Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of MAP Kinase–Directed Mitogenic and Protein Kinase B–Mediated Signaling by Cannabinoid Receptor Type 1 in Skeletal Muscle Cells

OBJECTIVE The endogenous cannabinoid (or endocannabinoid) system (ECS) is part of a central neuromodulatory system thought to play a key role in the regulation of feeding behavior and energy balance. However, increasing evidence suggests that modulation of the ECS may also act to regulate peripheral mechanisms involved in these processes, including lipogenesis in adipose tissue and liver, insulin release from pancreatic β-cells, and glucose uptake into skeletal muscle. It was recently shown that cannabinoid receptor type 1 (CB1) and type 2 (CB2), both key components of the ECS, are expressed in human and rodent skeletal muscle. However, their role in modulating insulin sensitivity in this metabolically active tissue has yet to be determined. Our aim was to establish the role, if any, of these receptors in modulating insulin sensitivity in skeletal muscle cells. RESEARCH DESIGN AND METHODS Cultured skeletal muscle cells were exposed to CB1 and/or CB2 pharmacological agonists/antagonists/inverse agonists, and the resulting effects on insulin-regulated phosphatidylinositol 3 kinase (PI 3-kinase)–protein kinase B (PKB) and extracellular signal–related kinases 1/2 (ERK1/2)-directed signaling were determined. RESULTS Here, we report that modulating the activity of the ECS in skeletal muscle regulates both insulin-dependent mitogen-activated protein (MAP) kinase (ERK1/2) and the canonical PI 3-kinase/PKB signaling pathways. We show that pharmacological activation or inhibition of CB1 receptor activity exerts a differential effect with regard to MAP kinase– and PKB-directed signaling. CONCLUSIONS Our study provides evidence that signaling via cannabinoid receptors can significantly modulate mitogenic and metabolic signaling in skeletal muscle with important implications for muscle growth and differentiation as well as the regulation of glucose and lipid metabolism.
Cerebellar learning using perturbations

The cerebellum aids the learning and execution of fast coordinated movements, with acquired information being stored by plasticity of parallel fibre—Purkinje cell synapses. According to the current consensus, erroneously active parallel fibre synapses are depressed by complex spikes arising when climbing fibres signal movement errors. However, this theory cannot solve the credit assignment problem of using the limited information from a global movement evaluation to optimise behaviour by guiding the plasticity in numerous neurones. We identify the possible implementation of an algorithm solving this problem, whereby spontaneous complex spikes perturb ongoing movements, create an eligibility trace for plasticity and signal resulting error changes to guide plasticity. These error changes are extracted by adaptively cancelling the average error. This framework, stochastic gradient descent with estimated global errors, generates specific predictions for synaptic plasticity rules that contradict the current consensus. However, in vitro plasticity experiments under physiological conditions verified our predictions, highlighting the sensitivity of plasticity studies to unphysiological conditions. Using numerical and analytical approaches we demonstrate the convergence and estimate the capacity of learning in our implementation. Finally, a similar mechanism may operate during optimisation of action sequences by the basal ganglia, where dopamine could both initiate movements and signal rewards, analogously to the dual perturbation and correction role of the climbing fibre outlined here.
Sex differences in the relationship of risk factors to subclinical carotid atherosclerosis measured 15 years later : the Tromsø study.

BACKGROUND AND PURPOSE Ultrasound measurement of carotid artery intima-media thickness (IMT) is regarded as a valid index of atherosclerosis. Determinants of IMT in cross-sectional studies have been established, but the long-term relationship between cardiovascular risk factors and subclinical atherosclerosis has not been investigated thoroughly. METHODS We included in the study 3128 middle-aged men and women in Tromsø, Norway, who in 1980 attended the baseline examination with measurements of cardiovascular risk factors and who underwent carotid ultrasonography after 15 years of follow-up. RESULTS Age, blood pressure, total cholesterol, HDL cholesterol, and body mass index were independent long-term predictors of IMT in both men and women. Triglyceride levels were associated with an increase in IMT in women only, while physical activity and smoking were predictors of IMT in men only. However, smoking was associated with increased risk of having atherosclerotic plaque in both men and women. There were no differences in the strength of risk factor effects on IMT in the common carotid artery and the carotid bifurcation. CONCLUSIONS The present study indicates that established cardiovascular risk factors are independent predictors of subclinical atherosclerosis measured after 15 years of follow-up. However, there may be significant sex differences in the relationship between triglycerides, smoking, and physical activity and the risk of atherosclerosis.
Control of Saccharomyces cerevisiae pre-tRNA processing by environmental conditions

