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PubMed2005

The native energy landscape for interleukin-1beta. Modulation of the population ensemble through native-state topology.

A minimalist Go-model, with no energetic frustration in the native conformation, has been shown to describe accurately the folding pathway of the beta-trefoil protein, interleukin-1beta (IL-1beta). While it appears that these models successfully model transition states and intermediates between the unfolded and native ensembles, it is unclear how accurately they capture smaller, yet biologically relevant, structural changes within the native ensemble after energetic perturbation. Here, we address the following questions. Can a simple Go-model of interleukin-1beta, based on native topology, describe changes in structural properties of the native ensemble as the protein stability is changed? Or is it necessary to include a more explicit representation of atoms, electrostatic, hydrogen bonding, and van der Waals forces to describe these changes? The native ensemble of IL-1beta was characterized using a variety of experimental probes under native (0 M NaCl, guanidine hydrochloride (Gdn-HCl)), moderately destabilized (0 M NaCl, 0.8 M Gdn-HCl), and in moderate salt concentration (0.8 M NaCl, 0 M Gdn-HCl). Heteronuclear (1)H-(15)N nuclear Overhauser effect spectroscopy (NOESY) and heteronuclear single quantum correlation (HSQC) NMR spectra confirmed that the beta-trefoil global fold was largely intact under these three conditions. However, 25 of the 153 residues throughout the chain did demonstrate (13)C and (1)H-(15)N chemical shifts when perturbed with 0.8 M NaCl or Gdn-HCl. Despite large differences in protection factors from solvent hydrogen-deuterium exchange for all residues between stable (0 M Gdn-HCl) and destabilized (0.8 M Gdn-HCl) IL-1beta, no difference in steady-state (15)N-(1)H NOE enhancements were measured. Thus, the chemical shifts correlate with a global but limited increase in residue flexibility in the presence of Gdn-HCl. Minimalist simulations highlight the regions of greatest position shift between native and 0.8 M Gdn-HCl, which were determined experimentally. This correlation demonstrates that structural changes within the native ensemble of IL-1beta are, at least partially, governed by the principle of minimal energetic frustration.

Amides↗
PubMed2004

A neural network underlying individual differences in emotion and aggression in male golden hamsters.

In rodents, aggressive behavior can be altered by experimental manipulations of emotional responsiveness. The goal of this study was to identify characteristics of emotional reactivity associated with individual differences in aggressive behavior and their integration within a common neural network. Male golden hamsters were first screened for offensive aggression. Then, the animals were trained through immediate reinforcement and tested for their adaptation to a delayed reward. Similar protocols have been used to test behaviors associated with frustration. At first, all hamsters showed increased frequency of bar pressing per reward during delayed reinforcement. However, Low-Aggression animals were able to adapt to the delay and showed a decreased rate of bar pressing per reward within 5 days. In contrast, High-Aggression animals maintained a high rate of bar pressing per reward. In addition, brains were collected after immediate reward training or delayed reward testing, and labeled for pCREB-immunoreactivity as a marker of trans-synaptic activity. In High-Aggression individuals, elevated density of cyclic AMP response element binding protein, phosphorylated (pCREB) immunostaining was found within the anterior hypothalamus, an area critical to the control of aggression. Delayed reinforcement was associated with enhanced pCREB immunostaining within the central amygdala, medial amygdala and preoptic area/hypothalamus continuum. Further analysis of the data also showed a positive correlation in labeling density between the lateral septum and the anterior hypothalamus, specifically in Low-Aggression animals exposed to delayed reward. Therefore, as High-Aggression individuals lack control of their emotional reactivity, they are also characterized by a de-synchronization between the inhibitory output of the septum and the aggression areas of the hypothalamus. Finally, our data also show that frustration is associated with an extensive activation of the preoptic area/hypothalamus continuum and amygdala.

Aggression↗
PubMed1992

Take charge. Getting the technical information you need.

