Miracle-dz/UniFAR-FTUs huggingface dataset:
Nrf2 deficiency improves autoimmune nephritis caused by the fas mutation lpr.

BACKGROUND Nrf2 is a basic leucine zipper transcriptional activator essential for the coordinate transcriptional induction of antioxidant and phase II drug metabolizing enzymes. We previously reported that Nrf2-deficient female mice develop lupus-like autoimmune nephritis (Kidney Int 60:1343-1353, 2001). The result suggested that nrf2 is a possible candidate gene in determining susceptibility to autoimmune diseases. MRL/lpr mice, defective in Fas-mediated apoptosis, develop glomerulonephritis due to the production of autoantibodies. METHODS To investigate the mechanism whereby Nrf2 contributes to the susceptibility to autoimmune diseases, we generated nrf2-/-lpr/lpr mice. RESULTS Unexpectedly, the lifespan of nrf2-/-lpr/lpr female mice was markedly prolonged and these mice showed an improvement in nephritis compared to nrf2+/+lpr/lpr female mice. Immunologic abnormalities and hypergammaglobulinemia were also alleviated in nrf2-/-lpr/lpr female mice. Furthermore, lymphadenopathy was suppressed as a result of increased apoptosis. To elucidate the molecular mechanism causing a stimulation of apoptosis, we analyzed the response made by nrf2-/-lpr/lpr mice to death signals. We show that nrf2-/-lpr/lpr mice are sensitive to tumor necrosis factor-alpha (TNF-alpha)-mediated apoptosis. Since intracellular glutathione levels are decreased in Nrf2-deficient cells, it is probable that a prolonged depletion in glutathione levels leads to the enhancement in TNF-alpha-mediated apoptosis. CONCLUSION These results indicate that a deficiency in Nrf2 enhances TNF-alpha-mediated apoptosis which in-turn ameliorates the abnormal apoptotic response that arises from a mutation in the lpr gene. Therefore, Nrf2 deficiency acts as a suppressor of the autoimmune accelerating gene lpr.
Mast cell mediators other than histamine induce pruritus in atopic dermatitis patients: a dermal microdialysis study

While histamine is the crucial mediator of pruritus in type 1 allergic reactions, its role in atopic dermatitis (AD) is unclear. In this study, the role of mast cell mediators in protein extravasation and pruritus was evaluated using intradermal microdialysis. The microdialysis capillaries were used to apply the mast cell degranulating substance compound 48/80 (C48/80; 0·05%) or histamine (0·01%) and also to deliver H1‐blockers (cetirizine, 200 μg mL−1) in nine AD patients and nine controls. Large pore size membranes (3000 kDa) enabled simultaneous analysis of protein extravasation. Itch sensation was measured psychophysically and weal and flare reaction were evaluated planimetrically. Protein extravasation induced by histamine and C48/80 was significantly reduced in AD patients. Blockade of H1‐receptors by cetirizine significantly reduced C48/80‐induced protein extravasation in AD patients and controls to an identical level. C48/80‐induced pruritus was abolished by cetirizine in controls, whereas pruritus in AD patients was unchanged after H1 blockade. We conclude that mast cell mediators others than histamine are involved in C48/80‐induced pruritus in AD patients. Whether the reduced capacity of AD patients to induce protein extravasation is of pathophysiological relevance for pruritus remains to be established.
Positron emission tomographic studies of cerebral benzodiazepine‐receptor binding in chronic alcoholics

Positron emission tomography was used with [11C] flumazenil (FMZ) and [18F] fluorodeoxyglucose to study GABA type A/benzodiazepine (GABA‐A/BDZ) receptors and cerebral metabolic rates for glucose (1CMRglc) in 17 male patients with severe chronic alcoholism (ALC), 8 with (ACD) and 9 without alcoholic cerebellar degeneration (non‐ACD). In comparison with male normal controls of similar ages, the ALC group had significantly reduced FMZ ligand influx (K1), FMZ distribution volume (DV), and 1CMRglc bilaterally in the medial frontal lobes, including superior frontal gyrus and rostral cingulate gyrus; the ACD group had significant reductions of K1, DV, and ICMRglc bilaterally in the same distribution, and also in the superior cerebellar vermis; and the non‐ACD group had significant reductions of K1, DV, and ICMRglc bilaterally in the same regions of the frontal lobes but not in the superior cerebellar vermis. When compared with the non‐ACD group, the ACD group had significant reductions of K1 and DV bilaterally in the superior cerebellar vermis. The results suggest that severe chronic alcoholism damages neurons containing GABA‐A/BDZ receptors in the superior medial apsects of the frontal lobes, and in patients with clinical signs of ACD, neurons containing GABA‐A/BDZ receptors in the superior cerebellar vermis.
Predicting Feelings of Cognitive Competence in Head Start Preschoolers

