Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular Regulation of Cytosolic Group IV Phospholipase A2 by Phosphatidylinositol Bisphosphate Levels1

Cytosolic group IV phospholipase A2 (cPLA2) is a ubiquitously expressed enzyme with key roles in intracellular signaling. The current paradigm for activation of cPLA2 by stimuli proposes that both an increase in intracellular calcium and mitogen-activated protein kinase-mediated phosphorylation occur together to fully activate the enzyme. Calcium is currently thought to be needed for translocation of the cPLA2 to the membrane via a C2 domain, whereas the role of cPLA2 phosphorylation is less clearly defined. Herein, we report that brief exposure of P388D1 macrophages to UV radiation results in a rapid, cPLA2-mediated arachidonic acid mobilization, without increases in intracellular calcium. Thus, increased Ca2+ availability is a dispensable signal for cPLA2 activation, which suggests the existence of alternative mechanisms for the enzyme to efficiently interact with membranes. Our previous in vitro data suggested the importance of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) in the association of cPLA2 to model membranes and hence in the regulation of cPLA2 activity. Experiments described herein show that PtdInsP2 also serves a similar role in vivo. Moreover, inhibition of PtdInsP2 formation during activation conditions leads to inhibition of the cPLA2-mediated arachidonic acid mobilization. These results suggest that cellular PtdInsP2 levels are involved in the regulation of group IV cPLA2 activation.
Role of the Inositol 1,4,5-Trisphosphate Receptor in Ca2+ Feedback Inhibition of Calcium Release-activated Calcium Current (I crac)*

We examined the activation and regulation of calcium release-activated calcium current (I crac) in RBL-1 cells in response to various Ca2+ store-depleting agents. With [Ca2+] i strongly buffered to 100 nm,I crac was activated by ionomycin, thapsigargin, inositol 1,4,5-trisphosphate (IP3), and two metabolically stable IP3 receptor agonists, adenophostin A andl-α-glycerophospho-d-myoinositol-4,5-bisphosphate (GPIP2). With minimal [Ca2+] i buffering, with [Ca2+] i free to fluctuateI crac was activated by ionomycin, thapsigargin, and by the potent IP3 receptor agonist, adenophostin A, but not by GPIP2 or IP3 itself. Likewise, when [Ca2+] i was strongly buffered to 500 nm, ionomycin, thapsigargin, and adenophostin A did and GPIP2 and IP3 did not activate detectableI crac. However, with minimal [Ca2+] i buffering, or with [Ca2+] i buffered to 500 nm, GPIP2 was able to fully activate detectableI crac if uptake of Ca2+intracellular stores was first inhibited. Our findings suggest that when IP3 activates the IP3 receptor, the resulting influx of Ca2+ quickly inactivates the receptor, and Ca2+ is re-accumulated at sites that regulateI crac. Adenophostin A, by virtue of its high receptor affinity, is resistant to this inactivation. Comparison of thapsigargin-releasable Ca2+ pools following activation by different IP3 receptor agonists indicates that the critical regulatory pool of Ca2+ may be very small in comparison to the total IP3-sensitive component of the endoplasmic reticulum. These findings reveal new and important roles for IP3 receptors located on discrete IP3-sensitive Ca2+ pools in calcium feedback regulation ofI crac and capacitative calcium entry.
VP1 and VP2 capsid proteins of Theiler's virus are targets of H-2D-restricted cytotoxic lymphocytes in the central nervous system of B10 mice.

Resistance to Theiler's virus-induced demyelination maps genetically to the MHC class I D region and is associated with up-regulation of class I products and the presence of MHC-restricted virus-specific cytotoxic CD8+ T cells in the CNS. To determine the targets of the cytotoxic response, transfected C57SV (Kb, Db) cells expressing LP (including the leader peptide, VP4, VP2, and VP3 coding sequences), VP4 (including the leader peptide and VP4), VP2, VP3, VP1, or RP (including P2 and P3) were generated. CNS-infiltrating lymphocytes obtained from virus-infected B10, B10.K (Kk, Dk), B10.RBF (Kb, Df). B10.RFB3 (Kf, Db), and B10.RBQ (Kb, Dq) mice were used as effectors. Specific cytotoxicity to the capsid proteins encoded in the LP construct, VP2 and VP1, was demonstrated to be H-2Db region restricted and was mediated by CD8+ T cells. No Kb-restricted virus-specific cytotoxicity response was observed. No specific cytotoxic response against RP-encoded proteins was observed in the CNS of B10 mice. Therefore, both VP1 and VP2 are targets for an H-2D-restricted cytotoxic immune response against Theiler's virus infection in the CNS of infected resistant B10 mice.
FNAC accuracy in diagnosis of thyroid neoplasms considering all diagnostic categories of the Bethesda reporting system: A single-institute experience