Remember that manufacturers want your business. Manufacturers want to provide what you need to use a product correctly. They believe they are meeting that need. It is up to you to decide your future. Your frustration and anxiety with new technology will never change unless you take charge and communicate your needs to manufacturers. Tell them what you like about a product and, just as important, how to make it better. Tell them what resources are needed to minimize the anxiety and frustration associated with using their products.

Disposable Equipment↗
PubMed1999

Participants' evaluation of a weight-loss program.

OBJECTIVE: The purpose of this study was to evaluate participants' perceptions of the weight-loss intervention used in a hypertension prevention clinical trial. DESIGN: A total of 308 overweight and moderately obese subjects participated in the weight-management intervention. After the 18-month program, 281 participants completed a questionnaire designed to evaluate their perceptions of the program's effectiveness. SUBJECTS/SETTING: Adult participants (224 men and 84 women) in the weight-loss modality of the Trials of Hypertension Prevention Phase I, surveyed in 1991. STATISTICAL ANALYSES PERFORMED: chi 2 Analyses were used to test for statistical significance of group differences. RESULTS: Intervention components that were most useful are presented. Older participants (older than 50 years) were most likely to attend sessions and women were most likely to identify stress and frustration because of disappointing results. Successful participants were more likely to incorporate exercise into their daily activities, exercise regularly, and use self-monitoring strategies. Few participants found group exercise to be useful. CONCLUSION: These findings suggest that interventionists in weight-loss programs need to find flexible and creative ways to maintain contact with participants, continue to develop better methods of self-monitoring, obtain the skills needed to recognize frustration and provide timely support, continue to couple the message of diet and exercise, and emphasize helping participants develop their problem-solving skills. This may require training outside the traditional field of dietetics.

Adult↗
PubMed1998

Salivary cortisol and cardiovascular activity during stress in oppositional-defiant disorder boys and normal controls.

BACKGROUND: Arousal-regulating mechanisms are important in explaining individual differences in antisocial behavior. METHODS: Alterations in salivary cortisol concentration and cardiovascular activity were studied in 21 boys with oppositional defiant disorder (ODD) and 31 normal controls (NC) during a 2-hour stressful procedure involving frustration and provocation. RESULTS: Baseline levels of heart rate (HR) were significantly lower in the ODD group, but their HR levels were higher during provocation and frustration. Cortisol levels in the ODD group were overall lower than those of the NC group, and the effect of stress seemed to be minimal and similar for both groups; however, individual differences were large. Since anxiety plays an important mediating role in cortisol response, subjects were divided into one of four groups based on the intensity of their externalizing behavior and anxiousness. Cortisol increase due to stress exposure was strongest in highly externalizing and highly anxious subjects; cortisol decrease was strongest in those subjects who were high in externalizing behavior and low in anxiousness. CONCLUSIONS: The results of the study support an important role for hypothalamic-pituitary-adrenal axis sympathetic autonomic functioning in persistent antisocial behavior in young boys.

Aggression↗
PubMed1996

Effects of unsaturation and curvature on the transverse distribution of intramolecular dynamics of dipyrenyl lipids.

The roles of acyl chain unsaturation and curvature in the excimer formation efficiency (EFE) of site-specific conjugated pyrene molecules in lipid membranes have been investigated by steady-state and time-resolved fluorescence spectroscopy. Six 1-2-(pyrenyl-n-acyl)-phosphatidylcholine (dipy(n)PC) probes, with pyrenyl chains of varying methylene units n from 4 to 14 carbons, were incorporated separately into dioleoylphosphatidylcholine (DOPC) or dioleoylphosphatidylethanolamine (DOPE) lipid membranes at 0.1 mol%. Both the excimer-to-monomer fluorescence intensity ratio and association-to-dissociation rate constant ratio of conjugated pyrenes were used to quantify EFE. At all temperatures (T = 0-30 degrees C) and for n = 4 and 6, the EFE for DOPE was always smaller than EFE for DOPC. At T < 10 degrees C (where DOPE and DOPC are in the liquid crystalline L alpha phase) and for n > 8, the EFE for curvature frustrated DOPE was significantly greater than EFE for nonfrustrated DOPC (control), and the difference increased gradually with n. At T> 18 degrees C (where DOPE is in the inverted hexagonal H(II) phase and DOPC is in the L alpha phase) and for n > 8, EFE for the curvature-relaxed DOPE was again smaller than the EFE for DOPC control. The contributions of splay conformation and internal dynamics of pyrenyl chains to EFE were examined separately using a lattice model. Our results suggest that i) the cis double bonds of the host lipid matrix strongly perturb both the conformation and dynamics of conjugated pyrenes at the specific location around n = 8, and ii) the lateral stress at the upper part (n < 8) of the curvature frustrated bilayer membranes (DOPE) may be significantly relaxed once the membrane surface adopts a favorable negative interfacial curvature.

