TY - JOUR. T1 - The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes. AU - Pacher, Pal. AU - Liaudet, Lucas. AU - Soriano, Francisco Garcia. AU - Mabley, Jon G.. AU - Szabó, Éva. AU - Szabó, Csaba. PY - 2002/1/1. Y1 - 2002/1/1. N2 - Patients with diabetes exhibit a high incidence of diabetic cardiomyopathy and vascular complications, which underlie the development of retinopathy, nephropathy, and neuropathy and increase the risk of hypertension, stroke, and myocardial infarction. There is emerging evidence that the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) importantly contributes to the development of endothelial dysfunction in a streptozotocin-induced model of diabetes. We investigated the role of PARP activation in the pathogenesis of cardiac dysfunction in streptozotocin-induced and genetic (nonobese diabetic) models of diabetes in rats and mice. Development of diabetes was accompanied by ...
Three experiments were performed to study the effects of immune challenge on the rewarding properties of opiates. Intraperitoneal injection of polyinosinic-polycytidylic acid (Poly I: C, 1 mg/kg) was used to trigger an immune challenge. Conditioned place preference (CPP) in rats trained with alternating subcutaneous injections of morphine (5 mg/kg) and saline was used to assess the rewarding effect of morphine. Poly I: C administered before CPP training had no effects on CPP acquisition. Poly I: C administered during CPP training enhanced CPP acquisition. Poly I: C administered after morphine-induced CPP acquisition retarded CPP extinction. These results show that the immune challenge by Poly I: C augmented morphine CPP in rats depending on the onset time of the challenge. The findings suggest that immune challenge may enhance the rewarding properties of opiates. Behavioural Pharmacology 21: 369-373 (C) 2010 Wolters Kluwer Health , Lippincott Williams & Wilkins. ...
TY - JOUR. T1 - Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. AU - Du, Xueliang. AU - Matsumura, Takeshi. AU - Edelstein, Diane. AU - Rossetti, Luciano. AU - Zsengellér, Zsuzsanna. AU - Szabo, Csaba. AU - Brownlee, Michael. PY - 2003/10. Y1 - 2003/10. N2 - In this report, we show that hyperglycemia-induced overproduction of superoxide by the mitochondrial electron transport chain activates the three major pathways of hyperglycemic damage found in aortic endothelial cells by inhibiting GAPDH activity. In bovine aortic endothelial cells, GAPDH antisense oligonucleotides activated each of the pathways of hyperglycemic vascular damage in cells cultured in 5 mM glucose to the same extent as that induced by culturing cells in 30 mM glucose. Hyperglycemia-induced GAPDH inhibition was found to be a consequence of poly(ADP-ribosyl)ation of GAPDH by poly(ADP-ribose) polymerase (PARP), which was activated by DNA ...
From Ampligen to Autoimmune. Due to the over-due nature of this particular blog posting the length might pose somewhat of an issue for some readers. I thought it best to break it up by dividing it into sections.. """""""""""""""""""""""""""`. My last Ampligen infusion was Feb. 3rd. As you may remember I stopped because of constant bronchitis / pneumonia and transient brief blindness. (Mostly the brief episodes of blindness.) When I stopped the Ampligen I was sent to an ophthalmologist who concluded that my eyes were anatomically fine, but the risk of blindness associated with the continuation of Ampligen was too great. When I stopped Ampligen I was enjoying a happy existence of about a 60 -70 KPS which was a far cry from the 40 where I started.. About two weeks after stopping Ampligen an old, familiar feeling began to creep into my hands and wrists and I cried because I knew what was coming next…. """"""""""""""""""""""""""""`. A brief recap -. I was diagnosed with CFS in 1989. Every test, ...
TY - JOUR. T1 - TLR3 ligand Poly IC Attenuates Reactive Astrogliosis and Improves Recovery of Rats after Focal Cerebral Ischemia. AU - Li, Yang. AU - Xu, Xu Lin. AU - Zhao, Dan. AU - Pan, Lin Na. AU - Huang, Chun Wei. AU - Guo, Lian Jun. AU - Lu, Qing. AU - Wang, Jian. PY - 2015/11/1. Y1 - 2015/11/1. N2 - Aims: Brain ischemia activates astrocytes in a process known as astrogliosis. Although this process has beneficial effects, excessive astrogliosis can impair neuronal recovery. Polyinosinic-polycytidylic acid (Poly IC) has shown neuroprotection against cerebral ischemia-reperfusion injury, but whether it regulates reactive astrogliosis and glial scar formation is not clear. Methods: We exposed cultured astrocytes to oxygen-glucose deprivation/reoxygenation (OGD/R) and used a rat middle cerebral artery occlusion (MCAO)/reperfusion model to investigate the effects of Poly IC. Astrocyte proliferation and proliferation-related molecules were evaluated by immunostaining and Western blotting. ...
