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1. De novo reconstruction of satellite repeat units from sequence data

Author

Zhang, Yujie, Chu, Justin, Cheng, Haoyu, and Li, Heng

Subjects
Quantitative Biology - Genomics
Abstract

Satellite DNA are long tandemly repeating sequences in a genome and may be organized as high-order repeats (HORs). They are enriched in centromeres and are challenging to assemble. Existing algorithms for identifying satellite repeats either require the complete assembly of satellites or only work for simple repeat structures without HORs. Here we describe Satellite Repeat Finder (SRF), a new algorithm for reconstructing satellite repeat units and HORs from accurate reads or assemblies without prior knowledge on repeat structures. Applying SRF to real sequence data, we showed that SRF could reconstruct known satellites in human and well-studied model organisms. We also found satellite repeats are pervasive in various other species, accounting for up to 12% of their genome contents but are often underrepresented in assemblies. With the rapid progress on genome sequencing, SRF will help the annotation of new genomes and the study of satellite DNA evolution even if such repeats are not fully assembled.

Published
2023

5. A draft human pangenome reference

Author

Liao, Wen-Wei, Asri, Mobin, Ebler, Jana, Doerr, Daniel, Haukness, Marina, Hickey, Glenn, Lu, Shuangjia, Lucas, Julian K, Monlong, Jean, Abel, Haley J, Buonaiuto, Silvia, Chang, Xian H, Cheng, Haoyu, Chu, Justin, Colonna, Vincenza, Eizenga, Jordan M, Feng, Xiaowen, Fischer, Christian, Fulton, Robert S, Garg, Shilpa, Groza, Cristian, Guarracino, Andrea, Harvey, William T, Heumos, Simon, Howe, Kerstin, Jain, Miten, Lu, Tsung-Yu, Markello, Charles, Martin, Fergal J, Mitchell, Matthew W, Munson, Katherine M, Mwaniki, Moses Njagi, Novak, Adam M, Olsen, Hugh E, Pesout, Trevor, Porubsky, David, Prins, Pjotr, Sibbesen, Jonas A, Sirén, Jouni, Tomlinson, Chad, Villani, Flavia, Vollger, Mitchell R, Antonacci-Fulton, Lucinda L, Baid, Gunjan, Baker, Carl A, Belyaeva, Anastasiya, Billis, Konstantinos, Carroll, Andrew, Chang, Pi-Chuan, Cody, Sarah, Cook, Daniel E, Cook-Deegan, Robert M, Cornejo, Omar E, Diekhans, Mark, Ebert, Peter, Fairley, Susan, Fedrigo, Olivier, Felsenfeld, Adam L, Formenti, Giulio, Frankish, Adam, Gao, Yan, Garrison, Nanibaa’ A, Giron, Carlos Garcia, Green, Richard E, Haggerty, Leanne, Hoekzema, Kendra, Hourlier, Thibaut, Ji, Hanlee P, Kenny, Eimear E, Koenig, Barbara A, Kolesnikov, Alexey, Korbel, Jan O, Kordosky, Jennifer, Koren, Sergey, Lee, HoJoon, Lewis, Alexandra P, Magalhães, Hugo, Marco-Sola, Santiago, Marijon, Pierre, McCartney, Ann, McDaniel, Jennifer, Mountcastle, Jacquelyn, Nattestad, Maria, Nurk, Sergey, Olson, Nathan D, Popejoy, Alice B, Puiu, Daniela, Rautiainen, Mikko, Regier, Allison A, Rhie, Arang, Sacco, Samuel, Sanders, Ashley D, Schneider, Valerie A, Schultz, Baergen I, Shafin, Kishwar, Smith, Michael W, Sofia, Heidi J, Abou Tayoun, Ahmad N, Thibaud-Nissen, Françoise, and Tricomi, Francesca Floriana

Subjects
Biological Sciences, Genetics, Aetiology, 2.1 Biological and endogenous factors, Generic health relevance, Humans, Diploidy, Genome, Human, Haplotypes, Sequence Analysis, DNA, Genomics, Reference Standards, Cohort Studies, Alleles, Genetic Variation, General Science & Technology
Abstract

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals1. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.