Kinetics↗
PubMed1997

DNA-lipid complexes: stability of honeycomb-like and spaghetti-like structures.

A molecular level theory is presented for the thermodynamic stability of two (similar) types of structural complexes formed by (either single strand or supercoiled) DNA and cationic liposomes, both involving a monolayer-coated DNA as the central structural unit. In the "spaghetti" complex the central unit is surrounded by another, oppositely curved, monolayer, thus forming a bilayer mantle. The "honeycomb" complex is a bundle of hexagonally packed DNA-monolayer units. The formation free energy of these complexes, starting from a planar cationic/neutral lipid bilayer and bare DNA, is expressed as a sum of electrostatic, bending, mixing, and (for the honeycomb) chain frustration contributions. The electrostatic free energy is calculated using the Poisson-Boltzmann equation. The bending energy of the mixed lipid layers is treated in the quadratic curvature approximation with composition-dependent bending rigidity and spontaneous curvature. Ideal lipid mixing is assumed within each lipid monolayer. We found that the most stable monolayer-coated DNA units are formed when the charged/neutral lipid composition corresponds (nearly) to charge neutralization; the optimal monolayer radius corresponds to close DNA-monolayer contact. These conclusions are also valid for the honeycomb complex, as the chain frustration energy is found to be negligible. Typically, the stabilization energies for these structures are on the order of 1 k(B)T/A of DNA length, reflecting mainly the balance between the electrostatic and bending energies. The spaghetti complexes are less stable due to the additional bending energy of the external monolayer. A thermodynamic analysis is presented for calculating the equilibrium lipid compositions when the complexes coexist with excess bilayer.

Computer Simulation↗
PubMed1996

Care-giver evaluation of anti-gastroesophageal reflux procedures in neurologically impaired children: what is the real-life outcome?

Although the pediatric surgical literature is replete with reports of the success of operations for gastroesophageal reflux, postoperative complications are being reported with increasing frequency for the neurologically impaired subpopulation. Because a large portion of a care-giver's life is involved in attending to a neurologically impaired child, parental satisfaction with the outcome of these operations should be an important consideration when the use of such procedures is contemplated. The purpose of the present study was to assess the impact of antireflux operations with respect to care-giver opinions regarding the procedure. The authors retrospectively reviewed 25 charts (of 13 girls and 12 boys; age range, 3 months to 18 years) and documented (through survey results) perceived child well-being, objective care requirements, and overall care-giver satisfaction with the procedure. Results indicate there was significant improvement in feeding indexes, care-giver perception of the child's comfort, and quality of life postoperatively. Moreover, there was significant improvement in the care-givers' attitudes regarding their child, including the level of frustration in caring for the child, and the parents' overall quality of life. Care-givers also believed that the operation's result was about or better than what they had expected. In conclusion, the study documents care-giver satisfaction with antireflux procedures. Postoperatively, child care is easier and the quality of time spent with the child is better. The impression of better quality of life postoperatively for a neurologically impaired child may be the greatest success in this sometimes frustrating endeavor.

Adolescent↗
PubMed1986

Preventing school failure: the physician as child advocate.

