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PubMed2004

Accelerated folding in the weak hydrophobic environment of a chaperonin cavity: creation of an alternate fast folding pathway.

Recent experiments suggest that the folding of certain proteins can take place entirely within a chaperonin-like cavity. These substrate proteins experience folding rate enhancements without undergoing multiple rounds of ATP-induced binding and release from the chaperonin. Rather, they undergo only a single binding event, followed by sequestration into the chaperonin cage. The present work uses molecular dynamics simulations to investigate the folding of a highly frustrated protein within this chaperonin cavity. The chaperonin interior is modeled by a sphere with a lining of tunable degree of hydrophobicity. We demonstrate that a moderately hydrophobic environment, similar to the interior of the GroEL cavity upon complexion with ATP and GroES, is sufficient to accelerate the folding of a frustrated protein by more than an order of magnitude. Our simulations support a mechanism by which the moderately hydrophobic chaperonin environment provides an alternate pathway to the native state through a transiently bound intermediate state.

Chaperonins↗
PubMed2024

The physical and evolutionary energy landscapes of devolved protein sequences corresponding to pseudogenes.

Protein evolution is guided by structural, functional, and dynamical constraints ensuring organismal viability. Pseudogenes are genomic sequences identified in many eukaryotes that lack translational activity due to sequence degradation and thus over time have undergone "devolution." Previously pseudogenized genes sometimes regain their protein-coding function, suggesting they may still encode robust folding energy landscapes despite multiple mutations. We study both the physical folding landscapes of protein sequences corresponding to human pseudogenes using the Associative Memory, Water Mediated, Structure and Energy Model, and the evolutionary energy landscapes obtained using direct coupling analysis (DCA) on their parent protein families. We found that generally mutations that have occurred in pseudogene sequences have disrupted their native global network of stabilizing residue interactions, making it harder for them to fold if they were translated. In some cases, however, energetic frustration has apparently decreased when the functional constraints were removed. We analyzed this unexpected situation for Cyclophilin A, Profilin-1, and Small Ubiquitin-like Modifier 2 Protein. Our analysis reveals that when such mutations in the pseudogene ultimately stabilize folding, at the same time, they likely alter the pseudogenes' former biological activity, as estimated by DCA. We localize most of these stabilizing mutations generally to normally frustrated regions required for binding to other partners.

Cyclophilin A↗
PubMed1996

A mean field model of ligand-protein interactions: implications for the structural assessment of human immunodeficiency virus type 1 protease complexes and receptor-specific binding.

We propose a general mean field model of ligand-protein interactions to determine the thermodynamic equilibrium of a system at finite temperature. The method is employed in structural assessments of two human immuno-deficiency virus type 1 protease complexes where the gross effects of protein flexibility are incorporated by utilizing a data base of crystal structures. Analysis of the energy spectra for these complexes has revealed that structural and thermo-dynamic aspects of molecular recognition can be rationalized on the basis of the extent of frustration in the binding energy landscape. In particular, the relationship between receptor-specific binding of these ligands to human immunodeficiency virus type 1 protease and a minimal frustration principle is analyzed.

Aspartic Acid Endopeptidases↗
PubMed1998

Tracking the motion of chemisorbed molecules on their adsorption sites.

A new method, the time of flight-electron-stimulated desorption ion angular distribution method (TOF-ESDIAD), is described. The method permits the mapping of the lateral momentum distribution of adsorbed species on their adsorption sites. Examples of the study of the rotation of chemisorbed PF3 molecules and the frustrated lateral translation of chemisorbed CO molecules, both on single-crystal metal surfaces, are given. The observed anisotropy of the frustrated translation of CO is postulated to occur as a result of the 2pi* orbital alignment in chemisorbed CO along the close packed direction of the Cu(110) substrate.

Journal Article↗
PubMed1989

Behavioural differences between laying hen populations selected for high and low efficiency of food utilisation.

