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  • Cell Research
    and for detection of drug resistance to anti retroviral therapies Current progress of China s free ART program Fu Jie ZHANG Jennifer PAN Lan YU Yi WEN and Yan ZHAO Cell Research 2005 15 877 882 doi 10 1038 sj cr 7290362 Full Text PDF China s Free ART Program was initiated in 2002 as an emergency response to save and improve the lives of AIDS patients living mainly in impoverished rural regions of central China With little experience in HIV AIDS treatment and care and resource limitations China s efforts to provide widespread access to free antiretroviral therapy has been a process fraught with difficulty However the Free ART Program is progressing from an emergency response to a standardized treatment and care system The development of national guidelines training programs a laboratory support network a national patient database programs for special populations such as children and patients living with co infections and operational research has improved the scope and quality of the free treatment program As of June 30 2005 a total of 19 456 patients in 28 provinces autonomous regions and special municipalities had received free ART Challenges stemming from the nature of China s health system and patient population persist but with strong government support and a diverse set of resources China has the capacity to overcome these challenges and to provide nationwide access to high quality treatment and care Care of HIV infected patients in China Yun Zhen CAO 1 and Hong Zhou LU 2 Cell Research 2005 15 883 890 doi 10 1038 sj cr 7290363 Full Text PDF Compared with high infection areas of the world the total HIV infection rate in China is relatively low Nonetheless because of China s vast territory and large population the potential infection risk must be taken seriously In the next few years needle sharing among injection drug users will remain the most common route of transmission for the HIV AIDS epidemic in China Unprotected sex is gradually becoming a major route of transmission China began to implement HAART in 1999 according to international standards Prior to 2003 there were only about 150 HIV AIDS patients were treated with HAART in some clinical trials and about 100 HIV AIDS patients were treated by private sources Results of those treatments are the scientific basis for development of the therapeutic strategies in China In March of 2003 the Chinese government initiated China CARES program In November of 2003 the Chinese Ministry of Health announced a national policy of free ARV treatment to all HIV Chinese citizens who were in poverty and required ARV therapy There are total of 19 456 HIV AIDS patients received free ARV drugs to date in 159 regions and 441 towns Current challenges are how to follow up and evaluate those patients in the clinical settings The longer the therapy is postponed the more side effects and the higher probability of drug resistance are going to occur It remains unclear therefore when HAART regimen should be started in the HIV AIDS population in China ORIGINAL ARTICLES Effects of drug relief hospital based AIDS educational methods on drug users Xiang Ping LI 1 Shun Zhen XIAO 1 Qiao Qin WAN 1 Sen Lin SONG 2 and Yan Xia TENG 2 Cell Research 2005 15 891 894 doi 10 1038 sj cr 7290364 Full Text PDF The objective of this study is to explore a potentially effective training method for the hospital professionals to educate drug users and to enhance their knowledge of HIV infection One hundred and sixty one subjects who came from 13 different provinces and were admitted in a drug relief hospital in Beijing were recruited for this study The average age of these subjects was 35 216 24 year old The average numbers of years for drug addiction were 7 years and the average numbers of drug relief treatment received in the past was 5 5 times The level of AIDS knowledge of these subjects including pathogenic factors source of infection route of transmission and preventive measures were evaluated before and after receiving the AIDS educational training to these drug users Our results showed that there was a statistically significant increase P REVIEWS Approaches to antiretroviral therapy in China Bruce L GILLIAM and Robert R REDFIELD Cell Research 2005 15 895 902 doi 10 1038 sj cr 7290365 Full Text PDF China has recognized the threat of HIV to its population and responded with a national antiretroviral treatment ART program However high ART failure rates and the spread of resistance within populations are important realities to consider when developing and managing ART programs in China and worldwide Concepts which will define treatment success and local and national programmatic goals are 