Miracle-dz/UniFAR-FTUs huggingface dataset:
Physical Properties of Sputum

The natural variation in viscosity and elasticity in a single 0.5-ml sample of sputum, as well as among several expectorates of a patient during a single day and during a three-day period, has been quantitated. Other properties of sputum, such as gross appearance, cellular density, percentage of solid content, types of cells present, and pH were also studied, and possible correlations were investigated. The viscosity variation (at a shear rate of 1 sec−1) averaged 11 ± 8 per cent (mean ± SD) for a single sample; 26 ± 18 per cent for three expectorates of a single patient during one day; 49 ± 33 per cent for one patient during three days. Variation in elasticity averaged 6 per cent for one sample; 25 ± 15 per cent for one day; 33 ± 9 per cent for three days. Samples classified by eye as mucoid or purulent according to pre-established color and opacity criteria showed a close correlation between this classification and the variables described above. Samples called purulent had a high density of cells with 8.
CX3CL1 and CCL14 Regulate Extracellular Matrix and Adhesion Molecules in the Trophoblast: Potential Roles in Human Embryo Implantation1

Abstract Embryo implantation is a complex process involving blastocyst attachment to the endometrial epithelium and subsequent trophoblast invasion of the decidua. We have previously shown that the chemokines CX3CL1 and CCL14 are abundant in endometrial vasculature, epithelial, and decidual cells at this time, and that their receptors, CX3CR1 and CCR1, are present on invading human trophoblasts. CX3CL1 and CCL14 promote trophoblast migration. We hypothesized that these endometrial chemokines promote trophoblast migration by regulating adhesion molecules and extracellular matrix (ECM) components on the trophoblast, similar to mechanisms used in leukocyte trafficking. Trophoblast cells (AC1M-88) used previously showed a marked increase in adhesion to fibronectin following treatment with CX3CL1 and CCL14. Alterations in trophoblast adhesion and ECM following chemokine stimulation were examined using pathway-specific oligo-arrays and quantitative real-time RT-PCR. More than 30 genes were affected by CX3CL1 treatment, and 15 genes were found to be regulated by CCL14 treatment. Real-time RT-PCR quantitation revealed significant changes in the mRNA transcripts of alpha-catenin (CTNNA1), extracellular matrix protein 1 (ECM1), osteopontin (SPP1), integrin alpha 6 (ITGA6), matrix metalloproteinase 12 (MMP12), and integrin beta 5 (ITGB5) following chemokine treatment. Several of these genes have previously been implicated in implantation. Immunohistochemistry confirmed the presence of integrin alpha 6 and SPP1 protein in first-trimester human implantation sites. The temporal and spatial expression of chemokines, their receptors, adhesion, and ECM at the maternal-fetal interface emphasizes an important role in the controlled directional migration of trophoblasts through the maternal decidua. For the first time, this study demonstrates the direct effects of CX3CL1 and CCL14 on trophoblast adhesion molecules and ECM, suggesting mechanisms by which trophoblast cells migrate during early pregnancy.
The Culture of Zygotes to the Blastocyst Stage Changes the Postnatal Expression of an Epigentically Labile Allele, Agouti Viable Yellow, in Mice1

Abstract Restricting the growth of the embryo can cause adverse whole-of-life changes in an organism's homeostasis. Such adverse long-term consequences may occur even when growth restriction occurs only during the preimplantation period. The molecular basis for these long-term effects has not been defined, although an epigenetic mechanism is suspected. Some loci seem to be more sensitive to epigenetic perturbation than others, and the agouti viable yellow allele (Avy) is the best studied example of this. It has active (hypomethylated) and inactive (hypermethylated) epialleles. This study used the Avy model to show that growth restriction of preimplantation embryos, as provided by culture of zygotes, induced persistent epigenetic changes that resulted in altered postnatal phenotype. C57BL/6 Avy/a males were mated to ovulation-induced FVB/N females, and then either zygotes were collected and cultured for 96 h and the resulting blastocysts were transferred to pseudopregnant recipient females, blastocysts were collected from females and transferred without embryo culture, or pregnancy was allowed to proceed after mating without intervention. Culture was in a commercial human in vitro fertilization media. The proportion of pups expressing the active (hypomethylated) epiallele and yellow coat was significantly higher following zygote culture compared to embryos that were transferred without culture (P = 0.014) or natural matings (P < 0.001). There was no difference in expression of the active epiallele in pups resulting from embryo transfer (without culture) compared to natural matings. These results show for the first time that the preimplantation embryo's growth environment can affect the postnatal expression of a defined epigenetically sensitive allele.
Surfactant Protein A Signaling Pathways in Human Uterine Smooth Muscle Cells1

