Miracle-dz/UniFAR-FTUs huggingface dataset:
Interleukin-4-Inducing Principle from Schistosoma mansoni Eggs Contains a Functional C-Terminal Nuclear Localization Signal Necessary for Nuclear Translocation in Mammalian Cells but Not for Its Uptake

ABSTRACT Interleukin-4-inducing principle from schistosome eggs (IPSE/alpha-1) is a protein produced exclusively by the eggs of the trematode Schistosoma mansoni. IPSE/alpha-1 is a secretory glycoprotein which activates human basophils via an IgE-dependent but non-antigen-specific mechanism. Sequence analyses revealed a potential nuclear localization signal (NLS) at the C terminus of IPSE/alpha-1. Here we show that this sequence (125-PKRRRTY-131) is both necessary and sufficient for nuclear localization of IPSE or IPSE-enhanced green fluorescent protein (EGFP) fusions. While transiently expressed EGFP-IPSE/alpha-1 was exclusively nuclear in the Huh7 and U-2 OS cell lines, a mutant lacking amino acids 125 to 134 showed both nuclear and cytoplasmic staining. Moreover, insertion of the IPSE/alpha-1 NLS into a tetra-EGFP construct rendered the protein nuclear. Alanine scanning mutagenesis revealed a requirement for the KRRR residues. Fluorescence microscopy depicted, and Western blotting further confirmed, that recombinant IPSE/alpha-1 protein added exogenously is rapidly internalized by CHO cells and accumulates in nuclei in an NLS-dependent manner. A mutant protein in which the NLS motif was disrupted by triple mutation (RRR to AAA) was able to penetrate CHO cells but did not translocate to the nucleus. Furthermore, the uptake of native glycosylated IPSE/alpha-1 was confirmed in human primary monocyte-derived dendritic cells and was found to be a calcium- and temperature-dependent process. Live-cell imaging showed that IPSE/alpha-1 is not targeted to lysosomes. In contrast, peripheral blood basophils do not take up IPSE/alpha-1 and do not require the presence of an intact NLS for activation. Taken together, our results suggest that IPSE/alpha-1 may have additional nuclear functions in host cells.
Nickel deficiency gives rise to the defective hydrogenase phenotype of hydc and fnr mutants in Escherichia coli

Hydrogenase activity and other hydrogenase‐related functions can be restored to hydC mutants by the specific addition of nickel salts to the growth medium. These mutants are defective in all three hydrogenase isoenzymes and the restoration is dependent upon protein synthesis. The cellular nickel content of the mutant when grown in LB medium is less than 1% of that of the parental strain. Partial suppression of the hydrogenase phenotype of hydC mutants occurs when growth takes place in a different medium. This correlates with an increased cellular nickel content. The phenotype of the mutant is also fully suppressed by growth in media of very low magnesium content. Such media facilitate nickel uptake via the magnesium transport system, which leads to the acquisition of a normal cellular nickel content. Mutations in the fnr gene, which encodes a transcriptional regulator for several anaerobically expressed enzymes, abolishes hydC expression and gives rise to a defective hydrogenase phenotype. The hydrogenase phenotype of fnr is closely similar to that of hydC in all respects examined. The hydrogenase activity of fnr strains can be restored by the presence of a functional hydC gene on a multicopy plasmid. The hydrogenase phenotype of fnr strains therefore arises indirectly via suppression of hydC, which leads to a low cellular nickel content. Nickel has no influence on fumarate reductase or nitrate reductase activities in fnr strains. The hydrogen‐metabolism phenotype of fnr strains is, therefore, dependent upon their ability to acquire nickel from growth media. It is likely that hydC encodes a specific transport system for nickel.
Arsenic contamination of Ronphibun residents associated with uses of arsenic-contaminated shallow-well water other than drinking

