Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoxia‐mediated stimulation of carcinoma cell invasiveness via upregulation of urokinase receptor expression

Tumor hypoxia and high levels of expression of the urokinase‐type plasminogen activator (uPA) receptor (uPAR) represent a poor clinical outcome for patients with various cancers. Here, we examined the effect of hypoxia on in vitro invasion of extracellular matrix and uPAR expression by human carcinoma cells. Compared with culture under 20% O2, culture for up to 24 hr under 1% or 4% O2 resulted in increased cell surface uPAR. However, the highest uPAR levels were observed in cells cultured under 1% O2. Culture of MDA‐MB‐231 breast carcinoma cells under hypoxia also resulted in increased uPAR mRNA levels. Furthermore, incubation with cobalt chloride or with an iron chelator also resulted in elevated uPAR expression, while presence of 30% carbon monoxide in the hypoxic atmosphere reduced the hypoxia‐mediated uPAR mRNA upregulation. Increased uPAR expression was paralleled by higher cell‐associated uPA levels and lower levels of secreted uPA as determined by gel zymography performed on cell extracts and culture‐conditioned media. In addition, the in vitro invasiveness of MDA‐MB‐231 breast carcinoma cells was significantly higher when the invasion assay was performed under hypoxic conditions. This effect of hypoxia on invasion was abrogated by including in the assay a monoclonal, function‐blocking anti‐uPAR antibody or by the presence of 30% carbon monoxide in the hypoxic atmosphere. Our findings indicate that hypoxia stimulates carcinoma cell invasiveness by upregulating uPAR expression on the cell surface through a mechanism that requires a putative heme protein. Through a similar mechanism, hypoxia may stimulate tumor invasion and metastasis in vivo. Int. J. Cancer 80:617–623, 1999. © 1999 Wiley‐Liss, Inc.
The rule of law, central bank independence and price stability

Abstract This work empirically investigates the effect of the interaction between the rule of law and legal central bank independence (CBI) on price stability (the level of inflation and inflation volatility), employing a panel dataset that covers up to 124 countries over the period from 1970 to 2013. A new, largely complete legal CBI dataset, covering 182 countries was used for the work. The results indicate that the effect of legal CBI on price stability depends on the strength of the rule of law. Moreover, the results reveal that legal CBI has no significant effect on price stability when the rule of law is weak. The findings also show that 67% of advanced countries possess a rule of law that is strong enough to maintain price stability by increasing central bank autonomy, while only 4.5% of developing countries possess it.
Differentiation of mitral cell dendrites in the developing main olfactory bulbs of normal and naris‐occluded rats

The morphological differentiation of mitral cell dendrites during embryonic and early postnatal development was examined in the main olfactory bulb of rats to determine a possible role of afferent activity in the development of the dendrites. Mitral cells and olfactory nerve fibers were labeled with 1,1`‐dioctadecyl‐3,3,3`,3`‐tetramethylindocarbocyanine perchlorate (DiI) and fluorescein‐conjugated lectin (Ulex europeus agglutinin‐I), respectively. Morphogenesis of mitral cell dendrites proceeded as previously described (Malun and Brunjes [1996] J. Comp. Neurol. 368:1–16); that is, undifferentiated dendrites with radial orientation were transformed into a single primary dendrite having a glomerular tuft and secondary dendrites extending tangentially into the external plexiform layer. Quantitative examinations in both pre‐ and postnatal rats revealed that the differentiation of primary dendrites, including tuft formation, increases in diameter and decreases in branching, started before birth, whereas differentiated secondary dendrites were only observed in postnatal animals. Mitral cells with more than two primary dendrites were found after embryonic day 21. The proportion of the mitral cells with differentiated dendrites increased postnatally. At postnatal day 10, almost all mitral cells had fully differentiated dendrites, and mitral cells with multiple primary dendrites were no longer seen. No significant change was found during development in the number of stem dendrites that arose directly from the cell body. Unilateral naris occlusion started on postnatal day 1 retarded differentiation of primary and secondary dendrites, and increased the proportion of mitral cells with multiple primary dendrites. These finding revealed that differentiation of mitral cell primary dendrites precedes that of secondary dendrites, and suggested that the differentiation of secondary dendrites proceeds in an activity‐dependent manner. J. Comp. Neurol. 418:402–410, 2000. © 2000 Wiley‐Liss, Inc.
Specificity of the Protective Antibody Response to Apical Membrane Antigen 1

