MedWorm: Cytology

Self-killing of melanoma cells by cytosolic delivery of dsRNA: Wiring innate immunity for a coordinated mobilization of endosomes, autophagosomes and the apoptotic machinery in tumor cells.

Autophagy — Fri, 20 Nov 2009 13:48:17 +0100

Authors: Alonso-Curbelo D, Soengas MS Patients with metastatic melanoma have a poor prognosis, primarily due to a generalized inefficacy of current anticancer treatments. Therefore, the identification of novel death inducers with good bioavailability and safety profiles is a main priority in this disease. Here we summarize recent work from our group uncovering an unexpected ability of the dsRNA mimic polyinosine-polycytidylic acid (pIC) to engage the endo/lysosomal machinery of melanoma cells and induce their self degradation by autophagy and apoptosis, without noticeable secondary effects in vivo. However the antimelanoma activity of pIC strictly required conjugation with carriers (e.g., polyethyleneimine, PEI) for cytosolic delivery. Combining transcriptome analyses with RNA interfer...

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The cysteine protease MoAtg4 interacts with MoAtg8 and is required for differentiation and pathogenesis in Magnaporthe oryzae.

Autophagy — Fri, 20 Nov 2009 13:48:14 +0100

Authors: Liu TB, Liu XH, Lu JP, Zhang L, Min H, Lin FC Atg4 is a unique cysteine protease responsible for the cleavage of the carboxyl terminus of Atg8 during the formation of autophagosomes in yeast. Here we report that MoAtg4, an Atg4 homologue in Magnaporthe oryzae, controls cell differentiation and pathogenicity by interacting with MoAtg8, an autophagic protein essential for autophagic cell death and pathogenicity. Yeast complementation assay revealed that MoATG4 can functionally complement the defects of the yeast ATG4 deletion mutant. The direct interaction between MoAtg4 and MoAtg8 was detected in both yeast two hybrid and bimolecular fluorescence complementation (BiFC) assays. We also specify a cysteine residue, Cys206, as the active residue within MoAtg4 for the cleavage of Mo...

Investigating autophagy: Quantitative morphometric analysis using electron microscopy.

Autophagy — Fri, 20 Nov 2009 13:48:10 +0100

Authors: Swanlund JM, Kregel KC, Oberley TD Autophagy is a compensatory pathway involving isolation and subsequent degradation of cytosolic material and organelles in eukaryotic cells.(1) The autophagic process can provide a "housekeeping" function by removing damaged proteins and organelles in a selective or nonselective fashion in order to exert a protective effect following stress.(2) Remarkably, after being discovered to be much more of a targeted process than a random one, the role of autophagy became implicated in many normal cellular and disease processes.(3) Several methodologies are routinely employed to monitor the entire autophagic process.(4) Microtubule-associated protein light chain 3, a mammalian homolog of yeast Atg8, has been widely used as a specific marker to monitor...

Autophagy augmented by troglitazone is independent of EGFR transactivation and correlated with AMP-activated protein kinase signaling.

Autophagy — Fri, 20 Nov 2009 13:48:07 +0100

We report here that troglitazone augments AMP-activated protein kinase-alpha (AMPKalpha) phosphorylation, reduces p70S6 kinase phosphorylation and stimulates autophagy that is independent of EGFR expression and transactivation. Troglitazone stimulus reduced neither lysosomal staining nor GFP-LC3 dots of HeLa cells, when the cells pretreated with AG1478, a specific EGFR kinase inhibitor. Furthermore, AG1478 additively enhanced the troglitazone-induced degradation of sequestosome 1 (SQSTM1/p62), which is a selective substrate of autophagy. Inhibition of AMPKalpha activity either by compound C or by RNA interference markedly reduced the accumulation of microtubule-associated protein 1 light chain 3-II (LC3-II ), a good indicator of autophagy; whereas blockage of PPARgamma activity by the irre...

The Polyhomeotic protein induces hyperplastic tissue overgrowth through the activation of the JAK/STAT pathway.

Cell Cycle — Fri, 20 Nov 2009 13:38:13 +0100

Authors: González I, Simón R, Busturia A Epigenetic mechanisms controlling cellular proliferation are essential to animal development. Moreover, altered levels of expression of the epigenetic regulator proteins are associated with the development and progression of human diseases like cancer. We have studied the effects of high levels of Polyhomeotic (PH) protein, a member of the Polycomb Group (PcG), during the proliferation of the imaginal discs in Drosophila. Overexpression of PH protein causes induction of proliferation, accompanied with induction of JNK-dependent apoptosis. As a result, massive hyperplastic overgrowth is produced and the corresponding differentiated tissues show phenotypes related with mis-regulation of homeotic gene expression. We have found that high l...

Genetic ablation of caveolin-1 increases neural stem cell proliferation in the subventricular zone (SVZ) of the adult mouse brain.

Cell Cycle — Fri, 20 Nov 2009 13:38:10 +0100

In this study, dual-label immunofluorescence analysis of the proliferation marker, Ki67, and the stem cell markers, nestin and Sox2, was performed on brains of 8 week-old wild-type (WT) and Cav-1 knockout (KO) mice. Our results demonstrate an increased number of Ki67-positive nuclei in the subventricular zone (SVZ) of Cav-1 KO brains. Importantly, our dual-label immunofluorescence analyses demonstrate increased co-localization of Ki67 with both nestin and Sox2 in the SVZ of Cav-1 KO brains. Remarkably similar results were also obtained with Cav-2 and Cav-3 KO mouse brains as well, with increased proliferation of adult neural stem cells. Thus, the SVZ of caveolin KO mouse brains displays an increased proliferation of adult neural stem cells. Caveolin proteins might represent new crucial reg...

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Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling

Cell — Fri, 20 Nov 2009 04:00:08 +0100

Kandice R. Levental, Hongmei Yu, Laura Kass, Johnathon N. Lakins, Mikala Egeblad, Janine T. Erler, Sheri F.T. Fong, Katalin Csiszar, Amato Giaccia, Wolfgang Weninger, Mitsuo Yamauchi, David L. Gasser, Valerie M. Weaver. Tumors are characterized by extracellular matrix (ECM) remodeling and stiffening. The importance of ECM remodeling to cancer is appreciated; the relevance of stiffening is less clear. We found tha.... (Source: Cell)

Localisation of translation initiation factors to talin/{beta}3-integrin-enriched adhesion complexes in spreading and migrating mammalian cells

Biology of the Cell — Fri, 20 Nov 2009 00:00:00 +0100

Conclusions Taken together, these findings demonstrate that repression, complex post-transcriptional regulation and modulation of mRNA stability could potentially be taking place along the distal edge of migrating lamellipodia. (Source: Biology of the Cell)

Suppression of ERK signaling evokes autocrine Fas-mediated death in arachidonic acid-treated human chronic myeloid leukemia K562 cells

Journal of Cellular Physiology — Fri, 20 Nov 2009 00:00:00 +0100

Arachidonic acid (AA)-induced apoptotic death of K562 cells (human chronic myeloid leukemic cells) was characteristic of reactive oxygen species (ROS) generation and mitochondrial depolarization. N-Acetylcysteine pretreatment rescued viability of AA-treated cells and abolished mitochondrial depolarization. In contrast to no significant changes in phospho-JNK and phospho-ERK levels, AA evoked notable activation of p38 MAPK. Unlike that of JNK and p38 MAPK, ERK suppression further reduced the viability of AA-treated cells. Increases in Fas/FasL protein expression, caspase-8 activation, the production of tBid and the loss of mitochondrial membrane potential were noted with K562 cells that were treated with a combination of U0126 and AA. Down-regulation of FADD attenuated U0126-evoked degradat...

MEPE evolution in mammals reveals regions and residues of prime functional importance.

Cellular and Molecular Life Sciences : CMLS — Fri, 20 Nov 2009 00:00:00 +0100

Authors: Bardet C, Delgado S, Sire JY In mammals, the matrix extracellular phosphoglycoprotein (MEPE) is known to activate osteogenesis and mineralization via a particular region called dentonin, and to inhibit mineralization via its ASARM (acidic serine-aspartate rich MEPE-associated motif) peptide that also plays a role in phosphatemia regulation. In order to understand MEPE evolution in mammals, and particularly that of its functional regions, we conducted an evolutionary analysis based on the study of selective pressures. Using 37 mammalian sequences we: (1) confirmed the presence of an additional coding exon in most placentals; (2) highlighted several conserved residues and regions that could have important functions; (3) found that dentonin function was recruited in a placental a...

Zyxin controls migration in epithelial-mesenchymal transition by mediating actin-membrane linkages at cell-cell junctions

Journal of Cellular Physiology — Thu, 19 Nov 2009 00:00:00 +0100

Development is punctuated by morphogenetic rearrangements of epithelial tissues, including detachment of motile cells during epithelial-mesenchymal transition (EMT). Dramatic actin rearrangements occur as cell-cell junctions are dismantled and cells become independently motile during EMT. Characterizing dynamic actin rearrangements and identifying actin machinery driving these rearrangements is essential for understanding basic mechanisms of cell-cell junction remodeling. Using immunofluorescence and live cell imaging of scattering MDCK cells we examine dynamic actin rearrangement events during EMT and demonstrate that zyxin-VASP complexes mediate linkage of dynamic medial actin networks to adherens junction (AJ) membranes. A functional analysis of zyxin in EMT reveals its role in regulati...

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Direct cell-cell contact between periodontal ligament fibroblasts and osteoclast precursors synergistically increases the expression of genes related to osteoclastogenesis

Journal of Cellular Physiology — Thu, 19 Nov 2009 00:00:00 +0100

The formation of bone resorbing osteoclasts in vivo is orchestrated by cells of the osteoblast lineage such as periodontal ligament fibroblasts that provide the proper signals to osteoclast precursors. Although the requirement of cell-cell interactions is widely acknowledged, it is unknown whether these interactions influence the expression of genes required for osteoclastogenesis and the ultimate formation of osteoclasts. In the present study we investigated the effect of cell-cell interaction on the mRNA expression of adhesion molecules and molecules involved in osteoclast formation in cultures of peripheral blood mononuclear cells (PBMCs) and human primary periodontal ligament fibroblasts, both as solitary cultures and in co-culture. We further analyzed the formation of multinucleated, ...

Muscarinic cholinoceptor activation by pilocarpine triggers apoptosis in human skin fibroblast cells

Journal of Cellular Physiology — Thu, 19 Nov 2009 00:00:00 +0100

The aim of the present work was to examine the role of muscarinic acetylcholine receptors (mAChRs) on apoptosis in human skin fibroblast cells. Neonatal human skin fibroblast cultures were stimulated with pilocarpine in the presence or absence of specific antagonists. Pilocarpine stimulates apoptosis, total inositol phosphates (InsP) accumulation and nitric oxide synthase (NOS) activity. All these effects were inhibited by atropine, mustard hydrochloride (4-DAMP) and pirenzepine, indicating that M1 and M3 mAChRs are implicated in pilocarpine action. Pilocarpine apoptotic action is accompanied by caspase-3 and JNK activation. The intracellular pathway leading to pilocarpine-induced biological effects involved phospholipase C, calcium/calmodulin and extracellular calcium as U-73122, W-7, ver...

Simulated diving after heat stress potentiates the induction of heat shock protein 70 and elevates glutathione in human endothelial cells.

Cell Stress and Chaperones — Thu, 19 Nov 2009 00:00:00 +0100

Authors: Djurhuus R, Nossum V, Lundsett N, Hovin W, Svardal AM, Havnes MB, Fismen L, Hjelde A, Brubakk AO Heat stress prior to diving has been shown to confer protection against endothelial damage due to decompression sickness. Several lines of evidence indicate a relation between such protection and the heat shock protein (HSP)70 and HSP90 and the major cellular red-ox determinant, glutathione (GSH). The present study has used human endothelial cells as a model system to investigate how heat stress and simulated diving affect these central cellular defense molecules. The results demonstrated for the first time that a simulated dive at 2.6 MPa (26 bar) had a potentiating effect on the heat-induced expression of HSP70, increasing the HSP70 concentration on average 54 times above control...