Abstract The present study investigated the ability of surfactant associated protein A1 (SFTPA1), a major component of lung surfactant, to bind and serve as a signal in human cultured myometrial cells. By using ligand blot analysis with 125I-SFTPA1, we consistently identified two myometrial SFTPA1 interacting proteins (55 and 200 kDa). We found that the SFTPA1 immunoreactive protein was present in myometrial cells. We also showed by indirect immunofluorescence the nuclear translocation of RELA (also known as NFkappaB p65 subunit) after activation of myometrial cells by SFTPA1. Neutralization of TLR4 did not reverse this effect. Moreover, SFTPA1 rapidly activated mitogen-activated protein kinase 1/3 (MAPK1/3) and protein kinase C zeta (PRKCZ). The prolonged treatment of myometrial cells with SFTPA1 upregulated PTGS2 (COX2) protein levels. We next evaluated whether SFTPA1 affected the actin dynamic. Stimulation of myometrial cells with SFTPA1 markedly enhanced the intensity of the filamentous-actin pool stained with fluorescein isothiocyanate-phalloidin. Inhibition of PRKC or Rho-associated, coiled-coil containing protein kinase 1 (ROCK) reduced the SFTPA1-mediated stress fiber formation. Our data support the hypothesis that human myometrial cells express functional SFTPA1 binding sites and respond to SFTPA1 to initiate activation of signaling events related to human parturition.
S-Adenosyl-l-methionine Modulates CO and NO• Binding to the Human H2S-generating Enzyme Cystathionine β-Synthase*

Cystathionine β-synthase (CBS) is a key enzyme in human (patho)physiology with a central role in hydrogen sulfide metabolism. The enzyme is composed of a pyridoxal 5′-phosphate-binding catalytic domain, flanked by the following two domains: a heme-binding N-terminal domain and a regulatory C-terminal domain binding S-adenosyl-l-methionine (AdoMet). CO or NO• binding at the ferrous heme negatively modulates the enzyme activity. Conversely, AdoMet binding stimulates CBS activity. Here, we provide experimental evidence for a functional communication between the two domains. We report that AdoMet binding significantly enhances CBS inhibition by CO. Consistently, we observed increased affinity (∼5-fold) and faster association (∼10-fold) of CO to the ferrous heme at physiological AdoMet concentrations. NO• binding to reduced CBS was also enhanced by AdoMet, although to a lesser extent (∼2-fold higher affinity) as compared with CO. Importantly, CO and NO• binding was unchanged by AdoMet in a truncated form of CBS lacking the C-terminal regulatory domain. These unprecedented observations demonstrate that CBS activation by AdoMet puzzlingly sensitizes the enzyme toward inhibition by exogenous ligands, like CO and NO•. This further supports the notion that CBS regulation is a complex process, involving the concerted action of multiple physiologically relevant effectors.
Avaliação nutricional subjetiva: Parte 1 - Revisão de sua validade após duas décadas de uso

BACKGROUND: The subjective global assessment is a clinical method for nutritional assessment that considers not only body composition alterations but also changes in physiological function. The method is simple, inexpensive and non-invasive, and it can be performed at bedside, and its use was described for the first time almost two decades ago. AIM: To review the validity studies of subjective global assessment described in literature in the last two decades of its use. METHODS:It was performed a systematic review in MEDLINE, using "subjective global assessment" as search term and the most relevant papers were selected. RESULTS: Being a subjective method, its precision depends on the observer's experience. Nevertheless, the method showed a good diagnostic precision when performed by trained observers. Subjective global assessment was validated by convergent validity, when this method was compared to other objective nutritional assessment methods, and by predictive validity, showing that subjective global assessment could identify patients who were at high risk for developing postoperative complications. CONCLUSIONS: Subjective global assessment has been a good option in nutritional assessment in surgical patients and some modifications have been suggested to adjust the method to other clinical situations. The observer experience is of extreme importance, since the precision of the method depends on it.
Papa Revisited: A Current Empirical Study of the Mason Framework

