Miracle-dz/UniFAR-FTUs huggingface dataset:
Epstein-Barr Virus SM Protein Interacts with mRNA In Vivo and Mediates a Gene-Specific Increase in Cytoplasmic mRNA

ABSTRACT SM is an Epstein-Barr virus (EBV) gene expressed during early lytic replication of EBV. SM encodes a nuclear phosphoprotein that functions as a posttranscriptional regulator of gene expression. SM has been implicated in several aspects of gene regulation, including nuclear mRNA stabilization, posttranscriptional processing, and nuclear mRNA export. Activation by SM is promoter independent but gene specific. The mechanism by which SM selectively activates some EBV target genes or heterologous reporter genes remains to be determined. SM binds RNA in vitro, suggesting that sequence- or structure-specific mRNA interactions might mediate SM specificity. We have further analyzed RNA binding by SM and demonstrated that proteolytic cleavage of SM and consequent exposure of an arginine-rich region are necessary to allow RNA binding in vitro. However, SM mutants with deletions of this arginine-rich region localized normally in the nucleus and were fully functional in gene activation. We therefore developed an assay to study in vivo interactions of SM with target mRNAs based on immunoprecipitation of SM from cell lysates followed by RNase protection analysis. Using this assay, we demonstrated that SM forms complexes with specific mRNAs in vivo. SM binds mRNAs from both SM-responsive as well as nonresponsive intronless genes and increases the nuclear accumulation of both types of mRNAs. In addition, SM preferentially associates with newly transcribed mRNAs. These data indicate that SM forms complexes with mRNAs in the nucleus and enhances their nuclear accumulation. However, SM does not enhance cytoplasmic accumulation of all transcripts that it binds to the same degree, suggesting that additional mRNA-specific characteristics, such as nuclear retention motifs or binding sites for cellular proteins, also determine responsiveness to SM.
Suicide literacy, suicide stigma and help-seeking intentions in Australian medical students

Objective: The purpose of this study was to measure levels of suicide literacy and stigma amongst Australian medical students in comparison to a general university population, and to assess medical students’ help-seeking intentions. Method: A cross-sectional survey was administered to 165 currently-enrolled Australian National University (ANU) postgraduate medical students and 54 final year undergraduate medical students at the University of Adelaide. These samples were compared to another sample of 676 general members of the ANU, undertaken six months earlier. Results: Final year postgraduate and undergraduate students had significantly higher levels of mental health literacy (measured using the Literacy of Suicide Scale) than other medical students or general university staff and students. Suicide stigma (measured using the Stigma of Suicide Scale) was comparable across the samples. Less exposure to suicide was associated with greater stigma and increased intentions of informal help seeking. Students who normalised suicide had significantly lower intentions of seeking help for thoughts of suicide. Conclusions: The findings indicate that exposure to suicidal people through clinical experience may improve knowledge about suicide but may lead to more negative attitudes toward informal help-seeking. The suicide prevention curriculum should aim to raise mental health literacy levels, reduce stigmatising attitudes and limit the normalisation of suicide.
SYNTHESIS AND PROPERTIES OF INORGANIC COMPOUNDS Synthesis and Luminescent Properties of Europium ( III , II ) Phosphates

⎯Nanosized europium phosphates Eu3PO7, Eu(PO3)3, and Eu(PO3)3 : Eu2+ have been prepared by low-temperature extraction-pyrolytic method. Optimal temperature and time of precursor pyrolysis for preparing luminophor containing europium in different oxidation states have been determined. Phosphate luminophors based on Eu3+ exhibit intense red luminescence with λmax ~ 600–650 nm. Luminescence spectra of Eu(PO3)3 : Eu2+ are characterized by emission bands in the region 400–700 nm typical for both Eu3+ (the bands of D0–Fj (j = 0, 1, 2) transitions), and Eu2+ (the band of 4f65d → S7/2 transition). Luminescenceexciting wavelengths provide different contribution to the radiation intensity of both Eu2+ and Eu3+.
Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions

Animal coronaviruses, such as infectious bronchitis virus (IBV), and arteriviruses, such as porcine reproductive and respiratory syndrome virus (PRRSV), are able to manifest highly contagious infections in their specific native hosts, thereby arising in critical economic damage to animal industries. This review discusses recent progress in studies of virus-host interactions during animal and human coronavirus and arterivirus infections, with emphasis on IBV-host cell interactions. These interactions may be directly involved in viral replication or lead to the alteration of certain signaling pathways, such as cell stress response and innate immunity, to facilitate viral replication and pathogenesis.
Changes in visual acuity of patients undergoing cataract surgery during the last two decades.