Polyadenylate-binding protein 1 is a protein that in humans is encoded by the PABPC1 gene. The protein PABP1 binds mRNA and facilitates a variety of functions such as transport out of the nucleus, degradation, translation, and stability. There are two separate PABP1 proteins, one which is located in the nucleus (PABPN1) and the other which is found in the cytoplasm (PABPC1). The location of PABP1 affects the role of that protein and its function with RNA. The poly(A)-binding protein (PAB or PABP), which is found complexed to the 3 poly(A) tail of eukaryotic mRNA, is required for poly(A) shortening and translation initiation. In humans, the PABPs comprise a small nuclear isoform and a conserved gene family that displays at least 3 functional proteins: PABP1 (PABPC1), inducible PABP (iPABP, or PABPC4; MIM 603407), and PABP3 (PABPC3; MIM 604680). In addition, there are at least 4 pseudogenes, PABPCP1 to PABPCP4.[supplied by OMIM] PABPC1 is usually diffused within the cytoplasm and concentrated at ...
Dept. of Biological Sciences. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1981 .B372. Source: Masters Abstracts International, Volume: 40-07, page: . Thesis (M.Sc.)--University of Windsor (Canada), 1981.
FDCS is a rare tumour with a spectrum of clinical behaviour. While some reports describe an indolent disease [4], others report higher rates of recurrence, metastases and mortality [5, 7]. There are a number of pathological features associated with a poorer prognosis, including size ≥6 cm, coagulative necrosis, high mitotic counts (≥5 per 10 high power field), significant cytologic atypia, younger age and abdominal involvement [5, 6, 15]. As molecular information becomes more readily available for this tumour type, it will also be important to determine its correlation with natural history and therapeutic significance.. This case report describes the use of a PARP inhibitor in combination with carboplatin in the treatment of a FDCS with a BRCA2 mutation. This is the first report of FDCS with a BRCA2 mutation and also the first report of the use of molecularly targeted therapy in this disease. BRCA2 is a tumour suppressor gene involved in deoxyribonucleic (DNA) repair via homologous ...
Clamped homogeneous electrical field electrophoresis allows the separation of DNA molecules up to 10 Mbp. The fraction of DNA fragments of this size is correlated with the number of DSB induced at random in chromosomes by radiation. Clamped homogeneous electrical field is therefore suitable for the determination of DSB in mammalian cell DNA. However, the sensitivity of the method is low, such that large doses of radiation must be applied for quantitative analysis of DSB formation and rejoining. The results are usually expressed as the fraction of activity released [i.e., the fraction of cell DNA (≤10 Mbp) migrating out of the plugs].. Cells for pulsed-field gel electrophoresis were prepared according to Stenerlöw et al. (44). In this method, embedded cells are lysed in the cold to prevent the conversion of abasic sites BD and SSB into DSB. Briefly, cells grown with [2-14C]thymidine as above were rinsed twice with HBSS, fed with fresh medium, and synchronized at the G1-S junction with a ...
It means that Ampligen will be most likely approved by the FDA. Ampligen, made by Hemispherx, regulates the RnaseL pathway, and has had success with a good number of patients. Dr. Charles Lapp is particularly upbeat about Ampligen, reporting that he gets good results with patients. Ampligen is infused through an IV, twice a week. Hemispherx is run by a bunch of bozos. They have dithered with the FDA, and screwed up the trials and the protocols for twenty-five years - even though Ampligen is seen as a functional drug for some people. As has been suggested by others, the FDA is complicit in this poorly managed process. Regardless of who is to blame the fact remains that this drug is at a standstill. This PA met a fellow in Reno who regained his normal activities for a number of years on this drug. Subsequently mismanagement by Hemispherx (or the FDA or both) cut him off from access to the drug. He got worse. Then he was able to get back on it, and he got better, and then the company cut him off ...
Polyadenylate-binding protein 2 (PABP-2) also known as polyadenylate-binding nuclear protein 1 (PABPN1) is a protein that in humans is encoded by the PABPN1 gene. This gene encodes an abundant nuclear protein that binds with high affinity to nascent poly(A) tails. The protein is required for progressive and efficient polymerization of poly(A) tails on the 3 ends of eukaryotic genes and controls the size of the poly(A) tail to about 250 nt. At steady-state, this protein is localized in the nucleus whereas a different poly(A) binding protein is localized in the cytoplasm. An expansion of the trinucleotide (GCN) repeat from normal 10 to 11-17 at the 5 end of the coding region of this gene leads to autosomal dominant oculopharyngeal muscular dystrophy (OPMD) disease. Multiple splice variants have been described but their full-length nature is not known. One splice variant includes introns 1 and 6 but no protein is formed. PABPN1 has been shown to interact with SNW1. GRCh38: Ensembl release 89: ...
