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1.  Hydraulic Experiments for Determination of In-situ Hydraulic Conductivity of Submerged Sediments 
Scientific Reports  2015;5:7917.
A new type of in-situ hydraulic permeameter was developed to determine vertical hydraulic conductivity (VHC) of saturated sediments from hydraulic experiments using Darcy's law. The system allows water to move upward through the porous media filled in the permeameter chamber driven into sediments at water-sediment interface. Darcy flux and hydraulic gradient can be measured using the system, and the VHC can be determined from the relationship between them using Darcy's law. Evaluations in laboratory and in field conditions were performed to see if the proposed permeameter give reliable and valid measures of the VHC even where the vertical flow at water-sediment interface and fluctuation of water stage exist without reducing the accuracy of the derived VHC. Results from the evaluation tests indicate that the permeameter proposed in this study can be used to measure VHC of saturated sandy sediments at water-sediment interface in stream and marine environment with high accuracy.
PMCID: PMC4300508  PMID: 25604984
2.  Functional Activation of ATM by the Prostate Cancer Suppressor NKX3.1 
Cell reports  2013;4(3):10.1016/j.celrep.2013.06.039.
The prostate tumor suppressor NKX3.1 augments response to DNA damage and enhances survival after DNA damage. Within minutes of DNA damage, NKX3.1 undergoes phosphorylation at tyrosine 222, which is required for a functional interaction with ataxia telangiectasia mutated (ATM) kinase. NKX3.1 binds to the N-terminal region of ATM, accelerates ATM activation, and hastens the formation of γhistone2AX. NKX3.1 enhances DNA-dependent ATM kinase activation by both the MRN complex and H2O2 in a DNA-damage-independent manner. ATM, bound to the NKX3.1 homeodomain, phosphorylates NKX3.1, leading to ubiquitination and degradation. Thus, NKX3.1 and ATM have a functional interaction leading to ATM activation and then NKX3.1 degradation in a tightly regulated DNA damage response specific to prostate epithelial cells. These findings demonstrate a mechanism for the tumor-suppressor properties of NKX3.1, demonstrate how NKX3.1 may enhance DNA integrity in prostate stem cells and may help to explain how cells differ in their sensitivity to DNA damage.
PMCID: PMC3838670  PMID: 23890999
3.  Direct Activation of ATM by Resveratrol under Oxidizing Conditions 
PLoS ONE  2014;9(6):e97969.
Resveratrol has been widely reported to reduce cancer progression in model systems and to selectively induce cell death in transformed cell lines. Many enzymes have been reported to respond to resveratrol in mammalian cells, including the Ataxia-Telangiectasia Mutated (ATM) protein kinase that acts in DNA damage recognition, signaling, and repair. Here we investigate the responses of ATM to resveratrol exposure in normal and transformed human cell lines and find that ATM autophosphorylation and substrate phosphorylation is stimulated by resveratrol in a manner that is promoted by reactive oxygen species (ROS). We observe direct stimulatory effects of resveratrol on purified ATM in vitro and find that the catalytic efficiency of the kinase on a model substrate is increased by resveratrol. In the purified system we also observe a requirement for oxidation, as the effect of resveratrol on ATM signaling is substantially reduced by agents that prevent disulfide bond formation in ATM. These results demonstrate that resveratrol effects on ATM are direct, and suggest a mechanism by which the oxidizing environment of transformed cells promotes ATM activity and blocks cell proliferation.
PMCID: PMC4059639  PMID: 24933654
4.  Compensation for Occupational Diseases by Chemical Agents in Korea 
Journal of Korean Medical Science  2014;29(Suppl):S78-S84.