1 access to ART 2 durability of ART at the patient level 3 scalability of treatment modalities and the 4 sustainability of the program at the community or national level In the face of limited resources China must also consider when to start ARV therapy which agents to use when to switch them and how to treat highly experienced patients with drug resistance The optimal ARV regimen to start with is changing frequently with the introduction of new agents and the presentation of new data Currently a regimen including tenofovir emtricitabine or lamivudine and a nonnucleoside reverse transcriptase inhibitor appears to have optimal characteristics to treat HIV AIDS in China However critical to all of these choices is the evaluation of programs implemented to insure wide scale success China has wisely begun this process of evaluating the performance of local programs through systematic monitoring and evaluation of treatment outcomes This will allow regimens and programs that work to be expanded and programs with high failure rates to be eliminated In the end evidence based data supporting treatment strategies will allow China to successfully confront its AIDS epidemic early and prevent its tragic consequences COMMENTARY Governmental policies on HIV infection in China Jie SHEN 1 and Dong Bao YU 2 Cell Research 2005 15 903

    Original URL path: http://www.cell-research.com/artsmore.asp?id=93 (2016-02-14)
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  • Cell Research
    are under continuous assault by environmental agents and endogenous metabolic byproducts Damage induced in DNA usually leads to a cascade of cellular events the DNA damage response Failure of the DNA damage response can lead to development of malignancy by reducing the efficiency and fidelity of DNA repair The NBS1 protein is a component of the MRE11 RAD50 NBS1 complex MRN that plays a critical role in the cellular response to DNA damage and the maintenance of chromosomal integrity Mutations in the NBS1 gene are responsible for Nijmegen breakage syndrome NBS a hereditary disorder that imparts an increased predisposition to development of malignancy The phenotypic characteristics of cells isolated from NBS patients point to a deficiency in the repair of DNA double strand breaks Here we review the current knowledge of the role of NBS1 in the DNA damage response Emphasis is placed on the role of NBS1 in the DNA double strand repair modulation of the DNA damage sensing and signaling cell cycle checkpoint control and maintenance of telomere stability ORIGINAL ARTICLES Preassembly and ligand induced restructuring of the chains of the IFN γ receptor complex the roles of Jak kinases Stat1 and the receptor chains Christopher D Krause 1 Natasha Lavnikova 1 Junxia Xie 1 Erwen Mei 2 Olga V Mirochnitchenko 1 Yiwei Jia 3 Robin M Hochstrasser 2 Sidney Pestka 1 4 5 Cell Research 2006 16 55 69 doi 10 1038 sj cr 7310008 published online 16 January 2006 Full Text PDF We previously demonstrated using noninvasive technologies that the interferon gamma IFN γ receptor complex is preassembled 1 In this report we determined how the receptor complex is preassembled and how the ligand mediated conformational changes occur The interaction of Stat1 with IFN γR1 results in a conformational change localized to IFN γR1 Jak1 but not Jak2 is required for the two chains of the IFN γ receptor complex IFN γR1 and IFN γR2 to interact however the presence of both Jak1 and Jak2 is required to see any ligand dependant conformational change Two IFN γR2 chains interact through species specific determinants in their extracellular domains Finally these determinants also participate in the interaction of IFN γR2 with IFN γR1 These results agree with a detailed model of the IFN γ receptor that requires the receptor chains to be pre associated constitutively for the receptor to be active Inflammatory bowel disease requires the interplay between innate and adaptive immune signals Dayna Shi 1 Jyoti Das 1 Gobardhan Das 1 Cell Research 2006 16 70 74 doi 10 1038 sj cr 7310009 published online 16 January 2006 Full Text PDF Inflammatory bowl disease IBD is a type 1 T helper cell Th1 mediated autoimmune disease Various studies have revealed that environmental pathogens also play a significant role in the initiation and progression of this disease Interestingly the pathogenesis of IBD has been shown to be related to nitric oxide NO released from innate immune cells Although NO is known to be highly toxic to the gut epithelia there is very little information about the regulation of NO production One major question in the etiology of IBD is how Th1 cells and pathogens interact in the induction of IBD In present study we focused on the regulation of NO We show