Fam83h is Associated with Intracellular Vesicles and ADHCAI

Ding, Y.,Estrella, M.R.P.,Hu, Y.Y.,Chan, H.L.,Zhang, H.D.,Kim, J.-W.,Simmer, J.P.,Hu, J.C.-C. SAGE Publications 2009 Journal of dental research Vol.88 No.11

<P>Defects in <I>FAM83H</I> on human chromosome 8q24.3 cause autosomal-dominant hypocalcified amelogenesis imperfecta (ADHCAI). <I>FAM83H</I> does not encode a recognizable signal peptide, so we predicted that the Fam83h protein functions within the cell. We tested this hypothesis by constitutively expressing mouse Fam83h with green fluorescent protein (GFP) fused to its C-terminus in HEK293 and HeLa cell lines. Green fluorescent signal from the Fam83h-GFP fusion protein was associated with perinuclear vesicles, usually in the vicinity of the Golgi apparatus. No signal was observed within the nucleus. In addition, we identified <I> FAM83H</I> nonsense mutations in Hispanic (C1330C>T; p.Q444X) and Caucasian (c.1192C>T; p.Q398X) families with ADHCAI. We conclude that Fam83h localizes in the intracellular environment, is associated with vesicles, and plays an important role in dental enamel formation. <I>FAM83H</I> is the first gene involved in the etiology of amelogenesis imperfecta (AI) that does not encode a secreted protein.</P>

FAM83H mutations cause ADHCAI and alter intracellular protein localization.

Lee, S-K,Lee, K-E,Jeong, T-S,Hwang, Y-H,Kim, S,Hu, J C-C,Simmer, J P,Kim, J-W Journal of Dental Research, Inc 2011 Journal of dental research Vol.90 No.3

<P>Mutations in a family with sequence similarity 83 member H (FAM83H) cause autosomal-dominant hypocalcification amelogenesis imperfecta (ADH CAI). All FAM83H ADHCAI-causing mutations terminate translation or shift the reading frame within the specific exon 5 segment that encodes from Ser(287) to Glu(694). Mutations near Glu(694) cause a milder, more localized phenotype. We identified disease-causing FAM83H mutations in two families with ADHCAI: family 1 (g.3115C>T, c.1993 C>T, p.Q665X) and family 2 (g.3151C>T, c.2029 C>T, p.Q677X). We also tested the hypothesis that truncation mutations alter the intracellular localization of FAM83H. Wild-type FAM83H and p.E694X mutant FAM83H fused to green fluorescent protein (GFP) localized in the cytoplasm of HEK293T cells, but the mutant FAM83H proteins (p.R325X, p.W460X, and p.Q677X) fused to GFP localized mainly in the nucleus with slight expression in the cytoplasm. We conclude that nuclear targeting of the truncated FAM83H protein contributes to the severe, generalized enamel phenotype.</P>

Enhanced anti-tumor efficacy and safety profile of tumor microenvironment-responsive oncolytic adenovirus nanocomplex by systemic administration

Choi, J.W.,Dayananda, K.,Jung, S.J.,Lee, S.H.,Kim, D.,Hu, J.,Bae, Y.H.,Yun, C.O. Elsevier BV 2015 ACTA BIOMATERIALIA Vol.28 No.-

Oncolytic adenovirus (Ad) holds great promise as a potential gene therapy for cancer. However, intravenously administered Ad may encounter difficulties due to unfavorable host responses, non-specific interactions, and the heterogeneity of the tumor cell population. As an approach to combine the advantages of oncolytic Ad and synthetic polymers and to address the associated difficulties, Ad was physically complexed with a pH-sensitive block copolymer, methoxy poly(ethylene glycol)-b-poly(l-histidine) (mPEG-b-pHis). The in vitro transduction efficiency at an acidic extracellular pH was remarkably enhanced in cancer cells when treated with the Ad expressing green fluorescent protein (GFP) coated with mPEG-b-pHis (c-dE1/GFP) as compared to that of naked Ad (n-dE1/GFP). Time-lapse total internal reflection fluorescence microscopic imaging revealed a significantly enhanced cellular uptake rate of c-dE1/GFP at acidic tumor pH when compared with that at neutral pH or naked cognate Ad (n-dE1/GFP). In addition, c-dE1/GFP remained relatively stable in human serum-containing media, and considerably reduced both the innate and adaptive immune response against Ad. Moreover, the therapeutic efficacy and survival benefit of mPEG-b-pHis-complexed oncolytic Ad (c-H5mT/Luc) by systemic treatment was significantly enhanced compared to that with naked oncolytic Ad (n-H5mT/Luc) in both coxsackie and adenovirus receptor-positive and -negative tumors. Whole-body bioluminescence imaging showed 7.3-fold higher luciferase expression at the tumor site and 23.0-fold less luciferase expression in liver tissue for c-H5mT/Luc relative to that for naked oncolytic Ad (n-H5mT/Luc). Considering the heterogeneity of tumor tissue, these results are important for guiding the development of more potent and specific treatment of devastating metastatic cancers using this viral system. Statement of significance: Although adenoviral systems have shown considerable promise and undergone extensive evaluation attempts to specifically target Ad vectors to cancer cells have met limited success. This shortcoming is due to the strong immune response stimulated by Ad and the hepatotoxicity of the viral particles. To overcome restricted vector issues, we generated Ad/mPEG-b-pHis for tumor microenvironment-targeting hybrid vector systems, an oncolytic Ad coated with a pH-responsive polymer, mPEG-b-pHis. The Ad/mPEG-b-pHis exhibited pH-dependent transduction efficiency and cancer-cell killing effects. Moreover, systemic administration of oncolytic Ad/mPEG-b-pHis led to marked suppression of tumor growth and tumor-specific viral replication. Ad successfully avoided the innate and adaptive immune responses and liver accumulation with the help of mPEG-b-pHis on its surface.