PURPOSE To compare preoperative visual acuities in patients who underwent cataract surgery between 1982 and 2000. METHODS Information on visual acuity (VA), ocular disease and general disease was obtained from records relating to samples of consecutive cataract operations in 1982, 1985, 1990, 1995 and 2000 in two hospitals in the Vaasa region of Finland. RESULTS Between 1982 and 2000, the average preoperative VA in the operated eye increased by 0.85 logMAR units (from logMAR 1.56 to logMAR 0.71) or 8.5 log lines. Corresponding decimal values are 0.03 and 0.2, respectively. In the better eye, VA increased from logMAR 0.64 to logMAR 0.37. Corresponding decimal values are 0.23 and 0.43, respectively. The incidence of cataract surgery increased from 1.0 to 7.2 operations per 1000 of the population per year over the period. For an annual increase of one operation per 1000 inhabitants, the increase in average VA before surgery is 1.3 log lines in the operated eye and 0.4 log lines in the better eye. The number of patients with visual impairment (WHO definition: VA < 0.3) before surgery fell from 47% to 15%, and the number of patients with profound visual handicaps (VA < 0.1) before surgery fell from 15% to 4%. CONCLUSION The preoperative vision of patients undergoing cataract surgery during the last two decades has improved significantly. Preoperative VA has increased linearly in line with the incidence of surgery. Only a small proportion of the increase in incidence of cataract surgery can be explained by the increasing average age of the population.
Patient Experience of Pain After Elective Noncardiac Surgery

The purpose of this study was to examine the extent and evolution of pain after common major surgical procedures and to establish correlates of three types of pain:pain at rest, pain with movement, and maximum pain over the previous 24 h. Patients completed a preoperative questionnaire to obtain data on age, gender, narcotic use, baseline level of pain, chronicity of pain, and level of anxiety. Patients were then interviewed on Postoperative Days 1, 2, and 3 to assess their pain on a scale of 0 (none) to 10 (worst imaginable). The mean pain score at rest was 2.6 on Postoperative Day 1 and decreased to 2.3 on Postoperative Day 3 (P = 0.06). The mean pain score with movement was 4.5 on Postoperative Day 1, which decreased to 4.2 on Postoperative Day 3 (P = 0.03). The mean maximum pain score over the previous 24 h was 6.3, which decreased to 5.6 (P = 0.0001). Preoperative narcotic use and high baseline preoperative pain, defined as a score >or=to4, were significantly (P < 0.05) associated with increased pain at rest, pain with movement, and maximum pain. Epidural analgesia was the only mode of analgesia significantly associated with both decreased postoperative pain at rest and decreased pain with movement (P < 0.05). These relatively high pain scores and minimum decreases in pain from Postoperative Days 1 to 3 emphasizes the need for more effective pain management continuing into the postoperative period to facilitate mobilization and recovery. (Anesth Analg 1997;85:117-23)
A comprehensive account on the role of efflux transporters in the gastrointestinal absorption of 13 commonly used substrate drugs in humans.