ABSTRACT Apical membrane antigen 1 (AMA1) is considered one of the leading candidates for inclusion in a vaccine against blood stages ofPlasmodium falciparum. Although the ama1 gene is relatively conserved compared to those for some other potential vaccine components, numerous point mutations have resulted in amino acid substitutions at many sites in the polypeptide. The polymorphisms in AMA1 have been attributed to the diversifying selection pressure of the protective immune responses. It was therefore of interest to investigate the impact of sequence diversity in P. falciparum AMA1 on the ability of anti-AMA1 antibodies to inhibit the invasion of erythrocytes in vitro by P. falciparummerozoites. For these studies, we used antibodies to recombinantP. falciparum 3D7 AMA1 ectodomain, which was prepared for testing in early clinical trials. Antibodies were raised in rabbits to the antigen formulated in Montanide ISA720, and human antibodies to AMA1 were isolated by affinity purification from the plasma of adults living in regions of Papua New Guinea where malaria is endemic. Both rabbit and human anti-AMA1 antibodies were found to be strongly inhibitory to the invasion of erythrocytes by merozoites from both the homologous and two heterologous lines of P. falciparum. The inhibitory antibodies targeted both conserved and strain-specific epitopes within the ectodomain of AMA1; however, it appears that the majority of these antibodies reacted with strain-specific epitopes in domain I, the N-terminal disulfide-bonded domain, which is the most polymorphic region of AMA1.
Residual Hearing Thresholds in Cochlear Implantation and Reimplantation

Implant and reimplantation surgery should be carried out with preservation of residual hearing. The aim of this study is to evaluate the effects of such a surgery on hearing threshold. We report the results on 40 patients, 20 males and 20 females, aged between 5 and 70 (mean 29) years, 16 pre-verbal and 24 post-verbal, with measurable pre-operative auditory thresholds. We used the following implants: Advanced Bionics, Med-El, Cochlear, and MXM Digisonic. Four of the patients underwent cochlear reimplantation owing to device failure. A complete insertion was obtained in all patients. Responses to pure-tone stimuli were evaluated in each ear in pre-implant conditions and 3 months after cochlear implant or reimplantation. The explantation was performed with minimal cochlear trauma and preservation of the explanted electrode integrity. 35% showed no change of the hearing threshold, 45% showed a slight worsening of the hearing threshold level in the implanted ear, and 20% had a total loss of residual hearing. Median increases of threshold levels were 10, 5, 10 and 3 dB HL respectively for 125, 250, 500 and 1 kHz. In the group of 4 patients who underwent cochlear reimplantation, 2 showed no variation of the hearing threshold, 1 preserved an appreciable hearing threshold, and 1 had a total loss of residual hearing. The data seem to suggest that hearing function is rather resistant to mechanical trauma during implant and reimplant surgery; the authors hypothesize a role for direct spiral ganglion activation under intense mechanical stimulation.
Humoral immunity against the proline-rich peptide epitope of the IgA1 hinge region in IgA nephropathy.

BACKGROUND The human IgA1 hinge region is a unique mucin-like O-linked proline-rich glycopeptide, and its core peptide was found to be exposed aberrantly by the underglycosylation in IgA nephropathy (IgAN). We describe here the presence of humoral immunity against the IgA1 hinge peptide epitope in IgAN and evaluate the relationship between the underglycosylation of the IgA1 hinge region and humoral immunity. METHOD The serum anti-IgA1 hinge peptide antibody (anti-alpha1HP ab) titre was measured and compared between the IgAN (n=37) and control groups (n=34) by enzyme-linked immunosorbent assay (ELISA) using a synthetic peptide corresponding to the human IgA1 hinge region, PVPSTPPTPSPSTPPTPSPS, as an antigen. Next, to evaluate the relationship between the underglycosylation of the IgA1 hinge region and the humoral immunity, the reactivity of the serum IgG from the patients with IgAN against monoclonal IgA1 which had been digested enzymatically to remove the carbohydrates from the IgA1 hinge region was measured by ELISA. RESULTS The anti-alpha1HP ab titre was significantly higher in the IgAN group than in the control group (OD value: IgG class, 0.564+/-0.344 vs 0. 331+/-0.154, P=0.0014; IgM class, 0.272+/-0.148 vs 0.141+/-0.072, P<0.0001) and it was positive in approximately 40% of the patients with IgAN. In addition, the reactivity of the serum IgG from the IgAN patients against the monoclonal IgA1 was found to be increased as the carbohydrates were enzymatically removed from the IgA1 hinge region (when native=100; asialo, 122+/-9.5; agalacto, 167+/-11.5; naked, 188+/-3.9). CONCLUSION These results suggested that the peptide epitope of the IgA1 hinge region which was aberrantly exposed by underglycosylation could induce the humoral immune response in IgAN.
Local recurrence of small cell lung cancer following radiofrequency ablation is induced by HIF-1α expression in the transition zone