Fusogenic activity of cationic lipids and lipid shape distribution.

Cellular and Molecular Life Sciences : CMLS — Thu, 19 Nov 2009 00:00:00 +0100

Authors: Lonez C, Lensink MF, Kleiren E, Vanderwinden JM, Ruysschaert JM, Vandenbranden M Addition of co-lipids into cationic lipid formulations is considered as promoting cell delivery of DNA by enhancing fusion processes with cell membranes. Here, by combining FRET and confocal microscopy, we demonstrate that some cationic lipids do not require a co-lipid to fuse efficiently with cells. These cationic lipids are able to self-organize into bilayers that are stable enough to form liposomes, while presenting some destabilizing properties reminiscent of the conically shaped fusogenic co-lipid, DOPE. We therefore analyzed the resident lipid structures in cationic bilayers by molecular dynamics simulations, clustering the individual lipid structures into populations of similarly shaped mol...

Targeted therapy of spinal cord glioma with a genetically modified Salmonella typhimurium

Cell Proliferation — Thu, 19 Nov 2009 00:00:00 +0100

Conclusions: These results suggest that S. typhimurium A1-R monotherapy can effectively treat spinal cord glioma. (Source: Cell Proliferation)

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Effects of Extracellular Matrix on Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Smooth Muscle Cell Lineage: Utility for Cardiovascular Tissue Engineering

Cells Tissues Organs — Wed, 18 Nov 2009 23:00:00 +0100

Cells Tissues Organs (DOI:10.1159/000260061) (Source: Cells Tissues Organs)

Does the Cranial Suspensory Ligament Have a Role in Cryptorchidism?

Cells Tissues Organs — Wed, 18 Nov 2009 23:00:00 +0100

Cells Tissues Organs (DOI:10.1159/000260062) (Source: Cells Tissues Organs)

Dynamic Expression and Heterogeneous Intracellular Location of En-1 during Late Mouse Embryonic Development

Cells Tissues Organs — Wed, 18 Nov 2009 23:00:00 +0100

Cells Tissues Organs (DOI:10.1159/000260063) (Source: Cells Tissues Organs)

Am J Physiol Cell Physiol; +26 new citations

Am J Physiol Cell Ph... — Wed, 18 Nov 2009 18:02:03 +0100

26 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Physiol Cell Physiol These pubmed results were generated on 2009/11/18PubMed, a service of the National Library of Medicine, includes over 15 million citations for biomedical articles back to the 1950's. These citations are from MEDLINE and additional life science journals. PubMed includes links to many sites providing full text articles and other related resources. (Source: Am J Physiol Cell Ph...)

Polarized traffic towards the cell surface: how to find the route.

Biology of the Cell — Wed, 18 Nov 2009 17:46:05 +0100

Authors: Carmosino M, Valenti G, Caplan M, Svelto M Polarity is the structural and functional hallmark of epithelia. The apical plasma membrane, facing the organism's exterior (the lumen of the gut, renal tubule and glandular duct), differs in many important respects from the basolateral plasma membrane that is apposed to the interior of the organism. The generation and maintenance of epithelial polarity require a highly specialized subcellular machinery to bring proteins to their appropriate sites of action. This is a dynamic process involving the interpretation of sorting signals, vectorial delivery mechanisms, membrane-specific fusion and retention processes. Here, we will provide a review of the field, highlighting recent advances within a historically relevant context. PMID: 1...

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Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle.

American Journal of Physiology. Cell Physiology — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Treebak JT, Taylor EB, Witczak CA, An D, Toyoda T, Koh HJ, Xie J, Feener EP, Wojtaszewski JF, Hirshman MF, Goodyear LJ TBC1D4 (also known as AS160) regulates GLUT4 translocation and glucose uptake in adipocytes and skeletal muscle. Its mode of action involves phosphorylation of Serine (S)/Threonine (T) residues by upstream kinases resulting in inactivation of Rab-GAP activity leading to GLUT4 mobilization. The majority of known phosphorylation sites on TBC1D4 lie within the Akt consensus motif and are phosphorylated by insulin stimulation. However, the 5 AMP activated protein kinase (AMPK) and other kinases may also phosphorylate TBC1D4, and therefore we hypothesized the presence of additional phosphorylation sites. Mouse skeletal muscles were contracted or stimulated with 5-a...

Extensive mononuclear infiltration and myogenesis characterize the recovery of dysferlin-null skeletal muscle from contraction-induced injuries.

American Journal of Physiology. Cell Physiology — Wed, 18 Nov 2009 00:00:00 +0100

We report that dysferlin-null myofibers retain 10 kDa dextran for 3 days after large-strain injury but are lost thereafter, following necrosis and inflammation. Recovery of dysferlin-null muscle requires myogenesis, which delays the return of contractile function compared to controls, which recover from large-strain injury by repairing damaged myofibers without significant inflammation, necrosis, or myogenesis. Recovery of control and dysferlin-null muscles from small-strain injury involved inflammation and necrosis followed by myogenesis, all of which were more pronounced in the dysferlin-null, which recovered more slowly. Both control and dysferlin-null muscles also retained 10 kDa dextran for 3 days after small-strain injury. We conclude that dysferlin-null myofibers can survive contrac...

Abnormalities in Focal Adhesion Complex Formation, Regulation and Function in Human Autosomal Recessive Polycystic Kidney Disease (ARPKD) Epithelial Cells.

American Journal of Physiology. Cell Physiology — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Israeli S, Amsler K, Zheleznova NN, Wilson PD Integrin-associated focal adhesion complex formation and turnover plays an essential role in directing interactions between epithelial cells and the extra-cellular matrix during organogenesis, leading to appropriate cell spreading, cell-matrix adhesion and migration. Autosomal Recessive Polycystic Kidney Disease (ARPKD) is associated with loss of function of PKHD1-encoded protein Fibrocystin-1 and is characterized by cystic dilation of renal collecting tubules (CT) in utero and loss of renal function in patients if they survive the perinatal period. Normal Polycystin1 (PC-1)/focal adhesion complex function is required for control of CT diameter during renal development and abnormalities in these complexes have been demonstrated in ...

PI(4,5)P2 and loss of PLC{gamma} activity inhibit TRPM channels required for oscillatory Ca2+ signaling.

American Journal of Physiology. Cell Physiology — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Xing J, Strange K The C. elegans intestinal epithelium generates rhythmic inositol 1,4,5-trisphosphate (IP3)-dependent Ca(2+) oscillations that control muscle contractions required for defecation. Two highly Ca(2+) selective TRPM channels, GON-2 and GTL-1, function with PLCgamma in a common signaling pathway that regulates IP(3)-dependent intracellular Ca(2+) release. A second PLC, PLCgamma, is also required for IP3-dependent Ca(2+) oscillations, but functions in an independent signaling mechanism. PLCgamma generates IP(3) that regulates IP3 receptor activity. We demonstrate here that PLCgamma via hydrolysis of PI(4,5)P2 (PIP(2)) also regulates GON-2/GTL-1 function. Knockdown of PLCgamma but not PLCgamma activity by RNA interference (RNAi) inhibits channel activity ~80%. Inhib...

Filamin and filamin-binding proteins in integrin-regulation and adhesion. Focus on: "FilaminA is required for vimentin-mediated cell adhesion and spreading"

American Journal of Physiology. Cell Physiology — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Macpherson M, Fagerholm S not required for this manuscript type. PMID: 19923422 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Cell Physiology)

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Cytoskeletal Structure Regulates Endothelial Cell Immunogenicity Independent of Fluid Shear Stress.

American Journal of Physiology. Cell Physiology — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Vartanian KB, Berny MA, McCarty OJ, Hanson SR, Hinds MT The cardiovascular disease atherosclerosis is directly linked to the functions of the endothelial cells (ECs), which are affected by fluid shear stress (FSS). High, unidirectional FSS causes EC elongation with aligned cytoskeletal components and non-immunogenic EC functions protecting against atherosclerosis. In contrast, low, oscillatory FSS is associated with cobblestone-shaped ECs with a randomly oriented cytoskeleton and pro-inflammatory EC functions that promote atherosclerosis. Whether EC shape plays a role in EC immunogenic functions, independent of FSS, has not been previously determined. The goal of this study was to determine the effect of EC elongation and cytoskeletal alignment on the expression of inflammator...

Caveolin gene transfer improves glucose metabolism in diabetic mice.

American Journal of Physiology. Cell Physiology — Wed, 18 Nov 2009 00:00:00 +0100

In conclusion, our results suggest that caveolin is an important regulator of glucose metabolism that can enhance insulin signals. PMID: 19923424 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Cell Physiology)

Why proteins without an alpha-crystallin domain should not be included in the human small heat shock protein family HSPB.

Cell Stress and Chaperones — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Kappé G, Boelens WC, de Jong WW The presence of an alpha-crystallin domain documents the evolutionary relatedness of the ubiquitous family of small heat shock proteins. Sequence and three-dimensional structure provide no evidence for the presence of such a domain in HSPC034, recently proposed as the 11th member of the human HSPB family. Also, phylogenetic analyses detect no relationship between HSPC034 and the human HSPB1-10 sequences. Arguments are provided as to why inclusion in the HSPB family of proteins like HSPC034, which resemble small heat shock proteins in being heat-inducible and having chaperone-like properties and a low monomeric mass, but are evolutionarily unrelated, is misleading and confusing. PMID: 19921466 [PubMed - as supplied by publisher] (Source:...

Lucifensin, the long-sought antimicrobial factor of medicinal maggots of the blowfly Lucilia sericata.

Cellular and Molecular Life Sciences : CMLS — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Ceřovský V, Zďárek J, Fučík V, Monincová L, Voburka Z, Bém R A novel homologue of insect defensin designated lucifensin (Lucilia defensin) was purified from the extracts of various tissues (gut, salivary glands, fat body, haemolymph) of green bottle fly (Lucilia sericata) larvae and from their excretions/secretions. The primary sequence of this peptide of 40 residues and three intramolecular disulfide bridges was determined by ESI-QTOF mass spectrometry and Edman degradation and is very similar to that of sapecin and other dipteran defensins. We assume that lucifensin is the key antimicrobial component that protects the maggots when they are exposed to the highly infectious environment of a wound during the medicinal process known as ...

The p200 family protein p204 as a modulator of cell proliferation and differentiation: a brief survey.

Cellular and Molecular Life Sciences : CMLS — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Lengyel P, Liu CJ The expression of the murine p200 family protein p204 in numerous tissues can be activated by a variety of distinct, tissue-specific transcription factors. p204 modulates cell proliferation, cell cycling, and the differentiation of various tissues, including skeletal muscle myotubes, beating cardiac myocytes, osteoblasts, chondrocytes, and macrophages. This protein modulates these processes in various ways, such as by (1) blocking ribosomal RNA synthesis in the nucleolus, (2) inhibiting Ras signaling in the cytoplasm, (3) promoting the activity of particular transcription factors in the nucleus by forming complexes with them, and (4) overcoming the block of the activity of other transcription factors by inhibitor of differentiation (Id) proteins. Much remains...

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Biological activity of phenolic lipids.

