Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of Cell Proliferation Pathways by the Hepatitis B Virus X Protein: A Potential Contributor to the Development of Hepatocellular Carcinoma

Globally, hepatocellular carcinoma (HCC) is the fifth most common cancer and the third highest cause of cancer-associated deaths. Although the development of HCC has been linked to exposure to various toxins or infectious agents, the majority of HCC cases are associated with chronic hepatitis B virus (HBV) infections [reviewed in (Block et al, 2003; Seeger et al, 2007)]. Worldwide, there are an estimated 350 million cases of chronic HBV infections, and approximately 25% of chronically HBV-infected individuals will eventually develop HCC [(Beasley et al, 1981); reviewed in (Seeger et al, 2007)]. The high global incidence of chronic HBV infections, high mortality rate of individuals with HCC, increased prevalence of HCC, and the close association between chronic HBV infections and HCC development have generated intense interest in understanding the molecular mechanisms that underlie the development of HBV-induced HCC. In this chapter, we provide a review of HBV biology and potential mechanisms that link a chronic HBV infection to the development of HCC. We specifically focus on activities of the HBV X protein (HBx), a multifunctional HBV protein that can alter hepatocyte physiology and stimulate HBV replication. While a brief survey of HBx activities that could influence HCC development is provided, we emphasize HBx regulation of intracellular calcium signaling and cell proliferation pathways as HBx activities that could potentially influence hepatocyte transformation.
Proliferation and differentiation of highly enriched mouse hematopoietic stem cells and progenitor cells in response to defined growth factors

Three distinct hematopoietic populations derived from normal bone marrow were analyzed for their response to defined growth factors. The Thy-1loT- B- G- M-population, composing 0.2% of bone marrow, is 370- fold enriched for pluripotent hematopoietic stem cells. The two other populations, the Thy-1- T- B- G- M- and the predominantly mature Thy-1+ T+ B+ G+ M+ cells, lack stem cells. Thy-1loT- B- G- M- cells respond with a frequency of one in seven cells to IL-3 in an in vitro CFU-C assay, and give rise to many mixed colonies as expected from an early multipotent or pluripotent progenitor. The Thy-1- T- B- G- M- population also contains progenitor cells which responded to IL-3. However, colonies derived from Thy-1- T- B- G- M- cells are almost exclusively restricted to the macrophage/granulocyte lineages. This indicates that IL-3 can stimulate at least two distinct clonogenic early progenitor cells in normal bone marrow: multipotent Thy-1loT- B- G- M- cells and restricted Thy-1- T- B- G- M- cells. Thy-1loT- B- G- M- cells could not be stimulated by macrophage colony-stimulating factor (M-CSF), granulocyte CSF (G-CSF) or IL-5 (Eosinophil-CSF). The hematopoietic precursors that react to these factors are enriched in the Thy-1- T- G- B- M- population. Thus, multipotent and restricted progenitors can be separated on the basis of the expression of the cell surface antigen Thy-1.
A complex of CaV1.2/PKC is involved in muscarinic signaling in smooth muscle

Here we present functional and biochemical evidence for a Ca2+ channel (CaV1.2) /protein kinase C (PKC) signaling complex being a key player in muscarinic regulation of urinary bladder smooth muscle. Muscarinic stimulation induced Ca2+ signals and concomitant contractions in detrusor muscle from mice that were dependent on functional Ca2+ channels. These signals were still present in muscles being depolarized by 85 mM extracellular K+. Muscarinic‐induced contractions were reduced by a PKC inhibitor [bisindolylmaleimide I (BIM‐I)] and a phospholipase D (PLD) inhibitor (1‐butanol). A phorbol ester (PDBu) enlarged muscarinic‐induced Ca2+ signals and contractions. The effects of BIM‐I and PDBu were inhibited by isradipine and/or absent in muscles from CaV1.2‐deficient mice. Both carbachol and PDBu increased CaV1.2 channel currents in isolated bladder myocytes. Blue native‐PAGE electrophoresis revealed that CaV1.2, PKC, and PLD are closely associated in muscles being previously stimulated by carbachol. Immunoprecipitation using anti‐CaV1.2 followed by Western blotting demonstrated that CaV1.2 and PKC are coupled in stimulated muscles from wild‐type mice. Autoradiography on immunoprecipitates showed that CaV1.2 is a substrate for PKC‐mediated phosphorylation. These findings suggest that a signaling complex consisting of CaV1.2, PKC, and, probably, PLD controls muscarinic‐mediated phasic contraction of urinary bladder smooth muscle. —Huster, M. , Frei, E. , Hofmann, F. , Wegener, J. W. A complex of CaV1.2/PKC is involved in muscarinic signaling in smooth muscle. FASEB J. 24, 2651–2659 (2010).
The human lamin B receptor/sterol reductase multigene family.