Local recurrence of lung cancer following radiofrequency ablation (RFA) treatment is common. The aims of the present study were to assess how RFA treatment affects the growth of small cell lung cancer (SCLC) micrometastases in the transition zone (TZ) surrounding the ablated region and in the reference zones (RZs) of the ablated or unablated lobes and to identify the molecular mechanism(s) of lung cancer recurrence following RFA treatment. After lung micrometastases of human SCLCs had formed, RFA treatment was applied to the right upper lobe (RUL) of the lung in nude mice. Hypoxia inducible factor (HIF)-1α expression, proliferation and angiogenesis potential both in the TZ and RZ were evaluated over time. Separately, at day 1, 7 and 14 following RFA treatment, the growth of micrometastases showed an ~2-fold increase in the TZ compared to the RZ of the unablated lobe, as the right lower lobe (RLL) and the growth of micrometastases in the RZ of the RUL was also induced by RFA. In addition, accelerated tumor growth in the TZ was induced by HIF-1α, but was not associated with tissue angiogenesis potential. We concluded that local recurrences of SCLCs caused by overproliferation of micrometastases following RFA treatment were driven by HIF-1α, although angiogenesis was not the driving force in the TZ.
Subject–verb agreement in Brazilian Portuguese: what low error rates hide

This study focuses on the acquisition of subject–verb agreement in Brazilian Portuguese. A quantitative analysis of the data produced by a Brazilian child between the ages of 3;02.07 and 3;04.08 is presented. The overall error rate is low. However, a further and more detailed analysis reveals important contrasts both in the frequency of production of different verb inflections (as regards the person/number variables within the verb morphological system) and in the rate of subject–verb agreement errors associated with them. Our findings not only suggest that subject–verb agreement may be acquired piecemeal, but also that the learning of particular verb inflections may itself be a gradual process. Alternatives to the idea of rule-governed production – such as the child's reproducing frozen subject–verb strings previously produced by adults and blending different frozen strings into novel combinations – are discussed as processes which can shed some light on the pattern of both erroneous and correct production shown by this child.
Accelerated senescence of endothelial progenitor cells in hypertension is related to the reduction of calcitonin gene-related peptide

Objectives To explore whether the accelerated senescence of endothelial progenitor cells (EPCs) is related to the reduction of calcitonin gene-related peptide (CGRP) in hypertension. Methods and results In-vivo studies, plasma levels of CGRP and the number of senescent EPCs were measured in hypertensive humans and animals, from which the EPCs were isolated to examine the production of CGRP. Moreover, rutaecarpine, as an agent or tool to stimulate CGRP production, was used in hypertensive animals. The effects of rutaecarpine on angiotensin II-induced EPCs senescence were evaluated in vitro. The results showed that the number of circulating senescent EPCs was significantly increased in hypertension concomitantly with the decreased plasma level of CGRP and the decreased CGRP mRNA expression in EPCs. Administration of rutaecarpine reversed EPC senescence along with an elevation in CGRP production in spontaneously hypertensive rats. In the angiotensin II-induced EPCs senescence, the CGRP mRNA expression was reduced, which was reversed by rutaecarpine. The effect of rutaecarpine on EPCs was canceled in the presence of capsazepine, a selective antagonist of transient receptor potential vanilloid 1. Conclusion The results suggest that CGRP may work as an endogenous protective substance to counteract EPCs senescence in hypertension and the accelerated EPCs senescence in hypertension was related to the reduction of CGRP.
A simple and powerful analysis of lateral subdiffusion using single particle tracking