Investigation into the frequency of compensation for occupational diseases (ODs) caused by hazardous chemicals revealed an important opportunity for the improvement and further development of occupational health and safety systems in Korea. In response to concerns after outbreaks of disease due to chemical exposure, specific criteria for recognition of ODs were established and included in the Enforcement Decree of the Labor Standard Act (LSA) and the Industrial Accident Compensation Insurance Act (IACIA) on June 28, 2013. However, the original versions of the LSA and IACIA contain several limitations. First, the criteria was listed inconsistently according to the symptoms or signs of acute poisoning. Second, all newly recognized hazardous chemicals and chemicals recognized as hazardous by the International Labor Organization (ILO) were not included in the LSA and IACIA. Although recent amendments have addressed these shortcomings, future amendments should strive to include all chemicals listed by the ILO and continuously add newly discovered hazardous chemicals as they are introduced into the workplace.
Graphical Abstract
PMCID: PMC4085180  PMID: 25006329
Industrial Accident Compensation Insurance Act; Chemical Agents; Workers' Compensation and Welfare Service; Labor Standard Act, Occupational Diseases; Korea
5.  Diagnostic Value of Facial Nerve Antidromic Evoked Potential in Patients With Bell's Palsy: A Preliminary Study 
Annals of Rehabilitation Medicine  2014;38(3):381-387.
To assess the practical diagnostic value of facial nerve antidromic evoked potential (FNAEP), we compared it with the diagnostic value of the electroneurography (ENoG) test in Bell's palsy.
In total, 20 patients with unilateral Bell's palsy were recruited. Between the 1st and 17th days after the onset of facial palsy, FNAEP and ENoG tests were conducted. The degeneration ratio and FNAEP latency difference between the affected and unaffected sides were calculated in all subjects.
In all patients, FNAEP showed prolonged latencies on the affected side versus the unaffected side. The difference was statistically significant. In contrast, there was no significant difference between sides in the normal control group. In 8 of 20 patients, ENoG revealed a degeneration ratio less than 50%, but FNAEP show a difference of more than 0.295±0.599 ms, the average value of normal control group. This shows FNAEP could be a more sensitive test for Bell's palsy diagnosis than ENoG. In particular, in 10 patients tested within 7 days after onset, an abnormal ENoG finding was noted in only four of them, but FNAEP showed a significant latency difference in all patients at this early stage. Thus, FANEP was more sensitive in detecting facial nerve injury than the ENoG test (p=0.031).
FNAEP has some clinical value in the diagnosis of facial nerve degeneration. It is important that FNAEP be considered in patients with facial palsy at an early stage and integrated with other relevant tests.
PMCID: PMC4092180  PMID: 25024963
Bell palsy; Electroneurography; Facial nerve; Antidromic evoked potential
6.  PHF20 regulates NF-κB signalling by disrupting recruitment of PP2A to p65 
Nature communications  2013;4:2062.
Constitutive NF-κB activation in cancer cells is caused by defects in the signalling network responsible for terminating the NF-κB response. Here we report that plant homeodomain finger protein 20 maintains NF-κB in an active state in the nucleus by inhibiting the interaction between PP2A and p65. We show that plant homeodomain finger protein 20 induces canonical NF-κB signalling by increasing the DNA-binding activity of NF-κB subunit p65. In plant homeodomain finger protein 20-overexpressing cells, the termination of tumour necrosis factor-induced p65 phosphorylation is impaired whereas upstream signalling events triggered by tumour necrosis factor are unaffected. This effect strictly depends on the interaction between plant homeodomain finger protein 20 and methylated lysine residues of p65, which hinders recruitment of PP2A to p65, thereby maintaining p65 in a phosphorylated state. We further show that plant homeodomain finger protein 20 levels correlate with p65 phosphorylation levels in human glioma specimens. Our work identifies plant homeodomain finger protein 20 as a novel regulator of NF-κB activation and suggests that elevated expression of plant homeodomain finger protein 20 may drive constitutive NF-κB activation in some cancers.
PMCID: PMC3942884  PMID: 23797602
7.  The Assessment of Reliability of Cognitive Evoked Potential in Normal Person 
Annals of Rehabilitation Medicine  2013;37(2):263-268.
