Miracle-dz/UniFAR-FTUs huggingface dataset:
Epstein-Barr Virus Latent Membrane Protein 1 Modulates Distinctive NF-κB Pathways through C-Terminus-Activating Region 1 To Regulate Epidermal Growth Factor Receptor Expression

ABSTRACT Epstein-Barr Virus (EBV) latent membrane protein 1 (LMP1) is required for EBV B-lymphocyte transformation, transforms rodent fibroblasts, and can induce lymphoma and epithelial hyperplasia in transgenic mice. Two domains have been identified within the intracellular carboxy terminus that can activate NF-κB, C-terminus-activating region 1 (CTAR1) and CTAR2, through interactions with tumor necrosis receptor-associated factors (TRAFs). CTAR1 can activate both the canonical and noncanonical NF-κB pathways and has unique effects on cellular gene expression. The epidermal growth factor receptor (EGFR) is highly induced by LMP1-CTAR1 in epithelial cells through activation of a novel NF-κB form containing p50 homodimers and Bcl-3. To further understand the regulation of NF-κB in CTAR1-induced EGFR expression, we evaluated the ability of CTAR1 to induce EGFR in mouse embryonic fibroblasts (MEFs) defective for different NF-κB effectors. CTAR1-mediated EGFR induction required the NF-κB-inducing kinase (NIK) but not the IκB kinase (IKK) complex components that regulate canonical or noncanonical NF-κB pathways. CTAR1-mediated induction of nuclear p50 occurred in IKKβ-, IKKγ-, and NIK-defective MEFs, indicating that this induction is not dependent on the canonical or noncanonical NF-κB pathways. EGFR and nuclear p50 were expressed at high levels in TRAF2−/− fibroblasts and were not induced by CTAR1. In TRAF3−/− MEFs, CTAR1 induced nuclear p50 but did not affect basal levels of STAT3 serine phosphorylation or induce EGFR expression. EGFR was induced by LMP1 in TRAF6−/− MEFs. These findings suggest that this novel NF-κB pathway is differentially regulated by TRAF2 and TRAF3, and that distinct interactions of LMP1 and its effectors regulate LMP1-mediated gene expression.
UTILIZING ORANGE PEELS FOR ESSENTIAL OIL PRODUCTION

Presently, in Nigeria orange peels are discarded as wastes after consumption of edible parts of orange fruits. However, the country depends on imported essential oil for use in industries for manufacture of products ranging from food, to beverage, cosmetics and pharmaceuticals. This research work was carried out to demonstrate the utilization of orange peel in the production of essential oils by employing different extraction methods. The methods considered in this work were steam distillation, water distillation and solvent extraction. For solvent extraction, Design Expert 7.0 was used to design experimental runs because of its relative popularity among the extraction methods. After the extraction, the oil was analysed to determine its physical and chemical properties. From the results obtained, it was discovered that the orange peels could give the maximum yields of essential oil to be 4.40%, 3.47% and 2.536% when steam distillation, water distillation and solvent extraction were employed, respectively, and that was an indication that the highest yield of essential oil was given by steam distillation among the methods considered. It was also discovered from the analysis of variance carried out on the results of experimental design done for solvent extraction method that a modified cubic model was able to represent the extraction process well because the model was obtained to be significant, and its square of correlation coefficient was reasonably high. Furthermore, the analysis of variance of the developed model revealed that the significant factors of the process were extraction time and extraction temperature. The characterization of the extracted oil gave its physical and chemical properties values that indicated that it could be used for production of other valuable products in different process industries.
Platelet membrane phospholipid asymmetry: from the characterization of a scramblase activity to the identification of an essential protein mutated in Scott syndrome