LBR (lamin B receptor) is an integral protein of the inner nuclear membrane encoded by a gene on human chromosome 1q42.1. LBR has a nucleoplasmic, amino-terminal domain of approximately 200 amino acids followed by a carboxyl-terminal domain similar in sequence to yeast and plant sterol reductases. We have determined the primary structures of two human proteins with strong sequence similarity to the carboxyl-terminal domain of LBR and sterol reductases. Their genes have recently been assigned the symbols TM7SF2 and DHCR7. TM7SF2 mRNA is most predominantly expressed in heart and DHCR7 mRNA mostly in liver and brain. Whereas LBR is localized to the inner nuclear membrane, these two related proteins are in the endoplasmic reticulum. The TM7SF2 gene contains 10 coding exons, and its intron positions are exactly conserved in the part of the LBR gene encoding its carboxyl-terminal domain. Intron positions in the DHCR7 gene are also similar. Both of these new LBR-like genes are on chromosome 11q13. These results describe a human gene family encoding proteins of the inner nuclear membrane and endoplasmic reticulum that function in nuclear organization and/or sterol metabolism.
Etomidate Versus Propofol for Electroconvulsive Therapy in Patients With Schizophrenia

Among drugs used for the anesthesia of electroconvulsive therapy (ECT), propofol reduces seizure duration to a greater degree than etomidate. The perceived difference between the 2 anesthetics is smaller in patients with schizophrenia than in patients who suffer depression. In this study, propofol and etomidate were compared during the ECT of patients with schizophrenia, on the basis of their impact on seizure activity and on seizure-induced hemodynamic reactions. Schizophrenics (n = 34) who were treated with ECT participated in this randomized crossover study. Propofol (1 mg/kg) and etomidate (0.2 mg/kg) were used alternately. The 2 drugs were compared on the basis of EEG- and EMG-registered seizure duration, mean arterial pressure (MAP), pulse frequency, energy index, and postictal suppression. We also analyzed the number of necessary restimulations. In case of anesthesia with etomidate, both EEG- (61.29 ± 22.4 s, 47.9 ± 21.3 s P = 0.014) and EMG- (46.3 ± 23.8 s, 33.6 ± 15.9 s P = 0.006) registered seizure durations were significantly longer than in case of propofol. When using propofol, the increase in MAP was significantly lower than when etomidate was used (8.1 ± 10.2 mm Hg, 18.3 ± 11.2 mm Hg, P = 0.001). There were no significant differences found in the postseizure increase in pulse frequency, in postictal suppression, or in the energy index, nor did the numbers of necessary restimulations differ significantly. Propofolwas found to reduce seizure duration to a significantly greater extent than etomidate. At the same time, in electrophysiological parameters that show a correlation with clinical efficacy, there was no significant difference found between the 2 anesthetics. However, the seizureinduced increase in MAP was reduced by propofol to a significantly greater degree than by etomidate.
Quantitative EEG in patients with alcohol-related seizures.

