Miracle-dz/UniFAR-FTUs huggingface dataset:
Erythrocyte membrane acetylcholinesterase activity in subjects with MTHFR 677C→T genotype

Abstract Background: Increased homocysteine (Hcy) blood levels are correlated with vascular and neurological problems. Aim: The aim of the present study was to investigate erythrocyte membrane acetylcholinesterase (AChE) activity in subjects with the MTHFR C677T genotype in relation to Hcy. Methods: Blood was obtained from 22 individuals with the MTHFR C677T genotype before and after folic acid supplementation and once from controls (n=30). Plasma folate, vitamin B12 and total antioxidant status (TAS) were measured with commercial kits, Hcy by a HPLC method and membrane enzyme activity spectrophotometrically. Results: In MTHFR C677T carriers, AChE activity was significantly higher (4.20±0.12 × mg protein) and decreased to normal levels (3.14±0.10 × mg protein; p<0.001) after therapy. TAS differed slightly before and after treatment. Hcy levels were significantly higher before (22.4±2.8μM) compared to after (12.1±2.0μM; p<0.001) therapy and compared to controls (10.5±2.5μmol/L; p<0.001). In an in vitro study, incubation of Hcy-activated membrane AChE from controls with phenylalanine resulted in restoration of activity, but failed to reverse the stimulated enzyme from hyperhomocysteinaemic MTHFR C677T subjects before therapy. Alanine incubation protected the enzyme from Hcy activation in controls. Conclusions: Increased membrane AChE activity may be due to high Hcy levels. In vitro, phenylalanine reversed the Hcy activation of the membrane enzyme from controls and alanine protected it from Hcy action.
Ebf1-mediated down-regulation of Id2 and Id3 is essential for specification of the B cell lineage

Gene knockout experiments in mice have suggested a hierarchical model of early B cell commitment wherein E2A proteins (E47 and E12) activate early B cell factor (Ebf1), which in turn activates expression of the B cell commitment factor, Pax5. In IL-7 receptor alpha (IL-7Rα) knockout mice, B cell development is blocked before B-lineage commitment at the prepro-B cell stage in adult animals. In IL-7Rα−/− prepro-B cells, E47 is expressed and yet is insufficient to transcriptionally activate the putative downstream target gene, Ebf1. In this study, we show that further increases of E47 expression in IL-7Rα−/− prepro-B cells fails to activate Ebf1, but rather leads to a dramatic induction of the E2A inhibitory factors, Id2 and Id3. In contrast, enforced expression of Ebf1 in IL-7Rα−/− bone marrow potently down-regulates Id2 and Id3 mRNA expression and restores B cell differentiation in vivo. Down-regulation of both Id2 and Id3 during B cell specification is essential in that overexpression of either Id2 or Id3 in wild-type bone marrow blocks B cell specification at the prepro-B cell stage. Collectively, these studies suggest a model where Ebf1 induction specifies the B cell fate by dramatically increasing activity of E47 at the posttranslational level.
Microvessel and Lymphatic Vessel Density and VEGFR-3 Expression of Papillary Thyroid Carcinoma with Comparative Analysis of Clinicopathological Characteristics

Background : This study was done to see if there were correlations between anatomic and molecular parameters such as microvessel density (MVD), lymphatic vessel density (LVD), and vascular endothelial growth factor receptor (VEGFR)-3 expression and various clinical parameters for papillary thyroid carcinomas of size > 1.0 cm (PTCs) and size ≤ 1.0 cm (papillary thyroid microcarcinomas, PTMCs). PTMCs were divided into two subgroups (0-5 mm and 6-10 mm). Methods : We analyzed 197 thyroid carcinomas including 113 PTCs and 84 PTMCs. Tissue samples form 30 patients from each group matched for clinical characteristics were selected for immunostaining. Results : Although PTCs and PTMCs showed significant differences in clinical characteristics, they did not show significant difference in MVD, LVD, or VEGFR-3 expression. There was a significantly higher LVD in the PTMC subgroup with the larger tumors but no difference in clinical characteristics. LVD was higher in patients > 45 years old (more apparent in the PTC group) and LVD had suggestive correlations with multicentricity and extrathyroidal extension depending on analytic conditions. Conclusions : Since LVD showed variable correlations with clinical variables for papillary carcinoma of the thyroid depending on analytic conditions, the individually planned treatments based on overall clinicopathological factors are advised.
The absolute bioavailability and metabolic disposition of the novel antimigraine compound zolmitriptan (311C90).

