SEARCH · Search PubMed

Results for “REST”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources

PubMed1989

Use of psychoactive medication and the quality of care in rest homes. Findings and policy implications of a statewide study.

Rest homes have become a major component of the health care system for frail elderly persons and deinstitutionalized psychiatric patients. Although psychoactive medications are frequently used in rest homes, there is little detailed information about the extent of such use, its supervision, or its effects. In a survey of a random sample of 55 rest homes in Massachusetts, we found that 55 percent of the residents were taking at least one psychoactive medication. Antipsychotic medications were being administered to 39 percent; of these, 18 percent were receiving two or more such drugs. In a follow-up investigation, we studied 837 residents in 44 rest homes with particularly high levels of antipsychotic-drug use. About half the residents had no evidence of participation by a physician in decisions about their mental health during the year of the study. A third of the residents had performance deficits on mental-status testing that indicated serious cognitive impairment, although the causal relation of such impairment to medication use could not be determined. Six percent had evidence of moderate or severe tardive dyskinesia, probably as a side effect of medication. An assessment of staff competence revealed a low level of comprehension of the purpose and side effects of commonly used psychoactive drugs. We conclude that psychoactive drugs are widely used in rest homes, with little medical supervision or understanding by staff members of their possible side effects.

Aged↗

PubMedDate not supplied

Effect of reversible hypoperfusion on left ventricular volumes measured with gated SPECT at rest and after adenosine infusion.

BACKGROUND: The aims of this study were to assess the degree of postischemic left ventricular (LV) dilatation after adenosine stress and to determine the extent to which LV volumes measured with gated single photon emission computed tomography (SPECT) correspond to those obtained by echocardiography. METHODS: Eight-frame gated SPECT with a 2-day technetium-99m tetrofosmin acquisition protocol was used. End-diastolic (EDV) and end-systolic (ESV) volumes were measured automatically with the quantitative gated SPECT algorithm. Reversible myocardial hypoperfusion was evaluated with a 16-segment, 4-point perfusion score model. LV volumes at rest were also measured with echocardiography by use of the biplane Simpson rule. RESULTS: Twenty-two patients (group 1) showed normal perfusion and normal LV systolic function, whereas 33 patients (group 2) had evident coronary heart disease with reversible hypoperfusion. Patients in group 2 had greater EDV and ESV than those in group 1 both at rest and poststress. A greater reduction in ESV from poststress to rest was seen in group 2, which resulted in a slight increase in ejection fraction for patients in this group. The change in ESV from poststress to rest was significantly influenced by the degree of reversible hypoperfusion and by the change in heart rate from poststress to rest. We found a good correlation between LV volumes measured with gated SPECT and echocardiography. CONCLUSION: LV volume measurements with quantitative gated SPECT are comparable to those obtained with echocardiography. Patients with ischemic heart disease have greater LV volumes than patients with normal perfusion. Exercise-augmented adenosine infusion in patients with ischemic heart disease affects ESV more than EDV. This response is partly modulated by the degree of reversible hypoperfusion and possibly represents a minor degree of poststress stunning.

Adenosine↗

PubMed2006

Reciprocal actions of REST and a microRNA promote neuronal identity.

MicroRNAs (miRNAs) are implicated in both tissue differentiation and maintenance of tissue identity. In most cases, however, the mechanisms underlying their regulation are not known. One brain-specific miRNA, miR-124a, decreases the levels of hundreds of nonneuronal transcripts, such that its introduction into HeLa cells promotes a neuronal-like mRNA profile. The transcriptional repressor, RE1 silencing transcription factor (REST), has a reciprocal activity, inhibiting the expression of neuronal genes in nonneuronal cells. Here, we show that REST regulates the expression of a family of miRNAs, including brain-specific miR-124a. In nonneuronal cells and neural progenitors, REST inhibits miR-124a expression, allowing the persistence of nonneuronal transcripts. As progenitors differentiate into mature neurons, REST leaves miR-124a gene loci, and nonneuronal transcripts are degraded selectively. Thus, the combined transcriptional and posttranscriptional consequences of REST action maximize the contrast between neuronal and nonneuronal cell phenotypes.

Animals↗

PubMed2003

Electroencephalographic signatures of attentional and cognitive default modes in spontaneous brain activity fluctuations at rest.