Nearly twenty years ago in MIS Quarterly, Richard Mason proposed that there were four key “issues of the information age. ” This influential article and concepts have been used by many researchers as the basis for information technology ethics studies. This manuscript revisits the current state of information technology ethics by empirically measuring current attitudes toward these “four issues of the information age” as originally proposed by Mason: privacy, accessibility, property, and accuracy (commonly referred to as PAPA). More than 200 individuals are polled with regard to recognition of the specific information technology issues and their views on the importance of these issues as ethical topics. The four issues raised directly map to the four Mason PAPA issues. The study validates the PAPA issues and finds all the topics are currently viewed as important ethical issues. The study also finds that overall there are high levels of concern with all four issues but finds that privacy is viewed as most important followed by accessibility and accuracy which are viewed equally and property which is viewed lowest, but still very important. A demographic analysis reveals that gender plays a significant role in determining recognition of privacy and accuracy as important ethical issues. The implications of the study are discussed.
Experimental Murine Endometriosis Induces DNA Methylation and Altered Gene Expression in Eutopic Endometrium1

Abstract The eutopic endometrium in women with endometriosis demonstrates diminished endometrial receptivity and altered gene expression. It is unknown if the endometrium being defective gives rise to a predisposition toward endometriosis and infertility or, alternatively, if endometriosis causes the altered endometrial receptivity. Here we created experimental endometriosis in mice and examined the expression of several markers of endometrial receptivity in the eutopic endometrium. Methylation of Hoxa10 was also evaluated as a potential mechanism responsible for altered gene expression. Expression of each gene was measured using quantitative real-time RT-PCR at 14 wk after induction of endometriosis. Expression of Hoxa10 and Hoxa11, which are necessary for endometrial receptivity, were decreased in the endometriosis group. Insulin-like growth factor binding protein-1 (Igfbp1) mRNA was decreased in the endometriosis group. However, there was no change in Integrin beta3 (Itgb3) mRNA expression. Total progesterone receptor (Pgr-AB) was increased in the endometriosis group and the ratio of Pgr-B to Pgr-AB was increased, indicating a shift from Pgr-A to Pgr-B expression. Basic transcription element-binding protein-1 (Bteb1), official symbol and name Klf9, Kruppel-like factor 9, which functionally interacts with Pgr in endometrium, was also decreased in the endometriosis group. In addition, hypermethylation of Hoxa10 in the endometriosis group was shown by methylation-specific PCR and confirmed by bisulfite sequencing. These findings demonstrate that normal endometrium, when placed in an ectopic location to create experimental endometriosis, led to characteristic changes in gene expression in eutopic endometrium. These data suggest the existence of a signal conduction pathway from endometriosis that alters endometrial gene expression through altered Pgr signaling and epigenetic programming.
Egg Water from the Amphibian Bufo arenarum Modulates the Ability of Homologous Sperm to Undergo the Acrosome Reaction in the Presence of the Vitelline Envelope1

Abstract Sperm from the toad Bufo arenarum must penetrate the egg jelly before reaching the vitelline envelope (VE), where the acrosome reaction is triggered. When the jelly coat is removed, sperm still bind to the VE, but acrosomal exocytosis is not promoted. Our previous work demonstrated that diffusible substances of the jelly coat, termed “egg water” (EW), triggered capacitation-like changes in B. arenarum sperm, promoting the acquisition of a transient fertilizing capacity. In the present work, we correlated this fertilizing capacity with the ability of the sperm to undergo the acrosome reaction, further substantiating the role of the jelly coat in fertilization. When sperm were exposed to the VE, only those preincubated in EW for 5 or 8 min underwent an increase in the intracellular Ca2+ concentration ([Ca2+]i), which led to acrosomal exocytosis. Responsiveness to the VE was not acquired on preincubation in EW for 2 or 15 min or in Ringer solution regardless of the preincubation time. In contrast, depletion of intracellular Ca2+ stores (induced by thapsigargin) promoted [Ca2+]i rise and the acrosome reaction even in sperm that were not exposed to EW. Acrosomal exocytosis was blocked by the presence of Ca2+ chelators independent of whether a physiological or pharmacological stimulus was used. However, Ni2+ and mibefradil prevented [Ca2+]i rise and the acrosome reaction of sperm exposed to the VE but not of sperm exposed to thapsigargin. These data suggest that the acrosomal responsiveness of B. arenarum sperm, present during a narrow period, is acquired during EW incubation and involves the modulation of a voltage-dependent Ca2+ channel.
Low interleukin‐10 production by monocytes of patients with a self‐limiting hepatitis C virus infection