ABSTRACT Little is known about what predicts the budding sense of self-competence in preschoolers. This is particularly true of cognitive competence, which may have implications for later schooling. Based on previous research with older children, it was expected that feelings of self-competence would be influenced by attitudes of significant others as well as intrapersonal dispositions. Forty-five Head Start preschoolers (M age = 4.36 years) served as participants. As expected, high effortful control and language competence, as well as teachers’ ratings of competence, predicted positive feelings about cognitive competence in children. Further analysis revealed that the teachers’ ratings were predicted by maternal education and language competence. The findings suggest that the development of cognitive self-concept in preschoolers is predicted by contextual and constitutional factors.
Molecular characterization of replication-competent variants of adenovirus vectors and genome modifications to prevent their occurrence

Adenovirus (Ad) vectors for gene therapy are made replication defective by deletion of E1 region genes. For isolation, propagation, and large-scale production of such vectors, E1 functions are supplied in trans from a stable cell line. Virtually all Ad vectors used for clinical studies are produced in the 293 cell, a human embryonic kidney cell line expressing E1 functions from an integrated segment of the left end of the Ad type 5 (Ad5) genome. Replication-competent vector variants that have regained E1 sequences have been observed within populations of Ad vectors grown on 293 cells. These replication-competent variants presumably result from recombination between vector and 293 cell Ad5 sequences. We have developed Ad2-based vectors and have characterized at the molecular level examples of replication-competent variants. All such variants analyzed are Ad2-Ad5 chimeras in which the 293 cell Ad5 E1 sequences have become incorporated into the viral genome by legitimate recombination events. A map of Ad5 sequences within the 293 cell genome developed in parallel is consistent with the proposed recombination events. To provide a convenient vector production system that circumvents the generation of replication-competent variants, we have modified the Ad2 vector backbone by deleting or rearranging the protein IX coding region normally present downstream from the E1 region such that the frequency of recombination between vector and 293 cell Ad5 sequences is greatly reduced. Twelve serial passages of an Ad2 vector lacking the protein IX gene were carried out without generating replication-competent variants. In the course of producing and testing more than 30 large-scale preparations of vectors lacking the protein IX gene or having a rearranged protein IX gene, only three examples of replication-competent variants were observed. Use of these genome modifications allows use of conventional 293 cells for production of large-scale preparations of Ad-based vectors lacking replication-competent variants.
Relationship between GDP, Foreign Direct Investment and Export Volume: Evidence from Indonesia

Using time-series and co-integration test from 1981 to 2013, this manuscript examines the long-run relations between FDI, GDP and export volume of Indonesia. The impact of Indonesian export volume and FDI on Indonesian GDP were measured in this article, it has been found that export volume and FDI have significant influence on economic growth of Indonesia. In addition, according to Johansen cointegration test, there is long-run relationship between GDP, FDI and export volume of Indonesia. The empirical findings are consistent with other academic articles.
Diversity and distribution of fungal communities in lakes of Antarctica.

This study assessed the diversity and distribution of filamentous fungi obtained from water sampled from six lakes in the Antarctic Peninsula. One hundred and twenty-eight fungal isolates were purified and identified by analysis of nuclear rDNA ITS region sequences as belonging to 31 fungal different operational taxonomic units (OTUs). The most frequently isolated fungi were Geomyces pannorum and Mortierella sp. ; these species occurred in six and three of the lakes sampled, respectively, and displayed the highest total colony-forming unit per L. Different species that have not been found to these lakes and/or had adapted to cold conditions were found. In general, the fungal community displayed low richness and high dominance indices. The species Cadophora cf. luteo-olivacea, Cadophora malorum, Davidiella tassiana, G. pannorum, Mortierella cf. alpina and Thelebolus cf. microsporus that were found in the lakes in question were also previously found in other cold ecosystems, such as Arctic, temperate and Alpine regions. The results of this study suggest the presence of an interesting aquatic fungal web, including symbionts, weak and strong saprophytes and parasite/pathogen fungal species. This aquatic web fungal may be a useful community model for further ecological and evolutionary studies of extreme habitats.
Sequence and mutational analysis of ESS1, a gene essential for growth in Saccharomyces cerevisiae