Cellular and Molecular Life Sciences : CMLS — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Stasiuk M, Kozubek A Phenolic lipids are a very diversified group of compounds derived from mono and dihydroxyphenols, i.e., phenol, catechol, resorcinol, and hydroquinone. Due to their strong amphiphilic character, these compounds can incorporate into erythrocytes and liposomal membranes. In this review, the antioxidant, antigenotoxic, and cytostatic activities of resorcinolic and other phenolic lipids are described. The ability of these compounds to inhibit bacterial, fungal, protozoan and parasite growth seems to depend on their interaction with proteins and/or on their membrane-disturbing properties. PMID: 19921485 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)

Sub-millimolar concentration of the novel phenol-based compound, 2-hydroxy benzoate zinc, induces apoptosis in human HT-1080 fibrosarcoma cells

Cell Proliferation — Wed, 18 Nov 2009 00:00:00 +0100

Conclusions: These results demonstrate that the novel phenolic compound 2HBZ is a potent apoptosis-inducing agent in HT-1080 cells and warrants further investigation as a potential chemotherapeutic agent in primary cancer cell models. (Source: Cell Proliferation)

Interstitial cell migration: integrin-dependent and alternative adhesion mechanisms

Cell and Tissue Research — Tue, 17 Nov 2009 23:47:51 +0100

Abstract Adhesion and migration are integrated cell functions that build, maintain and remodel the multicellular organism. In migrating cells, integrins are the main transmembrane receptors that provide dynamic interactions between extracellular ligands and actin cytoskeleton and signalling machineries. In parallel to integrins, other adhesion systems mediate adhesion and cytoskeletal coupling to the extracellular matrix (ECM). These include multifunctional cell surface receptors (syndecans and CD44) and discoidin domain receptors, which together coordinate ligand binding with direct or indirect cytoskeletal coupling and intracellular signalling. We review the way that the different adhesion systems for ECM components impact cell migration in two- and three-dimensional mig...

Special Features and New Developments.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Sweet DJ PMID: 19922861 [PubMed - as supplied by publisher] (Source: Developmental Cell)

Sorting Out Endosomes in the WASH.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Bear JE Two new studies published in this issue of Developmental Cell by Derivery et al. and Gomez and Billadeau reveal that WASH (Wiskott-Aldrich syndrome protein and SCAR homolog) activates Arp2/3 on endosomes and plays a critical role in the fission of tubules that serve as transport intermediates during endosome sorting. PMID: 19922862 [PubMed - as supplied by publisher] (Source: Developmental Cell)

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Developmental ECM Sculpting: Laying It Down and Cutting It Up.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Feinberg T, Weiss SJ In mammals, proteolytic remodeling of the embryonic extracellular matrix (ECM) controls morphogenesis, but the key players remain elusive. Two recent reports identify new roles for metalloproteinases belonging to the MT-MMP and ADAMTS families in branching morphogenesis and interdigital web regression. PMID: 19922863 [PubMed - as supplied by publisher] (Source: Developmental Cell)

Nuclei Take a Position: Managing Nuclear Location.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Burke B, Roux KJ Eukaryotic cells display considerable morphological plasticity linked to their abilities to carry out a myriad of complex functions. Structural rearrangements associated with cellular activities, from yeast mitosis to cell migration in the mammalian central nervous system, often involve relocation of the cell nucleus. Recent studies have provided insight into how nuclear components can be mechanically coupled to the cytoskeleton, providing a more complete understanding of the role of nuclear positioning in both health and disease. PMID: 19922864 [PubMed - as supplied by publisher] (Source: Developmental Cell)

The SUN Rises on Meiotic Chromosome Dynamics.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Hiraoka Y, Dernburg AF Recent studies in diverse eukaryotes have implicated a family of nuclear envelope proteins containing SUN domains as key components of meiotic nuclear organization and chromosome dynamics. In many cases, these transmembrane proteins are also known to contribute to centrosome or spindle pole body function in mitotically dividing cells. During meiotic prophase, the apparent role of these SUN-domain proteins, together with their partner KASH-domain proteins, is to connect chromosomes through the intact nuclear envelope to force-generating mechanisms in the cytoplasm. PMID: 19922865 [PubMed - as supplied by publisher] (Source: Developmental Cell)

Border Control at the Nucleus: Biogenesis and Organization of the Nuclear Membrane and Pore Complexes.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Hetzer MW, Wente SR Over the last decade, the nuclear envelope (NE) has emerged as a key component in the organization and function of the nuclear genome. As many as 100 different proteins are thought to specifically localize to this double membrane that separates the cytoplasm and the nucleoplasm of eukaryotic cells. Selective portals through the NE are formed at sites where the inner and outer nuclear membranes are fused, and the coincident assembly of approximately 30 proteins into nuclear pore complexes occurs. These nuclear pore complexes are essential for the control of nucleocytoplasmic exchange. Many of the NE and nuclear pore proteins are thought to play crucial roles in gene regulation and thus are increasingly linked to human diseases. PMID: 19922866 [PubMed - a...

Acting Out of Character: Regulatory Roles of Nuclear Pore Complex Proteins.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Xylourgidis N, Fornerod M Nuclear pore complexes (NPCs) mediate all selective bidirectional transport between the nucleus and the cytoplasm. Additional functions for NPCs and their constituent proteins (nucleoporins) are emerging, some independent of classical transport. Specifically, enzymatic activities at the NPC regulate nucleocytoplasmic transport and use the NPC as a regulatory scaffold. Also, nucleoporins may regulate gene expression by contacting chromatin. Discriminating between effects on transport, scaffolding, and gene expression is a major challenge in understanding the role of the NPC in signaling and development. PMID: 19922867 [PubMed - as supplied by publisher] (Source: Developmental Cell)

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The Nuclear Envelope as a Signaling Node in Development and Disease.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Dauer WT, Worman HJ The development of a membrane-bound structure separating DNA from other cellular components was the epochal evolutionary event that gave rise to eukaryotes, possibly occurring up to 2 billion years ago. Yet, this view of the nuclear envelope as a physical barrier greatly underestimates its fundamental impact on cellular organization and complexity, much of which is only beginning to be understood. Indeed, alterations of nuclear envelope structure and protein composition are essential to many aspects of metazoan development and cellular differentiation. Mutations in genes encoding nuclear envelope proteins cause a fascinating array of diseases referred to as "nuclear envelopathies" or "laminopathies" that affect different tissues and organ systems. We review...

Nuclear Bodies: Random Aggregates of Sticky Proteins or Crucibles of Macromolecular Assembly?

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Matera AG, Izaguire-Sierra M, Praveen K, Rajendra TK The principles of self-assembly and self-organization are major tenets of molecular and cellular biology. Governed by these principles, the eukaryotic nucleus is composed of numerous subdomains and compartments, collectively described as nuclear bodies. Emerging evidence reveals that associations within and between various nuclear bodies and genomic loci are dynamic and can change in response to cellular signals. This review will discuss recent progress in our understanding of how nuclear body components come together, what happens when they form, and what benefit these subcellular structures may provide to the tissues or organisms in which they are found. PMID: 19922869 [PubMed - as supplied by publisher] (Source: Devel...

MOR23 Promotes Muscle Regeneration and Regulates Cell Adhesion and Migration.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Griffin CA, Kafadar KA, Pavlath GK Odorant receptors (ORs) in the olfactory epithelium bind to volatile small molecules leading to the perception of smell. ORs are expressed in many tissues but their functions are largely unknown. We show multiple ORs display distinct mRNA expression patterns during myogenesis in vitro and muscle regeneration in vivo. Mouse OR23 (MOR23) expression is induced during muscle regeneration when muscle cells are extensively fusing and plays a key role in regulating migration and adhesion of muscle cells in vitro, two processes common during tissue repair. A soluble ligand for MOR23 is secreted by muscle cells in vitro and muscle tissue in vivo. MOR23 is necessary for proper skeletal muscle regeneration as loss of MOR23 leads to increased myofiber br...

A Family of microRNAs Encoded by Myosin Genes Governs Myosin Expression and Muscle Performance.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: van Rooij E, Quiat D, Johnson BA, Sutherland LB, Qi X, Richardson JA, Kelm RJ, Olson EN Myosin is the primary regulator of muscle strength and contractility. Here we show that three myosin genes, Myh6, Myh7, and Myh7b, encode related intronic microRNAs (miRNAs), which, in turn, control muscle myosin content, myofiber identity, and muscle performance. Within the adult heart, the Myh6 gene, encoding a fast myosin, coexpresses miR-208a, which regulates the expression of two slow myosins and their intronic miRNAs, Myh7/miR-208b and Myh7b/miR-499, respectively. miR-208b and miR-499 play redundant roles in the specification of muscle fiber identity by activating slow and repressing fast myofiber gene programs. The actions of these miRNAs are mediated in part by a collection of trans...

Moz and Retinoic Acid Coordinately Regulate H3K9 Acetylation, Hox Gene Expression, and Segment Identity.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

In conclusion, our data show that Moz regulates H3K9 acetylation at Hox gene loci and that RA can act independently of Moz to establish specific Hox gene expression boundaries. PMID: 19922872 [PubMed - as supplied by publisher] (Source: Developmental Cell)

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ADAMTS Metalloproteases Generate Active Versican Fragments that Regulate Interdigital Web Regression.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: McCulloch DR, Nelson CM, Dixon LJ, Silver DL, Wylie JD, Lindner V, Sasaki T, Cooley MA, Argraves WS, Apte SS We show that combinatorial mouse alleles for the secreted metalloproteases Adamts5, Adamts20 (bt), and Adamts9 result in fully penetrant soft-tissue syndactyly. Interdigital webs in Adamts5(-/-);bt/bt mice had reduced apoptosis and decreased cleavage of the proteoglycan versican; however, the BMP-FGF axis, which regulates interdigital apoptosis was unaffected. BMP4 induced apoptosis, but without concomitant versican proteolysis. Haploinsufficiency of either Vcan or Fbln1, a cofactor for versican processing by ADAMTS5, led to highly penetrant syndactyly in bt mice, suggesting that cleaved versican was essential for web regression. The local application of an aminotermina...

A FAM21-Containing WASH Complex Regulates Retromer-Dependent Sorting.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Gomez TS, Billadeau DD The Arp2/3 complex regulates endocytosis, sorting, and trafficking, yet the Arp2/3-stimulating factors orchestrating these distinct events remain ill defined. WASH (Wiskott-Aldrich Syndrome Protein and SCAR Homolog) is an Arp2/3 activator with unknown function that was duplicated during primate evolution. We demonstrate that WASH associates with tubulin and localizes to early endosomal subdomains, which are enriched in Arp2/3, F-actin, and retromer components. Although WASH localized with activated receptors, it was not essential for endocytosis. However, WASH did regulate retromer-mediated retrograde CI-MPR trafficking, which required its association with endosomes, Arp2/3-directed F-actin regulation, and tubulin interaction. Moreover, WASH exists in a ...

The Arp2/3 Activator WASH Controls the Fission of Endosomes through a Large Multiprotein Complex.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Derivery E, Sousa C, Gautier JJ, Lombard B, Loew D, Gautreau A The Arp2/3 complex generates branched actin networks when activated by Nucleation Promoting Factors (NPFs). Recently, the WASH family of NPFs has been identified, but its cellular role is unclear. Here, we show that WASH generates an actin network on a restricted domain of sorting and recycling endosomes. We found that WASH belongs to a multiprotein complex containing seven subunits, including the heterodimer of capping protein (CP). In vitro, the purified WASH complex activates Arp2/3-mediated actin nucleation and binds directly to liposomes. WASH also interacts with dynamin. WASH depletion gives rise to long membrane tubules pulled out from endosomes along microtubules, as does dynamin inhibition. Accordingly, WA...

SUMO Regulates the Assembly and Function of a Cytoplasmic Intermediate Filament Protein in C. elegans.

Developmental Cell — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Kaminsky R, Denison C, Bening-Abu-Shach U, Chisholm AD, Gygi SP, Broday L Sumoylation is a reversible posttranslational modification that plays roles in many processes, including transcriptional regulation, cell division, chromosome integrity, and DNA damage response. Using a proteomics approach, we identified approximately 250 candidate targets of sumoylation in C. elegans. One such target is the cytoplasmic intermediate filament (cIF) protein named IFB-1, which is expressed in hemidesmosome-like structures in the worm epidermis and is essential for embryonic elongation and maintenance of muscle attachment to the cuticle. In the absence of SUMO, IFB-1 formed ectopic filaments and protein aggregates in the lateral epidermis. Moreover, depletion of SUMO or mutation of the SUMO ...

