Miracle-dz/UniFAR-FTUs huggingface dataset:
p53 Activity Dominates That of p73 upon Mdm4 Loss in Development and Tumorigenesis

Mdm4 negatively regulates the p53 tumor suppressor. Mdm4 loss in mice leads to an embryonic lethal phenotype that is p53-dependent. Biochemical studies indicate that Mdm4 also binds p73, a member of the p53 family, with higher affinity than p53. In this study, the significance of the Mdm4 and p73 interaction in vivo during embryogenesis and tumorigenesis was examined. The data revealed that p73 loss did not rescue either the early Mdm4-deficient embryonic lethality or the runted phenotype of Mdm4Δ2/Δ2 p53+/− embryos. Furthermore, studies in the developing central nervous system wherein both genes have prominent roles indicated that loss of p73 also did not rescue the Mdm4-null brain phenotype as did p53 loss. This p53 dependency occurred despite evidence for p73-specific transcriptional activity. In tumor studies, the combination of Mdm4 overexpression and p73 loss did not alter survival of mice or the tumor spectrum as compared with Mdm4 overexpression alone. In summary, these data demonstrate that the Mdm4–p73 axis cannot override the dominant role of p53 in development and tumorigenesis. Implications: Genetic characterization of the Mdm4 and p73 interaction during development and tumorigenesis suggests new insight into the role of p53 family members, which may influence treatment options for patients. Mol Cancer Res; 14(1); 56–65. ©2015 AACR.
Salt fluoridation and oral health.

UNLABELLED The aim of this paper is to make known the potential of fluoridated salt in community oral health programs, particularly in South Eastern Europe. Since 1922, the addition of iodine to salt has been successful in Switzerland. Goiter is virtually extinct. By 1945, the caries-protective effect of fluorides was well established. Based on the success of water fluoridation, a gynecologist started adding of fluoride to salt. The sale of fluoridated salt began in 1956 in the Swiss Canton of Zurich, and several other cantons followed suit. Studies initiated in the early seventies showed that fluoride, when added to salt, inhibits dental caries. The addition of fluoride to salt for human consumption was officially authorized in 1980-82. In Switzerland 85% of domestic salt consumed is fluoridated and 67% in Germany. Salt fluoridation schemes are reaching more than one hundred million in Mexico, Colombia, Peru and Cuba. The cost of salt fluoridation is very low, within 0.02 and 0.05 € per year and capita. Children and adults of the low socio-economic strata tend to have substantially more untreated caries than higher strata. Salt fluoridation is by far the cheapest method for improving oral health. CONCLUSION Salt fluoridation has cariostatic potential like water fluoridation (caries reductions up to 50%). In Europe, meaningful percentages of users have been attained only in Germany (67%) and Switzerland (85%). In Latin America, there are more than 100 million users, and several countries have arrived at coverage of 90 to 99%. Salt fluoridation is by far the cheapest method of caries prevention, and billions of people throughout the world could benefit from this method.
Effects of urinary pH on renal interactions between probenecid and cefsulodin in rabbits

The effect of urinary pH on renal interaction of cefsulodin and probenecid was tested in rabbits. Probenecid was reabsorbed in acidic urine (fractional excretion [FE] = 8 +/- 4%) and secreted in alkaline urine (FE = 492 +/- 258%). Renal excretion of cefsulodin alone was not affected by the urinary pH (FE = ca. 100%). In acidic urine, probenecid significantly reduced tubular secretion of cefsulodin (FE = 74 +/- 8%). An inverse pattern was observed in alkaline urine (FE = 122 +/- 18%).
Fas Ligand-Mediated Lysis of Self Bystander Targets by Human Papillomavirus-Specific CD8+ Cytotoxic T Lymphocytes