A newly isolated gene, ESS1, was shown to encode a protein required for vegetative growth in Saccharomyces cerevisiae. The nucleotide sequence of ESS1 revealed a 172 amino acid open reading frame predicting a highly basic, 19·5 kilodalton product. Although the gene was isolated by cross‐hybridization with the vertebrate v‐sis oncogene, the primary amino acid sequence bears only a slight resemblance to the p28sis protein. ESS1 was shown to be single copy in the yeast genome and transcriptionally active during logarithmic growth. It is located on the right arm of chromosome X, 6 centimorgans distal to ilv3. The genetic map location indicates it is not allelic to any previously characterized mutation in this organism. Both inactivation of ESS1 by gene disruption and overexpression by fusion to a heterologous promoter were detrimental to growth in both haploid and diploid cell types. Under non‐permissive conditions, the terminal phenotype of strains containing a suppressible amber mutation within ESS1 was one of aberrant multibudded structures. Examination of this morphology indicates that loss of ESS1 function may lead to a defect in cytokinesis or cell separation.
The effect of tax harmonisation in the Southern African Development Community on Foreign Direct Investment

This paper investigates the effect of tax harmonisation on foreign direct investment (FDI) in the Southern African Development Community (SADC) region. Findings of a first attempt to investigate the linkage between taxation (tax rates and policy) and FDI (in all 15 countries), using an eclectic panel data modeling approach from 1990-2010 are presented. A new value added tax (VAT) harmonisation variable is introduced (in addition to a corporate income tax (CIT) harmonisation variable) via a tax policy harmonisation measure (TPHM) in the panel empirical investigation, complemented by a sensitivity analysis (using the extreme-bound analysis (EBA) technique) on the impact of taxation on FDI inflows to the SADC. The investigation shows that when errors in the regressors (for instance contemporaneous correlation, heteroskedasticity, cross-sectional dependence, endogeneity) are controlled for, tax harmonisation (amongst other contributing factors) does indeed have a significant causal relationship with FDI in the SADC. The study generally provides empirical evidence to support the argument for effectively using taxation towards higher FDI inflows in the region. Policy considerations towards improved tax harmonisation emanating from the paper include the need for individual SADC governments to promote national tax policies aimed at supporting regional tax harmonisation objectives, through strengthening existing tax agreements and treaties. This is necessary to reduce disparity in tax rates (including the definition of tax bases), improve existing level of tax co-movement, mitigate tax leakages and promote FDI inflows.
Evaluation of Whole-Cell and OspC Enzyme-Linked Immunosorbent Assays for Discrimination of Early Lyme Borreliosis from OspA Vaccination

ABSTRACT A recombinant Lyme borreliosis vaccine consisting of outer surface protein A (OspA) is commercially available for vaccination of humans against infection with Borrelia burgdorferi. Vaccination with OspA induces an antibody response that makes serologic interpretation of infection with B. burgdorferi difficult, especially by screening tests based on whole-cell preparations ofB. burgdorferi. We show that an enzyme-linked immunosorbent assay with B. burgdorferi sensu stricto 50772, which lacks the plasmid encoding OspA and OspB, or a full-length recombinant OspC protein can identify patients infected with B. burgdorferi. We found that 69 and 65% of serum samples from patients with case-defined early Lyme borreliosis had anti-B. burgdorferisensu stricto 50772 and anti-OspC reactivities, respectively. In addition, little or no reactivity was detected with sera obtained from individuals vaccinated with OspA. Unfortunately, 51 and 33% of sera from healthy patients and sera from patients with other illnesses were also reactive against B. burgdorferi sensu stricto 50772 and OspC, respectively. Although these assays can discriminate B. burgdorferi infection from vaccination with OspA, their lack of specificity highlights the necessity for confirming equivocal or positive reactivities with more specific serodiagnostic tests.
The Relationship of Nucleotide Polymorphism, Recombination Rate and Selection in Wild Tomato Species

