Miracle-dz/UniFAR-FTUs huggingface dataset:
Growth Factor-induced Phosphorylation and Activation of Aortic Smooth Muscle Na+/Ca2+Exchanger (*)

Although the Na+/Ca2+exchanger is one of the major Ca2+extrusion systems in excitable tissues, little is known about its regulation via protein phosphorylation. We now present evidence that the Na+/Ca2+exchanger is phosphorylated in quiescent and growth factor-stimulated cultured aortic smooth muscle cells. The Na+/Ca2+exchanger was isolated from 32P-labeled cells by immunoprecipitation with a specific polyclonal antibody. Phosphorylation of the exchanger was increased by up to 1.7-fold in response to platelet-derived growth factor-BB (PDGF-BB), α-thrombin, or phorbol 12-myristate 13-acetate (PMA). However, angiotensin II did not enhance the phosphorylation significantly. The extent of phosphorylation appeared to correlate with the growth factor-induced increase in cell 1,2-diacylglycerol. At least four phosphopeptides (P1 to P4) were detected by tryptic phosphopeptide map analysis of the phosphorylated exchanger, suggesting that phosphorylation occurred at multiple sites. PDGF-BB and PMA increased phosphorylation of the same phosphopeptides (in particular P1). Phosphorylated amino acids were exclusively serine residues in both quiescent and stimulated cells. We found that growth factors enhanced Na+/Ca2+exchange activity and that there was a good correlation between the growth factor-induced stimulations of phosphorylation and exchange activity. PDGF-BB-induced activation of the exchanger was abolished by prior long treatment of cells with PMA. These results suggest that the Na+/Ca2+exchanger is activated by protein kinase C-dependent phosphorylation in response to growth factors in vascular smooth muscle cells.
An ecotoxicological characterization of nanocrystalline cellulose (NCC)

Abstract The pulp and paper industry in Canada is developing technology for the production and use of nanocrystalline cellulose (NCC). A key component of the developmental work is an assessment of potential environmental risks. Towards this goal, NCC samples as well as carboxyl methyl cellulose (CMC), a surrogate of the parent cellulosic material, were subjected to an ecotoxicological evaluation. This involved toxicity tests with rainbow trout hepatocytes and nine aquatic species. The hepatocytes were most sensitive (EC20s between 10 and 200 mg/l) to NCC, although neither NCC nor CMC caused genotoxicity. In tests with the nine species, NCC affected the reproduction of the fathead minnow at (IC25) 0.29 g/l, but no other effects on endpoints such as survival and growth occurred in the other species at concentrations below 1 g/l, which was comparable to CMC. Based on this ecotoxicological characterization, NCC was found to have low toxicity potential and environmental risk.
The Role of TP 53 in Cervical Carcinogenesis

Functional loss of the tumor suppressor p53 by alterations in its TP53 gene is a frequent event in cancers of different anatomical regions. Cervical cancer is strongly linked to infection by high-risk human papillomavirus (HPV) types. The viral oncoprotein E6 has the ability to associate with and neutralize the function of p53. E6 interacts with a 100-kDa cellular protein, termed E6 associated protein (E6AP; also called ubiquitin-protein ligase E3A or UBE3A), which functions as an ubiquitin protein ligase. The dimeric complex then binds p53 and E6AP catalyzes multi-ubiquitination and degradation of p53. The ability to promote p53 degradation is an exclusive property of E6 from the high-risk HPV types. Indeed, the low-risk E6 proteins lack this activity, although they can bind p53. Consistent with the E6 function of the high-risk HPV types, the majority of cervical cancer cells have a wild-type p53 gene, but the protein levels are strongly decreased. Several independent studies have shown that in a small percentage of cervical tumors the p53 gene is mutated. However, this event appears to be unrelated to the presence or absence of HPV infection and the nature of the tumor. Hum Mutat 21:307–312, 2003. r 2003 WileyLiss, Inc.
Nutrigenetics in the Light of Human Evolution