AIMS Two open studies in healthy volunteers were conducted to determine the absolute bioavailability and metabolic disposition of zolmitriptan (311C90), a novel 5HT1D agonist for the acute treatment of migraine. METHODS After an initial test i.v. infusion, bioavailability was assessed by comparison of AUC after an i.v. infusion (3.5 mg) and an oral tablet (10 mg), in six men and six women using a randomised, crossover design. Disposition was studied by administration of a 25 mg capsule, labelled with 100 microCi [14C]-zolmitriptan, to five men and one woman on a single occasion. RESULTS Zolmitriptan was well tolerated by both i.v. and oral routes. Adverse events were mostly mild, consistent with earlier studies and characteristic of this class of drug. Reports were similar in nature and number after both oral and i.v. dosing. Mean +/- s.d. oral bioavailability was 0.49 +/- 0.24 (0.38 +/- 0.16 in men and 0.60 +/- 0.28 in women). After oral dosing, Cmax and AUC values in women were approximately double those in men. Relative to zolmitriptan concentrations, metabolite concentrations were higher after oral dosing than after i.v. , and higher in men compared with women. Half-life was significantly longer after oral dosing (mean 22%, 95% CI 6-35%). Mean +/- s.d. values for CL, V2 and t1/2,z after i.v. dosing (all subjects) were 8.7 +/- 1.7 ml min-1 kg-1, 122 +/- 321 and 2.30 +/- 0.59 h respectively. Following administration of 25 mg [14C]-zolmitriptan, 91.5% of the dose was recovered in 7 days, 64.4 +/- 6.5% in urine and 27.1 +/- 6.0% in faeces. Less than 10% was recovered unchanged in urine, with 31.1 +/- 6.4% recovered as the inactive indole acetic acid metabolite. Most of the faecal material was unchanged zolmitriptan, representing unabsorbed drug. Plasma concentrations of [14C] were slightly higher than those of the summed concentrations of known analytes zolmitriptan, the active N-desmethyl metabolite (183C91), the inactive N-oxide (1652W92) and indole acetic acid (2161W92) metabolites, which accounted for 86% of total plasma radioactivity. No other significant metabolites were detected in plasma. Some minor additional metabolites were detected in urine, none of which contributed more than 5% of the dose. CONCLUSIONS The data suggest that zolmitriptan undergoes first-pass metabolism and this is more extensive in men than in women. Zolmitriptan has suitable bioavailability for an acute oral migraine treatment and there are no significant unidentified metabolites in man.
Natural Killer Cells: Biology, Physiology and Medicine – Part 1

In this issue, as well as in the next issue of the Journal of Innate Immunity, a series of review articles on NK cells is published, summarizing some of the recent research activities within this growing field of research. Several leading scientists have made seminal contributions to the two issues. In the first issue (Vol. 3, Issue 3, 2011), a series of reviews relating to the molecular specificity of NK cells, including studies of their receptors and receptor signaling, is presented. These are followed by a series of reviews that discuss NK cell interactions with other immune cells and NK cell responses to infections. In the second issue (Vol. 3, Issue 4, 2011), we will publish reviews relating to the life span of NK cells, their development, differentiation and senescence. NK cell interactions with tumor cells will also be reviewed, as well as new insights into hematopoietic stem cell transplantations where NK cells may contribute to tumor eradication. Finally, two reviews will cover the role of NK cells in organ transplant rejection and in an inflammatory disease setting. The first review in this series of articles is an update on the molecular mechanisms for NK cell activation. With an array of activating and inhibitory receptors, Bryceson et al. [11] describe how NK cells upon target cell engagement can specifically get activated to eradicate infected and transformed cells. Likewise, it is described how similar receptors control the production of chemokines and cytokines, fulfilling important tasks in conIn the beginning of the 1970s, a number of groups observed unexpected spontaneous cytotoxic activities among lymphocytes. While at first considered as ‘annoying’ background phenomena, subsequent studies led to the realization that a new subpopulation of lymphocytes could be linked to this activity [1, 2] . The cells were termed ‘natural killer’ or, briefly, ‘NK’ cells [2] . Studies of these cells initially engaged a rather small community of scientists, who often had to fight for their existence among other fellow immunologist, many of whom were studying the more ‘sophisticated’ adaptive immune cells – the T cells and B cells. However, growing insights into the molecular specificity of NK cells [3–5] , and insights into their role in controlling virus and intracellular bacteria infections, certain tumors and their ability to regulate other immune cells, hence affecting complex diseases such as autoimmune and hypersensitivity conditions, have put NK cells in the front seat of modern immunology [6] . New insights are rapidly attributing new features to the cells, e.g. a possible role in controlling T-cell and macrophage homeostasis [7] and possibilities to use them in therapeutic settings of cancer [8] . Furthermore, the recent identification of adaptive immune cell features of NK cells is a ‘hot topic’ at the moment [9] . Studies of NK cells now engage a large community of scientists, working in diverse areas of NK cell research, in experimental model systems as well as in humans [10] . Published online: March 29, 2011 Journal of Innate Immunity
Is forceps more useful than visualization for measurement of colon polyp size?