To evaluate intra-tester reliability of P300 more precisely, this study was designed. Event-related potential (ERP) is the result of endogenous brain response following cognitive stimulus. The P300 component of the human ERP is a positive wave with a latency of 300 ms or greater. Our purpose of this study was to estimate reliability of P300 latency and amplitude with 30 normal persons without head injury, as well as to set up them as the reference values in the event that they would be found to be highly reliable.
ERP was performed at three separate times on 30 normal adults in their 20s and 30s. We measured P300 latency and amplitude among ERP.
P300 latency show excellent reliability with intraclass correlation coefficient (ICC) of 0.81. As to P300 amplitude, reliability was good to fair with ICC of 0.53. Average value of P300 latency was 311.3±37.0 ms, shorter than reference value of previous study in Korea.
P300 latency revealed higher reliability than P300 amplitude, although reliability of P300 was confirmed in both component. After further study including precise mechanism, influence factor on measurement and method standardization, it is expected to be an objective indicator to assess the cognitive state and predict prognosis.
PMCID: PMC3660489  PMID: 23705123
Event-related potentials; P300 component; Reliability
8.  Drosophila Tel2 Is Expressed as a Translational Fusion with EpsinR and Is a Regulator of Wingless Signaling 
PLoS ONE  2012;7(9):e46357.
Tel2, a protein conserved from yeast to vertebrates, is an essential regulator of diverse cellular processes including telomere maintenance, DNA damage checkpoints, DNA repair, biological clocks, and cell signaling. The Drosophila Tel2 protein is produced as a translational fusion with EpsinR, a Clathrin adapter that facilitates vesicle trafficking between the Golgi and endosomes. EpsinR and Tel2 are encoded by a Drosophila gene called lqfR. lqfR is required for viability, and its specific roles include cell growth, proliferation, and planar cell polarity. We find that all of these functions of lqfR are attributed entirely to Tel2, not EpsinR. In addition, we find that Drosophila LqfR/Tel2 is a component of one or more protein complexes that contain E-cadherin and Armadillo. Moreover, Tel2 modulates E-cadherin and Armadillo cellular dynamics. We propose that at least one of the functions of Drosophila Tel2 is regulation of Wingless signaling.
PMCID: PMC3460857  PMID: 23029494
9.  Prediction of Liver-Related Events Using Fibroscan in Chronic Hepatitis B Patients Showing Advanced Liver Fibrosis 
PLoS ONE  2012;7(5):e36676.
Liver stiffness measurement (LSM) using transient elastography (FibroScan®) can assess liver fibrosis noninvasively. This study investigated whether LSM can predict the development of liver-related events (LREs) in chronic hepatitis B (CHB) patients showing histologically advanced liver fibrosis.
Between March 2006 and April 2010, 128 CHB patients with who underwent LSM and liver biopsy (LB) before starting nucleot(s)ide analogues and showed histologically advanced fibrosis (≥F3) with a high viral loads [HBV DNA ≥2,000 IU/mL] were enrolled. All patients were followed regularly to detect LRE development, including hepatic decompensation (variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome) and hepatocellular carcinoma (HCC).
The mean age of the patient (72 men, 56 women) was 52.2 years. During the median follow-up period [median 27.8 (12.6–61.6) months], LREs developed in 19 (14.8%) patients (five with hepatic decompensation, 13 with HCC, one with both). Together with age, multivariate analysis identified LSM as an independent predictor of LRE development [P<0.044; hazard ratio (HR), 1.038; 95% confidence interval (CI), 1.002–1.081]. When the study population was stratified into two groups using the optimal cutoff value (19 kPa), which maximized the sum of sensitivity (61.1%) and specificity (86.2%) from a time-dependent receiver operating characteristic curve, patients with LSM>19 kPa were at significantly greater risk than those with LSM≤19 kPa for LRE development (HR, 7.176; 95% CI, 2.257–22.812; P = 0.001).
