Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.

Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

The Family Atherosclerosis Risk Intervention Study (FARIS): risk factor profiles of patients and their relatives following an acute cardiac event.

BACKGROUND: Relatives of patients with coronary heart disease have a heightened risk of cardiovascular disease. Attendance at a family-based screening clinic after an acute cardiac event could motivate patients and relatives to modify their lifestyles. AIMS: The Family Atherosclerosis Risk Intervention Study (FARIS) aimed to determine (i) whether a high proportion of patients and relatives would attend a special screening and prevention programme; (ii) whether the risk factor profiles of relatives would be worse than those in the general community; and (iii) whether ongoing management of patients and families together in a special clinic would improve risk factor profiles. METHODS: Consecutive patients, together with spouse, siblings and offspring, aged 18 to 69 years, were randomly allocated three months after an acute cardiac event to attend a special outpatient clinic, a screening and advice group, or a control group. Risk factor measures were total cholesterol, HDL cholesterol (HDLC), systolic blood pressure (SBP), body mass index (BMI) and smoking behaviour. This paper presents the risk factor profiles of all FARIS attenders and compares those of family members, age adjusted, with risk factors measured in a multicentre urban cross-sectional survey conducted in the same period. Differences between groups were compared using t-tests for numerical variables and ANOVA and chi-square for categorical variables. RESULTS: Six hundred and twenty-eight patients and 1723 family members were enrolled, representing 85.9% and 82.7% of eligible patients and relatives respectively. Risk factors were significantly worse amongst family members than among those in the population survey.

Vibrotactile threshold in young and old observers: the effects of spatial summation and the presence of a rigid surround.

Human psychophysical detection thresholds for ten frequencies of sinusoidal vibration ranging from 10 to 400 Hz were obtained on the left index fingertip and thenar eminence of young and older observers using a three-alternative forced-choice tracking procedure. The first experiment utilized a 7-mm (0.38 cm2) contactor and rigid surround with 1-mm gap. In the second experiment, three contactor sizes (1.6-, 7.0-, and 25.4-mm diameter) and two surround configurations (1-mm gap between contactor and surround, and no surround) were used. The results indicate that, although the shapes of the threshold versus frequency functions were similar in the two age groups, there was a reduction in sensitivity for the older group at all frequencies. Furthermore, taking into account the difference in sensitivity between the two age groups, spatial summation and the effects of a surround did not seem to differ between the two groups. These results are discussed in the context of physiological models of cutaneous sensitivity and changes in receptor function with age.

Cardiac rehabilitation based on group light exercise and discussion. An Australian hospital model.

Patients with cardiac disease potentially have many physical, psychological, and social problems. With adequate rehabilitation, most patients can return to enjoyable, productive lives. If rehabilitation programs can be provided at relatively low cost, they can be introduced more widely. It is obviously important that low-cost programs should include most of the effective components of more sophisticated programs. The program presented here, based on group light exercise and discussion, is effective and inexpensive. Therefore, it provides a potential model for group cardiac rehabilitation in situations where cost-containment is an important consideration.

Vibrotactile adaptation enhances frequency discrimination.

Human vibrotactile frequency discrimination (with respect to a 25-Hz standard stimulus, 20 dB above unadapted detection threshold) was measured on the thenar eminence and index fingerpad, using two-interval forced-choice tracking. Measurements were made in the unadapted state and following exposure to 25-Hz adapting stimuli of various amplitudes. The standard and all comparison stimuli were equated for perceived intensity, on the basis of matching experiments that were carried out separately under each adapting condition. Frequency difference thresholds were lowest when the amplitude of the adapting stimulus was equal to the amplitude of the standard. This result complements the earlier finding [A. K. Goble and M. Hollins, J. Acoust. Soc. Am. 93, 418-424 (1993)] that adaptation sharpens amplitude discrimination of supraliminal stimuli that are similar to the adapting stimulus. Taken together, these discoveries suggest that somatosensory mechanisms that are engaged by extended stimulation serve to enhance detection of changes in the properties, both quantitative and qualitative, of that stimulation.

Early programmes of high and low intensity exercise and quality of life after acute myocardial infarction.

