholds of F344 and Wistar rats are similar and that these strains do not differ in the degree to which amiloride raises this threshold.     

Rated taste perception in two cultural groups

Intensity and pleasantness ratings of various concentrationsof sucrose, caffeine and NaCl were examined in two culturallydifferent groups of subjects. One group was made up of studentsof European descent born in the United States while the othergroup was made up of students of Chinese descent born in Taiwan.A subsample of subjects from each group was retested similarlywith cookies containing varying levels of sucrose. The Taiwanesesubjects rated sucrose as tasting sweeter regardless of whetherit was in solution or cookies. Group differences in pleasantnessratings depended upon whether the sucrose was presented in acookie or a solution. The Taiwanese students assigned highersweetness ratings to sucrose in solution when compared to USstudents. When the sucrose was in cookies, the Taiwanese groupassigned higher pleasantness ratings at the lower sucrose concentrations.At the higher sucrose concentrations, the US group assignedhigher pleasantness ratings. There was no significant ethniceffect upon rated bitterness or pleasantness of caffeine. Taiwaneserated low concentrations of salt as tasting saltier and highconcentrations of salt as tasting less salty when compared toUS students. The Taiwanese generally rated the sodium chloridesolutions as tasting more pleasant. These group differencesmay be related to the way sucrose and salt are used in the twocultures.     

Taste responses of Drosophila melanogaster

The amounts of sugar solution consumed by Drosophila melanogaster flies were determined. Starved and desiccated flies of a wild type strain (QA) consume 7?9 × 10^?2 λ of a 0.3 M sucrose solution per fly during the first hour and less later. They consume more of the 0.3 M sucrose solution than of the more diluted and the more concentrated solutions. In preference-aversion tests the flies discriminated between water and various sugar solutions, and between different sugar concentrations. Contrary to other fly species these flies did not prefer 0.05 M fructose over 0.05 M glucose. 0.3–0.5 M NaCl added to 0.1 M sucrose turned a preference over 0.01 sucrose into an aversion. A mutant, Lot-94, selected for its increased consumption of a 1 M NaCl solution was found to consume more of all test solutions. The amount of NaCl that had to be added to 0.1 M sucrose to turn the preference over 0.01 M sucrose by the mutant flies into aversion was not different from that found for the wild type flies.     

Taste perception and diet in individuals with Chinese and European ethnic backgrounds

Relationships between taste perception and diet were investigatedin two ethnic groups. The Chinese subjects (n = 30) were bornin the People's Republic of China and were currently livingin the United States. The U.S. subjects (n = 30) were of Europeanancestry. Psychophysical taste intensity functions for sucrosesolutions, NaCl solutions and NaCl in soup were obtained usingmagnitude matching. Pleasantness ratings for the above stimuli,plus sucrose in cookies and NaCl in crackers were obtained usingcategory rating scales. Three-day dietary records and the frequencyof sweet food consumption were also collected. Chinese subjectsassigned higher pleasantness ratings to the higher concentrationsof sucrose in water and showed a tendency to rate sucrose incookies as tasting more pleasant. These higher pleasantnessratings of sucrose were not reflected in increased sugar intake.The Chinese subjects also assigned higher pleasantness ratingsto and preferred higher concentrations of salt in crackers andthis was reflected in the data from the dietary records. TheChinese Na/Kcal and Na/K ratios were greater than those of theU.S. group.     

帕金森病衣架样疼痛及治疗策略

目的:衣架样疼痛(coat-hanger ache,CHA)是帕金森病(Parkinson disease,PD)疼痛的一个少见类型,本文研究帕金森病合并衣架样疼痛的血压状况及治疗策略。方法:本文以15例伴有CHA的PD患者为研究对象,以不伴有CHA年龄、性别大致匹配的PD病人为对照,观察两组病人卧立位血压的变化及CHA组直立后出现疼痛的时间和评分,找到相应的治疗措施。结果:CHA组伴有体位性低血压(orthostatic hypotension,OH)的比例为80%,明显高于对照组(33%),站立后出现疼痛的时间为7.2±1.2,疼痛评分为3.5±2.1,给予改善OH的物理及药物治疗,大部分DHA病人有效。结论:PD病人伴有CHA可能与OH有关,改善血压状况后部分有效。     

