1. Mol Cell. 2010 Jul 30;39(2):196-208. Defining the pathway of cytoplasmic maturation of the 60S ribosomal subunit. Lo KY, Li Z, Bussiere C, Bresson S, Marcotte EM, Johnson AW. Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA. In eukaryotic cells the final maturation of ribosomes occurs in the cytoplasm, where trans-acting factors are removed and critical ribosomal proteins are added for functionality. Here, we have carried out a comprehensive analysis of cytoplasmic maturation, ordering the known steps into a coherent pathway. Maturation is initiated by the ATPase Drg1. Downstream, assembly of the ribosome stalk is essential for the release of Tif6. The stalk recruits GTPases during translation. Because the GTPase Efl1, which is required for the release of Tif6, resembles the translation elongation factor eEF2, we suggest that assembly of the stalk recruits Efl1, triggering a step in 60S biogenesis that mimics aspects of translocation. Efl1 could thereby provide a mechanism to functionally check the nascent subunit. Finally, the release of Tif6 is a prerequisite for the release of the nuclear export adaptor Nmd3. Establishing this pathway provides an important conceptual framework for understanding ribosome maturation. PMCID: PMC2925414 [Available on 2011/7/1] PMID: 20670889 [PubMed - indexed for MEDLINE] 2. J Neurosci. 2010 Jul 7;30(27):9166-71. Amyloid-beta peptide oligomers disrupt axonal transport through an NMDA receptor-dependent mechanism that is mediated by glycogen synthase kinase 3beta in primary cultured hippocampal neurons. Decker H, Lo KY, Unger SM, Ferreira ST, Silverman MA. Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada. Disruption of axonal transport is a hallmark of several neurodegenerative diseases, including Alzheimer's disease (AD). Even though defective transport is considered an early pathologic event, the mechanisms by which neurodegenerative insults impact transport are poorly understood. We show that soluble oligomers of the amyloid-beta peptide (AbetaOs), increasingly recognized as the proximal neurotoxins in AD pathology, induce disruption of organelle transport in primary hippocampal neurons in culture. Live imaging of fluorescent protein-tagged organelles revealed a marked decrease in axonal trafficking of dense-core vesicles and mitochondria in the presence of 0.5 microm AbetaOs. NMDA receptor (NMDAR) antagonists, including d-AP5, MK-801, and memantine, prevented the disruption of trafficking, thereby identifying signals for AbetaO action at the cell membrane. Significantly, both pharmacological inhibition of glycogen synthase kinase-3beta (GSK-3beta) and transfection of neurons with a kinase-dead form of GSK-3beta prevented the transport defect. Finally, we demonstrate by biochemical and immunocytochemical means that AbetaOs do not affect microtubule stability, indicating that disruption of transport involves a more subtle mechanism than microtubule destabilization, likely the dysregulation of intracellular signaling cascades. Results demonstrate that AbetaOs negatively impact axonal transport by a mechanism that is initiated by NMDARs and mediated by GSK-3beta and establish a new connection between toxic Abeta oligomers and AD pathology. PMID: 20610750 [PubMed - indexed for MEDLINE] 3. Opt Express. 2009 Dec 7;17(25):22386-92. doi: 10.1364/OE.17.022386. All-optical and polarization-independent spatial filter based on a vertically-aligned polymer-stabilized liquid crystal film with a photoconductive layer. Huang CY, Ma JM, Mo TS, Lo KC, Lo KY, Lee CR. Institute of Electro-Optical Science and Engineering and Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan, Taiwan 701, Republic of China. An all-optical and polarization-independent spatial filter was developed in a vertically-aligned (VA) polymer-stabilized liquid crystal (PSLC) film with a photoconductive (PC) layer. This spatial filter is based on the effect of light on the conductivity of PC layer: high (low)-intensity light makes the conductivity of the PC layer high (low), resulting in a low (high) threshold voltage of the PC-coated VA PSLC cell. Experimental results indicate that this spatial filter is a high-pass filter with low optical-power consumption (about 1.11 mW/cm(2)) in an optical Fourier transform system. The high-pass characteristic was confirmed by simulation. Accordingly, the all-optical and polarization-independent spatial filter can be used to enhance the edges of images. PMID: 20052162 [PubMed - indexed for MEDLINE] 4. J Cell Biol. 2009 Sep 21;186(6):849-62. Ribosome stalk assembly requires the dual-specificity