Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein S Protects Neurons from Excitotoxic Injury by Activating the TAM Receptor Tyro3–Phosphatidylinositol 3-Kinase–Akt Pathway through Its Sex Hormone-Binding Globulin-Like Region

The anticoagulant factor protein S (PS) protects neurons from hypoxic/ischemic injury. However, molecular mechanisms mediating PS protection in injured neurons remain unknown. Here, we show mouse recombinant PS protects dose-dependently mouse cortical neurons from excitotoxic NMDA-mediated neuritic bead formation and apoptosis by activating the phosphatidylinositol 3-kinase (PI3K)–Akt pathway (EC50 = 26 ± 4 nm). PS stimulated phosphorylation of Bad and Mdm2, two downstream targets of Akt, which in neurons subjected to pathological overstimulation of NMDA receptors (NMDARs) increased the antiapoptotic Bcl-2 and Bcl-XL levels and reduced the proapoptotic p53 and Bax levels. Adenoviral transduction with a kinase-deficient Akt mutant (Ad.AktK179A) resulted in loss of PS-mediated neuronal protection, Akt activation, and Bad and Mdm2 phosphorylation. Using the TAM receptors tyrosine kinases Tyro3-, Axl-, and Mer-deficient neurons, we showed that PS protected neurons lacking Axl and Mer, but not Tyro3, suggesting a requirement of Tyro3 for PS-mediated protection. Consistent with these results, PS dose-dependently phosphorylated Tyro3 on neurons (EC50 = 25 ± 3 nm). In an in vivo model of NMDA-induced excitotoxic lesions in the striatum, PS dose-dependently reduced the lesion volume in control mice (EC50 = 22 ± 2 nm) and protected Axl−/− and Mer−/− transgenic mice, but not Tyro3−/− transgenic mice. Using different structural PS analogs, we demonstrated that the C terminus sex hormone-binding globulin-like (SHBG) domain of PS is critical for neuronal protection in vitro and in vivo. Thus, our data show that PS protects neurons by activating the Tyro3–PI3K–Akt pathway via its SHGB domain, suggesting potentially a novel neuroprotective approach for acute brain injury and chronic neurodegenerative disorders associated with excessive activation of NMDARs.
Mechanisms responsible for the altered pharmacokinetics of Bosentan: analysis utilizing rats with bile duct ligation‐induced liver dysfunction

The purpose of this study was to evaluate the mechanisms responsible for the pharmacokinetic variability of bosentan utilizing rats with liver dysfunction induced by 7‐day bile duct ligation (BDL). Bosentan was administered intravenously at a constant infusion rate (I) of 24, 40 or 60 µg/min/kg. The blood bosentan concentration (BBC) following infusion was measured by HPLC, and apparent clearance (CL) of the drug was estimated as I/BBC. The CL values in normal rats were 30.5 and 19.3 ml/min/kg at infusion rates of 24 and 60 µg/min/kg, respectively, suggesting non‐linear pharmacokinetics of bosentan. The BBC in BDL rats was much higher than that in normal rats, and the CL values in BDL rats were 3.80 and 3.08 ml/min/kg at infusion rates of 24 and 60 µg/min/kg, respectively. The CL value of bosentan at an infusion rate of 40 µg/min/kg in normal rats was decreased significantly by the coadministration of taurocholic acid or bilirubin. In addition, the hepatic mRNA expression of CYP2C6, CYP3A2, Oatp1a1, Oatp1a4 and Oatp1b2 in BDL rats decreased to 77.6%, 34.0%, 65.4%, 84.8% and 44.2% of that in normal rats, respectively. These results suggested that bile acids and/or bilirubin accumulated in BDL rat plasma inhibited the hepatic uptake of bosentan, and that the decreased bosentan clearance in BDL rats was caused at least partly by the impaired expression of hepatic drug‐metabolizing enzymes and uptake transporters. Moreover, because the pharmacokinetics of bosentan was non‐linear at the tested doses, the increased BBC in BDL rats might further induce the saturation of hepatic uptake and/or metabolism of bosentan. Copyright © 2009 John Wiley & Sons, Ltd.
Insight Into the Molecular Program of Meiosis