Summary. Host factors seem to be crucial for the spontaneous clearance of hepatitis C virus (HCV). Monocytes play a pivotal role in innate immunity and help regulate adaptive responses. This study assesses the characteristics of monocytes from patients with self‐limiting HCV infections. We studied 35 consecutive patients [11 with a self‐limiting HCV infection, 16 chronically infected with HCV and sustained virological responders (SVR) following antiviral therapy, and eight chronically infected HCV but untreated] and eight healthy donors (HD). The production of interleukin (IL)‐10, tumour necrosis factor‐alpha (TNF‐α) and IL‐12p40 by monocytes stimulated with lipopolysaccharides(LPS) or HCV Core protein was measured by enzyme‐linked immunoassay. Monocyte surface markers were analysed by flow cytometry. LPS and Core protein triggered IL‐10 and TNF‐α production, but monocytes from self‐limiting infection patients produced significantly less IL‐10 and TNF‐α than those of SVR, chronically infected or HD (P < 0.05), while IL‐12p40 production was unchanged. This cytokine production profile did not appear to be due to expansion of the CD14+ CD16+ monocyte subset or to a classical or alternative activation monocyte profile. Monocytes from self‐limiting infection patients had more CCR7 than those from SVR or chronically infected patients (P < 0.05). Monocytes of self‐limiting infection patients appear to produce little IL‐10 and TNF‐α in response to viral or unspecific stimulation and to have a higher CCR7 expression. This profile seems to be independent to a particular monocyte subset or activation state. Low IL‐10 production may help establish an effective immune response and spontaneous HCV clearance.
Dynamic Nuclear Organization of Constitutive Heterochromatin During Fetal Male Germ Cell Development in Mice1

Abstract In mice, male germ cells enter mitotic arrest beginning at 13.5 days postcoitum (dpc), and remain suspended in the G0/G1 cell cycle stage until after birth. During this period, male germ cells undergo extensive epigenetic reprogramming, which is essential for their subsequent function as male gametes. A global reorganization and spatial clustering of constitutive heterochromatin has been implicated in epigenetic plasticity during cellular differentiation. Here, we have studied the dynamics of heterochromatin in fetal (12.5–19.5 dpc) and neonatal (4 days postpartum) male germ cells. We monitored constitutive heterochromatin-specific markers, and observed changes in the association of histone H3 trimethylation of lysine 9 (H3K9me3), binding of heterochromatin protein 1, and patterns of 4′,6-diamino-2-phenylindole staining in pericentric regions of chromosomes, along with a coincident loss of chromocenters in fetal prospermatogonia during mitotic arrest. We also observed a transient loss of H3K9me3 associated with major and minor satellite repeat sequences, plus inactivation of histone methyltransferases (Suv39h1 and Suv39h2), and transient activation of histone demethylase (Jmjd2b) in these same cells. These epigenetic changes were correlated with relocation of centromeric regions toward the nuclear periphery in prospermatogonia during mitotic arrest. Taken together, these results show that constitutive heterochromatin undergoes dramatic reorganization during prespermatogenesis. We suggest that these dynamic changes in heterochromatin contribute to normal epigenetic reprogramming of the paternal genome in fetal prospermatogonia suspended in the G0/G1 stage, and that this also represents an epigenomic state that is particularly amenable to reprogramming.
Fetal Exposure to Cocaine Causes Programming of Prkce Gene Repression in the Left Ventricle of Adult Rat Offspring1

