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Yukihito Ishizaka - One of the best experts on this subject based on the ideXlab platform.
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MOESM16 of Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response
2018Co-Authors: Kenta Iijima, Junya Kobayashi, Yukihito IshizakaAbstract:Additional file 16: Figure S15. XPG is required for Vpr-induced DDR and DSB. a, b Effects of downregulation of XPG on Vpr-induced DDR. The expression of XPG in Mit-23 cells was first downregulated by siRNA, and then Vpr expression was initiated on day 2 after introduction of XPG targeting siRNA. On day 1 after Vpr expression was started, phosphorylation of H2AX (a) and G2/M checkpoint activation (b) was analysed by flow cytometry. Downregulation of XPG significantly reduced Vpr-induced phosphorylation of H2AX (P = 4.4 × 10−5), and the G2/M arrest (P = 0.025). Data were obtained from three independent experiments. Error bar indicates ± SEM. c XPG is required for Vpr-induced DSBs. Neutral comet assay was performed using Mit-23 cell, the XPG expression of which was down-regulated. Data were obtained from three independent experiments. Error bar indicates ± SEM. P = 0.037. d XPG is required for rVpr-induced DSB in resting macrophages. Differentiated MM-6 cells were treated with 100 ng/ml of rVpr under the down-regulation of XPG, and subjected to neutral comet assay. Data were obtained from three independent experiments. Error bar indicates ± SEM. P = 0.001. e XPG is required for Vpr-induced upregulation of viral infection in resting macrophages. Differentiated MM-6 cells were infected with Vpr proficient (R+) or deficient (R−) NL4-3 viruses after transfection of siRNA, and the integration rate was quantitated by Alu-gag two-step nested qPCR; relative integration rates are shown. A representative result out of two independent experiments is depicted
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viral protein r of hiv type 1 induces retrotransposition and upregulates glutamate synthesis by the signal transducer and activator of transcription 1 signaling pathway
Microbiology and Immunology, 2015Co-Authors: Akihiro Doi, Kenta Iijima, Shigeyuki Kano, Yukihito IshizakaAbstract:Viral protein R (Vpr) of HIV-1 plays an important role in viral replication in macrophages. Various lines of evidence suggest that expression of Vpr in macrophages causes immunopathogenesis; however, the underlying mechanism is not yet fully understood. In this study, it was shown that recombinant Vpr (rVpr) induces retrotransposition of long interspersed element-1 in RAW264.7, a macrophage-like cell line, and activates reverse transcriptase-dependent immunotoxic cascades including production of IFN-β and phosphorylation of signal transducer and activator of transcription 1 (STAT1). Knockout experiments based on the CRISPR/Cas9 nickase system further demonstrated that cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) and stimulator of interferon gene (STING) are responsible for IFN-β production and STAT1 phosphorylation, respectively. Moreover, rVpr was found to increase production of glutaminase C, a regulator of glutamate synthesis, which is also dependent on the cGAS-STING pathway. Taken together with reports that glutaminase C is involved in the pathogenesis of HIV-associated neurocognitive disorder (HAND) and that Vpr is detectable in the cerebrospinal fluid of HIV-1-positive patients, a possible role of Vpr-induced L1-RTP and immunotoxic cascades in the development of HAND is discussed.
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hiv 1 Vpr induces tlr4 myd88 mediated il 6 production and reactivates viral production from latency
Journal of Leukocyte Biology, 2010Co-Authors: Shigeki Hoshino, Shigeyuki Kano, Mitsuru Konishi, Masako Mori, Mari Shimura, Chiaki Nishitani, Yoshio Kuroki, Yoshio Koyanagi, Hiroyuki Itabe, Yukihito IshizakaAbstract:Vpr, a HIV-1 accessory protein, was believed to be present in the plasma of HIV-1-positive patients, and our previous work demonstrated the presence of plasma Vpr in 20 out of 52 patients. Interestingly, our data revealed that patients' viral titer was correlated with the level of Vpr detected in their plasma. Here, we first show that rVpr, when incubated with human monocytes or MDMs, caused viral production from latently infected cells, and IL-6 was identified as a responsible factor. The induction of IL-6 by rVpr was dependent on signaling through TLR4 and its adaptor molecule, MyD88. We next provide evidence that rVpr induced the formation of OxPC and that a mAb against OxPC blocked rVpr-induced IL-6 production with the concomitant attenuation of MAPK activation. Moreover, the addition of NAC, a scavenger of ROS, abrogated the rVpr-induced formation of OxPC, the phosphorylation of C/EBP-beta, a substrate of MAPK, and IL-6 production. As rIL-6 reactivated viral replication in latently infected cells, our data indicate that rVpr-induced oxidative stress triggers cell-based innate immune responses and reactivates viral production in latently infected cells via IL-6 production. Our results suggest that Vpr should be monitored based on the viral titer, and they provide the rationale for the development of novel, anti-AIDS therapeutics targeting Vpr.