1. The effects on behaviour of selecting light-hybrid laying hens for high and low efficiency of food utilisation were investigated. Efficiency of food utilisation was measured as the proportional deviation of observed food consumption from expected food consumption. 2. Videograms of the day-time behaviour of 48 to 53-week-old individually caged hens from the F3 generation were analysed by instantaneous sampling. 3. Low-efficiency hens spent more time food-pecking, walking, pacing, and showing escape and aggressive behaviour than did high-efficiency hens. High-efficiency hens spent more than twice as much time resting and sleeping, and were never observed pacing prior to laying. 4. These differences were larger during the 2 h before laying than at other times of day. 5. Low-efficiency hens had poorer plumage, especially on the neck and the breast, and the poorer the plumage the more agitation they showed. 6. Time spent food-pecking was negatively correlated with laying frequency. 7. Differences in the occurrence of specific behaviour patterns, particularly those symptomatic of pre-laying frustration, partly explained differences in efficiency of food utilisation. Selection for higher efficiency of food utilisation might eliminate hens which are most frustrated prior to laying in cages.

Aggression↗
PubMed1980

Effects of fantasy behavior, level of fantasy predisposition, age, and sex on direction of aggression in young children.

The effect of fantasy behavior, fantasy predisposition, age, and sex upon direction of aggression in children was assessed in 57 kindergarten boys and girls. Ss from low to high levels of assessed fantasy predisposition were randomly designated as experimental or control. All Ss were exposed to an imposed frustrating condition. The experimental group was then exposed to a condition designed to elicit spontaneous fantasy behavior; the control group was exposed to a condition designed to be incompatible with fantasy. All Ss were then assessed for direction of aggression. Children who engaged in fantasy behavior following frustration were significantly more extrapunitive than control Ss (p less than .05); the findings did not support either the premise that fantasy results in drive-reduction or that fantasy results in the turning inward upon the self of hostile drive manifested by increased intropunitiveness. Age was found to be significantly but negatively correlated with extrapunitiveness (p less than .05).

Age Factors↗
PubMed1979

Marital sexuality and the psychological health of professional men.

A longitudinal study of married professional men explored the relation of adolescent and adult psychological health to marital sexual frequency, frustration, pleasure, and compatibility as well as the effects of sexual relations upon maturing. Psychological health was measured by seven adolescent and ten adult measures, including the MMPI, Rorschach, self- and judge-ratings, and questionnaires. Adolescent mental health did not predict any measure of adult sexual activity. Adult psychological health did not predict frequency of marital coital relations or degree of sexual frustration very consistently. It was associated more clearly with sexual pleasure and very consistently with marital sexual compatibility. Sexual relations did not contribute much to the men's maturing during adulthood; when they did, their principal effects were to further the integration and stabilization of the men's self-concepts.

Evaluation Studies as Topic↗
PubMed1992

Relationships between attributions and emotions in a laboratory-based sporting contest.

A series of one-vs-one fencing contests was staged in a laboratory to investigate the nature and extent of relationships between attributions and emotions. The experimenter had full control over the outcome and created a substantial defeat for one subject. A pre-contest measure of the importance of winning was obtained via a questionnaire. After the contest, questionnaire ratings of 12 attributions for outcome (winning/losing), 28 adjectives describing emotions, and a rating of satisfaction with performance were elicited. Factor analysis of emotion ratings revealed three factors of 'positive self-esteem', 'depression-frustration' and 'intropunitiveness'. Relationships between emotion factors and attributions involved primarily internal attributions. Multiple regression analyses showed that positive self-esteem for winners was best predicted by performance satisfaction, outcome importance and attributions, whereas depression-frustration was predicted only by attributions. For losers, positive self-esteem was predicted from attributions. These results suggest that attributions and emotions are related after sports competition but that non-attribution variables are also important predictors of sport-related emotion.