Bio-cultural adaptations to new foods played a key role in human evolution. The fossil record and sequence differences between human and chimpanzee genes point to a major dietary shift at the stem of human evolution. The earliest representatives of the human lineage diverged from the ancestors of chimpanzees because of their better adaptation to hard and abrasive foods. Bipedalism and modifications of the hand, which allowed tool manufacture and use, impacted on dietary flexibility, facilitating access to foods of animal origin. This promoted major anatomic, physiologic and metabolic adaptations. Encephalization, which requires high-quality diet, characterizes the evolutionary sequence that, through the Homo ergaster/erectus stages, led to our species, Homo sapiens, which originated in Africa about 200,000 years ago. At the end of the Ice Age, climatic changes and human impact determined a major food crisis, which triggered the agricultural revolution. This affected nutrition and health, with rapid evolutionary adaptations through the selection of genetic variants that allowed better utilization of new foods, different in relation to geography and culture. Today population growth, globalization and economic pressure powerfully affect diets worldwide. We must take into account our evolutionary past to meet the present nutritional challenges.
Prognostic Significance of the Location of Lymph Node Metastases in Patients With Adenocarcinoma of the Distal Esophagus or Gastroesophageal Junction

Objective: To identify the prognostic significance of the location of lymph node metastases in patients with esophageal or gastroesophageal junction (GEJ) adenocarcinoma treated with neoadjuvant therapy followed by esophagectomy. Background: Detection of lymph node metastases in the upper mediastinum and around the celiac trunk after neoadjuvant therapy and resection does not alter the TNM classification of esophageal carcinoma. The impact of these distant lymph node metastases on survival remains unclear. Methods: Between March 2003 and September 2013, 479 consecutive patients with adenocarcinoma of the distal esophagus or GEJ who underwent transthoracic esophagectomy with en bloc 2-field lymphadenectomy after neoadjuvant therapy were included, and survival was analyzed according to the location of positive lymph nodes in the resection specimen. Results: Two hundred fifty-three patients had nodal metastases in the resection specimen. Of these patients, 92 patients had metastases in locoregional nodes, 114 patients in truncal nodes, 21 patients in the proximal field of the chest, and 26 patients had both positive truncal and proximal field nodes. Median disease-free survival was 170 months in the absence of nodal metastases, 35 months for metastases limited to locoregional nodes, 16 months for positive truncal nodes, 15 months for positive nodes in the proximal field, and 8 months for nodal metastases in both truncal and the proximal field. On multivariate analysis, location of lymph node metastases was independently associated with survival. Conclusions: Location of lymph node metastases is an independent predictor for survival. Relatively distant lymph node metastases along the celiac axis and/or the proximal field have a negative impact on survival. Location of lymph node metastases should therefore be considered in future staging systems of esophageal and GEJ adenocarcinoma.
The origin of 1H NMR-visible triacylglycerol in human neutrophils. Highfatty acid environments result in preferential sequestration of palmitic acid into plasma membrane triacylglycerol.

Human neutrophils incubated for 1 h in vitro with 10% commercial pooled, human serum containing high levels of free fatty acids (1141 microM) displayed a distinct lipid signal, typical of triacylglycerol, in the 1H NMR spectrum. Concurrently their plasma membrane triacylglycerol mass increased 4.6-fold with a selective rise in the content of palmitic and linoleic acids. Although qualitatively similar, these effects were much greater than those observed after incubating neutrophils with 50 microg.mL-1 of lipopolysaccharide in the presence of 10% AB serum with normal free fatty acid content (345 microM, LPS/S). Incubation of neutrophils with an artificial mixture of free fatty acids at concentrations found in commercial serum, or with the fatty acid fraction isolated from commercial serum increased the 1H NMR-detectable triacylglycerol. The signal intensity of the 1H NMR-detectable triacylglycerol depended on the triacylglycerol composition, and correlated with increased membrane triacylglycerol mass. Cellular uptake of 3H-labelled palmitic or oleic acids increased in the presence of commercial serum but not with LPS/S, with little contribution in either case to the triacylglycerol pool that increased in mass. Pulse-chase experiments demonstrated that with LPS/S and commercial serum, radiolabelled palmitic acid was preferentially incorporated into triacylglycerol located in the plasma membrane. This process could occur at the plasma membrane, as cytoplasts efficiently convert exogenous fatty acids into triacylglycerol. We propose that LPS/S and serum containing high levels of free fatty acid, important in conditions of sepsis and inflammation, may facilitate the sequestration of palmitic acid into triacylglycerol by different pathways. This triacylglycerol originates from exogenous and endogenous free fatty acids, is 1H NMR-visible, and may have a role in regulating apoptosis.
Bupivacaine Induces Apoptosis via ROS in the Schwann Cell Line