Published
2023

6. Gaps and complex structurally variant loci in phased genome assemblies

Author

Porubsky, David, Vollger, Mitchell R, Harvey, William T, Rozanski, Allison N, Ebert, Peter, Hickey, Glenn, Hasenfeld, Patrick, Sanders, Ashley D, Stober, Catherine, Consortium, Human Pangenome Reference, Korbel, Jan O, Paten, Benedict, Marschall, Tobias, Eichler, Evan E, Abel, Haley J, Antonacci-Fulton, Lucinda L, Asri, Mobin, Baid, Gunjan, Baker, Carl A, Belyaeva, Anastasiya, Billis, Konstantinos, Bourque, Guillaume, Buonaiuto, Silvia, Carroll, Andrew, Chaisson, Mark JP, Chang, Pi-Chuan, Chang, Xian H, Cheng, Haoyu, Chu, Justin, Cody, Sarah, Colonna, Vincenza, Cook, Daniel E, Cook-Deegan, Robert M, Cornejo, Omar E, Diekhans, Mark, Doerr, Daniel, Ebler, Jana, Eizenga, Jordan M, Fairley, Susan, Fedrigo, Olivier, Felsenfeld, Adam L, Feng, Xiaowen, Fischer, Christian, Flicek, Paul, Formenti, Giulio, Frankish, Adam, Fulton, Robert S, Gao, Yan, Garg, Shilpa, Garrison, Erik, Garrison, Nanibaa’ A, Giron, Carlos Garcia, Green, Richard E, Groza, Cristian, Guarracino, Andrea, Haggerty, Leanne, Hall, Ira M, Haukness, Marina, Haussler, David, Heumos, Simon, Hoekzema, Kendra, Hourlier, Thibaut, Howe, Kerstin, Jain, Miten, Jarvis, Erich D, Ji, Hanlee P, Kenny, Eimear E, Koenig, Barbara A, Kolesnikov, Alexey, Kordosky, Jennifer, Koren, Sergey, Lee, HoJoon, Lewis, Alexandra P, Li, Heng, Liao, Wen-Wei, Lu, Shuangjia, Lu, Tsung-Yu, Lucas, Julian K, Magalhães, Hugo, Marco-Sola, Santiago, Marijon, Pierre, Markello, Charles, Martin, Fergal J, McCartney, Ann, McDaniel, Jennifer, Miga, Karen H, Mitchell, Matthew W, Monlong, Jean, Mountcastle, Jacquelyn, Munson, Katherine M, Mwaniki, Moses Njagi, Nattestad, Maria, Novak, Adam M, and Nurk, Sergey

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Humans, DNA, Satellite, Polymorphism, Genetic, Haplotypes, Segmental Duplications, Genomic, Sequence Analysis, DNA, Human Pangenome Reference Consortium, Medical and Health Sciences, Bioinformatics
Abstract

There has been tremendous progress in phased genome assembly production by combining long-read data with parental information or linked-read data. Nevertheless, a typical phased genome assembly generated by trio-hifiasm still generates more than 140 gaps. We perform a detailed analysis of gaps, assembly breaks, and misorientations from 182 haploid assemblies obtained from a diversity panel of 77 unique human samples. Although trio-based approaches using HiFi are the current gold standard, chromosome-wide phasing accuracy is comparable when using Strand-seq instead of parental data. Importantly, the majority of assembly gaps cluster near the largest and most identical repeats (including segmental duplications [35.4%], satellite DNA [22.3%], or regions enriched in GA/AT-rich DNA [27.4%]). Consequently, 1513 protein-coding genes overlap assembly gaps in at least one haplotype, and 231 are recurrently disrupted or missing from five or more haplotypes. Furthermore, we estimate that 6-7 Mbp of DNA are misorientated per haplotype irrespective of whether trio-free or trio-based approaches are used. Of these misorientations, 81% correspond to bona fide large inversion polymorphisms in the human species, most of which are flanked by large segmental duplications. We also identify large-scale alignment discontinuities consistent with 11.9 Mbp of deletions and 161.4 Mbp of insertions per haploid genome. Although 99% of this variation corresponds to satellite DNA, we identify 230 regions of euchromatic DNA with frequent expansions and contractions, nearly half of which overlap with 197 protein-coding genes. Such variable and incompletely assembled regions are important targets for future algorithmic development and pangenome representation.

