Miracle-dz/UniFAR-FTUs huggingface dataset:
Promoter Occupancy of STAT1 in Interferon Responses Is Regulated by Processive Transcription

ABSTRACT Interferons regulate immunity by inducing DNA binding of the transcription factor STAT1 through Y701 phosphorylation. Transcription by STAT1 needs to be restricted to minimize the adverse effects of prolonged immune responses. It remains unclear how STAT1 inactivation is regulated such that the transcription output is adequate. Here we show that efficient STAT1 inactivation in macrophages is coupled with processive transcription. Ongoing transcription feeds back to reduce the promoter occupancy of STAT1 and, consequently, the transcriptional output. Once released from the promoter, STAT1 is ultimately inactivated by Y701 dephosphorylation. We observe similar regulation for STAT2 and STAT3, suggesting a conserved inactivation mechanism among STATs. These findings reveal that STAT1 promoter occupancy in macrophages is regulated such that it decreases only after initiation of the transcription cycle. This feedback control ensures the fidelity of cytokine responses and provides options for pharmacological intervention.
Olanzapine Augmentation of Serotonin Uptake Inhibitors in Obsessive—Compulsive Disorder: An Open Study

Objective: This study evaluates the clinical response to olanzapine used in association with selective serotonin reuptake inhibitors (SSRIs) or clomipramine in treatment-resistant obsessive–compulsive disorder (OCD). Methods: We describe the cases of 9 patients with serotonin uptake inhibitor-resistant OCD who were given an open-label adjunctive treatment of olanzapine for a minimum of 6 weeks. The response was assessed by using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impression Scale (CGI). Results: Six patients showed improvement of symptoms after the augmentation with olanzapine. One patient (treated with clomipramine) discontinued olanzapine due to side effects, and another 2 did not respond. Conclusion: Olanzapine augmentation of SSRIs in treating OCD showed a good (two-thirds) response rate, and it could therefore be considered as a treatment option when conventional therapies have failed.
Keeping Memory Clear and Stable—The Contribution of Human Basal Ganglia and Prefrontal Cortex to Working Memory

Successful remembering involves both hindering irrelevant information from entering working memory (WM) and actively maintaining relevant information online. Using a voxelwise lesion–behavior brain mapping approach in stroke patients, we observed that lesions of the left basal ganglia render WM susceptible to irrelevant information. Lesions of the right prefrontal cortex on the other hand make it difficult to keep more than a few items in WM. These findings support basal ganglia–prefrontal cortex models of WM whereby the basal ganglia play a gatekeeper role and allow only relevant information to enter prefrontal cortex where this information then is actively maintained in WM.
Factors influencing the antioxidant activity determined by the ABTS.+ radical cation assay.

This study introduces a simple direct antioxidant assay, based on the reduction of the ABTS. + radical cation, and compares it with the myoglobin/ABTS. + assay. The methods give closely similar results, establishing that the antioxidants studied to date in the latter assay act by scavenging the ABTS. + radical cation and not by inhibiting its formation through reduction of ferryl myoglobin or reaction with H2O2.
Hospitalization for depressive syndrome in a cohort of HIV-infected patients contaminated through injecting drug use: MANIF 2000 cohort, France, 1995-1999

The objective of this study was to estimate the relative impact of hospitalization for depressive syndrome (DS) on all causes of hospitalization and characterize individuals more likely to experience hospitalization for DS in the French cohort study, Manif 2000, of patients HIV infected through injection drug use. We selected all patients followed-up to the 24-month visit (C24) who missed no more than one visit. Using medical records, dates and causes of hospitalizations, were collected retrospectively. A Poisson regression model based on generalized estimating equations was used to identify factors associated with hospitalization for DS. During the study period, 223 hospitalizations were recorded for 120 of the 335 selected patients. DS was the second reason for hospitalization after infections, accounting for 14.3% of the total number of hospitalizations. DS wasreported in 32 hospitalizations and involved 24 patients, five of them being hospitalized more than once for the same cause. Factors independently associated with hospitalization for DS were history of multiple incarceration (RR = 2.1, 95% CI: 1.0-4.7), polydrug use (RR = 2.6, 95% CI: 1.1-5.9) and lack of stable relationship (RR = 4.2, 95% CI: 1.6-11.1). In the HAARTera, DS represents an important cause of hospitalization of HIV-infected injecting drug users, mainly concerning patients presenting no stable relationship and signs of social instability. Scheduled psychiatric consultations for these patients would permit us to identify those for whom major depression might lead to hospitalization and provide them with timely and appropriate care.
α‐TEA induces apoptosis of human breast cancer cells via activation of TRAIL/DR5 death receptor pathway