Background: Thyroid fine-needle aspiration cytology (FNAC) is a valuable test used for diagnosing diseases of the thyroid gland. Aims: Using all satisfactory categories of the Bethesda system, this study aimed to determine the accuracy with which FNAC diagnoses thyroid neoplasms. We also discuss the factors that affect diagnosis accuracy. Settings and Design: A comparison was drawn between FNAC results and final histological diagnosis using samples collected over a period of 3 years. Materials and Methods: For all patients, age, sex, cytological features, and histological types were determined. All cases of false negative (FN) and false positive (FP) diagnosis were reanalyzed. Statistical Analysis Used: The chi-square test and univariate analysis were performed to examine the relationship between different variables. Results: About 52% of the cases were found malignant, and they were of six different histological types. Papillary carcinoma was the commonest type of malignancy at 76.9%. The rate of malignancy was 63% in males and 49.4% in females. In two of the FN cases, the tumor had a diameter of ≥35 mm. Of the 12 FP cases, nine were in the follicular neoplasm or suspicious for follicular neoplasm Bethesda category. FNAC diagnosis had 95.2% sensitivity, 68.4% specificity, 83.3% positive predictive value, 89.6% negative predictive value, and 85.14% accuracy. Conclusions: FNAC was found to have a high level of sensitivity and an acceptable degree of specificity in diagnosing different types of thyroid neoplasms. The presence of microfollicular structures or crowded cellular clusters is a challenge to diagnosis, particularly in low-quality specimens.
Highly resistant Salmonella Newport-MDRAmpC transmitted through the domestic US food supply: a FoodNet case-control study of sporadic Salmonella Newport infections, 2002-2003.

BACKGROUND A new multidrug-resistant (MDR) strain of Salmonella serotype Newport, Newport-MDRAmpC, has recently emerged. We sought to identify the medical, behavioral, and dietary risk factors for laboratory-confirmed Salmonella Newport infection, including that with Newport-MDRAmpC. METHODS A 12-month population-based case-control study was conducted during 2002-2003 in 8 sites of the Foodborne Diseases Active Surveillance Network (FoodNet), with 215 case patients with Salmonella Newport infection and 1154 healthy community control subjects. RESULTS Case patients with Newport-MDRAmpC infection were more likely than control subjects to have taken an antimicrobial agent to which Newport-MDRAmpC is resistant during the 28 days before the onset of diarrheal illness (odds ratio [OR], 5.0 [95% confidence interval {CI}, 1.6-16]). Case patients with Newport-MDRAmpC infection were also more likely to have eaten uncooked ground beef (OR, 7.8 [95% CI, 1.4-44]) or runny scrambled eggs or omelets prepared in the home (OR, 4.9 [95% CI, 1.3-19]) during the 5 days before the onset of illness. International travel was not a risk factor for Newport-MDRAmpC infection but was a strong risk factor for pansusceptible Salmonella Newport infection (OR, 7.1 [95% CI, 2.0-24]). Case patients with pansusceptible infection were also more likely to have a frog or lizard in their household (OR, 2.9 [95% CI, 1.1-7.7]). CONCLUSIONS Newport-MDRAmpC infection is acquired through the US food supply, most likely from bovine and, perhaps, poultry sources, particularly among persons already taking antimicrobial agents.
The CsdA cysteine desulphurase promotes Fe/S biogenesis by recruiting Suf components and participates to a new sulphur transfer pathway by recruiting CsdL (ex‐YgdL), a ubiquitin‐modifying‐like protein

Cysteine desulphurases are primary sources of sulphur that can eventually be used for Fe/S biogenesis or thiolation of various cofactors and tRNA. Escherichia coli contains three such enzymes, IscS, SufS and CsdA. The importance of IscS and SufS in Fe/S biogenesis is well established. The physiological role of CsdA in contrast remains uncertain. We provide here additional evidences for a functional redundancy between the three cysteine desulphurases in vivo. In particular, we show that a deficiency in isoprenoid biosynthesis is the unique cause of the lethality of the iscS sufS mutant. Moreover, we show that CsdA is engaged in two separate sulphur transfer pathways. In one pathway, CsdA interacts functionally with SufE–SufBCD proteins to assist Fe/S biogenesis. In another pathway, CsdA interacts with CsdE and a newly discovered protein, which we called CsdL, resembling E1‐like proteins found in ubiquitin‐like modification systems. We propose this new pathway to allow synthesis of an as yet to be discovered thiolated compound.
Gastric juice for the diagnosis of H pylori infection in patients on proton pump inhibitors.

