Chui Fann Wong, Joon Shin, Malathy Sony Subramanian Manimekalai, Wuan Geok Saw, Zhan Yin, Shashi Bhushan, Arvind Kumar, Priya Ragunathan, Gerhard Grüber,
Despite the highly oxidative environment of the phagosomal lumen, the need for maintaining redox homeostasis is a critical aspect of mycobacterial biology. The pathogens are equipped with the sophisticated thioredoxin- (Trx) and peroxiredoxin system, including TrxC and the alkyl hydroperoxide reductase subunit C (AhpC), whereby TrxC is one of the reducing partners of AhpC. Here we visualize the redox modulated dodecamer ring formation of AhpC from Mycobacterium bovis (BCG strain; MbAhpC) using electron ...
Tópico(s): Metal-Catalyzed Oxygenation Mechanisms
2017 - Nature Portfolio | Scientific Reports
Neelagandan Kamariah, Priya Ragunathan, Joon Shin, Wuan Geok Saw, Chui Fann Wong, Thomas Dick, Gerhard Grüber,
The causative agent of Tuberculosis (TB) Mycobacterium tuberculosis (Mtb) encounters unfavourable environmental conditions in the lungs, including nutrient limitation, low oxygen tensions and/or low/high pH values. These harsh conditions in the host triggers Mtb to enter a dormant state in which the pathogen does not replicate and uses host-derived fatty acids instead of carbohydrates as an energy source. Independent to the energy source, the bacterium's energy currency ATP is generated by oxidative ...
Tópico(s): Amoebic Infections and Treatments
2019 - Elsevier BV | Progress in Biophysics and Molecular Biology
Chui Fann Wong, Gerhard Grüber,
Mycobacterial F1Fo-ATP synthases (α3:β3:γ:δ:ε:a:b:b':c9 ) are incapable of ATP-driven proton translocation due to their latent ATPase activity. This prevents wasting of ATP and altering of the proton motive force, whose dissipation is lethal to mycobacteria. We demonstrate that the mycobacterial C-terminal extension of nucleotide-binding subunit α contributes mainly to the suppression of ATPase activity in the recombinant mycobacterial F1-ATPase. Using C-terminal deletion mutants, the regions responsible ...
Tópico(s): RNA modifications and cancer
2020 - American Society for Microbiology | Antimicrobial Agents and Chemotherapy
Chui Fann Wong, Aik‐Meng Lau, Amaravadhi Harikishore, Wuan Geok Saw, Joon Shin, Priya Ragunathan, Shashi Bhushan, SoFong Cam Ngan, Siu Kwan Sze, Roderick W. Bates, Thomas Dick, Gerhard Grüber,
In contrast to most bacteria, the mycobacterial F1 FO -ATP synthase (α3 :β3 :γ:δ:ε:a:b:b':c9 ) does not perform ATP hydrolysis-driven proton translocation. Although subunits α, γ and ε of the catalytic F1 -ATPase component α3 :β3 :γ:ε have all been implicated in the suppression of the enzyme's ATPase activity, the mechanism remains poorly defined. Here, we brought the central stalk subunit ε into focus by generating the recombinant Mycobacterium smegmatis F1 -ATPase (MsF1 -ATPase), whose 3D low-resolution structure ...
Tópico(s): RNA and protein synthesis mechanisms
2020 - Wiley | FEBS Journal
Chui Fann Wong, Wuan Geok Saw, Sandip Basak, Mio Sano, Hiroshi Ueno, Hwee Wen Kerk, Dennis Litty, Priya Ragunathan, Thomas Dick, Volker Müller, Hiroyuki Noji, Gerhard Grüber,
The F 1 F O -ATP synthase is required for the viability of tuberculosis (TB) and nontuberculous mycobacteria (NTM) and has been validated as a drug target. Here, we present the cryo-EM structures of the Mycobacterium smegmatis F 1 -ATPase and the F 1 F O -ATP synthase with different nucleotide occupation within the catalytic sites and visualize critical elements for latent ATP hydrolysis and efficient ATP synthesis.
Tópico(s): Amoebic Infections and Treatments
2022 - American Society for Microbiology | Antimicrobial Agents and Chemotherapy
Amaravadhi Harikishore, Chui Fann Wong, Priya Ragunathan, Dennis Litty, Volker Müller, Gerhard Grüber,
Mycobacteria regulate their energy (ATP) levels to sustain their survival even in stringent living conditions. Recent studies have shown that mycobacteria not only slow down their respiratory rate but also block ATP hydrolysis of the F-ATP synthase (α3:β3:γ:δ:ε:a:b:b':c9) to maintain ATP homeostasis in situations not amenable for growth. The mycobacteria-specific α C-terminus (α533-545) has unraveled to be the major regulative of latent ATP hydrolysis. Its deletion stimulates ATPase activity while ...