ABSTRACT Mouse cytotoxic T lymphocytes (CTL) reactive with a H-2Db-presented 9-mer peptide of the human papillomavirus type 16 protein E749-57 (RAHYNIVTF) were generated from the spleen cells of wild-type C57BL/6 (B6) or B6 perforin-deficient (B6.P0) mice. CD8+ B6 CTL displayed peptide-specific perforin- and Fas-mediated lysis of E7-transfected mouse RMA lymphoma cells (RMA-E7), while CD8+ CTL from B6.P0 mice lysed RMA-E7 cells via Fas ligand (FasL) exclusively. Rapid and efficient lysis of syngeneic bystander B6 blasts or RMA cells by either B6 or B6.P0 Ag-activated CTL was mediated by a FasL-Fas mechanism. Fas-resistant bystanders were not lysed, nor were allogeneic Fas-sensitive C3H/HeJ (H-2k ) or BALB/c (H-2d ) bystander blasts. Interestingly, however, phorbol myristate acetate-ionomycin preactivation of B6.P0 effectors enabled lysis of allogeneic H-2k andH-2d bystanders even in the absence of antigenic stimulation. Lysis of syngeneic bystander cells was always FasL-Fas dependent and required effector-bystander contact and, in particular, an interaction between CTL LFA-1 and bystander ICAM-1. Thus, in the context of major histocompatibility complex class I molecule-peptide ligation of the T-cell receptors of CD8+CTL, neighboring bystander cells that are syngeneic and Fas sensitive and express the adhesion molecule ICAM-1 are potential targets of CTL attack.
The NBU's Balance Sheet: Before, During, and After the Crisis

Looking at the evolution of the central bank’s balance sheet gives us a unique window on the forces that have shaped our economy and central bank reaction functions. This paper considers the evolution of the NBU’s balance sheet over the period from 2001-2016, focusing on explicit and implicit monetary policy priorities at different periods. We then make simulations on the NBU’s balance sheet for the next five years assuming current NBU priorities for monetary policy. We then draw conclusions on the likely financial position of the NBU in the future and recommendations to ensure the NBU’s financial strength – essential for its continued independence.
Does CSR Reporting Really Impact FERCs

ABSTRACT: As part of a study on the value of corporate social responsibility (CSR) reporting for market participants, Dhaliwal, Radhakrishnan, Tsang, and Yang (2012) document a positive future earnings response coefficient (FERC) related to CSR report issuance. They argue the reports allow investors to better identify companies' social and environmental performance and thus better predict their future earnings. Our concern is that they fail to consider that CSR reports are likely issued for reasons other than informing investors, and we further argue that the low average quality of CSR reports makes it unlikely that companies use them for informing investors of actual social and environmental performance. Focusing on only first-time issuances of CSR reports by U.S. firms, we find, in contrast to Dhaliwal et al. (2012), no significant impacts on FERCs. Our results are robust to consideration of report quality and potentially differing impacts for firms operating in industries facing higher levels of social.
Congenital heart disease in patients with Turner's syndrome. Italian Study Group for Turner Syndrome (ISGTS).

OBJECTIVE There is a high prevalence of congenital heart defects in patients with Turner's syndrome. Few studies have reported echocardiographic data in unselected patients according to the different chromosomal patterns. The aim of our study was to evaluate a large series of patients with Turner's syndrome, comparing these data with those of the general population. METHODS Five hundred ninety-four patients with Turner's syndrome, aged 1 month to 24 years, in the Italian Study Group for Turner Syndrome underwent full cardiologic evaluation. Karyotype distribution was: 45,X (54%), X-mosaicism (13%), and X-structural abnormalities (33%). RESULTS The prevalence of cardiac malformations was 23%. Bicuspid aortic valve (12.5%), aortic coarctation (6.9%), and aortic valve disease (3.2%) were the most prevalent malformations. In comparison with the general population, partial anomalous pulmonary venous drainage had the highest relative risk. A correlation was found between type of congenital heart defect and karyotype. The patients with 45,X karyotype had the greatest prevalence of partial anomalous pulmonary venous drainage and aortic coarctation, whereas bicuspid aortic valve and aortic valve disease were more common in the patients with X-structural abnormalities. The patients with severe dysmorphic signs showed a significantly higher relative risk of cardiac malformations. CONCLUSION X-linked factors may be involved in determining cardiac defects in Turner's syndrome.
Novel exon skipping mutation in the fibrillin‐1 gene: Two ‘hot spots’ for the neonatal Marfan syndrome