AIM To determine the efficacy of gastric juice polymerase chain reaction (PCR) for the detection of H pylori infection in comparison with histology and gastric antral biopsy PCR in patients on a proton pump inhibitor (PPI). METHODS Eighty-five consecutive patients with dyspeptic symptoms were enrolled. Gastric biopsies for histology, PCR and gastric juice were collected at endoscopy for PCR of the H pylori urease C gene (ure C). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive and negative likelihood ratio for PCR of gastric juice for the H pylori ure C gene was compared to histology and gastric antral biopsy H pylori ure C PCR in patients with and without PPI. RESULTS Gastric juice PCR was positive in 66 (78%) patients. Histology showed H pylori associated gastritis in 57 (67%). Gastric biopsy PCR was positive in 72 (85%). In patients not taking PPI, the sensitivity, specificity, PPV, NPV, accuracy and positive and negative likelihood ratio for gastric juice PCR were 89%, 72%, 91%, 67%, 90%, 85%, 3.1 and 0.1 respectively. In patients on PPI these values were 86%, 100%%, 100%, 29%, 86%, 9.5 and 1.4, respectively. CONCLUSION Gastric juice PCR for the diagnosis of H pylori infection has increased sensitivity compared to histology with PPI. The use of gastric juice PCR is recommended to confirm H pylori status in patients taking PPIs.
A retinal dark-light switch: A review of the evidence

Abstract We propose that there exists within the avian, and perhaps more generally in the vertebrate retina, a two-state nonadapting flip-flop circuit, based on reciprocal inhibitory interactions between the photoreceptors, releasing melatonin, the dopaminergic amacrine cells, and amacrine cells which contain enkephalin-, neurotensin-, and somatostatin-like immunoreactivity (the ENSL1 amacrine cells). This circuit consists of two loops, one based on the photoreceptors and dopaminergic amacrine cells, and the other on the dopaminergic and ENSLI amacrine cells. In the dark, the photoreceptors and ENSL1 amacrine cells are active, with the dopaminergic amacrine cells inactive. In the light, the dopaminergic amacrine cells are active, with the photoreceptors and ENSLI amacrine cells inactive. The transition from dark to light state occurs over a narrow (<1 log unit) range of low light intensities, and we postulate that this transition is driven by a graded, adapting pathway from photoreceptors, releasing glutamate, to ON-bipolar cells to dopaminergic amacrine cells. The properties of this pathway suggest that, once released from the reciprocal inhibitory controls of the dark state, dopamine release will show graded, adapting characteristics. Thus, we postulate that retinal function will be divided into two phases: a dopamine-independent phase at low light intensities, and a dopamine-dependent phase at higher light intensities. Dopamine-dependent functions may show two-state properties, or two-state properties on which are superimposed graded, adapting characteristics. Functions dependent upon melatonin, the enkephalins, neurotensin, and somatostatin may tend to show simpler two-state properties. We propose that the dark-light switch may have a role in a range of light-adaptive phenomena, in signalling night-day transitions to the suprachiasmatic nucleus and the pineal, and in the control of eye growth during development.
Evaluating vaccination strategies to control foot-and-mouth disease: a model comparison study

SUMMARY Simulation models can offer valuable insights into the effectiveness of different control strategies and act as important decision support tools when comparing and evaluating outbreak scenarios and control strategies. An international modelling study was performed to compare a range of vaccination strategies in the control of foot-and-mouth disease (FMD). Modelling groups from five countries (Australia, New Zealand, USA, UK, The Netherlands) participated in the study. Vaccination is increasingly being recognized as a potentially important tool in the control of FMD, although there is considerable uncertainty as to how and when it should be used. We sought to compare model outputs and assess the effectiveness of different vaccination strategies in the control of FMD. Using a standardized outbreak scenario based on data from an FMD exercise in the UK in 2010, the study showed general agreement between respective models in terms of the effectiveness of vaccination. Under the scenario assumptions, all models demonstrated that vaccination with ‘stamping-out’ of infected premises led to a significant reduction in predicted epidemic size and duration compared to the ‘stamping-out’ strategy alone. For all models there were advantages in vaccinating cattle-only rather than all species, using 3-km vaccination rings immediately around infected premises, and starting vaccination earlier in the control programme. This study has shown that certain vaccination strategies are robust even to substantial differences in model configurations. This result should increase end-user confidence in conclusions drawn from model outputs. These results can be used to support and develop effective policies for FMD control.
Lipid-lowering drugs as primary prevention in general practice: Do patients reach guideline goals and continue treatment? ADDITION Denmark