AIM To identify whether the forceps estimation is more useful than visual estimation in the measurement of colon polyp size. METHODS We recorded colonoscopy video clips that included scenes visualizing the polyp and scenes using open biopsy forceps in association with the polyp, which were used for an exam. A total of 40 endoscopists from the Busan Ulsan Gyeongnam Intestinal Study Group Society (BIGS) participated in this study. Participants watched 40 pairs of video clips of the scenes for visual estimation and forceps estimation, and wrote down the estimated polyp size on the exam paper. When analyzing the results of the exam, we assessed inter-observer differences, diagnostic accuracy, and error range in the measurement of the polyp size. RESULTS The overall intra-class correlation coefficients (ICC) of inter-observer agreement for forceps estimation and visual estimation were 0.804 (95%CI: 0.731-0.873, P < 0.001) and 0.743 (95%CI: 0.656-0.828, P < 0.001), respectively. The ICCs of each group for forceps estimation were higher than those for visual estimation (Beginner group, 0.761 vs 0.693; Expert group, 0.887 vs 0.840, respectively). The overall diagnostic accuracy for visual estimation was 0.639 and for forceps estimation was 0.754 (P < 0.001). In the beginner group and the expert group, the diagnostic accuracy for the forceps estimation was significantly higher than that of the visual estimation (Beginner group, 0.734 vs 0.613, P < 0.001; Expert group, 0.784 vs 0.680, P < 0.001, respectively). The overall error range for visual estimation and forceps estimation were 1.48 ± 1.18 and 1.20 ± 1.10, respectively (P < 0.001). The error ranges of each group for forceps estimation were significantly smaller than those for visual estimation (Beginner group, 1.38 ± 1.08 vs 1.68 ± 1.30, P < 0.001; Expert group, 1.12 ± 1.11 vs 1.42 ± 1.11, P < 0.001, respectively). CONCLUSION Application of the open biopsy forceps method when measuring colon polyp size could help reduce inter-observer differences and error rates.
Measuring the oxidation–reduction potential of important oxidants in drinking water

Oxidation–reduction (redox) reactions can affect drinking water treatment and distribution in significant ways. Measurements of oxidation–reduction potential (ORP) in water reflect the tendency of major constituents in the water to accept or lose electrons. Although ORP measurements are valuable and can provide useful information toward protecting public health, they are not widely undertaken by the drinking water community for a variety of reasons. The objective of this research was to determine the effect of five oxidants commonly used in drinking water treatment as well as the effect of pH on measured ORP. Results showed that the ORP of each oxidant system increased with increasing oxidant concentration to a maximum. The ORP also decreased with increasing pH. Water treated with chlorine and chlorine dioxide had the greatest ORP followed by water containing monochloramine and permanganate and water containing only oxygen. Duplicate ORP measurements revealed some inconsistencies with redox electrode measurements.
Metabolism of N-substituted 7-methoxy-4-(aminomethyl) -coumarins by cytochrome P450 2D6 mutants and the indication of additional substrate interaction points

Previous studies have shown the critical roles residues F120 and F483 play in the oxidative metabolism of 7-methoxy-4-(aminomethyl)-coumarin (MAMC) by cytochrome P450 2D6 (CYP2D6). In the present study, a series of N-alkyl-7-methoxy-4-(aminomethyl)-coumarins (MAMC analogues) were used as substrates for the F120A and F483A mutants in order to probe the CYP2D6 active site. The F120A and F483A mutants of CYP2D6 displayed significant activity towards the MAMC analogues. Automated docking studies of the MAMC analogues in a CYP2D6 homology model suggested a distal hydrophobic active site binding cleft for the substrate N-alkyl chains, consisting of the residues L213 and V308.
Aortic stiffness is an indicator of cognitive dysfunction before and after aortic valve replacement for aortic stenosis.