tRNA is essential for translation and decoding of the proteome. The yeast proteome responds to stress and tRNA biosynthesis contributes in this response by repression of tRNA transcription and alterations of tRNA modification. Here we report that the stress response also involves processing of pre-tRNA 3′ termini. By a combination of Northern analyses and RNA sequencing, we show that upon shift to elevated temperatures and/or to glycerol-containing medium, aberrant pre-tRNAs accumulate in yeast cells. For pre-tRNAUAUIle and pre-tRNAUUULys these aberrant forms are unprocessed at the 5′ ends, but they possess extended 3′ termini. Sequencing analyses showed that partial 3′ processing precedes 5′ processing for pre-tRNAUAUIle. An aberrant pre-tRNATyr that accumulates also possesses extended 3′ termini, but it is processed at the 5′ terminus. Similar forms of these aberrant pre-tRNAs are detected in the rex1Δ strain that is defective in 3′ exonucleolytic trimming of pre-tRNAs but are absent in the lhp1Δ mutant lacking 3′ end protection. We further show direct correlation between the inhibition of 3′ end processing rate and the stringency of growth conditions. Moreover, under stress conditions Rex1 nuclease seems to be limiting for 3′ end processing, by decreased availability linked to increased protection by Lhp1. Thus, our data document complex 3′ processing that is inhibited by stress in a tRNA-type and condition-specific manner. This stress-responsive tRNA 3′ end maturation process presumably contributes to fine-tune the levels of functional tRNA in budding yeast in response to environmental conditions.
Clinical significance of molecular detection of carcinoma cells in lymph nodes and peripheral blood by reverse transcription-polymerase chain reaction in patients with gastrointestinal or breast carcinomas.

PURPOSE This study evaluates the clinical significance of detection of carcinoembryonic antigen (CEA) mRNA in the dissected lymph nodes and peripheral blood samples of patients with gastrointestinal or breast carcinomas. PATIENTS AND METHODS A total of 406 lymph nodes obtained from 65 patients were analyzed by both histologic and molecular examination of CEA-specific reverse transcriptase-polymerase chain reaction (RT-PCR). Peripheral blood samples from another 102 patients were also analyzed by CEA-specific RT-PCR. Patients were followed up prospectively for 24 +/- 12 months. RESULTS Of 406 lymph nodes, the positive detection rate increased from 20% by histologic examination to 60% by RT-PCR examination. The recurrence rate was 40% in 15 cases showing positive results in both examinations, 14% in 29 cases showing histologically negative but RT-PCR positive results, and none in 21 cases showing negative results in both examinations. The positive detection rate for CEA mRNA in peripheral blood samples increased with advancing stage of disease. With respect to 62 curatively operated cases, CEA mRNA was detected in 12 cases. Four of these 12 cases developed metastatic disease after surgery whereas none of 50 cases negative by RT-PCR developed metastasis. CONCLUSION It has been shown that RT-PCR is a powerful tool to detect CEA mRNA in the lymph nodes or the peripheral blood. This is potentially very useful to determine high-risk patients for metastasis. Serial analysis is warranted to assess the long-term significance of this method and its therapeutic and prognostic implications.
Comparison of Shoplifting Behaviours in Patients with Eating Disorders, Psychiatric Control Subjects, and Undergraduate Control Subjects