Adolescent↗
PubMedDate not supplied

The Marc Dax (1770-1837)/Paul Broca (1824-1880) controversy over priority in science: left hemisphere specificity for seat of articulate language and for lesions that cause aphemia.

One of the most fascinating and frustrating issues in the priority of discovery in science is over just who, for the first time, went on record in the public forum, either orally at a conference or through a published communication, proclaiming that the faculty of articulate human speech was located in the left, not the right, cortical hemisphere. The disputed paper was purportedly written in 1836 by Marc Dax, who died subsequently in 1837. He was a physician in southern France in the city of Montpellier--far from the medical center of Paris. Little note was made of the presumed paper until the early and mid-1860s, when the issue of language localization in the human brain took on increased activity, as the clinico-pathological method of explanation continued to flourish in the "Art of Physick." Marc Dax's son, Gustave, happened to be studying medicine in Paris in the 1860s, and, as most of the neuroscientific and anthropological researchers, came to know of Broca's published work, which in 1861, agreed with phrenological theory that this faculty was, indeed, in the anterior lobes, but further claimed, de novo, that the region in the anterior lobe was more precisely focused at the foot of the 3rd frontal convolution in that lobe, still assuming with phrenological theory and the "Law of Symmetry" that the faculty was bilaterally located. It was not until 1865 that Broca clearly, non-hesitatingly, and unambiguously claimed that the faculty was in the left hemisphere. As it turned out, Gustave, six weeks before Broca's paper appeared, had published the paper he said his father had written in 1836. In 1863, in fact, Gustave had submitted his (Gustave's) long monograph on aphemia, integrating what he claimed to be his father's 1836 pronouncement along with his own data. He sent this communication to the French Academy of Sciences and to the French Academy of Medicine; he heard nothing back from either academy. After waiting two years, he managed to publish his material. Gustave's valiant move to promote his father's priority for one of the most significant conclusions in the history of the neurosciences is a lesson in frustration. Broca's attitude towards Gustave's case was disarmingly nonchalant; the issue deserves further historical inquiry.

Aphasia, Broca↗
PubMed2004

To be a helpless helpoholic--GPs' experiences of women patients with non-specific muscular pain.

OBJECTIVES: To explore and describe what it means to be a GP meeting patients with non-specific symptoms. DESIGN: Focus group interviews analysed in a phenomenological approach. SETTING: GPs at two urban healthcare centres from a big city, a low socioeconomic area with mostly immigrants and a high socioeconomic area, and from a smaller town. SUBJECTS: 14 GPs in 3 focus groups. RESULTS: The essence of the study was the GPs' feeling of being a "helpless helpoholic". All GPs specified the patient with non-specific symptoms as a female patient with muscular pain. The key constituents were: inconsistent patient, insufficient tools, frustration, helplessness, and devotion to help. The tools were described as communication skills, biomedical education, and holistic perspective. Even if most informants were trained in communication skills, this did not help to avoid the feeling of helplessness. CONCLUSIONS: To be a "helpless helpoholic" may make the GPs less patient-centred and may create even more feelings of frustration and helplessness. This can be an important reason why consultations with female patients with non-specific muscular pain often fail.

Attitude of Health Personnel↗
PubMed1999

Disentangling ethical and psychological issues--a guide for oncologists.

The rapid growth of bioethics has injected a new style of analysis into medicine. It requires philosophical rigor, yet is deeply embedded in human situations that frustrate abstract thinking and are laced with subjective factors. These interlaced ethical and psychological components can lead to conflicts and dilemmas. Doctors, as experts and decision-makers, play a key role, but will benefit from additional skills to disentangle these situations. This paper notes ways in which patients, families and caregivers are newly vulnerable and delineates how ethical dilemmas and psychological issues mold or frustrate decision-making. To help physicians manage such cases, a method of systematic analysis, the 'situational diagnosis', and a related hierarchy of interventions, is described and illustrated with case examples.

