Miracle-dz/UniFAR-FTUs huggingface dataset:
Abnormal mRNA splicing resulting from consensus sequence splicing mutations of ATP7B

More than 200 Wilson disease (WD) disease‐causing mutations have been defined to date. Missense mutations are largely prevalent while splice‐site mutations are limited in number. Most reside in the splice donor or acceptor sites and only a minority are detected in splicing consensus sequences. Furthermore, only a few splicing mutations have been studied at the RNA level to date. In this study, using the RT‐PCR method we performed the molecular characterization of four consensus splice‐site mutations identified by DNA analysis in patients with WD. One of them, previously described 1707+3insT, occurred at position 3 in the donor splice site of intron 4, while the other three, 2122‐8T>G, 2866‐6T>G, and 3061‐12T>A, are novel and occurred in the acceptor splice sites of introns 7, 12, and 13, respectively. Analysis revealed a prevalently abnormal splicing in the samples carrying the mutations compared to the normal controls. Comparison of RNA splicing with normal controls in liver and lymphocytes further suggests that abnormal splicing of the WD gene is also present and differentially regulated in normal tissues. The results produced in this study strongly suggest that DNA mutations residing in the consensus sequence of WD gene splice sites result in the WD phenotype by interfering with the production of the normal WD protein. Further studies are necessary to better quantify the amount of different transcripts produced by these mutations, and establish their correlation with the disease phenotype. Hum Mutat 20:260–266, 2002. © 2002 Wiley‐Liss, Inc.
Systemic tumor necrosis factor alpha mediates an increase in peripheral CD11bhigh osteoclast precursors in tumor necrosis factor alpha-transgenic mice.

OBJECTIVE To investigate the mechanisms whereby tumor necrosis factor alpha (TNFalpha) increases osteoclastogenesis in vivo. METHODS TNFalpha-transgenic (TNF-Tg) and wild-type mice injected with TNFalpha were studied. In vitro osteoclastogenesis assays, monocyte colony-forming assays, and fluorescence-activated cell sorting were performed using splenocytes, peripheral blood mononuclear cells (PBMCs), and bone marrow cells to quantify and characterize osteoclast precursors (OCPs). Etanercept, a TNFalpha antagonist, was used to block TNFalpha activity in vivo. The effects of TNFalpha on proliferation, apoptosis, and differentiation of OCPs were assessed using 5-bromo-2'-deoxyuridine labeling, annexin V staining, and reverse transcriptase-polymerase chain reaction. RESULTS OCP numbers were increased 4-7-fold in PBMCs and spleen, but not in bone marrow of TNF-Tg mice. The OCPs in spleen were in the CD11b(high) population and contained both c-Fms- and c-Fms+ cells. The increased number of OCPs correlated with the initiation of detectable TNFalpha in serum and the onset of inflammatory arthritis in TNF-Tg mice. Etanercept eliminated the increase in peripheral OCPs. TNFalpha did not affect proliferation, survival, or differentiation of CD11b(high) splenocytes in vivo or in vitro, but caused a rapid increase in CD11b+ cells in blood within 4 hours of a single injection and an accumulation of CD11b(high) OCPs in spleen after 3 days of multiple injections. CONCLUSION Systemic TNFalpha induces a marked increase in circulating OCPs that is reversible by anti-TNF therapy and may result from their mobilization from bone marrow. Our findings provide a new mechanism whereby TNFalpha stimulates osteoclastogenesis in patients with inflammatory arthritis, suggesting that CD11b+ PBMCs could be used to evaluate a patient's potential for erosive disease and the efficacy of anti-TNF therapy.
The informational contents of announcements on verified emissions in the EU ETS - An empirical investigation using a multi-country event study approach