Shoplifting behaviours were examined in an eating disorder group (EDG, n = 48), a psychiatric control group (PCG, n = 46), and an undergraduate control group (UCG, n = 82). They were examined in relation to self-esteem, depression, and eating disorder symptomatology. The 3 groups did not differ in overall history of shoplifting, but EDG women were more likely to have shoplifted in the past 6 months (current shoplifting) and to have shoplifted often than were women from the PCG or UCG. Across all 3 groups, current shoplifting was associated with low self-esteem, elevated depression, and purging behaviours at the time of the assessment. The implications of these findings with regard to the relationship between shoplifting and eating disorder symptomatology will be addressed.
Endocrinological disturbances in chronic obstructive pulmonary disease

In this overview, the available literature on endocrinological disturbances in chronic obstructive pulmonary disease (COPD) is reviewed, with stress on growth hormone/insulin-like growth factor I (IGF‐I), thyroid hormone and the anabolic steroids. In COPD, little is known about circulating growth hormone or IGF‐I concentrations. Some authors find a decrease in growth hormone or IGF‐I, others an increase. An increase of growth hormone might reflect a nonspecific response of the body to stress (for instance, hypoxaemia). Until now, only one controlled study on growth hormone supplementation has been published, which however did not reveal any functional benefits. Before growth hormone supplementation can be advised as part of the treatment in COPD, further controlled studies must be performed to investigate its functional efficacy. The prevalence of thyroid dysfunction in COPD and its role in pulmonary cachexia has not been extensively studied. So far, there is no evidence that thyroid function is consistently altered in COPD, except perhaps in a subgroup of patients with severe hypoxaemia. Further research is required to more extensively study the underlying mechanisms and consequences of disturbed thyroid function in this subgroup of COPD patients. A few studies have reported the results of anabolic steroid supplementation in chronic obstructive pulmonary disease. Although some studies have discerned that low circulating levels of testosterone are common in males with chronic obstructive pulmonary disease, little is known about the prevalence, the underlying causes or functional consequences of hypogonadism in these patients. The use of systemic glucocorticosteroids and an influence of the systemic inflammatory response have been suggested as contributing to low testosterone levels. It can be hypothesised that low anabolic hormones will reduce muscle mass and eventually result in a diminished muscle function. Further evidence is required before testosterone replacement can be recommended for males with chronic obstructive pulmonary disease.
Synaptic control of rat supraoptic neurones during osmotic stimulation of the organum vasculosum lamina terminalis in vitro.

1. The effects of osmotic or electrical stimulation of the organum vasculosum lamina terminalis (OVLT) were examined during intracellular recordings (32 degrees C) obtained from ninety‐five supraoptic nucleus magnocellular neurosecretory cells (MNCs) in superfused explants of rat hypothalamus. 2. Brief (10‐20 s) applications of hypertonic and hypotonic solutions to the area of the OVLT caused prolonged (> 1 min) increases and decreases, respectively, in electrical activity in seventy of seventy‐four trials performed on neurones with membrane potentials near spike threshold (approximately ‐55 mV). Changes in firing frequency were related to changes in external osmolality in a dose‐dependent manner between 275 and 355 mosmol kg‐1. 3. When 30 s periods recorded immediately before, and 30 s following, the application of an osmotic stimulus were examined, the frequency of spontaneous EPSPs (sEPSPs) was related in a dose‐dependent manner to the osmolality of the solution superfusing the OVLT region. The increased EPSP frequency was maintained and did not adapt if the osmolality of the medium was raised for periods of > 10 min. In contrast, the frequency of spontaneous IPSPs (sIPSPs) was virtually unaffected by changes in external osmotic pressure. 4. Osmotically evoked changes in MNC firing were strongly correlated with accompanying changes in the frequency of sEPSPs (slope, 0.9; correlation coefficient (r) = 0.7), but not sIPSPs (r = 0.2), suggesting that changes in firing rate following osmotic stimulation of the OVLT are selectively mediated by changes in synaptic excitation. 5. In the presence of bicuculline (5‐10 microM), electrical stimulation of the OVLT evoked fast EPSPs in forty‐seven of forty‐eight MNCs tested. These responses were reversibly reduced by application of 20‐40 microM kynurenic acid (n = 3) or 20‐40 microM 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX; n = 11). Similarly, bath application of CNQX (n = 3) or kynurenic acid (n = 4) reversibly abolished the excitatory response of supraoptic neurones following hypertonic stimulation of the OVLT. 6. Brief (10‐15 s) applications of gamma‐aminobutyric acid (GABA) over the OVLT reversibly abolished increases in sEPSP frequency and action potential firing rate evoked by hyperosmotic stimulation of the OVLT. In the presence of GABA, the rates of sEPSP and sIPSP frequency were reduced to 37 +/‐ 10 and 44 +/‐ 13% (means +/‐ S.E.M.), respectively, of those observed under isotonic conditions (295 mosmol kg‐1). 7. These results suggest that inhibitory and excitatory pathways originating from neurones located within the OVLT are tonically active under resting osmotic conditions in rat hypothalamic explants. Osmotically evoked changes in MNC firing, however, are selectively mediated through increases or decreases in the intensity of the excitatory component of OVLT‐derived inputs.
Concepts of negligence and intention in the assignment of moral responsibility.

