Miracle-dz/UniFAR-FTUs huggingface dataset:
Nuclear Export of Human β-Catenin Can Occur Independent of CRM1 and the Adenomatous Polyposis Coli Tumor Suppressor*

β-Catenin is a mediator of the Wnt-signaling pathway. In many cancers, β-catenin is stabilized and accumulates in the nucleus where it associates with lymphoid-enhancing factor 1/ T-cell transcription factors to activate genes involved in cell transformation. Previously, we showed that adenomatous polyposis coli (APC) protein can regulate β-catenin localization by nuclear export. In this study, we used in vitro transport assays to test whether cellular β-catenin can exit the nucleus independent of APC and the CRM1 export receptor. In digitonin-permeabilized SW480 (APCmut/mut) tumor cells, nuclear β-catenin decreased >60% in export reactions in the absence of exogenous factors. Under similar conditions, nuclear c-ABL was only exported after the addition of cytosolic extract, and the export was blocked by the CRM1-specific inhibitor, leptomycin B. The nuclear export of β-catenin was not blocked by leptomycin B treatment, revealing a CRM1- and APC-independent pathway. The export of β-catenin was sensitive to lower temperatures and the removal of ATP, indicating an active process. Ectopically expressed yellow fluorescent protein-β-catenin also displayed CRM1-independent export. Conversely, the overexpression of the CRM1 transporter moderately stimulated export of nuclear β-catenin, confirming that β-catenin exits the nucleus by at least two distinct pathways. The shuttling ability of tumor cell β-catenin has implications for its regulation and its role in transferring signals between the nucleus and plasma membrane.
‘Blind spot’ policing in Belgian multicultural neighbourhoods and the implications for human rights

This article reconsiders the findings of three years of qualitative empirical research in six Belgian multicultural neighbourhoods on the dynamics of policing in terms of its implications for human rights. Based on interviews with both police and ethnic minorities, as well as observations of police interventions on the beat, our findings show that police knowledge of certain groups in multicultural neighbourhoods influences their images of those groups. More specifically, these images strongly influence police actions in relation to those groups by generating over-policing and under-policing. This leads to some form of ‘blind spot policing’ with implications for the right to security of citizens living in these neighbourhoods. Furthermore, these findings generate questions in relation to whether police can be true guardians of human rights and to the intrinsic ambiguities emerging from the Belgian model of community oriented policing.
Transcompartmental Inflammatory Responses in Humans: IV Versus Endobronchial Administration of Endotoxin*

Objectives:Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following lipopolysaccharide-induced pulmonary and systemic inflammation. Design:Randomized, double-blind, placebo-controlled, crossover study. Setting:ICU. Subjects:Healthy male volunteers. Interventions:Fifteen volunteers (mean age, 23; SD, 2 yr) received Escherichia coli endotoxin (lipopolysaccharide, 4 ng/kg) IV or endobronchially on two different study days. Groups were evaluated by bronchoalveolar lavage at baseline (0 hr) and 2, 4, 6, 8, or 24 hours postchallenge. Cardiorespiratory variables were continuously recorded throughout the study day, and plasma and bronchoalveolar lavage fluid markers of inflammation were measured. Measurements and Main Results:IV endotoxin elicited a systemic inflammatory response with a time-dependent increase and peak in tumor necrosis factor-&agr;, interleukin-6, and leukocyte counts (all p < 0.001). Furthermore, a delayed (6–8 hr) increase in bronchoalveolar lavage fluid interleukin-6 concentration (p < 0.001) and alveolar leukocyte count (p = 0.03) and a minor increase in bronchoalveolar lavage fluid tumor necrosis factor-&agr; were observed (p = 0.06). Endobronchial endotoxin was followed by progressive alveolar neutrocytosis and increased bronchoalveolar lavage fluid tumor necrosis factor-&agr;, interleukin-6, and albumin (all p < 0.001); a systemic inflammatory response was observed after 2–4 hours, with no change in plasma tumor necrosis factor-&agr;. Conclusions:Acute lung or systemic inflammation in humans is followed by a transcompartmental proinflammatory response, the degree and differential kinetics of which suggests that the propagation of inflammation may depend on the primary site of injury.
Ghrelin/Leptin-imbalance in patients with primary biliary cirrhosis.