that macrophages require both interferon γ IFN γ mediated and TLR4 mediated signals for the production of NO which causes inflammation in the intestine and subsequently IBD Thus IBD is the result of concerted actions of innate immune signals such as the binding of LPS to TLR 4 and adaptive immune signals such as IFN γ produced by Th1 cells uPAR expression under hypoxic conditions depends on iNOS modulated ERK phosphorylation in the MDA MB 231 breast carcinoma cell line So Young Yoon 1 Yoo Jung Lee 2 Jae Hong Seo 3 Hwa Jung Sung 3 Kyong Hwa Park 3 In Keun Choi 3 Seok Jin Kim 3 Sang Cheul Oh 3 Chul Won Choi 3 Byung Soo Kim 3 Sang Won Shin 3 Yeul Hong Kim 3 Jun Suk Kim 3 Cell Research 2006 16 75 81 doi 10 1038 sj cr 7310010 published online 16 January 2006 Full Text PDF Urokinase plasminogen activator receptor uPAR plays a major role in cancer invasion and metastasis and uPAR expression is correlated with a poor prognosis in various cancer types Moreover the expression of uPAR is increased under hypoxic conditions Nitric oxide NO and its metabolites produced by inducible nitric oxide synthase iNOS are important products of hypoxic stress and NO may activate or modulate extracellular signal regulated kinase ERK Here we evaluated uPA uPAR and activated ERK levels under hypoxic conditions and the modulatory effects of iNOS andNO in the MDA MB 231 human breast cancer cell line Cells were incubated in a hypoxic or normoxic incubator andtreated with PD98059 a MEK 1 2 inhibitor which abrogates ERK phosphorylation and aminoguanidine a selective iNOS inhibitor uPAR expression ERK phosphorylation and uPA activity were found to be increased under hypoxic conditions Moreover when cells were treated with PD98059 under hypoxic conditions uPAR was downregulated whereas aminoguanidine markedly increased ERK phosphorylation in a dose dependent manner Furthermore aminoguanidine increased uPAR expression and prevented the inhibition of uPAR expression by PD98059 These results demonstrated that uPAR is induced by hypoxia and that increased uPAR expression is mediated by ERK phosphorylation which in turn is modulated by iNOS NO in MDA MB 231 cells We conclude that iNOS NO downregulates the expression of uPAR under hypoxic conditions via ERK pathway modulation Blocking of N acetylglucosaminyltransferase V induces cellular endoplasmic reticulum stress in human hepatocarcinoma 7721 cells Huan Fang 1 Wei Huang 2 Ying Ying Xu 1 Zong Hou Shen 1 Chao Qun Wu 2 Shou Yi Qiao 2 Yan Xu 2 Long Yu 2 Hui Li Chen 1 Cell Research 2006 16 82 92 doi 10 1038 sj cr 7310011 published online 16 January 2006 Full Text PDF N acetylglucosaminyltransferase V GnT V is an important tumorigenesis and metastasis associated

    Original URL path: http://www.cell-research.com/artsmore.asp?id=92 (2016-02-14)
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  • Cell Research
    cells Elaine Y Chung 1 Sun Jung Kim 2 Xiao Jing Ma 1 Cell Research 2006 16 154 161 doi 10 1038 sj cr 7310021 published online 13 February 2006 Full Text PDF Loss of self tolerance and expansion of auto reactive lymphocytes are the basis for autoimmunity Apoptosis and the rapid clearance of apoptotic cells by phagocytes usually occur as coordinated processes that ensure regulated cellularity and stress response with non pathological outcomes Defects in clearance of apoptotic cells would contribute to the generation of self reactive lymphocytes which drive autoimmune disorders such as rheumatoid arthritis RA and systemic lupus erythematosus SLE The IL 12 family of cytokines IL 12 IL 23 and IL 27 and IL 10 are produced by phagocytic macrophages and play critical roles in the regulation of antigen presenting cells APCs and effector lymphocytes during an immune response to pathogens Inappropriate expression of these cytokines and their dysregulated activities have been strongly implicated in the pathogenesis of several autoimmune diseases The production of pro and anti inflammatory cytokines by phagocytic APCs is delicately regulated during the ingestion of apoptotic cells as part of an intrinsic mechanism to prevent inflammatory autoimmune reactions How apoptotic cell derived signals regulate cytokine production is poorly understood A recent study by our group demonstrated that phagocytosis of apoptotic cells by activated macrophages results in strong inhibition of IL 12 p35 gene expression by activating a novel transcription repressor which we named GC binding protein GC BP through tyrosine dephosphorylation We are also beginning to understand the molecular mechanisms underlying apoptotic cell triggered production of IL 10 by phagocytes These studies will help to elucidate some novel immune regulatory mechanisms and explore the regulation of immune