Tópico(s): Biochemical and Molecular Research
2021 - Multidisciplinary Digital Publishing Institute | Antibiotics
Wuan Geok Saw, Chui Fann Wong, Thomas Dick, Gerhard Grüber,
The F-ATP synthase is an essential enzyme in mycobacteria, including the pathogenic Mycobacterium tuberculosis. Several new compounds in the TB-drug pipeline target the F-ATP synthase. In light of the importance and pharmacological attractiveness of this novel antibiotic target, tools have to be developed to generate a recombinant mycobacterial F1FO ATP synthase to achieve atomic insight and mutants for mechanistic and regulatory understanding as well as structure-based drug design. Here, we report ...
Tópico(s): RNA and protein synthesis mechanisms
2019 - Elsevier BV | Biochemical and Biophysical Research Communications
Joon Shin, Amaravadhi Harikishore, Chui Fann Wong, Priya Ragunathan, Thomas Dick, Gerhard Grüber,
Mycobacterium abscessus (Mab) is a nontuberculous mycobacterium of increasing clinical relevance. The rapidly growing opportunistic pathogen is intrinsically multi-drug-resistant and causes difficult-to-cure lung disease. Adenosine triphosphate, generated by the essential F1 FO ATP synthase, is the major energy currency of the pathogen, bringing this enzyme complex into focus for the discovery of novel antimycobacterial compounds. Coupling of proton translocation through the membrane-embedded FO ...
Tópico(s): Mycobacterium research and diagnosis
2022 - Wiley | FEBS Journal
Vikneswaran Mathiyazakan, Chui Fann Wong, Amaravadhi Harikishore, Kévin Pethe, Gerhard Grüber,
The mycobacterial cytochrome bcc:aa3 complex deserves the name "supercomplex" since it combines three cytochrome oxidases-cytochrome bc, cytochrome c, and cytochrome aa3-into one supramolecular machine and performs electron transfer for the reduction of oxygen to water and proton transport to generate the proton motive force for ATP synthesis. Thus, the bcc:aa3 complex represents a valid drug target for Mycobacterium tuberculosis infections. The production and purification of an entire M. tuberculosis ...
Tópico(s): Advanced Electron Microscopy Techniques and Applications
2023 - American Society for Microbiology | Antimicrobial Agents and Chemotherapy
Robert Freedman, Sherry Leonard,
... Yang, Sandy F-C Lee, Cathy S.J. Fann, Su-Hsien Wong, Shu-Hua Hsieh. 2001. Suggestive evidence for linkage ...
Tópico(s): Wnt/β-catenin signaling in development and cancer
2001 - Wiley | American Journal of Medical Genetics
Luting Poh, David Y. Fann, Peiyan Wong, Hong Meng Lim, Sok Lin Foo, Sung-Wook Kang, Vismitha Rajeev, Sharmelee Selvaraji, Vinaya Rajagopal Iyer, Nageiswari Parathy, Mohammad Badruzzaman Khan, David C. Hess, Dong‐Gyu Jo, Grant R. Drummond, Christopher G. Sobey, Mitchell K.P. Lai, Christopher Chen, Lina H. K. Lim, Thiruma V. Arumugam,
Chronic cerebral hypoperfusion is associated with vascular dementia (VaD). Cerebral hypoperfusion may initiate complex molecular and cellular inflammatory pathways that contribute to long-term cognitive impairment and memory loss. Here we used a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate its effect on the innate immune response—particularly the inflammasome signaling pathway. Comprehensive analyses revealed that chronic cerebral hypoperfusion induces a complex ...
Tópico(s): Neuroinflammation and Neurodegeneration Mechanisms
2020 - Springer Nature | Molecular Psychiatry
Chih‐Min Liu, Hai‐Gwo Hwu, Ming‐Wei Lin, Wen‐Chen Ouyang, Sandy F.‐C. Lee, Cathy S.J. Fann, Su‐Hsien Wong, Shu‐Hua Hsieh,
In order to evaluate the linkage of schizophrenia to loci at chromosome 15q, we genotyped six microsatellite markers at chromosome 15q11-14 in 52 Taiwanese schizophrenic families. Two phenotype models (narrow: DSM-IV schizophrenia only; and broad: including schizophrenia, schizoaffective, and other nonaffective psychotic disorders) were used to define the disease phenotype. Maximum nonparametric linkage scores (NPL scores) of 3.33 (P = 0.0003) and 2.96 (P = 0.0008) were obtained at the marker D15S976 under ...