Abstract : The bacterial transcription termination factor Rho-a ring-shaped molecular motor displaying directional, ATP-dependent RNA helicase/translocase activity-is an interesting therapeutic target. Recently, Rho from Mycobacterium tuberculosis (MtbRho) has been proposed to operate by a mechanism uncoupled from molecular motor action, suggesting that the manner used by Rho to dissociate transcriptional complexes is not conserved throughout the bacterial kingdom. Here, however, we demonstrate that MtbRho is a bona fide molecular motor and directional helicase which requires a catalytic site competent for ATP hydrolysis to disrupt RNA duplexes or transcription elongation complexes. Moreover, we show that idiosyncratic features of the MtbRho enzyme are conferred by a large, hydrophilic insertion in its N-terminal RNA binding domain and by a non-canonical R-loop residue in its C-terminal motor domain. We also show that the motor domain of MtbRho has a low apparent affinity for the Rho ...
In Argentina, rintatolimod (Ampligen) has just been commercially approved for the severe disabling form of ME/CFS. The number of patients with ME/CFS is estimated to be over three million worldwide, however, only a portion of these have the severe and disabling form of the disease which we are targeting with this drug," stated Tom Equels. "Until now, there has been no commercially available effective treatment and there are no advanced clinical candidates, other than rintatolimod, that we are aware of. This commercial approval in Argentina will dramatically improve our ability to treat patients suffering from severe ME/CFS in Latin America. We continue to work aggressively to clarify a path toward approval for those with severe ME/CFS in the United States, where we have Orphan Drug status, and therefore seven years of product exclusivity upon approval. We are greatly encouraged by this new regulatory approval in Argentina. This is the most significant accomplishment to date in Hemispherxs plan ...
Abstract : In Escherichia coli, binding of the hexameric Rho protein to naked C-rich Rut (Rho utilization) regions of nascent RNA transcripts initiates Rho-dependent termination of transcription. Although the ring-shaped Rho factor exhibits in vitro RNA-dependent ATPase and directional RNA-DNA helicase activities, the actual molecular mechanisms used by Rho to disrupt the intricate network of interactions that cement the ternary transcription complex remain elusive. Here, we show that Rho is a molecular motor that can apply significant disruptive forces on heterologous nucleoprotein assemblies such as streptavidin bound to biotinylated RNA molecules. ATP-dependent disruption of the biotin-streptavidin interaction demonstrates that Rho is not mechanistically limited to the melting of nucleic acid base pairs within molecular complexes and confirms that specific interactions with the roadblock target are not required for Rho to operate properly.. ...
2. The flame retardant poly(arylene ether) resin composition according to claim 1, wherein the poly(arylene ether) resin is one or more selected from poly(2,6-dimethyl-1,4-phenylene ether), poly(2,6-diethyl-1,4-phenylene ether), poly(2-methyl-6-ethyl-1,4-phenylene ether), poly(2-methyl-6-propyl-1,4-phenylene ether), poly(2,6-dipropyl-1,4-phenylene ether), poly(2-ethyl-6-propyl-1,4-phenylene ether), poly(2,6-dimethoxy-1,4-phenylene ether), poly(2,6-di(chloromethyl)-1,4-phenylene ether), poly(2,6-di(bromomethyl)-1,4-phenylene ether), poly(2,6-diphenyl-1,4-phenylene ether), poly(2,6-dichloro-1,4-phenylene ether), poly(2,6-dibenzyl-1,4-phenylene ether) and poly(2,5-dimethyl-1,4-phenylene ether ...
Transcription termination factor 1 is a protein that in humans is encoded by the TTF1 gene. GRCh38: Ensembl release 89: ENSG00000125482 - Ensembl, May 2017 "Human PubMed Reference:". Evers R, Grummt I (Aug 1995). "Molecular coevolution of mammalian ribosomal gene terminator sequences and the transcription termination factor TTF-I". Proc Natl Acad Sci U S A. 92 (13): 5827-31. doi:10.1073/pnas.92.13.5827. PMC 41594 . PMID 7597036. "Entrez Gene: TTF1 transcription termination factor, RNA polymerase I". Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1-2): 171-4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791-806. doi:10.1101/gr.6.9.791. PMID 8889548. Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full ...