responses to autoantigens with potentials to discover new therapeutic targets for the treatment of autoimmune disorders Insight into the biology of Macrophage Migration Inhibitory Factor MIF revealed by the cloning of its cell surface receptor Lin Leng 1 Richard Bucala 1 Cell Research 2006 16 162 168 doi 10 1038 sj cr 7310022 published online 13 February 2006 Full Text PDF The recent cloning of MIF receptor fills an important gap in our understanding of the molecular biology and immunology of MIF The MIF receptor like MIF does not fall into any established family of protein mediators providing both new challenges and opportunities for the structural and functional analysis of MIF signal transduction TGF β and cancer Is Smad3 a repressor of hTERT gene He Li 1 Dakang Xu 1 Ban Hock Toh 1 Jun Ping Liu 1 Cell Research 2006 16 169 173 doi 10 1038 sj cr 7310023 published online 13 February 2006 Full Text PDF Transforming growth factor β TGF β carries out tumor suppressor activity in epithelial and lymphoid cells whereas telomerase is required for most cancers Although the molecular mechanisms by which TGF β acts as a tumor suppressor are yet to be fully established a link between TGFb and its tumor suppressor activity by telomerase has been suggested Recently we have noted a novel mode of action for TGF β through which human telomerase reverse transcriptase hTERT gene is repressed in immortal and neoplastic cells confirming that one of the mechanisms underlying TGF β suppression of tumor growth may be through inhibiting hTERT gene transcription Moreover the inhibition of hTERT gene by TGF β suggests a cis action of the TGF β signaling molecule Smad3 on hTERT promoter directly This article examines our current understanding and investigation of TGF β regulation of telomerase activity and presents a model in which Smad3 participates in regulating hTERT gene transcription by acting as a repressor directly Engineering the interface between Smad3 and hTERT gene may lead to a new strategy to inhibit telomerase activity in cancer Midkine a cytokine that inhibits HIV infection by binding to the cell surface expressed nucleolin Ara G Hovanessian Cell Research 2006 16 174 181 doi 10 1038 sj cr 7310024 published online 13 February 2006 Full Text PDF The growth factor midkine MK is a cytokine that inhibits HIV infection in cell cultures in an autocrine and paracrine manner by blocking the attachment of HIV particles to permissive cells MK mRNA is systematically expressed in adult peripheral blood lymphocytes from healthy donors while its expression becomes markedly but transiently increased upon in vitro treatment of lymphocytes with IL 2 or IFN g and activation of T lymphocytes by PHA or through the engagement of the CD28 antigen The binding of MK to cells occurs specifically at a high and a low affinity binding site This low affinity binding site is the cell surface expressed nucleolin which is implicated in the mechanism of the initial attachment of HIV particles to cells Accordingly the nucleolin binding HB 19 pseudopeptide has no effect on the MK binding to the high affinity binding site whereas it prevents the binding of MK to the low affinity binding site thus suggesting the low affinity receptor of MK is the cell surface expressed nucleolin Confocal immunofluorescence laser microscopy revealed the colocalization of MK and the cell surface expressed nucleolin at distinct spots The use of various deletion constructs of nucleolin then indicates that the extreme C terminal end of nucleolin containing repeats of the amino acid motif RGG as the domain that binds MK The specific binding of MK to the surface nucleolin is independent of heparan sulfate and chondroitin sulfate proteoglycans After binding to cells MK enters cells by an active process in which nucleolin and lipid rafts appear to be implicated The potent and the distinct anti HIV action of MK along with its enhanced expression in lymphocytes by various physiological stimuli point out that MK is a cytokine that could be involved in HIV pathogenesis Therapy of cancer by cytokines mediated by gene therapy approach Cheng Qian 1 3 Xin Yuan Liu 1 2 Jesus Prieto 3 Cell Research 2006 16 182 188 doi 10 1038 sj cr 7310025 published online 13 February 2006 Full Text PDF Gene therapy offers

    Original URL path: http://www.cell-research.com/artsmore.asp?id=91 (2016-02-14)
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  • Cell Research