BACKGROUND The recently discovered peptide hormone ghrelin mainly produced in gastric oxyntic cells may act as a counterpart to leptin in the regulation of food intake and fat utilization. Leptin, involved in the stimulation of proinflammatory cytokines and catabolic energy balance, is elevated in patients with liver cirrhosis. In the present study, we evaluated serum ghrelin and bound leptin levels in patients with primary biliary cirrhosis (PBC) in relation to C-peptide and glucose concentration. METHODS In 22 female patients with PBC (Child-Pugh stage A) and in 36 female controls we measured serum ghrelin, bound leptin, and C-peptide levels using specific immunoassays. RESULTS In comparison to controls serum bound leptin levels were significantly higher in patients with PBC ( p < 0.01) whereas serum ghrelin levels were decreased compared to the control group ( p < 0.01). In parallel, C-peptide concentrations were increased ( p < 0.01) with no significant change in circulating glucose levels. CONCLUSION Our data confirm in PBC patients that serum bound leptin levels are increased and clearly show a parallel decrease in serum ghrelin concentrations acting as a physiological counterpart to leptin. Furthermore, we suggest that these changes are linked to the insulin resistance observed in our patients.
A COMPARATIVE ANALYSIS OF RETRIBUTIVE JUSTICE AND THE LAW OF QISAS

Discussion on penology generally revolves around the philosophy behind the ‘punishment’ and its ‘implementation’ in order to maintain a crime-free, harmonious society. To understand the philosophy of the major school of thoughts for punishment, this paper discusses the theory of retributivism as a punishment mechanism and relates it to Qisas - the theory of punishment that hinges on Islamic criminal law jurisprudence. The objective of this paper is to compare the retributive concept of punishment with the Islamic theory of Qisas and to unravel how Islam attempts to establish justice through punishment while implementing forgiveness. It is significant to note that we can find a nexus between the retributive and Qisas school of theory that perpetrators should be punished as a consequence of the crime or an act that is against norms of the community. Nonetheless, this paper concludes that Qisas is quite distinct from the concept of retributivism in the case of punishment. Whereas the core of the retributive justice system is to put the moral blame on the offender for the offence and to provide justice through similar punishment; the law of Qisas is more concerned with the fairness and forgivingness. Keywords: Forgiveness, Islamic criminal law, punishment, retributive justice, Qisas Cite as: Karim, R. , Newaz, S. , & Kabir, A.I. (2017). A comparative analysis of retributive justice and the law of qisas. Journal of Nusantara Studies, 2 (2), 169-177. http://dx.doi. org/10.24200/jonus.vol2iss2pp169-177
Maternal Lifetime Depressive/Anxiety Disorders and Children's Internalizing Symptoms: The Importance of Family Context.

OBJECTIVES This study investigated the interaction effects between mothers' lifetime depressive/anxiety disorders and other psychosocial correlates of 6 to 11 year-old children's self-reported internalizing symptoms in the Quebec Child Mental Health Survey. METHOD A representative subsample of 1,490 Quebec children aged 6 to 11 years was selected from the original sample. Multiple linear regression analyses were performed using children's internalizing symptoms and child, family and socioeconomic characteristics. RESULTS Four variables interacted significantly with mothers' lifetime depressive/anxiety disorders to predict 6 to 11 year-old children's internalizing symptoms: child age (t=2.415, P=0.016), mother's caring behaviours (t=2.950, P=0.003), mother's punitive behaviours (t=2.629, P=0.009) and parental social support (t=2.272, P=0.023). CONCLUSION Results highlight the important contribution of the family context to the intergenerational transmission of internalizing symptoms and the relevance of taking into account children's developmental period. They support the importance of early screening of children's self-reported internalizing symptoms, among children of depressed/anxious parents. It is suggested to develop preventive intervention programs oriented towards children of depressed/anxious parents and exposed to relational difficulties.
Erythrocyte O2 Transport and Metabolism and Effects of Vitamin B6 Therapy in Type II Diabetes Mellitus