“We estimate that >2,300 genes (~4% of the mouse genome) are dedicated to male germ cellspecific transcripts, 99% of which are first expressed during or after meiosis”. This quotation from a paper published by Schultz et al. (2003), reflects the tremendous complexity of gamete production, the essence of which is meiosis. Meiosis is a differantiative process in which seemingly contradicting molecular pathways are activated simultaneously. On one hand the regular components and checkpoints of the cell division machinery, which is complex enough by itself, are utilized, but on the other hand a whole array of genes are activated to enable the unique characteristics of the meiotic division, such as partition of homologous chromosomes, and not the sister chromatides, in meiosis I, or executing cell division without a prior DNA duplication in meiosis II. On one hand double strand breaks are deliberately formed to ensure pairing of homologous chromosomes and recombination, but on the other hand a whole array of genes involved in DNA repair and safeguarding genome integrity are alerted. The meiotic complexity is also exemplified by the extensive dependence on a cross-talk between germ cells themselves, and between the differentiating germ cells and their surrounding somatic cells, i.e. Sertoli cells in the testis or granulosa cells in the ovarian follicle. Finally, the complexity of the meiotic process is depicted by the differences between males and females, regarding both the outcome of the meiotic division (four basically similar post meiotic round spermatids in the male versus one functional egg and three polar body cells that degenerate in the female), and its kinetics (a continuous process in the male versus an in-continuous process in the female). It is, therefore, absolutely crucial that the very many different molecular pathways operating during meiosis be tightly concerted and regulated. However, Virginia Hughes, in a paper published in Nature medicine (2008), stated that: “So far, scientists have identified nearly 300 DNA mutations in man with reproductive defects”, implying that our understanding of the meiotic molecular network is still very limited, although significant progress has been made since 2008.
Highly Sensitive Fetal Goat Tongue Cell Line for Detection and Isolation of Foot-and-Mouth Disease Virus

ABSTRACT A fetal goat cell line (ZZ-R 127) supplied by the Collection of Cell Lines in Veterinary Medicine of the Friedrich Loeffler Institute was examined for susceptibility to infection by foot-and-mouth disease (FMD) virus (FMDV) and by two other viruses causing clinically indistinguishable vesicular conditions, namely, the viruses of swine vesicular disease and vesicular stomatitis. Primary bovine thyroid (BTY) cells are generally the most sensitive cell culture system for FMDV detection but are problematic to produce, particularly for laboratories that infrequently perform FMD diagnostic tests and for those in countries where FMD is endemic that face problems in sourcing thyroid glands from FMD-negative calves. Strains representing all seven serotypes of FMDV could be isolated in ZZ-R 127 cells with a sensitivity that was considerably higher than that of established cell lines and within 0.5 log of that for BTY cells. The ZZ-R 127 cell line was found to be a sensitive, rapid, and convenient tool for the isolation of FMDV and a useful alternative to BTY cells for FMD diagnosis.
Advances in Brief Single Step Selection of as-Diamminedichloroplatinum ( II ) Resistant Mutants from a Human Ovarian Carcinoma Cell Line 1

We have shown that m diamminedichloroplatinum-(II) (DDP) resist ant mutants can be isolated from the human ovarian carcinoma cell line A2780 using a single-step selection protocol with DDP. DDP resistant colonies were calculated to be present at a frequency of 1.7 x 10"6/viable cell using a fluctuation analysis. The mutational origin of these surviving colonies is inferred by the fact that their frequency is increased by treatment of the A2780 cells with the chemical mutagen ethyl methanesulfonate, with a maximum frequency observed after a 3-day expression time. Independently isolated clones maintain, in the absence of selection, a DDP resistant phenotype up to 7-fold more resistant than the parental A2780 cells. The resistance modifiers aphidicolin and buthionine sulfoximine have no effect on the frequency of DDP resistant mutants. There fore neither of these drugs appears to have an effect on increasing the sensitivity of DDP resistant mutants existing in a cell population prior to DDP exposure.
Three‐dimensional demonstration of the lymphatic system in the lower extremities with multi‐detector‐row computed tomography: A study in a cadaver model