Objective. To describe lipid-lowering treatment in a primary care setting and how well target levels are reached. Furthermore, the aim is to describe long-term adherence to treatment. Design. Population-based cross-sectional study with follow-up. Setting. A total of 139 general practices from three of five Danish regions, taking part in the ADDITION study from 2001 to 2006. Subjects. The study population comprises 1468 patients who started lipid-lowering drugs and were followed for a minimum of one year after starting treatment. Median time of follow-up after starting drug therapy was 936 days (range: 366–2068). Results. Of 1468 patients starting treatment, a total of 781 (53%) reached the treatment goal of total cholesterol <5.0 and low-density lipoprotein <3 mmol/l within one year after drug therapy start. The percentage increased throughout the study period from 27% of patients initiating treatment in 2001 to 66% of patients initiating treatment in 2005. Age over 50, repeated cholesterol measurements within three months after treatment start, larger initial dose, and calendar year of treatment start were associated with reaching the goal within the first year, and most recent total cholesterol measurement before start of treatment >7 mmol/L was associated with not reaching the goal in the first year. Among patients followed for a minimum of three years after drug therapy started (n = 536), adherence was 77%, 72%, 75% in the first, second, and third year respectively. Conclusion. Initial doses and the percentage reaching their goal increased substantially throughout the study period. Adherence to lipid-lowering treatment is relatively high in a primary care setting. However, current practice shows room for improvement if treatment recommendations are to be met.
Different distribution of HLA class II alleles in anti-topoisomerase I autoantibody responders between silicosis and systemic sclerosis patients, with a common distinct amino acid sequence in the HLA-DQB1 domain.

Autoantibodies against DNA topoisomerase I (anti-topo I) have been reported to be specific to systemic sclerosis (SSc), however, anti-topo I was detected in patients with silicone breast implants, SLE without features of SSc, and rheumatic diseases. We detected anti-topo I positive silicosis patients without any symptoms of autoimmune diseases. The correlation between anti-topo I autoantibody responses and HLA class II has been established. HLA-DRB1*1502; DQB1*0601 has been reported to be the most frequent anti-topo I associated haplotype among Japanese SSc patients. In this study, haplotype HLA-DR15; DQ6 was detected in all 4 anti-topo I positive Asian Japanese SSc patients randomly selected. Furthermore, HLA-DQB1*0402 was identified in 3 of 4 anti-topo I positive silicosis patients. These findings coincide with the results of a previous study, in which all 4 Japanese patients with anti-topo I had the DQB1*04 alleles, whereas no studies among Caucasian-Americans, African-Americans and Choctaw Indians found the involvement of DQB1*04. We investigated common features among various DQB 1 alleles. HLA-DQB I with a distinct characteristic is clearly involved in the anti-topo I response irrespective of ethnic groups, the main disease, or silica exposure. A common positioning of distinct amino acids, (i.e. positions 14, 30, 57 and 77 of the DQbeta1 domain are methionine, tyrosine, aspartic acid and threonine, respectively,) seems to be associated with anti-topo I response. The above-mentioned amino acid sequence is detected in alleles *0301, *0303, *0306, *0401, *0402, *0601 and *0602.
Analyse de la dynamique de l’innovation dans le secteur de la microfinance au Maroc Approche auprès des employés cadres

