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James B Lok

Lung-Yi Mak, Michael Ko, Elvis To, Danny Ka-Ho Wong, Justin Hei-Chun Ma, Teresa Lok-Yee Hui, Wai-Kay Seto, James Fung, Ching-Lung Lai, Man-Fung Yuen
BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) can still develop in chronic hepatitis B (CHB) patients receiving antiviral treatment. Serum Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel marker for liver fibrosis. We investigated its role on incidence of HCC in entecavir (ETV)-treated CHB patients. METHODS: We identified HCC cases diagnosed at ≥ 1 year of ETV treatment. CHB patients without HCC (matched for age, gender, baseline hepatitis B virus-DNA, and duration of ETV treatment) were identified in approximately 1:2 ratio (HCC: non-HCC) for comparison...
February 20, 2019: Journal of Gastroenterology and Hepatology
Sally Adams, Prachi Pathak, Hongguang Shao, James B Lok, Andre Pires-daSilva
Nematodes belong to one of the most diverse animal phyla. However, functional genomic studies in nematodes, other than in a few species, have often been limited in their reliability and success. Here we report that by combining liposome-based technology with microinjection, we were able to establish a wide range of genomic techniques in the newly described nematode genus Auanema. The method also allowed heritable changes in dauer larvae of Auanema, despite the immaturity of the gonad at the time of the microinjection...
January 24, 2019: Scientific Reports
Yee Hui Yeo, Hsiu J Ho, Hwai-I Yang, Tai-Chung Tseng, Tetsuya Hosaka, Huy N Trinh, Min-Sun Kwak, Young Min Park, James Yan Yue Fung, Maria Buti, Manuel Rodriguez, Sombat Treeprasertsuk, Carmen Monica Preda, Teerapat Ungtrakul, Phunchai Charatcharoenwitthaya, Xiangyong Li, Jiayi Li, Jian Zhang, Michael Huan Le, Bin Wei, Biyao Zou, An Le, Donghak Jeong, Nicholas Chien, Leslie Kam, Chiao-Chin Lee, Mar Riveiro-Barciela, Doina Istratescu, Tassanee Sriprayoon, Yutian Chong, Tawesak Tanwandee, Mariko Kobayashi, Fumitaka Suzuki, Man-Fung Yuen, Hyo-Suk Lee, Jia-Horng Kao, Anna S Lok, Chun-Ying Wu, Mindie H Nguyen
BACKGROUND & AIMS: Seroclearance of hepatitis B surface antigen (HBsAg) is a marker for clearance of chronic hepatitis B virus (HBV) infection but reported annual incidence rates of HBsAg seroclearance vary. We performed a systematic review and meta-analysis to provide more precise estimates of HBsAg seroclearance rates among subgroups and populations. METHODS: We searched PubMed, Embase, and Cochrane library for cohort studies that reported HBsAg seroclearance in adults with chronic HBV infection with more than 1 year of follow up and at least 1 repeat test for HBsAg...
October 17, 2018: Gastroenterology
James B Lok
No abstract text is available yet for this article.
August 31, 2018: Journal of Parasitology
Chon-Lok Lei, Joely A Kellard, Manami Hara, James D Johnson, Blanca Rodriguez, Linford J B Briant
Islet β-cells are responsible for secreting all circulating insulin in response to rising plasma glucose concentrations. These cells are a phenotypically diverse population that express great functional heterogeneity. In mice, certain β-cells (termed 'hubs') have been shown to be crucial for dictating the islet response to high glucose, with inhibition of these hub cells abolishing the coordinated Ca2+ oscillations necessary for driving insulin secretion. These β-cell hubs were found to be highly metabolic and susceptible to pro-inflammatory and glucolipotoxic insults...
2018: Islets
Norsyahida Arifin, Muhammad Hafiznur Yunus, Thomas J Nolan, James B Lok, Rahmah Noordin
Strongyloides stercoralis is a human parasite that can cause a long-term infection. In immunosuppressed patients, strongyloidiasis may be fatal when there is overwhelming autoinfection resulting in the migration of large numbers of larvae through many organs. Definitive diagnosis is still a challenge, and a combination of symptoms, microscopic identification, and serology test results are often used to arrive at a clinical decision. However, intermittent larval excretion, low parasite burden, and occult infections are challenges with parasitological diagnosis of infection with S...
April 2018: American Journal of Tropical Medicine and Hygiene
John B Patton, Sandra Bonne-Année, Jessica Deckman, Jessica A Hess, April Torigian, Thomas J Nolan, Zhu Wang, Steven A Kliewer, Amy C Durham, James J Lee, Mark L Eberhard, David J Mangelsdorf, James B Lok, David Abraham
Strongyloides stercoralis hyperinfection causes high mortality rates in humans, and, while hyperinfection can be induced by immunosuppressive glucocorticoids, the pathogenesis remains unknown. Since immunocompetent mice are resistant to infection with S. stercoralis , we hypothesized that NSG mice, which have a reduced innate immune response and lack adaptive immunity, would be susceptible to the infection and develop hyperinfection. Interestingly, despite the presence of large numbers of adult and first-stage larvae in S...
