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J D Cohen

Publications and source records attributed to J D Cohen.

At least 19 recordsLinked to original sources
PubMed2006

Indole-3-acetic acid protein conjugates: novel players in auxin homeostasis.

Indole-3-acetic acid (IAA) is found in plants in both free and conjugated forms. Within the group of conjugated IAA there is a unique class of proteins and peptides where IAA is attached directly to the polypeptide structure as a prosthetic group. The first gene, IAP1, encoding for a protein with IAA as a prosthetic group, was cloned from bean (Phaseolus vulgaris). It was shown that the expression of IAP1 as a major IAA modified protein in bean seed (PvIAP1) was correlated to a developmental period of rapid growth during seed development. Moreover, this protein underwent rapid degradation during germination. Since further molecular analysis was difficult in bean, the IAP1 gene was transformed into Arabidopsis thaliana and Medicago truncatula. Expression of the bean IAP1 gene in both plant species under the control of its native promoter targeted protein expression to the seeds. In Arabidopsis no IAA was found to be attached to PvIAP1. These results show that there is specificity to protein modification by IAA and suggests that protein conjugation may be catalyzed by species specific enzymes. Furthermore, subcellular localization showed that in Arabidopsis PvIAP1 was predominantly associated with the microsomal fraction. In addition, a related protein and several smaller peptides that are conjugated to IAA were identified in Arabidopsis. Further research on this novel class of proteins from Arabidopsis will both advance our knowledge of IAA proteins and explore aspects of auxin homeostasis that were not fully revealed by studies of free IAA and lower molecular weight conjugates.

Arabidopsis↗
PubMed2005

Sodium reduction for hypertension prevention in overweight adults: further results from the Trials of Hypertension Prevention Phase II.

Sodium reduction is efficacious for primary prevention of hypertension, but the feasibility of achieving this effect is unclear. The objective of the paper is detailed analyses of adherence to and effects of the sodium reduction intervention among overweight adults in the Trials of Hypertension Prevention, Phase II. Sodium reduction (comprehensive education and counselling about how to reduce sodium intake) was tested vs no dietary intervention (usual care) for 36-48 months. A total of 956 white and 203 black adults, ages 30-54 years, with diastolic blood pressure 83-89 mmHg, systolic blood pressure (SBP) <140 mmHg, and body weight 110-165% of gender-specific standard weight were included in the study. At 36 months, urinary sodium excretion was 40.4 mmol/24 h (24.4%) lower in sodium reduction compared to usual care participants (P<0.0001), but only 21% of sodium reduction participants achieved the targeted level of sodium excretion below 80 mmol/24 h. Adherence was positively related to attendance at face-to-face contacts. Net decreases in SBP at 6, 18, and 36 months of 2.9 (P<0.001), 2.0 (P<0.001), and 1.3 (P=0.02) mmHg in sodium reduction vs usual care were associated with an overall 18% lower incidence of hypertension (P=0.048); were relatively unchanged by adjustment for ethnicity, gender, age, and baseline blood pressure, BMI, and sodium excretion; and were observed in both black and white men and women. From these beneficial but modest results with highly motivated and extensively counselled individuals, sodium reduction sufficient to favourably influence the population blood pressure distribution will be difficult to achieve without food supply changes.

Adult↗
PubMed2005

Effect of bicycle racing saddle design on transcutaneous penile oxygen pressure.