GABAergic Signaling Increases Through the Postnatal Development to Provide the Potent Inhibitory Capability for the Maturing Demands of the Prefrontal Cortex.

Cellular and Molecular Neurobiology — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Cui J, Wang F, Wang K, Xiang H The developmental profile of the firing patterns and construction of synapse connection were studied in LTS interneurons of prefrontal cortex (PFC) in rats with age (from P7 to P30). We used whole cell patch-clamp recordings to characterize electrophysiological properties of LTS interneurons in PFC at different age stages, including the action potentials (APs), short-term plasticity (STP), evoked excitatory postsynaptic currents (eEPSCs), spontaneous excitatory postsynaptic currents (sEPSC), and spontaneous inhibitory postsynaptic current (sIPSC). The developmental profile of LTS interneurons in our research showed two phases changes. The early phase from P7-P11 to P16-P19 during which the development of individual LTS interneuron dominated and j...

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The role of scaffold proteins in JNK signalling

Cell Proliferation — Tue, 17 Nov 2009 00:00:00 +0100

This paper summarises how scaffold proteins affects and regulate the JNK signalling pathway. We believe that some of these scaffold proteins, by virtue of their anchoring and catalytic properties contribute to a high degree of specificity of intra cellular signalling pathways that regulate the progression through the cell cycle. (Source: Cell Proliferation)

Anti-proliferative effects of γ-tocotrienol on mammary tumour cells are associated with suppression of cell cycle progression

Cell Proliferation — Tue, 17 Nov 2009 00:00:00 +0100

Objectives: Previous studies have shown that [gamma]-tocotrienol induces potent anti-proliferative effects on +SA mammary tumour cells in culture; here, investigations have been conducted to determine its effects on intracellular signalling proteins involved in regulating cell cycle progression.Materials and methods: +SA cells were maintained in mitogen-free defined media containing 0 or 4 [mu]m[gamma]-tocotrienol, for 48 h to synchronize cell cycle in G0 phase, and then they were exposed to 100 ng/ml EGF to initiate cell cycle progression. Whole cell lysates were collected at various time points from each treatment group and were prepared for Western blot analysis.Results and conclusions: Treatment with 4 [mu]m[gamma]-tocotrienol significantly inhibited +SA cell proliferation over a 4-day...

Cellular responses and expression profiling of human bone marrow stromal cells stimulated with enamel matrix proteins in vitro

Cell Proliferation — Tue, 17 Nov 2009 00:00:00 +0100

Conclusions: EMPs promoted cell proliferation and differentiation and gene expression profiles of HBMSCs were affected. This may help elucidation of mechanisms involved in promoting regeneration of periodontal tissues by EMPs. (Source: Cell Proliferation)

Structural and Ontogenetic Study of the Urachus in Human Fetuses

Cells Tissues Organs — Mon, 16 Nov 2009 23:00:00 +0100

Cells Tissues Organs (DOI:10.1159/000258785) (Source: Cells Tissues Organs)

Transplantation of Mesenchymal Stem Cells exerts a greater long-term effect than Bone Marrow Mononuclear Cells in a chronic myocardial infarction model in rat.

Cell Transplantation — Mon, 16 Nov 2009 00:00:00 +0100

Conclusions: Altogether, results show that MSC provides a long-term superior benefit than whole BM-MNC transplantation in a rat model of chronic MI. PMID: 19919732 [PubMed - as supplied by publisher] (Source: Cell Transplantation)

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Immune tolerance induction by integrating innate and adaptive immune regulators.

Cell Transplantation — Mon, 16 Nov 2009 00:00:00 +0100

Authors: Suzuki J, Ricordi C, Chen Z A diversity of immune tolerance mechanisms have evolved to protect normal tissues from immune damage. Immune regulatory cells are critical contributors to peripheral tolerance. These regulatory cells, exemplified by the CD4Foxp3 regulatory T (Treg) cells and a recently identified population named myeloid-derived suppressor cells (MDSCs), regulate immune responses and limiting immune-mediated pathology. In a chronic inflammatory setting, such as allograft-directed immunity, there may be a dynamic "crosstalk" between the innate and adaptive immunomodulatory mechanisms for an integrated control of immune damage. CTLA4-B7-based interaction between the two branches may function as a molecular "bridge" to facilitate such "crosstalk". Understanding the int...

Fatigue in neuromuscular disorders: focus on Guillain-Barré syndrome and Pompe disease.

Cellular and Molecular Life Sciences : CMLS — Mon, 16 Nov 2009 00:00:00 +0100

Fatigue in neuromuscular disorders: focus on Guillain-Barré syndrome and Pompe disease. Cell Mol Life Sci. 2009 Nov 16; Authors: de Vries JM, Hagemans ML, Bussmann JB, van der Ploeg AT, van Doorn PA Fatigue accounts for an important part of the burden experienced by patients with neuromuscular disorders. Substantial high prevalence rates of fatigue are reported in a wide range of neuromuscular disorders, such as Guillain-Barré syndrome and Pompe disease. Fatigue can be subdivided into experienced fatigue and physiological fatigue. Physiological fatigue in turn can be of central or peripheral origin. Peripheral fatigue is an important contributor to fatigue in neuromuscular disorders, but in reaction to neuromuscular disease fatigue of central origin can be an importan...

Conference Calendar

Cells Tissues Organs — Sun, 15 Nov 2009 23:00:00 +0100

Cells Tissues Organs 2009;190:356 (DOI:10.1159/000260059) (Source: Cells Tissues Organs)

Acknowledgement to Referees

Cells Tissues Organs — Sun, 15 Nov 2009 23:00:00 +0100

Cells Tissues Organs 2009;190:357-358 (DOI:10.1159/000260064) (Source: Cells Tissues Organs)

Author Index Vol. 190, 2009

Cells Tissues Organs — Sun, 15 Nov 2009 23:00:00 +0100

Cells Tissues Organs 2009;190:359-360 (DOI:10.1159/000260065) (Source: Cells Tissues Organs)

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Subject Index Vol. 190, 2009

Cells Tissues Organs — Sun, 15 Nov 2009 23:00:00 +0100

Cells Tissues Organs 2009;190:361-362 (DOI:10.1159/000260066) (Source: Cells Tissues Organs)

Contents Vol. 190, 2009

Cells Tissues Organs — Sun, 15 Nov 2009 23:00:00 +0100

Cells Tissues Organs 2009;190:I-IV (DOI:10.1159/000260067) (Source: Cells Tissues Organs)

Generation of neural crest cells and peripheral sensory neurons from human embryonic stem cells.

Cell Research — Sun, 15 Nov 2009 01:14:04 +0100

Authors: Goldstein RS, Pomp O, Brokhman I, Ziegler L Peripheral somatic sensory neurons (PSNs) are responsible for the critical function of transmitting multiple modalities of information from the outside world, including heat, touch, and pain, as well as the position of muscles required for coordinated voluntary movement to the central nervous system. Many peripheral neuropathies exist, including hereditary neurodegeneration in Familial Dysautonomia, infections of PSNs by viruses such as Varicella zoster and damage to PSNs and/or their process resulting from other disease conditions such as diabetes. Understanding of the etiology of these diseases and development of treatments is hampered by the lack of normal and healthy human PSNs for study, which are only available from abortuses o...

Progress in phage display: evolution of the technique and its applications.

Cellular and Molecular Life Sciences : CMLS — Sun, 15 Nov 2009 00:00:00 +0100

Authors: Bratkovič T Phage display, the presentation of (poly)peptides as fusions to capsid proteins on the surface of bacterial viruses, celebrates its 25th birthday in 2010. The technique, coupled with in vitro selection, enables rapid identification and optimization of proteins based on their structural or functional properties. In the last two decades, it has advanced tremendously and has become widely accepted by the scientific community. This by no means exhaustive review aims to inform the reader of the key modifications in phage display. Novel display formats, innovative library designs and screening strategies are discussed. I will also briefly review some recent uses of the technology to illustrate its incredible versatility. PMID: 19915992 [PubMed - as supplied by ...

Homing endonucleases: from basics to therapeutic applications.

Cellular and Molecular Life Sciences : CMLS — Sun, 15 Nov 2009 00:00:00 +0100

Authors: Marcaida MJ, Muñoz IG, Blanco FJ, Prieto J, Montoya G Homing endonucleases (HE) are double-stranded DNAses that target large recognition sites (12-40 bp). HE-encoding sequences are usually embedded in either introns or inteins. Their recognition sites are extremely rare, with none or only a few of these sites present in a mammalian-sized genome. However, these enzymes, unlike standard restriction endonucleases, tolerate some sequence degeneracy within their recognition sequence. Several members of this enzyme family have been used as templates to engineer tools to cleave DNA sequences that differ from their original wild-type targets. These custom HEs can be used to stimulate double-strand break homologous recombination in cells, to induce the repair of defective genes wi...

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Erratum to: Drug Abuse in China: Past, Present and Future.

Cellular and Molecular Neurobiology — Sun, 15 Nov 2009 00:00:00 +0100

Authors: Lu L, Fang Y, Wang X PMID: 19916046 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Neurobiology)

ADP receptor P2Y(13) induce apoptosis in pancreatic beta-cells.

Cellular and Molecular Life Sciences : CMLS — Sat, 14 Nov 2009 00:00:00 +0100

Authors: Tan C, Salehi A, Svensson S, Olde B, Erlinge D Pancreatic beta-cell loss represents a key factor in the pathogenesis of diabetes. Since the influence of purinergic signaling in beta-cell apoptosis has not been much investigated, we examined the role of the ADP receptor P2Y(13) using the pancreatic insulinoma-cell line MIN6c4 as a model system. Real time-PCR revealed high expression of the ADP receptors P2Y(1) and P2Y(13). Adding the ADP analogue, 2MeSADP, to MIN6c4 cells induced calcium influx/mobilization and inhibition of cAMP production by activation of P2Y(1) and P2Y(13), respectively. 2MeSADP reduced cell proliferation and increased Caspase-3 activity; both these effects could be fully reversed by the P2Y(13) receptor antagonist MRS2211. We further discovered that blockin...

The p38/MAPK pathway regulates microtubule polymerization through phosphorylation of MAP4 and Op18 in hypoxic cells.

Cellular and Molecular Life Sciences : CMLS — Sat, 14 Nov 2009 00:00:00 +0100

Authors: Hu JY, Chu ZG, Han J, Dang YM, Yan H, Zhang Q, Liang GP, Huang YS In both cardiomyocytes and HeLa cells, hypoxia (1% O(2)) quickly leads to microtubule disruption, but little is known about how microtubule dynamics change during the early stages of hypoxia. We demonstrate that microtubule associated protein 4 (MAP4) phosphorylation increases while oncoprotein 18/stathmin (Op18) phosphorylation decreases after hypoxia, but their protein levels do not change. p38/MAPK activity increases quickly after hypoxia concomitant with MAP4 phosphorylation, and the activated p38/MAPK signaling leads to MAP4 phosphorylation and to Op18 dephosphorylation, both of which induce microtubule disruption. We confirmed the interaction between phospho-p38 and MAP4 using immunoprecipitation and found...

Taxol induces paraptosis independent of both protein synthesis and MAPK pathway

Journal of Cellular Physiology — Sat, 14 Nov 2009 00:00:00 +0100

In this report, we further explored the relationship between taxol-induced cell death and vacuolization, and the roles of protein synthesis, mitogen-activated protein kinase kinases (MEK), c-jun N-terminal kinase (JNK) and P38 in taxol-induced paraptosis. Enhanced green fluorescent protein (EGFP) was used to probe the cell morphological change, while ER-targeted red fluorescent protein (er-RFP) was used to probe ER spatial distribution. Real-time monitoring of the ER swelling dynamics during the formation of vacuolization inside single living cells co-expressing EGFP and er-RFP further demonstrated that taxol-induced cytoplasmic vacuolization was from the ER restructuring due to fusion and swelling. PI staining showed that taxol-induced vacuolization was not necrosis. These results further...