1. WahleE (1991) A novel poly(A)-binding protein acts as a specificity factor in the second phase of messenger RNA polyadenylation. Cell 66: 759-768.. 2. KuhnU, NemethA, MeyerS, WahleE (2003) The RNA binding domains of the nuclear poly(A)-binding protein. J Biol Chem 278: 16916-16925.. 3. KerwitzY, KuhnU, LilieH, KnothA, ScheuermannT, et al. (2003) Stimulation of poly(A) polymerase through a direct interaction with the nuclear poly(A) binding protein allosterically regulated by RNA. Embo J 22: 3705-3714.. 4. KuhnU, GundelM, KnothA, KerwitzY, RudelS, et al. (2009) Poly(A) tail length is controlled by the nuclear poly(A)-binding protein regulating the interaction between poly(A) polymerase and the cleavage and polyadenylation specificity factor. J Biol Chem 284: 22803-22814.. 5. KuhnU, WahleE (2004) Structure and function of poly(A) binding proteins. Biochim Biophys Acta 1678: 67-84.. 6. ApponiLH, LeungSW, WilliamsKR, ValentiniSR, CorbettAH, et al. (2010) Loss of nuclear poly(A)-binding protein 1 ...
How is Transcription Termination Factor 1 (protein) abbreviated? TTF1 stands for Transcription Termination Factor 1 (protein). TTF1 is defined as Transcription Termination Factor 1 (protein) somewhat frequently.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits potent antitumor activity via membrane receptors on cancer cells without deleterious side effects for normal tissue. Unfortunately, breast cancer cells, as many other cancer types, develop resistance to TRAIL; therefore, TRAIL sensitizing agents are currently being explored. 2-Tellurium-bridged β-cyclodextrin (2-TeCD) is a synthetic organotellurium compound, with both glutathione peroxidase-like catalytic ability and thioredoxin reductase inhibitor activity. In the present study, we reported that 2-TeCD sensitized TRAIL-resistant human breast cancer cells and xenograft tumors to undergo apoptosis. In vitro, 2-TeCD efficiently sensitized MDA-MB-468 and T47D cells, but not untransformed human mammary epithelial cells, to TRAIL-mediated apoptosis, as evidenced by enhanced caspase activity and poly (adenosine diphosphate-ribose) polymerase cleavage. From a mechanistic standpoint, we showed that 2-TeCD treatment of breast ...
A carboxy-terminal peptide of the poliovirus replicase protein (p63) was chemically synthesized, coupled to bovine serum albumin carrier, and injected into rabbits. The resulting antisera reacted with six virus-specific proteins from HeLa cells infected with poliovirus: NCVP 0b, NCVP 1b, NCVP 2, a protein of about 60,000 daltons, p63, and NCVP 6b. The identity of the 60,000-dalton protein is not known, but the other results were consistent with previous experimental approaches which demonstrated that p63 and the other four polypeptides have common coding sequences. An amino-terminal peptide of p63 failed to elicit an immune response in rabbits. Antibodies raised against the p63 carboxy-terminal peptide inhibited poliovirus replicase and polyuridylic acid polymerase activities in vitro, providing strong support for earlier suggestions that these activities are a property of a single virus-specific polypeptide. ...
Degradation of mRNA is a highly regulated step important for proper gene expression. Degradation of eukaryotic mRNA is initiated by shortening of the 3 end located poly(A) tail. Poly(A)-specific ribonuclease (PARN) is an oligomeric enzyme that degrades the poly(A) tail with high processivity. A unique property of PARN is its ability to interact not only with the poly(A) tail but also with the 5 end located mRNA cap structure. A regulatory role in protein synthesis has been proposed for PARN based on its ability to bind the cap that is required for efficient initiation of eukaryotic mRNA translation. Here we have investigated how the cap structure influences PARN activity and how PARN binds the cap. We show that the cap activates PARN and enhances the processivity of PARN. Further we show that the cap binding complex (CBC) inhibits PARN activity through a protein-protein interaction. To investigate the cap binding property of PARN, we identified the cap binding site at the molecular level using ...
Cytotoxic T- and NK-cell neoplasms constitute a rare clinico-pathological entity associated with aggressive clinical behaviour and a poor prognosis. The entity comprises a heterogenous group of different diseases classified by histologic, immunologic as well as clinical features. Recently, expression patterns of cytotoxicity-associated proteins such as T-cell intracellular antigen (TIA), perforin and granzyme B have been applied to differentiate between an immature (TIA positive) and a mature (TIA and perforin and/or granzyme B positive) phenotype of these malignant cells. In particular, expression of perforin and granzyme B are considered to mediate cytotoxic activity. This study assesses histology/cytology, immunophenotype, expression of cytotoxicity-associated proteins and the actual exhibition of cytotoxic activity of lymphoma cells of 10 patients suffering from different T- and NK-cell neoplasms. As investigated by PKH67 labelling of the target cells 6 out of 10 samples exhibited cytotoxic
Treatments with Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors have offered patients carrying cancers with mutated BRCA1 or BRCA2 genes a new and in many cases effective option for disease control. There is potentially a large patient population that may also benefit from PARP inhibitor treatment, either in monotherapy or in combination with chemotherapy. Here, we describe the multifaceted role of PARP inhibitors and discuss which treatment options could potentially be useful to gain disease control without potentiating side effects.