AIM: To determine the reliability of monitoring penile transcutaneous oxygen (tpO2) during cycling, and to assess the influence of seat design and cycling position on tpO2. METHODS EXPERIMENTAL DESIGN: repeated measures analysis of the effects of seat design and riding position on tpO2 values. PARTICIPANTS: 31 male cyclists between the ages of 20 and 50 years participated. Subject inclusion criteria were: averaged=or>80 miles of road bicycling per week during the 2 months prior to enrollment in this study; no history of vascular disease, diabetes, or sexual dysfunction; and had an erection within 15 days prior to study. MEASURES: mean tpO2 values were calculated for seated and standing positions using 3 current bicycle seat designs. RESULTS: Test-retest reliability for seated cycling tpO2 values had an ICC (3,1) of 0.76 and mean absolute difference of 5.1 mmHg. Test-retest reliability for standing cycling tpO2 values had an ICC(3,1) of 0.88 and mean absolute difference of 7.23 mmHg. No interaction effect occurred between seat design and position. Seat design had no significant effect on tpO2 values. Seated cycling significantly reduced tpO2 levels compared with standing cycling (P<0.05). Mean percent decreases in tpO2 from standing to seated cycling were; Vetta 76%, Terry 73%, and Specialized 62%. CONCLUSION: The data suggest that penile tpO2 monitoring is reliable for use during cycling studies. None of the seats exhibited any significant ability to spare penile tpO2. The implications of decreased penile tpO2 over different time intervals on penile physiology remain to be investigated.

Adult↗
PubMed2001

Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial.

BACKGROUND: RTS,S/AS02 is a pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg, incorporating a new adjuvant (AS02). We did a randomised trial of the efficacy of RTS,S/AS02 against natural P. falciparum infection in semi-immune adult men in The Gambia. METHODS: 306 men aged 18-45 years were randomly assigned three doses of either RTS,S/AS02 or rabies vaccine (control). Volunteers were given sulfadoxine/pyrimethamine 2 weeks before dose 3, and kept under surveillance throughout the malaria transmission season. Blood smears were collected once a week and whenever a volunteer developed symptoms compatible with malaria. The primary endpoint was time to first infection with P. falciparum. Analysis was per protocol. FINDINGS: 250 men (131 in the RTS,S/AS02 group and 119 in the control group) received three doses of vaccine and were followed up for 15 weeks. RTS,S/AS02 was safe and well tolerated. P. falciparum infections occurred significantly earlier in the control group than the RTS,S/AS02 group (Wilcoxon's test p=0.018). Vaccine efficacy, adjusted for confounders, was 34% (95% CI 8.0-53, p=0.014). Protection seemed to wane: estimated efficacy during the first 9 weeks of follow-up was 71% (46-85), but decreased to 0% (-52 to 34) in the last 6 weeks. Vaccination induced strong antibody responses to circumsporozoite protein and strong T-cell responses. Protection was not limited to the NF54 parasite genotype from which the vaccine was derived. 158 men received a fourth dose the next year and were followed up for 9 weeks; during this time, vaccine efficacy was 47% (4-71, p=0.037). INTERPRETATION: RTS,S/AS02 is safe, immunogenic, and is the first pre-erythrocytic vaccine to show significant protection against natural P. falciparum infection.

Adult↗
PubMed2001

An fMRI investigation of emotional engagement in moral judgment.

The long-standing rationalist tradition in moral psychology emphasizes the role of reason in moral judgment. A more recent trend places increased emphasis on emotion. Although both reason and emotion are likely to play important roles in moral judgment, relatively little is known about their neural correlates, the nature of their interaction, and the factors that modulate their respective behavioral influences in the context of moral judgment. In two functional magnetic resonance imaging (fMRI) studies using moral dilemmas as probes, we apply the methods of cognitive neuroscience to the study of moral judgment. We argue that moral dilemmas vary systematically in the extent to which they engage emotional processing and that these variations in emotional engagement influence moral judgment. These results may shed light on some puzzling patterns in moral judgment observed by contemporary philosophers.

Brain↗
PubMed2001

A role for flavin monooxygenase-like enzymes in auxin biosynthesis.

Although auxin is known to regulate many processes in plant development and has been studied for over a century, the mechanisms whereby plants produce it have remained elusive. Here we report the characterization of a dominant Arabidopsis mutant, yucca, which contains elevated levels of free auxin. YUCCA encodes a flavin monooxygenase-like enzyme and belongs to a family that includes at least nine other homologous Arabidopsis genes, a subset of which appears to have redundant functions. Results from tryptophan analog feeding experiments and biochemical assays indicate that YUCCA catalyzes hydroxylation of the amino group of tryptamine, a rate-limiting step in tryptophan-dependent auxin biosynthesis.