Etude du role de la negligence et de l'intention dans la determination de la responsabilite morale. On a fait lire a 67 etudiants des histoires dans lesquelles l'action d'un des protagonistes nuit ou avantage (intentionnellement, par negligence ou par accident) un autre personnage. Conformement aux hypotheses, la negligence est cruciale quand l'action est jugee nuisible alors que c'est l'intention qui est cruciale quand l'action est jugee profitable. On etablit des correlations entre jugement sur la cause et decisions a prendre sur la responsabilite morale
The Impact of Working Conditions, Social Roles, and Personal Characteristics on Gender Differences in Distress

This article analyzes gender differences in employee distress. Work stress has been studied differently for males and females. For males, the predominant focus has been on job conditions; for employed women, the focus has usually been on the multiple demands of domestic and work roles. In this analysis, we combine both approaches, examining the effects of working conditions, nonwork roles, and personal characteristics on self-reports of depression, irritability, and psychophysiological symptoms. Our study population consists of 992 Canadian postal workers, about half of whom are female. We find that males and females respond similarly to stressful jobs, although women tend to report slightly higher levels of distress. Regression analysis reveals that, while gender does exert a small but significant net effect, perceived job characteristics—especially receiving competing demands and the degree of variety and challenge—are the best predictors of distress. Nonwork social roles have no significant effect on distress.
Coordinated optical and radar observations of ionospheric pumping for a frequency pass through the second electron gyroharmonic at HAARP

On 4 February 2005, the High-frequency Active Auroral Research Program (HAARP) facility was operated in O and X mode while pointing into the magnetic zenith to produce artificial optical emissions in the ionospheric F layer. The pump frequency was set to 2.85 MHz to ensure passing through the second electron gyroharmonic of the decaying ionosphere. Optical recordings at 557.7 and 630 nm were performed simultaneously with the side-viewing high frequency (HF) and colocated ultra high frequency (UHF) ionospheric radars. No X-mode effects were found. For O-mode pumping, when passing from below to above the second gyroharmonic frequency, the optical intensity shows a distinct increase when the plasma frequency passes through the second electron gyroharmonic, while the UHF backscatter changes from persistent to overshoot in character. The optical intensity decreases when pump wave reflection ceases, dropping to zero when upper-hybrid resonance ceases. The HF radar backscatter increases when the upper-hybrid resonance frequency passes from below to above the second gyroharmonic frequency. These observations are consistent with the coexistence of the parametric decay and thermal parametric instabilities above the second gyroharmonic. The combined optical and radar data provide evidence that up to three electron-acceleration mechanisms are acting, sometimes simultaneously, depending on the pump frequency relative to the second gyroharmonic. In addition, we provide the first evidence of lower-hybrid waves in HF radar centerline data and show that the parametric decay instability producing Langmuir waves can be stimulated in the magnetic zenith at high latitudes despite the pump wave not reaching the nominal frequency-matching height.
Low Serum Mannose-Binding Lectin Level Increases the Risk of Death due to Pneumococcal Infection