Feedback Control of Adrenal Steroidogenesis via H₂O₂-Dependent, Reversible Inactivation of Peroxiredoxin III in Mitochondria

Kil, I.,Lee, S.,Ryu, K.,Woo, H.,Hu, M.C.,Bae, S.,Rhee, S. Cell Press 2012 Molecular cell Vol.46 No.5

Certain members of the peroxiredoxin (Prx) family undergo inactivation through hyperoxidation of the catalytic cysteine to sulfinic acid during catalysis and are reactivated by sulfiredoxin; however, the physiological significance of this reversible regulatory process is unclear. We now show that PrxIII in mouse adrenal cortex is inactivated by H<SUB>2</SUB>O<SUB>2</SUB> produced by cytochrome P450 enzymes during corticosterone production stimulated by adrenocorticotropic hormone. Inactivation of PrxIII triggers a sequence of events including accumulation of H<SUB>2</SUB>O<SUB>2</SUB>, activation of p38 mitogen-activated protein kinase, suppression of steroidogenic acute regulatory protein synthesis, and inhibition of steroidogenesis. Interestingly, levels of inactivated PrxIII, activated p38, and sulfiredoxin display circadian oscillations. Steroidogenic tissue-specific ablation of sulfiredoxin in mice resulted in the persistent accumulation of inactive PrxIII and suppression of the adrenal circadian rhythm of corticosterone production. The coupling of CYP11B1 activity to PrxIII inactivation provides a feedback regulatory mechanism for steroidogenesis that functions independently of the hypothalamic-pituitary-adrenal axis.

<i>LAMB3</i> Mutations Causing Autosomal-dominant Amelogenesis Imperfecta

Kim, J.W.,Seymen, F.,Lee, K.E.,Ko, J.,Yildirim, M.,Tuna, E.B.,Gencay, K.,Shin, T.J.,Kyun, H.K.,Simmer, J.P.,Hu, J.C.-C. SAGE Publications 2013 Journal of dental research Vol.92 No.10

<P>Amelogenesis imperfecta (AI) can be either isolated or part of a larger syndrome. Junctional epidermolysis bullosa (JEB) is a collection of autosomal-recessive disorders featuring AI associated with skin fragility and other symptoms. JEB is a recessive syndrome usually caused by mutations in both alleles of <I>COL17A1, LAMA3, LAMB3</I>, or <I>LAMC2</I>. In rare cases, heterozygous carriers in JEB kindreds display enamel malformations in the absence of skin fragility (isolated AI). We recruited two kindreds with autosomal-dominant amelogenesis imperfecta (ADAI) characterized by generalized severe enamel hypoplasia with deep linear grooves and pits. Whole-exome sequencing of both probands identified novel heterozygous mutations in the last exon of <I>LAMB3</I> that likely truncated the protein. The mutations perfectly segregated with the enamel defects in both families. In Family 1, an 8-bp deletion (c.3446_3453del GACTGGAG) shifted the reading frame (p.Gly 1149Glufs*8). In Family 2, a single nucleotide substitution (c.C3431A) generated an in-frame translation termination codon (p.Ser1144*). We conclude that enamel formation is particularly sensitive to defects in hemidesmosome/basement-membrane complexes and that syndromic and non-syndromic forms of AI can be etiologically related.</P>

Phospholipase C delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer

Hu, X -T,Zhang, F -B,Fan, Y -C,Shu, X -S,Wong, A H Y,Zhou, W,Shi, Q -L,Tang, H -M,Fu, L,Guan, X -Y,Rha, S Y,Tao, Q,He, C Macmillan Publishers Limited 2009 Oncogene Vol.28 No.26