Tópico(s): Autism Spectrum Disorder Research
2001 - Wiley | American Journal of Medical Genetics
Shih-Wei Chen, Yu-Sheng Hung, Jong‐Ling Fuh, Nien-Jung Chen, Yeh‐Shiu Chu, Shu-Cian Chen, Ming-Ji Fann, Yu‐Hui Wong,
Microglia, the immune cells of the central nervous system, play critical roles in brain physiology and pathology. We report a novel approach that produces, within 10 days, the differentiation of human induced pluripotent stem cells (hiPSCs) into microglia (iMG) by forced expression of both SPI1 and CEBPA. High-level expression of the main microglial markers and the purity of the iMG cells were confirmed by RT-qPCR, immunostaining, and flow cytometry analyses. Whole-transcriptome analysis demonstrated ...
Tópico(s): Immune cells in cancer
2021 - Elsevier BV | Stem Cell Reports
Stephen D. Raj, David Y. Fann, Esther Wong, Brian K. Kennedy,
Over the past decade, significant attention has been given to repurposing Food and Drug Administration approved drugs to treat age-related diseases. In contrast, less consideration has been given to natural bioactive compounds. Consequently, there have been limited attempts to translate these compounds. Autophagy is a fundamental biological pathway linked to aging, and numerous strategies to enhance autophagy have been shown to extend lifespan. Interestingly, there are a number of natural products ...
Tópico(s): Histone Deacetylase Inhibitors Research
2021 - Wiley | Medicinal Research Reviews
Alison E. Schwing, Y. Joel Wong, Melanie D. Fann,
African American men encounter unique experiences of stereotypes and racism (Hall, 2001; Majors & Billson, 1993). However, to date, conceptualizations and measures of racism-related stress have not adequately accounted for these unique experiences. Furthermore, although theories of masculinity provide useful conceptualizations of the stressful consequences of men’s masculinity experiences, they do not account for the unique gendered racism stress experienced by men of color. Therefore, the purpose ...
Tópico(s): Work-Family Balance Challenges
2012 - American Psychological Association | Psychology of Men & Masculinity
David E. Bernholdt, E. Apr�, Herbert A. Fr�chtl, Martyn F. Guest, Robert J. Harrison, Rick A. Kendall, Ramzi Kutteh, Xiting Long, John B. Nicholas, Jeffrey A. Nichols, Hamish Taylor, Adrian T. Wong, George I. Fann, R.J. Littlefield, Jarek Nieplocha,
We describe the design philosophy, structure, and supporting tool kits of the NWChem computational chemistry package. The primary purpose of this effort was to develop efficient parallel algorithms for a broad range of methods commonly used in computational chemistry. To facilitate this, we developed a shared nonuniform access memory model which simplifies parallel programming while at the same time providing for portability across both distributed- and shared-memory machines. In addition to this ...
Tópico(s): Distributed and Parallel Computing Systems
1995 - Wiley | International Journal of Quantum Chemistry
Jaime R. DeLuca, Callie Batts Maddox, Jacob J. Bustad,
... 11–12, 2014, pp. 419– 435. Chia, Stacey. “ Fann Wong Flaunts Slender Post-Pregnancy Physique; Christopher Misses Her ... Straits Times, 2015, https://www.straitstimes.com/lifestyle/fann-wong-flaunts-slender-post-pregnancy-physique-christopher-misses-her- ...
Tópico(s): Eating Disorders and Behaviors
2023 - Wiley | The Journal of Popular Culture
Chui Fann Wong, Chen-Yen Leow, Gerhard Grüber,
The cases of lung disease caused by non-tuberculous mycobacterium Mycobacterium abscessus (Mab) are increasing and not reliably curable. Repurposing of anti-tuberculosis inhibitors brought the oxidative phosphorylation pathway with its final product ATP, formed by the essential F1FO-ATP synthase (subunits α3:β3:γ:δ:ε:a:b:b':c9), into focus as an attractive inhibitor target against Mab. Because of the pharmacological attractiveness of this enzyme, we generated and purified a recombinant and enzymatically ...