Morphological Changes Induced by Insulin-Like Growth Factor-I Gene Therapy in Pituitary Cell Populations in Experimental Prolactinomas

Cells Tissues Organs — Fri, 13 Nov 2009 23:00:00 +0100

Cells Tissues Organs (DOI:10.1159/000258701) (Source: Cells Tissues Organs)

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Immunohistochemistry of Displaced Sensory Neurons in the Trigeminal Nerve Root

Cells Tissues Organs — Fri, 13 Nov 2009 23:00:00 +0100

Cells Tissues Organs (DOI:10.1159/000258702) (Source: Cells Tissues Organs)

The Structure and Composition of Deciduous Enamel Affected by Local Hypoplastic Autosomal Dominant Amelogenesis Imperfecta Resulting from an ENAM Mutation

Cells Tissues Organs — Fri, 13 Nov 2009 23:00:00 +0100

Cells Tissues Organs (DOI:10.1159/000258703) (Source: Cells Tissues Organs)

Proteinases involved in matrix turnover during cartilage and bone breakdown

Cell and Tissue Research — Fri, 13 Nov 2009 18:22:37 +0100

Abstract The joint is a discrete unit that consists of cartilage, bone, tendon and ligaments. These tissues are all composed of an extracellular matrix made of collagens, proteoglycans and specialised glycoproteins that are actively synthesised, precisely assembled and subsequently degraded by the resident connective tissue cells. A balance is maintained between matrix synthesis and degradation in healthy adult tissues. Different classes of proteinases play a part in connective tissue turnover in which active proteinases can cleave matrix protein during resorption, although the proteinase that predominates varies between different tissues and diseases. The metalloproteinases are potent enzymes that, once activated, degrade connective tissue and are inhibited by tissue inhi...

Control of basal autophagy by calpain1 mediated cleavage of ATG5.

Autophagy — Fri, 13 Nov 2009 04:10:10 +0100

Authors: Xia HG, Zhang L, Chen G, Zhang T, Liu J, Jin M, Ma X, Ma D, Yuan J Autophagy functions as an important catabolic mechanism by mediating the turnover of intracellular organelles and protein complexes. Although the induction of autophagy by starvation has been extensively studied, we still understand very little about how autophagy is regulated under normal nutritional conditions. Here we describe a study using a small molecule autophagy inducer, fluspirilene, as a tool to explore the mechanism of autophagy induction in normal living cells. We confirm the activity of fluspirilene in inhibiting Ca(2+) flux. Furthermore, we show that reducing intracellular Ca(2+) prevents the cleavage of ATG5, which in turn increases the levels of full-length ATG5 and ATG12-ATG5 conjugate. Using s...

Artificial induction of autophagy around polystyrene beads in nonphagocytic cells.

Autophagy — Fri, 13 Nov 2009 04:10:07 +0100

Authors: Kobayashi S, Kojidani T, Osakada H, Yamamoto A, Yoshimori T, Hiraoka Y, Haraguchi T Autophagy is an intracellular event that acts as an innate cellular defense mechanism to kill invading bacteria such as group A Streptococcus in nonphagocytic epithelial-like cells. The cellular events underlying autophagosome formation upon bacterial invasion remain unclear due to the biochemical complexity associated with uncharacterized bacterial components, and the difficulty of predicting the location as well as the timing of where/when autophagosome formation will take place. To overcome these problems, we monitored autophagosome formation in living nonphagocytic cells by inducing autophagy around artificial micrometer-sized beads instead of bacteria. Beads conjugated with bio-reactive mo...

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Bacillus calmette-guerin cell wall cytoskeleton enhances colon cancer radiosensitivity through autophagy.

Autophagy — Fri, 13 Nov 2009 04:10:05 +0100

Authors: Yuk JM, Shin DM, Song KS, Lim K, Kim KH, Lee SH, Kim JM, Lee JS, Paik TH, Kim JS, Jo EK The cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Guerin (BCG/CWS) is an effective antitumor immunotherapy agent. Here, we demonstrate that BCG/CWS has a radiosensitizing effect on colon cancer cells through the induction of autophagic cell death. Exposure of HCT116 colon cancer cells to BCG/CWS before ionizing radiation (IR) resulted in increased cell death in a caspase-independent manner. Treatment with BCG/CWS plus IR resulted in the induction of autophagy in colon cancer cells. Either the autophagy inhibitor 3-methyladenine or knockdown of beclin 1 or Atg7 significantly reduced tumor cell death induced by BCG/CWS plus IR, whereas the caspase inhibitor z-VAD-fmk failed to d...

A Reciprocal Interdependence between Nck and PI(4,5)P2 Promotes Localized N-WASp-Mediated Actin Polymerization in Living Cells

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Gonzalo M. Rivera, Dan Vasilescu, Venizelos Papayannopoulos, Wendell A. Lim, Bruce J. Mayer. Modulation of actin dynamics through the N-WASp/Arp2/3 pathway is important in cell locomotion, membrane trafficking, and pathogen infection. Here, we demonstrate that Nck is essential for actin r.... (Source: Molecular Cell)

Activation of the WAVE Complex by Coincident Signals Controls Actin Assembly

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Andres M. Lebensohn, Marc W. Kirschner. WAVE proteins link upstream signals to actin nucleation by activating the Arp2/3 complex and are at the core of regulatory pathways driving membrane protrusion. They are found in heteropentameric .... (Source: Molecular Cell)

GM1-Ganglioside Accumulation at the Mitochondria-Associated ER Membranes Links ER Stress to Ca2+-Dependent Mitochondrial Apoptosis

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Renata Sano, Ida Annunziata, Annette Patterson, Simon Moshiach, Elida Gomero, Joseph Opferman, Michael Forte, Alessandra d'Azzo. Mitochondria-associated ER membranes, or MAMs, define the sites of endoplasmic reticulum/mitochondria juxtaposition that control Ca2+ flux between these organelles. We found that in a m.... (Source: Molecular Cell)

Stepwise Activation of BAX and BAK by tBID, BIM, and PUMA Initiates Mitochondrial Apoptosis

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Hyungjin Kim, Ho-Chou Tu, Decheng Ren, Osamu Takeuchi, John R. Jeffers, Gerard P. Zambetti, James J.-D. Hsieh, Emily H.-Y. Cheng. While activation of BAX/BAK by BH3-only molecules (BH3s) is essential for mitochondrial apoptosis, the underlying mechanisms remain unsettled. Here we demonstrate that BAX undergoes stepwise struc.... (Source: Molecular Cell)

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C-Raf Inhibits MAPK Activation and Transformation by B-RafV600E

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Florian A. Karreth, Gina M. DeNicola, Stephen P. Winter, David A. Tuveson. Activating B-Raf mutations that deregulate the MAPK pathway commonly occur in cancer. Whether additional proteins modulate the enzymatic activity of oncogenic B-Raf is unknown. Here we show that t.... (Source: Molecular Cell)

Suppression of Cancer Cell Growth by Promoting Cyclin D1 Degradation

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Jing Shan, Wenhui Zhao, Wei Gu. The cyclin D1 proto-oncoprotein is a crucial regulator in cell-cycle progression, and aberrant overexpression of cyclin D1 is linked to tumorigenesis of many different cancer types. By screening u.... (Source: Molecular Cell)

Ubiquitin Ligase Nedd4L Targets Activated Smad2/3 to Limit TGF-β Signaling

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Sheng Gao, Claudio Alarcón, Gopal Sapkota, Sadia Rahman, Pan-Yu Chen, Nina Goerner, Maria J. Macias, Hediye Erdjument-Bromage, Paul Tempst, Joan Massagué. TGF-β induces phosphorylation of the transcription factors Smad2 and Smad3 at the C terminus as well as at an interdomain linker region. TGF-β-induced linker phosphorylation marks the activated Sm.... (Source: Molecular Cell)

Hierarchical Rules for Argonaute Loading in Drosophila

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Benjamin Czech, Rui Zhou, Yaniv Erlich, Julius Brennecke, Richard Binari, Christians Villalta, Assaf Gordon, Norbert Perrimon, Gregory J. Hannon. Drosophila Argonaute-1 and Argonaute-2 differ in function and small RNA content. AGO2 binds to siRNAs, whereas AGO1 is almost exclusively occupied by microRNAs. MicroRNA duplexes are intrin.... (Source: Molecular Cell)

Distinct Mechanisms for MicroRNA Strand Selection by Drosophila Argonautes

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Katsutomo Okamura, Na Liu, Eric C. Lai. In Drosophila, miRNA strands are predominantly sorted into AGO1 to regulate seed-matched target transcripts, while their partner miRNA∗ strands are thought to be mostly degraded..... (Source: Molecular Cell)

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Rhythmic PER Abundance Defines a Critical Nodal Point for Negative Feedback within the Circadian Clock Mechanism

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Rongmin Chen, Aaron Schirmer, Yongjin Lee, Hyeongmin Lee, Vivek Kumar, Seung-Hee Yoo, Joseph S. Takahashi, Choogon Lee. Circadian rhythms in mammals are generated by a transcriptional negative feedback loop that is driven primarily by oscillations of PER and CRY, which inhibit their own transcriptional activators, .... (Source: Molecular Cell)

The Homeodomain Protein HOXB13 Regulates the Cellular Response to Androgens

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

John D. Norris, Ching-Yi Chang, Bryan M. Wittmann, Rebecca S. Kunder, Huaxia Cui, Daju Fan, James D. Joseph, Donald P. McDonnell. HOXB13 is a member of the homeodomain family of sequence-specific transcription factors and, together with the androgen receptor (AR), plays a critical role in the normal development of the prosta.... (Source: Molecular Cell)

Regulation of Meiotic Recombination via Mek1-Mediated Rad54 Phosphorylation

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Hengyao Niu, Lihong Wan, Valeria Busygina, YoungHo Kwon, Jasmina A. Allen, Xue Li, Ryan C. Kunz, Kazuishi Kubota, Beatrice Wang, Patrick Sung, Kevan M. Shokat, Steven P. Gygi, Nancy M. Hollingsworth. A preference for homologs over sister chromatids in homologous recombination is a fundamental difference in meiotic versus mitotic cells. In budding yeast, the bias for interhomolog recombination .... (Source: Molecular Cell)

GAMT, a p53-Inducible Modulator of Apoptosis, Is Critical for the Adaptive Response to Nutrient Stress

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Takao Ide, Lauren Brown-Endres, Kiki Chu, Pat P. Ongusaha, Takao Ohtsuka, Wafik S. El-Deiry, Stuart A. Aaronson, Sam W. Lee. The p53 tumor suppressor protein has a well-established role in cell-fate decision-making processes. However, recent discoveries indicate that p53 has a non-tumor-suppressive role. Here we identif.... (Source: Molecular Cell)

A Nuclear Poly(ADP-Ribose)-Dependent Signalosome Confers DNA Damage-Induced IκB Kinase Activation

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Michael Stilmann, Michael Hinz, Seda Çöl Arslan, Anja Zimmer, Valérie Schreiber, Claus Scheidereit. Upon genotoxic stresses, cells activate IκB kinases (IKKs) and the transcription factor NF-κB to modulate apoptotic responses. The SUMO-1 ligase PIASy and the kinase ataxia talengiectasia mutated .... (Source: Molecular Cell)

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Emerging Role for Members of the Bcl-2 Family in Mitochondrial Morphogenesis

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Arnaud Autret, Seamus J. Martin. Bcl-2 family proteins regulate apoptosis by controlling the release of mitochondrial cytochrome c via the Bax/Bak channel. However, recent studies have also implicated several members of th.... (Source: Molecular Cell)

BAX and BAK Caught in the Act

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Yong Yao, Francesca M. Marassi. In this issue of Molecular Cell, Kim et al. (2009) describe the steps involved in the direct activation of the proapoptotic proteins BAX and BAK by their BH3-only partners, resolving the co.... (Source: Molecular Cell)

p53 and Metabolism: The GAMT Connection

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Yan Zhu, Carol Prives. In this issue of Molecular Cell, Ide et al. (2009) have identified the enzyme guanidinoacetate methyltransferase (GAMT) that regulates creatine metabolism as a p53 target involved in apopto.... (Source: Molecular Cell)

A PAR-SUMOnious Mechanism of NEMO Activation

Molecular Cell — Fri, 13 Nov 2009 04:00:17 +0100

Kevin McCool, Shigeki Miyamoto. In this issue of Molecular Cell, Stilmann et al. (2009) demonstrate a new mode of prosurvival NF-κB activation through the formation of a PARP-1-poly(ADP-ribose) signaling scaffold in respo.... (Source: Molecular Cell)

Drugging the heat shock factor 1 pathway: Exploitation of the critical cancer cell dependence on the guardian of the proteome.