High levels of urinary arsenic have been reported among residents of an area of southern Thailand where many households have shallow wells heavily contaminated with arsenic. However, the finding that very few of the residents in this area have used contaminated shallow-well water for drinking or cooking in the last 10 years prompted this investigation. The aim was to identify the uses of shallow-well water by adult residents that were related to a positive association between shallow-well water and urinary arsenic levels. Information on shallow-well water use for all personal and domestic purposes was obtained and arsenic levels of household shallow-well water and urine (after refraining from seafood for 2 days) were measured. Urinary and shallow-well water arsenic levels were strongly positively associated among residents who regularly used shallow-well water for bathing (including washing face, hair, hands and feet) but not among residents regularly using arsenic-safe water for bathing or regularly using shallow-well water for other purposes, such as brushing teeth, domestic cleaning or washing food and utensils. The findings suggest that appreciable transdermal absorption of arsenic is possible and that successful abatement of human contamination with arsenic may require the provision of arsenic-safe water, not only for consumption but also for personal hygiene purposes.
Shigella Outer Membrane Protein PSSP-1 Is Broadly Protective against Shigella Infection

ABSTRACT In developing countries, Shigella is a primary cause of diarrhea in infants and young children. Although antibiotic therapy is an effective treatment for shigellosis, therapeutic options are narrowing due to the emergence of antibiotic resistance. Thus, preventive vaccination could become the most efficacious approach for controlling shigellosis. We have identified several conserved protein antigens that are shared by multiple Shigella serotypes and species. Among these, one antigen induced cross-protection against experimental shigellosis, and we have named it pan-Shigella surface protein 1 (PSSP-1). PSSP-1-induced protection requires a mucosal administration route and coadministration of an adjuvant. When PSSP-1 was administered intranasally, it induced cross-protection against Shigella flexneri serotypes 2a, 5a, and 6, Shigella boydii, Shigella sonnei, and Shigella dysenteriae serotype 1. Intradermally administered PSSP-1 induced strong serum antibody responses but failed to induce protection in the mouse lung pneumonia model. In contrast, intranasal administration elicited efficient local and systemic antibody responses and production of interleukin 17A and gamma interferon. Interestingly, blood samples from patients with recent-onset shigellosis showed variable but significant mucosal antibody responses to other conserved Shigella protein antigens but not to PSSP-1. We suggest that PSSP-1 is a promising antigen for a broadly protective vaccine against Shigella.
Cytosolic herpes simplex virus capsids not only require binding inner tegument protein pUL36 but also pUL37 for active transport prior to secondary envelopment

As the inner tegument proteins pUL36 and pUL37 of alphaherpesviruses may contribute to efficient intracellular transport of viral particles, we investigated their role in cytosolic capsid motility during assembly of herpes simplex virus type 1 (HSV1). As reported previously for pUL36, untagged pUL37 and UL37GFP bound to cytosolic capsids before these acquired outer tegument and envelope proteins. Capsids tagged with CheVP26 analysed by live cell imaging were capable of directed long‐distance cytoplasmic transport during the assembly of wild‐type virions, while capsids of the HSV1‐ΔUL37 or HSV1‐ΔUL36 deletion mutants showed only random, undirected motion. The HSV1‐ΔUL37 phenotype was restored when UL37GFP had been overexpressed prior to infection. Quantitative immunoelectron microscopy revealed that capsids of HSV1‐ΔUL37 still recruited pUL36, whereas pUL37 did not colocalize with capsids of HSV1‐ΔUL36. Nevertheless, the cytosolic capsids of neither mutant could undergo secondary envelopment. Our data suggest that pUL36 and pUL37 are important prior to their functions in linking the inner to the outer tegument. Efficient capsid transport to the organelle of secondary envelopment requires recruitment ofpUL37 onto capsids, most likely via its interaction with pUL36, while capsid‐associated pUL36 alone is insufficient.
Favorable efficacy of long‐term lamivudine therapy in patients with chronic hepatitis B: An 8‐year follow‐up study