BACKGROUND To investigate whether quantitative electroencephalography (QEEG) recorded within a few days after a generalized seizure can improve the discrimination between alcohol-related seizures (ARSs), seizures in epilepsy and other seizures. In addition, we wanted to evaluate the influence of various external factors on QEEG, e.g., drug use, time from seizure occurrence, and alcohol intake. METHODS An ARS was defined by (i) scores ≥8 in the Alcohol Use Disorders Identification Test (AUDIT) and (ii) no history of epilepsy. Twenty-two ARS patients, 21 epileptic patients with seizures (ES), 30 AUDIT-negative patients with seizures (OS), and 37 well-controlled epileptic outpatients (EPO) were included. EEG from 79 sciatica patients (SC) served as an additional control group. EEG was recorded in relaxed wakefulness with eyes closed. Spectral analysis of ongoing resting EEG activity was performed. For the main analysis, spectral band amplitudes were averaged across 14 electrodes. RESULTS Major quantitative EEG abnormalities were mainly seen in the ES group. AUDIT score correlated negatively with QEEG band amplitudes in patients with seizures unrelated to alcohol, but not in the ARS group. Recent alcohol intake correlated negatively with delta and theta amplitude. We could not confirm that beta activity is increased in ARS subjects. CONCLUSIONS A QEEG with slightly reduced alpha amplitude supports a clinical diagnosis of ARS. An abnormally slow QEEG profile and asymmetry in the temporal regions indicates ES. QEEG predicted the clinical diagnosis better than standard EEG.
Experimental retrieval of the effective parameters of metamaterials using a strip line method

In this paper, a new method based on strip line structures is presented for characterization of metamaterials. The proposed method is suitable for characterization of all types of artificial structures including Single Negative (SNG) and Double Negative (DNG) media. The new method has the advantages of easy fabrication and low cost, when compared to free space [1] or the waveguide methods [2]. Furthermore, it has the advantage of extracting both permittivity, ε, and permeability, μ, with a single measurement, when compared to microstrip line method [3].
Legislative Politics in Latin America: EXPLAINING LEGISLATIVE POLITICS IN LATIN AMERICA

Instead of focusing on presidents, militaries, financial sector bureaucrats, or social actors, the preceding pages have placed the Argentine, Brazilian, Chilean, and Mexican legislatures at the center of democratic politics. While the authors all agree that the legislatures are potent, it is also clear that the legislatures take a less proactive role than does the U.S. Congress. In this chapter I draw on the previous chapters to argue that the legislatures take a generally reactive role, but within this role there is great variance in the way in which the legislatures assert their power and insert themselves into the policy process. I argue further that the chapters have also offered significant evidence that, as postulated in the introduction, many of the differences are explicable by institutional variation. The country chapters are arranged to focus on substantive questions about executive–legislative relations and the role of parties in organizing the business of the legislature. In this conclusion I return to the thematic questions raised in the introduction about the importance of reelection rates, electoral systems, partisan alignments, and constitutional powers on legislative politics. In doing so, this chapter has two primary goals. First, a main methodological strategy of this book has been to borrow from the U.S. model in deriving descriptions of key pieces of the legislative process and explanations for legislative behavior in Latin America. But, we have also shown that the assumptions embedded in models of the U.S. Congress must become variables in a comparative context.
Hypothalamic obesity in children: pathophysiology to clinical management

Abstract Hypothalamic obesity (HyOb) is a complex neuroendocrine disorder caused by damage to the hypothalamus, which results in disruption of energy regulation. The key hypothalamic areas of energy regulation are the ARC (arcuate nucleus), the VMH (ventromedial hypothalamus), the PVN (paraventriculer nuclei) and the LHA (lateral hypothalamic area). These pathways can be disrupted mechanically by hypothalamic tumors, neurosurgery, inflammatory disorders, radiotherapy and trauma or functionally as such seen in genetic diseases. Rapid weight gain and severe obesity are the most striking features of HyOb and caused by hyperphagia, reduced basal metabolic rate (BMR) and decreased physical activity. HyOb is usually unresponsive to diet and exercise. Although, GLP-1 and its anologs seem to be a new agent, there is still no curative treatment. Thus, prevention is of prime importance and the clinicians should be alert and vigilant in patients at risk for development of HyOb.
Cortisol awakening response in patients with anorexia nervosa or bulimia nervosa: relationships to sensitivity to reward and sensitivity to punishment