The effects of vitamin B6 on erythrocyte metabolism, erythrocyte hemoglobin O2 affinity (P50), and nonenzymatic glycosylation were studied in 15 Caucasian men with type II (non-insulin-dependent) diabetes mellitus. A control group of 13 healthy Caucasian men was also evaluated. Before treatment, diabetic subjects had low mean cell hemoglobin concentration values and increases in both erythrocyte 2,3-diphosphoglycerate (2,3-DPG) levels and erythrocyte hexokinase activities. Although all three of these changes are associated with a decrease in hemoglobin O2 (Hb-O2) affinity, P50 values were normal in diabetic subjects. Moreover, P50 values normalized to pH 7.4 (P507.4) were inversely related to the level of glycosylated hemoglobin (HbA1c). Both erythrocyte 2,3-DPG and erythrocyte ATP were also inversely related to HbA1c. Vitamin B6 nutriture, as determined by erythrocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, was normal in all diabetic subjects before vitamin B6 therapy. Nonetheless, HbA1c levels decreased after 6 wk of treatment with 150 mg/day pyridoxine and increased again during placebo administration. These changes were not explained by changes in fasting blood glucose. Pyridoxine therapy also decreased P507.4values and increased erythrocyte AST and ALT activities but had no effect on 2,3-DPG, ATP, or the activities of hexokinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. These observations suggest that 1) nonenzymatic glycosylation may play a role in regulating both erythrocyte metabolism and Hb-O2affinity in diabetic subjects, and 2) vitamin B6 therapy may modify nonenzymatic glycosylation of hemoglobin in this population.
Reconsidering the attribution-adjustment relation following a major negative event: coping with the loss of a child.

Field studies have not yet conclusively established how attributions affect adjustment to unanticipated traumatic events. This may be due, in part, to the adoption of several untested assumptions in most prior research. It has usually been assumed that attributional issues are important to people who experience a traumatic event, that such concern is adaptive, and that specific attributions (e.g., self-blame) influence subsequent adjustment. These assumptions were tested with longitudinal data collected over 18 months from 124 parents whose child died of Sudden Infant Death Syndrome. By 3 weeks postloss, 45% of parents were not concerned with attributional issues. These parents were less distressed and less likely to blame themselves or others for the death. Longitudinal analyses did not support the assumption that attributions influence subsequent adjustment. Rather, attributions to onself or others appear to be symptomatic of distress.
Platelet glycoprotein VI‐related clinical defects

Human patients with defects associated with the platelet collagen receptor, glycoprotein (GP)VI, are rare and usually described as having a mild bleeding disorder. However, here we review clinical profiles of patients with familial or acquired GPVI defects, revealing the bleeding defect is often severe and associated with immune dysfunction. GPVI is a member of the immunoreceptor family, and co‐expressed on platelets with Fc receptor γ‐chain (FcRγ). Ligand binding to GPVI leads to activation of platelet integrins, in particular αIIbβ3 that mediates platelet aggregation; and activation of endogenous platelet metalloproteinases resulting in ectodomain shedding and release of a soluble GPVI fragment. Increasing evidence supports the functional importance of GPVI/FcRγ in thrombus formation at arterial shear rates, and expression levels of platelet GPVI may be a marker of thrombotic risk. Over the past 20 years, patients have been reported with GPVI‐related defects involving: (i) an acquired deficiency, resulting from (a) anti‐GPVI autoantibodies or (b) other causes; or (ii) a congenital deficiency, where (c) GPVI is not expressed or (d) is expressed in a dysfunctional form with defective signalling to αIIbβ3. Clinical consequences of GPVI‐related defects may be uniquely informative about the role of platelet GPVI in health and disease.
Early prediction of functional outcome after stroke

Objectives: (I) To obtain biomechanical parameters and assessment scores applied at a very early stage after stroke that predict best the functional outcome after rehabilitation. (II) To evaluate the predictive value of changes (i.e. increase or decrease) of these parameters during the first week in relation to the predictive value of their absolute scores. Design: Prospective outcome study. Subjects: Forty-one stroke patients, admitted to the stroke unit within 24 hours. Main outcome measures: Barthel Index, Rivermead Motor Assessment, Motor Club Assessment and Functional movement activities, NIH-Stroke scale (NIH-SS), Grip strength. Results: Parameters assessed within the first hours after stroke correlated only weakly with the outcome. The best model predicting functional outcome and independence in activities of daily living of stroke patients after 6 months was that including NIH-SS, grip strength, age and previous stroke explaining 79% of the variance. These parameters assessed on day 7 post-stroke are more predictive than the difference between stroke onset and day 7 post-stroke. Conclusion: Parameters for predicting outcome should not be assessed before day 7 post-stroke.
The N‐terminal transmembrane domain (TMD0) and a cytosolic linker (L0) of sulphonylurea receptor define the unique intrinsic gating of KATP channels