LSM can be a useful predictor of LRE development in CHB patients showing histologically advanced liver fibrosis.
PMCID: PMC3344942  PMID: 22574212
10.  Draft Genome Sequence of Shewanella sp. Strain HN-41, Which Produces Arsenic-Sulfide Nanotubes 
Journal of Bacteriology  2011;193(18):5039-5040.
The dissimilatory metal reducing bacterium Shewanella sp. strain HN-41 was first reported to produce novel photoactive As-S nanotubes via reduction of As(V) and S2O32− under anaerobic conditions. Here we report the draft genome sequence and annotation of strain HN-41.
PMCID: PMC3165682  PMID: 21868804
11.  Novel Pyrrolopyrimidine-Based α-Helix Mimetics: Cell-Permeable Inhibitors of Protein-Protein Interactions 
There is considerable interest in developing nonpeptidic, small molecule α-helix mimetics to disrupt α-helix-mediated protein-protein interactions. Herein, we report the design of a novel pyrrolopyrimidine-based scaffold for such α-helix mimetics with increased conformational rigidity. We also developed a facile solid phase synthetic route, which is amenable to divergent synthesis of a large library. Using a fluorescence polarization-based assay, we identified cell permeable, dual MDMX/MDM2 inhibitors, demonstrating that the designed molecules can act as α-helix mimetics.
PMCID: PMC3079198  PMID: 21171592
12.  True Neurogenic Thoracic Outlet Syndrome Following Hyperabduction during Sleep - A Case Report - 
Annals of Rehabilitation Medicine  2011;35(4):565-569.
True neurogenic thoracic outlet syndrome (TOS) is an uncommon disease and is difficult to diagnose at the early stage and then completely cure. We experienced a case of true neurogenic TOS with typical clinical symptoms and electrophysiologic findings as a result of repetitive habitual sleep posture. A 31-year-old woman who had complained of progressive tingling sensation on the 4th and 5th fingers with shoulder pain was diagnosed of brachial plexopathy at the lower trunk level by electrodiagnostic studies. There was no other cause of brachial plexopathy except her habit of hyperabduction of shoulder during sleep. This case demonstrated that the habitual abnormal posture can be the only major cause of neurogenic TOS. It is of importance to consider TOS with the habitual cause because simple correction of the posture could stabilize or even reverse disease progress.
PMCID: PMC3309244  PMID: 22506174
Thoracic outlet syndrome; Neurogenic; Hyperabduction sleep
13.  A forward chemical genetic screen reveals an inhibitor of the Mre11–Rad50–Nbs1 complex 
Nature chemical biology  2008;4(2):119-125.
The MRN (Mre11-Rad50-Nbs1)-ATM (ataxia-telangiectasia mutated) pathway is essential for sensing and signaling from DNA double-strand breaks. The MRN complex acts as a DNA damage sensor, maintains genome stability during DNA replication, promotes homology-dependent DNA repair and activates ATM. MRN is essential for cell viability, which has limited functional studies of the complex. Small-molecule inhibitors of MRN could circumvent this experimental limitation and could also be used as cellular radio- and chemosensitization compounds. Using cell-free systems that recapitulate faithfully the MRN-ATM signaling pathway, we designed a forward chemical genetic screen to identify inhibitors of the pathway, and we isolated Z-5-(4-hydroxybenzylidene)-2-imino-1,3-thiazolidin-4-one (mirin, 1) as an inhibitor of MRN. Mirin prevents MRN-dependent activation of ATM without affecting ATM protein kinase activity, and it inhibits Mre11-associated exonuclease activity. Consistent with its ability to target the MRN complex, mirin abolishes the G2/M checkpoint and homology-dependent repair in mammalian cells.
PMCID: PMC3065498  PMID: 18176557
14.  The Functions of Auxilin and Rab11 in Drosophila Suggest That the Fundamental Role of Ligand Endocytosis in Notch Signaling Cells Is Not Recycling 
PLoS ONE  2011;6(3):e18259.