Summary. Like all eukaryotic cells, platelets maintain plasma membrane phospholipid asymmetry in normal blood circulation via lipid transporters, which control transbilayer movement. Upon platelet activation, the asymmetric orientation of membrane phospholipids is rapidly disrupted, resulting in a calcium‐dependent exposure of the anionic phospholipid, phosphatidylserine (PS), at the outer platelet surface. This newly‐exposed PS surface is a major component of normal hemostasis because it supports platelet procoagulant function. Binding of blood clotting enzyme complexes to this negatively‐charged membrane surface allows a dramatic increase in the rate of conversion of zymogens to active serine proteases, which in turn produce a burst of thrombin leading to the formation of a fibrin clot and further platelet activation. Cells have the capacity to catalyze transbilayer phospholipid exchange via ATP‐requiring translocase enzymes (flippases and floppases), which control unidirectional phospholipid transport against a concentration gradient. They also use an energy‐independent, calcium‐dependent scramblase activity to govern the bidirectional exchange of phospholipids between the two leaflets of the bilayer; this activity is essential for PS exposure during platelet activation. Scramblase activity, biochemically characterized in the 1980s, is deficient in patients with Scott syndrome, a rare inherited bleeding disorder with defective platelet procoagulant activity. Despite considerable efforts, the platelet scramblase protein remained elusive for years but a significant advance has recently been made with the identification of TMEM16F, a membrane protein essential for calcium‐dependent PS exposure whose loss of function mutations are found in Scott syndrome. This review recalls historical aspects of platelet membrane asymmetry characterization, summarizes the mechanisms and roles of PS exposure following platelet activation and discusses the recent identification of TMEM16F and its significance in the scrambling process.
Extended preservation of rat liver graft by induction of heme oxygenase‐1

Livers can be preserved only for a short period without jeopardizing the transplantation outcome. Heat shock proteins (HSPs) protect against ischemia and reperfusion injury. We studied whether their induction and, in particular, the induction of heme oxygenase 1 (HO‐1), improves transplantation survival after an extended time of cold storage. Rats were subjected to heat preconditioning (42°C for 20 minutes). Livers were harvested 24 hours later, preserved in cold University of Wisconsin solution for 44 hours, and transplanted in isogeneic rats (arterialized transplantation). HO‐1 was specifically induced and inhibited by cobalt protoporphyrin and tin protoporphyrin, respectively. All animals receiving a graft without preconditioning and subjected to 44 hours of cold preservation died within 3 days, whereas 89% of rats who received a graft exposed to heat survived for 3 weeks (P = .0004). Preconditioning reduced serum aspartate transaminase (AST) and lactate dehydrogenase activities after reperfusion, improved bile flow, and decreased the histologic lesions of reperfusion injury. These significant effects of heat preconditioning were prevented by administration of tin protoporphyrin and could be reproduced by administration of cobalt protoporphyrin. In grafts without preconditioning, only a small fraction (<5%) of hepatocytes were positive with the terminal deoxynucleotide transferase‐mediated dUTP nick‐end labeling (TUNEL) assay, and even less expressed activated caspase 3. Preconditioning tended to reduce the number of positive cells and to stimulate the expression of antiapoptotic Bcl‐XL. In conclusion, heat preconditioning and, specifically, overexpression of HO‐1 improve posttransplantation survival and graft function after prolonged cold ischemia preservation. The mechanism underlying these beneficial effects does not appear to be prevention of apoptosis.
Role of microRNA in the detection, progression, and intervention of acute kidney injury

Acute kidney injury, characterized by sharply decreased renal function, is a common and important complication in hospitalized patients. The pathological mechanism of acute kidney injury is mainly related to immune activation and inflammation. Given the high morbidity and mortality rates of hospitalized patients with acute kidney injury, the identification of biomarkers useful for assessing risk, making an early diagnosis, evaluating the prognosis, and classifying the injury severity is urgently needed. Furthermore, investigation into the development of acute kidney injury and potential therapeutic targets is required. While microRNA was first discovered in Caenorhabditis elegans, Gary Ruvkun’s laboratory identified the first microRNA target gene. Together, these two important findings confirmed the existence of a novel post-transcriptional gene regulatory mechanism. Considering that serum creatinine tests often fail in the early detection of AKI, testing for microRNAs as early diagnostic biomarkers has shown great potential. Numerous studies have identified microRNAs that can serve as biomarkers for the detection of acute kidney injury. In addition, as microRNAs can control the expression of multiple proteins through hundreds or thousands of targets influencing multiple signaling pathways, the number of studies on the functions of microRNAs in AKI progression is increasing. Here, we mainly focus on research into microRNAs as biomarkers and explorations of their functions in acute kidney injury. Impact statement Firstly, we have discussed the potential advantages and limitations of miRNA as biomarkers. Secondly, we have summarized the role of miRNA in the progress of AKI. Finally, we have made a vision of miRNA’s potential and advantages as therapeutic target intervention AKI.
Human endothelial cells generate Th17 and regulatory T cells under inflammatory conditions