OBJECTIVE: To determine whether a group programme of light exercise could improve quality of life in patients after acute myocardial infarction to the same extent as a high intensity exercise training programme. SETTING: Australian teaching hospital. PATIENTS: 224 men from a consecutive series of 339 men under 70 admitted to a coronary care unit with transmural acute myocardial infarction. INTERVENTION: Patients were randomly allocated in hospital to a group programme lasting eight weeks of either high intensity exercise training or light exercise. MAIN OUTCOME MEASURES: Physical working capacity based on metabolic equivalents achieved from treadmill exercise tests at entry, after 11 weeks, and after one year. Quality of life based on self report scores of anxiety, depression, denial, and wellbeing and interview assessments of activities and psychosocial adjustment at entry, after four months, and after one year. RESULTS: The two groups were well matched at entry. At 11 weeks the mean results of treadmill testing were 10.7 (95% confidence interval 10.20 to 11.20) metabolic equivalents for exercise training and 9.7 (9.26 to 10.14) for light exercise (t = 2.85, df = 181, p = 0.005). Apart from this small temporary benefit in mean physical working capacity, there were no significant differences between groups. Improvement in occupational adjustment score from baseline to four months was greater after exercise training than after light exercise, but at one year repeated measures analysis of variance showed no significant effects of treatment or interaction between treatment and time point. CONCLUSION: The effects on quality of life of a low cost programme of light exercise are similar to those obtained from a high intensity exercise training programme.

Vibrotactile adaptation enhances amplitude discrimination.

Human psychophysical detection and amplitude discrimination thresholds for 25-Hz sinusoidal vibrations were measured on the thenar eminence using two-interval forced-choice tracking, in the unadapted state and following exposure to 25-Hz adapting stimuli representing a range of amplitudes (5-25 dB SL). As expected, detection threshold was elevated 6 to 7 dB for each 10-dB increase in the adapting stimulus. In contrast, amplitude difference thresholds for 10 and 20 dB SL standard stimuli were generally lowest when the amplitude of the adapting stimulus was equal to the amplitude of the standard. The results indicate that while adaptation impairs detection of a liminal vibrotactile stimulus, it improves intensity discrimination of supraliminal stimuli that are close in amplitude to the adapting stimulus. The compatability between these results and a recently proposed model of cortical dynamics (Whitsel et al., 1989) suggests that cortical events may contribute significantly to the physiological basis of vibrotactile adaptation.

Maintenance of behaviour change in patients with coronary artery disease.

This paper comments upon patterns of behavioural change after acute cardiac illness and discusses determinants of longterm compliance with advice. The importance of comprehensive rehabilitation during convalescence is emphasised. Education, motivation and support of the patients are essential for the adoption of healthier lifestyles. Despite comprehensive rehabilitation, however, recidivism to former habits is common, particularly with smoking and physical inactivity. This is partly determined by premorbid social and personality characteristics of patients. Social and behavioural support at the workplace and within the community may well be of significant benefit in supporting patients to maintain their necessary health behaviour changes. Some of the evidence related to these issues is discussed and recommendations are made regarding future directions for patient support.

Effect of early programmes of high and low intensity exercise on physical performance after transmural acute myocardial infarction.

Does a programme of light exercise training after acute myocardial infarction produce the same improvement in treadmill performance as aerobic exercise training? Three hundred and eight men from a consecutive series of 479 men with transmural (Q wave) acute myocardial infarction, admitted to a single coronary care unit, were randomly allocated to eight weeks of group aerobic exercise training or group light exercise. Groups were well matched for all characteristics other than site of infarction, which did not significantly affect results. Mean (SD) physical working capacity (metabolic equivalents) determined by treadmill testing at the start of the study (in the third week after infarction) was 6.8 (2.2) v 6.7 (2.5) METs, at the end (in the eleventh week after infarction) 10.8 (2.3) v 9.9 (2.4) METs, and at 12 month review 10.8 (2.4) v 10.7 (1.9) METs for the exercise training group and the light exercise group respectively. The difference of 0.9 METs at the end of the study was the only significant difference between groups. There were no significant intergroup differences at any stage in resting and maximal heart rate, resting and maximal systolic blood pressure, or rate-pressure product. Apart from a small temporarily greater physical working capacity, the physical benefits of aerobic exercise training were equally well achieved by group light exercise.