    layer to the understanding of the physiological function of rice PIP genes Molecular and functional characterization of sulfiredoxin homologs from higher plants Xian Peng Liu 1 2 Xue Ying Liu 1 2 Juan Zhang 1 2 Zong Liang Xia 1 2 Xin Liu 1 Huan Ju Qin 1 Dao Wen Wang 1 Cell Research 2006 16 287 296 doi 10 1038 sj cr 7310036 published online 16 March 2006 Full Text PDF By reducing cysteine sulfinic acid in oxidized peroxiredoxin sulfiredoxin Srx plays an important role in oxidation stress resistance in yeast and human cells Here we report the first molecular and functional characterization of Srx homolog from higher plants Bioinformatic analysis revealed the presence of potential Srx encoding sequences in both monocot and dicot plant species Putative plant Srx proteins exhibited significant identities to their orthologs from yeast and human and contained the conserved signature sequence and residues essential for catalysis However unlike yeast and human orthologs plant Srxs were all predicted to possess chloroplast transit peptide in their primary structure The Srx proteins from Arabidopsis and rice designated as AtSrx and OsSrx respectively complemented functional defi ciency of Srx in the SRX1 deletion yeast cells A GFP fusion protein of AtSrx was targeted to chloroplast in Arabidopsis mesophyll protoplast AtSrx transcription occurred in both vegetative and reproductive organs and the highest transcript level was detected in leaves Under oxidation stress AtSrx transcript level was substantially increased which paralleled with enhanced transcription of 2 Cys peroxiredoxins that have been found essential in maintaining chloroplast redox balance In addition to oxidation stress osmotic water deficit or cold treatments also raised AtSrx transcript level Consistent with above findings the knock out mutant of AtSrx was significantly more susceptible to oxidation stress than wild type Arabidopsis plant Taken together the results of this work indicate the existence of functional Srx homolog in higher plants that is essential for plants to cope with oxidation stress Reduced cardiac output is associated with decreased mitochondrial efficiency in the non ischemic ventricular wall of the acute myocardial infarcted dog Zakaria A Almsherqi 1 Craig S McLachlan 2 Malgorzata B Slocinska 1 Francis E Sluse 3 Rachel Navet 3 Cell Research 2006 16 297 305 doi 10 1038 sj cr 7310037 published online 16 March 2006 Full Text PDF Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction MI Understanding the mechanisms for acute pump failure is therefore important The aim of this study is to examine in an acute MI dog model whether mitochondrial bio energetic function within non ischemic wall regions are associated with pump failure Anterior MI was produced in dogs via ligation of left anterior descending LAD coronary artery that resulted in an infract size of about 30 of the left ventricular wall Measurements of hemodynamic status mitochondrial function free radical production and mitochondrial uncoupling protein 3 UCP3 expression were determined over 24 h period Hemodynamic measurements revealed a 50 reduction in cardiac output at 24 h

    Original URL path: http://www.cell-research.com/artsmore.asp?id=90 (2016-02-14)
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  • Cell Research
    kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line Xiao Xia Wang Rong Liu Shun Qian Jin Fei Yue Fan Qi Min Zhan Cell Research 2006 16 356 366 doi 10 1038 sj cr 7310046 published online 13 April 2006 Full Text PDF Aurora A kinase a serine threonine protein kinase is a potential oncogene Amplification and overexpression of Aurora A have been found in several types of human tumors including esophageal squamous cell carcinoma ESCC It hasbeen demonstrated that cells overexpressing Aurora A are more resistant to cisplatin induced apoptosis However the molecular mechanisms mediating these effects remain largely unknown In this report we showed that overexpression of Aurora A through stable transfection of pEGFP Aurora A in human ESCC KYSE150 cells significantly promoted cell proliferation and inhibited cisplatin or UV irradiation induced apoptosis Cleavages of caspase 3 and poly ADPribose polymerase PARP in Aurora A overexpressing cells were substantially reduced after cisplatin or UV treatment Furthermore we found that silencing of endogenous Aurora A kinase with siRNA substantially enhanced sensitivity to cisplatin or UV induced apoptosis in human ESCC EC9706 cells In parallel overexpression of Aurora A potently upregulated the expression of Bcl 2 Moreover the knockdown of Bcl 2 by siRNA abrogated the Aurora A s effect on inhibiting apoptosis Taken together these data provide evidence that Aurora A overexpression promoting cell proliferation and inhibiting apoptosis suggesting a novel mechanism that is closely related to malignant phenotype and anti cancer drugs resistance of ESCC cells Microfilament binding properties of N terminal extension of the isoform of smooth muscle long myosin light chain