The long‐term efficacy of lamivudine therapy in patients with hepatitis B virus (HBV) infection is still not clear. In this study, 20 non‐cirrhotic Japanese patients infected with HBV received lamivudine therapy for more than 1 year and were followed for a median period of 8.5 years (range, 6.7–8.7 years). The rates of HBe antigen (HbeAg) negative, HBV‐DNA undetectable, and alanine aminotransferase (ALT) normal level at the start of lamivudine were 55%, 25%, and 20% and 85%, 80%, and were 80%, respectively, at the last visit, including patients who received additional treatment. The values at the last visit tended to and were significantly higher than those at the start. The values improved at the last visit regardless of the emergence of YMDD motif mutant and continuation of lamivudine. YMDD mutant and biochemical relapse with mutant virus (breakthrough hepatitis) appeared in 65% and 45% during follow‐up, respectively, but severe breakthrough hepatitis occurred in only 5%. Furthermore, 80% of patients who received additional treatment for breakthrough hepatitis, regardless of continuation of lamivudine, were ALT normal level at the last visit, in contrast to 25% untreated. HBsAg clearance occurred in two patients of the discontinuous lamivudine group with non‐vertical transmission, who were relatively young. One was infected with HBV genotype C with breakthrough hepatitis and the other had no YMDD mutant and was infected with genotype D, a rare type in Japan. None developed cirrhosis or hepatocellular carcinoma (HCC) during follow‐up. Our results suggest that long‐term lamivudine therapy improves long‐term prognosis, especially when additional treatment for breakthrough hepatitis is used. J. Med. Virol. 75:491–498, 2005. © 2005 Wiley‐Liss, Inc.
Physical Qualities of International Female Rugby League Players by Playing Position

Abstract Jones, B, Emmonds, S, Hind, K, Nicholson, G, Rutherford, Z, and Till, K. Physical qualities of International Female Rugby League players by playing position and injury history. J Strength Cond Res 30(5): 1333–1340, 2016—The purpose of this study was to investigate the anthropometric, body composition, and fitness characteristics of female rugby league players by playing position. Data were collected on 27 players who were part of the English elite women's rugby league squad. Player assessments comprised anthropometric (stature and body mass), body composition (dual-energy X-ray absorptiometry) and fitness {lower-body power (countermovement jump [CMJ], 20 kg jump squat [JS], and 30 cm drop jump), 5, 10, 20, 30, and 40 m sprint, 505 agility, Yo-Yo intermittent recovery test level 1} measures. Players were classified into playing position (i.e., forwards and backs) before analysis. A multivariate analysis of variance demonstrated significant (p ⩽ 0.05) differences for body mass, stature, total fat, lean mass, and percentage body fat between forwards and backs. Positional differences were also observed for speed, agility, and lower-body power. Significant relationships were observed between total body fat and all fitness variables, and total lean mass was related to CMJ and JS peak power. This study provides comparative data for female rugby league forwards and backs. Body fat was strongly associated with performance and should therefore be considered in developing fitness characteristics. The relationship to match performance and trainability of these characteristics warrants further investigation.
Chromophobe renal cell carcinoma in Iceland: An epidemiological and clinicopathological study

Abstract Objective. Numerous studies have suggested that the rare chromophobe renal cell carcinoma (CRCC) has a more favourable prognosis than the other more common subtypes of RCC, clear cell RCC (CCRCC) and papillary RCC (PRCC). These studies have, however, usually involved selected patient cohorts and not whole populations. This study compared CRCC patients with patients with the other two major histological subtypes and established a population-based age-standardized incidence rate (ASR). Material and methods. Of 828 histopathologically confirmed RCCs diagnosed between 1971 and 2005 in Iceland, 15 CRCC cases were identified. Histological material was reviewed, the TNM system was used for staging and cancer-specific survival was estimated. Univariate and multivariate analysis was used to compare CRCC to both CCRCC (n = 740) and PRCC (n = 66). Mean follow-up was 6.7 years. Results. CRCC accounted for 1.8% of RCCs, the ASR being 0.17/100 000 per year. Compared to other subtypes, CRCC was detected incidentally less often (7% vs 29%, p = 0.02), but was more often diagnosed at lower stages (73% vs 45% at stage I + II, p < 0.001). One patient had synchronous metastasis and another developed recurrent CRCC; both died of CRCC. Five-year survival for CRCC, CCRCC and PRCC was 86%, 59% and 50%, respectively (p = 0.004). After correcting for TNM stage (odds ratio 1.98), multivariate analysis did not indicate that CRCC subtype was an independent predictive factor for survival. Conclusion. CRCC is a rare neoplasm with an ASR of 0.17/100 000 per year. These tumours often present with symptoms despite being at lower stages than the other RCC subtypes. The more favourable survival of the CRCC subtype appears to be explained by these tumours being diagnosed at low stages. These findings may suggest that CRCC has a different biological behaviour.
Protein folding and association: Insights from the interfacial and thermodynamic properties of hydrocarbons