ATP‐sensitive potassium (KATP) channels comprise four pore‐forming Kir6 and four regulatory sulphonylurea receptor (SUR) subunits. SUR, an ATP‐binding cassette protein, associates with Kir6 through its N‐terminal transmembrane domain (TMD0). TMD0 connects to the core domain of SUR through a cytosolic linker (L0). The intrinsic gating of Kir6.2 is greatly altered by SUR. It has been hypothesized that these changes are conferred by TMD0. Exploiting the fact that the pancreatic (SUR1/Kir6.2) and the cardiac (SUR2A/Kir6.2) KATP channels show different gating behaviours, we have tested this hypothesis by comparing the intrinsic gating of Kir6.2 with the last 26 residues deleted (Kir6.2Δ26) co‐expressed with SUR1, S1‐TMD0, SUR2A and S2‐TMD0 at −40 and −100 mV (S is an abbreviation for SUR; TMD0/Kir6.2Δ26, but not TMD0/Kir6.2, can exit the endoplastic reticulum and reach the cell membrane). Single‐channel kinetic analyses revealed that the mean burst and interburst durations are shorter for TMD0/Kir6.2Δ26 than for the corresponding SUR channels. No differences were found between the two TMD0 channels. We further demonstrated that in isolation even TMD0‐L0 (SUR truncated after L0) cannot confer the wild‐type intrinsic gating to Kir6.2Δ26 and that swapping L0 (SUR truncated after L0)between SUR1 and SUR2A only partially exchanges their different intrinsic gating. Therefore, in addition to TMD0, L0 and the core domain also participate in determining the intrinsic gating of Kir6.2. However, TMD0 and L0 are responsible for the different gating patterns of full‐length SUR1 and SUR2A channels. A kinetic model with one open and four closed states is presented to explain our results in a mechanistic context.
A Minimal Tat System from a Gram-positive Organism

The Tat system transports folded proteins across bacterial and thylakoid membranes. In Gram-negative organisms, a TatABC substrate-binding complex and separate TatA complex are believed to coalesce to form an active translocon, with all three subunits essential for translocation. Most Gram-positive organisms lack a tatB gene, indicating major differences in organization and possible differences in mode of action. Here, we have studied Tat complexes encoded by the tatAdCd genes of Bacillus subtilis. Expression of tatAdCd in an Escherichia coli tat null mutant results in efficient export of a large, cofactor-containing E. coli Tat substrate, TorA. We show that the tatAd gene complements E. coli mutants lacking either tatAE or tatB, indicating a bifunctional role for this subunit in B. subtilis. Second, we have identified and characterized two distinct Tat complexes that are novel in key respects: a TatAdCd complex of ∼230 kDa that is significantly smaller than the analogous E. coli TatABC complex (∼370 kDa on BN gels) and a separate TatAd complex. The latter is a discrete entity of ∼270 kDa as judged by gel filtration chromatography, very different from the highly heterogeneous E. coli TatA complex that ranges in size from ∼50 kDa to over 600 kDa. TatA heterogeneity has been linked to the varying size of Tat substrates being translocated, but the singular nature of the B. subtilis TatAd complex suggests that discrete TatAC and TatA complexes may form a single form of translocon.
The Effect of Dofetilide on the Heart Rate of GD11 and GD13 Rat Embryos, in vivo, Using Ultrasound.