OBJECTIVES Post-cardiac surgical cognitive dysfunction occurs more commonly following valvular procedures. Cognitive function has been related to vascular health status; however, the relation between pre-existent arterial stiffness and perioperative cognitive dysfunction is yet to be defined. The objective of this study was to assess whether aortic stiffness is related to cognitive dysfunction in surgical aortic stenosis (AS) pre- and postoperatively. METHODS Between June 2010 and August 2012, patients undergoing aortic valve replacement (AVR) for AS were recruited for inclusion in this prospective observational study. Aortic pulse wave velocity (PWV) was used as a measure of aortic stiffness and cognitive function was assessed using the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB) preoperatively and (409 ± 159 days) post-AVR. RESULTS Fifty-six patients (age 71 ± 8.4 years) were recruited. Of the total, 50 (89%) completed postoperative follow-up. Pre- and postoperatively, patients with normal PWV (PWV-norm) had significantly superior delayed memory, sustained visual attention and executive function compared with those with high PWV (PWV-high). Immediate memory and decision-making were similar between groups. Postoperatively, improvement in cognitive function was more marked in PWV-high compared with PWV-norm patients. In two models of multiple regression analysis, PWV as a continuous variable was independently related to all preoperative main cognitive components as well as postoperative executive function. PWV as a dichotomous variable was independently related to all pre- and postoperative main cognitive function components. CONCLUSIONS AVR may not be associated with an independent or homogeneous effect on cognitive decline. Aortic PWV might be useful as an additional indicator for cognitive dysfunction before and after surgical intervention for AS.
Field scale evaluation of seasonal wastewater treatment efficiencies of free surface-constructed wetlands in ICRISAT, India

The disparity between volume of wastewater generated and treated has resulted in severe water pollution and eutrophication of the water bodies in most Indian cities. Constructed wetlands (CWs) present a low-cost wastewater treatment option; however, field scale studies with real life wastewater are limited. Eichhornia crassipes (water hyacinth), Typha latifolia (Typha) and Pistia stratiotes (water lettuce) grow abundantly in eutrophicated water bodies, and are known for their nutrient uptake ability. In the present study, the wastewater of a nearby urban residential colony was treated by two-field scale free water surface CWs operating under identical hydraulic loading. The first treatment cells, in each of these two CWs were vegetated with Typha. The second treatment cells were vegetated with water hyacinth (CW-1) in one of the CWs and with water lettuce (CW-2) in the other. Wastewater treatment efficiencies of these free water surface CWs were evaluated, in terms of the removal efficiencies for key parameters, viz. chemical oxygen demand (COD), ammoniacal and nitrate nitrogen, phosphate, sulphate and total suspended solids (TSS). The CW-1 showed greater seasonal variation in performance. A steady removal efficiency of 35–40% was observed for ammoniacal nitrogen in both the free water surface CWs throughout the year, though removal efficiency of nitrate nitrogen reduced significantly during the winter. Plant sample analysis showed that the N, P and K uptake capacities of water lettuce were 1.53, 1.55 and 1.34 times higher than that of water hyacinth, for identical wastewater loading. The dry weight of the harvested biomass for water lettuce, during summer months, was much higher at 5.63 g/m2/d compared to 3.8 g/m2/d for water hyacinth.
Colchicine Overdose-Induced Acute Renal Failure and Electrolyte Imbalance

Colchicine has been used to control gouty arthritis for long time; colchicine overdose, however, causes multiple organ dysfunction. To date, no investigation has revealed the site of kidney lesion or dysfunction. This investigation describes the case of a male with a history of gout who ingested a large amount of colchicine and developed renal, hematopoietic, gastrointestinal, muscular, electrolytic, and hepatic disorder. Glucosuria was noted during hospital days. Colchicine intoxication is shown to induce proximal tubule damage. Severe electrolytes imbalance was noted, including hypomagnesemia, hypophosphatemia, and hypocalcemia. After management, the renal function and serum electrolyte of the patient recovered on the sixth day of hospitalization.
Expression of transforming growth factor-beta receptor type II and tumorigenicity in human breast adenocarcinoma MCF-7 cells.