Published
2023

11. The 8-bromobaicalein inhibited the replication of dengue, and Zika viruses and targeted the dengue polymerase

Author

Boonyasuppayakorn, Siwaporn, Saelee, Thanaphon, Huynh, Thao Nguyen Thanh, Hairani, Rita, Hengphasatporn, Kowit, Loeanurit, Naphat, Cao, Van, Vibulakhaophan, Vipanee, Siripitakpong, Panattida, Kaur, Parveen, Chu, Justin Jang Hann, Tunghirun, Chairat, Choksupmanee, Opas, Chimnaronk, Sarin, Shigeta, Yasuteru, Rungrotmongkol, Thanyada, and Chavasiri, Warinthorn

Published
2023
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12. Author Correction: The 8-bromobaicalein inhibited the replication of dengue, and Zika viruses and targeted the dengue polymerase

Author

Boonyasuppayakorn, Siwaporn, Saelee, Thanaphon, Huynh, Thao Nguyen Thanh, Hairani, Rita, Hengphasatporn, Kowit, Loeanurit, Naphat, Cao, Van, Vibulakhaophan, Vipanee, Siripitakpong, Panattida, Kaur, Parveen, Chu, Justin Jang Hann, Tunghirun, Chairat, Choksupmanee, Opas, Chimnaronk, Sarin, Shigeta, Yasuteru, Rungrotmongkol, Thanyada, and Chavasiri, Warinthorn

Published
2023
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13. GapPredict: A Language Model for Resolving Gaps in Draft Genome Assemblies

Author

Chen, Eric, Chu, Justin, Zhang, Jessica, Warren, Rene L., and Birol, Inanc

Subjects
Quantitative Biology - Genomics, Computer Science - Artificial Intelligence
Abstract

Short-read DNA sequencing instruments can yield over 1e+12 bases per run, typically composed of reads 150 bases long. Despite this high throughput, de novo assembly algorithms have difficulty reconstructing contiguous genome sequences using short reads due to both repetitive and difficult-to-sequence regions in these genomes. Some of the short read assembly challenges are mitigated by scaffolding assembled sequences using paired-end reads. However, unresolved sequences in these scaffolds appear as "gaps". Here, we introduce GapPredict, a tool that uses a character-level language model to predict unresolved nucleotides in scaffold gaps. We benchmarked GapPredict against the state-of-the-art gap-filling tool Sealer, and observed that the former can fill 65.6% of the sampled gaps that were left unfilled by the latter, demonstrating the practical utility of deep learning approaches to the gap-filling problem in genome sequence assembly., Comment: 9 pages, 7 figures. IEEE/ACM Trans Comput Biol Bioinform (2021)

Published
2021
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18. Pan-conserved segment tags identify ultra-conserved sequences across assemblies in the human pangenome

Author

Liao, Wen-Wei, Asri, Mobin, Ebler, Jana, Doerr, Daniel, Haukness, Marina, Hickey, Glenn, Lu, Shuangjia, Lucas, Julian K., Monlong, Jean, Abel, Haley J., Buonaiuto, Silvia, Chang, Xian H., Cheng, Haoyu, Chu, Justin, Colonna, Vincenza, Eizenga, Jordan M., Feng, Xiaowen, Fischer, Christian, Fulton, Robert S., Garg, Shilpa, Groza, Cristian, Guarracino, Andrea, Harvey, William T., Heumos, Simon, Howe, Kerstin, Jain, Miten, Lu, Tsung-Yu, Markello, Charles, Martin, Fergal J., Mitchell, Matthew W., Munson, Katherine M., Mwaniki, Moses Njagi, Novak, Adam M., Olsen, Hugh E., Pesout, Trevor, Porubsky, David, Prins, Pjotr, Sibbesen, Jonas A., Tomlinson, Chad, Villani, Flavia, Vollger, Mitchell R., Antonacci-Fulton, Lucinda L., Baid, Gunjan, Baker, Carl A., Belyaeva, Anastasiya, Billis, Konstantinos, Carroll, Andrew, Chang, Pi-Chuan, Cody, Sarah, Cook, Daniel E., Cornejo, Omar E., Diekhans, Mark, Ebert, Peter, Fairley, Susan, Fedrigo, Olivier, Felsenfeld, Adam L., Formenti, Giulio, Frankish, Adam, Gao, Yan, Giron, Carlos Garcia, Green, Richard E., Haggerty, Leanne, Hoekzema, Kendra, Hourlier, Thibaut, Ji, Hanlee P., Kolesnikov, Alexey, Korbel, Jan O., Kordosky, Jennifer, Lee, HoJoon, Lewis, Alexandra P., Magalhães, Hugo, Marco-Sola, Santiago, Marijon, Pierre, McDaniel, Jennifer, Mountcastle, Jacquelyn, Nattestad, Maria, Olson, Nathan D., Puiu, Daniela, Regier, Allison A., Rhie, Arang, Sacco, Samuel, Sanders, Ashley D., Schneider, Valerie A., Schultz, Baergen I., Shafin, Kishwar, Sirén, Jouni, Smith, Michael W., Sofia, Heidi J., Abou Tayoun, Ahmad N., Thibaud-Nissen, Françoise, Tricomi, Francesca Floriana, Wagner, Justin, Wood, Jonathan M.D., Zimin, Aleksey V., Popejoy, Alice B., Bourque, Guillaume, Chaisson, Mark J.P., Flicek, Paul, Phillippy, Adam M., Zook, Justin M., Eichler, Evan E., Haussler, David, Jarvis, Erich D., Miga, Karen H., Wang, Ting, Garrison, Erik, Marschall, Tobias, Hall, Ira, Li, Heng, Paten, Benedict, Greer, Stephanie U., Pavlichin, Dmitri S., Zhou, Bo, Urban, Alexander E., and Weissman, Tsachy