Local anesthetics have been generally accepted as being safe. However, recent clinical trials and basic studies have provided strong evidence for the neurotoxicity of local anesthetics, especially through apoptosis. We hypothesized that local anesthetics cause neural complications through Schwann cell apoptosis. Among local anesthetics tested on the Schwann cell line, RT4-D6P2T, bupivacaine significantly induced cell death, measured by the methyl tetrazolium (MTT) assay, in a dose- (LD50 = 476 μM) and time-dependent manner. The bupivacaine-induced generation of reactive oxygen species (ROS), which was initiated within 5 hrs and preceded the activation of caspase-3 and poly ADP-ribose polymerase (PARP) degradation, was suggested to trigger apoptosis, exhibited by Hoechst 33258 nuclear staining and DNA fragmentation. Furthermore, concomitant block of ROS by anti-oxidants significantly inhibited bupivacaine-induced apoptosis. Among the local anesthetics for peripheral neural blocks, bupivacaine induced apoptosis in the Schwann cell line, which may be associated with ROS production.
Percutaneous treatment of hydatid cysts of the liver: long-term results.

OBJECTIVE The purpose of the study was to present the long-term results of percutaneous treatment of liver hydatid cysts. SUBJECTS AND METHODS Seventy-two patients (44 male and 28 female, ranging in age between 10 and 69 years; mean age, 35 years) with 106 liver hydatid cysts underwent percutaneous treatment with albendazole prophylaxis. Puncture, aspiration, injection, and reaspiration (PAIR) were used for hydatid cysts smaller than 6 cm (n = 66). Larger cysts (n = 40) were treated by catheterization. Hypertonic saline solution and absolute alcohol were used as the cytotoxic and sclerosing agents. Sonographic guidance with or without fluoroscopy was used in all patients. Follow-up was mainly by sonography every third month of the first year, every sixth month of the second year, and once a year thereafter. The mean follow-up time was 37 months. RESULTS The mean reduction in volume at the time of the first follow-up was 87.0% and 73.5% in catheterization and PAIR patients, respectively. The immediate sonographic changes after treatment were detachment of the endocyst and disappearance of the regular endocyst, with a reduction in the fluid component. The solid appearance of the cyst remnant indicated complete cure as the cyst wall became irregular and thicker. The average time for development of a solid appearance was 19 months in PAIR patients and 26 months in catheterization patients. Seventy of 72 patients were cured, whereas two recurrences (2.8%) were observed. No mortality, abdominal dissemination, or tract seeding occurred. Minor complications were urticaria and fever in eight patients (11.1%). Major complications were infection of the cyst cavity in two patients (2.8%) and development of biliary fistula in four patients (5.6%). Mean hospitalization times were 17 days for complicated cases and I day for uncomplicated cases. CONCLUSION The long-term results of percutaneous liver hydatid cyst treatment accord with short-term results, indicating that the procedure is efficient and safe and offers complete cure in selected patients with a short hospitalization.
Isolation, identification and characterization of feather degrading bacteria

The present study deals with isolation, identification and characterization of feather degrading bacterium. The keratinolytic bacteria were isolated from feather dumped soil. The colonies showed higher keratinase production was identified as Bacillius sp, as per Bergey’s manual method. Keratinase producing Bacillus sp, showed higher enzymes production. The crude filtrate showed specific activity of (>2.825)IU/mg and the protein of 4 mg/ml. Bacillus sp, produced keratinase at the pH 7 – 7.5 at the temperature of 40°C 2% feather meal as a substrate and incubation time of 96 hrs respectively which indicated that the crude keratinase enzyme produce by Bacillus sp was classified as an alkaline protease. The protein profile of Bacillus sp was analyzed in SDS – PAGE. It showed that the presence of single band which corresponds to keratinase activity. FTIR Fourier Transform Infra red Spectroscopy showed that the change in the functional group was catalyzed by unique enzymes of Bacillus sp. The keratin degrading gene sequence of isolated Bacillus sp, was analysed further studies.
Improving the Light-Load Regulation Capability of LLC Series Resonant Converter Using Impedance Analysis