To analyze transforming growth factor-beta (TGF-beta) response during MCF-7 cell progression, early passage (MCF-7E, < 200 passage) and late passage (MCF-7L, > 500 passage) cells were compared. MCF-7E cells showed an IC50 of approximately 10 ng/ml of TGF-beta1, whereas MCF-7L cells were insensitive. MCF-7E cells contained approximately threefold higher levels of TGF-beta receptor type II (TbetaRII) mRNA than MCF-7L, but their TbetaRI levels were similar. MCF-7E parental cells showed higher TbetaRII promoter activity than MCF-7L cells, which could be attributed to changes in Sp1 nuclear protein levels. Receptor cross-linking studies indicated that the cell surface receptor levels parallel mRNA levels in both cell lines. Limiting dilution clones of MCF-7E cells were established to determine the heterogeneity of TbetaRII expression in this cell line, and they showed varying degrees of TbetaRII expression. Fibronectin was induced at higher levels in cells expressing higher TbetaRII levels. All three TGF-beta isoforms were detected in limiting dilution clones and parental cells, but TGF-beta1 was more abundant relative to TGF-beta2 or 3, and no correlation between TGF-beta isoform profile with TGF-beta sensitivity was found. MCF-7L cells were tumorigenic and formed xenografts rapidly and progressively, whereas MCF-7E parental and limiting dilution clonal cells showed transient tumor formation followed by regression. These results indicate that decreased TbetaRII transcription in breast cancer cells leads to a loss of TbetaRII expression, resulting in cellular resistance to TGF-beta which contributes to escape from negative growth regulation and tumor progression.
EFFECT OF PHYTASE ENZYME SUPPLEMENTATION IN DEFICIENT PHOSPHATE DIET ON BROILER PERFORMANCE AND SOME BLOOD TRAITS

The experiment was conducted to determine the effect of microbial phytase in Ca deficient and available aP diets on broiler performance and some blood traits. Three hundred day-old chicks (Ross 308) were distributed into five equal groups with two replicates. The control diets (T 1) contained Corn-SBM, 0.9% Ca and 0.40% aP without enzyme, whereas T2, T3, T4 and T5 contained Corn-SBM, 0.60% Ca and 0.30% aP+1000 phytase/ kg; T2+ 2000 phytase /kg; Corn-SBM, 0.30% Ca and 0.20% aP + 1000 phytase /kg; T4 + 2000 phytase/ kg respectively. All diets were formulated to be iso -caloric (3150 kcal/ kg) and iso-nitrogenous (20.2%). Supplemented diets with 2000 units phytase kg resulted in a significant decrease in feed consumption (P  0.05) with the lowest for (T 5), while no significant effects on weight gain, carcass dressing, carcass cuts, and Giblets. In addition, none of the biochemical and hematological parameters tested differed significantly for all treatments (P  0.05). Phytase supplementation to diets did not influence calcium, phosphorus, and iron contents with no detrimental impact on blood parameters of broiler chick s.
Why Do Racial Slurs Remain Prevalent in the Workplace? Integrating Theory on Intergroup Behavior

Racial slurs are prevalent in organizations; however, the social context in which racial slurs are exchanged remains poorly understood. To address this limitation, we integrate three intergroup theories (social dominance, gendered prejudice, and social identity) and complement the traditional emphasis on aggressors and targets with an emphasis on observers. In three studies, we test two primary expectations: (1) when racial slurs are exchanged, whites will act in a manner more consistent with social dominance than blacks; and (2) this difference will be greater for white and black men than for white and black women. In a survey ( n = 471), we show that whites are less likely to be targets of racial slurs and are more likely to target blacks than blacks are to target them. We also show that the difference between white and black men is greater than the difference between white and black women. In an archival study that spans five years ( n = 2,480), we found that white men are more likely to observe racial slurs than are black men, and that the difference between white and black men is greater than the difference between white and black women. In a behavioral study ( n = 133), analyses showed that whites who observe racial slurs are more likely to remain silent than blacks who observe slurs. We also find that social dominance orientation (SDO) predicts observer silence and that racial identification enhances the effect of race on SDO for men, but not for women. Further, mediated moderation analyses show that SDO mediates the effect of the interaction between race, gender, and racial identification on observer silence.