Published
2023
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22. Combination of gefitinib and methotrexate to treat tubal ectopic pregnancy (GEM3): a multicentre, randomised, double-blind, placebo-controlled trial

Author

Ahmed, Amna, Alexander, Hazel, Anderson, Sonal, Arya, Rita, Awadzi, Gabriel, Baumgarten, Miriam, Behrens, Renee, Bingham, Kelly, Bottomley, Cecilia, Bourne, Tom, Cheong, Ying, Chu, Justin, Collins, Frances, Cresswell, Janet, Devarajan, Sangeetha, Durgadevi, Punukollu, Esen, Umo, Faraj, Radwan, Fernandez, Priscilla, Fletcher, Joanne, Galea, Benjamin, Granne, Ingrid, Gupta, Pratima, Hogg, Susannah, Huda, Shahzya, Iyengar, Sucheta, Izuwah-Njoku, Ngozi, Izzat, Feras, Katimada-Annaiah, Thangamma, Khatri, Pinky, King, Kathleen, Kirk, Emma, Kumar, Chitra, Kumar, Geeta, Linsell, Louise, Madhra, Mayank, Madhvani, Krupa, McKay, Rebecca, Memon, Fouzia, Menon, Usha, Mohan, Shruti, Nelson, Scott, Nik, Helena, Nosib, Hema, Oghoetuoma, Jerry, Oliver, Abigail, Pande, Binita, Pathak, Mamta, Peace-Gadsby, Alexandra, Putran, Janaki, Raajkumar, Sundararajah, Raheja, Vinita, Raja, Malar, Raje, Gautam, Rao, Sandhya, Robshaw, Penny, Rodger, Faye, Ross, Jackie, Saleh, Sherif, Sankharan, Sridevi, Sharma, Mona, Sinha, Sanjay, Stewart, Kate, Sutherland, Lauren, Thompson, Rebecca, Tirumuru, Sakunthala, Watson, Nicola, Watson, Sandra, Winters, Ursula, Wykes, Catherine, Horne, Andrew W, Tong, Stephen, Moakes, Catherine A, Middleton, Lee J, Duncan, W Colin, Mol, Ben W, Whitaker, Lucy H R, Jurkovic, Davor, Coomarasamy, Arri, Nunes, Natalie, Holland, Tom, Clarke, Fiona, Doust, Ann M, and Daniels, Jane P

Published
2023
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23. Modified Frailty Index Does Not Provide Additional Value in Predicting Outcomes in Patients Undergoing Elective Transforaminal Lumbar Interbody Fusion

Author

Tran, Khoa S., Lambrechts, Mark J., Issa, Tariq Z., Tecce, Eric, Corr, Andrew, Toci, Gregory R., Wong, Ashley, DiMaria, Stephen, Kirkpatrick, Quinn, Chu, Justin, Gilmore, Griffin, Kurd, Mark F., Rihn, Jeffery A., Woods, Barrett I., Kaye, Ian David, Canseco, Jose A., Hilibrand, Alan S., Kepler, Christopher K., Vaccaro, Alexander R., and Schroeder, Gregory D.