BACKGROUND The potential absorption-limiting effect of intestinal efflux transporters such as P-glycoprotein (P-gp) has been well recognized, primarily based on results of numerous Caco-2 cell studies showing that flux, permeability, or transport clearance of drugs from the basolateral to the apical (B --> A) compartment is greater than that from the apical to the basolateral (A --> B) compartment. Except for very limited examples such as celiprolol, talinolol, pafenolol and paclitaxel, the potential clinical impact of these transporters on oral absorption of the vast number of commonly prescribed drug substrates in humans has not been closely examined to date. OBJECTIVE To evaluate whether these efflux transporters may play a significant role in limiting oral absorption of 13 commonly used drugs (digoxin, etoposide, felodipine, fexofenadine, furosemide, indinavir, losartan, nadolol, propranolol, ritonavir, saquinavir, tacrolimus, and verapamil) in humans. METHODS Drug absorption properties such as the rate (as judged by the Cmax and tmax) and extent (as judged by AUC or urinary excretion of drugs) of absorption as a function of dose, as well as the completeness of oral absorption were obtained from the literature. RESULTS The absorption properties of these 13 drugs are not consistent with absorption-retarding expectations from in vitro studies because they all show apparent dose-independent kinetics in absorption or bioavailability and completeness of oral absorption is shown for most of the drugs evaluated. CONCLUSIONS In spite of being substrates of intestinal efflux transporters such as P-gp, the in vivo oral absorption of 13 drugs examined apparently is not significantly impeded by efflux transporters. Thus, there may exist an apparent discrepancy between in vitro "expectations" and in vivo results; potential reasons for this are discussed. The present findings, however, do not de-emphasize potential in vivo importance of efflux transporters in affecting (increasing or decreasing) oral absorption of certain substrate drugs, especially those with low to moderate intestinal permeability and with low therapeutic index, or the importance of efflux transporters in the study of mechanisms of drug absorption and some potentially clinically significant drug-drug and drug-food interactions.
Extracellular virulence factors in Bacillus cereus endophthalmitis: methods and implication of involvement of hemolysin BL

Bacillus cereus is a common cause of highly fulminant posttraumatic and metastatic endophthalmitis. Exotoxins or enzymes likely contribute to the severity of the infection, but specific virulence factors have not been identified. We developed two methods for the identification of B. cereus ocular virulence factors. In an in vitro assay that allows screening of multiple samples, retinal toxicity was estimated by measuring the release of lactate dehydrogenase from retinal buttons treated with B. cereus toxins. The results from this assay were confirmed with a sterile endophthalmitis model in which the histopathologic effect of intravitreally injected toxins was assessed. We tested pure hemolysin BL (HBL), a tripartite dermonecrotic vascular permeability factor of B. cereus, and crude exotoxin (CET) preparations, consisting of concentrated, cell-free B. cereus culture supernatant. In the in vitro assay, both CET and HBL caused rapid release of lactate dehydrogenase and retinal disintegration. In vivo, the toxins caused endophthalmitis clinically characteristic of B. cereus within 4 h. Histological changes included rapid retinal necrosis and detachment, choroidal edema, detachment and disruption of the retinal pigment epithelium, and rapid infiltration of polymorphonuclear leukocytes. Neutralization of HBL in CET preparations inhibited toxicity in vitro by 54%, and pure HBL was less toxic than CET with equal HBL contents in both methods. The results suggest that B. cereus ocular virulence is multifactorial and that HBL contributes to virulence.
Mutual prodrug concept: Fundamentals and applications

A therapeutically significant drug may have limited utilization in clinical practice because of poor organoleptic properties, poor bioavailability, short duration of action, nonspecificity, incomplete absorption, poor aqueous solubility, high first-pass metabolism or other adverse effects. There is a great emphasis on research to discover methods aimed at improving their therapeutic efficacy by minimizing or eliminating these undesirable properties. Sometimes, an adequate pharmaceutical formulation can overcome these drawbacks, but often the galenic formulation is inoperant and a chemical modification of active molecule is necessary to correct its pharmacokinetic insufficiencies. This chemical formulation process, whose objective is to convert an interesting active molecule into a clinically acceptable drug, often involves the so-called ‘Prodrug design. ’ Mutual prodrug is a type of carrier-linked prodrug, where the carrier used is another biologically active drug instead of some inert molecule. A mutual prodrug consists of two pharmacologically active agents coupled together so that each acts as a promoiety for the other agent and vice versa. Mutual prodrug design is really no different from the general drug discovery process, in which a unique substance is observed to have desirable pharmacological effects, and studies of its properties lead to the design of better drugs. It is a very fruitful area of research, and its introduction in human therapy has given successful results in improving the clinical and therapeutic effectiveness of drugs suffering from some undesirable properties that otherwise hinder their clinical usefulness. The present article takes a review of various applications of mutual prodrugs and the developments in this field during the last few decades.
Symptom Severity of Nicotiana benthamiana Plants Inoculated with Agrobacterium Containing Infectious DNA-A Clones of Honeysuckle Yellow Vein Virus (HYVV)