Vitamin E derivative RRR‐α‐tocopherol ether‐linked acetic acid analog (α‐TEA) induces apoptosis in MCF‐7 and HCC‐1954 human breast cancer cells in a dose‐ and time‐dependent manner. α‐TEA induces increased levels of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and death receptor‐5 (DR5) and decreased levels of antiapoptotic factor, cellular FLICE‐like inhibitory protein (c‐FLIP L). DR5/TRAIL induced apoptosis involves downregulation of c‐FLIP (L), caspase‐8 activation, activated proapoptotic mediators tBid and Bax, mitochondrial permeability transition, and activation of caspase‐9. siRNA knockdown of either DR5 or TRAIL blocks the ability of α‐TEA to enhance DR5 protein levels, downregulate c‐FLIP(L) protein levels and induce apoptosis. Combination of α‐TEA + TRAIL acts cooperatively to induce apoptosis, and increase DR5 and decrease c‐FLIP (L) protein levels. siRNA knockdown of c‐FLIP produces a low level of spontaneous apoptosis and enhances α‐TEA‐ and TRAIL‐induced apoptosis. Taken together, these studies show that α‐TEA induces TRAIL/DR5 mitochondria‐dependent apoptosis in human breast cancer cells, and that TRAIL/DR5‐dependent increases in DR5 and decreases in c‐FLIP expression are triggered by TRAIL or α‐TEA treatments. © 2010 Wiley‐Liss, Inc.
The Association of Diabetes With Job Absenteeism Costs Among Obese and Morbidly Obese Workers

Objective: To determine the extent to which absenteeism costs associated with obesity and morbid obesity are traceable to diabetes, and whether obesity and morbid obesity remain predictors of absenteeism costs after controlling for diabetes. Methods: Data from the Medical Expenditure Panel Survey for 2000–2004 are examined. Outcomes are probability of missing work in the previous year and number of workdays missed. Predictors include diabetes, obesity and morbid obesity, age, education, occupation category, and race. Models are estimated by gender. Results: Probability of missing work in the past year, number of days missed, and absenteeism costs rise significantly with diabetes among the obese and morbidly obese, with costs higher for the morbidly obese, after controlling for diabetes. Conclusions: Diabetes is strongly predictive of absenteeism among obese and morbidly obese workers. Employer efforts to reduce absenteeism should include consideration of anti-obesity interventions and diabetes prevention.
Association between work-family conflict and smoking quantity among daily smokers.

INTRODUCTION Recent work demonstrated a direct relation between work-family conflict and likelihood of smoking. This study furthered this area of research by (a) testing the association between work-family conflict and smoking quantity and (b) testing demographic, workplace, and home factors as moderators of this relation. METHODS Participants (N = 423) were daily smokers from a Midwestern community-based sample. Ordinal regression analysis tested work-to-home and home-to-work conflict as predictors (after controlling for demographic characteristics, home factors, and workplace factors) of smoking quantity. Additionally, we tested whether the demographic, home, and workplace factors moderated the effects of work-to-home conflict and home-to-work conflict on smoking quantity. RESULTS Males (OR = 8.81, p = .005), older participants (OR = 1.09, p = .012), those with less educational attainment (OR = 1.87, p = .001), those who reported lower levels of workplace smoking restrictions (OR = 0.87, p = .019), and those who reported higher levels of work-to-home conflict (OR = 1.39, p = .026) smoked more cigarettes per day. There was no significant main effect of home-to-work conflict on smoking quantity (OR = 1.46, p = .099). A significant interaction (OR = 0.55, p = .043) revealed that home-to-work conflict was associated with smoking quantity for females but not for males. CONCLUSIONS After controlling for demographic characteristics and potential confounders, work-to-home conflict had a negative impact on smoking quantity for all participants, and home-to-work conflict was associated with smoking quantity for women. Workplace wellness programs to reduce smoking among employees should take into account the direction of conflict and how the effect of the conflict on smoking behavior may vary based on other factors.
Protein Kinase B Localization and Activation Differentially Affect S6 Kinase 1 Activity and Eukaryotic Translation Initiation Factor 4E-Binding Protein 1 Phosphorylation