Empirical studies on the relation of the European Union Emissions Trading Scheme (EU ETS) and its impact on stock prices of affected companies concentrate so far mostly on the mechanism between emissions allowance (EUA) price and stock returns. This study in contrast examines the relation of stock returns and the announcement on verified emissions (VE). We use event study methodology and find on the 15th of May 2006, the first time when allocation could be justified, a negative cumulated and significant impact of the announcement of VE on stock returns and a positive cumulated (and marginal significant) impact on the 28th of April 2008, the last announcement of VE in the first period. Using the results from the event-study for cross sectional analysis we find evidence for a change in how announcements on VE were incorporated in stock markets.
A novel transport and delivery mechanism underpins the effectiveness of prolyl‐m‐sarcolysyl‐p‐fluorophenylalanine (PSF) in a human melanoma xenograft nude‐mouse model

The alkylating peptide PSF shows very promising results in vitro on different cancer cells but its efficacy in animals has not been assessed. Here we evaluate the efficacy of PSF in human melanoma‐bearing nude mice and examine the underlying mechanism. In melanoma‐bearing nude mice, escalating doses of PSF showed dose‐dependent responses and reached tumor regression with an optimal dose of 20 mg/kg for 1 month. A comparison of PSF with its free moiety m‐sarcolysin and melphalan showed a highly significant advantage of PSF. Furthermore, dose fractionation yielded an even better control of tumor regrowth. In vitro studies unraveled an original delivery mechanism based on the rapid binding of PSF mainly due to red blood cells to form a pro‐drug complex and the subsequent release of active metabolites by tumor‐associated proteolytic enzymes. Blood kinetics showed one major metabolite partially released over time, while in the presence of melanoma cells three additional metabolites are generated. Interestingly, tumor‐shed proteases also induce the production of these metabolites and varying combinations of enzyme inhibitors indicate the involvement of metallo‐ and other families of proteases in the delivery process. This particular transport and delivery of such an alkylating agent may have several benefits, mainly lowering the drug‐free moiety in plasma and at the same time increasing its concentration in protease rich areas such as tumors.
Banking “on-the-go”: examining consumers’ adoption of mobile banking services

Purpose This paper aims to examine consumers’ adoption of mobile technology to facilitate their banking services and activities, and to investigate the factors influencing their adoption and engagement. Design/methodology/approach An online survey is used to test proposed relationships between factors and consumers’ mobile banking adoption. Structural equation modeling is performed to analyze consumers’ intentions toward mobile banking. Findings Traditional technology acceptance model factors – perceived usefulness and perceived ease of use – are identified as effective factors in influencing consumers to adopt mobile technology for facilitating banking services. Moreover, technology safety concerns, including reliability and privacy factors, are found to play an important role in motivating consumers to embrace mobile banking. The “fun” feature of the technology and consumers’ innovativeness characteristics are considered important in influencing mobile banking adoption. Trust in the banks has its predominant role in mobile technology adoption for banking services. Practical implications A bank gaining trust from its clients is key to active adoption of mobile banking technology. Bankers are advised to pay more attention to reliability and privacy features when designing and promoting mobile banking technology to consumers. Moreover, advertisements to bank clients should stress the “fun” aspects of the mobile banking apps to attract them to the use of mobile banking technology. Originality/value This paper investigates the factors influencing bank consumers to adopting mobile banking apps to facilitate their banking services. Nine key factors in the technology adoption area are examined to provide a comprehensive understanding of bank clients’ use of mobile banking apps, which advances the understanding of mobile technology applied in the banking industry in the literature.
In vitro activation of Escherichia coli prohaemolysin to the mature membrane‐targeted toxin requires HlyC and a low molecular‐weight cytosolic polypeptide