In biological membranes many factors such as cytoskeleton, lipid composition, crowding and molecular interactions deviate lateral diffusion from the expected random walks. These factors have different effects on diffusion but act simultaneously so the observed diffusion is a complex mixture of diffusive behaviors (directed, >Brownian, anomalous or confined). Therefore commonly used approaches to quantify diffusion based on averaging of the displacements, such as the mean square displacement, are not adapted to the analysis of this heterogeneity. We introduce a new parameter, the packing coefficient Pc, which gives an estimate of the degree of free movement that a molecule displays in a period of time independently of its global diffusivity. Applying this approach to two different situations (diffusion of a lipid probe and trapping of receptors at synapses), we show that Pc detected and localized temporary changes of diffusive behavior both in time and in space. More importantly, it allowed the detection of periods with very high confinement (~immobility), their frequency and duration, and thus it can be used to calculate the effective kon and koff of scaffolding interactions such those that immobilize receptors at synapses.
Standards of care in cauda equina syndrome

Abstract What constitutes cauda equina syndrome (CES), how it should be subclassified and how urgently to image and operate on patients with CES are all matters of debate. A structured review of the literature has led us to evaluate the science and to propose evidence-based guidelines for the management of CES. Our conclusions include this guidance: pain only; MRI negative – recommend: analgesia, ensure imaging complete (not just lumbar spine) adequate follow-up. Bilateral radiculopathy (CESS) with a large central disc prolapse – recommend: discuss with the patient and if for surgery, the next day (unless deteriorates to CESI in which case emergency surgery); CESI – recommend: the true emergency for surgery by day or night; a large central PLID with uncertainty as to whether CESI or CESR (e.g. catheterised prior to CESR) or where there is residual cauda equina nerve root function or early CESR – recommend: treat as an emergency by day or night. Where there has been prolonged CESR and/or no residual sacral nerve root function – recommend: treat on the following day’s list.
In vitro metabolism of TAK-438, vonoprazan fumarate, a novel potassium-competitive acid blocker

Abstract 1. TAK-438, vonoprazan fumarate, is a novel orally active potassium-competitive acid blocker, developed as an antisecretory drug. In this study, we investigated the in vitro metabolism of 14C-labeled TAK-438. In human hepatocytes, M-I, M-II, M-III and M-IV-Sul were mainly formed, and these were also detected in clinical studies. N-demethylated TAK-438 was also formed as an in vitro specific metabolite. Furthermore, CYP3A4 mainly contributed to the metabolism of TAK-438 to M-I, M-III, and N-demethylated TAK-438, and CYP2B6, CYP2C19 and CYP2D6 partly catalyzed the metabolism of TAK-438. The sulfate conjugation by SULT2A1 also contributed to the metabolism of TAK-438 to form TAK-438 N-sulfate, and CYP2C9 mediated the formation of M-IV-Sul from TAK-438 N-sulfate. The metabolite M-IV, which could be another possible intermediate in the formation of M-IV-Sul, was not observed as a primary metabolite of TAK-438 in any of the in vitro studies. 2. In conclusion, TAK-438 was primarily metabolized by multiple metabolizing enzymes including CYP3A4, CYP2B6, CYP2C19, CYP2D6, and a non-CYP enzyme SULT2A1, and the influence of the CYP2C19 genotype status on gastric acid suppression post TAK-438 dosing could be small. The multiple metabolic pathways could also minimize the effects of co-administrated CYP inhibitors or inducers on the pharmacokinetics of TAK-438.
Effect of dietary and injectable vitamin E and selenium in weanling swine antigenically challenged with sheep red blood cells.