ABSTRACT Recent studies indicate that phosphatidylinositide-3OH kinase (PI3K)-induced S6 kinase (S6K1) activation is mediated by protein kinase B (PKB). Support for this hypothesis has largely relied on results obtained with highly active, constitutively membrane-localized alleles of wild-type PKB, whose activity is independent of PI3K. Here we set out to examine the importance of PKB signaling in S6K1 activation. In parallel, glycogen synthase kinase 3β (GSK-3β) inactivation and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation were monitored as markers of the rapamycin-insensitive and -sensitive branches of the PI3K signaling pathway, respectively. The results demonstrate that two activated PKBα mutants, whose basal activity is equivalent to that of insulin-induced wild-type PKB, inhibit GSK-3β to the same extent as a highly active, constitutively membrane-targeted wild-type PKB allele. However, of these two mutants, only the constitutively membrane-targeted allele of PKB induces S6K1 activation. Furthermore, an interfering mutant of PKB, which blocks insulin-induced PKB activation and GSK-3β inactivation, has no effect on S6K1 activation. Surprisingly, all the activated PKB mutants, regardless of constitutive membrane localization, induce 4E-BP1 phosphorylation and the interfering PKB mutant blocks insulin-induced 4E-BP1 phosphorylation. The results demonstrate that PKB mediates S6K1 activation only as a function of constitutive membrane localization, whereas the activation of PKB appears both necessary and sufficient to induce 4E-BP1 phosphorylation independently of its intracellular location.
Changes in lower limb muscle cross-sectional area and tissue fluid volume after transition from standing to supine.

Lower limbs show acute fluid shift in response to transition from upright to supine body position. It is hypothesized that this would affect tomographic estimations of muscle mass and composition. Seven healthy subjects were investigated during the initial 120 min of bed rest, using repeated computerized tomography (CT) and continuous bioelectrical impedance analysis (BIA). Thigh and calf muscle cross-sectional area (CSA) decreased (P < 0.05) by 1.9 and 5.5% whereas fat CSA decreased (P < 0.05) by 4.1 and 4.4%, respectively. Radiological density (RD) of muscle showed a simultaneous increase (P < 0.05) by 4.8% in calf but not (P > 0.05) in thigh. No changes occurred (P > 0.05) in muscle or fat CSA or muscle RD in either thigh or calf between the first and second hour of bed rest. Fluid shift, as estimated by BIA, showed an exponential decay in thigh (tau th = 30 min) and calf (tau c2 = 37 min) by 2.5 and 8.7%, respectively, from first to 120 min of bed rest. Moreover, the calf showed an initial rapid (tau c1 = 8 s) 2.2% decrease. The demonstrated short-term changes in leg CSA were more pronounced in the calf than in the thigh. They were similar in muscle and subcutaneous fat. These fluid shifts merit consideration when tomographic imaging techniques are used to estimate muscle mass and composition.
Sampling from binary measurements - on reconstructions from Walsh coefficients

Reconstructing infinite-dimensional signals from a limited amount of linear measurements is a key problem in many applications such as medical imaging [35], single-pixel and lensless cameras [27], fluorescence microscopy [39] etc. Efficient techniques for such a problem include generalized sampling [6], [23], [31], [43] and its compressed versions [5], [27], as well as methods based on data assimilation [9], [11], [20]. All of these methods have in common that the reconstruction quality depends highly on the subspace angle between the sampling and the reconstruction space. In this paper we consider the case of binary measurements, which, after a standard subtraction trick, can be converted to a 1 and −1 setup. These measurements are modelled with Walsh functions, which form the kernel for the Hadamard transform. For the reconstruction we use wavelets. We show that the relation between the amount of data sampled and the coefficients reconstructed has to be only linear to ensure that the angle is bounded from below and hence the reconstruction is accurate and stable.
Arylamine N-acetyltransferase 2 gene polymorphism in an Algerian population