Adaptation, Psychological↗
PubMed2000

Prospective and retrospective memory in normal ageing and dementia: a questionnaire study.

Frequency of prospective memory and retrospective memory failures was rated on a 16-item questionnaire by 862 volunteers, from five groups: patients with Alzheimer Disease (rated by carers), carers of Alzheimer Disease patients, elderly, young, and a group of married couples. Reported memory failures were highest for Alzheimer Disease patients, and lowest for carers, with elderly and young controls in between. More prospective memory than retrospective memory failures were reported in all groups, although the difference was small for Alzheimer Disease patients who were rated near ceiling for both. Prospective memory failures of Alzheimer Disease patients were reported as more frustrating for carers than retrospective memory failures; prospective memory and retrospective memory failures frustrated Alzheimer Disease patients equally. Data from the couples indicated that there were no biases resulting from rating on behalf of someone else. These results suggest that: (1) normal ageing has no greater effect on self-reported retrospective memory than prospective memory failures, (2) the relatively small number of memory failures reported by carers may result from comparing themselves with the Alzheimer Disease patients in their care, and (3) prospective memory failures have a greater impact on the lives of the carers and are therefore more likely to be reported as early indicants of the disease.

Adolescent↗
PubMed1992

A new technique of laparoscopic cholangiography.

With the advent and rapid proliferation of laparoscopic cholecystectomy, numerous techniques and "tips" have been described. Intraoperative cholangiography during laparoscopic cholecystectomy can be tedious, frustrating, and time consuming. Described herein is a technique of intraoperative cholangiography during laparoscopic cholecystectomy which has proven to be easy, fast, and succinct. This method utilizes a rigid cholangiogram catheter which is placed into the peritoneal cavity through a small additional puncture site. This catheter is easily inserted into the cystic duct by extracorporeal manipulation. We suggest this method to surgeons who have shared our prior frustration with intraoperative cholangiography.

Catheterization↗
PubMed2002

Medically unexplained symptoms and the problem of power in the primary care consultation: a qualitative study.

BACKGROUND: Patients presenting in primary care frequently exhibit physical symptoms that may be unrelated to organic pathology. Such symptoms are commonly regarded as products of psychological or emotional problems, and their legitimacy as 'medical' matters is often called into question. OBJECTIVES: Our aim was to explore GPs' attitudes to the management of patients that present with medically unexplained symptoms in primary care. METHODS: Semi-structured interviews were conducted with 15 GPs in North-West England. Interviews were audio-taped and subsequently transcribed and analysed using a constant comparison technique. RESULTS: Subjects conceptualized patients presenting with medically unexplained symptoms as the presentation of psychological distress. They presented problems of control and authority in the consultation, and difficulties in managing this had a negative impact on the doctor-patient relationship. Such consultations were frustrating for the GP and potentially harmful to the patient. CONCLUSION: Patients with medically unexplained symptoms were seen to be presenting with inappropriate symptoms that were a manifestation of emotional or social distress. GPs felt ill-equipped to deal with the presentations and the frustrations they felt and may need help in actively and productively managing these patients.

Attitude of Health Personnel↗
PubMed2002

Age excuses: conversational management of memory failures in older adults.

The social consequences of appealing to age to excuse memory failure were examined in 2 vignette-based studies. In Study 1, 75 older (M = 72 years) and 78 young (M = 22 years) adults evaluated forgetful older targets in their 70s who used their age, lack of ability, lack of effort, or the situation to explain forgetting. In Study 2, 105 older (M = 72 years) and 105 young participants (M = 19 years) evaluated forgetful targets with no specific age given in 4 excuse conditions (age, ability, situation, and no excuse). In support of the prediction of positive consequences, age excuses were rated as more believable than situation in both studies and more believable and socially fluent than effort in Study 1. In support of predictions of negative consequences, both groups in Study 2 rated target persons who used an age excuse to be much older than their peers and, along with ability excuse users, as eliciting more worry and frustration than the others. Moreover, young adults showed additional sensitivity to the negative aspects of age excuses in terms of worry and frustration in Study 1 and anticipated repeat forgetting in Study 2. These results suggest that although age excuses may relieve socially awkward situations, this strategy reinforces negative age stereotyping of the older forgetter.