Alleles↗
PubMed2001

Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia.

BACKGROUND: Previously we proposed that dorsolateral prefrontal cortex (PFC) supports a specific working memory (WM) subcomponent: the ability to represent and maintain context information necessary to guide appropriate task behavior. By context, we mean prior task-relevant information represented in such a form that it supports selection of the appropriate behavioral response. Furthermore, we hypothesized that WM deficits in schizophrenia reflect impaired context processing due to a disturbance in dorsolateral PFC. We use functional magnetic resonance imaging to examine PFC activation in medication-naive, first-episode patients with schizophrenia during a WM, task-isolating context processing. METHODS: Fourteen first-episode, medication-naive patients with schizophrenia and 12 controls similar in age, sex, and parental education underwent functional magnetic resonance imaging during performance of an A-X version of the Continuous Performance Test. RESULTS: Patients with schizophrenia demonstrated deficits in dorsolateral PFC activation in task conditions requiring context processing but showed intact activation of posterior and inferior PFC. In addition, patients demonstrated intact activation of the primary motor and somatosensory cortex in response to stimulus processing demands. CONCLUSIONS: These results demonstrate selectivity in dorsolateral PFC dysfunction among medication-naive first-episode patients with schizophrenia, suggesting that a specific deficit in PFC function is present at illness onset, prior to the administration of medication or the most confounding effects of illness duration. Furthermore, these results are consistent with the hypothesis that WM deficits in patients with schizophrenia reflect an impairment in context processing due to a disturbance in dorsolateral PFC function.

Adult↗
PubMed2001

Hematologic masquerade of rhabdomyosarcoma.

We present the case of a 12-year-old boy admitted with the diagnosis of acute leukemia, but found to have an infiltration of the marrow by an alveolar rhabdomyosarcoma (RMS) as determined by the cytogenetic demonstration of a t(2;13)(q25;q14). A primary tumor could not be found. With this case as a basis, we have tabulated features of all similar cases in the literature and discuss the possible optimal approaches to establishing the correct diagnosis in such patients.

Acute Disease↗
PubMed2001

Anterior cingulate cortex, conflict monitoring, and levels of processing.

It has been hypothesized that the anterior cingulate cortex (ACC) contributes to cognition by detecting conflicts that might occur during information processing, to signal the need to engage top-down attentional processes. The present study was designed to investigate which levels of processing are being monitored by the ACC for the presence of conflict. Event-related fMRI was used to measure the response of the ACC during an interference task in which distracting information could be congruent, conflicting at the level of stimulus identification, or conflicting at the response level. Although both types of conflict caused reaction time interference, the fMRI data showed that the ACC is responsive only to response conflict, even when controlling for reaction times. These results suggest a highly specific contribution of the ACC to executive functions, through the detection of conflicts occurring at later or response-related levels of processing.

Adult↗
PubMed2001

Conflict monitoring and cognitive control.

A neglected question regarding cognitive control is how control processes might detect situations calling for their involvement. The authors propose here that the demand for control may be evaluated in part by monitoring for conflicts in information processing. This hypothesis is supported by data concerning the anterior cingulate cortex, a brain area involved in cognitive control, which also appears to respond to the occurrence of conflict. The present article reports two computational modeling studies, serving to articulate the conflict monitoring hypothesis and examine its implications. The first study tests the sufficiency of the hypothesis to account for brain activation data, applying a measure of conflict to existing models of tasks shown to engage the anterior cingulate. The second study implements a feedback loop connecting conflict monitoring to cognitive control, using this to simulate a number of important behavioral phenomena.

Cognition↗
PubMed2001

Sex differences in chest pain in patients with documented coronary artery disease and exercise-induced ischemia: Results from the PIMI study.