January 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
Hongguang Shao, James B Lok
Splinkerette PCR (spPCR) is a newly developed and efficient method to ascertain and characterize genomic insertion sites of transgenes. The method described in this protocol was successfully applied to confirm piggyBac transposon-mediated integration of transgenes into chromosomes of the parasitic nematode Strongyloides ratti . This work is described in detail in Shao et al . (2012) and presented here in a simplified diagram (Figure 1). Using this method, chromosomal loci of integration were determined based on target site and 5'- and 3' flanking sequences...
January 5, 2014: Bio-protocol
Wei-Qiang Lei, James B Lok, Wang Yuan, Yue-Zhou Zhang, Jonathan D Stoltzfus, Robin B Gasser, Si-Yuan He, Huan Zhou, Rui Zhou, Jun-Long Zhao, Min Hu
RIO kinases are essential atypical protein kinases in diverse prokaryotic and eukaryotic organisms, playing significant roles in yeast and humans. However, little is known about their functions in parasitic nematodes. In the present study, we have isolated and characterized the full-length cDNA, gDNA and a putative promoter of a RIOK-2 protein kinase (Ss-RIOK-2) encoding gene (Ss-riok-2) from Strongyloides stercoralis, a medically important parasitic nematode (Order Rhabditida). A three-dimensional structure (3D) model of Ss-RIOK-2 was generated using the Chaetomium thermophilum RIOK-2 protein kinase (Ct-RIOK-2) crystal structure 4GYG as a template...
August 18, 2017: Scientific Reports
Tegegn G Jaleta, Siyu Zhou, Felix M Bemm, Fabian Schär, Virak Khieu, Sinuon Muth, Peter Odermatt, James B Lok, Adrian Streit
Strongyloidiasis is a much-neglected soil born helminthiasis caused by the nematode Strongyloides stercoralis. Human derived S. stercoralis can be maintained in dogs in the laboratory and this parasite has been reported to also occur in dogs in the wild. Some authors have considered strongyloidiasis a zoonotic disease while others have argued that the two hosts carry host specialized populations of S. stercoralis and that dogs play a minor role, if any, as a reservoir for zoonotic S. stercoralis infections of humans...
August 2017: PLoS Neglected Tropical Diseases
James B Lok
Signaling or communication between host and parasite may occur over relatively long ranges to enable host finding and acquisition by infective parasitic nematode larvae. Innate behaviors in infective larvae transmitted from the soil that enhance the likelihood of host contact, such as negative geotaxis and hypermotility, are likely mediated by mechanoreception and neuromuscular signaling. Host cues such as vibration of the substratum, elevated temperature, exhaled CO2, and other volatile odorants are perceived by mechanosensory and chemosensory neurons of the amphidial complex...
December 2016: Current Clinical Microbiology Reports
Wang Yuan, Huan Zhou, James B Lok, Weiqiang Lei, Siyuan He, Robin B Gasser, Rui Zhou, Rui Fang, Yanqin Zhou, Junlong Zhao, Min Hu
Protein kinase RIOK-1 is a non-ribosomal factor essential for rRNA cleavage and ribosome small subunit maturation. It is encoded in all eukaryotic organisms. The RIOK-1 encoding gene of Caenorhabditis elegans (Ce-riok-1) is expressed in the neuronal and reproductive systems in larvae and adults of this free-living nematode, and it supports larval growth and development of the adult gonad. In spite of its recognised roles in model organisms such as C. elegans, little is known about the function of this molecule in parasitic nematodes...
December 2017: International Journal for Parasitology
Todd Bradley, Justin Pollara, Sampa Santra, Nathan Vandergrift, Srivamshi Pittala, Chris Bailey-Kellogg, Xiaoying Shen, Robert Parks, Derrick Goodman, Amanda Eaton, Harikrishnan Balachandran, Linh V Mach, Kevin O Saunders, Joshua A Weiner, Richard Scearce, Laura L Sutherland, Sanjay Phogat, Jim Tartaglia, Steven G Reed, Shiu-Lok Hu, James F Theis, Abraham Pinter, David C Montefiori, Thomas B Kepler, Kristina K Peachman, Mangala Rao, Nelson L Michael, Todd J Suscovich, Galit Alter, Margaret E Ackerman, M Anthony Moody, Hua-Xin Liao, Georgia Tomaras, Guido Ferrari, Bette T Korber, Barton F Haynes
The RV144 Thai trial HIV-1 vaccine of recombinant poxvirus (ALVAC) and recombinant HIV-1 gp120 subtype B/subtype E (B/E) proteins demonstrated 31% vaccine efficacy. Here we design an ALVAC/Pentavalent B/E/E/E/E vaccine to increase the diversity of gp120 motifs in the immunogen to elicit a broader antibody response and enhance protection. We find that immunization of rhesus macaques with the pentavalent vaccine results in protection of 55% of pentavalent-vaccine-immunized macaques from simian-human immunodeficiency virus (SHIV) challenge...