We assessed the relation between hemodynamic and electrical indices of brain function by performing simultaneous functional MRI (fMRI) and electroencephalography (EEG) in awake subjects at rest with eyes closed. Spontaneous power fluctuations of electrical rhythms were determined for multiple discrete frequency bands, and associated fMRI signal modulations were mapped on a voxel-by-voxel basis. There was little positive correlation of localized brain activity with alpha power (8-12 Hz), but strong and widespread negative correlation in lateral frontal and parietal cortices that are known to support attentional processes. Power in a 17-23 Hz range of beta activity was positively correlated with activity in retrosplenial, temporo-parietal, and dorsomedial prefrontal cortices. This set of areas has previously been characterized by high but coupled metabolism and blood flow at rest that decrease whenever subjects engage in explicit perception or action. The distributed patterns of fMRI activity that were correlated with power in different EEG bands overlapped strongly with those of functional connectivity, i.e., intrinsic covariations of regional activity at rest. This result indicates that, during resting wakefulness, and hence the absence of a task, these areas constitute separable and dynamic functional networks, and that activity in these networks is associated with distinct EEG signatures. Taken together with studies that have explicitly characterized the response properties of these distributed cortical systems, our findings may suggest that alpha oscillations signal a neural baseline with "inattention" whereas beta rhythms index spontaneous cognitive operations during conscious rest.

Attention↗

PubMed1976

Resting state in normal and simian virus 40 transformed Chinese hamster lung cells.

Normal cell deprived of amino acids or serum factors enter a resting state, whereas cells transformed by wild-type simian virus 40 do not. The ability to enter a resting state is temperature-sensitive (ts) in cells transformed by a tsA mutant of simian virus 40. We shown further: (i) that when complete medium is added to resting cells, the length of time until the onset of DNA synthesis often exceeds the length of G1 in growing cells; (ii) that the length of this interval depends upon the conditions used to arrest cell growth; but (iii) that transferring cultures from medium depleted for one factor to medium depleted in a second factor never leads to a round of DNA synthesis; and (iv) that DNA synthesis does not resume rapidly when a resting culture of cells transformed by the tsA mutant is transferred to the permissive temperature in suboptimal medium. A model proposing that in suboptimal conditions cells leave the cell cycle and traverse a branch pathway to enter the resting state is consistent with these findings.

Cell Division↗

PubMed1990

Resting and activated subsets of mouse multipotent hematopoietic stem cells.

The fluorescent vital dye rhodamine 123 (Rh-123), which preferentially accumulates in mitochondrial membranes, can be used as a probe to indicate mitochondrial and hence cellular activity. In this study, mouse bone marrow hematopoietic stem cells were subdivided into Rh-123lo, Rh-123med, and Rh-123hi populations. The Rh-123lo (resting) population was significantly enriched in cells with a higher proliferative potential compared to the Rh-123hi (activated) population. The resting population exhibited a 20-fold greater ability to differentiate into splenic colony-forming units (CFU-S) relative to the activated population, whereas the activated population contained about 4-fold more day 13 CFU-S on primary transfer relative to the resting population. The two populations produced morphologically distinct splenic colonies; however, the frequency and morphology of in vitro colonies were very similar. Only the resting population provided sufficient stem cells to transfer long-term hematopoietic repopulation to secondary recipient animals after lethal irradiation. On a single cell level, the resting and activated populations exhibited an equivalent ability to differentiate into lymphoid and myeloid progeny. These observations provide further insight into the heterogeneous nature of CFU-S and directly demonstrate that multipotent hematopoietic stem cells are heterogeneous with regard to their clonogenic capacities.

Animals↗

PubMed2001

Acetylcholine receptor channel structure in the resting, open, and desensitized states probed with the substituted-cysteine-accessibility method.