Generally, an LLC series resonant converter (LLC SRC) is an attractive topology for applications, which require wide input variation and high conversion efficiency because of its wide gain capability and soft-switching capability. However, there is a regulation problem in which the output voltage increases as the load current decreases. In this paper, Bode plot and impedance asymptote analysis were conducted to obtain an intuitive sense of the regulation characteristic of LLC SRC under the light-load condition. Moreover, to improve the regulation capability, a new resonant tank with an additional capacitor is proposed. Its design guidelines were determined by Bode plot and impedance asymptote analysis. Therefore, the proposed LLC SRC achieves very light load regulation, while it maintains the advantages of typical LLC SRCs.
2 . State of validation of biomarkers of carcinogen exposure and effect 2 . 1 . Generic biomarkers 2

Dose–response for adduct formation and carcinogenesis In a review of the relationship between DNA adduct levels and tumour incidence in laboratory rodents, Poirier and Beland [1] summarised the data from experiments using 2-acetylaminofluorene, 2-aminobiphenyl, aflatoxin B1, N,N-diethylnitrosamine, or 4-(N-methyl-N-nitrosoamino)-1-(3-pyridyl)-1-butanone in a total of nine different combinations of carcinogen, species, sex and target organ. Of these combinations, there were five in which dose–response relationships for DNA adduct formation reflected those for tumorigenesis and, in these, linearity with dose for both tumours and DNA adducts appeared to be the norm at the lowest doses. In two situations, the levels of DNA adducts formed were low, presumably below the threshold for extensive tumorigenesis. In two other combinations, even though DNA adducts increased linearly with dose, tumours did not appear at the lower doses. These data suggest that when extrapolating from high doses to low doses within an animal model, the extent of DNA adduct formation will generally reflect the extent of tumorigenesis.
Human fertility decline?

To the Editor: Sallmén et al investigated bias in studying trends in the capacity to conceive given unprotected intercourse using the methodology of time-to-pregnancy (TTP) studies. They argued that without effective contraception or induced abortion, some highly fertile couples conceive accidental pregnancies, leaving a relatively subfertile subset to conceive nonaccidental, and therefore TTP-eligible, pregnancies. With rising use of effective contraception and abortion, this effect declines, and so the more recent pregnancies arise from a more fertile group; contraception or abortion now keep the most fertile couples in the “at-risk” population. We do not dispute the biases illustrated by their stylized calculations, but we disagree that the bias is “probably impossible” to investigate. Information on accidental pregnancies can, in fact, be obtained. It is standard methodology to use this information, but Sallmén and colleagues ignored this. If the proportion of accidental pregnancies does not fall over time, then logically the bias cannot be present. The standard sensitivity analysis, including accidental pregnancies in a TTP analysis with imputed TTP 1, overcompensates the bias. Bias associated with changing rates of induced abortion can also be investigated by comparing the observed trend in fertility with national data on the annual abortion rate. Furthermore, reality is much more complex than the authors’ stylized calculations. The issue is whether these underlying trends actually occur. One of the cited studies found that increasing fertility was not accompanied by a decreasing proportion of accidental pregnancies, nor was the observed trend altered by excluding TTP values of zero and one. The other TTP study cited by Sallmén and colleagues included accidental pregnancies, a practice that reverses the direction of bias, yet this study also showed increasing fertility. Couple behavior cannot simply be extrapolated from efficacy of contraception and use of legal abortion. In our 4 Danish and 2 British datasets, in the periods before 1970, 1970–1984, and after 1984, the percentages of accidental pregnancies were, respectively, 6.8%, 6.6%, and 2.9% (Denmark) and 12.5%, 11.2%, and 17.5% (Britain) (detailed data available on request). The predicted fall between the first 2 periods is not seen in the data. Finally, some small points. Why would changing family size affect analysis of first births? Changing age at first birth can be readily adjusted for statistically. TTP eligibility is based on behavior affecting biology (contraceptive practice), not a psychologic construct such as intended, planned, or wanted.
Comparing the pre- and post-impact ball and racquet kinematics of elite tennis players' first and second serves: a preliminary study