The c. 110kDa haemolysin toxin secreted by Escherichia coli and other pathogenic Gram‐negative bacteria is synthesized as the non‐toxic precursor, prohaemolysin (proHlyA), which is unable to target mammalian cell membranes until activated intracellularly by an unknown mechanism dependent upon the coexpressed c. 20kDa protein, HlyC. We have established in vitro post‐translational activation of proHlyA in membrane‐depleted cell extract fractions from E. coli recombinant strains containing (separately) the proHlyA and HlyC proteins. In vitro activation was calcium‐independent and effective over a pH range of 6 to 9 and at temperatures from 42°C to 4°C. HlyC cell extract was also able to activate proHlyA which had been secreted out of cells containing the export proteins HlyB and HlyD. Fractionation of HlyC cell extracts by sucrose gradient centrifugation and molecular weight chromatography revealed activating fractions as having a molecular mass of 40kDa, suggesting that the HlyC activator is present physiologically in a multimeric form. Cell extracts containing activation‐competent HlyC and proHlyA were inactive following dialysis, but activity was restored by complementation with a cell extract lacking both proteins. HlyC and proHlyA proteins which were overproduced separately from recombinant expression plasmids were inactive following purification, but activity could again be restored with a Hly‐negative cell extract. These experiments demonstrated that HlyC is not sufficient for activation; an additional cellular factor is required. The cellular factor was found in enterobacteria but not other bacteria or eukaryotic cells. It was cytosolic, protease‐sensitive, and behaved as a c. 10kDa polypeptide in a number of assays including dialysis, sucrose gradient centrifugation, and gel filtration chromatography. Thus activation was possible in a defined in vitro reaction containing only purified proHlyA, HlyC, and the cellular factor. Ki stic studies in which the relative concentrations of the three components of proHlyA activation were varied suggested that neither HlyC nor the cellular factor acts as a conventional enzyme, with each participating in a finite number of activation events.
Impact of Interpersonal Problems in Borderline Personality Disorder Inpatients on Treatment Outcome and Psychopathology

Background: Borderline personality disorder (BPD) is a very common illness; interpersonal problems are one of the core features. The purpose of this study was to investigate the changes in interpersonal problems after transference-focused psychotherapy (TFP)-based disorder-specific treatment and to explore whether the severity of interpersonal problems could serve as a predictor for other variables. Sampling and Methods: A sample of 37 inpatients with BPD was assessed with the Structured Clinical Interviews for DSM-IV Axis I and II Disorders (SCID I and II) and had to complete a questionnaire including the Inventory of Interpersonal Problems (IIP-C), Inventory of Personality Organization (IPO), Beck Depression Inventory (BDI), Spielberger State and Trait Inventory (STAI), Spielberger State and Trait Anger Inventory (STAXI), and Symptom Checklist-90 (SCL-90-R). After 12 weeks of TFP-based disorder-specific treatment, the patients repeated the same questionnaire; 7 patients had to be excluded from the study, and thus calculations were conducted with 30 patients. Results: After treatment, the patients showed a significant decrease in the IIP total item score and all 8 subscales except the domineering, intrusive, and cold scales. The IIP total item baseline score was correlated with borderline symptomatic and psychopathology [e.g. anxiety, Global Severity Index (GSI)] after 12 weeks as well as with most IIP postsubscales. Conclusions: Although interpersonal problems are considered one of the more stable features of BPD, our results showed a significant improvement after 12 weeks of TFP-based disorder-specific inpatient treatment, especially in the total score and the subscales on the friendly submissive level. The severity of interpersonal problems at baseline was connected to outcome values of other borderline features as well as general psychiatric complaints. It therefore seems important to consider the treatment of interpersonal problems in therapy to be of greater significance.
Towards More Effective Water Quality Governance: A Review of Social-Economic, Legal and Ecological Perspectives and Their Interactions

In this article, social-economic, legal and ecological perspectives on effectiveness of water quality governance and their interactions have been studied. Worldwide, authorities are facing the challenge of restoring and preserving aquatic ecosystems in accordance with the United Nations Sustainable Development Goals (SDG 6). Over the last few decades, governance approaches have often been used to realise these ambitions. To date, scholars have identified that it is difficult to relate governance approaches to water quality improvement and have offered several different explanations for this. Combined with a targeted conceptualisation of the perspectives and their interactions, the systematic literature review demonstrates the gap that exists in the current understanding of these interactions and what their effects are on water quality improvement, especially in regard to the identification of ecological issues and their boundary conditions for the legal framework and the development of measures and follow-up. The review also reveals that the scientific debate is focused on the planning rather than implementation phase. A step forward can be made by supplementing existing analytical frameworks by the interactions between the different perspectives, especially those related to problem definition and the development and realisation of measures.
Outcome of a strategy to reduce surgical site infection in a tertiary-care hospital.

