G-quadruplex formation in human telomeric (TTAGGG)4 sequence with complementary strand in close vicinity under molecularly crowded condition

Chromosomes in vertebrates are protected at both ends by telomere DNA composed of tandem (TTAGGG)n repeats. DNA replication produces a blunt-ended leading strand telomere and a lagging strand telomere carrying a single-stranded G-rich overhang at its end. The G-rich strand can form G-quadruplex structure in the presence of K+ or Na+. At present, it is not clear whether quadruplex can form in the double-stranded telomere region where the two complementary strands are constrained in close vicinity and quadruplex formation, if possible, has to compete with the formation of the conventional Watson–Crick duplex. In this work, we studied quadruplex formation in oligonucleotides and double-stranded DNA containing both the G- and C-rich sequences to better mimic the in vivo situation. Under such competitive condition only duplex was observed in dilute solution containing physiological concentration of K+. However, quadruplex could preferentially form and dominate over duplex structure under molecular crowding condition created by PEG as a result of significant quadruplex stabilization and duplex destabilization. This observation suggests quadruplex may potentially form or be induced at the blunt end of a telomere, which may present a possible alternative form of structures at telomere ends

Sequence-dependent abnormal aggregation of human Tau fragment in an inducible cell model

AbstractA pathological hallmark of Alzheimer disease (AD) is the accumulation of misfolded hyperphosphorylated microtubule-associated protein Tau within neurons, forming neurofibrillary tangles and leading to synaptic dysfunction and neuronal death. Here we study sequence-dependent abnormal aggregation of human fragment Tau244–372 in an inducible cell model. As evidenced by confocal laser scanning microscopy, Western blot, and immunogold electron microscopy, fibril-forming motifs are essential and sufficient for abnormal aggregation of Tau244–372 in SH-SY5Y neuroblastoma cells induced by Congo red: when its two fibril-forming segments PHF6 and PHF6* are deleted, Tau244–372 does lose its ability to form fibrils in SH-SY5Y cells, and the replacement of PHF6 and PHF6* with an unrelated amyloidogenic sequence IFQINS from human lysozyme does rescue the fibril-forming ability of Tau244–372 in SH-SY5Y cells. By contrast, insertion of a non-fibril forming peptide GGGGGG does not drive the disabled Tau244–372 to misfold in SH-SY5Y cells. Furthermore, as revealed by quantum dots based probes combined with annexin V staining, annexin V-FITC apoptosis detection assay, and immunofluorescence, fibril-forming motifs are essential and sufficient for early apoptosis of living SH-SY5Y cells induced by abnormal aggregation of Tau244–372. Our results suggest that fibril-forming motifs could be the determinants of Tau protein tending to misfold in living cells, thereby inducing neuronal apoptosis and causing the initiation and development of AD

Preservasi, Konservasi dan Renovasi Kawasan Kota Tua Jakarta

“Great nation is a nation who\u27s always appreciates their own history,” that was a statement from Bung Karno. This paper is trying to lift a heritage district in Kota Tua Jakarta. A legacy that full of arts, cultures, stories, romance and tragedy that happened, and how the origin of the city formed. It\u27s very unfortunate if you see the condition right now. When all of the nations soo proud of their culture and history, everyone is competing to maintain and conserve their heritage and run the management very well. What happened with our heritage? Nowadays, Kota Tua district has been revitalized, but sadly, the process didn\u27t maintained well. So the results looks neglected and not in the good shape

AAV-Mediated Cone Rescue in a Naturally Occurring Mouse Model of CNGA3-Achromatopsia

Achromatopsia is a rare autosomal recessive disorder which shows color blindness, severely impaired visual acuity, and extreme sensitivity to bright light. Mutations in the alpha subunits of the cone cyclic nucleotide-gated channels (CNGA3) are responsible for about 1/4 of achromatopsia in the U.S. and Europe. Here, we test whether gene replacement therapy using an AAV5 vector could restore cone-mediated function and arrest cone degeneration in the cpfl5 mouse, a naturally occurring mouse model of achromatopsia with a CNGA3 mutation. We show that gene therapy leads to significant rescue of cone-mediated ERGs, normal visual acuities and contrast sensitivities. Normal expression and outer segment localization of both M- and S-opsins were maintained in treated retinas. The therapeutic effect of treatment lasted for at least 5 months post-injection. This study is the first demonstration of substantial, relatively long-term restoration of cone-mediated light responsiveness and visual behavior in a naturally occurring mouse model of CNGA3 achromatopsia. The results provide the foundation for development of an AAV5-based gene therapy trial for human CNGA3 achromatopsia

Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients

This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored

Ni-based bimetallic heterogeneous catalysts for energy and environmental applications

Bimetallic catalysts have attracted extensive attention for a wide range of applications in energy production and environmental remediation due to their tunable chemical/physical properties. These properties are mainly governed by a number of parameters such as compositions of the bimetallic systems, their preparation method, and their morphostructure. In this regard, numerous efforts have been made to develop “designer” bimetallic catalysts with specific nanostructures and surface properties as a result of recent advances in the area of materials chemistry. The present review highlights a detailed overview of the development of nickel-based bimetallic catalysts for energy and environmental applications. Starting from a materials science perspective in order to obtain controlled morphologies and surface properties, with a focus on the fundamental understanding of these bimetallic systems to make a correlation with their catalytic behaviors, a detailed account is provided on the utilization of these systems in the catalytic reactions related to energy production and environmental remediation. We include the entire library of nickel-based bimetallic catalysts for both chemical and electrochemical processes such as catalytic reforming, dehydrogenation, hydrogenation, electrocatalysis and many other reactions

Construction and On-site Performance of the LHAASO WFCTA Camera

The focal plane camera is the core component of the Wide Field-of-view Cherenkov/fluorescence Telescope Array (WFCTA) of the Large High-Altitude Air Shower Observatory (LHAASO). Because of the capability of working under moonlight without aging, silicon photomultipliers (SiPM) have been proven to be not only an alternative but also an improvement to conventional photomultiplier tubes (PMT) in this application. Eighteen SiPM-based cameras with square light funnels have been built for WFCTA. The telescopes have collected more than 100 million cosmic ray events and preliminary results indicate that these cameras are capable of working under moonlight. The characteristics of the light funnels and SiPMs pose challenges (e.g. dynamic range, dark count rate, assembly techniques). In this paper, we present the design features, manufacturing techniques and performances of these cameras. Finally, the test facilities, the test methods and results of SiPMs in the cameras are reported here.Comment: 45 pages, 21 figures, articl