The nicotinic acetylcholine (ACh) receptors cycle among classes of nonconducting resting states, conducting open states, and nonconducting desensitized states. We previously probed the structure of the mouse-muscle ACh receptor channel in the resting state obtained in the absence of agonist and in the open states obtained after brief exposure to ACh. We now have probed the structure in the stable desensitized state obtained after many minutes of exposure to ACh. Muscle-type receptor has the subunit composition alpha(2)betagammadelta. Each subunit has four membrane-spanning segments, M1-M4. The channel lumen in the membrane domain is lined largely by M2 and to a lesser extent by M1 from each of the subunits. We determined the rates of reaction of a small, sulfhydryl-specific, charged reagent, 2-aminoethyl methanethiosulfonate with cysteines substituted for residues in alphaM2 and the alphaM1-M2 loop in the desensitized state and compared these rates to rates previously obtained in the resting and open states. The reaction rates of the substituted cysteines are different in the three functional states of the receptor, indicating significant structural differences. By comparing the rates of reaction of extracellularly and intracellularly added 2-aminoethyl methanethiosulfonate, we previously located the closed gate in the resting state between alphaG240 and alphaT244, in the predicted M1-M2 loop at the intracellular end of M2. Now, we have located the closed gate in the stable desensitized state between alphaG240 and alphaL251. The gate in the desensitized state includes the resting state gate and an extension further into M2.

Acetylcholine↗

PubMed2004

Catalytic residues of the telomere resolvase ResT: a pattern similar to, but distinct from, tyrosine recombinases and type IB topoisomerases.

ResT is a member of the telomere resolvases, a newly discovered class of DNA breakage and reunion enzymes. These enzymes are involved in the formation of co-valently closed hairpin DNA ends that are found in linear prokaryotic chromosomes and plasmids. The hairpins are generated by telomere resolution, where the replicated linear DNA ends are processed by DNA breakage followed by joining of DNA free ends to the complementary strand of the same molecule. Previous studies have shown that ResT catalyzes hairpin formation through a two-step transesterification similar to tyrosine recombinases and type IB topoisomerases. In the present study we have probed the reaction mechanism of ResT. The enzyme was found to efficiently utilize a substrate with a 5'-bridging phosphorothiolate at each cleavage site, similar to tyrosine recombinases/type IB topoisomerases. Using such a substrate to trap the covalent protein-DNA intermediate, coupled with affinity purification and mass spectroscopy, we report a new, non-radioactive approach to directly determine the position of the amino acid in the protein, which is linked to the DNA. We report that tyrosine 335 is the active site nucleophile in ResT, strengthening the link between ResT and tyrosine recombinases/type IB topoisomerases. However, a distinct pattern of catalytic residues with similarities, but distinct differences from the above enzymes was suggested. The differences include the apparent absence of a general acid catalyst, as well as the dispensability of the final histidine in the RKHRHY hexad. Finally, two signature motifs (GRR(2X)E(6X)F and LGH(4-6X)T(3X)Y) near the catalytic residues of aligned telomere resolvases are noted.

Amino Acid Motifs↗

PubMed2001

Metabolic response to small and large 13C-labelled pasta meals following rest or exercise in man.

The metabolic response to a 150 or 400 g 13C-labelled pasta meal was studied for 8 h following rest or exercise at low or moderate workload (n 6). Following rest, the 400 g meal totally suppressed fat oxidation (v. 14.1 g following the 150 g meal) and a small amount of glucose was converted into fat (4.6 g), but fat oxidation remained high in subjects who had exercised following both the small (21.8 and 34.1 g) and large meal (14.1 and 32.3 g). Exogenous glucose oxidation was significantly higher in subjects who had remained at rest both following the small (67.6 g v. 60.4 and 51.3 g in subjects who exercised at low and moderate workloads) and large meal (152.2 v. 123.0 and 127.2 g). Endogenous glucose oxidation was similar in the three groups following the 150 g meal (42.3-58.0 g), but was significantly lower following the 400 g meal in subjects who had exercised at low workload (24.2 v. 72.2 g following rest; and was totally suppressed in those who had exercised at moderate workload. As a consequence, a larger positive glycogen balance was observed in subjects who exercised before the large meal (182.8-205.1 g v. 92.4 g following rest; Total fat oxidation calculated from 08.00 hours to 20.00 hours was similar in subjects who exercised at low and moderate workloads. These results indicate that: (1) de novo lipogenesis, which plays only a minor role for the disposal of an acute dietary carbohydrate load, is totally suppressed following exercise, even when a very large carbohydrate load is ingested; (2) the reduction in glycogen turnover as well as a preferential conversion of glucose into glycogen are responsible for the increase in glycogen stores following exercise; (3) for a similar energy expenditure, exercise at low workload for a longer period does not favour fat oxidation when the post-exercise period is taken into account.

