376 research outputs found

    A heparin-mimicking polymer conjugate stabilizes basic fibroblast growth factor.

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    Basic fibroblast growth factor (bFGF) is a protein that plays a crucial role in diverse cellular functions, from wound healing to bone regeneration. However, a major obstacle to the widespread application of bFGF is its inherent instability during storage and delivery. Here, we describe the stabilization of bFGF by covalent conjugation with a heparin-mimicking polymer, a copolymer consisting of styrene sulfonate units and methyl methacrylate units bearing poly(ethylene glycol) side chains. The bFGF conjugate of this polymer retained bioactivity after synthesis and was stable to a variety of environmentally and therapeutically relevant stressors--such as heat, mild and harsh acidic conditions, storage and proteolytic degradation--unlike native bFGF. Following the application of stress, the conjugate was also significantly more active than the control conjugate system in which the styrene sulfonate units were omitted from the polymer structure. This research has important implications for the clinical use of bFGF and for the stabilization of heparin-binding growth factors in general

    Modulation of Immune System by Kaposi’s Sarcoma-Associated Herpesvirus: Lessons from Viral Evasion Strategies

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    Kaposi’s sarcoma-associated herpesvirus (KSHV), a member of the herpesvirus family, has evolved to establish a long-term, latent infection of cells such that while they carry the viral genome gene expression is highly restricted. Latency is a state of cryptic viral infection associated with genomic persistence in their host and this hallmark of KSHV infection leads to several clinical–epidemiological diseases such as KS, a plasmablastic variant of multicentric Castleman’s disease, and primary effusion lymphoma upon immune suppression of infected hosts. In order to sustain efficient life-long persistency as well as their life cycle, KSHV dedicates a large portion of its genome to encode immunomodulatory proteins that antagonize its host’s immune system. In this review, we will describe our current knowledge of the immune evasion strategies employed by KSHV at distinct stages of its viral life cycle to control the host’s immune system

    Identification of a Novel Single Nucleotide Polymorphism of HADHA Gene at a Referred Primer-binding Site During Pre-diagnostic Tests for Preimplantation Genetic Diagnosis

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    The pre-diagnostic test for preimplantation genetic diagnosis (PGD) of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency was performed by polymerase chain reaction (PCR) and direct sequencing for hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (HADHA) gene. We obtained unexpected genotyping results of HADHA gene by allele drop-out in the analysis of patients' genomic DNA samples with a referred PCR primer set. Upon further analysis with a re-designed primer set, we found a novel single nucleotide polymorphism (SNP) at the referred primer-binding site in the normal allele of HADHA gene (NT_022184, 5233296 a>t). We found that the frequency of this novel SNP was 0.064 in Korean population. Pre-diagnostic test using single lymphocytes and clinical PGD were successfully performed with the re-designed primer set. Nineteen embryos (95.0%) among 20 were successfully diagnosed to 5 homozygous mutated, 8 heterozygous carrier and 6 wild type. Among 6 normal embryos, well developed and selected 4 embryos were transferred into the mother's uterus, but a pregnancy was not achieved. We proposed that an unknown SNP at primer-binding sites would be a major cause of allele drop-out in the PGD for single gene disorder

    Postprandial hypoglycemic effect of mulberry leaf in Goto-Kakizaki rats and counterpart control Wistar rats

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    Postprandial hypoglycemic effect of mulberry leaf (Morus alba L.) was compared in two animal models: Goto-Kakizaki (GK) rats, a spontaneous non-obese animal model for type II diabetes, and their counterpart control Wistar rats. First, the effect of a single oral administration of mulberry leaf aqueous extract (MLE) on postprandial glucose responses was determined using maltose or glucose as substrate. With maltose-loading, MLE reduced peak responses of blood glucose significantly in both GK and Wistar rats (P < 0.05), supporting the inhibition of α-glucosidase by MLE in the small intestine. With glucose-loading, MLE also significantly reduced blood glucose concentrations, measured at 30 min, in both animal models (P < 0.01), proposing the inhibition of glucose transport by MLE. Next, dried mulberry leaf powder (MLP) was administered for 8 weeks by inclusion in the diet. By MLP administration, fasting blood glucose was significantly reduced at weeks 4 and 5 (P < 0.05), but then returned to values that were similar to those of the control at the end of experimental period in GK rats. Insulin, HOMA-IR, C-reactive protein, and triglycerides tended to be decreased by MLP treatment in GK rats. All other biochemical parameters were not changed by MLP administration in GK rats. Collectively, these findings support that MLE has significant postprandial hypoglycemic effect in both non-obese diabetic and healthy animals, which may be beneficial as food supplement to manage postprandial blood glucose. Inhibitions of glucose transport as well as α-glucosidase in the small intestine were suggested as possible mechanisms related with the postprandial hypoglycemic effect of MLE