Abstract Background: The arylamine N-acetyltransferase 2 (NAT2) is a key enzyme in the biotransformation of xenobiotics. NAT2 gene polymorphisms have been associated with the risk of isoniazid hepatotoxicity and these polymorphisms change among different populations. Aim: The objective of this study is to investigate NAT2 polymorphisms in order to predict the prevalence of NAT2 phenotype in an Algerian population. Subjects and methods: Genotyping of NAT2 was done using a PCR-RFLP method. Haplotype was analysed using the software package PHASE, version 2.0. Results: The major haplotypes were NAT2*5B (23.72%), NAT2*6 A (18.61%), NAT2*4 (14.60%) and NAT2*5 F (10%). The average of the expected slow acetylator phenotype was 53%. Conclusion: Our results suggest that the high frequency of slow acetylator phenotype requires investigation into its possible association with ATDH.
Women and the War Story

In a book that radically and fundamentally revises the way we think about war, Miriam Cooke charts the emerging tradition of women's contributions to what she calls the "War Story," a genre formerly reserved for men. Concentrating on the contemporary literature of the Arab world, Cooke looks at how alternatives to the master narrative challenge the authority of experience and the permission to write. She shows how women who write themselves and their experiences into the War Story undo the masculine contract with violence, sexuality, and glory. There is no single War Story, Cooke concludes; the standard narrative--and with it the way we think about and conduct war--can be changed. As the traditional time, space, organization, and representation of war have shifted, so have ways of describing it. As drug wars, civil wars, gang wars, and ideological wars have moved into neighborhoods and homes, the line between combat zones and safe zones has blurred. Cooke shows how women's stories contest the acceptance of a dyadically structured world and break down the easy oppositions--home vs. front, civilian vs. combatant, war vs. peace, victory vs. defeat--that have framed, and ultimately promoted, war.
Spatiotemporal organization and thalamic modulation of seizures in the mouse medial thalamic‐anterior cingulate slice

Purpose: Seizure‐like activities generated in anterior cingulate cortex (ACC) are usually classified as simple partial and are associated with changes in autonomic function, motivation, and thought. Previous studies have shown that thalamic inputs can modulate ACC seizure, but the exact mechanisms have not been studied thoroughly. Therefore, we investigated the role of thalamic inputs in modulating ACC seizure‐like activities. In addition, seizure onset and propagation are difficult to determine in vivo in ACC. We studied the spatiotemporal changes in epileptiform activity in this cortex in a thalamic–ACC slice to clearly determine seizure onset.
Prognosis of Depression in the Elderly

Fifty-six consecutively admitted elderly (65 and over) patients with depression were assessed on mental, physical and social states. They were followed up and assessed at home one year later. A group of 24 depressed in-patients aged under 65 years admitted to the same ward during the same period was also assessed. Outcome was different for the two groups, with 68% of the elderly ‘well’ at one year, against 50% of the younger group. The younger group were more likely to have ‘poor’ outcome (41 %) than the elderly (16%). However, there were more deaths than expected, particularly in the elderly. These findings differ from some previous studies, and indicate an excellent prognosis for depression in the elderly. Outcome in younger patients is less good.
Comparison of Coping Strategy and Disease Knowledge in Dyads of Parents and Their Adolescent With Congenital Heart Disease