Two experiments were conducted to evaluate the effect of supplemental vitamin E and (or) Se, provided either in the diet or by injection, on humoral antibody production in weanling swine after an antigenic challenge with sheep red blood cells (SRBC). In the first experiment, a 2 x 2 factorial design was used, with pigs fed either 0 or . 5 ppm Se and 0 or 220 IU vitamin E/kg diet. The basal diet contained a natural Se and alpha-tocopherol content of . 02 ppm and 7 mg/kg, respectively. In a second 2 x 2 factorial trial, 0 or 6 mg Se and 0 or 220 mg alpha-tocopherol were injected intramuscularly into weaning pigs fed the basal diet without supplemental Se or vitamin E. A fifth treatment group was fed a positive control diet containing both nutrients (.5 ppm Se and 220 IU vitamin E/kg). In both experiments, intraperitoneal injections of SRBS (1 x 10(8)) were administered weekly, with hemagglutination titers determined at these intervals. Hemagglutination assays indicated that vitamin E and Se independently enhanced the immune response, particularly during the latter weeks of the experiment. The combination of both nutrients, provided either in the diet or via injection, resulted in a further increase in hemagglutination titers, suggesting an additive response. Pigs receiving either Se or vitamin E had higher serum concentrations of the nutrient provided. Dietary sources of these nutrients resulted in greater serum and tissue levels than did injections.
Real-Time PCR Assay To Differentiate Listeriolysin S-Positive and -Negative Strains of Listeria monocytogenes

ABSTRACT Due to the severity of the food-borne infection listeriosis, strict legislation governs the detectable and permissible limits at which Listeria monocytogenes is permitted in foods. These requirements, coupled with the ubiquitous nature of L. monocytogenes strains and the potential for epidemic outbreaks, mean that the pathogen can devastate affected sectors of the food industry. Although almost all L. monocytogenes strains have the potential to cause listeriosis, those implicated in the vast majority of epidemics belong to a subset of strains belonging to evolutionary lineage I. It has been established that a significant proportion of these strains, including those implicated in the majority of outbreaks, produce an additional hemolysin, designated listeriolysin S (LLS), which may be responsible for the enhanced virulence of these strains. In order to ultimately establish this definitively, it is important to first be able to rapidly discriminate between LLS-positive and -negative strains. Here, after essential genes within the LLS-encoding cluster, Listeria pathogenicity island 3, were identified by deletion mutagenesis, a real-time PCR assay which targets one such gene, llsX, was developed as a means of identifying LLS-positive L. monocytogenes. The specificity of the assay was validated against a panel of 40 L. monocytogenes strains (20 of which were LLS positive) and 25 strains representative of other Listeria species. Furthermore, 1 CFU of an LLS-positive strain per 25 g/ml of spiked foods was detected in less than 30 h when the assay was coupled with culture enrichment. The detection limit of this assay was 10 genome equivalents.
The Impact of focusing students' attention on themselves as future professionals on their professional calling

Researchers express ideas about the relationship between focusing students' attention on themselves as future professionals during their studies and students' professional calling. However, empirical evidence on this relationship is still lacking. The research aimed to answer the question: "What is the impact of focusing students' attention on themselves as future professionals on their professional calling? " In order to answer this question the quasi-experiment with the non-equivalent comparison group without the pre-test design has been carried out. The quasi-experimental programme was implemented in the experimental group of 31 student of the social pedagogy study programme of Klaipėda University in 2009-2014. The control group consisted of 79 students from three other Lithuanian universities. The final measurement was carried out in the control and experimental groups on May-June, 2014. The results argue that focusing students' attention on themselves as future professionals during their studies has an impact on their professional calling.
Factors affecting the intensity of reinfection with Schistosoma haematobium following treatment with praziquantel

SUMMARY Infection with Schistosoma haematobium was studied in a rural community of approximately 500 persons in eastern Zimbabwe. The overall prevalence of infection, as determined by urine egg counts, was 40·1%, and of heavy infections (≥ 50 eggs/10 ml urine) was 11·0%. The prevalence of both heavy and all infections was highest in the 8 to 10-year-old age class. During 1987–88 data were obtained from 102 individuals on intensity of reinfection 14 weeks after treatment with praziquantel, the efficacy of treatment having been determined after 4 weeks. The water contact made by these individuals during 2-week periods immediately following treatment was recorded. The relative abundance of patent infected intermediate host snails, Bulinus globosus, was also monitored. An index of exposure was developed which weighted each water contact by its duration, the type of activity, the time of day, and the abundance of infected snails at the site used. The relationships between rates of reinfection, rates of exposure, and age were examined. Although only 13 individuals showed positive rates of reinfection, there were statistically significant and independent effects of both exposure and age on reinfection rate. Quantitative estimates of reinfection rates suggested that individuals aged 12 years or less acquired substantially more infection (measured as egg output) than individuals more than 12 years old.