The Marfan syndrome is an autosomal dominant heritable disorder of connective tissue that involves principally the skeletal, ocular, and cardiovascular systems. The most severe end of the phenotypic spectrum, the neonatal Marfan syndrome (nMFS), is characterized by pronounced atrioventricular valve dysfunction, and death often occurs within the first year of life due to congestive heart failure. Mutations in the gene coding for fibrillin‐1, FBN1, are known to cause Marfan syndrome, and have been identified in almost all exons of FBN1. Here, we describe a novel mutation affecting the invariant +1 position of the splice donor site in intron 31, associated with skipping of exon 31, in a patient with nMFS. Published reports of nMFS are reviewed and a strict definition for nMFS is suggested. If this definition is used, all nMFS mutations reported to date lie in one of two hot spots, comprising mainly missense mutations in FBN1 exons 24–27 and mutations causing skipping of exon 31 or 32.
Expression of microRNA 210 associates with poor survival and age of tumor onset of soft‐tissue sarcoma patients

Expression of microRNAs can affect age of tumor onset and prognosis of cancer patients. However, nothing is known about the effects of microRNAs on altered age of cancer onset and disease‐specific survival of soft‐tissue sarcoma (STS) patients. The levels of miR‐210, also known as hypoxia‐regulated microRNA, were analyzed by quantitative real‐time (RT)‐PCR in the tumors of 78 STS patients. The patients were stratified according to their microRNA levels with low, intermediate and high expression levels and the association of microRNA expression and patients' survival was analyzed using multivariate Cox's regression hazard analyses. A significant correlation between an intermediate miR‐210 expression and disease‐specific death of STS patients [relative risk (RR) = 3.19; p = 0.018] was observed compared with patients with high expression levels in their tumors. Interestingly, the association between an intermediate expression of miR‐210 and a poor prognosis was only significant in female STS patients (RR = 11.28; p = 0.010), but not observed in male individuals. Furthermore, the expression of miR‐210 showed a significant association with the age of tumor onset in a gender‐specific manner. Specifically, male patients with an intermediate expression of miR‐210 associated with a 9.6‐year later age of tumor onset (p = 0.017) compared with males with a low expression of miR‐210 in their tumors. However, no significant differences in the female patients were observed. This study provides the first evidence of a correlation of expression levels of a single microRNA (miR‐210) with the prognosis and age of tumor onset in a gender‐specific manner in STS patients.
Extrahepatic Lesions Induced by Acetaminophen in the Mouse

Acetaminophen in acute overdose is primarily recognized as potentially hepatotoxic with few descriptions of extrahepatic lesions other than nephrotoxicity. Fasted adult, male mice, both standard and germ-free, were given acetaminophen orally and killed at selected times, from 30 minutes to 48 hours after treatment. In addition to the expected hepatic effects after 600 mg acetaminophen/kg, degenerative and necrotic changes were found in four non-hepatic tissues. Nephrosis developed 2 to 4 hours after treatment and paralleled the course of hepatic damage. Necrosis of bronchiolar epithelium in the absence of inflammation was evident 4 to 6 hours after acetaminophen administration as was onset of testicular changes. Spermatidic degeneration with early development of spermatidic multinucleated giant cells were characteristic features. Areas of lymphoid necrosis were also visible in splenic follicles and Peyer's patches 18 to 24 hours after treatment. These observations have demonstrated that other tissues in addition to liver and kidney are damaged by acetaminophen toxicity and should be considered in cases of acetaminophen overdosage.
Community-Level CSR Implementation through the Lens of Institutional Theory: An Empirical Study