We demonstrate in this work that the surface tension, water‐organic solvent, transfer‐free energies and the thermodynamics of melting of linear alkanes provide fundamental insights into the nonpolar driving forces for protein folding and protein binding reactions. We first develop a model for the curvature dependence of the hydrophobic effect and find that the macroscopic concept of interfacial free energy is applicable at the molecular level. Application of a well‐known relationship involving surface tension and adhesion energies reveals that dispersion forces play little or no net role in hydrophobic interactions; rather, the standard model of disruption of water structure (entropically driven at 25°C) is correct. The hydrophobic interaction is found, in agreement with the classical picture, to provide a major driving force for protein folding. Analysis of the melting behavior of hydrocarbons reveals that close packing of the protein interior makes only a small free energy contribution to folding because the enthalpic gain resulting from increased dispersion interactions (relative to the liquid) is countered by the freezing of side chain motion. The identical effect should occur in association reactions, which may provide an enormous simplification in the evaluation of binding energies. Protein binding reactions, even between nearly planar or concave/convex interfaces, are found to have effective hydrophobicities considerably smaller than the prediction based on macroscopic surface tension. This is due to the formation of a concave collar region that usually accompanies complex formation. This effect may preclude the formation of complexes between convex surfaces.
Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated beta-galactosidase gene

We have constructed a HeLa cell line that both expresses high levels of CD4 and contains a single integrated copy of a beta-galactosidase gene that is under the control of a truncated human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). This cell line, called CD4-LTR/beta-gal, can be used to determine quantitatively the titer of laboratory-adapted HIV strains, and the method used to do so is as sensitive as the determination of viral titers in a T-cell line by end point dilution. Using this cell line as a titer system, we calculated that HIV-1 stocks contain only one infectious particle per 3,500 to 12,000 virions. Virus derived from a molecular clone of a macrophagetropic provirus will not infect this cell line. We have also cocultivated peripheral blood lymphocyte cultures from HIV-infected individuals with the CD4-LTR/beta-gal indicator cells. In a majority of primary isolates (five of eight), including isolates from asymptomatic patients, rare virus-infected cells that can activate the beta-galactosidase gene are present.
Novel Methods for Assessing Oral Direct Factor Xa and Thrombin Inhibitors: Use of Point-of-Care Testing and Urine Samples

Abstract Rivaroxaban and dabigatran are new oral anticoagulants (NOACs) that inhibit directly factor Xa and thrombin, respectively. These NOACs effectively prevent thromboembolic complications using fixed doses without the need for dose adjustment according to laboratory results. About 60% of rivaroxaban is cleared from circulation by glomerular filtration, 30% of which is excreted as active drug. About 80% of dabigatran is excreted into urine as active compound. Accordingly, both NOACs can be determined in urine by means of chromatographic methods. Only a few laboratories are able to perform such methods, and results are not available within short time frames. New methods have to be developed to obtain results within minutes and possibly as point-of-care (POC) techniques. This testing may be useful for special patient populations such as those with acute deterioration of renal function due to any disease, before surgical interventions, during unexpected bleeding or thrombotic episodes while on therapy with NOACs, the oldest and youngest populations, pregnancy, suspicion of overdose and intoxication, and to determine adherence to therapy. Here we describe results of a POC qualitative assay using urine samples from patients on treatment with dabigatran and rivaroxaban.
Murine models susceptibility to distinct Trypanosoma cruzi I genotypes infection