Background Sensitivity to punishment (SP) and sensitivity to reward (SR) are personality characteristics that may have relevance for the pathophysiology of eating disorders (EDs). Moreover, personality characteristics are known to modulate the activity of the hypothalamus–pituitary–adrenal (HPA) axis, which is the main component of the endogenous stress response system. As stress has been implicated in the aetiology and the maintenance of EDs, we aimed to study the HPA axis activity in relation to SP and SR, as conceptualized by Gray's reinforcement sensitivity theory (RST), in patients with anorexia nervosa (AN) or bulimia nervosa (BN). Method Twenty-five women with AN, 23 women with BN and 19 healthy women volunteered for the study. HPA axis activity was assessed by measurement of the salivary cortisol awakening response (CAR). The subjects’ SP and SR were measured by the behavioural inhibition system (BIS)/behavioural approach system (BAS) scales. Results The CAR was significantly enhanced in AN patients, but not in BN patients, compared to healthy women. The CAR correlated significantly with BAS measures, negatively in healthy controls and positively in binge-purging AN patients and BN women. SP, measured by the BIS scale, was higher in patients than in controls. Conclusions These findings confirm the occurrence of an enhanced activity of the HPA axis in symptomatic AN, but not in symptomatic BN, and show for the first time that the CAR is associated with SR, as conceptualized by the RST, negatively in healthy subjects but positively in binge-purging ED patients.
Validation of a culturally appropriate quantitative food frequency questionnaire for Inuvialuit population in the Northwest Territories, Canada.

BACKGROUND The estimation of dietary intake in population-based studies is often assessed by a food frequency questionnaire (FFQ). This present study aimed to establish the validity of a 142-item quantitative FFQ (QFFQ) developed to assess dietary intake in a population living in the Northwest Territories, Canada, and undergoing rapid nutrition transition. METHODS Sixty-four randomly selected Inuvialuit adults were recruited. The mean of one to three 24-h recalls was used as the reference to measure the validity of the QFFQ. Spearman rank correlations (ρ), cross-classification and weighted kappa were computed as measures of concordance, adjusting for the daily dietary intake variations in the recalls. Bland - Altman plots were used for additional assessment. RESULTS Four participants with daily energy intake of >25.1 MJ were not included in the analysis. For all nutrients, mean daily intake estimations were higher from the QFFQ than from the recalls. De-attenuated ρ's for macronutrients ranged from 0.33 (protein) to 0.45 (carbohydrate). The best de-attenuated ρ amongst micronutrients was observed for vitamin C (0.53). Overall correlation between the two dietary tools improved after correction for within-person variance (from 0.32 to 0.35). When nutrient intakes were categorised into quartiles, the QFFQ and 24-h recalls indicated relative agreement (same or adjacent quartiles) for 77% for energy and macronutrients, 86% for total sugar and 72% for micronutrients. Bland-Altman plots showed a tendency for increased scatter of the differences at higher intakes. CONCLUSIONS The QFFQ developed is valid and can be used to assess usual dietary intake and dietary adequacy, determine the contribution of foods to specific nutrient intakes, and identify dietary risk factors for chronic disease amongst Inuvialuit.
[Susceptibility to varicella-zoster, measles, rosacea and mumps among health care workers in a Northern Italy hospital].

BACKGROUND Nosocomial transmission of varicella (V), rubella (R), mumps (Mu) and measles (Me) may be a significant cause of morbidity in health care workers (HCW). Susceptible HCW might be a relevant part of the workforce. METHODS A seroprevalence study was performed in a public hospital. Antibodies (Ab) against V, R, Mu and Me were determined by ELISA. Sociodemographic, clinical, occupational data and sera were obtained during health surveillance. RESULTS 2934 tests on 1106 HCW were performed. Seropositivity was 91% for V, 89% for R, 80% for Mu, 92% for Me. No significant differencies were found for the variables tested, except for age (< 36 years) and certain job tasks (e.g. residents). 22% of HCW tested were seronegative for at least 1 virus. More seronegatives were detected as compared with the majority of literature data. DISCUSSION This study showed a relevant number of susceptible to V, R, Mu and Me. Seroprevalence data are useful for risk assessment, HCW health surveillance, to evaluate fitness for work and to promote vaccination programmes, according to scientific guidelines. OP should include serological screening for Me, Mu, V and R to protect HCW and third parties.
Effect of mutS and recDMutations on Salmonella Virulence