How to Play Pin the Tail on the Donkey. Pin the Tail on the Donkey is a classic childrens game, often associated with birthday parties. Easy to play and fun for all ages, Pin the Tail on the Donkey costs next to nothing to play. As an...
TY - JOUR. T1 - Inhibition of BRCT(BRCA1)-phosphoprotein interaction enhances the cytotoxic effect of olaparib in breast cancer cells. T2 - A proof of concept study for synthetic lethal therapeutic option. AU - Pessetto, Ziyan Yuan. AU - Yan, Ying. AU - Bessho, Tadayoshi. AU - Natarajan, Amarnath. PY - 2012/7. Y1 - 2012/7. N2 - Synthetic lethal therapeutic strategy using poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor olaparib in carriers of BRCA1 or BRCA2 mutation has shown promise in clinical settings. Since ≤5 % of patients are BRCA1 or BRCA2 mutation carriers, small molecules that functionally mimic BRCA1 or BRCA2 mutations will extend the synthetic lethal therapeutic option for non-mutation carriers. Here we provide proof of principle for this strategy using a BRCA1 inhibitor peptide 2 that targets the BRCT(BRCA1)-phosphoprotein interaction and mimics the M177R/K BRCA1 mutation. Reciprocal immunoprecipitation and immunoblotting of BRCA1 and Abraxas was used to ...
Polyadenylated and nonpolyadenylated mRNA were prepared from polysomes and from the postribosomal supernatant of noninduced and DMSO-induced Friend cells. The mRNA preparations were translated in a wheat germ cell-free system and the in vitro synthesized proteins, fractionated by polyacrylamide gel electrophoresis, were compared by fluorography. The electrophoretic analysis shows that four preparations of poly (A) + RNA code for many different peptides and that most of these peptides are present in each of the poly (A) + RNA translation products. However, the electrophoretic patterns of these translation products differ in the relative amounts of peptides comigrating in the gel electrophoresis. After DMSO treatment, Friend cells show significative differences in the polysomal and nonpolysomal mRNA pools. With induction, globin becomes the most abundant product of the polysomal poly (A) + RNA, while the relative amounts of peptides coded by nonglobin polysomal poly (A) + RNA are reduced. In ...
Arabidopsis mRNA polyadenylation machinery: comprehensive analysis of protein-protein interactions and gene expression profiling. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Discussion. Hepatic dysfunction and megalosplenia were the main clinical manifestations in this patient. She was negative for markers of viral hepatitis and autoimmune liver diseases and had no history of alcohol or drug use. Furthermore, cirrhosis and portal hypertension were excluded based on abdominal CT angiographic and gastroscopic findings. In patients with fever and marasmus, the differential diagnosis may include tuberculosis, leishmaniasis and other hematological malignancies. However, no space-occupying lesions were found on thoracic and abdominal CT imaging, and the PPD skin and the T-SPOT test for tuberculosis were negative. In addition, leishmania for leishmaniasis was not detected in the bone marrow or spleen biopsy. The biopsies revealed the typical pathological characteristics of EBV+T-LPD. The infiltrating lymphocytes in tissues were positive for CD3, cytotoxic molecules, cytotoxic T cell intracellular antigen-1, telomerase B, and EBV (EBER+). Additionally, T-cell receptor γ ...
AtCPSF30 is the only Arabidopsis protein with a degree of sequence similarity to other eukaryotic CPSF30 proteins that extends beyond the typical spacing of Cys and His residues in the CCCH zinc-finger motif, and a number of lines of evidence support the conclusion that AtCPSF30 is an authentic polyadenylation factor subunit. As is the case with its yeast counterpart (Yth1p; Barabino et al., 1997), AtCPSF30 interacts with another Arabidopsis polyadenylation subunit homolog, AtFip1(V) (Forbes et al., 2006); AtFip1(V) also interacts with poly(A) polymerase and thereby provides a conceptual link between AtCPSF30 and poly(A) polymerase. The results presented in this study show that AtCPSF30 is present in the nucleus (Fig. 2B), as would be expected of a polyadenylation factor subunit. The coimmunoprecipitation of AtCPSF30 by antibodies raised against AtCPSF100 (Fig. 2C) indicates that AtCPSF30 resides, at least in part, in a complex with another Arabidopsis polyadenylation factor subunit. AtCPSF30 is ...
This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. This particular collagen IV subunit, however, is only found in a subset of basement membranes. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. Mutations in this gene are associated with type II autosomal recessive Alport syndrome (hereditary glomerulonephropathy) and with familial benign hematuria (thin basement membrane disease). Two transcripts, differing only in their transcription start sites, have been identified for this gene and, as is common for collagen genes, multiple polyadenylation sites are found in the 3 UTR ...