Organ transplantation represents a unique therapeutic option for irreparable organ dysfunction and rejection of transplants results from a breakdown in operational tolerance. Although endothelial cells (ECs) are the first target in graft rejection following kidney transplantation, their capacity to alloactivate and generate particular T lymphocyte subsets that could intervene in this process remains unknown. By using an experimental model of microvascular endothelium, we demonstrate that, under inflammatory conditions, human ECs induced proliferation of memory CD4+CD45RA− T cells and selectively amplified proinflammatory Th17 and suppressive CD45RA−HLA-DR+FoxP3bright regulatory CD4+ T lymphocytes (Tregs). Although HLA-DR expression on resting microvascular ECs was sufficient to induce proliferation of memory CD4+ T cells, Treg amplification was dependent on the interaction with CD54, highly expressed only under inflammatory conditions. Moreover, expansion of Th17 cells was dependent on IL-6 and STAT-3, and inhibition of either specifically impaired Th17, without altering Treg expansion. Collectively these data reveal that the HLA-DR+ ECs regulate the local inflammatory allogeneic response, promoting either an IL-6/STAT-3–dependent Th17 response or a contact-CD54–dependent regulatory response according to the cytokine environment. Finally, these data open therapeutic perspectives in human organ transplantation based on targeting the IL-6/STAT-3 pathway and/or promoting CD54 dependent Treg proliferation.
Disruption of the Interface between the Pleckstrin Homology (PH) and Kinase Domains of Akt Protein Is Sufficient for Hydrophobic Motif Site Phosphorylation in the Absence of mTORC2*

The pro-survival kinase Akt requires phosphorylation at two conserved residues, the activation loop site (Thr-308) and the hydrophobic motif site (Ser-473), for maximal activation. Previous reports indicate that mTORC2 is necessary for phosphorylation of the hydrophobic motif and that this site is not phosphorylated in cells lacking components of the mTORC2 complex, such as Sin1. Here we show that Akt can be phosphorylated at the hydrophobic motif site (Ser-473) in the absence of mTORC2. First, increasing the levels of PIP3 in Sin1−/− MEFs by (i) expression of a constitutively active PI3K or (ii) relief of a negative feedback loop on PI3K by prolonged inhibition of mTORC1 or S6K is sufficient to rescue hydrophobic motif phosphorylation of Akt. The resulting accumulation of PIP3 at the plasma membrane results in Ser-473 phosphorylation. Second, constructs of Akt in which the PH domain is constitutively disengaged from the kinase domain are phosphorylated at the hydrophobic motif site in Sin1−/− MEFs; both myristoylated-Akt and Akt lacking the PH domain are phosphorylated at Ser-473. Thus, disruption of the interface between the PH and kinase domains of Akt bypasses the requirement for mTORC2. In summary, these data support a model in which Akt can be phosphorylated at Ser-473 and activated in the absence of mTORC2 by mechanisms that depend on removal of the PH domain from the kinase domain.
The Effects of Process Parameters on Residual Stresses in Single Point Incremental Forming of A1050 Aluminum Using ANOVA Model

Incremental sheet metal forming is a modern technique of sheet metal forming in which a uniform sheet is locally deformed during the progressive action of a forming tool. The tool movement is governed by a CNC milling machine. The tool locally deforms and by this way the sheet with pure deformation stretching. The aim of the present work is to inspect, experimentally, the state of the residual stresses induced in SPIF parts made by A1050 aluminum. The forming surface was measured at four different angles using a ORIONRKS 6000 test (the X-ray diffraction technology was used to detect the residual stress) measuring instrument with the angles (0o, 15o, 30o and 45o) and the average residual stress value is recorded in (MPa), the residual stress in original blanks is (-6.29MPa). This specialized stress analysis system using the side-inclination method includes stress analysis software, the stress analysis sample stand and X-ray tube. A comparison study is made for tabulated values and experimental values for residual stress by using ANOVA model with the contribution of rotational speed, feed rate and forming depth with respect to residual stress is (63.7, 4.3 and 32)%
Pharmacokinetic evaluation of oblimersen sodium for the treatment of chronic lymphocytic leukemia

