Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel lipoprotein expressed by Neisseria meningitidis but not by Neisseria gonorrhoeae

The ppk gene, which codes for the enzyme polyphosphate kinase in Neisseria meningitidis strain BNCV, is preceded by an open reading frame coding for a protein with a predicted size of 19.2 kDa with a typical lipoprotein signal sequence of 21 amino acids. The protein has significant homology to the N-terminal portion of an outer membrane protein from Haemophilus somnus (J. Won and R. W. Griffith, Infect. Immun. 61:2813-2821, 1993). Sequencing of the same open reading frame from meningococcus strain M1080 predicted an almost identical protein. Antisera were raised against the lipoprotein, expressed in Escherichia coli as a fusion protein with glutathione S-transferase. The antisera reacted with meningococcal membrane fractions on a Western blot (immunoblot) but did not elicit complement-dependent bactericidal activity. Restriction enzyme digestion demonstrated conservation of this portion of the meningococcal and gonococcal chromosomes. However, antisera raised to the recombinant protein showed that the protein was absent from all strains of gonococcus tested. The sequences of the gene from several strains of Neisseria gonorrhoeae and N. meningitidis were compared and found to be almost identical, except that the coding sequences from all of the gonococcal strains were terminated prematurely as a result of a frameshift mutation. The significance of the remarkable conservation of these gonococcal genes is discussed.
Human T‐lymphotropic virus type II and neurological disease

Human T‐lymphotropic virus type I (HTLV‐I) and type II (HTLV‐II) are closely related retroviruses with similar biological properties and common modes of transmission. HTLV‐I infection is endemic in well‐defined geographic regions, and it is estimated that some 20 million individuals are infected worldwide. Although most infected individuals are asymptomatic carriers, some 2 to 5% will develop a chronic encephalomyelopathy, HTLV‐I–associated myelopathy/tropical spastic paraparesis (HAM/TSP). In contrast with HTLV‐I, the role of HTLV‐II in the development of neurological disorders is much less clear. HTLV‐II is endemic in many native Amerindian groups and epidemic in injecting drug users (IDUs) worldwide. To evaluate the role of HTLV‐II in neurological disease, we have critically reviewed all reported cases of HTLV‐II–associated disorders. This has confirmed that although rare infection is associated with a disorder clinically similar or identical to HAM/TSP. However, most reports that have attributed infection to a range of other neurological disorders are difficult to evaluate in that in many cases either the association appears to be fortuitous or the presentations were confounded by a background of concomitant human immunodeficiency virus–1 infection and/or active IDU. In view of the many HTLV‐II–infected individuals in urban areas of North America and Europe, neurologists should be aware of the potential clinical consequences of this infection.
Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases

Previous findings have suggested that class IIa histone deacetylases (HDACs) (HDAC4, -5, -7, and -9) are inactive on acetylated substrates, thus differing from class I and IIb enzymes. Here, we present evidence supporting this view and demonstrate that class IIa HDACs are very inefficient enzymes on standard substrates. We identified HDAC inhibitors unable to bind recombinant human HDAC4 while showing inhibition in a typical HDAC4 enzymatic assay, suggesting that the observed activity rather reflects the involvement of endogenous copurified class I HDACs. Moreover, an HDAC4 catalytic domain purified from bacteria was 1,000-fold less active than class I HDACs on standard substrates. A catalytic Tyr is conserved in all HDACs except for vertebrate class IIa enzymes where it is replaced by His. Given the high structural conservation of HDAC active sites, we predicted the class IIa His-Nε2 to be too far away to functionally substitute the class I Tyr-OH in catalysis. Consistently, a Tyr-to-His mutation in class I HDACs severely reduced their activity. More importantly, a His-976-Tyr mutation in HDAC4 produced an enzyme with a catalytic efficiency 1,000-fold higher than WT, and this “gain of function phenotype” could be extended to HDAC5 and -7. We also identified trifluoroacetyl-lysine as a class IIa-specific substrate in vitro. Hence, vertebrate class IIa HDACs may have evolved to maintain low basal activities on acetyl-lysines and to efficiently process restricted sets of specific, still undiscovered natural substrates.
Effects of parental presence and child characteristics on children's neuropsychological test performance: Third party observer effect confirmed

