Miracle-dz/UniFAR-FTUs huggingface dataset:
A Double Residue Substitution in the Coenzyme-binding Site Accounts for the Different Kinetic Properties between Yeast and Human Formaldehyde Dehydrogenases*

Glutathione-dependent formaldehyde dehydrogenase (FALDH) is the main enzymatic system for formaldehyde detoxification in all eukaryotic and many prokaryotic organisms. The enzyme of yeasts and some bacteria exhibits about 10-fold higherk cat and K m values than those of the enzyme from animals and plants. Typically Thr-269 and Glu-267 are found in the coenzyme-binding site of yeast FALDH, but Ile-269 and Asp-267 are present in the FALDH of animals. By site-directed mutagenesis we have prepared the T269I and the D267E mutants and the D267E/T269I double mutant of Saccharomyces cerevisiae FALDH with the aim of investigating the role of these residues in the kinetics. The T269I and the D267E mutants have identical kinetic properties as compared with the wild-type enzyme, although T269I is highly unstable. In contrast, the D267E/T269I double mutant is stable and shows low K m (2.5 μm) and low k cat (285 min−1) values with S-hydroxymethylglutathione, similar to those of the human enzyme. Therefore, the simultaneous exchange at both residues is the structural basis of the two distinct FALDH kinetic types. The local structural perturbations imposed by the substitutions are suggested by molecular modeling studies. Finally, we have studied the effect of FALDH deletion and overexpression on the growth of S. cerevisiae. It is concluded that the FALDH gene is not essential but enhances the resistance against formaldehyde (0.3–1 mm). Moreover, the wild-type enzyme (with highk cat and K m ) provides more resistance than the double mutant (with lowk cat and K m ).
Increased CD59 protein expression predicts a PSA relapse in patients after radical prostatectomy

Human protectin (CD59) is a regulator of complement activation that inhibits complement‐mediated cell lysis, and thus might confer immune resistance to tumor cells. CD59 expression has been described in a variety of human malignancies, including breast cancer. Since a comprehensive investigation of CD59 expression in prostate cancer has not been conducted yet, we aimed to determine the significance of CD59 expression in prostate cancer.
Another Look at the Macroeconomic Information Content of Aggregate Earnings: Evidence from the Labor Market

We examine the macroeconomic information content of aggregate earnings from the labor market's perspective. We use insights from the labor economics literature to characterize the information contained in aggregate GAAP earnings and its components that is relevant for predicting aggregate job creation and destruction. Our results suggest that not only does aggregate earnings news convey information about future labor market aggregates, but its information content is incremental to other macroeconomic variables at near-term horizons. Further, the source of this information stems primarily from two earnings components: aggregate core earnings and special items. Shocks to core earnings signal persistent changes in economy-wide profitability that predict aggregate job creation up to four quarters ahead, while shocks to special items predict job destruction up to one quarter. Taken together, our results suggest that aggregate earnings contain useful information about future labor market conditions, with the nature of such information varying across earnings components. JEL Classifications: E37; E44; G17; G24; M41.
Demethylation of dimethylsulfoniopropionate to 3-S-methylmercaptopropionate by marine sulfate-reducing bacteria

The initial step in the anaerobic degradation of the algal osmolyte dimethylsulfoniopropionate (DMSP) in anoxic marine sediments involves either a cleavage to dimethylsulfide and acrylate or a demethylation to 3-S-methylmercaptopropionate. Thus far, only one anaerobic bacterial strain has been shown to carry out the demethylation, namely, Desulfobacterium sp. strain PM4. The aims of the present work were to study how common this property is among certain groups of anaerobic bacteria and to obtain information on the affinities for DMSP of DMSP-demethylating strains. Screening of several pure cultures of sulfate-reducing and acetogenic bacteria showed that Desulfobacterium vacuolatum DSM 3385 and Desulfobacterium niacini DSM 2059 are also able to demethylate DMSP; a very slow demethylation of DMSP was observed with a salt-tolerant strain of Eubacterium limosum. From a 10(5) dilution of intertidal sediment a new marine DMSP-demethylating sulfate-reducing bacterium (strain WN) was isolated. Strain WN was a short, gram-negative, nonmotile rod that grew on betaine, sarcosine, palmitate, H2 plus CO2, and several alcohols, organic acids, and amino acids. Extracts of betaine-grown cells had hydrogenase, formate dehydrogenase, and CO dehydrogenase activities but no alpha-ketoglutarate oxidoreductase activity, indicating the presence of the acetyl coenzyme A-CO dehydrogenase pathway. Analysis of the 16S rRNA gene sequence of strain WN revealed a close relationship with Desulfobacter hydrogenophilus, Desulfobacter latus, and Desulfobacula toluolica. Strain PM4 was shown to group with Desulfobacterium niacini. The K(m) of strain WN for DMSP, as derived from substrate progress curves in cell suspensions, was approximately 10 microM. A similar value was found for D. niacini PM4.
Evidence for a noradrenergic mechanism causing hypertension and abnormal glucose metabolism in rats with relative deficiency of γ‐melanocyte‐stimulating hormone