TY - JOUR. T1 - Punicalagin induces apoptotic and autophagic cell death in human U87MG glioma cells. AU - Wang, Shyang Guang. AU - Huang, Ming Hung. AU - Li, Jui Hsiang. AU - Lai, Fu I.. AU - Lee, Horng Mo. AU - Hsu, Yuan Nian. PY - 2013/11. Y1 - 2013/11. N2 - Aim: To investigate the effects of punicalagin, a polyphenol isolated from Punica granatum, on human U87MG glioma cells in vitro. Methods: The viability of human U87MG glioma cells was evaluated using MTT assay. Cell cycle was detected with flow cytometry analysis. The levels of Bcl-2, cleaved caspase-9, cleaved poly(ADP-ribose) polymerase (PARP), phosphor-AMPK and phosphor-p27 at Thr198 were measured using immunoblot analyses. Caspase-3 activity was determined with spectrophotometer. To determine autophagy, LC3 cleavage and punctate patterns were examined. Results: Punicalagin (1-30 μg/mL) dose-dependently inhibited the cell viability in association with increased cyclin E level and decreased cyclin B and cyclin A levels. The treatment ...
Although picornavirus RNA genomes contain a 3-terminal poly(A) tract that is critical for their replication, the impact of encephalomyocarditis virus (EMCV) infection on the host poly(A)-binding protein (PABP) remains unknown. Here, we establish that EMCV infection stimulates site-specific PABP proteolysis, resulting in accumulation of a 45-kDa N-terminal PABP fragment in virus-infected cells. Expression of a functional EMCV 3C proteinase was necessary and sufficient to stimulate PABP cleavage in uninfected cells, and bacterially expressed 3C cleaved recombinant PABP in vitro in the absence of any virus-encoded or eukaryotic cellular cofactors. N-terminal sequencing of the resulting C-terminal PABP fragment identified a 3C(pro) cleavage site on PABP between amino acids Q437 and G438, severing the C-terminal protein-interacting domain from the N-terminal RNA binding fragment. Single amino acid substitution mutants with changes at Q437 were resistant to 3C(pro) cleavage in vitro and in vivo, ...
This study evaluated the effects of ultrasound intensity on the ultrastructural morphology of Achilles tendon healing. Twenty Sprague-Dawley rats with surgically hemi-transected Achilles tendons were randomly assigned into four groups of 0, 0.5, 1.2 and 2 W/cm2 for ultrasound treatment, with five rats in each group. The treatments were administered with 1 MHz continuous ultrasound daily starting from day 5 after injury. On day 30, ultrathin slides of the Achilles tendons were prepared and examined with transmission electron microscopy. Results showed that the mean collagen fibril size of all treatment groups was higher than the control (p < 0.05). There was no significant difference in the collagen fibril size among the treatment groups. These findings suggest that therapeutic ultrasound can enhance the maturation of collagen fibrils of repairing tendons, and this was not dependent on the intensity of ultrasound applied. (E-mail: [email protected] ...
Males or non-pregnant, non-lactating females: Females must be of non-child bearing potential (either post-menopausal for two years or surgically sterile including tubal ligation) or using an effective means of contraception (birth control pills, intrauterine device, diaphragm). Alternatively, female patients with a male partner having a successful vasectomy (considered successful if a volunteer reports that a male partner has either documentation of azoospermia by microscopy or a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post-vasectomy).Females who are less than two (2) years post-menopausal, those with tubal ligations and those using contraception must have a negative serum pregnancy test at baseline within the four (4) weeks prior to the first study medication infusion. Every four weeks, and at study termination a pregnancy test should be performed, either serum or urine stick test. However, if the urine result is positive, a serum pregnancy test will ...
Vitamin D Binding Protein antibody (group-specific component (vitamin D binding protein)) for ICC/IF, IHC-P, WB. Anti-Vitamin D Binding Protein pAb (GTX109955) is tested in Human, Mouse samples. 100% Ab-Assurance.
Cleavage factor Im (CFIm) is one of six factors necessary for correct cleavage and polyadenylation of pre-mRNAs. CFIm is composed of three different subunits of 25, 59, and 68 kDa, and it functions as a heterotetramer, with a dimer of the 25 kDa subunit binding to two of the 59 or 68 kDa subunits. The protein encoded by this gene represents the 59 kDa subunit, which can interact with the splicing factor U2 snRNP Auxiliary Factor (U2AF) 65 to link the splicing and polyadenylation complexes. [provided by RefSeq, Oct 2016 ...