SUMMARY Chagas disease is a complex zoonosis that affects around 8 million people worldwide. This pathology is caused by Trypanosoma cruzi, a kinetoplastid parasite that shows tremendous genetic diversity evinced in six distinct Discrete Typing Units (TcI-TcVI) including a recent genotype named as TcBat and associated with anthropogenic bats. TcI presents a broad geographical distribution and has been associated with chronic cardiomyopathy. Recent phylogenetic studies suggest the existence of two genotypes (Domestic (TcIDom) and sylvatic TcI) within TcI. The understanding of the course of the infection in different mouse models by these two genotypes is not yet known. Therefore, we infected 126 animals (ICR-CD1, National Institute of Health (NIH) and Balb/c) with two TcIDom strains and one sylvatic strain for a follow-up period of 60 days. We quantified the parasitaemia, immune response and histopathology observing that the maximum day of parasitaemia was achieved at day 21 post-infection. Domestic strains showed higher parasitaemia than the sylvatic strain in the three mouse models; however in the survival curves Balb/c mice were less susceptible to infection compared with NIH and ICR-CD1. Our results suggest that the genetic background plays a fundamental role in the natural history of the infection and the sympatric TcI genotypes have relevant implications in disease pathogenesis.
Randomized controlled trial of a healthy brain ageing cognitive training program: effects on memory, mood, and sleep.

BACKGROUND With the rise in the ageing population and absence of a cure for dementia, cost-effective prevention strategies for those 'at risk' of dementia including those with depression and/or mild cognitive impairment are urgently required. OBJECTIVE This study evaluated the efficacy of a multifaceted Healthy Brain Ageing Cognitive Training (HBA-CT) program for older adults 'at risk' of dementia. METHODS Using a single-blinded design, 64 participants (mean age = 66.5 years, SD = 8.6) were randomized to an immediate treatment (HBA-CT) or treatment-as-usual control arm. The HBA-CT intervention was conducted twice-weekly for seven weeks and comprised group-based psychoeducation about cognitive strategies and modifiable lifestyle factors pertaining to healthy brain ageing, and computerized cognitive training. RESULTS In comparison to the treatment-as-usual control arm, the HBA-CT program was associated with improvements in verbal memory (p = 0.03), self-reported memory (p = 0.03), mood (p = 0.01), and sleep (p = 0.01). While the improvements in memory (p = 0.03) and sleep (p = 0.02) remained after controlling for improvements in mood, only a trend in verbal memory improvement was apparent after controlling for sleep. CONCLUSION The HBA-CT program improves cognitive, mood, and sleep functions in older adults 'at risk' of dementia, and therefore offers promise as a secondary prevention strategy.
Self-rated health and risk factors for metabolic syndrome among middle-aged men.

OBJECTIVES To examine lifestyle and clinical risk factors for metabolic syndrome (MBO) and compare their significance between levels of self-rated health among middle-aged men. DESIGN A cross-sectional baseline study. SAMPLE 273 men, aged 40, living in Helsinki, Finland. METHODS Postal questionnaires and health examinations by public health nurses were used in data collection. Statistical differences between groups of self-rated health and risk factors were analyzed by chi-square tests. RESULTS Of all the respondents, 55% rated their health as good and 45% as average. Two thirds were overweight or obese, and 35% had waist-hip ratio more than 100 cm. Approximately 43% had diastolic blood pressure greater than 90 mmHg. Over half of the men smoked daily, and 28% used alcohol excessively. CONCLUSIONS The men in this sample were found to be at high risk of developing MBO. The results underscore the importance of understanding the contradiction that exists between subjective and objective health ratings. Public health nurses are in a key position to educate men on how to use simple measurements to objectively assess their risk factors and, thus, potentially reduce their risk of developing diabetes, heart attack, or stroke.
Escherichia coli gene that controls sensitivity to alkylating agents

A new type of Escherichia coli mutant which shows increased sensitivity to methyl methane sulfonate but not to UV light or to gamma rays was isolated after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. The mutant is unable to reactivate phage lambdavir or double-stranded phiX174 DNA (replicative form) that had been treated with methyl methane sulfonate. The mutant is sensitive to other alkylating agents, such as ethyl methane sulfonate, mitomycin C, and N-methyl-N'-nitro-N-nitrosoguanidine, as well. It grows normally and exhibits almost normal recombination proficiency. The mutant possesses normal levels of DNA polymerase I, exonuclease I, exonuclease V, endonuclease specific for methyl methane sulfonate-treated DNA, and 3-methyladenine-DNA glycosidase activities. The genetic locus responsible has been named alk and is located near his on the chromosome.