Tópico(s): RNA modifications and cancer
2023 - Elsevier BV | Biochemical and Biophysical Research Communications
Wuan Geok Saw, Khoa C. M. Le, Joon Shin, Jes Hui Min Kwek, Chui Fann Wong, Priya Ragunathan, Tuck Choy Fong, Volker Müller, Gerhard Grüber,
Abstract The Acinetobacter baumannii F 1 F O ‐ATP synthase (α 3 :β 3 :γ:δ:ε: a : b 2 : c 10 ), which is essential for this strictly respiratory opportunistic human pathogen, is incapable of ATP‐driven proton translocation due to its latent ATPase activity. Here, we generated and purified the first recombinant A. baumannii F 1 ‐ATPase ( Ab F 1 –ATPase) composed of subunits α 3 :β 3 :γ:ε, showing latent ATP hydrolysis. A 3.0 Å cryo‐electron microscopy structure visualizes the architecture and regulatory element of ...
Tópico(s): RNA modifications and cancer
2023 - Wiley | The FASEB Journal
Martyn F. Guest, Edoardo Aprà, David E. Bernholdt, H.A. Früchtl, Robert J. Harrison, Ricky A. Kendall, Ramzi Kutteh, Xiting Long, J.B. Nicholas, Jeffrey A. Nichols, Henry L. Taylor, Adrian T. Wong, George I. Fann, R.J. Littlefield, Jarek Nieplocha,
The impact of high-performance computing in computational chemistry is considered in the light of increasing demands for both the number and complexity of chemical systems amenable to theoretical treatment. Using self-consistent field Density Functional Theory (DFT) as a prototypical application, we describe the development, implementation and performance of the NWChem computational chemistry package that is targeting both present and future generations of massively parallel processors (MPP). The ...
Tópico(s): Cloud Computing and Resource Management
1996 - Elsevier BV | Future Generation Computer Systems
Luting Poh, David Y. Fann, Peiyan Wong, Vismitha Rajeev, Sharmelee Selvaraji, Christopher Chen, Mitchell K.P. Lai, Hsiu Kim Lina Lim, Thiruma V. Arumugam,
Chronic cerebral hypoperfusion is associated with vascular dementia (VaD). Cerebral hypoperfusion may initiate complex molecular and cellular inflammatory pathways that contribute to long term cognitive impairment and memory loss. Inflammasome is an intracellular multi-protein complex that initiates an innate immune response, and is involved in multiple acute and chronic neurological diseases such as ischemic stroke, Alzheimer's disease (AD), Parkinson's Disease (PD), and amyotrophic lateral sclerosis ( ...
Tópico(s): Inflammasome and immune disorders
2021 - Wiley | Alzheimer s & Dementia
Hung-Hsi Chen, Yu‐Hui Wong, Anne-Marie Genevière, Ming-Ji Fann,
Due to the strong sequence homology it has been suggested that CDC2L5 and CDK12 belong to a high molecular weight subfamily of CDC2 family with PITAI/VRE motifs [F. Marques, J.L. Moreau, G. Peaucellier, J.C. Lozano, P. Schatt, A. Picard, I. Callebaut, E. Perret, A.M. Geneviere, A new subfamily of high molecular mass CDC2-related kinases with PITAI/VRE motifs, Biochem. Biophys. Res. Commun. 279 (2000) 832-837]. Recently, we reported that CDK12 interacts with L-type cyclins and is involved in alternative ...
Tópico(s): RNA and protein synthesis mechanisms
2007 - Elsevier BV | Biochemical and Biophysical Research Communications
Hong‐Ru Chen, Hsien-Chia Juan, Yu‐Hui Wong, Jin‐Wu Tsai, Ming-Ji Fann,
DNA damage response (DDR) pathways are critical for ensuring that replication stress and various types of DNA lesion do not perturb production of neural cells during development. Cdk12 maintains genomic stability by regulating expression of DDR genes. Mutant mice in which Cdk12 is conditionally deleted in neural progenitor cells (NPCs) die after birth and exhibit microcephaly with a thinner cortical plate and an aberrant corpus callosum. We show that NPCs of mutant mice accumulate at G2 and M phase, ...
Tópico(s): RNA Research and Splicing
2016 - Oxford University Press | Cerebral Cortex
April Budd, Stephanie Lukas, Unarose Hogan, Kamugisha Priscille, Kanamugire Fann, Pauline Hill, Ndikumana Edouard, Jean Bosco Byukusenge, Placide Ntigurirwa, Mutayomba Aimable, Rex Wong,
Health-care-associated infections (HCAIs) are a major global safety concern for patients, health- care professionals and public health particularly in developing countries where access to hand washing facilities is limited due to infrastructure. Alcohol-based hand sanitizer offers a viable alternative where water sources are unreliable or insufficient. However, in resource-limited settings, the introduction of alcohol-based hand sanitizer has been slow due to economic, manufacturing and procurement ...