Adult↗
PubMed2000

Empty follicle syndrome: evidence for recurrence.

The empty follicle syndrome (EFS) is a frustrating condition in which no oocytes are retrieved in an IVF cycle. Although this is an infrequent event in IVF patients, the economic consequences as well as the emotional frustration of a cancelled cycle due to the inability to obtain oocytes are enormous. The mechanisms responsible for EFS remain obscure, though many hypotheses have been put forward ranging from dysfunctional folliculogenesis to a drug-related problem. We found that the EFS is a rare event (1.8% of oocyte retrievals) but with profound implications for counselling the couple about their future reproductive performance. The chances of recurrence of EFS increase with the age of the patient (24% recurrence rate for the 35-39 year age group, and 57% for those over 40 years). We postulate that ovarian ageing, through altered folliculogenesis, may be implicated in the aetiology of EFS and its recurrence.

Adult↗
PubMed2002

Physicians' perceptions of institutional and leadership factors influencing their job satisfaction at one academic medical center.

PURPOSE: Academic physicians' perceptions about their institution's function and leadership should provide insights toward improving faculty recruitment and retention. METHOD: The authors surveyed 105 non-management and non-emeritus physicians who had been hired by (57%) or left (43%) the University of Missouri-Columbia School of Medicine (MUHC) in 1991-1998. The questionnaire measured both the importance and the availability of 14 institutional and leadership factors and the physicians' perceptions of satisfaction with their careers. Open-ended questions assessed additional concerns. RESULTS: In all, 56% of the overall satisfaction scores were unfavorable and, when grouped by faculty department, correlated inversely with departure rates (p =.04). Scores were surprisingly similar between those who left and those who remained at the institution. "Protected time for research or personal use" was the highest faculty priority regardless of level of overall satisfaction. "Equitable distribution of salary/resources" (p =.007) and "trust-communication with chair/division head" (p =.003) predicted good satisfaction independently. Openended responses for remaining at the university related to the pleasant local community (49%), intellectual issues (46%), and humanitarian issues (5%). Responses for considering opportunities elsewhere were administrative frustration (59%), income enhancement (18%), career advancement (9%), academic frustration (9%), and other (5%). Recommendations for enhancing recruitment and retention were fix administrative concerns (45%); improve research (20%), income (9%), physician support (9%), clinical programs (8%), and autonomy (5%); and other (4%). CONCLUSIONS: Surveying physicians who were recently hired or who have left an institution provides useful information to promote organizational changes that could improve physician retention.

Attitude of Health Personnel↗
PubMed1996

Cross-sectional analysis of Alzheimer disease effects on oral discourse in a picture description task.

To examine the relation of dementia severity to the quality and quantity of oral discourse of individuals with Alzheimer disease (AD), a picture description task was administered to elicit oral discourse samples from 63 AD subjects, five individuals with very mild cognitive impairment, and 52 normal controls. Eight measures of discourse were used: total words, information units, conciseness, circumlocutions, frustrations, aborted phrases, revisions, and ideational repetitions. Information units, which decreased with increased dementia severity, proved to be the best measure for evaluating the effects of AD on oral descriptive discourse. The conciseness index also decreased with increased dementia severity, and a significantly greater proportion of AD discourse samples contained ideational repetitions. Circumlocutions and frustrations rarely occurred, and although the discourse of AD subjects was more likely to contain an aborted phrase, the frequency of aborted phrases did not vary by stage of dementia. Revisions were commonly observed in the discourse of both normal controls and AD subjects and did not differentiate the two groups.

Aged↗