Introduction: Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the western hemisphere. Developing new therapies remains a priority as present treatment options do not offer a cure. BCL-2 overexpression in CLL is associated with aggressive disease features and resists chemotherapy. Oblimersen sodium (G3139) is a phosphorothioate oligonucleotide antisense drug targeting the BCL-2 mRNA and is the first antisense to reach advanced clinical testing in oncology. Preclinical evaluation has demonstrated good antineoplastic effect in B-cell cancers; several clinical trials have confirmed its safety and efficacy both alone and in combination with other therapeutics. Areas covered: This review focuses on the chemistry, pharmacodynamics, pharmacokinetics and clinical evaluation of oblimersen in CLL. PubMed and MEDLINE searches assisted in data collection. Expert opinion: Bcl-2 is an important target in CLL. Antisense therapy is a novel approach to target oncoproteins; this can be beneficial in the clinical setting. Oblimersen sodium demonstrates the clinical safety of the antisense therapeutic approach and, with chemotherapy, shows survival advantage in a subset of CLL patients. However, future approval of oblimersen sodium in CLL remains uncertain. Nevertheless, BCL-2 remains a critical target in drug development and is an area of high-priority research.
Knowledge of Primary School Teachers Regarding First Aid In Baghdad Al-Rusafa

Al – Kindy Col Med J 2013; Vol. 9 No. 1 P: 54 Abstract Background: A basic knowledge and understanding of first aid can be invaluable for individuals to be able to provide emergency care in the event of an accident, possibly saving lives and minimizing injury. Since injury is the fifth leading cause of death and children at the age of primary school are liable for accidents and lack of knowledge and good judgment of their teachers may lead to dangerous consequences when emergencies occur. Training teachers how to deal with accidents is of obvious importance. Objectives: To estimate the adequacy of primary school teachers’ knowledge of first aid concerning external bleeding and fractures and Whether there's a difference in knowledge in regard to years spent in teaching or the teaching subject and to decide whether primary school teachers need training or not. Methods: This study is a cross-sectional Study was done over 5 months (from 01/Dec/2010 to 01/May/ 2011) in five randomly chosen primary schools in different regions in Baghdad/ Al-Rusafa,carried out on 100 primary school teachers without inclusion or exclusion criteria. Statistical analysis: Chi-Square was calculated by MiniTab Program to estimate significance. The significance level was set at P<0.05. Results: Of the 100 participants, 4% had good knowledge, 19% had fair knowledge and 77% had poor knowledge, 26% were science teachers, 9% were social studies teachers, 43% were literature teachers and 22% were sport/art teachers. No significant difference was found for their knowledge (p value=0.41). Also participants were classified according to the years they spent in teaching. No significance was found for their knowledge (p value=0.82). Conclusions: Primary school teachers' knowledge of first aid concerning external bleeding and fractures is poor and certainly inadequate.No difference was found in regard to how many years spent in teaching and difference in teaching subjects also has no effect on their knowledge.
3-D Vectorial Optical Model for High-Contrast Grating Vertical-Cavity Surface-Emitting Lasers

High-Contrast Gratings (HCG) are modeled in a rigorous way by a new mode-matching approach. They are highly attractive because they have recently proved suitable to replace distributed Bragg mirrors in Vertical-Cavity Surface-Emitting Lasers (VCSELs). Through a change of basis from plane to cylindrical waves, the generalized transmission matrix of the grating layer is obtained in a form that can be directly used within VCSEL ELectroMagnetic (VELM) code. This is the fully 3-D vectorial code developed at IEIIT-CNR (Turin, Italy) for a decade, which has proven to have the capability to reproduce the experimental details of the various structures investigated so far. The inclusion of HCG in VELM is performed on the same footing as all other geometrical details and in a way that preserves the code accuracy and numerical efficiency. A full set of modes of a large-size HCG VCSEL can be computed in a few minutes on an ordinary laptop.
Pravastatin Effects on Placental Prosurvival Molecular Pathways in a Mouse Model of Preeclampsia