An observer's presence during neuropsychological testing can impair task performance in adults, but this phenomenon has yet to be examined as it pertains to neuropsychological testing of children. The current study focused on parental presence effects on nonverbal intelligence and verbal learning performance of children aged 6 to 8 years. Each of 53 children completed one form of the Test of Nonverbal Intelligence–3rd Edition (TONI-3) and the Selective Reminding Test (SRT) with his/her parent in the room and an alternate form of each with only the experimenter with the child in the testing room. Of several possible covariates, only the child's age was significant and included in final analyses. Using a doubly multivariate MANCOVA it was discovered that parent's observation status significantly interacted with the order of observation to impact task performance. This significant effect can mainly be attributed to a steeper positive slope (i.e., children's greater improvement over time) for TONI-3 T scores in children whose parent observed first; children whose parents were absent for the first half of testing improved to a lesser extent over time. No significant relationship was found between observation and SRT scores. These results lend some support to the assertion of previous studies that the presence of third party observers may affect the validity of neuropsychological test results.
CYP3A5 Genotype-Phenotype Analysis in the Human Kidney Reveals a Strong Site-Specific Expression of CYP3A5 in the Proximal Tubule in Carriers of the CYP3A5*1 Allele

Interindividual variability in the drug-metabolizing activity of the CYP3A5 enzyme is mainly due to a single nucleotide polymorphism in CYP3A5, leading to low expression in homozygous CYP3A5*3/*3 individuals compared with CYP3A5*1 allele carriers. In the human kidney, expression of CYP3A5 has been implicated in blood pressure regulation and calcineurin inhibitor-associated nephrotoxicity. The effect of the CYP3A5*1/*3 polymorphism on the expression level and protein distribution within the human kidney is not well characterized. Therefore, we performed a genotype-phenotype analysis of CYP3A5 mRNA and protein expression in the human kidney. To this end, we analyzed sections of normal kidney tissue obtained from 93 white individuals undergoing nephrectomy by quantitative mRNA expression analysis. Qualitative protein expression analysis of CYP3A5 was performed by immunohistochemistry. Mean renal mRNA expression of carriers of the CYP3A5*1 (n = 12) allele was more than 18-fold higher than that of CYP3A5*3/*3 carriers (n = 81, p < 0.001). Immunohistochemical analysis demonstrated CYP3A5 protein in all epithelia of the nephron in kidney sections with the CYP3A5*3/*3 genotype. In carriers of the CYP3A5*1 allele, a strong increase in protein expression of CYP3A5 was detected, and this was confined to the proximal tubule. This study confirms a significant effect of the CYP3A5*1/*3 polymorphism on CYP3A5 expression in the normal human kidney and reveals a strong nephron segment-specific difference in the CYP3A5 protein expression limited to the proximal tubule.
Phytotoxicity of foliar-applied urea.

Recent work in our laboratory showed that the adverse effect of urea fertilizer on seed germination and seedling growth in soil is due to ammonia produced through hydrolysis of urea by soil urease (NH(2)CONH(2) + H(2)O --> 2NH(3) + CO(2)) and can be eliminated by amending the fertilizer with a small amount of a urease inhibitor such as phenylphosphorodiamidate. Because the leaf-tip necrosis often observed after foliar fertilization of plants with urea is usually attributed to ammonia formed through hydrolysis of urea by plant urease, we studied the possibility that this necrosis could be eliminated or reduced by adding phenylphosphorodiamidate to the urea fertilizer. We found that, although addition of this urease inhibitor to foliar-applied urea increased the urea content and decreased the ammonia content and urease activity of soybean [Glycine max. (L.) Merr. ] leaves fertilized with urea, it increased the leaf-tip necrosis observed after fertilization. We conclude that this necrosis resulted from accumulation of toxic amounts of urea rather than from formation of toxic amounts of ammonia. This conclusion was supported by our finding that the necrotic areas of soybean leaves treated with urea or with urea and phenylphosphorodiamidate contained much higher concentrations of urea than did the nonnecrotic areas.
Development of an Issue-Situation-Based Board Game: A Systemic Learning Environment for Water Resource Adaptation Education

