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Tim Johnson

Publications and source records attributed to Tim Johnson.

8 recordsLinked to original sources
PubMed2006

How tyrosine 15 phosphorylation inhibits the activity of cyclin-dependent kinase 2-cyclin A.

Inhibition of cyclin-dependent kinase 1 (CDK1) activity by Tyr-15 phosphorylation directly regulates entry into mitosis and is an important element in the control of the unperturbed cell cycle. Active site phosphorylation of other members of the CDK family that regulate cell cycle progression instates checkpoints that are fundamental to eukaryotic cell cycle regulation. Kinetic and crystallographic analyses of CDK2-cyclin A complexes reveal that this inhibitory mechanism operates through steric blockade of peptide substrate binding and through the creation of an environment that favors a non-productive conformation of the terminal group of ATP. By contrast, tyrosine phosphorylation of CDK2 alters neither its Km for ATP nor its significant intrinsic ATPase activity. Tyr-15-phosphorylated CDK2 retains trace protein phosphorylation activity that should be considered in quantitative and qualitative cell cycle models.

CDC2 Protein Kinase↗
PubMed2005

Sociality as a defensive response to the threat of loss.

Laboratory research studying behavior in the Prisoner's Dilemma (PD) game is consistent with the commonplace perception that social exchange is risky. Although they often do cooperate, people also often defect. Thus, the decision to enter a PD game with a stranger, about whom one has no good basis for predicting behavior, is a bet on cooperation. Many investigators have explored a range of cognitive processes and individual differences putatively bearing on the choice to enter such games, but few have asked how people perceive, assess, and respond to social risk in general. That is what we ask here. From the well known finding that people are risk-averse in the domain of gains and risk-tolerant in the domain of losses, we predict that, with game incentives constant, people will be more willing to enter social relationships when game payoffs are framed as losses than when they are framed as gains. We tested this prediction in a student population playing PD games. Results strongly supported the prediction, suggesting that human sociality may have evolved more as a defensive response to the possibility of loss than as an opportunistic attempt to capture gain.

Journal Article↗
PubMed2005

Human behaviour: Egalitarian motive and altruistic punishment.

Altruistic punishment is a behaviour in which individuals punish others at a cost to themselves in order to provide a public good. Fehr and Gächter present experimental evidence in humans indicating that negative emotions towards non-cooperators motivate punishment, which, in turn, provokes a high degree of cooperation. Using Fehr and Gächter's original data, we provide an alternative analysis of their experiment that suggests that egalitarian motives are more important than motives for punishing non-cooperative behaviour. This finding is consistent with evidence that humans may have an evolutionary incentive to punish the highest earners in order to promote equality, rather than cooperation.

Altruism↗
PubMed2003

The magnitude of hedgehog signaling activity defines skin tumor phenotype.

Gain-of-function mutations in SMO have been implicated in constitutive activation of the hedgehog signaling pathway in human basal cell carcinomas (BCCs). We used a truncated keratin 5 (DeltaK5) promoter to assess the potential role of the human M2SMO mutant in BCC development in adult transgenic mice. DeltaK5-M2SMO mouse epidermis is hyperproliferative, ex presses BCC protein markers and gives rise to numerous epithelial downgrowths invading the underlying dermis. Lesions strikingly similar to human basaloid follicular hamartomas develop, but BCCs do not arise even in elderly mice. Hedgehog target gene transcripts were only modestly upregulated in mouse and human follicular hamartomas, in contrast to the high levels detected in BCCs. Cyclins D1 and D2 were selectively upregulated in mouse BCCs. Our data suggest that the levels of hedgehog pathway activation and G(1) cyclins are major determinants of tumor phenotype in skin, and strongly implicate deregulated hedgehog signaling in the genesis of human basaloid follicular hamartomas. Expression of an activated SMO mutant in keratinocytes appears to be insufficient for the development and/or maintenance of full-blown BCCs.

Alopecia↗
PubMed2003

Limitations on residents' working hours at New York teaching hospitals: a status report.

Teaching hospitals in New York have been subject to regulations that limit the working hours of residency trainees since July 1989. Following a period of enhanced survey activity by the State Department of Health in the late 1990s, the state awarded a contract to a third-party organization to conduct annual audits of the state's teaching hospitals to assess compliance with the regulations. As of October 2002, preliminary results indicate that 75 of the 118 teaching hospitals in the state (63.6%) were found to be out of compliance with some component of the regulations. The most common citations for noncompliance were (1) working in excess of 24 consecutive hours (45%), and (2) working in excess of 80 hours per week, averaged over four weeks (28%). For New York teaching hospitals, the key factors identified as posing significant challenges to achieving full compliance with the regulations included (1) assuming responsibility for the work schedules of residents; (2) scheduling and monitoring difficulties; (3) the education efforts associated with the regulations; (4) the documentation requirements; (5) variations in learning abilities among the residents; and (6) mistaking verbal compliance for actual compliance. As the state begins a new round of surveys, it will be expecting better compliance efforts, and New York teaching hospitals are committed to this difficult but worthy goal.

General Surgery↗
PubMed2002

Postoperative cognitive dysfunction in middle-aged patients.

BACKGROUND: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent. METHODS: The authors compared the changes in neuropsychological test results at 1 week and 3 months in patients aged 40-60 yr, using a battery of neuropsychological tests, with those of age-matched control subjects using Z-score analysis. They assessed risk factors and associations of POCD with measures of subjective cognitive function, depression, and activities of daily living. RESULTS: At 7 days, cognitive dysfunction as defined was present in 19.2% (confidence interval [CI], 15.7-23.1) of the patients and in 4.0% (CI, 1.6-8.0) of control subjects (P < 0.001). After 3 months, the incidence was 6.2% (CI, 4.1-8.9) in patients and 4.1% (CI, 1.7-8.4) in control subjects (not significant). POCD at 7 days was associated with supplementary epidural analgesia and reported avoidance of alcohol consumption. At 3 months, 29% of patients had subjective symptoms of POCD, and this finding was associated with depression. Early POCD was associated with reports of lower activity scores at 3 months. CONCLUSIONS: Postoperative cognitive dysfunction occurs frequently but resolves by 3 months after surgery. It may be associated with decreased activity during this period. Subjective report overestimates the incidence of POCD. Patients may be helped by recognition that the problem is genuine and reassured that it is likely to be transient.

Adult↗