Sentinel lymph node biopsy (SLNB) has had a great impact on the staging and treatment of cancer. The purpose of this study was to study the lymphatic anatomy of the lower extremities by constructing three‐dimensional images using multi‐detector‐row computed tomography (MDCT). To select appropriate contrast media for MDCT lymphatic imaging in a cadaver, we tested four kinds of contrast media by injecting them into fresh swine kidneys. After the suitable contrast medium was selected, 10 lower extremities from 5 fresh cadavers were studied. After injection of the contrast medium, each lower extremity was scanned with high‐spatial‐resolution MDCT. The zinc oxide mixture was found to be the most appropriate contrast formula for MDCT imaging of cadaver lymphatics in terms of CT value and no extravasation. The high‐resolution MDCT imaging revealed two different superficial lymphatic pathways in the legs. One lymphatic pathway accompanying the great saphenous vein had a constant course and was connected to the superficial inguinal lymph nodes. However, another pathway, along the small saphenous vein, was variable. Some of the deep lymphatic vessels bypassed the inguinal lymph nodes. Using a new protocol, we were able to construct three‐dimensional images of the lower extremity lymphatics in a cadaver model. MDCT imaging provided novel information about two different superficial lymphatic pathways in the lower extremities. Clin. Anat. , 2013. © 2013 Wiley Periodicals, Inc.
Hyperosmotic stress response and regulation of cell wall integrity in Saccharomyces cerevisiae share common functional aspects

The osmosensitive phenotype of the hog1 strain is suppressed at elevated temperature. Here, we show that the same holds true for the other commonly used HOG pathway mutant strains pbs2 and sho1ssk2ssk22, but not for ste11ssk2ssk22. Instead, the ste11ssk2ssk2 strain displayed a hyperosmosensitive phenotype at 37°C. This phenotype is suppressed by overexpression of LRE1, HLR1 and WSC3, all genes known to influence cell wall composition. The suppression of the temperature‐induced hyperosmosensitivity by these genes prompted us to investigate the role of STE11 and other HOG pathway components in cellular integrity and, indeed, we were able show that HOG pathway mutants display sensitivity to cell wall‐degrading enzymes. LRE1 and HLR1 were also shown to suppress the cell wall phenotypes associated with the HOG pathway mutants. In addition, the isolated multicopy suppressor genes suppress temperature‐induced cell lysis phenotypes of PKC pathway mutants that could be an indication for shared targets of the PKC pathway and high‐osmolarity response routes.
Effects of thyroid hormones on oxidative phosphorylation.

Introduction I t has long been known that the administration of thyroid hormones results in increases in oxygen consumption and in heat production, and that subnormal levels of thyroid hormones result in the opposite effects. Mitochondria from the livers of rats that have been treated with thyroid hormones ('hyperthyroid mitochondria') have oxygen-consurnption rates that are greater than the rates determined for euthyroid controls, and mitochondria from the livers of hypothyroid rats ('hypothyroid mitochondria') have lower oxygen-consumption rates than euthyroid controls [ 1 , 2). These changes in oxygen-consumption rate are also observed in hepatocytes that have been isolated from hyperthyroid and from hypothyroid rats 131. Such changes are thought to be an important part of the thyroid-horriione-induced changes in metabolic rate and in heat production (4-61. The focus of this brief review is on the effects of thyroid hormones on oxidative ptiosptiorylation at the levels of liver mitochondria and of hepatocytes. 'Hie effects o f thyroid hormones on oxygen consumption and on energy metabolism in mitochondria and in cells have been categorized into short-term and long-term effects. The mechanisms and the sites of action for the shortand long-term effects of thyroid hormones are discussed in another paper in this colloquium (S. Soboll, this colloquium). The discussion here will be limited to the long-term effects (that is, occurring after a period of 24 h) in rats; emphasis will be placed on the results of recent studies that have used the top-down elasticity-analysis approach (described in M. I). I h n d , I,. I;. Chien and I). F. S. Rolfe, this colloquium) to identify the important sites of action of thyroid hormones. Despite there being a substantial literature on the effects of thyroid hormones on oxidative phosphorylation, it is still not clear which of the effects on component enzymes and on pathways are quantitatively the most important. For example, it has
MIDAS: Integrated Design and Simulation of Distributed Systems

An approach called MIDAS is described that supports the design of distributed systems via iterative refinement of hybrid models. A hybrid model is a partially implemented design where some components exist as simulation models and others as operational subsystems. It is an executable model and may be used to determine the stochastic performance characteristics of a partially elaborated design. MIDAS enhances the applicability of hybrid models in system design with its support for interrupts and its inclusion of distributed components in the partially implemented design. The authors describe how an existing simulation language may be extended to program hybrid models, and show how simulation algorithms may be adapted to execute hybrid models. A prototype MIDAS implementation is operational and was used to develop a set of applications. The experimental results of the exercise are also described. >
Dynamic localization of C. elegans TPR-GoLoco proteins mediates mitotic spindle orientation by extrinsic signaling