Notch signaling requires ligand internalization by the signal sending cells. Two endocytic proteins, epsin and auxilin, are essential for ligand internalization and signaling. Epsin promotes clathrin-coated vesicle formation, and auxilin uncoats clathrin from newly internalized vesicles. Two hypotheses have been advanced to explain the requirement for ligand endocytosis. One idea is that after ligand/receptor binding, ligand endocytosis leads to receptor activation by pulling on the receptor, which either exposes a cleavage site on the extracellular domain, or dissociates two receptor subunits. Alternatively, ligand internalization prior to receptor binding, followed by trafficking through an endosomal pathway and recycling to the plasma membrane may enable ligand activation. Activation could mean ligand modification or ligand transcytosis to a membrane environment conducive to signaling. A key piece of evidence supporting the recycling model is the requirement in signaling cells for Rab11, which encodes a GTPase critical for endosomal recycling. Here, we use Drosophila Rab11 and auxilin mutants to test the ligand recycling hypothesis. First, we find that Rab11 is dispensable for several Notch signaling events in the eye disc. Second, we find that Drosophila female germline cells, the one cell type known to signal without clathrin, also do not require auxilin to signal. Third, we find that much of the requirement for auxilin in Notch signaling was bypassed by overexpression of both clathrin heavy chain and epsin. Thus, the main role of auxilin in Notch signaling is not to produce uncoated ligand-containing vesicles, but to maintain the pool of free clathrin. Taken together, these results argue strongly that at least in some cell types, the primary function of Notch ligand endocytosis is not for ligand recycling.
PMCID: PMC3063240  PMID: 21448287
15.  Crystallographic plane-orientation dependent atomic force microscopy-based local oxidation of silicon carbide 
Nanoscale Research Letters  2011;6(1):235.
The effect of crystalline plane orientations of Silicon carbide (SiC) (a-, m-, and c-planes) on the local oxidation on 4H-SiC using atomic force microscopy (AFM) was investigated. It has been found that the AFM-based local oxidation (AFM-LO) rate on SiC is closely correlated to the atomic planar density values of different crystalline planes (a-plane, 7.45 cm-2; c-plane, 12.17 cm-2; and m-plane, 6.44 cm-2). Specifically, at room temperature and under about 40% humidity with a scan speed of 0.5 μm/s, the height of oxides on a- and m-planes 4H-SiC is 6.5 and 13 nm, respectively, whereas the height of oxides on the c-plane increased up to 30 nm. In addition, the results of AFM-LO with thermally grown oxides on the different plane orientations in SiC are compared.
PMCID: PMC3211294  PMID: 21711752
16.  Anti-reflective nano- and micro-structures on 4H-SiC for photodiodes 
Nanoscale Research Letters  2011;6(1):236.
In this study, nano-scale honeycomb-shaped structures with anti-reflection properties were successfully formed on SiC. The surface of 4H-SiC wafer after a conventional photolithography process was etched by inductively coupled plasma. We demonstrate that the reflection characteristic of the fabricated photodiodes has significantly reduced by 55% compared with the reference devices. As a result, the optical response Iillumination/Idark of the 4H-SiC photodiodes were enhanced up to 178%, which can be ascribed primarily to the improved light trapping in the proposed nano-scale texturing.
PMCID: PMC3211295  PMID: 21711744
17.  Rad50 Adenylate Kinase Activity Regulates DNA Tethering by Mre11/Rad50 Complexes 
Molecular cell  2007;25(5):647-661.