kinase Chun Xiang Yang Hua Qun Chen Chen Chen Wei Ping Yu Wen Cheng Zhang Ya Jin Peng Wei Qi He Dong Mei Wei Xiang Gao Min Sheng Zhu Cell Research 2006 16 367 376 doi 10 1038 sj cr 7310047 published online 13 April 2006 Full Text PDF Myosin light chain kinases MLCK phosphorylate the regulatory light chain of myosin II in thick filaments and bind to F actin containing thin filaments with high affinity The ability of short myosin light chain kinase S MLCK to bind F actin is structurally attributed to the DFRXXL regions in its N terminus The long myosin light chain kinase L MLCK has two additional DFRXXL motifs and six Ig like modules in its N terminal extension The six Ig like modules are capable of binding to stress fibers independently Our results from the imaging analysis demonstrated that the first two intact Ig like modules 2Ig in N terminal extension of L MLCK is the minimal binding module required for microfilament binding Binding assay confirmed that F actin was able to bind 2Ig Stoichiometries of 2Ig peptide were similar for myofilament or pure F actin The binding affinities were slightly lower than 5DFRXXL peptide as reported previously Similar to DFRXXL peptides the 2Ig peptide also caused efficient F actin bundle formation in vitro In the living cell over expression of 2Ig fragment

    Original URL path: http://www.cell-research.com/artsmore.asp?id=88 (2016-02-14)
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  • Cell Research
    domain of BRI1 induces kinase activation and dimerization with another receptor kinase BAK1 Activated BRI1 or BAK1 then regulate possibly indirectly the activities of BIN2 kinase and or BSU1 phosphatase which directly regulate the phosphorylation status and nuclear accumulation of two homologous transcription factors BZR1 and BES1 BZR1 and BES1 directly bind to promoters of BR responsive genes to regulate their expression The BR signaling pathway has become a paradigm for both receptor kinase signaling in plants and steroid signaling by cell surface receptors in general A RHOse by any other name a comparative analysis of animal and plant Rho GTPases Tore Brembu Per Winge Atle Magnar Bones Zhenbiao Yang Cell Research 2006 16 435 445 doi 10 1038 sj cr 7310055 published online 15 May 2006 Full Text PDF Rho GTPases are molecular switches that act as key regulators of a many cellular processes including cell movement morphogenesis host defense cell division and gene expression Rho GTPases are found in all eukaryotic kingdoms Plants lack clear homologs to conventional Rho GTPases found in yeast and animals instead they have over time developed a unique subfamily ROPs also known as RAC The origin of ROP like proteins appears to precede the appearance of land plants This review aims to discuss the evolution of ROP RAC and to compare plant ROP and animal Rho GTPases focusing on similarities and differences in regulation of the GTPases and their downstream effectors ORIGINAL ARTICLES BUD2 encoding an S adenosylmethionine decarboxylase is required for Arabidopsis growth and development Chunmin Ge Xia Cui Yonghong Wang Yuxin Hu Zhiming Fu Dongfen Zhang Zhukuan Cheng Jiayang Li Cell Research 2006 16 446 456 doi 10 1038 sj cr 7310056 published online 15 May 2006 Full Text PDF Polyamines are implicated in regulating various developmental processes in plants but their exact roles and how they govern these processes still remain elusive We report here an Arabidopsis bushy and dwarf mutant bud2 which results from the complete deletion of one member of the small gene family that encodes S adenosylmethionine decarboxylases SAMDCs necessary for the formation of the indispensable intermediate in the polyamine biosynthetic pathway The bud2 plant has enlarged vascular systems in inflorescences roots and petioles and an altered homeostasis of polyamines The double mutant of bud2 and samdc1 a knockdown mutant of another SAMDC member is embryo lethal demonstrating that SAMDCs are essential for plant embryogenesis Our results suggest that polyamines are required for the normal growth and development of higher plants Plant fertility defects induced by the enhanced expression of microRNA167 Peng Ru Lin Xu Hong Ma Hai Huang Cell Research 2006 16 457 465 doi 10 1038 sj cr 7310057 published online 15 May 2006 Full Text PDF The plant hormone auxin plays a critical role in regulating plant growth and development Recent advances have been made in the understanding of auxin response pathways primarily by the characterization of auxin response mutants in Arabidopsis In addition microRNAs miRNAs have been shown to be critical regulators of genes important for normal plant development and physiology However little is known about possible interactions between miRNAs