To investigate the pathogenicity and virulence of the Honeysuckle yellow vein virus (HYVV) lacking betasatellites, PCR amplified unit-lengths of DNA-A genome of HYVV-[DJ] were cloned into binary vector pRI101-AN, and generated HYVV-[DJ]-1mer, -1.3mer and -2mer genomes. Each construct was transformed into Agrobacterium cells and agro-inoculated into young leaves of Nicotiana benthamiana. Except for the HYVV-[DJ]-1mer, HYVV-[DJ]-1.3mer and -2mer clones caused pronounced disease symptoms in N. benthamiana. HYVV-[DJ]-2mer agro-inoculated plants showed more severe plant stunting with downward leaf curling and crinkling than those of HYVV-[DJ]-1.3mer agro-inoculated plants. To discriminate the clone’s virulence quantitatively, SYBR Green-based real-time PCR was performed for the quantification of the target virulence gene DNA in agro-inoculated plants that were collected at weekly intervals for 4 weeks. Regression analysis was obtained from the standard curves by plotting Ct values over the logarithm of the amount of V1 protein gene DNA present in a dilution series of plasmid containing the full-length HYVV-[DJ] genome. Equation of the HYVV V1 DNA standard curve was used to quantify V1 gene DNA concentration in agro-inoculated plants with each clone. The accumulation of V1 gene DNA in HYVV-[DJ]-1.3mer agro-inoculated plants reached the peak level at 4 weeks post inoculation, while the accumulation of V1 gene DNA in HYVV-[DJ]-2mer agro-inoculated plants reached the peak level at 3 weeks post inoculation. The amount of V1 DNA in HYVV-[DJ]-1.3mer agro-inoculated plants was significantly more than that in HYVV-[DJ]-2mer agro-inoculated plants. Considering the results, there was a difference between the accumulation of virus DNA and the symptom severity of the analyzed plants agro-inoculated with each clone. It suggested that the infectious clones’ virulence is not necessarily correlated with the symptom severity.
Determinants and patterns of physical activity practice among Spanish university students

Abstract The purpose of the present study was to investigate the socio-demographic and lifestyle determinants of physical activity practice, as well as the motivations for being or not being physically active in Spanish university students. A representative sample of students from a Spanish university (n = 2,051; 42.1% males; mean age 21.9, s = 4.8 years) participated in the present cross-sectional study. A questionnaire including questions regarding lifestyle, dietary habits, parents' characteristics, and physical activity habits was administered to the students. The socio-demographic and lifestyle determinants of physical activity practice were assessed using multivariable logistic regression. 68.4% of men and 48.4% of women reported to practise physical activity in the present sample. Those who practised physical activity consumed more fruits and were less likely to be smokers compared to non-physically active students. Also, physically inactive men spent more time in front of the computer and physically inactive women spent more time in front of the TV and were more likely to be frequent alcohol consumers. Maternal educational level and maternal physical activity habits were also important determinants of physical activity practice among men and women respectively. In conclusion, physically active students tended to engage in other healthy habits in the present population, suggesting the clustering of healthy or unhealthy lifestyle factors among specific subgroups.
Comparison of the effect of semen from HIV-infected and uninfected men on CD4+ T-cell infection

Objectives:Semen composition is influenced by HIV-1 infection, yet the impact of semen components on HIV infection of primary target cells has only been studied in samples from HIV-uninfected donors. Design:We compared the effect of seminal plasma (SP) from chronically HIV-infected (SP+) versus uninfected donors (SP–) on HIV-1 infection of peripheral blood mononuclear cells (PBMCs) and CD4+ T cells. Methods:Primary cells were infected with HIV-1 in the presence of SP+ or SP– and analyzed for infection level, metabolic activity, HIV receptor expression, proliferation and activation. SP+ and SP– were compared for infection-enhancing peptides, cytokines and prostaglandin E2 levels. Results:SP– efficiently enhanced HIV-1 R5 infection of CD4+ T cells, whereas SP+ enhancing activity was significantly reduced. RANTES (CCL5) concentrations were elevated in SP+ relative to SP–, whereas the concentrations of infectivity-enhancing peptides [semen-derived enhancer of viral infection (SEVI), SEM1, SEM2] were similar. CCR5 membrane expression levels were reduced on CD4+ T cells shortly postexposure to SP+ compared with SP– and correlated to R5-tropic HIV-1 infection levels, and CCR5 ligands’ concentrations in semen. SP+ and SP– displayed similar enhancing activity on PBMC infection by X4-tropic HIV-1. Addition/depletion of RANTES (regulated on activation, normal T-cell expressed and secreted) from SPs modulated their effect on PBMC infection by R5-tropic HIV-1. Conclusion:Semen from HIV-infected donors exhibits a significantly reduced enhancing potential on CD4+ T-cell infection by R5-tropic HIV-1 when compared with semen from uninfected donors. Our data indicate that elevated seminal concentrations of RANTES in HIV-infected men can influence the ability of semen to enhance infection.
Measurement of Carpal Canal and Median Nerve Pressure in Patients With Carpal Tunnel Syndrome