Effect of taste deafferentation on the preference for solutions of saccharose, saccharin and salt in rats

The preference of sucrose, saccharin and salt solutions to water was analyzed during 5 days in rats with bilateral section of the lingual nerve comprising the taste nerve--chorda tympani. In the process of the analysis of daily consumption and choice of solutions, different types of behavioural reactions were found: stable preference and change of preference. The number of rats preferring NaCl was greater among the animals with sectioned lingual nerve than among sham-operated control rats and rats with ligated ducts of submaxillary and sublingual salivary glands. The number of rats with the lingual nerve section preferring sucrose or saccharin solutions to water was equal to that among the sham-operated rats. At the same time the mean volume of sucrose solution taken in daily by rats with sectioned lingual nerve was twice as great as the volume of saccharin, drunk by the same animals. The role of taste in the process of choice and preference of NaCl to sweet solutions is discussed.     

Amiloride-sensitive signals and NaCl preference and appetite: a lick-rate analysis

Rats prefer hypotonic and isotonic NaCl solutions to water in long-access drinking paradigms. To focus on the role of taste signals in NaCl preference, licking patterns of rats with 30-s exposure to NaCl solutions (0-0.5 M) were examined when they were either water deprived, sodium depleted, or not deprived (NaCl mixed in dilute sucrose). In all three conditions, rats displayed a preference for NaCl. The addition of 100 microM amiloride, a sodium channel blocker, to NaCl did not change rats' licking when they were sodium replete but dramatically reduced licking when they were deplete. Transection of the chorda tympani (CT) nerve, an afferent pathway for amiloride-sensitive Na(+) signals, had no effect on NaCl preference in nondeprived rats and only a modest effect on those that were Na(+) deplete. Amiloride was found to exert significant suppression of NaCl intake in Na(+)-depleted rats with transection of the CT, supporting the existence of other afferent pathways for transmission of amiloride-sensitive Na(+) signalling. Together, these studies argue for the involvement of different neural signalling mechanisms in NaCl preference in the presence and absence of explicit Na(+) need.     

Induction of salivary gurmarin-binding proteins in rats fed gymnema-containing diets.

Gymnema sylvestre, a tropical plant, contains gurmarin that selectively suppresses sucrose responses of the chorda tympani nerve in rats and mice. We investigated preference for taste solutions and saliva composition in rats fed a diet containing this plant (gymnema diet). Preference for 0.01 M sucrose and a mixture of 0.03 M sucrose and 0.03 mM quinine-HCl significantly decreased at 1-2 days after the start of the gymnema diet and subsequently returned closely to the control levels within about a week. There was no significant change in preference for NaCl, monosodium glutamate and quinine-HCl during feeding trials. Submandibular saliva of rats fed the gymnema diet for 4 and 14 days showed an inhibitory effect on immunoreaction between gurmarin and antigurmarin serum. Analyses using electrophoresis and affinity chromatography indicated that the saliva contains gurmarin binding proteins with molecular weights of 15, 16, 45, 60 and 66 kDa. These results suggest that reduction of preference for sucrose was probably caused by gurmarin contained in the gymnema diet and subsequent restoration of the preference may be due to suppression of the effect of gurmarin by salivary gurmarin-binding proteins induced by the gymnema diet.     