PRIMARY OBJECTIVES:. I. To determine the feasibility, tolerability, and toxicities of ABT-888 (veliparib) when administered alone and in combination with topotecan hydrochloride with or without carboplatin in patients with relapsed or refractory acute leukemia, high-risk myelodysplasia, or aggressive myeloproliferative disorders.. II. To determine the maximum tolerated dose of ABT-888 when administered with topotecan hydrochloride and carboplatin in these patients.. III. To determine if ABT-888 when administered with topotecan hydrochloride and carboplatin can induce clinical responses in these patients.. SECONDARY OBJECTIVES:. I. To determine the pharmacokinetics of ABT-888 when administered alone and in combination with topotecan hydrochloride with or without carboplatin in these patients.. II. To obtain pharmacodynamic data regarding the ability of ABT-888 to inhibit poly (ADP-ribose) levels in leukemic blasts.. III. To obtain descriptive data regarding the mutational status and/or ...
A technique that permitted the reversible dissociation of rat liver ribosomes was used to study the difference in protein-synthetic activity between liver ribosomes of normal and hypophysectomized rats. Ribosomal subunits of sedimentation coefficients 38S and 58S were produced from ferritin-free ribosomes by treatment with 0.8m-KCl at 30°C. These recombined to give 76S monomers, which were as active as untreated ribosomes in incorporating phenylalanine in the presence of poly(U). Subunits from normal and hypophysectomized rats were recombined in all possible combinations and the ability of the hybrid ribosomes to catalyse polyphenylalanine synthesis was measured. The results show that the defect in ribosomes of hypophysectomized rats lies only in the small ribosomal subunit. The 40S but not the 60S subunit of rat liver ribosomes bound poly(U). The only requirement for the reaction was Mg2+, the optimum concentration of which was 5mm. No apparent difference was seen between the poly(U)-binding ...
Author Summary Almost all eukaryotic messenger RNAs (mRNAs) have a string of 150-200 adenylates at the 3′ end. This poly(A) tail has been implicated as important for regulating mRNA translation, stability and export. During the lytic phase of infection of Kaposis Sarcoma-Associated Herpesvirus (KSHV), a noncoding viral RNA is synthesized that resembles an mRNA in that it is transcribed by RNA polymerase II, is methyl-G capped at the 5′ end, and is polyadenylated at the 3′ end; yet this RNA is never exported to the cytoplasm for translation. Rather, it builds up in the nucleus to exceedingly high levels. We present evidence that the function of this abundant, polyadenylated nuclear (PAN) RNA is to bind poly(A) binding protein, which normally binds poly(A) tails of mRNAs in the cytoplasm but is re-localized into the nucleus during lytic KSHV infection. The interaction between PAN RNA and re-localized poly(A) binding protein is important for formation of new virus, in particular for the synthesis of
Flow cytometry is conventionally used to measure cell-surface antigen expression. However, many antigens are found within the cytoplasm, and it is necessary to fix and permeabilize cells to enable antibodies to gain access to them. In this study we have established the conditions for studying intracellular antigens in human trophoblast cells by flow cytometry using an antibody to TAP1 (a key molecule in the process of Class I MHC assembly). We have previously shown by immunocytochemistry that TAP1 expression is apparently greater on Class 1 positive extravillous cytotrophoblast than on any other fetal or maternal tissue. However, as immunohistochemistry is not quantitative we have used three-colour flow cytometry to measure the expression of TAP1 in different trophoblast populations. Villous and extravillous cytotrophoblast were identified in first trimester and term placental and decidual digests on the basis of their expression of cytokeratin and Class I MHC antigens. The level of expression of TAP1
Inflammatory skin diseases such as atopic dermatitis and psoriasis represent a complex interaction between the skin and infiltrating immune cells, resulting in damage to the skin barrier and increased inflammation. Polymorphisms in PHF11 have been associated with dermatitis and allergy and PHF11 regulates the transcription of T-cell cytokines as well as class switching to IgE in activated B-cells. The importance of skin barrier homeostasis in the context of inflammatory skin diseases, together with reports identifying PHF11 as an interferon-induced gene, have led us to examine its role in the innate immune response of keratinocytes. We developed a cell culture model that allowed us to analyze the effects of the double-stranded RNA analogue poly(I:C) on a confluent cell monolayer immediately after a 24-h treatment, as well as three days after withdrawal of treatment. Immediately after treatment with poly(I:C), PHF11, IL8, and interferon-dependent ISG15 RNA expression was increased. This was accompanied
A polynucleotide molecule is a biopolymer composed of 13 or more nucleotide monomers covalently bonded in a chain. DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are examples of polynucleotides with distinct biological function. The prefix poly comes from the ancient Greek πολυς (polys, many). DNA consists of two chains of polynucleotides, with each chain in the form of a helical spiral. Although DNA and RNA do not generally occur in the same polynucleotide, the four species of nucleotides may occur in any order in the chain. The sequence of DNA or RNA species for a given polynucleotide is the main factor determining its function in a living organism or a scientific experiment. Polynucleotides occur naturally in all living organisms. The genome of an organism consists of complementary pairs of enormously long polynucleotides wound around each other in the form of a double helix. Polynucleotides have a variety of other roles in organisms. Polynucleotides are used in biochemical ...