Attending school heralds the end of the relative protection and nurture of home life. During the school day, a child experiences successes and failures that portend future feelings of self-worth and self-esteem. Usually children experiencing difficulty at school are identified by teachers, however, children are overlooked. When they are and subsequently experience chronic failure and frustration, long-term morbidity may ensue. Ideally, methods to identify potential learning problems should be available. Unfortunately, the state of the art does not allow accurate identification of problems before they occur. After any number of screening tests, we can accurately predict school successes, but predicting failure is elusive. Early school failure, however, like many maladies, can be diagnosed, particularly if a physician has a high index of suspicion and looks for signs and symptoms of ongoing failure and frustration. Family history, neonatal course, presence of minor congenital anomalies and soft neurological signs, attention problems and lack of age-appropriate processing skills in the preschool period should place a child at risk. Close observation should designate those children who fail to mobilize associated strengths that maintain development. Early intervention will reduce morbidity associated with academic difficulty. Longitudinally, reduction of chronic failure may be the most crucial intervention. The unfortunate cycle of developmental dysfunction leading to school failure and lowered self esteem with subsequent social pathology and delinquency is well known. To the extent that physicians are able to ensure appropriate school services for children experiencing failure, this cycle can be short circuited, adding significantly to the physician's traditional armamentarium.

Adolescent↗
PubMed1997

Personality traits of Japanese patients in remission from an episode of primary unipolar depression.

Personality traits were assessed by means of the Munich Personality Test (MPT) in 75 Japanese subjects, 27 patients in remission from an episode of moderate to severe primary unipolar depression, with melancholic features during one episode or more of the disorder, in 24 patients in remission from other non-organic mental disorders and in 24 healthy controls. Compared with healthy controls, unipolar depressives displayed decreased Frustration Tolerance and elevated Rigidity as well as a stronger Orientation towards Social Norms. No significant difference was found between patients in remission from either unipolar depression or other mental disorders. However, the increase in Rigidity in comparison with healthy subjects was significant in the depressives only whereas the other patients, in contrast to the depressives, had significantly lower scores in Extraversion than the healthy subjects. Our results in Japanese patients are similar to findings of previous German studies, including two high risk studies, in which the same assessment instrument was used. This suggests that, beyond cultural differences, Rigidity, possibly in combination with a strong Orientation towards Social Norms and a reduced Frustration Tolerance, is a stable vulnerability marker for at least the more severe forms of primary unipolar depression.

Adult↗
PubMed2000

Development of stereotypies and polydipsia in wild caught bank voles (Clethrionomys glareolus) and their laboratory-bred offspring. Is polydipsia a symptom of diabetes mellitus?

The development of stereotypies and polydipsia was studied in wild caught bank voles (P: n=92) and their laboratory-bred offspring (F1: n=248). All animals were kept isolated in barren cages in the laboratory. In the P generation, no individuals developed stereotypies, but 22% developed polydipsia (>21 ml/day water intake against normally 10 ml/day). Polydipsia was more frequent among males (34%) than females (13%). In F1, 30% developed locomotor stereotypies alone, 21% showed polydipsia alone, and, additionally, 7% developed both stereotypies and polydipsia. Fewer males than females developed stereotypies (23% vs. 38%), whereas polydipsia was more frequent in males than in females (30% vs. 11%). The occurrence and distribution of polydipsia among sexes were the same in F1 and P. The distribution of different types of stereotypies in stereotyping voles were backward somersaulting (BS, 80%), high-speed jumping (JUMP, 29%), pacing following a fixed route (PF, 12%) and windscreen wiper movement (WIN, 5%). Some individuals (10%) showed two or more different types of stereotypies. The average age for developing stereotypies was 96 days while polydipsia was registered at the age of 63 days in both sexes. Voles showing both polydipsia and stereotypies developed polydipsia later (79 days) than polydipsic voles not showing stereotypies. This difference was especially pronounced in stereotyping females in which the occurrence of polydipsia was postponed to the age of 114 days. Polydipsic voles were tested positive for glucosuria indicating that polydipsia could be a symptom of diabetes mellitus. It is suggested that the development of stereotypies and polydipsia among bank voles in the laboratory are the results of frustration and prolonged stress. Stereotypies seem to depend on frustrative experiences early in life, while polydipsia may be related to diabetes mellitus caused by the experience of prolonged stress. Moreover, circumstances related to the development of stereotypies may be adaptive by reducing the risks of prolonged stress, including the development of fatal polydipsia.