The conformational properties of sucrose in aqueous solution: intramolecular hydrogen-bonding

A detailed analysis is presented of the nuclear (¹H and ¹³C) magnetic resonance (n.m.r.) properties of sucrose, using both D₂O and dimethyl sulfoxide-d₆ as solvents, based on measurements of coupling constants, chemical shifts, T₁ relaxation times, and nuclear Overhauser enhancements. Molecular modelling (HSEA calculations) suggests a strong conformational preference about the glycosidic linkages that is near to that for sucrose in the crystalline state, and this conformational rigidity is fully supported by the n.m.r. data, in terms of lack of influence of changes in concentration and temperature on the relevant n.m.r. parameters. The restricted rotation for the 1-hydroxymethyl group of the fructose residue is related to the persistence of the intramolecular hydrogen-bond between O-1^f and O-2^g. The presence of this bond was established for solutions in (CD₃)₂SO by the observation of isotopic chemicashifts on partial deuteration of the hydroxyl groups. The orientation of the 6-hydroxyl methyl group of the fructose residue is not that present in the crystalline state but, in (CD₃)₂SO, it may be intramolecularly hydrogen-bonded, as was demonstrated by titration of the hydroxyl groups with CD₃OD. Observations are made regarding hydrophobic topographies common to sucrose, saccharin, and 1-chloro-1-deoxysucrose, which may have a bearing on sweetness.     

An antigen capture assay for the measurement of serum clusterin concentrations

We have developed and validated a robust antigen capture assay for the measurement of serum clusterin. Increased clusterin expression, and alterations in serum clusterin levels have been associated with a number of disease states. In particular, clusterin has been shown to be associated with tissue regression and apoptosis in the rat ventral prostate in response to androgen ablation or administration of anti-androgens. The object of this study was to determine if changes in human serum clusterin can be used as a diagnostic or prognostic marker to monitor the response to hormonal therapy in patients with prostate cancer, and to determine if clusterin concentrations increase with the progression towards androgen independence. The antigen capture assay was used for an extensive analysis of human serum clusterin concentration in fasting males, and to determine if there is any relationship between clusterin and age or cholesterol levels. The average clusterin level in serum is 101+/-42 microg/ml (n=96). There is no correlation to age or serum cholesterol levels. Analysis of serum clusterin levels in patients with newly diagnosed prostate cancer (n=5), hormone responsive tumors (n=5), and hormone refractory disease (n=5), demonstrates that no significant changes in serum clusterin levels accompany the progression of prostatic disease, or response to hormone therapy.     

Sucrose transport into the phloem of Ricinus communis L. seedlings as measured by the analysis of sieve-tube sap

Careful cutting of the hypocotyl of Ricinus communis L. seedlings led to the exudation of pure sieve-tube sap for 2–3 h. This offered the possibility of testing the phloem-loading system qualitatively and quantitatively by incubating the cotyledons with different solutes of various concentrations to determine whether or not these solutes were loaded into the sieve tubes. The concentration which was achieved by loading and the time course could also be documented. This study concentrated on the loading of sucrose because it is the major naturally translocated sieve-tube compound. The sucrose concentration of sieve-tube sap was approx. 300 mM when the cotyledons were buried in the endosperm. When the cotyledons were excised from the endosperm and incubated in buffer, the sucrose concentration decreased gradually to 80–100 mM. This sucrose level was maintained for several hours by starch breakdown. Incubation of the excised cotyledons in sucrose caused the sucrose concentration in the sieve tubes to rise from 80 to 400 mM, depending on the sucrose concentration in the medium. Thus the sucrose concentration in the sieve tubes could be manipulated over a wide range. The transfer of labelled sucrose to the sieve-tube sap took 10 min; full isotope equilibration was finally reached after 2 h. An increase of K⁺ in the medium or in the sieve tubes did not change the sucrose concentration in the sievetube sap. Similarly the experimentally induced change of sucrose concentration in the sieve tubes did not affect the K⁺ concentration in the exudate. High concentrations of K⁺, however, strongly reduced the flow rate of exudation. Similar results were obtained with Na⁺ (data not shown). The minimum translocation speed in the sieve tubes in vivo was calculated from the growth increment of the seedling to be 1.03 m·h^-1, a value, which on average was also obtained for the exudation system with the endosperm attached. This comparison of the in-vivo rate of phloem transport and the exudation rate from cut hypocotyls indicates that sink control of phloem transport in the seedlings of that particular age was small, if there was any at all, and that the results from the experimental exudation system were probably not falsified by removal of the sink tissues.Abbreviations PTS 3-hydroxy-5,8, 10-pyrenetrisulfonate     