June 8, 2017: Nature Communications
Hongguang Shao, Xinshe Li, James B Lok
Heretofore, transgenesis in the parasitic nematode genus Strongyloides has relied on microinjecting transgene constructs into gonadal syncytia of free-living females. We now report transgenesis in Strongyloides stercoralis by microinjecting constructs into the syncytial testes of free-living males. Crosses of individual males microinjected with a construct encoding GFP with cohorts of 12 non-injected females produced a mean of 7.28±2.09 transgenic progeny. Progeny of males and females microinjected with distinct reporter constructs comprised 2...
August 2017: International Journal for Parasitology
Jinzhao Song, Changchun Liu, Michael G Mauk, Shelley C Rankin, James B Lok, Robert M Greenberg, Haim H Bau
BACKGROUND: The wide array of pathogens responsible for infectious diseases makes it difficult to identify causative pathogens with single-plex tests. Although multiplex PCR detects multiple targets, it is restricted to centralized laboratories, which delays test results or makes multiplexing unavailable, depriving healthcare providers of critical, real-time information. METHODS: To address the need for point-of-care (POC) highly multiplexed tests, we propose the 2-stage, nested-like, rapid (<40 min) isothermal amplification assay, dubbed rapid amplification (RAMP)...
March 2017: Clinical Chemistry
Hans P Verkerke, James A Williams, Miklos Guttman, Cassandra A Simonich, Yu Liang, Modestas Filipavicius, Shiu-Lok Hu, Julie Overbaugh, Kelly K Lee
UNLABELLED: Soluble forms of trimeric HIV-1 envelope glycoprotein (Env) have long been sought as immunogens and as reagents for analysis of Env structure and function. Isolation of trimers that mimic native Env, derived from diverse viruses, however, represents a major challenge. Thus far, the most promising native-like (NL) structures have been obtained by engineering trimer-stabilizing mutations, termed SOSIP, into truncated Env sequences. However, the abundances of NL trimeric conformers vary among Envs, necessitating purification by monoclonal antibodies (MAbs) like PGT145, which target specific epitopes...
October 15, 2016: Journal of Virology
Joseph Ahn, Joseph K Lim, Hannah M Lee, Anna S Lok, Mindie Nguyen, Calvin Q Pan, Ajitha Mannalithara, Helen Te, K Rajender Reddy, Huy Trinh, Danny Chu, Tram Tran, Daryl Lau, Truong-Sinh Leduc, Albert Min, Loc Trong Le, Ho Bae, Sang Van Tran, Son Do, Hie-Won L Hann, Clifford Wong, Steven Han, Anjana Pillai, James S Park, Myron Tong, Steve Scaglione, Jocelyn Woog, W Ray Kim
OBJECTIVES: Data from the United States are lacking regarding the impact of entecavir (ETV) on the risk of hepatocellular carcinoma (HCC). Our aim is to determine whether treatment with ETV is associated with a reduced HCC risk by calculating the expected HCC incidence based on the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model and comparing it with the observed HCC incidence. METHODS: The incidence of HCC in US patients treated with ETV between 2005 and 2013 in a retrospective cohort was obtained...
September 2016: American Journal of Gastroenterology
James B Lok
No abstract text is available yet for this article.
March 2016: PLoS Pathogens
Fa-Cai Li, Robin B Gasser, James B Lok, Pasi K Korhonen, Li He, Wen-Da Di, Fang-Yuan Yin, Rui Zhou, Yan-Qin Zhou, Jun-Long Zhao, Min Hu
BACKGROUND: Phosphoinositide-dependent protein kinase-1 (PDK-1), which functions downstream of phosphoinositide 3-kinase (AGE-1) and activates protein kinases of the AGC family, plays critical roles in regulating biology processes, such as metabolism, growth, development and survival. In the free-living nematode Caenorhabditis elegans, PDK-1 is a key component of the insulin-like signalling pathway, regulating the entry into and exit from dauer (arrested development). Although it is proposed that similar molecular mechanisms control the transition from the free-living to the parasitic stages of nematodes, nothing is known about PDK-1 in Haemonchus contortus, a socioeconomically important gastric nematode of ruminants...
February 3, 2016: Parasites & Vectors
Namitha Mohandas, Min Hu, Andreas J Stroehlein, Neil D Young, Paul W Sternberg, James B Lok, Robin B Gasser
BACKGROUND: In the present study, we reconstructed the insulin/insulin-like growth factor 1 signalling (IIS) pathway for Haemonchus contortus, which is one of the most important eukaryotic pathogens of livestock worldwide and is related to the free-living nematode Caenorhabditis elegans. METHODS: We curated full-length open-reading frames from assembled transcripts, defined the complement of genes that encode proteins involved in this pathway and then investigated the transcription profiles of these genes for all key developmental stages of H...
February 3, 2016: Parasites & Vectors
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