ABSTRACT Hybrid derivatives of closely related bacteria may be used to dissect strain-specific functions that contribute to virulence within a host. However, mismatches between DNA sequences are a potent barrier to recombination. Recipients with mutS and recDmutations overcome this barrier, allowing construction of genetic hybrids. To determine whether Salmonella hybrids constructed in a mutS recD host can be used to study virulence, we assayed the effect of mutS andrecD mutations on the virulence of Salmonella typhimurium 14028s in mice. Mutants defective in eithermutS or recD do not affect the time course or the 50% lethal dose (LD50) of the infection. In contrast, the inactivation of both mutS and recD results in a synthetic phenotype which substantially increases the time required to cause a lethal infection without changing the LD50. This phenotype results from an inability ofmutS recD double mutants to rapidly adapt to purine-limiting conditions present within macrophages. Although the disease progression is slower, S. typhimurium mutS recDmutants retain the ability to cause lethal infections, and, thus, hybrids constructed in mutS recD hosts may permit the analysis of virulence factors in a surrogate animal model.
Discrepancy between feedback negativity and subjective evaluation in gambling

Feedback negativity is a negative event-related potential elicited by feedback indicating incorrect performance or monetary loss. It is unclear whether this negativity is elicited by neutral feedback (e.g. a draw in gambling) or is affected by the subjective rating of punishment. To investigate these issues, we performed a modified and computerized game of ‘rock–paper–scissors’ as a gambling task and measured feedback negativity in response to feedback indicating the outcome, which was accompanied by a monetary reward. The data demonstrated that feedback negativity was elicited not only by a monetary loss but also by an even outcome and was independent of the magnitude of monetary loss. Our results suggest feedback negativity is not always specific to both monetary loss and subjective rating of punishment.
Loss of Flexibility in Alcohol-Taking Rats: Promoting Factors

Alcohol consumption in humans can move from a flexible pattern of intake to an inflexible (addictive) one. Several endogenous and exogenous factors are discussed to be involved in this transition. The purpose of this study was to examine factors that might promote the development of inflexibility. Over a period of 52 weeks (long-term) rats had continuously free choice between differently concentrated alcohol solutions and tap water (four-bottle paradigm). After 4 months of alcohol deprivation, a retest with free choice of alcohol was performed. Bitter-taste conditions were used to test the flexibility of alcohol taking. In the retest alcohol-experienced rats revealed a much higher alcohol intake than previously alcohol-naive ones. Part of the alcohol-experienced animals showed impairment of flexibility in alcohol taking. During long-term choice, some groups were submitted to experimental interventions that might affect addiction development (stress, withdrawal, limited access, adverse consequences). Rats with limited access to alcohol at the end of the long-term choice period took more alcohol and were less flexible in the retest than any other group. It is suggested that an unsatisfied urge for alcohol leads to impairment of control over alcohol drinking.
Monoclonal antibodies as probes of tetanus toxin structure and function

Monoclonal antibodies specific for fragment B, fragment C, and light chain of tetanus toxin were prepared by fusion of P3X63Ag8 BALB/c myeloma cells with spleen cells from BALB/c mice immunized with tetanus toxoid or fragment B. Hybridoma colonies were assayed for antibody production by an enzyme-linked immunosorbent assay. Fourteen positive clones were identified, cloned by limiting dilution, and injected intraperitoneally into mice to obtain ascites fluids. Thirteen of the monoclonal antibodies were of the immunoglobulin G1 subclass and one was immunoglobulin G2. Two of the antibodies were directed against sites on fragment C, nine were directed against the light chain, and three were directed against the portion of fragment B which does not comprise the light chain of tetanus toxin. At least one antibody in each group exhibited significant toxin neutralization activity. However, only one of these neutralizing antibodies strongly inhibited the binding of 125I-tetanus toxin to ganglioside-coated plates. These data indicate that interference with receptor recognition is not the only means of neutralizing tetanus toxin. Monoclonal antitoxins as potential therapeutic and prophylactic reagents are discussed.