The aim of this study was to compare the pre- and post-impact three-dimensional kinematics of the ball and racquet during first and second serves performed by elite tennis players. Data were collected from four male and four female right-handed professional players during competition using two high-speed cameras (200 Hz). For each player, one first serve and one second serve from the 'deuce' or right service court that landed within the specified target area were analysed. To test for significant differences between the first and second serves, Wilcoxon tests (P⩽0.05) were performed on selected parameters. The results indicate that the ball travelled forward and to the left during the flight phase of the toss in all but one trial. The average pre-impact ball forward location for the first serve was significantly more in front and had a higher associated forward ball velocity than the corresponding values for the second serve. On average, the decrease in post-impact ball speed from the first to the second serve was 24.1%. No significant differences between the first and second serves were found in the pre-impact racquet head speed and orientation, which was represented as a unit vector perpendicular to the racquet face. The major adjustments made by the players when going from the first to second serve were a decrease in pre-impact ball forward location (P⩽0.01) and an increase in the pre-impact racquet vertical and lateral velocities (both P⩽0.05). This implies that the players tossed the ball closer to the body and imparted topspin and sidespin on the ball by changing the racquet vertical and lateral velocities when going from the first to the second serve.
Neglected Outcomes of Customer Satisfaction

Although there is significant evidence that customer satisfaction is an important driver of firm profitability, extant literature has largely neglected two intermediate outcomes of customer satisfaction, namely, a firm's advertising and promotion efficiency and its human capital performance. On the basis of longitudinal analyses of large-scale secondary data from multiple sources, the authors find that customer satisfaction boosts the efficiency of future advertising and promotion investments. This finding can be explained by the possibility that customer satisfaction generates free word-of-mouth advertising and saves subsequent marketing costs. In addition, customer satisfaction has a positive influence on a company's excellence in human capital (employee talent and manager superiority). This finding is highly novel, indicating that human resources managers should have a strong interest in customer satisfaction as well. Finally, the authors investigate the moderating influence of market concentration on both relationships. The uncovered results have important implications for marketers in their dialogue with financial executives and human resources managers.
Insulin resistance, beta-cell function, and glucose tolerance in Brazilian adolescents with obesity or risk factors for type 2 diabetes mellitus.

OBJECTIVE To evaluate insulin resistance (IR), beta-cell function, and glucose tolerance in 119 Brazilian adolescents with obesity or risk factors (RF) for type 2 diabetes mellitus (T2DM). STUDY DESIGN We analyzed weight (kg), height (m), body mass index (BMI; kg/m(2)), waist (W; cm), acanthosis nigricans (AN), systolic and diastolic blood pressure (SBP and DBP; mm Hg), fasting plasma glucose (FPG), and 2-h plasma glucose (2hPG) on oral glucose tolerance test (OGTT; 1.75 g of glucose/weight), lipid profile [total cholesterol (TC), fractions, and triglycerides (TGs)], fasting insulin (FI) and 2-h insulin on OGTT (2hI-RIA), HOMA-B (%; beta-cell function--HOMA program), HOMA-S (%; insulin sensitivity--HOMA program) and HOMA-IR [fasting plasma insulin (mU/ml)xfasting plasma glucose (mmol/L)/22.5]. Division according to number of RF-family history of T2DM (FHT2DM), obesity, hypertension, dyslipidemia, polycystic ovary syndrome (PCOS), and AN. G1: subjects with no or one RF; G2: subjects with two or more RFs. Statistical data were nonparametrical. RESULTS Fasting plasma glucose (G2: 81.6+/-10.2 vs. G1: 79.8+/-9.9 mg/dl) and 2hPG (88.1+/-18.0 vs. 87.0+/-19.9 mg/dl) were not different between G2 (n=67) and G1 (n=52), and all adolescents had normal glucose tolerance (NGT). Fasting insulin (13.0+/-7.9 vs. 7.6+/-3.9 microIU/ml; P<.001) and 2hI (60.2+/-39.1 vs. 38.3+/-40.0 microIU/ml; P<.001), HOMA-B (169.1+/-131.6% vs. 106.1+/-39.9%; P<.001), and HOMA-IR (2.62+/-1.7 vs. 1.52+/-0.8; P<.001) were higher in G2. HOMA-S (92.5+/-59.5% vs. 152.2+/-100.5%; P<.001) was also lower in this latter group. CONCLUSION Brazilian adolescents with two or more RFs for the development of T2DM have higher IR and beta-cell function and lower insulin sensitivity. However, adolescents with impaired glucose tolerance (IGT) or DM have not been found, differently from similar studies. Differences in ethnic background, environment, and lifestyle factors may account for this disparity.