Abstract Background. Previous studies have shown associations between low mannose-binding lectin (MBL) level or variant MBL2 genotype and sepsis susceptibility. However, MBL deficiency has not been rigorously defined, and associations with sepsis outcomes have not been subjected to multivariable analysis. Methods. We reanalyzed MBL results in a large cohort with use of individual data from 4 studies involving a total of 1642 healthy control subjects and systematically defined a reliable deficiency cutoff. Subsequently, data were reassessed to extend previous MBL and sepsis associations, with adjustment for known outcome predictors. We reanalyzed individual data from 675 patients from 5 adult studies and 1 pediatric study of MBL and severe bacterial infection. Results. XA/O and O/O MBL2 genotypes had the lowest median MBL concentrations. Receiver operating characteristic analysis revealed that an MBL cutoff value of 0.5 ≪g/mL was a reliable predictor of low-producing MBL2 genotypes (sensitivity, 82%; specificity, 82%; negative predictive value, 98%). MBL deficiency was associated with increased likelihood of death among patients with severe bacterial infection (odds ratio, 2.11; 95% confidence interval, 1.30–3.43). In intensive care unit–based studies, there was a trend toward increased risk of death among MBL-deficient patients (odds ratio, 1.58; 95% confidence interval, 0.90–2.77) after adjustment for Acute Physiology and Chronic Health Enquiry II score. The risk of death was increased among MBL-deficient patients with Streptococcus pneumoniae infection (odds ratio, 5.62; 95% confidence interval, 1.27–24.92) after adjustment for bacteremia, comorbidities, and age. Conclusions. We defined a serum level for MBL deficiency that can be used with confidence in future studies of MBL disease associations. The risk of death was increased among MBL-deficient patients with severe pneumococcal infection, highlighting the pathogenic significance of this innate immune defence protein.
An Advocacy Exercise for a Psychology and Law Course

This article describes an active learning component of an advanced course in psychology and law. The assignment is to present, in the context of a mock appellate court, the best available psychological data in support of one party in a legal case. Students choose one side of a hypothetical case, locate and review the relevant scientific literature, prepare written analyses and arguments, and present those analyses to a panel of student-justices who question them about the nature of their evidence and the validity of their conclusions. Postcourse assessments showed that the exercise enhanced students' conceptual knowledge of psychology and law as well as their ability to organize and synthesize empirical data, form an argument on the basis of data, and present that argument to the public.
Friends and family: A cross-cultural investigation of social support and subjective well-being among college students

Despite the growing number of cross-cultural studies focusing on well-being, little is known about social support outside of western civilization, particularly among people in Middle Eastern cultures. The current study examined the relationships between perceived social support and components of subjective well-being (i.e. positive and negative affect, satisfaction with life) among college students in Iran, Jordan, and the United States. Perceived support from family significantly predicted each aspect of well-being within each country. However, perceived support from friends did not predict any component of well-being in Iran; yet, in Jordan and the US, friend support predicted higher levels of positive mood. These results will be examined in terms of roles and relationship norms in these countries.
Dangerous decisions: the impact of first impressions of trustworthiness on the evaluation of legal evidence and defendant culpability

Abstract There is little support for the long-standing assumption that judges and jurors can accurately assess credibility. According to Dangerous Decisions Theory (DDT; Porter & ten Brinke, Legal and Criminological Psychology, 14, 119–134, 2009), intuitive evaluations of trustworthiness based on the face may strongly bias the interpretation of subsequent information about a target. In a courtroom setting, the assessment of evidence provided by or concerning a defendant may be fundamentally flawed if its interpretation is influenced by an initial, spontaneous assessment of trustworthiness. In an empirical test of DDT, participants were presented with two vignettes describing major or minor crimes, accompanied by a photograph of the supposed defendant, previously rated as highly trustworthy or untrustworthy in appearance. Participants evaluated culpability following the presentation of evidence in each case. Participants required less evidence to arrive at a guilty verdict and were more confident in this decision for untrustworthy-appearing defendants. The current evidence supports DDT and has implications for legal decision-making practices.