BACKGROUND: Sex differences in the pathophysiologic course of coronary artery disease (CAD) are widely recognized, yet accurate diagnosis of coronary artery disease in women remains challenging. METHODS: To determine sex differences in the clinical manifestation of CAD, we studied chest pain reported during daily activities, exercise, and mental stress in 170 men and 26 women. All patients had documented CAD (>50% narrowing in at least 1 major coronary artery or prior myocardial infarction) and all had 1-mm ST-segment depression on treadmill exercise. We collected psychologic test results, serum samples (potassium, epinephrine, norepinephrine, cortisol, b-endorphin, and glucose), and cardiac function, sensory threshold, and autonomic function data at specified times before, during, or after exercise and mental stress tests to assess measures of depression, anxiety, and neurohormonal and thermal pain perception. RESULTS: Women reported chest pain more often than men during daily activities (P =.04) and during laboratory mental stressors (P =.01) but not during exercise. Men had lower scores than women on measures of depression, trait anxiety, harm avoidance, and reward dependence (P <.05 for all). Women had significantly lower plasma b-endorphin levels at rest (4.2 +/- 3.9 vs 5.0 +/- 2.5 pmol/L for men, P =.005) and at maximal mental stress (6.4 +/- 5.1 vs 7.4 +/- 3.5 pmol/L for men, P <.01). A higher proportion of women than men had marked pain sensitivity to graded heat stimuli applied to skin (hot pain threshold <41 degrees C, 33% vs 10%, P =.001). CONCLUSIONS: Our results reflect sex differences in the affective and discriminative aspects of pain perception and may help explain sex-related differences in clinical presentations.

Activities of Daily Living↗
PubMed2001

An integrative theory of prefrontal cortex function.

The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed

Animals↗
PubMed2001

Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia.

OBJECTIVE: The dorsolateral prefrontal cortex has been implicated in both working memory and the pathophysiology of schizophrenia. A relationship among dorsolateral prefrontal cortex activity, working memory dysfunction, and symptoms in schizophrenia has not been firmly established, partly because of generalized cognitive impairments in patients and task complexity. Using tasks that parametrically manipulated working memory load, the authors tested three hypotheses: 1) patients with schizophrenia differ in prefrontal activity only when behavioral performance differentiates them from healthy comparison subjects, 2) dorsolateral prefrontal cortex dysfunction is associated with poorer task performance, and 3) dorsolateral prefrontal cortex dysfunction is associated with cognitive disorganization but not negative or positive symptoms. METHOD: Seventeen conventionally medicated patients with schizophrenia and 16 healthy comparison subjects underwent functional magnetic resonance imaging while performing multiple levels of the "n-back" sequential-letter working memory task. RESULTS: Patients with schizophrenia showed a deficit in physiological activation of the right dorsolateral prefrontal cortex (Brodmann's area 46/9) in the context of normal task-dependent activity in other regions, but only under the condition that distinguished them from comparison subjects on task performance. Patients with greater dorsolateral prefrontal cortex dysfunction performed more poorly. Dorsolateral prefrontal cortex dysfunction was selectively associated with disorganization symptoms. CONCLUSIONS: These results are consistent with the hypotheses that working memory dysfunction in patients with schizophrenia is caused by a disturbance of the dorsolateral prefrontal cortex and that this disturbance is selectively associated with cognitive disorganization. Further, the pattern of behavioral performance suggests that dorsolateral prefrontal cortex dysfunction does not reflect a deficit in the maintenance of stimulus representations per se but points to deficits in more associative components of working memory.

Adult↗
PubMed2001

Context processing in older adults: evidence for a theory relating cognitive control to neurobiology in healthy aging.

A theory of cognitive aging is presented in which healthy older adults are hypothesized to suffer from disturbances in the processing of context that impair cognitive control function across multiple domains, including attention, inhibition, and working memory. These cognitive disturbances are postulated to be directly related to age-related decline in the function of the dopamine (DA) system in the prefrontal cortex (PFC). A connectionist computational model is described that implements specific mechanisms for the role of DA and PFC in context processing. The behavioral predictions of the model were tested in a large sample of older (N = 81) and young (N = 175) adults performing variants of a simple cognitive control task that placed differential demands on context processing. Older adults exhibited both performance decrements and, counterintuitively, performance improvements that are in close agreement with model predictions.

Adult↗