phosphatase Yvh1 for the exchange of Mrt4 with P0. Lo KY, Li Z, Wang F, Marcotte EM, Johnson AW. Department of Chemistry and Biochemistry, Section of Molecular Genetics and Microbiology, The Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA. The ribosome stalk is essential for recruitment of translation factors. In yeast, P0 and Rpl12 correspond to bacterial L10 and L11 and form the stalk base of mature ribosomes, whereas Mrt4 is a nuclear paralogue of P0. In this study, we show that the dual-specificity phosphatase Yvh1 is required for the release of Mrt4 from the pre-60S subunits. Deletion of YVH1 leads to the persistence of Mrt4 on pre-60S subunits in the cytoplasm. A mutation in Mrt4 at the protein-RNA interface bypasses the requirement for Yvh1. Pre-60S subunits associated with Yvh1 contain Rpl12 but lack both Mrt4 and P0. These results suggest a linear series of events in which Yvh1 binds to the pre-60S subunit to displace Mrt4. Subsequently, P0 loads onto the subunit to assemble the mature stalk, and Yvh1 is released. The initial assembly of the ribosome with Mrt4 may provide functional compartmentalization of ribosome assembly in addition to the spatial separation afforded by the nuclear envelope. PMCID: PMC2753163 PMID: 19797078 [PubMed - indexed for MEDLINE] 5. Opt Express. 2009 Jul 20;17(15):12910-21. Color cone lasing emission in a dye-doped cholesteric liquid crystal with a single pitch. Lee CR, Lin SH, Yeh HC, Ji TD, Lin KL, Mo TS, Kuo CT, Lo KY, Chang SH, Fuh AY, Huang SY. Institute of Electro-Optical Science and Engineering and Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan, Taiwan 701, Republic of China. crlee@mail.ncku.edu.tw This work investigates a novel color cone lasing emission (CCLE) based on a one-dimensional photonic crystal-like dye-doped cholesteric liquid crystal (DDCLC) film with a single pitch. The lasing wavelength in the CCLE is distributed continuously at 676.7-595.6 nm, as measured at a continuously increasing oblique angle relative to the helical axis of 0-50 degrees . This work demonstrates that lasing wavelength coincides exactly with the wavelength at the long wavelength edge of the CLC reflection band at oblique angles of 0-50 degrees . Simulation results of dispersion relations at different oblique angles using Berreman's 4X4 matrix method agrees closely with experimental results. Some unique and important features of the CCLE are identified and discussed. PMID: 19654696 [PubMed - indexed for MEDLINE] 6. Hong Kong Med J. 2009 Jun;15(3):201-8. Refractory thrombotic thrombocytopenic purpura and membranoproliferative glomerulonephritis successfully treated with rituximab: a case associated with hepatitis C virus infection. Mak SK, Lo KY, Lo MW, Chan SF, Lo KC, Wong YY, Tong GM, Wong PN, Ma ES, Wong AK. Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, Kowloon, Hong Kong. maksk@ha.org.hk Plasmapheresis remains the main treatment modality for patients with thrombotic thrombocytopenic purpura. We report a patient who had simultaneous onset of membranoproliferative glomerulonephritis and thrombotic thrombocytopenic purpura. She did not improve after 48 plasmapheresis sessions. A 6-week course of weekly intravenous doses of rituximab was then given. This achieved complete remission of her nephrotic syndrome and improvement in her renal function, so plasmapheresis was ceased. She had a low ADAMTS13 antigen level and a positive ADAMTS13 antibody, both of which reverted to normal after treatment with rituximab. This coincided with a rise in her hepatitis C virus RNA and liver transaminases. Liver biopsies did not reveal active fibrosis. Her hepatitis C virus RNA titre dropped afterwards, and she had no relapses of her thrombotic thrombocytopenic purpura and nephrotic syndrome, for more than 2 years after remission. The simultaneous onset and successful outcomes of both the membranoproliferative glomerulonephritis and thrombotic thrombocytopenic purpura illustrate the usefulness of rituximab. We discuss its use and risks, in the context of chronic hepatitis C infection. PMID: 19494376 [PubMed - indexed for MEDLINE] 7. Ren Fail. 2009;31(2):149-52. Hepatitis C virus-associated type II mixed cryoglobulinemia vasculitis complicated with membranous proliferative glomerulonephritis. Lo KY, Chen CY, Lee CS. Department of Urology, Tian-Sheng Memorial Hospital, Ping-Tong, Taiwan. Essential mixed cryoglobulinemia (type II) has turned out to be secondary to hepatitis C virus (HCV) infection in the large majority of patients. Interferon might be anticipated to be effective only in HCV-associated