BACKGROUND Surgical site infection (SSI) is a preventable complication. Achieving a zero SSI rate for all clean operations should be the goal of all surgeons. AIM We aimed to reduce our SSI rate by 50% for patients undergoing elective gastrointestinal and hernia operations. METHODS The study was conducted in a tertiary-care hospital department of surgery from January 2006 to December 2007 for all clean and clean-contaminated elective gastrointestinal and hernia operations. Four interventions targeted at reducing SSI were implemented in January 2006: Use of clippers instead of shavers for surgical site hair removal; standardized prophylactic antibiotic regimen and antibiotic administration within 30 min before incision; standardized glucose monitoring for diabetics; and maintenance of postoperative normothermia. Prospective data were collected and compared with historical data from January to December 2005. RESULTS A total of 2,408 patients underwent elective gastrointestinal and hernia operations from January 2006 to December 2007. After implementation, we were able to achieve 91%, 87%, 89%, and 76% overall compliance with the respective interventions, but postoperative normothermia was achieved in only 44% of our patients. With the bundle of interventions, our overall SSI rate was reduced from 3.1% to 0.5% (p < 0.001), an 84% reduction within two years. The incidence of SSI was 1.7% in colorectal operations, 1.2% in upper gastrointestinal operations, 0.3% in hepatopancreaticobiliary operations, and zero in inguinal and ventral hernia operations. The estimated cost saving for both the patients and the hospital was S$208,562 (US$147,967). CONCLUSIONS Surgical site infections could be reduced with the bundle of interventions. With these encouraging results, the good practices should be sustained and promulgated. Such a SSI prevention program must be embedded in the work processes for all surgical disciplines.
A review of the literature on rural suicide: risk and protective factors, incidence, and prevention.

BACKGROUND Suicide is a major cause of mortality worldwide. Differences in rates of suicide exist between urban and rural areas; however, little rigorous research has examined the phenomena of rural suicide. OBJECTIVE This review examines the current body of literature on rural suicide and investigates differences between rural and urban suicide, including socioeconomic, psychological, and cultural variables. Prevention and intervention strategies specific to rural communities are discussed. DESCRIPTION OF STUDIES: All empirical and epidemiological studies of rural suicide were included in the review regardless of study design or methodology. RESULTS Although findings are mixed, research and epidemiological data indicate that suicide is a public health concern in rural areas, with suicide rates often greater than in urban areas. DISCUSSION Rural locale may create geographic, psychological, and sociocultural barriers to treatment of suicide. A better understanding of the role of rurality in the development and maintenance of suicidal thoughts and behaviors is needed and may inform prevention and intervention efforts.
Density‐Dependent Sex Ratio Adjustment and the Allee Effect: A Model and a Test Using a Sex‐Changing Fish

Positive density dependence (i.e., the Allee effect; AE) often has important implications for the dynamics and conservation of populations. Here, we show that density‐dependent sex ratio adjustment in response to sexual selection may be a common AE mechanism. Specifically, using an analytical model we show that an AE is expected whenever one sex is more fecund than the other and sex ratio bias toward the less fecund sex increases with density. We illustrate the robustness of this pattern, using Monte Carlo simulations, against a range of body size–fecundity relationships and sex‐allocation strategies. Finally, we test the model using the sex‐changing polygynous reef fish Parapercis cylindrica; positive density dependence in the strength of sexual selection for male size is evidenced as the causal mechanism driving local sex ratio adjustment, hence the AE. Model application may extend to invertebrates, reptiles, birds, and mammals, in addition to over 70 reef fishes. We suggest that protected areas may often outperform harvest quotas as a conservation tool since the latter promotes population fragmentation, reduced polygyny, a balancing of the sex ratio, and hence up to a 50% decline in per capita fecundity, while the former maximizes polygyny and source‐sink potential.
Impacto de la globalización y la apertura comercial en el gasto público social subnacional