Mre11 and Rad50 are the catalytic components of a highly conserved DNA repair complex that functions in many aspects of DNA metabolism involving double-strand breaks. The ATPase domains in Rad50 are related to the ABC transporter family of ATPases, previously shown to share structural similarities with adenylate kinases. Here we demonstrate that Mre11/Rad50 complexes from three organisms catalyze the reversible adenylate kinase reaction in vitro. Mutation of the conserved signature motif reduces the adenylate kinase activity of Rad50 but does not reduce ATP hydrolysis. This mutant resembles a rad50 null strain with respect to meiosis and telomere maintenance in S. cerevisiae, correlating adenylate kinase activity with in vivo functions. An adenylate kinase inhibitor blocks Mre11/Rad50-dependent DNA tethering in vitro and in cell-free extracts, indicating that adenylate kinase activity by Mre11/Rad50 promotes DNA-DNA associations. We propose a model for Rad50 that incorporates both ATPase and adenylate kinase reactions as critical activities that regulate Rad50 functions.
PMCID: PMC3050042  PMID: 17349953
18.  Cutaneous Metastasis from Cholangiocarcinoma as the First Clinical Sign: A Report of Two Cases 
Gut and Liver  2011;5(1):100-104.
Cutaneous metastases from internal malignancies are uncommon. Furthermore, cutaneous metastases from cholangiocarcinoma are extremely rare. Here we report a case of two patients with distant cutaneous metastases of cholangiocarcinoma: 1) a 66-year-old man who presented with a solitary, erythematous nodule on the scalp and 2) a 44-year-old man who presented with multiple, erythematous nodules on the scalp, the chest wall, and the back. In both cases, the erythematous nodules were the first clinical signs of cholangiocarcinoma. Histopathological analyses of skin biopsy specimens of the two patients revealed adenocarcinomas with features similar to the original cholangiocarcinoma. Two cases of cholangiocarcinoma in which metastatic skin nodules appeared as the first sign of the disease are reported here, with a review of the relevant literature.
PMCID: PMC3065084  PMID: 21461082
Cutaneous metastasis; Cholangiocarcinoma
19.  Ancient and Recent Adaptive Evolution of Primate Non-Homologous End Joining Genes 
PLoS Genetics  2010;6(10):e1001169.
In human cells, DNA double-strand breaks are repaired primarily by the non-homologous end joining (NHEJ) pathway. Given their critical nature, we expected NHEJ proteins to be evolutionarily conserved, with relatively little sequence change over time. Here, we report that while critical domains of these proteins are conserved as expected, the sequence of NHEJ proteins has also been shaped by recurrent positive selection, leading to rapid sequence evolution in other protein domains. In order to characterize the molecular evolution of the human NHEJ pathway, we generated large simian primate sequence datasets for NHEJ genes. Codon-based models of gene evolution yielded statistical support for the recurrent positive selection of five NHEJ genes during primate evolution: XRCC4, NBS1, Artemis, POLλ, and CtIP. Analysis of human polymorphism data using the composite of multiple signals (CMS) test revealed that XRCC4 has also been subjected to positive selection in modern humans. Crystal structures are available for XRCC4, Nbs1, and Polλ; and residues under positive selection fall exclusively on the surfaces of these proteins. Despite the positive selection of such residues, biochemical experiments with variants of one positively selected site in Nbs1 confirm that functions necessary for DNA repair and checkpoint signaling have been conserved. However, many viruses interact with the proteins of the NHEJ pathway as part of their infectious lifecycle. We propose that an ongoing evolutionary arms race between viruses and NHEJ genes may be driving the surprisingly rapid evolution of these critical genes.
Author Summary
Because all cells experience DNA damage, they must also have mechanisms for repairing DNA. When the proteins that repair DNA malfunction, mutation and disease often result. Based on their fundamental importance, DNA repair proteins would be expected to be well preserved over evolutionary time in order to ensure optimal DNA repair function. However, a previous genome-wide study of molecular evolution in Saccharomyces yeast identified the non-homologous end joining (NHEJ) DNA repair pathway as one of the two most rapidly evolving pathways in the yeast genome. In order to analyze the evolution of this pathway in humans, we have generated large evolutionary sequence sets of NHEJ genes from our primate relatives. Similar to the scenario in yeast, several genes in this pathway are evolving rapidly in primate genomes and in modern human populations. Thus, complex and seemingly opposite selective forces are shaping the evolution of these important DNA repair genes. The finding that NHEJ genes are rapidly evolving in species groups as diverse as yeasts and primates indicates a systematic perturbation of the NHEJ pathway, one that is potentially important to human health.