cryoglobulinemias. We found that interferon was highly effective in an HCV-positive patient with true essential type II mixed cryoglobulinemia. The patient presented with symptomatic cryoglobulinemic vasculitis without underlying immunologic, infectious, or neoplastic diseases. Tests for HCV viremia, a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, and anti-HCV antibodies (third-generation assays) were positive before therapy. The patient had severe cryoglobulinemic vasculitis with purpura, peripheral neuropathy, and membranous proliferative glomerulonephritis. The cryocrit before therapy was 6 percent in the patient. Recombinant interferon alfa-2a (Roferon-A, Hoffmann-LaRoche, Basel, Switzerland) was administered at a dose of 3 million units per day for three months and 3 million units every other day for the subsequent nine months, a protocol adopted for HCV-associated cryoglobulinemia. The patient had a complete clinical response, with the disappearance of serum cryoglobulins and all signs of cutaneous vasculitis and with the normalization of kidney-function results and urinary values in the patient with nephropathy. The patient has remained in complete remission for more than one year since the withdrawal of therapy. True essential mixed cryoglobulinemia with HCV infection complicated with glomerulonephritis represents a therapeutic challenge. PMID: 19212913 [PubMed - indexed for MEDLINE] 8. Mol Biol Cell. 2009 Mar;20(5):1545-54. Epub 2009 Jan 14. Reengineering ribosome export. Lo KY, Johnson AW. Institute for Cellular and Molecular Biology, the University of Texas at Austin, Austin, TX 78712, USA. Large cargoes require multiple receptors for efficient transport through the nuclear pore complex. The 60S ribosomal subunit is one of the bulkiest transport cargoes, and in yeast three different receptors, Crm1, Mex67/Mtr2, and Arx1, collaborate in its export. However, only Crm1, recruited by the adapter Nmd3, appears to be conserved for 60S export in higher eukaryotes. We asked if export of the large subunit requires specific receptors. We made protein fusions between mutant Nmd3 and various export receptors. Surprisingly, fusions of Mex67, the tRNA exportin Los1, Mtr2, Cse1, or Msn5 to Nmd3, lacking its Crm1-dependent nuclear export signal (NES), all functioned in export. Furthermore, these chimeric proteins supported 60S export even in the presence of the Crm1 inhibitor leptomycin B, indicating that export was now independent of Crm1. These results suggest that there is not a requirement for a specific export receptor for the large subunit, as recruitment of any receptor will suffice. Finally we show that the addition of an NES directly to the 60S ribosomal subunit protein Rpl3 promotes export. These results imply remarkable flexibility in the export pathway for the 60S subunit and help explain how different export receptors could have evolved in different eukaryotic lineages. PMCID: PMC2649259 PMID: 19144820 [PubMed - indexed for MEDLINE] 9. Chem Commun (Camb). 2008 Sep 28;(36):4324-6. Epub 2008 Jul 18. Transistors from a conjugated macrocycle molecule: field and photo effects. Zhao W, Tang Q, Chan HS, Xu J, Lo KY, Miao Q. Department of Chemistry, the Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. This study explores a conjugated macrocycle molecule and details its synthesis, molecular structure, assemblies in the solid state and application in phototransistors. PMID: 18802558 [PubMed] 10. IEEE Trans Vis Comput Graph. 2008 Sep-Oct;14(5):982-98. Dual Poisson-Disk Tiling: an efficient method for distributing features on arbitrary surfaces. Li H, Lo KY, Leung MK, Fu CW. Department of Computer Science and Engineering, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong. lihw@cse.ust.hk This paper introduces a novel surface-modeling method to stochastically distribute features on arbitrary topological surfaces. The generated distribution of features follows the Poisson disk distribution, so we can have a minimum separation guarantee between features and avoid feature overlap. With the proposed method, we not only can interactively adjust and edit features with the help of the proposed Poisson disk map, but can also efficiently re-distribute features on object surfaces. The underlying mechanism is our dual tiling scheme, known as the Dual Poisson-Disk Tiling. First, we compute the dual of a given surface parameterization, and tile the dual surface by our specially-designed dual tiles; during the pre-processing, the Poisson disk distribution has been pre-generated on these tiles. By dual tiling, we can nicely avoid the problem of corner heterogeneity when tiling arbitrary parameterized surfaces, and can also reduce the tile set complexity. Furthermore, the dual tiling scheme is non-periodic, and we can also maintain a manageable tile set. To demonstrate the applicability of this technique, we explore a number of surface-modeling applications: pattern and shape distribution, bump-mapping, illustrative rendering, mold simulation, the modeling of separable features in texture and BTF, and the distribution of geometric textures in shell space. PMID: 18599912 [PubMed - indexed for MEDLINE] 11. J Nanosci Nanotechnol. 