Carpal tunnel syndrome is a compression neuropathy wherein the median nerve is compressed inside of the carpal canal. Its diagnosis is made clinically, electrophysiologically, and sometimes by carpal canal pressure measurement. The objective of surgical management of this condition is the decompression of the median nerve. We usually measure carpal canal pressure preoperatively and postoperatively using a continuous infusion technique for diagnoses as well as for postoperative evaluation of decompression following our Universal Subcutaneous Endoscope system procedure. To evaluate whether our procedure effectively decompressed the median nerve, we measured intraneural pressure preoperatively and postoperatively in the resting position, with active power grip, and in the Okutsu test position. Correlation between the carpal canal pressure and intraneural median nerve pressure was statistically analyzed using the Kendall rank correlation coefficient (n = 157 hands). A significant correlation was present preoperatively in resting position and postoperatively with active power grip and in the Okutsu test position. Because of this correlation, we conclude that our endoscopic operative procedure effectively decompresses the median nerve and that simple carpal canal pressure measurement is sufficient to confirm diagnoses and to evaluate the status of postoperative decompression.
Formal verification of probabilistic SystemC models with statistical model checking

Transaction‐level modeling with SystemC has been very successful in describing the behavior of embedded systems by providing high‐level executable models, in which many of them have inherent probabilistic behaviors, eg, random data and unreliable components. It is thus crucial to have both quantitative and qualitative analysis of the probabilities of system properties.
ADAPTATION AND THE COST OF COMPLEXITY

Abstract. — Adaptation is characterized by the movement of a population toward a many‐character optimum, movement that results in an increase in fitness. Here I calculate the rate at which fitness increases during adaptation and describe the curve giving fitness versus time as a population approaches an optimum in Fisher's model of adaptation. The results identify several factors affecting the speed of adaptation. One of the most important is organismal complexity—complex organisms adapt more slowly than simple ones when using mutations of the same phenotypic size. Thus, as Fisher foresaw, organisms pay a kind of cost of complexity. However, the magnitude of this cost is considerably larger than Fisher's analysis suggested. Indeed the rate of adaptation declines at least as fast as n‐1, where n is the number of independent characters or dimensions comprising an organism. The present results also suggest that one can define an effective number of dimensions characterizing an adapting species.
Characterization of a Two-component Alkanesulfonate Monooxygenase from Escherichia coli*

The Escherichia coli ssuEADCB gene cluster is required for the utilization of alkanesulfonates as sulfur sources, and is expressed under conditions of sulfate or cysteine starvation. The SsuD and SsuE proteins were overexpressed and characterized. SsuE was purified to homogeneity as an N-terminal histidine-tagged fusion protein. Native SsuE was a homodimeric enzyme of M r 58,400, which catalyzed an NAD(P)H-dependent reduction of FMN, but it was also able to reduce FAD or riboflavin. The SsuD protein was purified to >98% purity using cation exchange, anion exchange, and hydrophobic interaction chromatography. The pure enzyme catalyzed the conversion of pentanesulfonic acid to sulfite and pentaldehyde and was able to desulfonate a wide range of sulfonated substrates including C-2 to C-10 unsubstituted linear alkanesulfonates, substituted ethanesulfonic acids and sulfonated buffers. SsuD catalysis was absolutely dependent on FMNH2 and oxygen, and was maximal for SsuE/SsuD molar ratios of 2.1 to 4.2 in 10 mm Tris-HCl, pH 9.1. Native SsuD was a homotetrameric enzyme of M r 181,000. These results demonstrate that SsuD is a broad range FMNH2-dependent monooxygenase catalyzing the oxygenolytic conversion of alkanesulfonates to sulfite and the corresponding aldehydes. SsuE is the FMN reducing enzyme providing SsuD with FMNH2.