Depuis 2012, le secteur de la microfinance au Maroc connait une amelioration reguliere et progressive de ses principaux indicateurs d’activite. Cette dynamique resulte d’une transformation structurelle et organisationnelle globale du secteur mais aussi de la pratique de l’innovation adoptee par les associations qui y operent. Cependant, les organismes du secteur se situent a des niveaux divers dans la prise en compte et l’integration de l’innovation. Plusieurs facteurs favorisent l’innovation dans les organismes mobilises autour de cette activite : l’adossement a un grand groupe, des ressources humaines competentes, la bonne sante financiere de l’institution, son anciennete et des dirigeants qui croient a l’innovation. Cette recherche a revele, par ailleurs, des facteurs de contrainte endogenes et exogenes limitant la pratique de l’innovation dans les organismes les moins actifs en la matiere : cout de l’innovation Vs un budget limite, le manque de disponibilite du personnel, la mentalite des dirigeants qui craignent l’echec, le manque d’employes qualifies et de ressources humaines creatives, le cadre juridique dans le secteur …
Synthesis of 2′‐Deoxyoxanosine from 2′‐Deoxyguanosine, Conversion to Its Phosphoramidite, and Incorporation into Oxanine‐Containing Oligodeoxynucleotides

Oxanine (Oxa, O) is one of the damaged bases produced from guanine (G) through nitrosative deamination induced by nitric oxide (NO) or nitrous acid (HNO2). Large‐scale preparation of Oxa‐containing oligodeoxynucleotide (Oxa‐ODN) with the desired base sequence is a prerequisite for exploring detailed properties of Oxa in DNA. This can be accomplished by incubation of G nucleosides with NaNO2 in acetic acid buffer (pH 3.5) to produce Oxa nucleosides (e.g., 2′‐deoxyoxanosine or dOxo), conversion of dOxo to DMT‐dOxo‐amidite by tritylation and conventional phosphoramidation, and subsequent synthesis of Oxa‐ODN. The presence of Oxa in the synthetic ODN is confirmed by enzymatic digestion. Oxa‐ODN is useful for analyzing the biochemical and biophysical properties of Oxa in DNA, which is believed to be involved in NO‐induced genotoxicity and cytotoxicity. In addition, since Oxa possesses the carbodiimide‐activated carboxylate function (O‐acylisourea structure), Oxa‐ODN can be used as a functional DNA oligomer that makes covalent cross‐linkages with amine or amine‐containing biomolecules and amine‐modified solid surfaces. Curr. Protoc. Nucleic Acid Chem. 41:4.39. 1‐4.39. 20. © 2010 by John Wiley & Sons, Inc.
Preventable Incidence and Mortality of Carcinoma Associated With Lifestyle Factors Among White Adults in the United States.

IMPORTANCE Lifestyle factors are important for cancer development. However, a recent study has been interpreted to suggest that random mutations during stem cell divisions are the major contributor to human cancer. OBJECTIVE To estimate the proportion of cases and deaths of carcinoma (all cancers except skin, brain, lymphatic, hematologic, and nonfatal prostate malignancies) among whites in the United States that can be potentially prevented by lifestyle modification. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study analyzes cancer and lifestyle data from the Nurses' Health Study, the Health Professionals Follow-up Study, and US national cancer statistics to evaluate associations between lifestyle and cancer incidence and mortality. EXPOSURES A healthy lifestyle pattern was defined as never or past smoking (pack-years <5), no or moderate alcohol drinking (≤1 drink/d for women, ≤2 drinks/d for men), BMI of at least 18.5 but lower than 27.5, and weekly aerobic physical activity of at least 75 vigorous-intensity or 150 moderate-intensity minutes. Participants meeting all 4 of these criteria made up the low-risk group; all others, the high-risk group. MAIN OUTCOMES AND MEASURES We calculated the population-attributable risk (PAR) by comparing incidence and mortality of total and major individual carcinomas between the low- and high-risk groups. We further assessed the PAR at the national scale by comparing the low-risk group with the US population. RESULTS A total of 89 571 women and 46 339 men from 2 cohorts were included in the study: 16 531 women and 11 731 men had a healthy lifestyle pattern (low-risk group), and the remaining 73 040 women and 34 608 men made up the high-risk group. Within the 2 cohorts, the PARs for incidence and mortality of total carcinoma were 25% and 48% in women, and 33% and 44% in men, respectively. For individual cancers, the respective PARs in women and men were 82% and 78% for lung, 29% and 20% for colon and rectum, 30% and 29% for pancreas, and 36% and 44% for bladder. Similar estimates were obtained for mortality. The PARs were 4% and 12% for breast cancer incidence and mortality, and 21% for fatal prostate cancer. Substantially higher PARs were obtained when the low-risk group was compared with the US population. For example, the PARs in women and men were 41% and 63% for incidence of total carcinoma, and 60% and 59% for colorectal cancer, respectively. CONCLUSIONS AND RELEVANCE A substantial cancer burden may be prevented through lifestyle modification. Primary prevention should remain a priority for cancer control.