2008 May;8(5):2500-4. The integration solution of copper barrier deposition for nanometer interconnect process. Chen KW, Wang YL, Tsao JC, Lo KY. Department of Materials Science, National University of Tainan, Tainan, Taiwan. As the dimensions of devices are shrunk quickly, the requirements of metallization become more critical. For VIA barrier and seeding layer filling and deposition, the process was mostly applied with the copper physical vapor deposition methodology in the back-end of line flow of the interconnection metallization. The criteria for barrier and seeding layer deposition are the metal continuity inside the VIA feature and grain size and orientation control for film diffusion barrier and qualities. Besides, while the interconnection size shrunk to nano-scale, the barrier thickness would be very thinner to maintain the VIA resistance; however, it would face the film conformity and continuity consistence within the wafer and different features. The integration solution would be developed and studied with the re-sputter process step adding into the convectional physical vapor deposition process. The resputter process step could not only improve the film conformity and continuity in the VIA's sidewall; but also reduce the resistance of VIA feature over 20%. The improvement of the resputter method adding into the deposition process would be contributed to the standard barrier deposition in the nano-scale feature of the interconnect. Besides, we also discussed the effect of the film properties after the resputter process introduced into the barrier deposition. PMID: 18572673 [PubMed] 12. Nephrology (Carlton). 2008 Jun;13(4):331-6. Efficacy of enteric-coated mycophenolate sodium in patients with active lupus nephritis. Mak SK, Lo KY, Lo MW, Chan SF, Tong GM, Wong PN, Wong AK. Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, Kowloon, Hong Kong. maksk@ha.org.hk BACKGROUND: The ideal treatment of lupus nephritis has yet to be defined. Both cyclophosphamide and mycophenolate mofetil have been used with encouraging results, but adverse events are frequently seen. There are no data on the use of enteric-coated mycophenolate sodium. METHODS: We retrospectively reviewed 12 patients with active forms of lupus nephritis (1 class III, 7 class IV and 4 class V) treated with enteric-coated mycophenolate sodium combined with corticosteroids. RESULTS: The mean age of the patients was 32.3 +/- 11.2 years and the average length of follow up was 25.9 +/- 8.9 months. The mean serum creatinine clearance was 93 +/- 30.1 mL/min per 1.73 m(2) and the mean proteinuria level was 4.5 +/- 3.6 g/day. All had features that warranted aggressive treatment. Mycophenolate sodium was given for 12.9 +/- 9.7 months with an averaged starting dose of 1350 +/- 163 mg/day. Six patients attained complete remission and six attained partial remission with treatment. The mean interval to attain first remission (complete or partial) was 8.3 +/- 5.7 weeks. At last follow up, all patients were in complete or partial remission. Apart from herpes zoster that developed in one patient, no other significant side-effects were encountered. CONCLUSION: Enteric-coated mycophenolate sodium was effective and well-tolerated in the treatment of active lupus nephritis. PMID: 18476916 [PubMed - indexed for MEDLINE] 13. Perit Dial Int. 2008 Mar-Apr;28(2):155-62. Treatment of fungal peritonitis with a combination of intravenous amphotericin B and oral flucytosine, and delayed catheter replacement in continuous ambulatory peritoneal dialysis. Wong PN, Lo KY, Tong GM, Chan SF, Lo MW, Mak SK, Wong AK. Renal Unit, Department of Medicine & Geriatrics, Kwong Wah Hospital, Hong Kong SAR, China. apnwong@alumni.cuhk.net Comment in: Perit Dial Int. 2008 Mar-Apr;28(2):130-3. BACKGROUND: Fungal peritonitis (FP) is associated with significant mortality and high risk of peritoneal failure. The optimum treatment for peritoneal dialysis (PD)-associated FP remains unclear. Since January 2000 we have been