Researchers world over are increasingly realising that use of a theoretical framework is necessary for designing and conducting research on corporate-community relations. There are no empirical studies in India, to the best of our knowledge, which look at Corporate Social Responsibility (CSR) initiatives of a corporate in local community through theoretical lens. The research questions we examine through this study are – firstly, how institutional pressure at the level of local community drives CSR practices of a company and secondly, to assess how community has perceived these CSR initiatives. To answer the same, the researchers studied CSR practices of Cairn India in Barmer region of Rajasthan as a single case within the theoretical framework provided by the institutional theory. This empirical study, based on interviews with employees and NGO partners of Cairn and perceptual study in the community, offers an on-the-ground glimpse of how the company is implementing CSR initiatives and associated challenges it is facing. The findings testify that managing local community expectations has certainly helped Cairn India to integrate community expectations into its CSR strategy. The study brings to light the fact Government and NGOs are important drivers of CSR at the local community level in developing countries like India.
Prohormone Convertase 1 in Obesity, Gestational Diabetes Mellitus, and NIDDM: No Evidence for a Major Susceptibility Role

Improved understanding of the primary molecular events underlying NIDDM and obesity is essential if more effective therapies are to be devised. Individual susceptibility to these interrelated conditions is under genetic influence (1), and clues to the identity of the major aetiological genes may come from physiological studies that pinpoint candidate pathways. A characteristic feature of NIDDM and certain prediabetic states, such as gestational diabetes mellitus (GDM), is a marked increase in the proportion of circulating insulin precursor molecules (proinsulin and split proinsulin intermediates) (2,3). Release of disproportionate amounts of these biologically inactive precursors may contribute to the relative insulin deficiency apparent in GDM and NIDDM (2). The processing of proinsulin to mature insulin is catalyzed by prohormone convertase (PC) enzymes active in (3-cell granules. PCI (also named PC3) cleaves intact proinsulin to produce 32,33 split proinsulin. PC2 and carboxypeptidase E (CPE) catalyze subsequent reactions (4). Functional defects in any of these candidate genes could contribute to the NIDDM phenotype. Furthermore, recent studies indicate a role for these loci in the determination of obesity. Mutations in the Cpe gene resulting in absent enzyme activity in islets and pituitary underlie the phenotype of the fat/fat mouse (5). More recently, Jackson et al. (6) reported on a family segregating two distinctPCi mutations. The mother was a compound heterozygote who had presented with childhood obesity, GDM, and a variety of
The role of catastrophizing in the pain and depression of women with fibromyalgia syndrome.

OBJECTIVE Although 2 recent studies have found associations between catastrophizing and poor medical outcomes in patients with fibromyalgia syndrome (FMS), neither assessed these findings in comparison with a similar group of patients with chronic pain. Our study examined the complex relationships between depression, catastrophizing, and the multidimensional aspects of pain in women with FMS and compared these relationships with those in women with rheumatoid arthritis (RA). METHODS Sixty-four FMS patients and 30 RA patients completed the Coping Strategies Questionnaire (CSQ), the Beck Depression Inventory II (BDI-II), and the McGill Pain Questionnaire. RESULTS Compared with subjects with RA, FMS subjects scored significantly higher on the catastrophizing subscale of the CSQ. FMS patients also earned higher scores on overall depression and on the cognitive subscale of the BDI-II. Furthermore, the relationship between catastrophizing and depression was significant in the FMS group only. Regression analyses revealed that in FMS, catastrophizing as a measure of coping predicted patients' perception of pain better than demographic variables such as age, duration of illness, and education. CONCLUSION Cognitive factors, such as catastrophizing and depressive self-statements, have a more pronounced role in the self-reported pain of patients with FMS than in patients with RA. Clinically, this indicates that treating pain and depression in FMS by adding cognitive therapy and coping skills components to a comprehensive treatment program may improve the outcomes obtained with pharmacologic interventions.
New Insights in the Pathophysiology of Antiphospholipid Syndrome