PMCID: PMC2958818  PMID: 20975951
20.  High-Temperature Stable Operation of Nanoribbon Field-Effect Transistors 
Nanoscale Research Letters  2010;5(11):1795-1799.
We experimentally demonstrated that nanoribbon field-effect transistors can be used for stable high-temperature applications. The on-current level of the nanoribbon FETs decreases at elevated temperatures due to the degradation of the electron mobility. We propose two methods of compensating for the variation of the current level with the temperature in the range of 25–150°C, involving the application of a suitable (1) positive or (2) negative substrate bias. These two methods were compared by two-dimensional numerical simulations. Although both approaches show constant on-state current saturation characteristics over the proposed temperature range, the latter shows an improvement in the off-state control of up to five orders of magnitude (−5.2 × 10−6).
PMCID: PMC2964476  PMID: 21124629
Field-effect transistors (FETs); Electron mobility; Variation of the current level; Nanoribbon FET
21.  High-Temperature Stable Operation of Nanoribbon Field-Effect Transistors 
Nanoscale Research Letters  2010;5(11):1795-1799.
We experimentally demonstrated that nanoribbon field-effect transistors can be used for stable high-temperature applications. The on-current level of the nanoribbon FETs decreases at elevated temperatures due to the degradation of the electron mobility. We propose two methods of compensating for the variation of the current level with the temperature in the range of 25–150°C, involving the application of a suitable (1) positive or (2) negative substrate bias. These two methods were compared by two-dimensional numerical simulations. Although both approaches show constant on-state current saturation characteristics over the proposed temperature range, the latter shows an improvement in the off-state control of up to five orders of magnitude (−5.2 × 10−6).
PMCID: PMC2964476  PMID: 21124629
Field-effect transistors (FETs); Electron mobility; Variation of the current level; Nanoribbon FET
22.  Drosophila liquid facets-Related encodes Golgi epsin and is an essential gene required for cell proliferation, growth, and patterning 
Developmental biology  2009;331(1):1-13.
Epsin and epsin-Related (epsinR) are multi-modular proteins that stimulate clathrin-coated vesicle formation. Epsin promotes endocytosis at the plasma membrane, and epsinR functions at the Golgi and early endosomes for trans-Golgi network/endosome vesicle trafficking. In Drosophila, endocytic epsin is known as Liquid facets, and it is essential specifically for Notch signaling. Here, by generating and analyzing loss-of-function mutants in the liquid facets-Related (lqfR) gene of Drosophila, we investigated the function of Golgi epsin in a multicellular context. We found that LqfR is indeed a Golgi protein, and that like liquid facets, lqfR is essential for Drosophila viability. In addition, primarily by analyzing mutant eye discs, we found that lqfR is required for cell proliferation, insulin-independent cell growth, and cell patterning, consistent with a role in one or several signaling pathways. Epsins in all organisms share an ENTH (epsin N-terminal homology) domain, which binds phosphoinositides enriched at the plasma membrane or the Golgi membrane. The epsinR ENTH domain is also the recognition element for particular cargos. By generating wild-type and mutant lqfR transgenes, we found that all apparent LqfR functions are independent of its ENTH domain. These results suggest that LqfR transports specific cargo critical to one or more signaling pathways, and lays the foundation for identifying those proteins.
PMCID: PMC2693448  PMID: 19376106
23.  Biogenic Formation of As-S Nanotubes by Diverse Shewanella Strains▿ †  
Applied and Environmental Microbiology  2009;75(21):6896-6899.