K H Nicolaides - One of the best experts on this subject based on the ideXlab platform.
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umbilical and fetal middle cerebral artery doppler at 35 37 weeks gestation in the prediction of adverse perinatal outcome
Ultrasound in Obstetrics & Gynecology, 2015Co-Authors: Ranjit Akolekar, Dahiana M Gallo, Leona Poon, Argyro Syngelaki, K H NicolaidesAbstract:Objective To investigate the potential value of cerebroplacental ratio (CPR) at 36 weeks' gestation in the prediction of adverse perinatal outcome. Methods This was a screening study in 6178 singleton pregnancies at 35–37 weeks' gestation. Umbilical artery (UA) and fetal middle cerebral artery (MCA) pulsatility index (PI) were measured and the values were converted to multiples of the median (MoM) after adjustment from variables in maternal characteristics and medical history that affect the measurements. CPR was calculated by dividing MCA-PI MoM by UA-PI MoM. Multivariable logistic regression analysis was used to determine if measuring CPR improved the prediction of adverse perinatal outcome provided by maternal characteristics, medical history and obstetric factors. The detection rate (DR) and false-positive rate (FPR) of screening by CPR were estimated for stillbirth, Cesarean section for fetal distress, umbilical arterial cord blood pH ≤ 7.0, umbilical venous cord blood pH ≤ 7.1, 5-min Apgar score < 7 and admission to the neonatal unit (NNU) and neonatal intensive care unit (NICU). Results There was a linear association between CPR and both birth-weight Z-score and arterial or venous umbilical cord blood pH, but the steepness of the regression lines was inversely related to the interval from assessment to delivery. The performance of low CPR < 5th percentile in screening for each adverse outcome was poor, with DRs of 6–15% and a FPR of about 6%. In the small subgroup of the population delivering within 2 weeks of assessment, the DRs improved to 14–50%, but with a simultaneous increase in FPR, to about 10%. Conclusion The performance of CPR in routine screening for adverse perinatal outcome at 36 weeks' gestation is poor. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
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umbilical and fetal middle cerebral artery doppler at 30 34 weeks gestation in the prediction of adverse perinatal outcome
Ultrasound in Obstetrics & Gynecology, 2015Co-Authors: Spyros Bakalis, Ranjit Akolekar, Dahiana M Gallo, Leona Poon, K H NicolaidesAbstract:Objective To investigate the potential value of cerebroplacental ratio (CPR) at 30–34 weeks' gestation in the prediction of adverse perinatal outcome. Methods This was a screening study in 30 780 singleton pregnancies at 30–34 weeks' gestation. Umbilical artery (UA) and fetal middle cerebral artery (MCA) pulsatility index (PI) were measured and the values were converted to multiples of the median (MoM) after adjustment from variables in maternal characteristics and medical history that affect the measurements. CPR was calculated by dividing MCA-PI MoM by UA-PI MoM. Multivariable logistic regression analysis was used to determine if measuring CPR improved the prediction of adverse perinatal outcome provided by screening with maternal characteristics, medical history and obstetric factors. The detection rate (DR) and false-positive rate (FPR) of screening by CPR were estimated for stillbirth, Cesarean section for fetal distress, umbilical arterial cord blood pH ≤ 7.0, umbilical venous cord blood pH ≤ 7.1, 5-min Apgar score < 7 and admission to the neonatal unit (NNU) and neonatal intensive care unit (NICU). Results There was a significant association between CPR and birth-weight Z-score. In addition to maternal characteristics, medical history and obstetric factors, measuring CPR provided a significant contribution to the prediction of arterial cord blood pH ≤ 7.0, venous cord blood pH ≤ 7.1 and admission to NNU. The performance of CPR in screening for each adverse outcome was poor, with DR of 5–11% and a FPR of about 5%. In the small subgroup of the population delivering within 2 weeks following assessment, the DR improved to 20–50%, but with a simultaneous increase in FPR to 10–23%. Conclusion The performance of CPR in routine screening for adverse perinatal outcome at 30–34 weeks' gestation is poor. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Margherita Doria - One of the best experts on this subject based on the ideXlab platform.