A close association between salt‐sensitive hypertension and insulin resistance has been recognized for more than two decades, although the mechanism(s) underlying this relationship have not been elucidated. Recent data in mice with genetic disruption of the γ‐melanocyte‐stimulating hormone (γ‐MSH) system suggest that this system plays a role in the pathophysiological relationship between hypertension and altered glucose metabolism during ingestion of a high‐sodium diet (8% NaCl, HSD). We tested the hypothesis that these two consequences of interrupted γ‐MSH signalling were the result of sympathetic activation by studying rats treated with the dopaminergic agonist bromocriptine (5 mg kg−1i.p., daily for 1 week; Bromo) to cause relative γ‐MSH deficiency. Bromo‐treated rats fed the HSD developed hypertension and also exhibited fasting hyperglycaemia (P < 0.005) and hyperinsulinaemia (P < 0.025). Furthermore, Bromo‐treated rats on the HSD had impaired glucose tolerance and blunted insulin‐mediated glucose disposal. Intravenous infusion of γ2‐MSH, or of the α‐adrenergic receptor antagonist phentolamine, to Bromo–HSD rats lowered both mean arterial pressure (MAP) and blood glucose to normal after 15 min (P < 0.001 versus control), but had no effect in rats receiving vehicle and fed the HSD; γ2‐MSH infusion also reduced the elevated plasma noradrenaline to control levels in parallel with the reductions in MAP and blood glucose concentration. Infusion of hydralazine to Bromo–HSD rats lowered MAP but had only a trivial effect on blood glucose. We conclude that rats with relative γ‐MSH deficiency develop abnormal glucose metabolism, with features of insulin resistance, in association with hypertension when ingesting the HSD. Elevated plasma noradrenaline concentration in Bromo–HSD rats is normalized by γ2‐MSH infusion, suggesting that an adrenergic mechanism may link the salt‐sensitive hypertension and the impaired glucose metabolism of relative γ‐MSH deficiency.
Expression of the BCRP gene (ABCG2/MXR/ABCP) in childhood acute lymphoblastic leukaemia

Summary. The breast cancer resistance protein (BCRP), also known as mitoxantrone resistance protein (MXR) or placenta ABC protein (ABC‐P), is the second member of the ABCG subfamily of ABC transport proteins (gene symbol ABCG2). BCRP has been detected in acute myeloid leukaemia and in breast, colon and gastric cancer but there has been no reports regarding BCRP expression in acute lymphoblastic leukaemia (ALL). We report the first results of BCRP expression in childhood ALL. Sixty‐seven children (47 initial stage, 20 relapses) with ALL were analysed for BCRP gene expression by TaqMan real‐time polymerase chain reaction. The expression of BCRP in mononuclear cells obtained from the bone marrow (BM) and peripheral blood (PB) of healthy donors was also investigated. There was no relationship between BCRP expression and age, sex, initial blast cell count, prednisolone response or BM response on d 15 and 33. Patients with T‐lineage ALL showed a lower expression of BCRP (P = 0·044). Kaplan–Meier analysis of the relapse‐free interval showed no prognostic significance of BCRP expression when different levels of BCRP expression were used as cut‐off points. No significant difference in expression of BCRP mRNA was measured between initial‐stage and relapsed‐stage ALL or between normal MNC obtained from BM and ALL patients. The results indicate a low expression of BCRP in childhood ALL. Relationships between BCRP and clinical, molecular or in vivo resistance characteristics of the patients were not observed.
Plant-Parasitic Nematodes Associated with Grapevines, Vitis vinifera, in Oregon Vineyards.