Shewanella sp. strain HN-41 was previously shown to produce novel, photoactive, As-S nanotubes via the reduction of As(V) and S2O32− under anaerobic conditions. To determine if this ability was unique to this bacterium, 10 different Shewanella strains, including Shewanella sp. strain HN-41, Shewanella sp. strain PV-4, Shewanella alga BrY, Shewanella amazonensis SB2B, Shewanella denitrificans OS217, Shewanella oneidensis MR-1, Shewanella putrefaciens CN-32, S. putrefaciens IR-1, S. putrefaciens SP200, and S. putrefaciens W3-6-1, were examined for production of As-S nanotubes under standardized conditions. Of the 10 strains examined, three formed As-S nanotubes like those of strain HN-41. While Shewanella sp. strain HN-41 and S. putrefaciens CN-32 rapidly formed As-S precipitates in 7 days, strains S. alga BrY and S. oneidensis MR-1 reduced As(V) at a much lower rate and formed yellow As-S after 30 days. Electron microscopy, energy-dispersive X-ray spectroscopy, and extended X-ray absorption fine-structure spectroscopy analyses showed that the morphological and chemical properties of As-S formed by strains S. putrefaciens CN-32, S. alga BrY, and S. oneidensis MR-1 were similar to those previously determined for Shewanella sp. strain HN-41 As-S nanotubes. These studies indicated that the formation of As-S nanotubes is widespread among Shewanella strains and is closely related to bacterial growth and the reduction rate of As(V) and thiosulfate.
PMCID: PMC2772418  PMID: 19717628
24.  A Case of Lumbar Metastasis of Choriocarcinoma Masquerading as an Extraosseous Extension of Vertebral Hemangioma 
We report here on an uncommon case of metastatic choriocarcinoma to the lung, brain and lumbar spine. A 33-year-old woman was admitted to the pulmonary department with headache, dyspnea and hemoptysis. There was a history of cesarean section due to intrauterine fetal death at 37-weeks gestation and this occurred 2 weeks before admission to the pulmonary department. The radiological studies revealed a nodular lung mass with hypervascularity in the left upper lobe and also a brain parenchymal lesion in the parietal lobe with marginal bleeding and surrounding edema. She underwent embolization for the lung lesion, which was suspected to be an arteriovenous malformation according to the pulmonary arteriogram. Approximately 10 days after discharge from the pulmonary department, she was readmitted due to back pain and progressive paraparesis. The neuroradiological studies revealed a hypervascular tumor occupying the entire L3 vertebral body and pedicle, and the tumor extended to the epidural area. She underwent embolization of the hypervascular lesion of the lumbar spine, and after which injection of polymethylmethacrylate in the L3 vertebral body, total laminectomy of L3, subtotal removal of the epidural mass and screw fixation of L2 and L4 were performed. The result of biopsy was a choriocarcinoma.
PMCID: PMC2836452  PMID: 20224716
Metastatic choriocarconoma; Spinal metastasis
25.  Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo 
The Journal of Cell Biology  2008;183(5):777-783.
Cellular responses to both physiological and pathological DNA double-strand breaks are initiated through activation of the evolutionarily conserved ataxia telangiectasia mutated (ATM) kinase. Upon DNA damage, an activation mechanism involving autophosphorylation has been reported to allow ATM to phosphorylate downstream targets important for cell cycle checkpoints and DNA repair. In humans, serine residues 367, 1893, and 1981 have been shown to be autophosphorylation sites that are individually required for ATM activation. To test the physiological importance of these sites, we generated a transgenic mouse model in which all three conserved ATM serine autophosphorylation sites (S367/1899/1987) have been replaced with alanine. In this study, we show that ATM-dependent responses at both cellular and organismal levels are functional in mice that express a triple serine mutant form of ATM as their sole ATM species. These results lend further support to the notion that ATM autophosphorylation correlates with the DNA damage–induced activation of the kinase but is not required for ATM function in vivo.
PMCID: PMC2592823  PMID: 19047460

Results 1-25 (28)