Journal Article↗
PubMed2000

Indication of a genetic basis of stereotypies in laboratory-bred bank voles (Clethrionomys glareolus).

The development of stereotypies was studied in two successive laboratory-bred generations of bank voles representing F1 (n=248) and F2 (n=270) of an originally wild caught stock. It was shown that the propensity to develop stereotypies under barren housing conditions strongly relates to the same propensity of the parents. Stereotypies were approximately seven times more frequent in the offspring of stereotyping parents than in the offspring of permanent non-stereotypers. This held true even when only one of the parents was stereotyper. The paternal and maternal contributions to stereotypies in the offspring appeared to be equal. Males showing stereotypies but prevented from any physical contact with the offspring were as potent as stereotyping females in producing stereotyping offspring. Moreover, the specific type of stereotypy appearing in the offspring after isolation was very much related to the type of stereotypy developed in the mothers. We found no support for the possible importance of social facilitation from littermates, in that the development of stereotypies was independent of the length of time the voles were kept socially with littermates before isolation. We suggest that the possible genetic basis of individual differences in the propensity to develop stereotypies in captivity may result from differences in genetic predispositions and their interactions with discrete frustrating stimuli early in life and/or to genetically different predispositions to cope with frustrating experiences later in life.

Journal Article↗
PubMed2001

Do broiler chicks have a cognitive representation of food quality?. Appetitive, behavioural and ingestive responses to a change in diet quality.

It has been observed that when a new diet formulation, or a new batch of the same diet formulation, is presented to poultry, there is a transitory suppression of feeding. It appears that the birds do not recognise the food as being edible, or classify it as being 'unknown'. In order to understand more about food recognition and rejection, the aim of this experiment was to determine whether cognitive processes are involved. Sixteen groups of four broiler chicks were used, and were fed a low quality diet in their home pens. The groups of chicks were trained to run a winding maze to gain access to a high quality diet in a test trough for 15min per day. When training was completed, the feed in the test trough for eight of the groups was changed to that which they received in the home pen, while the other eight groups received no change as a control. Time to traverse the runway did not show an immediate decrease on the day after the change (P>0.05) as would be expected if the birds used a cognitive comparison to determine speed of approach to the test trough. However, the experimental groups were significantly slower compared to the control groups after 4 days (P<0.05). The behaviour observed on the day of the change was indicative of frustration with more scratching and hurried movements shown (P<0.05), and less pecking at feed (P<0.01). Food consumption was lower for experimental groups compared to control groups on all days from the day of change onward (P<0.001). It was concluded that although there was no definitive evidence for the presence of a cognitive representation of food, this may have been due in part to the testing of groups of birds rather than individuals, and the way in which food quality is perceived. The occurrence of behaviours indicative of frustration suggest that a cognitive expectation may have been present.

Journal Article↗
PubMed1988

Flea allergy dermatitis.

Flea allergy dermatitis is one of the most common causes of pruritus in dogs and cats. The degree of pruritus observed in the allergic animal varies widely and is dependent on numerous factors. Management of the flea-allergic patient is extremely frustrating for the owner and the veterinarian. Establishing an organized flea control program for use on the patient and in the environment will help to avoid frustration when dealing with this common ectoparasite of cats and dogs.

Animals↗
PubMed1992

Inflammatory oral cavity diseases of the cat.

There is a great deal of frustration among veterinarians about the diagnosis and treatment of inflammatory diseases of the oral cavity of the cat. This frustration is due to both the high frequency of feline oral inflammatory lesions and our poor understanding of their causes. This poor understanding can be blamed on several things: (1) a rapidly emerging, but still relatively poor, understanding of feline diseases in general and nutrition in particular; (2) a tendency to lump rather than separate specific oral inflammations; (3) a tendency not to use a thorough and systematic approach to diagnosing oral cavity disease; and (4) the reluctance of veterinarians to apply what is already known about human oral cavity diseases to cats. When problems 2 through 4 are adequately addressed, it becomes apparent that we really know more about oral cavity disease in the cat than we thought we knew and that great progress has been made. The task ahead is to define, in precise medical terms, those remaining disease entities of the oral cavity that pose the greatest health risk to cats, to apply what has been already been discovered from human disease counterparts, and to study them systematically.