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the human immunodeficiency virus type 1 Vpr protein upregulates pvr via activation of the atr mediated dna damage response pathway
Journal of General Virology, 2013Co-Authors: Lia Vassena, Erica Giuliani, Giulia Matusali, Eric A Cohen, Margherita DoriaAbstract:Viral infection may induce the cell-surface expression of PVR (CD155) that, upon recognition by its cognate activating DNAM-1 receptor present on cytotoxic lymphocytes, may promote antiviral immune responses. Here we show that expression of the human immunodeficiency virus type 1 (HIV-1) Vpr protein in Jurkat T cells increases cell-surface and total PVR levels. Analysis of mutated Vpr variants indicated that Vpr uses the same protein surfaces, and hence probably the same mechanisms, to upregulate PVR and arrest the cell cycle in the G2 phase. Moreover, we found that PVR upregulation by Vpr relied on the ability of the protein to activate the ATR kinase that triggers the DNA damage response pathway and G2 arrest. Finally, we showed that Vpr contributes to PVR up-modulation in HIV-infected CD4+ T lymphocytes and inhibits the PVR downregulating activity of the viral Nef protein.
Gillang Eka Prasetya 131511123035 - One of the best experts on this subject based on the ideXlab platform.
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PENGARUH CAWTHORNE-COOKSEY EXERCISE TERHADAP RESIKO JATUH PADA LANSIA DI UPT PELAYANAN SOSIAL LANJUT USIA MAGETAN PENELITIAN PRA-EXPERIMENTAL
2017Co-Authors: Gillang Eka Prasetya 131511123035Abstract:Pendahuluan: Jatuh pada usia lanjut merupakan isu utama untuk petugas kesehatan di dunia. Morbiditas tertinggi terjadi pada usia lebih dari 65 tahun. Penurunan fungsi sistem vestibular pada lansia mengakibatkan gangguan keseimbangan dan peningkatan resiko jatuh. Tujuan dari penelitian adalah untuk menganalisis perbedaan skor resiko jatuh, skor keseimbangan, Knee Pess Reflex (KPR), dan Ankle Pess Reflex (APR) sebelum dan sesudah pemberian latihan Cawthorne-Cooksey pada lansia di UPT Pelayanan Sosial Lanjut Usia Magetan. Metode: Desain penelitian ini pre experiment dengan pendekatan one group pretest-post test, dengan Total Sampling sejumlah 20 orang. Variabel independen adalah latihan Cawthorne-Cooksey, variabel dependen adalah skor resiko jatuh, skor keseimbangan, KPR, dan APR. Pengambilan data menggunakan Berg Balance Scale untuk Resiko jatuh, Performance-Oriented Mobility Assesment untuk keseimbangan, dan pemeriksaan ketuk tendon untuk KPR dan APR. Uji statistik menggunakan paired t-test p
Gillang Eka Prasetya - One of the best experts on this subject based on the ideXlab platform.
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pengaruh cawthorne cooksey exercise terhadap resiko jatuh pada lansia di upt pelayanan sosial lanjut usia magetan penelitian pra experimental
2017Co-Authors: Gillang Eka PrasetyaAbstract:Pendahuluan: Jatuh pada usia lanjut merupakan isu utama untuk petugas kesehatan di dunia. Morbiditas tertinggi terjadi pada usia lebih dari 65 tahun. Penurunan fungsi sistem vestibular pada lansia mengakibatkan gangguan keseimbangan dan peningkatan resiko jatuh. Tujuan dari penelitian adalah untuk menganalisis perbedaan skor resiko jatuh, skor keseimbangan, Knee Pess Reflex (KPR), dan Ankle Pess Reflex (APR) sebelum dan sesudah pemberian latihan Cawthorne-Cooksey pada lansia di UPT Pelayanan Sosial Lanjut Usia Magetan. Metode: Desain penelitian ini pre experiment dengan pendekatan one group pretest-post test, dengan Total Sampling sejumlah 20 orang. Variabel independen adalah latihan Cawthorne-Cooksey, variabel dependen adalah skor resiko jatuh, skor keseimbangan, KPR, dan APR. Pengambilan data menggunakan Berg Balance Scale untuk Resiko jatuh, Performance-Oriented Mobility Assesment untuk keseimbangan, dan pemeriksaan ketuk tendon untuk KPR dan APR. Uji statistik menggunakan paired t-test p<0,05 untuk resiko jatuh, wilcoxon signed rank test p<0,05 untuk variabel Keseimbangan, KPR, dan APR.. Hasil dan Analisa: Terdapat perbedaan skor resiko jatuh nilai p= 0,002 < (0,05), skor keseimbangan nilai p= 0,014 < (0,05), KPR nilai p= 0,025 < (0,05), dan APR nilai p=0,025 < (0,05). Hasil uji statistik tersebut berarti ada pengaruh latihan Cawthorne-Cooksey terhadap resiko jatuh pada lansia. Diskusi: Penelitian ini membuktikan bahwa latihan Cawthorne-Cooksey melatih keseimbangan dan meningkatkan stabilitas postural sehingga mengurangi skor resiko jatuh pada lansia. Diharapkan latihan Cawthorne-Cooksey dapat digunakan sebagai metode alternatif dalam upaya pencegahan jatuh pada pada lansia di panti sosial.