and hormonal signaling during normal development Here we show that an Arabidopsis microRNA miR167 which has a complementary sequence to a portion of the AUXIN RESPONSE FACTOR6 ARF6 and ARF8 mRNAs can cause transcript degradation for ARF8 but not for ARF6 We report phenotypic characterizations of 35S MIR167b transgenic lines and show that severe 35S MIR167b transgenic lines had phenotypes similar to those of an arf6 arf8 double mutant The transgenic phenotypes suggest that miR167 may repress ARF6 at the level of translation We demonstrate that the transgenic plants are defective in all four whorls of floral organs In the transgenic flowers filaments were abnormally short anthers could not properly release pollen and pollen grains did not germinate Our results provide an important link between the miRNA mediated regulatory pathway of gene expression and the auxin signaling network promoting plant reproductive development MORN motifs in plant PIPKs are involved in the regulation of subcellular localization and phospholipid binding Hui Ma Ying Lou Wen Hui Lin Hong Wei Xue Cell Research 2006 16 466 478 doi 10 1038 sj cr 7310058 published online 15 May 2006 Full Text PDF Multiple repeats of membrane occupation and recognition nexus MORN motifs were detected in plant phosphatidylinositl monophosphate kinase PIPK a key enzyme in PI signaling pathway Structural analysis indicates that all the MORN motifs with varied numbers at ranges of 7 9 which shared high homologies to those of animal ones were located at N terminus and sequentially arranged except those of OsPIPK1 and AtPIPK7 in which the last MORN motif was separated others by an 100 amino acid island region revealing the presence of two kinds of MORN arrangements in plant PIPKs Through employing a yeast based SMET sequence of membrane targeting system the MORN motifs were shown being able to target the fusion proteins to cell plasma membrane which were further confirmed by expression of fused MORN GFP proteins Further detailed analysis via deletion studies indicated the MORN motifs in OsPIPK1 together with the 104 amino acid island region are involved in the regulation of differential subcellular localization i e plasma membrane or nucleus of the fused proteins Fat Western blot analysis of the recombinant MORN polypeptide expressed in Escherichia coli showed that MORN motifs could strongly bind to PA and relatively slightly to PI4P and PI 4 5 P2 These results provide informative hints on mechanisms of subcellular localization as well as regulation of substrate binding of plant PIPKs Arabidopsis thaliana histone deacetylase 1 AtHD1 is localized in euchromatic regions and demonstrates histone deacetylase activity in vitro Paulus M Fong Lu Tian Z Jeffrey Chen Cell Research 2006 16 479 488 doi 10 1038 sj cr 7310059 published online 15 May 2006 Full Text PDF Arabidopsis thaliana histone deacetylase 1 AtHD1 or AtHDA19 a homolog of yeast RPD3 is a global regulator of many physiological and developmental processes in plants In spite of

    Original URL path: http://www.cell-research.com/artsmore.asp?id=87 (2016-02-14)
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  • Cell Research
    to hypoxia Here we used quantitative real time RT PCR and immunoblotting to determine the activation of HIF 3α vs HIF 1α by hypoxia HIF 3α was strongly induced by hypoxia 1 O 2 both at the level of protein and mRNA due to an increase in protein stability and transcriptional activation whereas HIF 1α protein and mRNA levels enhanced transiently and then decreased because of a reduction in its mRNA stability in A549 cells as measured on mRNA and protein levels Interestingly HIF 3α and HIF 1α exhibited strikingly similar responses to a variety of activating or inhibitory pharmacological agents These results demonstrate that HIF 3α is expressed abundantly in lung epithelial cells and that the transcriptional induction of HIF 3α plays an important role in the response to hypoxia in vitro Our findings suggest that HIF 3α as a member of the HIF system is complementary rather than redundant to HIF 1α induction in protection against hypoxic damage in alveolar epithelial cells Cell Research 2006 16 548 558 doi 10 1038 sj cr 7310072 published online 15 June 2006 Keywords hypoxia inducible factor alveolar epithelial type II cells hypoxia gene expression in vitro MEF2C mediates the activation induced cell death AICD of macrophages Wenxia Fu Jinxue Wei Jun Gu Cell Research 2006 16 559 565 doi 10 1038 sj cr 7310073 published online 15 June 2006 Full Text PDF Activation induced cell death AICD of immune cells is widely believed to be crucial for the regulation of immune responses Although macrophage apoptosis has been observed under a variety of pathological