Animals↗
PubMed1997

Finite one-dimensional spin systems as models of biopolymers.

New models are proposed for describing various properties of biopolymers, especially those of proteins and nucleic acids. Each model is constituted of a set of spins arranged on a chain, and each pair of spins produces an interaction. We examine the transitions of these spin systems between the ground state and the disordered state. It is found that the transitions of the present spin systems demonstrate various properties in response to values of the so-called interaction energy. If we define interaction energy parameters with no so-called frustration, the system exhibits two-state transitions, similar to the folding-unfolding transition of small proteins. The addition of frustrations to the model produces effects similar to those of mutations in proteins. On the other hand, if the interactions between two spins attenuate as a function of their separation along the chain, the transition of the system has characteristics similar to those of nucleic acids. Thus, the present spin systems can offer a unified view of the folding-unfolding transition of biopolymers in terms of differences in the pairwise interactions between spins. Based on our models, we propose a condition for two-state transition behavior for proteins.

Journal Article↗
PubMed1997

Chronic abacterial prostatitis--a urological chronic pain syndrome?

Chronic abacterial prostatitis has all the hallmarks of a chronic pain syndrome without having been identified as such, either in the urology literature or in the pain literature. This review proposes that this common urological syndrome merits consideration as a 'chronic pain syndrome', as it is commonly defined. The presentation of this syndrome in PAIN results from the unlikely collaboration of a clinical psychologist and a urologist with an interest in exploring unconventional assessment and treatment recommendations for the patients he saw in a university-based Prostatitis Clinic. In addition to providing a review of the chronic prostatitis syndrome as it appears in the urology literature, we surveyed the journal, PAIN, from 1985 through 1995 to identify the 'body parts' specifically named in titles of articles on non-malignant pain. There was only one case study report on male genital or urological pain. Similar to other more commonly accepted chronic pain syndromes, chronic abacterial prostatitis has the following characteristics: pain as a primary complaint, low correspondence between symptoms and medical findings, a history of multiple, unsuccessful treatments. The consequence of recognizing this very common urological syndrome as a chronic pain syndrome is that a large group of symptomatic men for whom urologists have little to offer stands to benefit from a different perspective. Experience with other chronic pain syndromes, including back pain and headaches; has shown that interventions based on a multidisciplinary approach can prove complementary to traditional 'organ system' approaches to treatment of these frustrated, and frustrating, patients.

Chronic Disease↗
PubMed2002

The effects of lavender (Lavendula angustifolium) baths on psychological well-being: two exploratory randomised control trials.

OBJECTIVE: Two important aspects of psychological well-being are positive mood state and a positive outlook with respect to the future. This study investigates the use of lavender baths to improve these aspects of psychological well-being. DESIGN: A single blind, randomised control trial. SETTING: The participants' home and interview rooms at the University of Wolverhampton. PARTICIPANTS: Eighty women not receiving treatment for psychological disorders who were staff or students at the University of Wolverhampton. Forty participated in Study 1 and 40 in Study 2. INTERVENTION: Participants were randomly allocated to use either grapeseed oil or 80% grapeseed oil and 20% lavender oil in their bath for 14 days. MAIN OUTCOME MEASURES: In Study 1, the UWIST mood adjective checklist. In Study 2, the MacLeod and Byrne Future Events procedure. RESULTS: In Study 1 psychologically positive mood changes were found after the bathing regimen for energetic arousal, tense arousal, hedonic tone and anger-frustration. Only anger-frustration showed a selective effect for lavender oil. In the second study negative responses about the future were selectively reduced after lavender oil baths. CONCLUSIONS: These results are encouraging and suggest further investigation using potential patients may result in the development of a useful procedure for improving psychological well-being.

Adult↗