A survey of vineyards in western Oregon was conducted in 1994 and 1995 to determine the association of plant-parasitic nematodes with vine health. Seventy vineyards in four regions of western Oregon (16 to 21 vineyards per region) were sampled. The regions were the northern, middle, and southern Willamette Valley, and southern Oregon. Vineyards were selected and partitioned into blocks by variety, age of planting, crop history, and soil characteristics. Mesocriconema xenoplax, Xiphinema americanum, Pratylenchus spp. , and Paratylenchus spp. were recovered from more than 85% of the vineyards; only 10% of vineyards had detectable populations of Meloidogyne hapla. Mesocriconema xenoplax and X. americanum were found in 20% and 8% of vineyard blocks, respectively, at population densities reported to cause moderate yield loss in California. Mesocriconema xenoplax was found at greatest population densities in vineyards older than 10 years and on former Prunus orchard sites in the northern Willamette Valley. Populations of Mesocriconema xenoplax and X. americanum were associated with both healthy and stunted vines. The long-term impact of M. xenoplax, X. americanum, and other nematodes on Oregon vineyard production has not yet been determined.
BMP-7 Attenuates TGF-β1-Induced Fibronectin Secretion and Apoptosis of NRK-52E Cells by the Suppression of miRNA-21

Bone morphogenetic protein-7 (BMP-7) inhibited the pathogenesis of renal injury in response to a variety of stimuli. However, little is known about the molecular regulation and mechanism of endogenous BMP-7 and its renoprotective functions. This study examined the regulation of BMP-7 and its role in the fibronectin secretion and apoptosis of NRK-52E cells resulting from transforming growth factor-β1 (TGF-β1) in vitro. Results showed that TGF-β1 promoted factor-associated suicide (FAS), FAS ligand (FASL), fibronectin (FN), and miRNA-21 expression, while it downregulated phospho-Smad1 (pSmad1), pSmad5, and pSmad8 expressions in NRK-52E cells. In contrast, BMP-7 alleviated TGF-β1-induced cell apoptosis, inhibited TGF-β1-induced higher expression of miRNA-21 and FN, and enhanced TGF-β1-attenuated phosphorylation of Smad1, Smad5, and Smad8. Furthermore, a chemical inhibitor of miRNA-21 also negatively affected TGF-β1-induced apoptosis and FN secretion. On the other hand, overexpression of miRNA-21 counteracted the inhibitory effect of BMP-7 on TGF-β1-induced FN secretion and apoptosis. However, BMP-7 showed no effects on TGF-β1-induced FN secretion and apoptosis following knockdown of miRNA-21. Taken together, these findings demonstrated that BMP-7 might inhibit TGF-β1-induced FN secretion and apoptosis by the suppression of miRNA-21 in NRK-52E cells.
Expression of nestin, CD133 and ABCG2 in relation to the clinical outcome in pediatric sarcomas.

BACKGROUND Nestin, CD133 and ABCG2 are recently discussed as putative markers, co-expression of which might determine a cancer stem cell (CSC) phenotype in sarcomas. OBJECTIVE Our study is focused on immunohistochemical analysis of nestin, CD133 and ABCG2 expression in rhabdomyosarcoma, Ewing sarcoma and osteosarcoma. Furthermore, we also analyzed the possible correlation of nestin, CD133 and ABCG2 expression levels with the patient outcome to identify potential prognostic values of these three putative CSC markers in the same cohorts. METHODS Using immunohistochemistry, expression of nestin, CD133 and ABCG2 was analyzed in 24 rhabdomyosarcoma, 22 Ewing sarcoma and 10 osteosarcoma tissue samples and expression levels of these markers were correlated with clinical outcome. RESULTS High nestin levels indicate poor prognosis in patients with Ewing sarcoma (P = 0.001), and high CD133 expression is associated with shorter survival in rhabdomyosarcoma patients (P = 0.002). In contrast, no significant relationship was found between ABCG2 expression and the clinical outcome. CONCLUSIONS Our analysis represents the first complex study of these three putative CSCs markers together in three different types of pediatric sarcomas and showed their possible prognostic values in these tumors.
Immediate and midterm follow-up results of using an electrodetachable, fully retrievable SOLO stent system in the endovascular coil occlusion of wide-necked cerebral aneurysms.