Cell divisions are sometimes oriented by extrinsic signals, by mechanisms that are poorly understood. Proteins containing TPR and GoLoco-domains (C. elegans GPR-1/2, Drosophila Pins, vertebrate LGN and AGS3) are candidates for mediating mitotic spindle orientation by extrinsic signals, but the mechanisms by which TPR-GoLoco proteins may localize in response to extrinsic cues are not well defined. The C. elegans TPR-GoLoco protein pair GPR-1/2 is enriched at a site of contact between two cells – the endomesodermal precursor EMS and the germline precursor P2 – and both cells align their divisions toward this shared cell-cell contact. To determine whether GPR-1/2 is enriched at this site within both cells, we generated mosaic embryos with GPR-1/2 bearing a different fluorescent tag in different cells. We were surprised to find that GPR-1/2 distribution is symmetric in EMS, where GPR-1/2 had been proposed to function as an asymmetric cue for spindle orientation. Instead, GPR-1/2 is asymmetrically distributed only in P2. We demonstrate a role for normal GPR-1/2 localization in P2 division orientation. We show that MES-1/Src signaling plays an instructive role in P2 for asymmetric GPR-1/2 localization and normal spindle orientation. We ruled out a model in which signaling localizes GPR-1/2 by locally inhibiting LET-99, a GPR-1/2 antagonist. Instead, asymmetric GPR-1/2 distribution is established by destabilization at one cell contact, diffusion, and trapping at another cell contact. Once the mitotic spindle of P2 is oriented normally, microtubule-dependent removal of GPR-1/2 prevented excess accumulation, in an apparent negative-feedback loop. These results highlight the role of dynamic TPR-GoLoco protein localization as a key mediator of mitotic spindle alignment in response to instructive, external cues.
Segmentation of Magnetic Resonance Images Using Discrete Curve Evolution and Fuzzy Clustering

The region clustering of a magnetic resonance imaging (MRI) image is more complicate than a computed topography (CT) image because a MRI image composes of three components such as Tl -weighted, T2-weighted, and proton density (PD) in each layer. However, the MRI images provide more detail than the CT images. Therefore, we propose a technique of the region clustering of MRI image by using fuzzy c-means (PCM). The fuzzy c-means algorithm is an iterative operation, that is very time-consuming and makes the algorithm impractical for using in image segmentation. To cope with this problem, the discrete curve evolution (DCE) technique is applied to find the actual cluster center to refine the initial value of the fuzzy c-means algorithm, which reduces the convergence time. In experimental results, the proposed technique provides the same segmentation accuracy as the fuzzy c-means technique. Moreover, this technique takes lower computational time comparing to the previous method.
Treatment of Leg Vein Telangiectases: 1‐Year Results With a New 940 nm Diode Laser

BACKGROUNDShort-term results obtained with a 940 nm diode laser indicate that this laser is effective in the treatment of leg vein telangiectasia. Long-term studies are needed to evaluate the definitive clinical end results. OBJECTIVETo evaluate long-term results in the treatment of leg vein telangiectasia with a 940 nm diode laser and to compare these with short-term results. METHODSTwenty patients were treated with 940 nm diode laser, 300–350 J/cm2, 40–70 msec, 1 mm spot, single pass. Photographs for evaluation of clearance were taken before treatment and 4 weeks and 12 months after the last treatment. RESULTSAt 12 months follow-up, clearing rates were greater than 75% in 15 patients (75%) and 50–75% in 5 patients. In 7 patients (35%) the clearing rate had improved considerably during follow-up. CONCLUSIONDefinitive results with the 940 nm laser occur only after prolonged follow-up. They are considerably better than the short-term results.
Infections of the spine in patients with human immunodeficiency virus.