Climate change has severely affected water resources (WRs) today, highlighting the importance of promoting education on WR adaptation (WRA). The goal of WRA education is to cultivate learners’ cross-oriented system knowledge (COSK), responsibility for WR environment (RWRE), value of public benefits (VPB), and empathy and negotiating thinking (EaNT). This study developed an issue-situation-based board game, namely Water Ark, to enhance participants’ WR knowledge. In this study, participants were divided into four groups with each playing the role of a WR-related organization: the government, agricultural sector, industrial sector and public guild. Scales and interviews were used to assess participants’ performance. The findings revealed that during the game, participants gradually changed from profit-oriented self-interest strategies to altruistic strategies based on social public benefit. Furthermore, after playing Water Ark, participants’ COSK, RWRE, VPB, and EaNT were found to have improved substantially. Thus, Water Ark is believed to be a useful tool for assisting WRA education.
The human carotid body transcriptome with focus on oxygen sensing and inflammation – a comparative analysis

• The carotid body (CB) is the key oxygen sensor and governs the ventilatory response to hypoxia. • CB oxygen sensing and signalling gene expression is well described in animals whereas human data are absent. • Here we have characterized the human CB global gene expression in comparison with functionally related tissues and mouse CB gene expression. • We show that the human CB expresses oxygen sensing genes in common with mice but also differs on key genes such as certain K+ channels. There is moreover increased expression of inflammatory response genes in human and mouse CBs in comparison with related tissues. • The study establishes similarities but also important differences between animal and human CB gene expression profiles and provides a platform for future functional studies on human CBs.
The Caregiver Activity Survey (CAS): development and validation of a new measure for caregivers of persons with Alzheimer's disease

Background. Most instruments that measure the impairments associated with Alzheimer's disease assess symptom severity. Little attention has been paid to the illness's impact on the time formal and informal caregivers spend caring for Alzheimer's individuals. A tool that measures the time spent caregiving would help to determine the economic impact of the illness. The Caregiver Activity Survey (CAS) was developed to measure the time caregivers spend aiding Alzheimer's patients with their day‐to‐day activities.
Merchant Storage Investment in a Restructured Electricity Industry

Restructuring and liberalisation of the electricity industry creates opportunities for investment in energy storage, which could be undertaken by a profit-maximising merchant storage operator. Because such a firm is concerned solely with maximising its own profit, the resulting storage-investment decision may be socially suboptimal (or detrimental). This paper develops a bi-level model of an imperfectly competitive electricity market. The modelling framework assumes electricity-generation and storage-operations decisions at the lower level and storage investment at the upper level. Our analytical results demonstrate that a relatively high (low) amount of market power in the generation sector leads to low (high) storage-capacity investment by the profit-maximising storage operator relative to a welfare maximiser. This can result in net social welfare losses with a profit-maximising storage operator compared to a no-storage case. Moreover, there are guaranteed to be net social welfare losses with a profit-maximising storage operator if the generation sector is sufficiently competitive. Using a charge on generation ramping between off- and on-peak periods, we induce the profit-maximising storage operator to invest in the same level of storage capacity as the welfare-maximising firm. Such a ramping charge can increase social welfare above the levels that are attained with a welfare-maximising storage operator.
Overview of results of randomized clinical trials in heart disease. I. Treatments following myocardial infarction.

WHEN Daniel 1 requested that he and his compatriots be served pulse and water while Nebuchadnezzar's other young servants be served the king's food and wine, he was inaugurating the first recorded clinical trial. Today we would criticize Daniel's attempt to demonstrate the superiority of his simple diet. He failed to assign the two diets at random; neither the experimental subjects nor the eunuchs who were to measure the ten-day outcome, fairness of countenance, were blinded to the treatment; and the sample size, four subjects on the experimental diet and a larger unspecified number on kingly fare, was too small to be likely to detect a difference in outcome. Despite, or perhaps because of, the faulty design, the results supported Daniel's hypothesis. "And at the end of ten days their countenances appeared fairer, and they were fatter in flesh, than all the youths that did eat of the king's food. "
Multi-Layer Model Based on Multi-Scale and Multi-Feature Fusion for SAR Images