Published
2023
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30. Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses

Author

Li, Mingxi, Ren, Yifei, Aw, Zhen Qin, Chen, Bo, Yang, Ziqing, Lei, Yuqing, Cheng, Lin, Liang, Qingtai, Hong, Junxian, Yang, Yiling, Chen, Jing, Wong, Yi Hao, Wei, Jing, Shan, Sisi, Zhang, Senyan, Ge, Jiwan, Wang, Ruoke, Dong, Jay Zengjun, Chen, Yuxing, Shi, Xuanling, Zhang, Qi, Zhang, Zheng, Chu, Justin Jang Hann, Wang, Xinquan, and Zhang, Linqi

Published
2022
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36. DUSP4 modulates RIG-I- and STING-mediated IRF3-type I IFN response

Author

Jiao, Huipeng, primary, James, Sharmy J., additional, Png, Chin Wen, additional, Cui, Chaoyu, additional, Li, Heng, additional, Li, Liang, additional, Chia, Wan Ni, additional, Min, Nyo, additional, Li, Weiyun, additional, Claser, Carla, additional, Rénia, Laurent, additional, Wang, Hongyan, additional, Chen, Mark I-Cheng, additional, Chu, Justin Jang Hann, additional, Tan, Kevin Shyong Wei, additional, Deng, Yinyue, additional, and Zhang, Yongliang, additional

Published
2024
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42. Approaches to improving embryo implantation

Author

Chu, Justin Jamie

Subjects
618.3, QH301 Biology, RC Internal medicine, RG Gynecology and obstetrics
Abstract

Embryo implantation represents a complex process vital in ensuring the normal development of pregnancy. Whether embryo implantation is the goal of natural conception or assisted reproductive treatment, the environment within the uterine cavity must be optimised in order to increase the chance of pregnancy. This thesis uses a mixture of research methods to investigate potential approaches to improving embryo implantation. Below are the key findings from this thesis: 1. The vitamin D status in women undergoing assisted reproductive treatment is important. An interventional trial would prove or disprove the merits of vitamin D deficiency treatment in these women. 2. There is not enough evidence to suggest a clear association between vitamin D and recurrent miscarriage, however there is a strong argument for biological plausibility. 3. The use of endometrial fluid collected at the time of embryo transfer in women undergoing assisted reproductive treatments for metabolomics analysis is possible. 4. Women with hydrosalpinx associated tubal infertility should be offered salpingostomy as a treatment option as the natural conception rates are similar to that achieved in in vitro fertilisation treatment.

Published
2016

44. The molecular epidemiology of a dengue virus outbreak in Taiwan: population wide versus infrapopulation mutation analysis.

Author

Tsai, You-Yuan, Cheng, Dayna, Huang, Sheng-Wen, Hung, Su-Jhen, Wang, Ya-Fang, Lin, Yih-Jyh, Tsai, Huey-Pin, Chu, Justin Jang Hann, and Wang, Jen-Ren

Subjects
DENGUE viruses, NUCLEOTIDE sequencing, MOLECULAR epidemiology, REVERSE genetics, GENETIC variation, CHLOROPLAST DNA
Abstract

Dengue virus (DENV) causes approximately 390 million dengue infections worldwide every year. There were 22,777 reported DENV infections in Tainan, Taiwan in 2015. In this study, we sequenced the C-prM-E genes from 45 DENV 2015 strains, and phylogenetic analysis based on C-prM-E genes revealed that all strains were classified as DENV serotype 2 Cosmopolitan genotype. Sequence analysis comparing different DENV-2 genotypes and Cosmopolitan DENV-2 sequences prior to 2015 showed a clade replacement event in the DENV-2 Cosmopolitan genotype. Additionally, a major substitution C-A314G (K73R) was found in the capsid region which may have contributed to the clade replacement event. Reverse genetics virus rgC-A314G (K73R) showed slower replication in BHK-21 and C6/36 cells compared to wildtype virus, as well as a decrease in NS1 production in BHK-21-infected cells. After a series of passaging, the C-A314G (K73R) mutation reverted to wildtype and was thus considered to be unstable. Next generation sequencing (NGS) of three sera collected from a single DENV2-infected patient at 1-, 2-, and 5-days post-admission was employed to examine the genetic diversity over-time and mutations that may work in conjunction with C-A314G (K73R). Results showed that the number of haplotypes decreased with time in the DENV-infected patient. On the fifth day after admission, two new haplotypes emerged, and a single non-synonymous NS4A-L115I mutation was identified. Therefore, we have identified a persistent mutation C-A314G (K73R) in all of the DENV-2 isolates, and during the course of an infection, a single new non-synonymous mutation in the NS4A region appears in the virus population within a single host. The C-A314G (K73R) thus may have played a role in the DENV-2 2015 outbreak while the NS4A-L115I may be advantageous during DENV infection within the host. Author summary: Dengue virus (DENV) is an RNA virus which causes many infections worldwide. Taiwan experienced the largest DENV-2 outbreak in 2015 which resulted in many fatalities. Specific reasons for the increase in severity during this outbreak remains unclear. The molecular epidemiology of this outbreak showed that clade replacement may have occurred, with the 2015 isolates forming a new clade and the old clade consisted of sequences from 2001–2004 in Taiwan. A dominant C-A314G (K73R) substitution was found in the 2015 DENV-2 outbreak isolates, which may have resulted in a clade replacement in the DENV-2 Cosmopolitan genotype. Further analysis of genetic variation of the virus population of one DENV-2 infected patient showed a decrease of haplotypes during the progression of infection and an NS4A-L115I mutation that did not appear until a later time-point. These show the difference between the variations found in a population wide analysis compared to an infrapopulation analysis which can influence viral infection. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Brimonidine Can Prevent In Vitro Hydroquinone Damage on Retinal Pigment Epithelium Cells and Retinal Müller Cells.