Physiology of feeding-preference patterns of female black blowflies (Phormia regina Meigen): Modification in responsiveness to salts subsequent to salt feeding

Behavioural experimentation on Phormia regina shows that females previously fed only sucrose, and thus in a state of yeast preference, will ingest single-salt-sucrose mixtures in volumes similar to that of 10% yeast (Rachman et al., 1982). In particular, females will ingest NaCl 0.1 M in 0.2 M sucrose in volumes not statistically different from 10% yeast. In the experiments reported here, groups of females were given ad libitum access to both 0.2 M sucrose and NaCl 0.1 M in 0.2 M sucrose from days 0–4 after eclosion. Potassium and sodium salts were added to 0.2 M sucrose over a spectrum of concentrations and presented to the flies on day 6. The flies rejected all single-salt-sucrose mixtures offered. Even when the pre-test sodium salt was changed to a potassium salt during days 0–4, the flies still rejected the single-salt-sucrose mixtures offered subsequently. However, when sodium and potassium salts were mixed together in 0.2 M sucrose, females ingested the solutions in amounts similar to 10% yeast. Several different concentrations of the double-salt-sucrose solutions were ingested in volumes not statistically different from 10% yeast. Results support the underlying hypothesis that activity in the salt-sensitive chemosensory neurones is involved in protein preference.     

Influence of physical exercise on human preferences for various taste solutions

The effects of physical exercise on preference for various sapid solutions was studied in 58 healthy university students. After 30 min of exercise using a bicycle ergometer at 50% VO2max (maximal oxygen uptake) intensity, a rating scale test on taste hedonic tone and the triangle test for taste absolute threshold were done. The test solutions were sucrose, NaCl, citric acid, caffeine and monosodium glutamate (MSG). Preference scale values for sucrose and citric acid increased after exercise, whereas the values for NaCl, caffeine and MSG were not changed. The absolute thresholds for all the sapid solutions did not differ for pre- and post-exercise. These findings indicate that in humans preference for sucrose and citric acid increase after physical exercise.      

Affective responses by adults with autism are reduced to social images but elevated to images related to circumscribed interests

Individuals with autism spectrum disorders (ASD) demonstrate increased visual attention and elevated brain reward circuitry responses to images related to circumscribed interests (CI), suggesting that a heightened affective response to CI may underlie their disproportionate salience and reward value in ASD. To determine if individuals with ASD differ from typically developing (TD) adults in their subjective emotional experience of CI object images, non-CI object images and social images, 213 TD adults and 56 adults with ASD provided arousal ratings (sensation of being energized varying along a dimension from calm to excited) and valence ratings (emotionality varying along dimension of approach to withdrawal) for a series of 114 images derived from previous research on CI. The groups did not differ on arousal ratings for any image type, but ASD adults provided higher valence ratings than TD adults for CI-related images, and lower valence ratings for social images. Even after co-varying the effects of sex, the ASD group, but not the TD group, gave higher valence ratings to CI images than social images. These findings provide additional evidence that ASD is characterized by a preference for certain categories of non-social objects and a reduced preference for social stimuli, and support the dissemination of this image set for examining aspects of the circumscribed interest phenotype in ASD.     

The Effect of Sucrose Concentration on Olfactory-Based Associative Learning in Culex quinquefasciatus Say (Diptera: Culicidae)

A classical conditioning approach was used to examine the ability of Culex quinquefasciatus Say (Diptera: Culicidae) to associate odor with a sugar-meal of varying quality. The objectives of this study were to investigate the impact of different sucrose concentrations (5 %, 10 %, or 50 %) on positive response to conditioning and to examine sucrose concentration preference following exposure to a 10 % solution. Mosquitoes conditioned in conjunction with all three sucrose concentrations showed evidence of learning; including the concentration of the conditioning stimulus, and the sex of the mosquito. Using colored solutions to determine feeding patterns of experienced mosquitoes indicated male mosquitoes showed no preference but females showed a preference for 10 % over 5 % sucrose but not between 10 % and 50 % sucrose solutions.