Cell Cycle — Fri, 13 Nov 2009 04:00:12 +0100

Authors: de Billy E, Powers MV, Smith JR, Workman P PMID: 19901525 [PubMed - as supplied by publisher] (Source: Cell Cycle)

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SnapShot: Mouse piRNAs, PIWI Proteins, and the Ping-Pong Cycle

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Jogender S. Tushir, Phillip D. Zamore, Zhao Zhang. (Source: Cell)

Structural Insight into Processive Human Mitochondrial DNA Synthesis and Disease-Related Polymerase Mutations

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Young-Sam Lee, W. Dexter Kennedy, Y. Whitney Yin. (Source: Cell)

Adult Neurogenesis Modulates the Hippocampus-Dependent Period of Associative Fear Memory

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Takashi Kitamura, Yoshito Saitoh, Noriko Takashima, Akiko Murayama, Yosuke Niibori, Hiroshi Ageta, Mariko Sekiguchi, Hiroyuki Sugiyama, Kaoru Inokuchi. SummaryAcquired memory initially depends on the hippocampus (HPC) for the process of cortical permanent memory formation. The mechanisms through which memory becomes progressively independent from.... (Source: Cell)

KIF26A Is an Unconventional Kinesin and Regulates GDNF-Ret Signaling in Enteric Neuronal Development

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Ruyun Zhou, Shinsuke Niwa, Noriko Homma, Yosuke Takei, Nobutaka Hirokawa. The kinesin superfamily proteins (KIFs) are motor proteins that transport organelles and protein complexes in a microtubule- and ATP-dependent manner. We identified KIF26A as a new member of the m.... (Source: Cell)

Cdc42-Mediated Tubulogenesis Controls Cell Specification

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Gokul Kesavan, Fredrik Wolfhagen Sand, Thomas Uwe Greiner, Jenny Kristina Johansson, Sune Kobberup, Xunwei Wu, Cord Brakebusch, Henrik Semb. Understanding how cells polarize and coordinate tubulogenesis during organ formation is a central question in biology. Tubulogenesis often coincides with cell-lineage specification during organ de.... (Source: Cell)

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Structural Convergence between Cryo-EM and NMR Reveals Intersubunit Interactions Critical for HIV-1 Capsid Function

Cell — Fri, 13 Nov 2009 04:00:11 +0100

In-Ja L. Byeon, Xin Meng, Jinwon Jung, Gongpu Zhao, Ruifeng Yang, Jinwoo Ahn, Jiong Shi, Jason Concel, Christopher Aiken, Peijun Zhang, Angela M. Gronenborn. Mature HIV-1 particles contain conical-shaped capsids that enclose the viral RNA genome and perform essential functions in the virus life cycle. Previous structural analysis of two- and three-dime.... (Source: Cell)

A trans-Acting Riboswitch Controls Expression of the Virulence Regulator PrfA in Listeria monocytogenes

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Edmund Loh, Olivier Dussurget, Jonas Gripenland, Karolis Vaitkevicius, Teresa Tiensuu, Pierre Mandin, Francis Repoila, Carmen Buchrieser, Pascale Cossart, Jörgen Johansson. Riboswitches are RNA elements acting in cis, controlling expression of their downstream genes through a metabolite-induced alteration of their secondary structure. Here, we demonstrate that.... (Source: Cell)

Nuclear CDKs Drive Smad Transcriptional Activation and Turnover in BMP and TGF-β Pathways

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Claudio Alarcón, Alexia-Ileana Zaromytidou, Qiaoran Xi, Sheng Gao, Jianzhong Yu, Sho Fujisawa, Afsar Barlas, Alexandria N. Miller, Katia Manova-Todorova, Maria J. Macias, Gopal Sapkota, Duojia Pan, Joan Massagué. TGF-β and BMP receptor kinases activate Smad transcription factors by C-terminal phosphorylation. We have identified a subsequent agonist-induced phosphorylation that plays a central dual role in .... (Source: Cell)

Structures of Asymmetric ClpX Hexamers Reveal Nucleotide-Dependent Motions in a AAA+ Protein-Unfolding Machine

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Steven E. Glynn, Andreas Martin, Andrew R. Nager, Tania A. Baker, Robert T. Sauer. ClpX is a AAA+ machine that uses the energy of ATP binding and hydrolysis to unfold native proteins and translocate unfolded polypeptides into the ClpP peptidase. The crystal structures presented .... (Source: Cell)

Singularity in Polarization: Rewiring Yeast Cells to Make Two Buds

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Audrey S. Howell, Natasha S. Savage, Sam A. Johnson, Indrani Bose, Allison W. Wagner, Trevin R. Zyla, H. Frederik Nijhout, Michael C. Reed, Andrew B. Goryachev, Daniel J. Lew. For budding yeast to ensure formation of only one bud, cells must polarize toward one, and only one, site. Polarity establishment involves the Rho family GTPase Cdc42, which concentrates at polari.... (Source: Cell)

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Nonoptimal Microbial Response to Antibiotics Underlies Suppressive Drug Interactions

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Tobias Bollenbach, Selwyn Quan, Remy Chait, Roy Kishony. Suppressive drug interactions, in which one antibiotic can actually help bacterial cells to grow faster in the presence of another, occur between protein and DNA synthesis inhibitors. Here, we sho.... (Source: Cell)

Dissociation of EphB2 Signaling Pathways Mediating Progenitor Cell Proliferation and Tumor Suppression

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Maria Genander, Michael M. Halford, Nan-Jie Xu, Malin Eriksson, Zuoren Yu, Zhaozhu Qiu, Anna Martling, Gedas Greicius, Sonal Thakar, Timothy Catchpole, Michael J. Chumley, Sofia Zdunek, Chenguang Wang, Torbjörn Holm, Stephen P. Goff, Sven Pettersson, Richard G. Pestell, Mark Henkemeyer, Jonas Frisén. Signaling proteins driving the proliferation of stem and progenitor cells are often encoded by proto-oncogenes. EphB receptors represent a rare exception; they promote cell proliferation in the in.... (Source: Cell)

Centrioles, Centrosomes, and Cilia in Health and Disease

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Erich A. Nigg, Jordan W. Raff. Centrioles are barrel-shaped structures that are essential for the formation of centrosomes, cilia, and flagella. Here we review recent advances in our understanding of the function and biogenesis.... (Source: Cell)

Polarity Is Destiny

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Liang Cai, Keith Mostov. The GTPase Cdc42 specifies polarity in various biological processes. Kesavan et al. (2009) now demonstrate that Cdc42 also regulates epithelial cell polarity in the developing mouse pancreas, wher.... (Source: Cell)

Finale: The Last Minutes of Smads

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Ye-Guang Chen, Xiao-Fan Wang. TGF-β ligands induce phosphorylation of receptor-activated Smads at both the C-terminal tail and the linker region. Two papers from Massagué and colleagues (Alarcón et al., 2009; Gao et al., 2009).... (Source: Cell)

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Compete Globally, Bud Locally

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Andrew R. Houk, Arthur Millius, Orion D. Weiner. How cells generate a single axis of polarity for mating, division, and movement is unknown. In this issue, Howell et al. (2009) use a synthetic biology approach to demonstrate that rapid competiti.... (Source: Cell)

Transformation Locked in a Loop

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Jarno Drost, Reuven Agami. During neoplastic transformation, cells can promote their own growth by activating proto-oncogenes. Reporting in Cell, Iliopoulos et al. (2009) now show that in certain cell types, a transi.... (Source: Cell)

Putting Two Heads Together to Unwind DNA

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Thomas J. Takara, Stephen P. Bell. The loading of replicative helicases onto DNA is tightly regulated in all organisms, yet the molecular mechanisms for this event remain poorly defined. Remus et al. (2009) provide important insigh.... (Source: Cell)

Stem Cell Research: Toward Greater Unity in Europe?

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Christiane Druml. There are four major positions on human embryonic stem cell research in the different member states of the European Union, ranging from permissive to very restrictive. This reflects the diversity .... (Source: Cell)

Science, Policy, and the U.S. Congress

Cell — Fri, 13 Nov 2009 04:00:11 +0100

David Goldston. Scientists often misunderstand the role science plays and should play in policy making. Those misconceptions are captured well in the debate over whether Congress should recreate an Office of Tech.... (Source: Cell)

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The RAE: An Assessment Too Far?

Cell — Fri, 13 Nov 2009 04:00:11 +0100

Colin Macilwain. A 20 year quantitative assessment of research in British universities has coincided with a renaissance in their international status. But even as other nations seek to emulate the approach, domest.... (Source: Cell)

Molecular Biology Select

Cell — Fri, 13 Nov 2009 04:00:10 +0100

The process of gene expression relies on large macromolecular complexes at almost every step, making mechanistic and structural studies a challenge. This Molecular Biology Select highlights recent.... (Source: Cell)

In This Issue

Cell — Fri, 13 Nov 2009 04:00:10 +0100

(Source: Cell)

Meiotic Chromosome Homology Search Involves Modifications of the Nuclear Envelope Protein Matefin/SUN-1

Cell — Fri, 13 Nov 2009 04:00:10 +0100

Alexandra M. Penkner, Alexandra Fridkin, Jiradet Gloggnitzer, Antoine Baudrimont, Thomas Machacek, Alexander Woglar, Edina Csaszar, Pawel Pasierbek, Gustav Ammerer, Yosef Gruenbaum, Verena Jantsch. Genome haploidization during meiosis depends on recognition and association of parental homologous chromosomes. The C. elegans SUN/KASH domain proteins Matefin/SUN-1 and ZYG-12 have a conse.... (Source: Cell)

Cytoskeletal Forces Span the Nuclear Envelope to Coordinate Meiotic Chromosome Pairing and Synapsis

Cell — Fri, 13 Nov 2009 04:00:09 +0100

Aya Sato, Berith Isaac, Carolyn M. Phillips, Regina Rillo, Peter M. Carlton, David J. Wynne, Roshni A. Kasad, Abby F. Dernburg. During meiosis, each chromosome must pair with its unique homologous partner, a process that usually culminates with the formation of the synaptonemal complex (SC). In the nematode Caenorhabdit.... (Source: Cell)

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Disruption of the PP1/GADD34 complex induces calreticulin exposure.

Cell Cycle — Fri, 13 Nov 2009 04:00:09 +0100

Authors: Kepp O, Galluzzi L, Giordanetto F, Tesniere A, Vitale I, Martins I, Schlemmer F, Adjemian S, Zitvogel L, Kroemer G In response to some chemotherapeutic agents, tumor cells can translocate calreticulin (CRT), which is usually contained in the lumen of the endoplasmic reticulum, to the surface of the plasma membrane. This effect requires the phosphorylation of the eukaryotic initiation factor 2alpha(eIF2alpha) by the eIF2alpha kinase PERK, yet may also be triggered by inhibition of the eIF2alpha phosphatase, which is composed by a catalytic subunit (PP1) and a regulatory subunit (GADD34). Here, we addressed the question whether the dissociation of the PP1/GADD34 complex would be sufficient to trigger CRT exposure. Molecular modeling led to the design of a GADD34-derived peptide ...