    Primordial Nucleosynthesis Constraints on Z' Properties

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    In models involving new TeV-scale Z' gauge bosons, the new U(1)' symmetry often prevents the generation of Majorana masses needed for a conventional neutrino seesaw, leading to three superweakly interacting ``right-handed'' neutrinos nu_R, the Dirac partners of the ordinary neutrinos. These can be produced prior to big bang nucleosynthesis by the Z' interactions, leading to a faster expansion rate and too much ^4He. We quantify the constraints on the Z' properties from nucleosynthesis for Z' couplings motivated by a class of E_6 models parametrized by an angle theta_E6. The rate for the annihilation of three approximately massless right-handed neutrinos into other particle pairs through the Z' channel is calculated. The decoupling temperature, which is higher than that of ordinary left-handed neutrinos due to the large Z' mass, is evaluated, and the equivalent number of new doublet neutrinos Delta N_nu is obtained numerically as a function of the Z' mass and couplings for a variety of assumptions concerning the Z-Z' mixing angle and the quark-hadron transition temperature T_c. Except near the values of theta_E6 for which the Z' decouples from the right-handed neutrinos, the Z' mass and mixing constraints from nucleosynthesis are much more stringent than the existing laboratory limits from searches for direct production or from precision electroweak data, and are comparable to the ranges that may ultimately be probed at proposed colliders. For the case T_c = 150 MeV with the theoretically favored range of Z-Z' mixings, Delta N_nu 4.3 TeV for any value of theta_E6. Larger mixing or larger T_c often lead to unacceptably large Delta N_nu except near the nu_R decoupling limit.Comment: 22 pages, 5 figures; two additional references adde

    Hypermethylation of p16INK4a in Korean Non-small Cell Lung Cancer Patients

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    Promoter hypermethylation of the p16INK4a gene was investigated in 81 sets of samples of tumor tissue and adjacent normal tissue from Korean patients with primary lung cancer, using the modified real-time polymerase chain reaction (PCR)/ SYBR Green detection method. The results showed hypermethylation of p16INK4a in 27.2% of tumor tissues, and in 11.1% of adjacent normal tissue. No significant association was found between the overall aberrant methylation in tumor and corresponding normal specimens (r=0.137, p=0.219). In 22 cases with p16INK4a hypermethylation in tumor tissues, only 4 (18.1%) cases were found to have a hypermethylated normal tissue specimen. The findings of this study show that smoking can influence the methylation level of the promoter region of p16INK4a, and that this occurs in tumor tissues more frequently than in normal tissues. Other clinicopathological characteristics, including age, sex, tumor stage, and histologic type were not found to be correlated with p16INK4a methylation

    WALLABY Pilot Survey: HI gas kinematics of galaxy pairs in cluster environment

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    We examine the H I gas kinematics of galaxy pairs in two clusters and a group using Australian Square Kilometre Array Pathfinder (ASKAP) WALLABY pilot survey observations. We compare the H I properties of galaxy pair candidates in the Hydra I and Norma clusters, and the NGC 4636 group, with those of non-paired control galaxies selected in the same fields. We perform H I profile decomposition of the sample galaxies using a tool, BAYGAUD which allows us to de-blend a line-of-sight velocity profile with an optimal number of Gaussian components. We construct H I super-profiles of the sample galaxies via stacking of their line profiles after aligning the central velocities. We fit a double Gaussian model to the super-profiles and classify them as kinematically narrow and broad components with respect to their velocity dispersions. Additionally, we investigate the gravitational instability of H I gas disks of the sample galaxies using Toomre Q parameters and H I morphological disturbances. We investigate the effect of the cluster environment on the H I properties of galaxy pairs by dividing the cluster environment into three subcluster regions (i.e., outskirts, infalling and central regions). We find that the denser cluster environment (i.e., infalling and central regions) is likely to impact the H I gas properties of galaxies in a way of decreasing the amplitude of the kinematically narrow H I gas (⁠MnarrowHI role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3eMHInarrowMnarrowHI/MtotalHI role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3eMHItotalMtotalHI⁠), and increasing the Toomre Q values of the infalling and central galaxies. This tendency is likely to be more enhanced for galaxy pairs in the cluster environment
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