A multi-layer classification approach based on multi-scales and multi-features (ML–MFM) for synthetic aperture radar (SAR) images is proposed in this paper. Firstly, the SAR image is partitioned into superpixels, which are local, coherent regions that preserve most of the characteristics necessary for extracting image information. Following this, a new sparse representation-based classification is used to express sparse multiple features of the superpixels. Moreover, a multi-scale fusion strategy is introduced into ML–MFM to construct the dictionary, which allows complementation between sample information. Finally, the multi-layer operation is used to refine the classification results of superpixels by adding a threshold decision condition to sparse representation classification (SRC) in an iterative way. Compared with traditional SRC and other existing methods, the experimental results of both synthetic and real SAR images have shown that the proposed method not only shows good performance in quantitative evaluation, but can also obtain satisfactory and cogent visualization of classification results.
A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE B cell depletion with rituximab has allowed remissions in relapsing or refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in small studies. The aim of this study was to determine the efficacy and safety of rituximab for ANCA-associated vasculitis in a larger multicenter cohort. This permitted comparison of rituximab dosing regimens, the value of continuing immunosuppression, and investigation of ANCA and B cell levels as re-treatment biomarkers. METHODS Retrospective, standardized data collection from 65 sequential patients receiving rituximab for refractory ANCA-associated vasculitis at 4 centers in the UK was used. RESULTS All patients achieved B cell depletion. Complete remission occurred in 49 of the 65 patients (75%), partial remission in 15 (23%), and no response in 1 (2%). The prednisolone dosage was reduced from 12.5 mg/day (median) to 9.0 mg/day at 6 months (P = 0.0006). Immunosuppressive therapy was withdrawn in 37 of 60 patients (62%). Twenty-eight of 49 patients who achieved full remission (57%) experienced relapse (median 11.5 months). B cell return preceded relapse in 14 of 27 patients (52%). Although ANCA levels fell after rituximab therapy, relapse was not associated with ANCA positivity or a rise in ANCA levels. Neither the initial rituximab regimen (4 infusions of 375 mg/m(2) each given 1 week apart or 2 infusions of 1 gm each given 2 weeks apart) nor withdrawal of immunosuppressive therapy (37 of 60 patients [62%]) influenced the timing of relapse. Thirty-eight patients received >or=2 courses of rituximab, and complete remission was induced or maintained in 32 of them (84%). IgM levels fell, although IgG levels remained stable. Forty-six serious adverse events occurred, including 2 episodes of late-onset neutropenia, which were attributed to rituximab. CONCLUSION Rituximab was effective remission induction therapy for refractory ANCA-associated vasculitis in this study. There was no difference in efficacy between the 2 main treatment regimens. Continuing immunosuppression did not reduce relapses. Relapses occurred, but re-treatment was effective and safe. There was no clear influence of rituximab on the frequency of serious adverse events. ANCA and B cell levels lacked sufficient sensitivity to guide the timing of re-treatment.
A Preliminary Assessment of Rotavirus Vaccine Effectiveness in Zambia.

BACKGROUND Diarrhea is the third leading cause of child death in Zambia. Up to one-third of diarrhea cases resulting in hospitalization and/or death are caused by vaccine-preventable rotavirus. In January 2012, Zambia initiated a pilot introduction of the Rotarix live, oral rotavirus vaccine in all public health facilities in Lusaka Province. METHODS Between July 2012 and October 2013, we conducted a case-control study at 6 public sector sites to estimate rotavirus vaccine effectiveness (VE) in age-eligible children presenting with diarrhea. We computed the odds of having received at least 1 dose of Rotarix among children whose stool was positive for rotavirus antigen (cases) and children whose stool was negative (controls). We adjusted the resulting odds ratio (OR) for patient age, calendar month of presentation, and clinical site, and expressed VE as (1 - adjusted OR) × 100. RESULTS A total of 91 rotavirus-positive cases and 298 rotavirus-negative controls who had under-5 card-confirmed vaccination status and were ≥6 months of age were included in the case-control analysis. Among rotavirus-positive children who were age-eligible to be vaccinated, 20% were hospitalized. Against rotavirus diarrhea of all severity, the adjusted 2-dose VE was 26% (95% confidence interval [CI], -30% to 58%) among children ≥6 months of age. VE against hospitalized children ≥6 months of age was 56% (95% CI, -34% to 86%). CONCLUSIONS We observed a higher point estimate for VE against increased severity of illness compared with milder disease, but were not powered to detect a low level of VE against milder disease.
Neurotoxic Aβ peptides increase oxidative stress in vivo through NMDA‐receptor and nitric‐oxide‐synthase mechanisms, and inhibit complex IV activity and induce a mitochondrial permeability transition in vitro