Anti-malaria drug blocks proteotoxic stress response: Anti-cancer implications.

Cell Cycle — Fri, 13 Nov 2009 04:00:06 +0100

Authors: Neznanov N, Gorbachev AV, Neznanova L, Komarov AP, Gurova KV, Gasparian AV, Banerjee AK, Almasan A, Fairchild RL, Gudkov AV The number of physical conditions and chemical agents induce accumulation of misfolded proteins creating proteotoxic stress. This leads to activation of adaptive pro-survival pathway, known as heat shock response (HSR), resulting in expression of additional chaperones. Several cancer treatment approaches, such as proteasome inhibitor Bortezomib and hsp90 inhibitor geldanamycin, involve activation of proteotoxic stress. Low efficacy of these therapies is likely due to the protective effects of HSR induced in treated cells, making this pathway an attractive target for pharmacological suppression. We found that the anti-malaria drugs quinacrine (QC) and emet...

A role for the phosphatidylinositol 3-kinase - protein kinase C zeta - Sp1 pathway in the 1,25-dihydroxyvitamin D3 induction of the 25-hydroxyvitamin D3 24-hydroxylase gene in human kidney cells.

Cellular Signalling — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Dwivedi PP, Gao XH, Tan JC, Evdokiou A, Ferrante A, Morris HA, May BK, Hii CS The molecular mechanisms that underlie non-genomic induction of the 25-hydroxyvitamin D3 24-hydroxylase (CYP24) gene promoter by the steroid hormone, 1,25-Dihydroxyvitamin D3 (1,25D), are poorly understood. Although we have previously identified a functional inverted GC-box in the early promoter at -113/-105 bp, it is not known whether this site is important for 1,25D induction of the promoter. Using transfected human embryonic kidney (HEK) 293T cells, we now report the functional characterisation of the GC box and that 1,25D induction of the promoter requires PI3-kinase, PKCzeta and Sp1 but not Sp3. The data show that 1,25D rapidly stimulates PI3-kinase activity which is required for the activation ...

Effects of angiopoietins-1 and -2 on the receptor tyrosine kinase tie2 are differentially regulated at the endothelial cell surface.

Cellular Signalling — Fri, 13 Nov 2009 00:00:00 +0100

In this study we have investigated binding of Ang1 and Ang2 to Tie2 in endothelial cells. In contrast to Ang1, binding of Ang2 to Tie2 was found to be not affected by Tie1. Neither PMA-induced Tie1 ectodomain cleavage nor suppression of Tie1 expression by siRNA affected the ability of Ang2 to bind Tie2. Analysis of the level of Tie1 co-immunoprecipitating with angiopoietin-bound Tie2 demonstrated that Ang2 can bind Tie2 in Tie2:Tie1 complexes whereas Ang1 preferentially binds non-complexed Tie2. Stimulation of Tie1 ectodomain cleavage did not increase the agonist activity of Ang2 for Tie2. Similarly, the Tie2-agonist activity of Ang2 was not affected by siRNA suppression of Tie1 expression. Consistent with previous reports, loss of Tie1 ectodomain enhanced the agonist activity of Ang1 for ...

Serotonin 4 receptor (5-HT4R) internalization is isoform-specific: Effects of 5-HT and RS67333 on isoforms A and B.

Cellular Signalling — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Mnie-Filali O, Amraei MG, Benmbarek S, Archer-Lahlou E, Peñas-Cazorla R, Vilaró MT, Boye SM, Piñeyro G Serotonin 4 receptors (5-HT4Rs) are particularly abundant within the limbic system, where they constitute potential targets for the development of novel, rapid acting antidepressants. However, the population of limbic 5-HT4Rs is not homogenous, comprising various isoforms of which 5-HT4(a) and 5-HT4(b) are among the most abundant variants. Sequence divergence at their C-termini is predictive of specificity in isoform signalling and regulation, but the differences, if any, remain ill-defined. The present study compared isoforms 5-HT4(a) and 5-HT4(b) in their ability to undergo endocytic regulation following exposure to 5-HT and to the putatively fast acting anti...

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PPARgamma regulates LIF-induced growth and self-renewal of mouse ES cells through Tyk2-Stat3 pathway.

Cellular Signalling — Fri, 13 Nov 2009 00:00:00 +0100

In this study we demonstrate that the PPARgamma antagonist Bisphenol A diglycidyl ether (BADGE) and 2-Chloro-5-nitro-N-(4-pyridyl)benzamide (T0070907) reverse the inhibition of ES cell proliferation by PPARgamma agonists. Stable transfection of ES cells with a dominant negative PPARgamma1 mutant also reduced the inhibition of proliferation by PPARgamma agonists. While 15d-PGJ2 and ciglitazone induced growth-arrest in ES cells by blocking LIF signaling, PPARgamma antagonists and dominant negative PPARgamma1 mutant reversed proliferation by restoring LIF-induced Tyk2-Stat3 signaling. These results suggest that PPARgamma regulates LIF-induced growth and self-renewal of mouse ES cells through Tyk2-Stat3 pathway. PMID: 19922793 [PubMed - as supplied by publisher] (Source: Cellular Signallin...

Impaired TNF-alpha Control of IP(3)R-mediated Ca(2+) Release in Alzheimer's Disease Mouse Neurons TNF-alpha signaling in 3xTg-AD neurons.

Cellular Signalling — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Park KM, Yule DI, Bowers WJ The misguided control of inflammatory signaling has been previously implicated in the pathogenesis of several neurological disorders, including Alzheimer's disease (AD). Induction of tumor necrosis factor-alpha (TNF-alpha), a central mediator of neuroinflammation, occurs commensurate with the onset of early disease in 3xTg-AD mice, which develop both amyloid plaque and neurofibrillary tangle pathologies in an age- and region-dependent pattern. Herein, we describe regulation inherent to 3xTg-AD neurons, which results in the loss of TNF-5 mediated enhancement of inositol 1,4,5 trisphosphate (IP(3)R)-mediated Ca(2+) release. This modulation also leads to significant down regulation of IP(3)R signaling following protracted cytokine exposure. Through the...

Bortezomib induces autophagic death in proliferating human endothelial cells.

Experimental Cell Research — Fri, 13 Nov 2009 00:00:00 +0100

We report that endothelial cells (EC) exposed to Bortezomib undergo death to an extent that depends strictly on their activation state. Indeed, while quiescent EC are resistant to Bortezomib, the drug results maximally toxic in EC switched toward angiogenesis with FGF, and exerts a moderate effect on sub-confluent HUVEC. Moreover, EC activation state deeply influences the death pathway elicited by Bortezomib: after treatment, angiogenesis-triggered EC display typical features of apoptosis. Conversely, death of sub-confluent EC is preceded by ROS generation and signs typical of autophagy, including intense cytoplasmic vacuolization with evidence of autophagosomes at electron microscopy, and conversion of the cytosolic MAP LC3 I form toward the autophagosome-associated LC3 II form. Treatment...

The GIT/PIX complexes regulate the chemotactic response of rat basophilic leukemia cells

Biology of the Cell — Fri, 13 Nov 2009 00:00:00 +0100

Conclusions. Our results show that endogenous GIT complexes are involved in the regulation of chemoattractant-induced cell motility and receptor trafficking, and support previous findings indicating an important function of the GIT complexes in the regulation of different G protein-coupled receptors. Our data also indicate that endogenous GIT1 and GIT2 regulate distinct subsets of agonist-induced responses, and suggest a possible functional link between the control of receptor trafficking and the regulation of cell motility by GIT proteins. (Source: Biology of the Cell)

Proteomic identification of heterogeneous nuclear ribonucleoprotein L as a novel component of SLM/Sam68 Nuclear Bodies

BMC Cell Biology - Latest articles — Fri, 13 Nov 2009 00:00:00 +0100

Conclusions: Here we identify hnRNP L as a novel SNB component. We show that, compared with other identified Sam68-associated hnRNP proteins and hnRNP LL, this co-localisation within SNBs is specific to hnRNP L. Our data suggest that the novel Sam68-hnRNP L protein interaction may have a distinct role within SNBs. (Source: BMC Cell Biology - Latest articles)

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Paclitaxel and beta-lapachone synergistically induce apoptosis in human retinoblastoma Y79 cells by downregulating the levels of phospho-Akt

Journal of Cellular Physiology — Fri, 13 Nov 2009 00:00:00 +0100

Paclitaxel (PTX) and beta-lapachone (LPC) are naturally occurring compounds that have shown a large spectrum of anticancer activity. In this article we show for the first time that PTX/LPC combination induces potent synergistic apoptotic effects in human retinoblastoma Y79 cells. Combination of suboptimal doses of PTX (0.3 nM) and LPC (1.5 µM) caused biochemical and morphological signs of apoptosis at 48 h of treatment. These effects were accompanied by potent lowering in inhibitor of apoptosis proteins and by activation of Bid and caspases 3 and 6 with lamin B and PARP breakdown. PTX/LPC combination acted by favoring p53 stabilization through a lowering in p-Akt levels and in ps166-MDM2, the phosphorylated-MDM2 form that enters the nucleus and induces p53 export and degradation. Treatmen...

Dual role of parathyroid hormone in endothelial progenitor cells and marrow stromal mesenchymal stem cells

Journal of Cellular Physiology — Fri, 13 Nov 2009 00:00:00 +0100

Hematopoietic stem cells derive regulatory information also from parathyroid hormone (PTH). To explore the possibility that PTH may have a role in regulation of other stem cells residing in bone marrow, such as mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) we assessed the effect of this hormone on the in vitro behavior of MSCs and EPCs. We evidenced that MSCs were much more responsive to PTH than EPCs. PTH increased the proliferation rate of MSCs with a diminution of senescence and apoptosis. Taken together, our results may suggest a protective effect of PTH on MSCs that reduces stress phenomena and preserve genome integrity. At the opposite, PTH did not modify the fate of EPCs in culture. J. Cell. Physiol. © 2009 Wiley-Liss, Inc. (Source: Journal of Cellular Physi...

Endoglin is involved in BMP-2-induced osteogenic differentiation of periodontal ligament cells through a pathway independent of Smad-1/5/8 phosphorylation

Journal of Cellular Physiology — Fri, 13 Nov 2009 00:00:00 +0100

The periodontal ligament (PDL), a connective tissue located between the cementum of teeth and the alveolar bone of mandibula, plays a crucial role in the maintenance and regeneration of periodontal tissues. The PDL contains fibroblastic cells of a heterogeneous cell population, from which we have established several cell lines previously. To analyze characteristics unique for PDL at a molecular level, we performed cDNA microarray analysis of the PDL cells versus MC3T3-E1 osteoblastic cells. The analysis followed by validation by reverse transcription-polymerase chain reaction and immunochemical staining revealed that endoglin, which had been shown to associate with transforming growth factor (TGF)-[beta] and bone morphogenetic proteins (BMPs) as signaling modulators, was abundantly express...

Intracellular redox imbalance and extracellular amino acid metabolic abnormality contribute to arsenic-induced developmental retardation in mouse preimplantation embryos

Journal of Cellular Physiology — Fri, 13 Nov 2009 00:00:00 +0100

In conclusion, we suggest that p66Shc-linked redox imbalance and abnormal extracellular amino acid metabolism mediate arsenite-induced embryonic retardation. J. Cell. Physiol. © 2009 Wiley-Liss, Inc. (Source: Journal of Cellular Physiology)

Burst discharges in neurons of the thalamic reticular nucleus are shaped by calcium-induced calcium release.