Author

Ramírez, Claudio, Cáceres-del-Carpio, Javier, Chu, Justin, Chu, Joshua, Moustafa, M, Chwa, Marilyn, Limb, G, Kuppermann, Baruch, and Kenney, Maria

Subjects
Antihypertensive Agents, Apoptosis, Brimonidine Tartrate, Cells, Cultured, Cytoprotection, Ependymoglial Cells, Humans, Hydroquinones, In Vitro Techniques, L-Lactate Dehydrogenase, Membrane Potential, Mitochondrial, Oxidative Stress, Reactive Oxygen Species, Retinal Pigment Epithelium
Abstract

PURPOSE: Brimonidine is a selective alpha-2 adrenergic agonist used to reduce intraocular pressure and it has been shown to have some neuroprotective effects. Hydroquinone (HQ) is a toxicant present in cigarette smoke, and other sources. In this study, we investigated the cyto-protective effects in vitro of Brimonidine on human retinal pigment epithelium cells (ARPE-19) and human retinal Müller cells (MIO-M1) that had been treated with HQ. METHODS: Cells were pretreated for 6 h with different doses of Brimonidine tartrate 0.1% (1/2×, 1×, 5×, 10×), followed by a 24-h exposure to 100 μM of HQ, while the Brimonidine was still present. Assays were used to measure cell viability, mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) production, and lactate dehydrogenase (LDH) release. RESULTS: Brimonidine increased the cell viability at all concentrations studied in both cell lines studied. ΔΨm also improved at all Brimonidine doses in ARPE-19 cells and in the 5× and 10× dosages MIO-M1 cells. The ROS levels decreased at 1×, 5×, and 10× doses of Brimonidine in ARPE-19 but only at 10× on MIO-M1 cells. The 10×-Brimonidine ARPE-19 cells had decreased LDH release, but no LDH changes were observed on MIO-M1 cells. CONCLUSION: HQ-induced toxicity is mediated through mitochondrial damaging, oxidative stress-related and necrosis-related pathways; Brimonidine significantly prevented the mitochondrial damaging and oxidative stress-related effects but had little effect on blocking the necrosis component of HQ-toxicity. Brimonidine protective effects differ between the different retinal cell types and high concentrations of Brimonidine (10×) have minimal damaging effects on human retinal cells.

Published
2016

50. Flavivirus genome recoding by codon optimisation confers genetically stable in vivo attenuation in both mice and mosquitoes

Author

Chin, Wei-Xin, primary, Kong, Hao Yuin, additional, Zhu, Isabelle Xin Yu, additional, Teo, Zi Yun, additional, Faruk, Regina, additional, Lee, Regina Ching Hua, additional, Ho, Si Xian, additional, Aw, Zhen Qin, additional, Yi, Bowen, additional, Hou, Xin Jun, additional, Tan, Antson Kiat Yee, additional, Yogarajah, Thinesshwary, additional, Huber, Roland G., additional, Cai, Yu, additional, Wan, Yue, additional, and Chu, Justin Jang Hann, additional

Published
2023
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