OBJECT Stent-assisted embolization is an alternative endovascular treatment method for wide-necked intracranial aneurysms. Currently available stents have the limitations of poor radial force, difficult delivery systems, and lack of full retrievability. The authors report on their preliminary experience with the use of a new, fully retrievable, self-expanding neurovascular stent, which has a high radial force and easy delivery system, combined with coil or Onyx embolization for the treatment of wide-necked aneurysms, including 6-month follow-up data. METHODS Fifteen patients with 18 wide-necked intracranial aneurysms were treated using the SOLO stent system and detachable platinum coils. Aneurysms were located at the posterior communicating artery (seven lesions), midbasilar artery (one lesion), internal carotid artery (ICA) bifurcation (one lesion), ICA-ophthalmic artery segment (eight lesions), and posterior cerebral artery (one lesion). Eleven aneurysms were small, six were large, and one was giant. Only one of these aneurysms was in the acute stage of subarachnoid hemorrhage; balloon remodeling alone failed to keep the coils in the aneurysm sac. RESULTS Only one stent required retrieving and repositioning after it had been fully deployed, and retrieval was easy and successful. No thromboembolic complication, dissection/rupture, or vasospasm occured during stent placement. Follow-up angiograms obtained at 6 months posttreatment in the 18 aneurysms demonstrated that all stents were patent with no evidence of intimal hyperplasia or stenosis. In all cases but one, 100% lesion occlusion was observed at the 6-month control angiography examination. Only one aneurysm had recanalized. CONCLUSIONS The fully retrievable self-expandible SOLO stent is a feasible, secure, and effective system with a high radial force and ease of delivery in treating wide-necked intracranial aneurysms in combination with coil embolization.
Hemodynamic profiles of advanced heart failure: association with clinical characteristics and long-term outcomes.

BACKGROUND Classifying patients with advanced congestive heart failure (CHF) by baseline measures of congestion and perfusion has been used to estimate hemodynamic status and to select and titrate therapy. We describe clinical characteristics of 4 hemodynamic profiles-wet/cold, wet/warm, dry/cold, and dry/warm-in patients with advanced CHF and assess relations between symptoms, physical signs, and outcomes with each profile. METHODS AND RESULTS We retrospectively assessed baseline symptoms, physical-examination variables, and 1-year outcomes of 440 patients in a randomized trial. With univariable and multivariable logistic regression, we examined relations of physical-examination variables to hemodynamic profiles. We also assessed the rates of death and death or readmission by profile. Severity of CHF symptoms did not predict the wet-versus-dry profile or cold-versus-warm status, despite significant differences in hemodynamics among groups. Of the physical-examination variables, only a lower proportional pulse pressure was a significant multivariable predictor of the wet category. Among wet patients (n = 348), this same variable was the only significant multivariable predictor of the cold category. For dry patients (n = 92), the cold category was predicted in multivariable analysis by supine heart rate and hepatomegaly. Survival was similar among profiles: wet/cold, 54.2% (n = 91); wet/warm, 58.3% (n = 105); dry/cold, 78.9% (n = 15); and dry/warm, 67.1%, P =. 13 (n = 49). Event-free survival also was similar among profiles: wet/cold, 22.0% (n = 37); wet/warm, 29.4% (n = 53); dry/cold, 42.1% (n = 8); and dry/warm, 31.5%, P =. 44 (n = 23). CONCLUSIONS The patient's history and physical examination alone may lead to inaccurate estimation of hemodynamic status and thus suboptimal management for patients with advanced CHF.
Daily Social Exchanges and Affect in Middle and Later Adulthood: The Impact of Loneliness and Age

Although daily social exchanges are important for well-being, it is unclear how different types of exchanges affect daily well-being, as well as which factors influence the way in which individuals react to their daily social encounters. The present study included a sample of 705 adults aged 31 to 91, and using Multilevel Modeling analyses investigated whether loneliness or age moderate the relationship between daily affect and daily social exchanges with family and friends. Results indicated differences between events involving family and those involving friends. Furthermore, lonelier individuals benefitted more from positive events than less lonely adults but were not more negatively reactive to negative events. Moreover, results suggested that older adults' affect is more independent of both positive and negative social events compared to younger people. Implications are discussed for the importance of daily social exchanges, daily social stress vulnerability, and the influences of loneliness across middle and later adulthood.
Quantitative and qualitative peritoneal immune profiles, T‐cell apoptosis and oxidative stress‐associated characteristics in women with minimal and mild endometriosis