We analyzed the effects of mating system and recombination rate on single nucleotide polymorphisms using 14 single-copy nuclear loci from single populations of five species of wild tomatoes (Solanum section Lycopersicon). The taxa investigated comprise two self-compatible (SC) and three self-incompatible (SI) species. The observed reduction in nucleotide diversity in the SC populations compared to the SI populations is much stronger than expected under the neutral effects of the mating system on effective population size. Importantly, outgroup sequences available for 11 of the 14 loci yield strong positive correlations between silent nucleotide diversity and silent divergence, indicative of marked among-locus differences in mutation rates and/or selective constraints. Furthermore, using a physical estimate of local recombination rates, we find that silent nucleotide diversity (but not divergence) is positively correlated with recombination rate in two of the SI species. However, this correlation is not nearly as strong as in other well-characterized species (in particular, Drosophila). We propose that nucleotide diversity in Lycopersicon is dominated mainly by differences in neutral mutation rates and/or selective constraints among loci, demographic processes (such as population subdivision), and background selection. In addition, we hypothesize that the soil seed bank plays an important role in the maintenance of the large genetic diversity in the SI species (in particular L. peruvianum).
Antigens and Alternatives for Control of Anaplasma marginale Infection in Cattle

SUMMARY Anaplasmosis, a tick-borne cattle disease caused by the rickettsia Anaplasma marginale, is endemic in tropical and subtropical areas of the world. The disease causes considerable economic loss to both the dairy and beef industries worldwide. Analyses of 16S rRNA, groESL, and surface proteins have resulted in the recent reclassification of the order Rickettsiales. The genus Anaplasma, of which A. marginale is the type species, now also includes A. bovis, A. platys, and A. phagocytophilum, which were previously known as Ehrlichia bovis, E. platys, and the E. phagocytophila group (which causes human granulocytic ehrlichiosis), respectively. Live and killed vaccines have been used for control of anaplasmosis, and both types of vaccines have advantages and disadvantages. These vaccines have been effective in preventing clinical anaplasmosis in cattle but have not blocked A. marginale infection. Thus, persistently infected cattle serve as a reservoir of infective blood for both mechanical transmission and infection of ticks. Advances in biochemical, immunologic, and molecular technologies during the last decade have been applied to research of A. marginale and related organisms. The recent development of a cell culture system for A. marginale provides a potential source of antigen for the development of improved killed and live vaccines, and the availability of cell culture-derived antigen would eliminate the use of cattle in vaccine production. Increased knowledge of A. marginale antigen repertoires and an improved understanding of bovine cellular and humoral immune responses to A. marginale, combined with the new technologies, should contribute to the development of more effective vaccines for control and prevention of anaplasmosis.
A silent chemokine receptor regulates steady-state leukocyte homing in vivo

The location of leukocytes in different microenvironments is intimately connected to their function and, in the case of leukocyte precursors, to the executed differentiation and maturation program. Leukocyte migration within lymphoid organs has been shown to be mediated by constitutively expressed chemokines, but how the bioavailability of these homeostatic chemokines is regulated remains unknown. Here, we report in vivo evidence for the role of a nonsignaling chemokine receptor in the migration of leukocytes under physiological, i.e., noninflammatory, conditions. We have studied the in vivo role of the silent chemokine receptor CCX-CKR1 by both loss- and gain-of-function approaches. CCX-CKR1 binds the constitutively expressed chemokines CC chemokine ligand (CCL)19, CCL21, and CCL25. We find that CCX-CKR1 is involved in the steady-state homing of CD11c+MHCIIhigh dendritic cells to skin-draining lymph nodes, and it affects the homing of embryonic thymic precursors to the thymic anlage. These observations indicate that the silent chemokine receptor CCX-CKR1, which is exclusively expressed by stroma cells, but not hematopoietic cells themselves, regulates homeostatic leukocyte migration by controlling the availability of chemokines in the extracellular space. This finding adds another level of complexity to our understanding of leukocyte homeostatic migration.
Nurses' experiences of using a smart mobile device application to assist home care for patients with chronic disease: a qualitative study.