Beta amyloid (Aβ) peptides accumulate in Alzheimer's disease and are neurotoxic possibly through the production of oxygen free radicals. Using brain microdialysis we characterized the ability of Aβ to increase oxygen radical production in vivo. The 1–40 Aβ fragment increased 2,3‐dehydroxybenzoic acid efflux more than the 1–28 fragment, in a manner dependent on nitric oxide synthase and NMDA receptor channels. We then examined the effects of Aβ peptides on mitochondrial function in vitro. Induction of the mitochondrial permeability transition in isolated rat liver mitochondria by Aβ(25–35) and Aβ(35–25) exhibited dose dependency and required calcium and phosphate. Cyclosporin A prevented the transition as did ruthenium red, chlorpromazine, or N‐ethylmaleimide. ADP and magnesium delayed the onset of mitochondrial permeability transition. Electron microscopy confirmed the presence of Aβ aggregates and swollen mitochondria and preservation of mitochondrial structure by inhibitors of mitochondrial permeability transition. Cytochrome c oxidase (COX) activity was selectively inhibited by Aβ(25–35) but not by Aβ(35–25). Neurotoxic Aβ peptide can increase oxidative stress in vivo through mechanisms involving NMDA receptors and nitric oxide sythase. Increased intracellular Aβ levels can further exacerbate the genetically driven complex IV defect in sporadic Alzheimer's disease and may precipitate mitochondrial permeability transition opening. In combination, our results provide potential mechanisms to support the feed‐forward hypothesis of Aβ neurotoxicity.
The Correlation Risk Premium: International Evidence

In this paper we carry out the first cross-country analysis of the correlation risk premium. We examine the statistical properties of the implied and realized correlation in European equity markets and relate the resulting premium to the US equity market correlation risk and a global correlation risk premium. We find evidence of strong co-movement of correlation risk premiums in European and US equity markets. Our results support the existence of a global correlation risk premium that is priced in international equity option markets. We document the dependence of the correlation risk premium on macroeconomic policy uncertainty and related variables.
Hepatitis C Virus Infection in Scotland: Epidemiological Review and Public Health Challenges

Introduction In 2004, Scotland's Health Minister stated that the hepatitis C virus (HCV) “is one of the most serious and significant public health risks of our generation” Methods To appreciate the prevention and care challenges posed by HCV in Scotland, we reviewed all country-specific data on i) the prevalence of infection among different populations, ii) the numbers infected with HCV, and iii) the current and future HCV disease burden Results An estimated 1% of Scotland's population has HCV; 85-90% of those infected were injecting drug users (IDUs). Reductions in HCV prevalence among young IDUs during the early 1990s suggest that the incidence of HCV had decreased; since then, the absence of further reductions highlight that existing prevention measures are insufficient. Two-thirds of the estimated 37,500 chronically HCV-infected individuals in Scotland remain undiagnosed and two-thirds of this group are former IDUs. An estimated 9,000 former IDUs were living with either moderate or severe HCV disease in 2004; if the current uptake of antiviral therapy continues, this number was estimated to double by 2016. Approximately 1,200 HCV-infected IDUs had developed liver failure by 2004; this figure was predicted to increase to 3,200 by 2020. Conclusions Scotland faces three principal public health challenges: i) the prevention of HCV among current IDUs, ii) the diagnosis of HCV-infected persons, particularly those most in need of therapy to prevent severe HCV disease, and iii) the current and future provision of adequate resources to ensure that the movement of patients through the diagnostic and clinical care pathway is optimal