Adult↗

PubMed2000

Muscular rest and gap frequency as EMG measures of physical exposure: the impact of work tasks and individual related factors.

Owing to an orderly recruitment of motor units, low threshold type I fibres are presumed to be vulnerable in contractions of long duration. To study load on these fibres muscular rest was registered as the time fraction of electromyographic (EMG) activity below a threshold. Moreover, the frequency of periods with muscular rest, EMG gaps, was derived, since a low gap frequency has been shown to be a risk factor for musculoskeletal disorders. Trapezius EMG was registered in 24 female hospital cleaners, 21 female office workers and 13 male office workers during one working day. Cleaners have a high risk of neck/shoulder pain and had much less muscular rest than office workers measured as a percentage of total registered time (median value = 1.5%, range = 0.2-13% vs. median value = 12%, range = 0.0-32%, respectively). Gap frequency showed no difference between the two occupational groups. Both measures displayed a wide inter-individual variation. For the cleaners, some of the variance was explained by body mass index (BMI) and age, with lower values of muscular rest for older subjects with a high BMI. Among the office workers, low values of muscular rest and a high gap frequency were registered in subjects with a low subjective muscular tension tendency. Gender, strength, smoking, job strain, employment time and musculoskeletal symptoms had no impact on either EMG measure.

Adult↗

PubMed2003

The effect of work-rest schedules and type of task on the discomfort and performance of VDT users.

Consideration of the literature survey indicates that video display terminal (VDT) operators tend to have a high incidence of musculoskeletal problems, visual fatigue, and job stress. Although a number of ergonomic improvements in workstation design and work environment can help to reduce these problems, a proper work-rest schedule deserves consideration since it is easily applicable and inexpensive. The objective of this study was to compare the work-rest schedules for VDT operators considering data entry and mental arithmetic tasks. An experiment was conducted with 10 male college students as participants. The methodology included a discomfort questionnaire and performance measures. The independent variables were the work-rest schedule (60-minute work/10-minute rest, 30-minute work/5-minute rest, and 15-minute work/micro breaks) and the type of task (data entry and a mental arithmetic task). The results were analysed using multiple analysis of variance followed by separate analyses. The 15/micro schedule resulted in significantly lower discomfort in the neck, lower back, and chest than the other schedules for data entry task. The 30/5 schedule followed by 15/micro schedule resulted in the lowest eyestrain and blurred vision. Discomfort in the elbow and arm was the lowest with the 15/micro schedule for the mental arithmetic task. The 15/micro schedule resulted in the highest speed, accuracy, and performance for both of the tasks, compared with the 60/10 and 30/5 schedules. The data entry task resulted in significantly increased speed, accuracy, and performance, and lower shoulder and chest discomfort than the mental arithmetic task.

Adult↗

PubMed1994

Intermittent microclimate cooling during rest increases work capacity and reduces heat stress.

Requirements for special protective equipment while working in hazardous environments can present a significantly increased thermal burden and early onset of physical fatigue. Ambulatory (backpack) or tethered personal cooling can accelerate metabolic heat removal, but is often not practical from an ergonomic standpoint. The efficacy of incorporating personal cooling during non-ambulatory rest periods was evaluated in subjects (n = 8) with varying levels of fitness. Treadmill work (approximately 475 W, 40% VO2 max) was alternately performed for 30 min followed by 30 min of rest. Subjects walked and rested under three separate experimental conditions: (1) control (C), in which light clothing was worn; (2) CPE, in which a chemical protective ensemble (CPE) was worn, and (3) CPE plus intermittent microclimate cooling (COOL). The WBGT condition for all trials was 31 degrees C. During the COOL trial the subjects additionally wore a personal cooling vest which allowed for the circulation of chilled liquid over the torso during rest. Under C conditions, relatively modest changes in rectal temperature (Tre) were observed, which stabilized over time. CPE wear resulted in a progressive rise in Tre and early fatigue. The addition of intermittent cooling during each rest cycle (COOL trial) significantly attenuated heat storage such that an oscillating, but equilibrated Tre was established and work capacity was at least doubled. Moreover, the perceived cooling effect was appreciable for all subjects. Therefore, intermittent personal cooling provided a useful means of enhancing work productivity and may have application for certain military and industrial personnel performing heavy work in hot environments. This approach should provide a practical alternative for reducing stress/fatigue when work/rest cycles are employed.