treating FP with a combination of intravenous amphotericin B and oral flucytosine, together with deferred catheter replacement. We examined the clinical course and outcome of the FP patients treated with this approach (study group). An outcome comparison was also made to an alternatively treated historic cohort (control group). METHODS: This was a single-center retrospective study. The clinical course and outcome of 13 consecutive episodes of FP occurring in 13 patients treated between January 2000 and April 2005 with the study approach were examined. The patients were treated with an incremental dose of intravenous amphotericin B to a target dose of 0.75 - 1 mg/kg body weight/day, and oral flucytosine 1 g/day upon a diagnosis of FP at 3.77 +/- 0.93 days from presentation. Replacement of the peritoneal catheter was intended after complete clearing of effluent, after which, antifungal chemotherapy was continued for another 1 - 2 weeks. Their outcome was compared with 14 historic controls that were treated between April 1995 and December 1999. RESULTS: Mean age of the study group was 58.7 +/- 13.2 years; male-to-female ratio was 2:11; 6 (46.1%) were diabetic. All FP were caused by Candida species (C. albicans, 2; C. parapsilosis, 8; C. glabrata, 3). Two (15.4%) patients died before resolution of the peritonitis. The dialysate effluent cleared in 11 patients (84.6%) after 13.2 +/- 3.3 days of treatment, but 2 patients died of acute myocardial infarction before catheter replacement. Nine patients had their catheters replaced at day 26.7 +/- 7.7 of treatment; all 9 returned to PD after a total of 31 +/- 12.2 days of antifungal chemotherapy. Reversible liver dysfunction was common with this regimen. When compared with the 14 cases in the historic control group (Candida species, 13; Trichosporon, 1), who were treated with amphotericin B, fluconazole, or a combination of the two, and the majority (78.6%) of whose catheters were removed before day 10 of presentation, the study group appeared to have a lower technique failure rate (30.8% vs 78.6%, p = 0.013) and similar all-cause mortality (30.7% vs 28.5%, p = NS), FP-related mortality (15.4% vs 28.5%, p = NS), and length of hospitalization (48.5 +/- 30.2 vs 57.0 +/- 37.7 days, p = NS). However, a significantly earlier commencement of antifungal treatment in the study group (3.8 +/- 0.9 vs 5.8 +/- 2.4 days, p = 0.012) could be an important confounder of outcome. CONCLUSIONS: Combination of intravenous amphotericin B and oral flucytosine with deferred catheter replacement appears to be associated with a relatively low incidence of PD technique failure, without affecting mortality in patients suffering from FP due to yeasts in this preliminary study. Nonetheless, drug-induced hepatic dysfunction was common; close monitoring during treatment is of paramount importance. The reasons accounting for the observed distinctive outcome remain unclear and further study is required to confirm the results and to investigate for the underlying mechanism. PMID: 18332451 [PubMed - indexed for MEDLINE] 14. Mol Biol Cell. 2008 Feb;19(2):735-44. Epub 2007 Dec 12. Arx1 is a nuclear export receptor for the 60S ribosomal subunit in yeast. Hung NJ, Lo KY, Patel SS, Helmke K, Johnson AW. Section of Molecular Genetics and Microbiology and the Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA. We previously showed that nuclear export of the large (60S) ribosomal subunit relies on Nmd3 in a Crm1-dependent manner. Recently the general mRNA export factor, the Mtr2/Mex67 heterodimer, was shown to act as an export receptor in parallel with Crm1. These observations raise the possibility that nuclear export of the 60S subunit in Saccharomyces cerevisiae requires multiple export receptors. Here, we show that the previously characterized 60S subunit biogenesis factor, Arx1, also acts as an export receptor for the 60S subunit. We found that deletion of ARX1 was synthetic lethal with nmd3 and mtr2 mutants and was synthetic sick with several nucleoporin mutants. Deletion of ARX1 led to accumulation of pre-60S particles in the nucleus that were enriched for Nmd3, Crm1, Mex67, and Mtr2, suggesting that in the absence of Arx1, 60S export is impaired even though the subunit is loaded with export receptors. Finally, Arx1 interacted with several nucleoporins in yeast two-hybrid as well as in vitro assays. These results show that Arx1 can directly bridge the interaction between the pre-60S particle and the NPC and thus is a third export receptor for the 60S subunit in yeast. PMCID: PMC2230582 PMID: 18077551 [PubMed - indexed for MEDLINE]