Vibrotactile adaptation on the face.

Threshold amplitude for vibration is elevated if testing is preceded by extended exposure to a vibratory adapting stimulus of appropriate amplitude and frequency. This phenomenon, previously studied almost exclusively on the hand, is here shown for the first time to occur on the face as well. Adaptation is then used analytically to determine that the two-branched threshold-versus-frequency function obtained on the face by Verrillo and Ecker (1977) represents the activity of two distinct mechanisms. Action spectra of vibrotactile adaptation reveal the presence of both mechanisms even in subjects whose unadapted threshold function (like that reported by Barlow, 1987) shows no sign of duplexity. Finally, the data suggest that on the face (unlike the hand), cross-channel adaptation may occur at high adapting amplitudes.

Time course and action spectrum of vibrotactile adaptation.

In a series of experiments designed to explore the processes underlying adaptation of the sense of flutter-vibration, vibrotactile threshold was measured on the pad of the index finger, using Békésy tracking. Unadapted thresholds were first measured, for a number of frequencies (4-90 Hz) and contactor sizes (1-8 mm diameter). As expected, these measurements indicated the presence of (1) a Pacinian system possessing spatial summation and increasing in sensitivity, as frequency was raised, at the rate of 12 dB/octave; and (2) a non-Pacinian system showing little spatial summation, and with a frequency characteristic matching that of the NP I mechanism of Bolanowski et al. (1988). These baseline data of Experiment 1 guided the selection of stimulus parameters for subsequent experiments, in which threshold for a test stimulus was measured before, during, and after periods of vibrotactile adaptation. In Experiment 2, test stimuli of 10 Hz and 50 Hz were combined factorially with 30-dB SL adapting stimuli of the same two frequencies. When the test stimulus was 10 Hz, the two adapting frequencies were equally effective in raising threshold; however, when the 50-Hz test stimulus was used, the 50-Hz adapting stimulus raised threshold by a greater amount than did the 10-Hz adapter. These results confirm on the finger the independence of adaptation in Pacinian and non-Pacinian channels, a result previously established on the thenar by other workers. For all four frequency combinations, threshold rose exponentially with a time constant of 1.5-2 min. In Experiment 3, an action spectrum was determined, showing the adapting amplitude needed at each of a series of frequencies to raise the threshold of a 10-Hz stimulus by 10 dB; this spectrum was essentially flat from 30 to 90 Hz. The results, taken in conjunction with what is known about rapidly adapting cutaneous mechanoreceptors, imply that the effectiveness of an adapting stimulus is not determined solely by the amount of activity it generates in first-order afferents.

Myocardial salvage with streptokinase combined with nitroglycerine and verapamil in acute myocardial infarction.

We tested the hypothesis that preservation of left ventricular function results from treatment with intravenous streptokinase given in the first 2 hours from onset of acute transmural myocardial infarction together with nitroglycerine and verapamil. Thirty-three consecutive patients with onset of pain less than 2 hours prior to admission, received intravenous streptokinase 1.5 x 10(6) units with intravenous nitroglycerine and verapamil; 23 concurrently admitted "control" patients with pain onset 2-4 hours received intravenous nitroglycerine and verapamil only. Radionuclide ventriculographic assessment at 2 days revealed a significantly greater left ventricular ejection fraction in the streptokinase-treated patients (54.5 +/- 2.8 vs 46.1 +/- 2.9; P less than 0.05), which persisted at 28-35 days (50.1 +/- 2.3 vs 41.2 +/- 2.9; P less than 0.05). Streptokinase-treated patients had a significantly increased incidence of ischaemic events in the 35 days following infarction, but a lower incidence of death, congestive cardiac failure and non-fatal ventricular tachycardia than control group patients. Infarct-related artery patency assessed at 3-5 days was 94% in streptokinase-treated patients. We conclude that early presentation and treatment with intravenous streptokinase, nitroglycerine and verapamil is associated with a high incidence of successful thrombolysis and significant preservation of left ventricular function. Nitroglycerine and verapamil may augment the efficacy of streptokinase in this group of patients.