conditions questions as to whether there is AICD of macrophages and how macrophage life span is regulated have not been well addressed AICD in macrophages requires two signals One is cell activation triggered by LPS or other bacterial components The other is an event that exists in AICD susceptible primed but not unsusceptible resting macrophages Here we show that RAW264 7 cell is susceptible to LPS stimulation when it is primed with Salmonella typhimurium type 5 adenovirus Ad5 or IFN γ We found that the stability of the transcription factor MEF2C is increased in primed RAW264 7 cell Transfection of a dominant negative form of MEF2C protects primed macrophage from cell death triggered by LPS Our data demonstrate that the increase of MEF2C protein stability is a key factor in the AICD of macrophage Effects of histone deacetylase inhibitors on transcriptional regulation of the hsp70 gene in Drosophila Yan Mei Zhao Xia Chen Hui Sun Zhi Gen Yuan Guo Ling Ren Xiao Xue Li Jun Lu Bai Qu Huang Cell Research 2006 16 566 576 doi 10 1038 sj cr 7310074 published online 15 June 2006 Full Text PDF Histone acetyltransferases deacetylases contribute to the activation or inactivation of transcription by modifying the structure of chromatin Here we examined the effects of histone deacetylase inhibitors HDIs trichostatin A and sodium butyrate on hsp70 gene transcriptional regulation in Drosophila The chromatin immunoprecipitation assays revealed that HDI treatments induced the

    Original URL path: http://www.cell-research.com/artsmore.asp?id=86 (2016-02-14)
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  • Cell Research
    and TBP during cell cycle showed that both factors proceeded through cell cycle in a similar pace except that TRF3 was slightly delayed than TBP in entering the nucleus when cells were exiting the M phase Data from expression and biochemical analyses therefore support the hypothesis that TRF3 plays a role in early mouse development In addition results from co localization study suggest that TRF3 may be also involved in Pol I transcription Inhibition of the α mannosidase Man2c1 gene expression enhances adhesion of Jurkat cells Li Qu Ji Yu Ju Shuang Ling Chen Yan Shi Zhi Guang Xiang Yi Qun Zhou Yun Tian Yin Liu Li Ping Zhu Cell Research advance online publication 23 May 2006 doi 10 1038 sj cr 7310065 Full Text PDF Protein N glycosylation plays very important roles in immunity and α mannosidase is one of the key enzymes in Nglycosylation This paper reports that inhibition of α mannosidase Man2c1 gene expression enhances adhesion of Jurkat T cells In comparison to the controls with normal expression of the enzyme Jurkat cells with the inhibition of Man2c1 gene expression AS cell formed larger aggregates in culture indicating an enhancement of adhesion between the cells mRNA differential display analysis discovered up regulation of several adhesion molecule genes in the AS cell Because of the pivotal role played by CD54 LFA 1 interaction in immune cell interaction this study focused on the contribution of enhanced expression of CD54 and LFA 1 to the enhanced adhesion of AS Jurkat cells These facts including increased binding of AS cells to ICAM 1 Fc Mg2 activation of the binding of AS cells to ICAM 1 Fc and enhanced aggregation of AS cells together with the inhibiting effect of a blocking CD11a mAb on the binding to ICAM 1 Fc and aggregation of the cells demonstrate an important contribution of enhanced CD54 LFA 1 interaction to increased adhesion between AS cells The enhanced CD54 LFA 1 interaction also resulted in increased adhesion between AS Jurkat T cells and Raji B cells In addition AS cells showed cytoskeletal rearrangement The data imply a biological significance of MAN2C1 in T cell functioning In vitro reassembly of nuclear envelopes and organelles in Xenopus egg extracts In vitro reassembly of nuclear envelopes and organelles in Xenopus egg extracts Cell Research advance online publication 30 May 2006 doi 10 1038 sj cr 7310066 Full Text PDF We reconstituted bilayer nuclear membranes multilayer membranes and organelles from mixtures of Xenopus laevis egg extracts and demembranated Xenopus sperm nuclei Varying proportions of the cytosolic and vesicular fractions from the eggs were used in the reconstitution mixtures A cytosol vesicle ratio of 10 1 promoted reassembly of the normal bilayer nuclear membrane with inserted nuclear pore complexes around the decondensed Xenopus sperm chromatin A cytosol vesicle ratio of 5 1 caused decondensed and dispersed sperm chromatin to be either surrounded by or divided by unusual multilayer membrane structures with inlaid pore complexes A cytosol vesicle ratio of 2 5 1

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