BACKGROUND Musculoskeletal infections in patients with the human immunodeficiency virus (HIV) have been described. However, the prevalence, specific characteristics, and outcomes of spinal infections in these patients have not been studied in a large group of patients to our knowledge. METHODS The computerized records of all patients discharged with the diagnosis of spinal osteomyelitis, discitis, epidural abscess, or tuberculosis from our institution from October 1994 through September 2000 were reviewed. Patients with the diagnosis of HIV were identified, and the charts were examined in detail. RESULTS During the six-year period, 7338 unique patients who were HIV positive were admitted. Seventeen (0.23%) of them were treated for a spinal infection. The prevalence of spinal infection was 23.2 per 10,000 admissions of HIV-positive patients and 7.1 per 10,000 admissions of HIV-negative patients (p < 0.0001). Eight patients who had discitis and/or osteomyelitis had a mean CD4 T-cell count of 339.6 cells/mm(3), and all eight had clinical resolution of the infection after six to twelve weeks of appropriate antibiotic therapy. In contrast, six patients who had spinal tuberculosis had a mean CD4 count of 75.7 cells/mm(3) (p = 0.005), and one of them died during the hospitalization. The remaining three patients, who had epidural abscesses, had a mean CD4 count of 20.67 cells/mm(3) (p = 0.001), and two of them died. CONCLUSIONS Discitis and/or osteomyelitis occurs in HIV-positive patients with a mild-to-moderate decrease (>/=200 cells/mm(3)) in the CD4 T-cell count, and the infection responds to appropriate antibiotics. Patients with a more severely decreased CD4 count (50 to 200 cells/mm(3)) may have spinal tuberculosis develop, and patients with the lowest CD4 counts are more likely to have epidural abscesses develop. The three fatalities in this study occurred in these two groups of patients. As a group, HIV-positive patients are significantly more likely to have a spinal infection develop than are HIV-negative patients (p < 0.0001). Although the CD4 count can be used as a predictor of the clinical course, identification of the organism remains paramount in the treatment of this complex patient population.
Preparation of Nano-ZnO and Its Application to the Textile on Antistatic Finishing

Nano-ZnO was prepared by direct precipitation method with zinc chloride and sodium carbonate anhydrous as raw materials, and its particle size and dispersion were characterized by TEM. The effects of concentration and the ratio of reactants and reaction temperature on its dispersion in aqueous solution were analyzed and the best reaction conditions were as follows: reaction temperature 60 centi degree, ultrasonic vibration time 40 min, concentration of the reactant 0.5mol/l and molar ratio of reactants 1:2 for the preparation. The cotton fabric and the polyester fabric which were both finished by pad-dry-cure process with antistatic finishing agent, which was compounded with nano-ZnO, were tested on their antistatic property. According to the comparation between the cotton and the polyester treated fabrics on antistatic property, the results showed that the charge density of the polyester fabric was reduced to 9.5×10-8 C/m2 from 5.8×10-6 C/m2, which was about 10 times as that of the cotton fabric.
Cervical Consistency Index: A New Concept in Uterine Cervix Evaluation

Objective: To search an ultrasonographic marker to measure cervix consistency throughout pregnancy quantitatively by transvaginalultrasonography and compare these values with the current pattern�the cervicometry. In a randomly selected population of pregnant andnonpregnant women using a new cervical consistency index (CCI) and compare these changes with the findings using cervicometry.Methods: The cervical consistency index (CCI) and cervicometry were measured using transvaginal ultrasonography in a reference populationof randomly selected women who were mature enough for reproduction, and women in their first, second and third trimester of pregnancy.Patients with history of cervical conization, two or more dilations and miscarriages, M�llerian abnormalities and history of cervix incompetencewere excluded from this study. Furthermore, patients with multiple pregnancies and cervical cerclage were not allowed to participate in thisstudy.Results: A total of 162 patients were evaluated for cervicometry and CCI. Eighty of these women were not pregnant and the remaining 82were pregnant. The database was analyzed using EPI-INFO version 6.0. Statistical values, such as the average, median and standarddeviation between two groups, were analyzed. Statistically significant differences were found between nonpregnant and pregnant women inthe first, second and third trimester regarding CCI with p < 0.0001. The cervix of pregnant women loses an average of 1.2% of consistencyper week of pregnancy. Cervicometry did not show statistically significant difference among the groups (p = 0.4459). Conclusion: CCI can quantitatively assess cervix consistency in pregnant and nonpregnant women, also found statistically significantdifferences between these groups and between the different trimesters of gestation, CCI also shows a remarkably circumscribed linearregression trend from early pregnancy. This ultrasound marker may serve in future for the early identification of patients at risk for pretermdelivery. On cervicometry, there was no statistically significant differences between groups mentioned above.