Please cite this paper as: Mier‐Cabrera J, Jiménez‐Zamudio L, García‐Latorre E, Cruz‐Orozco O, Hernández‐Guerrero C. Quantitative and qualitative peritoneal immune profiles, T‐cell apoptosis and oxidative stress‐associated characteristics in women with minimal and mild endometriosis. BJOG 2011;118:6–16.
ChloroP, a neural network‐based method for predicting chloroplast transit peptides and their cleavage sites

We present a neural network based method (ChloroP) for identifying chloroplast transit peptides and their cleavage sites. Using cross‐validation, 88% of the sequences in our homology reduced training set were correctly classified as transit peptides or nontransit peptides. This performance level is well above that of the publicly available chloroplast localization predictor PSORT. Cleavage sites are predicted using a scoring matrix derived by an automatic motif‐finding algorithm. Approximately 60% of the known cleavage sites in our sequence collection were predicted to within 62 residues from the cleavage sites given in SWISS‐PROT. An analysis of 715 Arabidopsis thaliana sequences from SWISS‐PROT suggests that the ChloroP method should be useful for the identification of putative transit peptides in genome‐wide sequence data. The ChloroP predictor is available as a web‐server at http://www.cbs. dtu.dk/services/ChloroP/.
The ACE gene polymorphism and cough threshold for capsaicin after cilazapril usage.

Persistent dry cough is an occasional but clinically important adverse reaction to angiotensin I-converting enzyme (ACE) inhibitors (ACEI). Its reported incidence is variable, and why cough occurs in only certain individuals has been unclear. An insertion/deletion (I/D) polymorphism of the ACE gene is associated with serum ACE activity. We have previously shown that susceptibility to cough induced by ACEI is associated with this polymorphism such that patients with genotype II are more susceptible to cough than patients with other genotypes. In order to confirm and extend our previous observation, we conducted a randomized, placebo-controlled, double-blind, cross-over study in 10 healthy volunteers with genotype II and 10 with genotype DD. The cough threshold was determined by the concentration of inhaled capsaicin causing two or more coughs. After the usage of an ACEI, cilazapril, for 4 weeks, changes in the cough threshold in subjects with genotype II [before: 6.6+/-3.7 nM (mean+/-SD); after: 5.0+/-4.6 nM] significantly differed from those in subjects with genotype DD (before: 9.0+/-9.4 nM; after: 9.3+/-9.1 nM). Skin responses to intradermal bradykinin, which is a substrate of ACE and tussigenic, were significantly increased in subjects with genotype II (before: 1.6+/-0.6 vs. after: 2.6+/-0.5 cm2, P<0.05) but not in subjects with genotype DD (before: 1.4+/-0.5 vs. after: 1.6+/-0.6 cm2, n.s.) after usage of cilazapril. By contrast, skin responses to intradermal substance P did not change in subjects with either genotype. These findings provide further evidence of a link between ACEI-induced cough and I/D polymorphism of the ACE gene and suggest that ACEIs induce cough by modulating the tissue level of bradykinin.
Stock return predictability in the spanish stock market : a conventional and an alternative methodology

We carry out an empirical analysis on the Spanish Stock Market from July 2003 to June 2015, with an aim to examine whether the monthly returns can be predicted. We test the return predictability of the Spanish Stock Market through two different methodologies. First, we use a linear estimator, the FGLS and, secondly, we use a non-parametric approach, the RE-EM tree. The latter is tested in-sample and out-of-sample. We use a total of nine predictors, two of which are non-traditional variables: gold and oil returns. We conclude that macroeconomic variables are more relevant forecasting monthly returns than the business performance (ratios) predictors. We also find evidence in favour of in-sample return predictability. Although we find a 56.7% of success forecasting the sign of the real returns in the out-of-sample period through the RE-EM tree, it may not be enough to outperform the market once all the transaction costs are discounted. We also find that the return predictability is heterogeneous among different sectors.
Disambiguation of Rich Inflection - Computational Morphology of Czech

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