Tópico(s): Medical Device Sterilization and Disinfection
2016 - Scientific Research Publishing | Journal of Service Science and Management
Hsin‐Liang Chen, Yida Huang, Tsong‐Shin Lim, Chun‐Jen Su, P. H. Chen, A. C. Su, Ken‐Tsung Wong, Tzu Cheng Chao, Shu‐Hua Chan, Wunshain Fann,
By means of time-resolved photoluminescence and photothermal techniques, after-effects from excited-state dynamics, energy migration, and conformational rearrangement of poly(9,9-di-n-octyl-2,7-fluorene) (PFO) and its homologues has been examined and interpreted with rotational potential maps from quantum mechanical calculations. Steady-state photoluminescence spectral changes and time-resolved photoluminescence measurements of oligofluorenes and PFO diluted in toluene suggest excited state ring ...
Tópico(s): Advanced Chemical Physics Studies
2009 - American Chemical Society | The Journal of Physical Chemistry B
Ricky A. Kendall, Edoardo Aprà, David E. Bernholdt, Eric J. Bylaska, Michel Dupuis, George I. Fann, Robert J. Harrison, Jialin Ju, Jeffrey A. Nichols, Jarek Nieplocha, Tjerk P. Straatsma, Theresa L. Windus, Adrian T. Wong,
NWChem is the software package for computational chemistry on massively parallel computing systems developed by the High Performance Computational Chemistry Group for the Environmental Molecular Sciences Laboratory. The software provides a variety of modules for quantum mechanical and classical mechanical simulation. This article describes the design and some implementation details of the overall NWChem architecture. The architecture facilitates rapid development and portability of fully distributed ...
Tópico(s): Scientific Computing and Data Management
2000 - Elsevier BV | Computer Physics Communications
Hsin‐Liang Chen, Yi-Fang Huang, Chao‐Ping Hsu, Tsong‐Shin Lim, Li-Chung Kuo, Man‐kit Leung, Teng‐Chih Chao, Ken‐Tsung Wong, Show‐An Chen, Wunshain Fann,
Photothermal calorimetry and fluorescence spectroscopy were used to determine the relaxations of the photoexcited singlet state of two PPV and polyfluorene oligomers, (E,E)-1,4-bis[(2-benzyloxy)styryl]benzene (PVDOP) and ter(9,9'-spirobifluorene) (TSBF). The decay rates of different S1 relaxation channels, which include intersystem crossing (ISC), radiative, and nonradiative decay can be determined by the combination of photoacoustic calorimetry (PAC) and the time-correlated single photon counting (TCSPC) ...
Tópico(s): Luminescence and Fluorescent Materials
2007 - American Chemical Society | The Journal of Physical Chemistry A
Negareh Mousavi, Douglas C. Shook, Niamh Kilcullen, Sary F. Aranki, Raymond Y. Kwong, Michael J. Landzberg, Ron Blankstein,
... 1958; 148: 433– 436.CrossrefMedlineGoogle Scholar3. Wasserman SM, Fann JI, Atwood JE, Burdon TA, Fadel BM. Acquired left ventricular-right atrial communication: Gerbode-type defect. Echocardiography. 2002; 19: 67– 72.CrossrefMedlineGoogle Scholar4. Srichai MB, Lim RP, Wong S, Lee VS. Cardiovascular applications of phase-contrast ...
Tópico(s): Coronary Artery Anomalies
2012 - Lippincott Williams & Wilkins | Circulation
Khoa C. M. Le, Chui Fann Wong, Volker Müller, Gerhard Grüber,
Abstract Priority 1: critical WHO pathogen Acinetobacter baumannii depends on ATP synthesis and ATP:ADP homeostasis and its bifunctional F 1 F O ‐ATP synthase. While synthesizing ATP, it regulates ATP cleavage by its inhibitory ε subunit to prevent wasteful ATP consumption. We determined cryo‐electron microscopy structures of the ATPase active A. baumannii F 1 ‐αßγε Δ134–139 mutant in four distinct conformational states, revealing four transition states and structural transformation of the ε's C‐terminal ...
Tópico(s): RNA modifications and cancer
2024 - Wiley | The FASEB Journal
Vikneswaran Mathiyazakan, Chui Fann Wong, Amaravadhi Harikishore, Kévin Pethe, Gerhard Grüber,
Tópico(s): Advanced Materials Characterization Techniques
2024 - Elsevier BV | Biochimica et Biophysica Acta (BBA) - Bioenergetics