espanolEl objetivo de este trabajo es estudiar los efectos de la apertura economica y la globalizacion sobre la estructura del gasto publico provincial en la Argentina. En particular, resultan de interes los efectos sobre el gasto social y sus componentes como expresion del Estado de bienestar. La mayor parte de la literatura se ha ocupado de identificar esta relacion a nivel de paises y un aspecto novedoso de este trabajo es la extension del analisis al sector subnacional. Otra contribucion es la estimacion de un indice de globalizacion provincial adaptada del indice KOF propuesto por Dreher (2006). Se estima un modelo dinamico mediante el metodo generalizado de momentos en diferencias, utilizando un panel de datos para las 24 jurisdicciones de la Argentina para el periodo 1993-2010. Los resultados indican que la apertura y la globalizacion de la economia impactan negativamente en la participacion del gasto social, resultado esperable desde el punto de vista del efec - to “eficiencia” versus el efecto “compensacion”, aunque hay indicios de politicas compensatorias del gasto en educacion. EnglishThe aim of this paper is to study the effects of economic liberalization and globalization on the structure of provincial government spending in Argentina. In particular, the effects on social expenditure and its components as an expression of the welfare state. Most of the literature has focused on identifying this relationship at the country level and a novel aspect of this work is to extend the analysis to the province. Another contribution is to estimate an index of provincial globalization adapted from Index KOF (Dreher, 2006). A dynamic model is estimated using the generalized method of moments and a panel data for 24 jurisdictions of Argentina for the period 1993-2010. The results indicate that openness and globalization of the economy, negatively impact the share of social spending, the result expected from the point of view of the “efficiency” effects versus the “compensation” effects; although there are indications of compensatory policies related to education spending.
End-stage renal disease in African-American and white men. 16-year MRFIT findings.

OBJECTIVE To determine reasons for the 4-fold higher incidence of treated end-stage renal disease (ESRD) in African-American men compared with white men. DESIGN Prospective study. SETTING Men screened in 1973 through 1975 for entry into the Multiple Risk Factor Intervention Trial (MRFIT). PARTICIPANTS A total of 332544 men (300645 white, 20222 African American, and 11677 other ethnic groups) aged 35 to 57 years. MAIN OUTCOME MEASURES Incidence of ESRD assessed through 1990 using the Health Care Financing Administration national ESRD treatment registry and by surveillance for death from renal disease from data of the National Death Index and the Social Security Administration. RESULTS Over a mean follow-up of 16 years, age-adjusted ESRD incidence was 13.90 per 100000 person-years in white men and 44.22 per 100000 person-years in African-American men. Higher blood pressure and lower socioeconomic status were associated with higher incidence of ESRD in both ethnic groups. With adjustment for baseline age, systolic blood pressure, number of cigarettes smoked, previous myocardial infarction, diabetes, income, and serum cholesterol level, relative risk of ESRD in African-American men compared with white men was reduced from 3.20 to 1.87 (95% confidence interval, 1.47-2.39). Both higher systolic blood pressure and lower income in African-American men as compared with white men were particularly related to this reduced relative risk. Results were similar when hypertensive ESRD was used as the outcome. CONCLUSION Both higher blood pressure and lower income are associated with a higher incidence of ESRD in both white and African-American men. Disparities in blood pressure and socioeconomic status relate importantly to the excess risk of ESRD in African-American men compared with white men.