Abstract The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by an elevated risk for arterial and venous thrombosis and pregnancy-related morbidity. Since the discovery of the disease in 1980s, numerous studies in cell culture systems, in animal models, and in patient populations have been reported, leading to a deeper understanding of the pathogenesis of APS. These studies have determined that circulating autoantibodies, collectively called antiphospholipid antibodies (aPL), the majority of which recognize cell surface proteins attached to the plasma membrane phospholipids, play a causal role in the development of the disease. The binding of aPL to the cell surface antigens triggers interaction of the complex with transmembrane receptors to initiate intracellular signaling in critical cell types, including platelets, monocytes, endothelial cells, and trophoblasts. Subsequent alteration of various cell functions results in inflammation, thrombus formation, and pregnancy complications. Apolipoprotein E receptor 2 (apoER2), a lipoprotein receptor family member, has been implicated as a mediator for aPL actions in platelets and endothelial cells. Nitric oxide (NO) is a signaling molecule known to exert potent antithrombotic, anti-inflammatory, and anti-atherogenic effects. NO insufficiency and oxidative stress have been linked to APS pathogenesis. This review will focus on the recent findings on how apoER2 and dysregulation of NO production contribute to aPL-mediated pathologies in APS.
Economic mobility along the business cycle. The case of Peru

ABSTRACT The performance of Latin American countries in reducing poverty and expanding the middle class has been remarkable. By taking a close look at the Peruvian experience, we examine how this aggregate behavior relates to business cycle conditions and whether different population groups share this behavior. We find that social mobility is cyclical; it decreases in recessions but increases with strong economic growth. The reduction in poverty in Peru appears to be the result of a sustained increase in the poverty exit rate together with a prolonged decrease in the poverty entry rate. These results hold among heterogeneous groups and are particularly marked for households regarded as initially disadvantaged.
Prognostic factors in CAPD patients: a retrospective study of a 10-year period.

A prognostic study was retrospectively performed on a cohort of 201 ESRD patients having started CAPD in one single centre between 1983 and 1993 (mean follow-up 24 months). At the end of the study 74 patients had died, 63 were transplanted, and 19 had been transferred to another dialysis modality. The purpose of the study was to estimate patient and technique survivals according to clinical and biological variables recorded at the beginning of the treatment. The authors decided to focus on the possible prognostic role of urea kinetic parameters which are still controversial in the literature. Concerning patient survival, the Cox proportional hazards model selected seven prognostic factors, including urea Kt/V (relative risk = 1.69). The division of the study group according to three levels of Kt/V (< or = 1.7, between 1.7 and 2.2, and > 2.2) allowed us to estimate 1.7 as an index of an adequate CAPD prescription. NPCR at the limit of significance for patient survival was clearly a prognostic factor for technique survival (relative risk = 2.50). Creatinine clearance was closely linked to both technique and patient survival (relative risk > 3). These three factors, in addition to the clinical and biological variables generally described in the literature, must be taken into account in the evaluation of a prognosis for CAPD.
Police community engagement and outreach in a counterterrorism context

ABSTRACT Police engagement of Muslim communities to prevent terrorism is fraught with tension. This paper presents results from in-depth interviews with members of the Australian Federal Police Community Liaison Team (CLT) to understand the practice of community engagement and the tactical and strategic considerations that are required when police engage Muslim communities. The interview data illustrate the different attributes of trust judged as essential to effective engagement by CLT members, with displays of integrity regarded as important. Data demonstrate how Australian Federal Police liaison officers navigate the fine line between intelligence gathering and community engagement, with the provision of intelligence seen as an outcome rather than an aim of effective outreach. Strategies to manage the community impact from counterterrorism arrests are explored, with the interview data indicating that forms of outreach have some inherent limitations due to the contingencies surrounding counterterrorism operations. The uncertainties and risks of engaging some hard to reach groups, such as Muslim youth are highlighted. Evidence of the outputs and outcomes of engagement efforts are illustrated, with the willingness of Muslims to voluntarily approach members of the CLT regarded as an important outcome. Broader lessons for counterterrorism community engagement are highlighted.