Body Temperature Regulation↗

PubMed2003

Line bisection task performance and resting EEG alpha power.

Neurologically normal subjects generally err to the left of veridical center when performing a line bisection task, a phenomenon termed "pseudoneglect." We hypothesized that resting electroencephalogram (EEG) alpha oscillations may show relationships with attentional mechanisms and give some clues about the underlying mechanisms of pseudoneglect. We recorded resting EEGs of 41 subjects and tested them with a paper-pencil line bisection task. Our results showed that line bisection scores of men (n=18) were less biased and their performance was higher compared to those of women (n=20), but these differences only approached significance. The eyes open resting EEG alpha power of women was significantly and positively correlated with their line bisection performance. In general, significant relationships were related to the left hand performance when the lines were presented in the left hemispace. Greater resting alpha power was correlated with lower absolute bisection score or, in other words, higher bisection performance. Greater alpha power also correlated with diminished leftward bisection bias (or reduced pseudo-neglect). The resting EEG alpha of men was weakly associated with bisection performance. Results discussed in terms of Kinsbourne's activation-orientation theory and Basar's view on brain oscillations.

Adult↗

PubMed2001

The inhibition of oxygen radical release from human neutrophils by resting platelets is reversed by administration of acetylsalicylic acid or clopidogrel.

Resting platelets inhibit oxygen radical release from neutrophils. Antiplatelet therapy may support this function by preventing platelet activation. Whether antiplatelet agents affect the antioxidative action of resting platelets in the absence of platelet activation is unknown. The effect of acetylsalicylic acid or clopidogrel administration on the antioxidative action of resting platelets was therefore studied in ten healthy volunteers. Preparations of resting platelets were obtained from 5 subjects each - before, during and after an eight-day course of daily treatment with 100 mg of acetylsalicylic acid or 75 mg of the thienopyridine clopidogrel. Human peripheral blood neutrophils were pretreated with the platelets at a ratio of (1/5)0 for 45 min; then formyl-Met-Leu-Phe-triggered oxygen radical release was measured fluorometrically. The inhibitory effect of platelets on oxygen radical release from neutrophils which was seen before treatment was abolished by antiplatelet therapy with either of the drugs, and inhibition was restored gradually after discontinuing acetlsalicylic acid/ clopidogrel intake. Results suggest that the protective role of resting platelets in controlling oxygen radical release from neutrophils in the absence of platelet activation may be impaired by antiplatelet therapy.

Adult↗

PubMedDate not supplied

Resting energy expenditure of children attending a rehabilitation programme following head injury.

STATEMENT OF PURPOSE: Increased resting energy expenditure following head injury is well documented, but whether this increase extends into rehabilitation and whether this is affected by changes in body composition have not been studied. The aim of this study was to determine whether children attending a rehabilitation program following head injury had altered energy expenditure and body composition. METHODS: Measurements of resting energy expenditure by indirect calorimetry were performed in 21 head injured children (mean age 10.2 +/- 3.8 years). Measurement of body composition was performed using total body potassium. RESULTS: Measured resting energy expenditure values were widely distributed, ranging from 52.3-156.4% of predicted values, yet the mean percentage predicted using Schofield weight, Schofield weight and height and World Health Organization predictive equations were 97.5%, 97.4% and 98.6%, respectively. Mean percentage of expected total body potassium for weight, height and age for head injured children were 85.1 +/- 15.5%, 89.1 +/- 14.1% and 86.9 +/- 15.9%, thus all showed significant depletion. CONCLUSIONS: During rehabilitation, using predictive equations to estimate resting energy expenditure in this group revealed a small bias on average but very large bias at the individual level. Head injured children had altered resting energy expenditure and body composition.

Adolescent↗

PubMed2001

Ultradian and circadian activity-rest rhythms of preterm neonates compared to full-term neonates using actigraphic monitoring.