Identifying key cellular events that facilitate stem cell function and tissue organization is critical for understanding the process of regeneration. Planarians are powerful model system to study regeneration and stem cell (neoblast) function. Here, using planaria, we show that the initial events of regeneration, such as epithelialization and epidermal organization are critically regulated by a novel cytoplasmic Poly A binding protein, SMED-PABPC2. Knockdown (KD) of Smed-pabpc2 leads to defects in epidermal lineage specification, disorganization of epidermis and ECM, and deregulated wound healing resulting in the selective failure of neoblast proliferation near the wound region. Polysome profiling suggested epidermal lineage transcripts, including zfp-1, to be translationally regulated by SMED-PABPC2. Together, our results uncover a novel role of SMED-PABPC2 in the maintenance of epidermal and ECM integrity, critical for wound healing, and subsequent processes for regeneration. ...
RNA-binding proteins have diverse functions in the regulation of gene expression. This is the first report, to our knowledge, that a KH motif RNA-binding protein is regulated by p53 and that it serves as a mediator in inducing apoptosis and cell cycle arrest in G2-M. We have demonstrated that deletion of either of the KH domains or a point mutation in the C-terminal KH domain of MCG10as abrogates or severely diminishes the activity of MCG10 and MCG10as in binding RNA. As a result, the MCG10 and MCG10as mutants defective in RNA binding are also defective in inducing apoptosis and cell cycle arrest. These results indicate that, like other RNA-binding proteins, the RNA-binding activity is critical for the function of MCG10 and MCG10as. Interestingly, a 55-amino-acid insertion in the N-terminal KH domain does not interfere with the RNA-binding activity of MCG10.. Previously, we and others have shown that p53 cellular target genes are differentially regulated by p73 (21, 50, 107). We found that the ...
摘要 构建重组表达载体是转基因动物生产制备研究中非常关键的一步,包括构建完整的外源基因表达盒,包含目的基因、调控序列(启动子、终止子)和筛选报告基因等。本文概述了转基因大动物制备技术,归纳统计了近10年转基因猪、牛、羊制备过程中常用的载体和频数,统计结果表明,转基因猪中启动子频数从多到少依次为酪蛋白、CAG、CMV启动子,终止子频数依次为兔β-globin poly A、酪蛋白poly A、SV40 poly A和BGH poly A;转基因羊中启动子频数从多到少依次为酪蛋白、BLG和CMV启动子,终止子依次为酪蛋白poly A、BLG poly A、BGH poly A、SV40 poly A和兔β-globin poly A;转基因牛中启动子频数从多到少依次为酪蛋白、CMV、人乳清白蛋白启动子等,终止子依次为SV40 poly A、BGH poly A和酪蛋白poly ...
Objective: The Learning Health System for Spinal Cord Injury (LHS-SCI) is an initiative embedded in the World Health Organizations (WHOs) Global Disability Plan and requires the statistical collection of data on the lived experience of persons with SCI to consequently formulate recommendations and policies. The International Spinal Cord Injury (InSCI) community survey has been developed as an initial step to gain information about the lived experience of persons with SCI within and across diverse nations.Design: InSCI is a multinational community survey based on the International Classification of Functioning, Disability and Health Core Sets for SCI and involves 28 countries from all six WHO regions. The study will be implemented in 2017. Overall aims, guiding principles on sampling strategies, data collection modes, and reminder management are described.Conclusions: InSCI will be the first survey to be conducted simultaneously in many countries and in all six WHO world regions that identifies ...
The Department of Mechanical Engineering of the Hong Kong Polytechnic University (PolyU) has developed a novel technology of embedding highly conductive nanostructure into semi-conductor nanofibre. The novel composite so produced has superb charge conductivity, and can therefore be widely applied, especially in environmental arena. The innovation was awarded the Gold Medal with congratu ..
Translation is important in the regulation of gene expression and is implicated in the control of cell growth, proliferation, and differentiation (32-34). In eukaryotes, initiation is the rate-limiting step of translation under most circumstances, and initiation is a major target for regulation (33). Paip1 is a mammalian PABP that binds to eIF4A and eIF3 and stimulates translational initiation. In the present study, we showed that the Paip1 protein was degraded by the HECT ubiquitin ligase WWP2. The following findings from the present study directly support the use of Paip1 as a physiological substrate of WWP2. WWP2 directly interacted with Paip1, and the interaction depended on the integrity of the WW domain of WWP2. The loss of WWP2 impeded Paip1 turnover. WWP2 promoted Paip1 ubiquitination both in vivo and in a reconstituted in vitro system. The ubiquitin ligase activity of WWP2 and the PXXY motif of Paip1 were critical for ubiquitination and degradation. Previous studies have demonstrated ...
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