Located at the important tumor suppressor locus, 3p22, PLCD1 encodes an enzyme that mediates regulatory signaling of energy metabolism, calcium homeostasis and intracellular movements. We identified PLCD1 as a downregulated gene in aerodigestive carcinomas through expression profiling and epigenetic characterization. We found that PLCD1 was expressed in all normal adult tissues but low or silenced in 84% (16/19) gastric cancer cell lines, well correlated with its CpG island (CGI) methylation status. Methylation was further detected in 62% (61/98) gastric primary tumors, but none of normal gastric mucosa tissues. PLCD1 methylation was significantly correlated with tumor high stage. Detailed methylation analysis of 37 CpG sites at the PLCD1 CGI by bisulfite genomic sequencing confirmed its methylation. PLCD1 silencing could be reversed by pharmacological demethylation with 5-aza-2′-deoxycytidine, indicating a direct epigenetic silencing. Ectopic expression of PLCD1 in silenced gastric tumor cells dramatically inhibited their clonogenicity and migration, possibly through downregulating MMP7 expression and hampering the reorganization of cytoskeleton through cofilin inactivation by phosphorylation. Thus, epigenetic inactivation of PLCD1 is common and tumor-specific in gastric cancer, and PLCD1 acts as a functional tumor suppressor involved in gastric carcinogenesis.Oncogene (2009) 28, 2466–2475; doi:10.1038/onc.2009.92; published online 18 May 2009

DISCOVERY OF AN X-RAY-EMITTING CONTACT BINARY SYSTEM 2MASS J11201034−2201340

Hu, Chin-Ping,Yang, Ting-Chang,Chou, Yi,Liu, L.,Qian, S.-B.,Hui, C. Y.,Kong, Albert K. H.,Lin, L. C. C.,Tam, P. H. T.,Li, K. L.,Ngeow, Chow-Choong,Chen, W. P.,Ip, Wing-Huen American Astronomical Society 2016 The Astronomical journal Vol.151 No.6

<P>We report the detection of orbital modulation, a model solution, and the X-ray properties of a newly discovered contact binary, Two Micron All Sky Survey (2MASS) J11201034-2201340. We serendipitously found this X-ray point source outside the error ellipse when searching for possible X-ray counterparts of 7-ray millisecond pulsars among the unidentified objects detected by the Fermi Gamma-ray Space Telescope. The optical counterpart of the X-ray source (unrelated to the 7-ray source) was then identified using archival databases. The long-term Catalina Real-Time Transient Survey detected a precise signal with a period of P = 0.28876208 (56) days. A follow-up observation made by the Super Light Telescope of Lulin Observatory revealed the binary nature of the object. Utilizing archived photometric data of multi-band surveys, we construct the spectral energy distribution (SED), which is well fit by a K2V spectral template. The fitting result of the orbital profile using the Wilson Devinney code suggests that 2MASS J11201034-2201340 is a short-period A-type contact binary and the more massive component has a cool spot. The X-ray emission was first noted in observations made by Swift, and then further confirmed and characterized by an XMM-Newton observation. The X-ray spectrum can be described by a power law or thermal Bremsstrahlung. Unfortunately, we could not observe significant X-ray orbital modulation. Finally, according to the SED, this system is estimated to be 690 pc from Earth with a calculated X-ray intensity of (0.7 - 1.5) x 10(30) erg s(-1), which is in the expected range of an X-ray emitting contact binary.</P>

Effects of Copper-bearing Montmorillonite on Growth Performance and Digestive Function of Growing Pigs

Hu, C.H.,Xia, M.S.,Xu, Z.R.,Xiong, L. Asian Australasian Association of Animal Productio 2004 Animal Bioscience Vol.17 No.11

A total of 96 growing barrows (Duroc${\times}$Landrace${\times}$Yorkshire) at an average BW of 20.2 kg were used to investigate the effects of montmorillonite (MMT) or copper-bearing montmorillonite (Cu-MMT) on growth performance, intestinal microflora, digestive enzyme activities of pancreas and small intestinal contents, and the apparent nutrient digestion. The pigs were allocated to three groups with 32 pigs per treatment for 42 days and the average BW at the end of the experiment was 49.7 kg. The three dietary treatments were basal diet only (control group), basal diet +1.5 g/kg MMT, and basal diet +1.5 g/kg Cu-MMT. The results showed that supplementation with Cu-MMT significantly improved growth performance as compared to control and pigs fed with Cu-MMT had higher average daily gain than those fed with MMT. As compared to control, supplementation with Cu-MMT significantly reduced the total viable counts of Escherichia coli and Clostridium in the small intestine and proximal colon. Supplementation with MMT had no significant influence on intestinal microflora, although there was a tendency for Escherichia coli and Clostridium to be lower than the control. Pigs fed with Cu-MMT had lower viable counts of Escherichia coli in colonic contents than those fed with MMT. Although supplementation with MMT improved the activities of the digestive enzymes in the small intestinal contents, the tendency was not significant. Supplementation with Cu-MMT significantly improved the activities of total protease, amylase and lipase in the small intestinal contents. Supplementation with MMT or Cu-MMT improved the apparent nutrient digestion.

개산고정사시

허춘훤(C H Hu),라상훈(S H Rah),김순현(S H Kim) 대한안과학회 1996 대한안과학회지 Vol.37 No.1

<i>WDR72</i> Mutations Associated with Amelogenesis Imperfecta and Acidosis

Zhang, H.,Koruyucu, M.,Seymen, F.,Kasimoglu, Y.,Kim, J.-W.,Tinawi, S.,Zhang, C.,Jacquemont, M.L.,Vieira, A.R.,Simmer, J.P.,Hu, J.C.C. SAGE Publications 2019 Journal of dental research Vol.98 No.5