During the first weeks of life, preterm neonates show fewer circadian rhythms in their physiological parameters than full-term neonates. To determine whether preterm neonates differ in their temporal adaptation to the day-night cycle from full-term neonates at the early age of 1 week, we compared activity-rest behavior of both groups. Activity-rest behavior of 10 neurologically healthy preterm neonates (born in 34th to 36th week of gestation) and 10 neurologically healthy full-term neonates (born in 37th to 42nd week of gestation) was monitored longitudinally for 8 successive days in the first 2 weeks of life. Actigraphy was used to register and display time patterns of activity and rest in neonates by using small actometers, which resemble a wristwatch. Nursing/feeding was recorded using the actometer's integrated event marker button. Recordings for preterm neonates were conducted in the hospital, recordings for full-term neonates were carried out in the hospital and in their homes. In addition to the actigraphic recordings, a standardized diary was kept regularly. To assess periodic characteristics, frequency components of activity-rest behavior were analyzed using fast Fourier transformation (FFT). Amounts of daily sleep time, nightly sleep time, and sleep time during 24h were compared. Nursing/feeding epochs were also analyzed for 5 preterm and 5 full-term neonates to compare their food intake behavior. The majority of preterm neonates showed a multitude of ultradian frequencies in their spectra. In contrast, several full-term neonates showed a distinct circadian frequency. In preterm neonates, average nightly sleep and average daily sleep of all recorded days were very similar, but after the fourth day of life, only average nightly sleep increased. In full-term neonates, average nightly and daily sleep time of all recorded days differed by about 1h. Average sleep time during 24h for preterm and full-term neonates was similar. Preterm neonates showed longer intervals between events of food intake than full-term neonates. The circadian peaks in the frequency spectra of full-term neonates may indicate the initial adaptation in the first week of life to a 24h day. This is in agreement with our results concerning the different durations of nightly and daily sleep. The increase in nightly sleep time of preterm neonates may be attributed to the progressing adaptation to a circadian activity-rest pattern.

Activity Cycles↗

PubMed2002

Contribution of the rest-activity circadian rhythm to quality of life in cancer patients.

Quality of life (QoL) is estimated from patients scores to items related to everyday life, including rest and activity. The rest-activity rhythm reflects endogenous circadian clock function. The relation between the individual rhythm in activity and QoL was investigated in 200 patients with metastatic colorectal cancer. Patients wore a wrist actigraph (Ambulatory Monitoring Inc., New York. NY) for 3-5 d before chronotherapy, and completed a QoL questionnaire developed by the European Organization for Research and Treatment of Cancer (QLQ-C30) plus the Hospital Anxiety and Depression Scale. The rest-activity circadian rhythm was characterized by the mean activity level (m), autocorrelation coefficient at 24h (r24), and the dichotomy index (I < O). a ratio between the amount of activity while in and out of bed. The distribution of the rest-activity cycle parameters and that of QoL scores was independent of sex, age, primary tumor, number of metastatic sites, and prior treatment. Both the 24h rhythm indicators were positively correlated with global QoL score as well as physical, emotional, and social functioning. Negative correlations were found between m, r24, or I < O and fatigue, appetite loss, and nausea. The rest-activity circadian rhythm appeared to be an objective indicator of physical welfare and QoL. This analysis suggests that circadian function may be one of the biological determinants of QoL in cancer patients.

Adult↗

PubMed1998

CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand.

4-1BB ligand (4-1BBL) is a member of the tumor necrosis factor (TNF) family expressed on activated antigen-presenting cells. Its receptor, 4-1BB, is a member of the TNF receptor family expressed on activated CD4 and CD8 T cells. We have produced a soluble form of 4-1BBL using the baculovirus expression system. When coimmobilized on plastic with anti-CD3, soluble 4-1BBL induces interleukin (IL)-2 production by resting CD28+ or CD28- T cells, indicating that 4-1BBL can function independently of other cell surface molecules, including CD28, in costimulation of resting T cell activation. At low concentrations of anti-CD3, 4-1BBL is inferior to anti-CD28 in T cell activation. However, when 4-1BB ligand is provided together with strong TCR signals, then 4-1BBL and anti-CD28 are equally potent in stimulation of IL-2 production by resting T cells. We find that TNF receptor-associated factor (TRAF)1 or TRAF2 associate with a glutathione S-transferase-4-1BB cytoplasmic domain fusion protein in vitro. In T cells, we find that association of TRAF1 and TRAF2 with 4-1BB requires 4-1BB cross-linking. In support of a functional role for TRAF2 in 4-1BB signaling, we find that resting T cells isolated from TRAF2-deficient mice or from mice expressing a dominant negative form of TRAF2 fail to augment IL-2 production in response to soluble 4-1BBL. Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent costimulatory signals to resting T cells.

Animals↗