Background:Adolescents with congenital heart disease adopt their illness as a part of their lives using their own knowledge and coping strategies. Those who use task-oriented coping strategies, such as relying on education to obtain sufficient disease-related knowledge, demonstrate much higher resilience. However, most health providers tend to provide information about congenital heart disease mainly to the parents instead of the child, and many parents tend to be uncomfortable talking about the disease with their child. Objectives:The purpose of this study was to evaluate and compare adolescent patients’ and their parents’ coping strategies and knowledge of congenital heart disease. Methods:A descriptive and exploratory study design was used. After approval of the institutional review board was obtained, 40 adolescents with congenital heart disease and their parents were recruited from a congenital heart clinic between October 2012 and February 2013. We assessed the coping strategies and disease-related knowledge of both the adolescent patients and their parents. Results:The knowledge level of adolescent patients and their parents had significant gaps between categories, and parents presented with significantly higher knowledge than their adolescents did (P < .01). Parents reported significantly higher mean scores on task-oriented and emotion-oriented coping than their adolescents did (P < .001). In addition, both adolescents and parents of a religious background reported significantly higher scores on emotion-oriented coping than did those who did not report a religion (P < .05). Conclusion:It is essential for healthcare providers to understand the ways in which adolescents and their parents cope with stress as well as the degree of their knowledge to better explicate the process of adaptation to the illness. Therefore, it is critical to develop effective structured and continuous intervention programs not only for adolescent patients and but also for their parents to enhance coping and knowledge of lifelong congenital heart disease.
Acyl Carriers Used as Substrates by the Desaturases and Elongases Involved in Very Long-chain Polyunsaturated Fatty Acids Biosynthesis Reconstituted in Yeast*

The health benefits attributed to very long-chain polyunsaturated fatty acids and the long term goal to produce them in transgenic oilseed crops have led to the cloning of all the genes coding for the desaturases and elongases involved in their biosynthesis. The encoded activities have been confirmed in vivo by heterologous expression, but very little is known about the actual acyl substrates involved in these pathways. Using a Δ6-elongase and front-end desaturases from different organisms, we have reconstituted in Saccharomyces cerevisiae the biosynthesis of arachidonic acid from exogenously supplied linoleic acid in order to identify these acyl carriers. Acyl-CoA measurements strongly suggest that the elongation step involved in polyunsaturated fatty acids biosynthesis is taking place within the acyl-CoA pool. In contrast, detailed analyses of lipids revealed that the two desaturation steps (Δ5 and Δ6) occur predominantly at the sn-2 position of phosphatidylcholine when using Δ5- and Δ6-desaturases from lower plants, fungi, worms, and algae. The specificity of these Δ6-desaturases for the fatty acid acylated at this particular position as well as a limiting re-equilibration with the acyl-CoA pool result in the accumulation of γ-linolenic acid at the sn-2 position of phosphatidylcholine and prevent efficient arachidonic acid biosynthesis in yeast. We confirm by using a similar experimental approach that, in contrast, the human Δ6-desaturase uses linoleoyl-CoA as substrate, which results in high efficiency of the subsequent elongation step. In addition, we report that Δ12-desaturases have no specificity toward the lipid polar headgroup or the sn-position.
Effect of previous nutrition on body composition and maintenance energy costs of growing lambs

1. Forty-eight intact male lambs (30 kg) were fed to gain 16 (H), 5 (M) or –6 (L) kg during a 42 d interval (period 1). Lambs from each of the H and M groups were fed to gain either 16 (HH, MH), 5 (HM, MM) or –6 (HL, ML) kg and lambs from the L group were fed to gain 27 (LS), 16 (LH) or 5 (LM) kg during the ensuing 42 d (period 2). 2. Fasting heat production (FHP) of four lambs from each treatment was determined at the end of period 2. 3. Weights and compositions of the carcass, offal and digesta-free body as well as weights of major internal organs were determined for four lambs of each treatment at the end of periods 1 and 2. 4. Within groups of lambs of similar weight at the end of period 2, body composition was, in general, similar, but FHP was greater in lambs that had been on higher planes of nutrition during period 2. 5. Within groups of lambs of similar weight, lambs that were fed at higher planes of nutrition during period 2 had greater weights or proportions of liver, small intestine, large intestine and stomach. 6. Neither weight of the liver, kidney, stomach, small intestine, large intestine nor daily fasting heat production were constant functions of body-weight. Relations of these traits to body-weight changed with rate of gain. 7. Regression analysis indicated that the feeding of lambs at higher planes of nutrition during period 1 resulted in higher maintenance requirements of those lambs during period 2.