BACKGROUND There are a wide range of drugs including antidepressants, anticonvulsants and antipsychotics that cause embryonic bradycardia in vitro but it is unknown if they have a similar effect in vivo. One way to verify whether these in vitro findings are replicated in vivo is by the use of ultrasound examination of dosed pregnant rats. We tested this by examining the effect of dofetilide on embryonic heart rate (HR) in vivo using ultrasound. METHODS Rats were dosed with dofetilide (4 or 2.5 mg/kg) on GD11 or (5 or 2.5 mg/kg) on GD13 and embryonic HR assessed by ultrasound, 2 and 24 hr later. Fetuses were examined for malformations on GD20. RESULTS HR of control rat embryos showed a wide range at each gestational day. Dosing with dofetilide on GD11 caused severe bradycardia (∼ 60% reduction) 2 hours after dosing with recovery after 24 h of >60% of LD but death and slow HR among the HD embryos. At term, 32% of the LD surviving fetuses had hypoplastic upper lip while >90% of HD embryos had died. On GD13, embryonic HR was reduced in a dose-dependent manner with >85% of LD and HD recovered by 24 hr. At term, all LD fetuses were normal while 29% of HD fetuses had limb defects. CONCLUSIONS Ultrasound is a useful technique to investigate the effect of maternally administered drugs on the embryonic HR in the rat. The results may provide more information about the safety of these drugs in pregnancy leading to better risk assessment for the human.
“Healing Alone?”: Social Capital, Racial Diversity and Health Care Inequality in the American States

There is an influential tradition in political science that social capital, defined as mutual trust and civic engagement, is linked to better substantive outcomes for citizens in democracies. Recently, scholars who link social capital to race and inequality have challenged this favorable picture of social capital. This study draws from the scholarly discussion on how social capital affects inequality in diverse societies. Focusing on the health care domain, I use a new dynamic measure of social capital to evaluate the “social capital thesis” and “racial diversity thesis” of inequality. Moreover, I explore how these two political forces are intertwined with each other in shaping the unequal health care access across American states. Key empirical findings confirm that social capital and racial diversity are counterbalancing forces shaping health care inequality. Despite it reduces health care inequality, the impact of social capital is tempered with high level of racial diversity.
Body mass index and mortality: the influence of physical activity and smoking.

PURPOSE To study the association between body mass index (BMI) and mortality, and to evaluate the effect of physical activity during leisure time and smoking on this association in a general male population. METHODS During 1974-1978, all men aged 35-49 yr living in three Norwegian counties were invited to a cardiovascular screening, and 87.1% attended and had their weight and height measured. Men with recognized cardiovascular diseases, diabetes mellitus, or cancer at screening were excluded. The cohort (N = 22,304) was followed for an average of 16.3 yr with respect to total and cause-specific mortality. RESULTS During follow-up, 1909 men died. We found a J-shaped association between BMI and total mortality, and the form of association was similar for death from cardiovascular diseases. Although not statistically significant, a J-shaped association was also suggested in never-smokers. Irrespective of BMI level, ex- and never-smokers had lower mortality than current smokers. Obese smoking men had a relative risk of dying of 2.01 (95% CI: 1.29-3.11) compared with obese never-smokers, and a relative risk of 4.55 (95% CI: 3.34-6.20) compared with normal weight never-smokers (BMI 22-24.9 kg x m(-2)). Within each category of physical activity during leisure time, obese men had a similar increased relative risk of death compared with normal-weight individuals. However, the U- to J-shaped association between BMI and mortality seemed to disappear by increasing level of physical activity, but this finding was not significant. CONCLUSION This study suggests a J-shaped association between BMI and total mortality, also when stratified on smoking habits and physical activity. The suggested linear trend in the most physical active men needs to be reassessed.
Large-Scale Analysis of Adeno-Associated Virus Vector Integration Sites in Normal Human Cells

ABSTRACT The integration sites of viral vectors used in human gene therapy can have important consequences for safety and efficacy. However, an extensive evaluation of adeno-associated virus (AAV) vector integration sites has not been completed, despite the ongoing use of AAV vectors in clinical trials. Here we have used a shuttle vector system to isolate and analyze 977 unique AAV vector-chromosome integration junctions from normal human fibroblasts and describe their genomic distribution. We found a significant preference for integrating within CpG islands and the first 1 kb of genes, but only a slight overall preference for transcribed sequences. Integration sites were clustered throughout the genome, including a major preference for integration in ribosomal DNA repeats, and 13 other hotspots that contained three or more proviruses within a 500-kb window. Both junctions were localized from 323 proviruses, allowing us to characterize the chromosomal deletions, insertions, and translocations associated with vector integration. These studies establish a profile of insertional mutagenesis for AAV vectors and provide unique insight into the chromosomal distribution of DNA strand breaks that may facilitate integration.