Objective: Using an animal model of preeclampsia induced by overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1), we previously showed that pravastatin prevents the development of a preeclampsia phenotype. Our objective is to determine whether pravastatin treatment may be explained by its effects on apoptotic/survival pathways in the placenta. Methods: Pregnant CD1 mice at day 8 of gestation (length of gestation 19 days) were randomly allocated to injection via tail vein with either adenovirus carrying sFlt-1 or adenovirus carrying the murine immunoglobulin G2α Fc fragment (mFc virus control group). Mice from the sFlt group were randomly assigned to receive pravastatin (5 mg/kg/d) in their drinking water from day 9 until killing (sFlt-1 + Pravastatin) or water (sFlt-1). The mFc control received water only. Mice were killed on day 18, and the placentas were collected. Protein mitogen-activated protein kinase (MAPK) pathway substrates were assayed using Bioplex Multiplex Immunoassay (Bio-Rad, Hercules, California). Data are reported as mean ± standard error of the mean or median (interquartile range) when appropriate. One-way analysis of variance followed by post hoc analysis was performed. Two-sided P value < . 05 was considered statistically significant. Results: The sFlt-1 + Pravastatin mice had significantly higher placental protein concentrations of prosurvival/ antiapoptotic factors (activating transcription factor 2, pp38, phosphorylated c-jun N-terminal kinase, and phosphorylated extracellular signal-regulated kinase) and of heat-shock protein 27 and signal transducer and activator of transcription 3, 2 factors crucial for embryonic and placental development during oxidative stress, compared to sFlt-1 mice (P < .05) and similar to the mFc control group. No differences were noted in substrates of the proapoptotic pp53 pathway. Conclusion: Pravastatin ability to prevent preeclampsia phenotype may be mediated through pleiotropic mechanisms involving a prosurvival/ antiapoptotic MAPK pathway in the placenta. Our results further support continued research in the role for statins in the prevention of preeclampsia.
Estimation of sub-diurnal noise level in GPS time series

This paper contains the studies of the noise level in GPS (Global Positioning System) time series. As the data for this research the authors used changes of the geodetic coordinates of the ASG-EUPOS and associated (Slovak and Czech) sites. The method of precise GPS observations processing in short-time intervals was worked out in the Centre of Applied Geomatics, Military University of Technology. The authors focus on the diurnal and sub-diurnal frequency bands (tidal) as the tidal effects influence the sites’ positions at the most and the model used in the standard processing software does not contain geodetic coefficients. Thus the residual values of the geodetic coordinates time series should hold some information in the shape of coloured noise. The paper comprise short description of the Earth tides phenomenon, the concept of the tidal parameters determination, character of the white and coloured noise and the assessment of the noise estimation from GPS data. As the processed network contains 130 sites the spatial distribution of the noise’s parameters is also investigated.
Antioxidant enzyme activity and MDA level in the rat testis following chronic administration of ghrelin

Ghrelin has recently been reported to exert beneficial effects on various oxidative stresses as a result of its antioxidant properties. Therefore, we designed this study to explore the probable antioxidative effects of this peptide in the testis. Twenty‐eight male adult Wistar rats were divided into equal control and treatment groups. In the treatment group, 1 nmol of ghrelin was administered as subcutaneous injection for 10 consecutive days or vehicle (physiological saline) to the control rats. The control and treated rats were killed on days 6 and 10 after beginning of ghrelin injection (n = 7 from each group on each day). The testes were taken and measured for antioxidant enzyme activity and malondialdehyde (MDA) content. Glutathione peroxidase activity significantly increased on day 10 in the treated animals compared with the control group (P < 0.05). Although the mean activity of glutathione peroxidase was greater on day 6 in the ghrelin‐treated group than in the control animals, it was not statistically significant. There were no significant differences in superoxide dismutase and catalase activities between the groups. However, MDA level decreased by ghrelin treatment on day 10 compared with the control rats (P < 0.05). The results of this study indicate for the first time novel evidences for antioxidant properties of ghrelin in the rat testis.