Abstract Previous studies demonstrated that maternal cocaine administration caused a significant decrease in protein kinase C epsilon (PRKCE) abundance in the left ventricle and an increase in susceptibility of the heart to ischemic injury in adult male offspring. The present study tested the hypothesis that epigenetic modification has a key role in cocaine-mediated programming of cardiac Prkce gene repression. Pregnant Sprague-Dawley rats were administered saline or cocaine (30 mg/kg/day i.p.) from Days 15 to 21 of gestational age, and hearts of 3-mo-old adult offspring were studied. Cocaine exposure significantly decreased Prkce mRNA levels in the left ventricle of male but not female offspring. CpG dinucleotides identified in Bhlhb2, Pparg, E2f, and Egr1 binding sites at the Prkce gene promoter were densely methylated in males and females and were unaffected by cocaine exposure. In contrast, methylation of CpGs in the two Sp1 binding sites (−346 and −268) was low and was significantly increased by cocaine exposure in male offspring. In females, methylation of the Sp1 binding site at −268 but not −346 was increased. Reporter gene assays showed that both Sp1 binding sites had a strong stimulatory role in Prkce gene activity. Methylation of the Sp1 binding sites significantly decreased SP1 binding to the Prkce promoter. Cocaine exposure did not affect nuclear SP1 protein levels but decreased the SP1 binding affinity to its binding site at −268. The results demonstrate an epigenetic mechanism of DNA methylation in programming of cardiac Prkce gene repression, linking fetal cocaine exposure and pathophysiological consequences in the heart of adult male offspring in a gender-dependent manner.
Slow Off-rates and Strong Product Binding Are Required for Processivity and Efficient Degradation of Recalcitrant Chitin by Family 18 Chitinases*

Background: The role of slow off-rates of processive enzymes acting on recalcitrant polysaccharides is poorly understood. Results: Chitinase variants with high off-rates and weak product binding were inefficient in degradation of recalcitrant chitin. Conclusion: Slow off-rates and strong product binding are required for high efficiency and processivity. Significance: Knowledge of determinants of processivity aids to design better enzymes. Processive glycoside hydrolases are the key components of enzymatic machineries that decompose recalcitrant polysaccharides, such as chitin and cellulose. The intrinsic processivity (PIntr) of cellulases has been shown to be governed by the rate constant of dissociation from polymer chain (koff). However, the reported koff values of cellulases are strongly dependent on the method used for their measurement. Here, we developed a new method for determining koff, based on measuring the exchange rate of the enzyme between a non-labeled and a 14C-labeled polymeric substrate. The method was applied to the study of the processive chitinase ChiA from Serratia marcescens. In parallel, ChiA variants with weaker binding of the N-acetylglucosamine unit either in substrate-binding site −3 (ChiA-W167A) or the product-binding site +1 (ChiA-W275A) were studied. Both ChiA variants showed increased off-rates and lower apparent processivity on α-chitin. The rate of the production of insoluble reducing groups on the reduced α-chitin was an order of magnitude higher than koff, suggesting that the enzyme can initiate several processive runs without leaving the substrate. On crystalline chitin, the general activity of the wild type enzyme was higher, and the difference was magnifying with hydrolysis time. On amorphous chitin, the variants clearly outperformed the wild type. A model is proposed whereby strong interactions with polymer in the substrate-binding sites (low off-rates) and strong binding of the product in the product-binding sites (high pushing potential) are required for the removal of obstacles, like disintegration of chitin microfibrils.
Cubic spline wavelets with four vanishing moments on the interval and their applications to option pricing under Kou model

The paper is concerned with the construction of a cubic spline wavelet basis on the unit interval and an adaptation of this basis to the first-order homogeneous Dirichlet boundary conditions. The wavelets have four vanishing moments and they have the shortest possible support among all cubic spline wavelets with four vanishing moments corresponding to B-spline scaling functions. We provide a rigorous proof of the stability of the basis in the space [Formula: see text] or its subspace incorporating boundary conditions. To illustrate the applicability of the constructed bases, we apply the wavelet-Galerkin method to option pricing under the double exponential jump-diffusion model and we compare the results with other cubic spline wavelet bases and with other methods.