AIMS AND OBJECTIVES To examine nurses' experiences regarding the benefits and obstacles of using a smart mobile device application in home care. BACKGROUND The popularity of mobile phones and Internet technology has established an opportunity for interaction between patients and health care professionals. Line is an application allowing instant communication that is available for free globally. However, the literature relating to use of Line in this area is limited. DESIGN A qualitative study involving individual in-depth interviews. METHODS Participants included community nurses (N = 17) from six home care facilities in southern Taiwan who had used Line for home care of chronically ill patients for at least six months. The study was conducted using semi-structured in-depth interviews, which were recorded and converted into transcripts for content analysis. RESULTS Seven themes emerged from data analysis: reduction in medical care consumption and costs, reduction in workload and stress, facilitating improvement in the quality of care, promotion of the nurse-patient relationship, perceived risk, lack of organisational incentives and operating procedures and disturbance to personal life. CONCLUSIONS Nurses considered Line valuable for use in home care. While this application has diverse functions, its video transfer function could in particular help nursing staff make prompt decisions about patients' problems and promote nurse-patient relationships. However, there might be hidden risks including legal consequences, safety risks to patients, possible violations of professionalism and increased risk of nurse burnout. Increasing nursing staff awareness of using mobile messaging software applications is necessary. RELEVANCE TO CLINICAL PRACTICE This study provides relevant information about the benefits, disadvantages, risks and limitations of nurses' use of Line. The study also provides suggestions for software programmers and future organisational strategy and development.
Predicting Neurologic Outcome After Targeted Temperature Management for Cardiac Arrest: Systematic Review and Meta-Analysis*

Objectives:Targeted temperature management improves survival and neurologic outcomes for adult out-of-hospital cardiac arrest survivors but may alter the accuracy of tests for predicting neurologic outcome after cardiac arrest. Data Sources:We systematically searched Medline, Embase, CINAHL, and CENTRAL from database inception to September 2012. Study Selection:Citations were screened for studies that examined diagnostic tests to predict poor neurologic outcome or death following targeted temperature management in adult cardiac arrest survivors. Data Extraction:Data on study outcomes and quality were abstracted in duplicate. We constructed contingency tables for each diagnostic test and calculated sensitivity, specificity, and positive and negative likelihood ratios. Data Synthesis:Of 2,737 citations, 20 studies (n = 1,845) met inclusion criteria. Meta-analysis showed that three tests accurately predicted poor neurologic outcome with low false-positive rates: bilateral absence of pupillary reflexes more than 24 hours after a return of spontaneous circulation (false-positive rate, 0.02; 95% CI, 0.01–0.06; summary positive likelihood ratio, 10.45; 95% CI, 3.37–32.43), bilateral absence of corneal reflexes more than 24 hours (false-positive rate, 0.04; 95% CI, 0.01–0.09; positive likelihood ratio, 6.8; 95% CI, 2.52–18.38), and bilateral absence of somatosensory-evoked potentials between days 1 and 7 (false-positive rate, 0.03; 95% CI, 0.01–0.07; positive likelihood ratio, 12.79; 95% CI, 5.35–30.62). False-positive rates were higher for a Glasgow Coma Scale motor score showing extensor posturing or worse (false-positive rate, 0.09; 95% CI, 0.06–0.13; positive likelihood ratio, 7.11; 95% CI, 5.01–10.08), unfavorable electroencephalogram patterns (false-positive rate, 0.07; 95% CI, 0.04–0.12; positive likelihood ratio, 8.85; 95% CI, 4.87–16.08), myoclonic status epilepticus (false-positive rate, 0.05; 95% CI, 0.02–0.11; positive likelihood ratio, 5.58; 95% CI, 2.56–12.16), and elevated neuron-specific enolase (false-positive rate, 0.12; 95% CI, 0.06–0.23; positive likelihood ratio, 4.14; 95% CI, 1.82–9.42). The specificity of available tests improved when these were performed beyond 72 hours. Data on neuroimaging, biomarkers, or combination testing were limited and inconclusive. Conclusion:Simple bedside tests and somatosensory-evoked potentials predict poor neurologic outcome for survivors of cardiac arrest treated with targeted temperature management, and specificity improves when performed beyond 72 hours. Clinicians should use caution with these predictors as they carry the inherent risk of becoming self-fulfilling.