Cell Calcium — Thu, 12 Nov 2009 00:00:00 +0100

Authors: Coulon P, Herr D, Kanyshkova T, Meuth P, Budde T, Pape HC The nucleus reticularis thalami (NRT) is a layer of inhibitory neurons that surrounds the dorsal thalamus. It appears to be the 'pacemaker' of certain forms of slow oscillations in the thalamus and was proposed to be a key determinant of the internal attentional searchlight as well as the origin of hypersynchronous activity during absence seizures. Neurons of the NRT exhibit a transient depolarization termed low threshold spike (LTS) following sustained hyperpolarization. This is caused by the activation of low-voltage-activated Ca(2+) channels (LVACC). Although the role of these channels in thalamocortical oscillations was studied in great detail, little is known about the downstream intracellular Ca(2+) signalling pat...

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Structure, function and contribution of polysaccharide intercellular adhesin (PIA) to Staphylococcus epidermidis biofilm formation and pathogenesis of biomaterial-associated infections.

European Journal of Cell Biology — Thu, 12 Nov 2009 00:00:00 +0100

Authors: Rohde H, Frankenberger S, Zähringer U, Mack D Staphylococcus epidermidis is of major importance in infections associated with indwelling medical devices. The tight pathogenic association is essentially linked to the species ability to form adherent biofilms on artificial surfaces. Aiming at identifying novel targets for vaccination or therapy much effort has been made to unravel the molecular mechanisms leading to S. epidermidis biofilm formation. At present, polysaccharide intercellular adhesin (PIA) is the best studied factor involved in S. epidermidis biofilm accumulation. PIA is a glycan of beta-1,6-linked 2-acetamido-2-deoxy-D-glucopyranosyl residues of which 15 % are non-N-acetylated. PIA-producing S. epidermidis are widespread in clinical strain collections and PIA...

Rho-kinase inhibitors as therapeutics: from pan inhibition to isoform selectivity.

Cellular and Molecular Life Sciences : CMLS — Thu, 12 Nov 2009 00:00:00 +0100

This article discusses the therapeutic benefits of novel ROCK inhibitors in development, and highlights the recent advances in the current understanding of disease-dependent and isoform-specific functions of ROCK and their potential impact on future therapeutic strategies. PMID: 19907920 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)

Systemic Administration of Lipopolysaccharide Induces Cyclooxygenase-2 Immunoreactivity in Endothelium and Increases Microglia in the Mouse Hippocampus.

Cellular and Molecular Neurobiology — Thu, 12 Nov 2009 00:00:00 +0100

In this study, we observed the effects of lipopolysaccharide (LPS) on neurodegeneration and immune response in the hippocampus. LPS is a gram-negative bacterial cell surface proteoglycan and known as a bacterial endotoxin. For this, we investigated the optimal concentration of LPS influencing the ICR mouse hippocampus to measure the LPS receptor, e.g., toll-like receptor 4 (TLR4), expression in mouse hippocampal homogenates. TLR4 expression was significantly and prominently increased in the hippocampal homogenates of the LPS (1 mg/kg)-treated group. Next, we examined pro-inflammatory response in the hippocampus using cyclooxygenase-2 (COX-2, a marker for inflammatory response) immunohistochemistry after LPS treatment. COX-2 immunoreactivity was significantly increased in the endothelium of...

Members of the CIP4 family of proteins participate in the regulation of platelet-derived growth factor receptor-{beta}-dependent actin reorganization and migration

Biology of the Cell — Thu, 12 Nov 2009 00:00:00 +0100

Conclusions Our findings shows that CIP4-like proteins induced membrane tubulation downstream of Cdc42 and that they have important roles in PDGF-dependent actin reorganization and cell migration by regulating internalization and activity of the PDGFRβ. Moreover, the data suggest an important role for the CIP4-like proteins in the regulation of the activity of the PDGF β-receptor. (Source: Biology of the Cell)

Resolving the Role of Plant Glutamate Dehydrogenase. I. in vivo Real Time Nuclear Magnetic Resonance Spectroscopy Experiments

Plant and Cell Physiology — Wed, 11 Nov 2009 15:54:39 +0100

(Source: Plant and Cell Physiology)

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A Highly Sensitive, Quick and Simple Quantification Method for Nicotianamine and 2'-Deoxymugineic Acid from Minimum Samples Using LC/ESI-TOF-MS Achieves Functional Analysis of These Components in Plants

Plant and Cell Physiology — Wed, 11 Nov 2009 15:54:39 +0100

A highly sensitive quantitative method for assaying nicotianamine (NA) and 2'-deoxymugineic acid (DMA) using liquid chromatography/electrospray ionization time-of-flight mass spectrometry (LC/ESI-TOF-MS) was developed. The amino and hydroxyl groups of NA and DMA were derivatized using 9-fluorenylmethoxycarbonyl chloride. The amounts of NA and DMA in 10 µl of xylem sap from rice cultivated under iron (Fe)-sufficient and Fe-deficient conditions were quantified without concentration. In Fe-sufficient plants, the concentrations of NA and DMA were almost equal to that of Fe. In Fe-deficient plants, the concentration of NA did not change significantly, whereas that of DMA increased markedly. (Source: Plant and Cell Physiology)

The Poplar GT8E and GT8F Glycosyltransferases are Functional Orthologs of Arabidopsis PARVUS Involved in Glucuronoxylan Biosynthesis

Plant and Cell Physiology — Wed, 11 Nov 2009 15:54:39 +0100

The poplar GT8E and GT8F glycosyltransferases have previously been shown to be associated with wood formation, but their roles in the biosynthesis of wood components are not known. Here, we show that PoGT8E and PoGT8F are expressed in vessels and fibers during wood formation and their encoded proteins are predominantly located in the endoplasmic reticulum. We demonstrate that expression of PoGT8E and PoGT8F in the Arabidopsis parvus mutant rescues the defects in the content and structure of glucuronoxylan conferred by the parvus mutation. These findings suggest that PoGT8E and PoGT8F are involved in glucuronoxylan biosynthesis during wood formation in poplar. (Source: Plant and Cell Physiology)

Arabidopsis NIP1;1 Transports Antimonite and Determines Antimonite Sensitivity

Plant and Cell Physiology — Wed, 11 Nov 2009 15:54:39 +0100

In this study, we identified an antimonite [Sb(III)] transporter from Arabidopsis thaliana. We examined the Sb(III) tolerance of the disruption mutant plants of arsenite [As(III)] transporters, nodulin 26-like intrinsic proteins (NIPs), since Sb(III) is similar to As(III) in structure. One of the mutants, nip1;1, showed Sb(III) tolerance and accumulated less Sb. Furthermore, yeast expressing NIP1;1 accumulated twice as much Sb as control. These data indicate that NIP1;1 transports Sb(III) and determines the Sb(III) sensitivity of A. thaliana. (Source: Plant and Cell Physiology)

Arabidopsis Replication Protein A 70a is Required for DNA Damage Response and Telomere Length Homeostasis

Plant and Cell Physiology — Wed, 11 Nov 2009 15:54:39 +0100

In this study, we analyzed the functions of AtRPA70a, which is most similar to human RPA70 among four paralogs in Arabidopsis thaliana. RNA blot analysis showed that AtRPA70a is expressed ubiquitously in plant organs containing differentiated and meristematic tissues, while its expression was up-regulated in response to DNA damage stress. Yeast two-hybrid and co-immunoprecipitation analyses showed that AtRPA70a interacted preferentially with Arabidopsis RPA32a, one of two paralogs. Inactivation of AtRPA70a by T-DNA insertion did not affect growth under normal conditions, but resulted in increased sensitivity to genotoxic agents such as methylmethane sulfonate, bleomycin and hydroxyurea. Terminal restriction fragment analysis revealed that telomere lengths in an AtRPA70a-deficient line were...

MYB83 Is a Direct Target of SND1 and Acts Redundantly with MYB46 in the Regulation of Secondary Cell Wall Biosynthesis in Arabidopsis

Plant and Cell Physiology — Wed, 11 Nov 2009 15:54:39 +0100

It has been proposed that the transcriptional regulation of secondary wall biosynthesis in Arabidopsis is controlled by a transcriptional network mediated by SND1 and its close homologs. Uncovering all the transcription factors and deciphering their interrelationships in the network are essential for our understanding of the molecular mechanisms underlying the transcriptional regulation of biosynthesis of secondary walls, the major constituent of wood and fibers. Here, we present functional evidence that the MYB83 transcription factor is another molecular switch in the SND1-mediated transcriptional network regulating secondary wall biosynthesis. MYB83 is specifically expressed in fibers and vessels where secondary wall thickening occurs. Its expression is directly activated by SND1 and its...

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Ectopic Overexpression of The Transcription Factor OsGLK1 Induces Chloroplast Development in Non-Green Rice Cells

Plant and Cell Physiology — Wed, 11 Nov 2009 15:54:39 +0100

For systematic and genome-wide analyses of rice gene functions, we took advantage of the full-length cDNA overexpresser (FOX) gene-hunting system and generated >12 000 independent FOX-rice lines from >25 000 rice calli treated with the rice-FOX Agrobacterium library. We found two FOX-rice lines generating green calli on a callus-inducing medium containing 2,4-D, on which wild-type rice calli became ivory yellow. In both lines, OsGLK1 cDNA encoding a GARP transcription factor was ectopically overexpressed. Using rice expression-microarray and northern blot analyses, we found that a large number of nucleus-encoded genes involved in chloroplast functions were highly expressed and transcripts of plastid-encoded genes, psaA, psbA and rbcL, increased in the OsGLK1-FOX calli. Transmission e...

Arabidopsis OPT6 is an Oligopeptide Transporter with Exceptionally Broad Substrate Specificity

Plant and Cell Physiology — Wed, 11 Nov 2009 15:54:39 +0100

Oligopeptide transporters (OPTs) are found in fungi, bacteria and plants. The nine Arabidopsis thaliana OPT genes are expressed mainly in the vasculature and are thought to transport tetra- and pentapeptides, and peptide-like substrates such as glutathione. Expression of AtOPT6 in Xenopus laevis oocytes demonstrated that AtOPT6 transports many tetra- and pentapeptides. In addition, AtOPT6 transported reduced glutathione (GSH), a tripeptide, but not oxidized glutathione (GSSG). Recent data showed that Candida albicans OPTs can transport peptides up to eight amino acids in length. AtOPT6 transported mammalian signaling peptides up to 10 amino acids in length and, in addition, known plant development- and nematode pathogenesis-associated peptides up to 13 amino acids long. AtOPT6 displayed hi...

High Temperatures Cause Male Sterility in Rice Plants with Transcriptional Alterations During Pollen Development

Plant and Cell Physiology — Wed, 11 Nov 2009 15:54:39 +0100

Plant male reproductive development is highly organized and sensitive to various environmental stressors, including high temperature. We have established an experimental procedure to evaluate high temperature injury in japonica rice plants. High temperature treatment (39°C/30°C) starting at the microspore stage repeatedly reduced spikelet fertility in our system. Morphological observations revealed that pollen viability in plants exposed to high temperatures was lower than that in control plants. Most pollen grains in high temperature-treated plants displayed a normal round shape and stained reddish purple with Alexander’s reagent; however, the pollen grains were very poorly attached and displayed limited germination on the stigma. To investigate gene regulatory mechanisms in...

The TL29 Protein is Lumen Located, Associated with PSII and Not an Ascorbate Peroxidase

Plant and Cell Physiology — Wed, 11 Nov 2009 15:54:39 +0100

The TL29 protein is one of the more abundant proteins in the thylakoid lumen of plant chloroplasts. Based on its sequence homology to ascorbate peroxidases, but without any supporting biochemical evidence, TL29 was suggested to be involved in the plant defense system against reactive oxygen species and consequently renamed to APX4. Our in vivo and in vitro analyses failed to show any peroxidase activity associated with TL29; it bound neither heme nor ascorbate. Recombinant overexpressed TL29 had no ascorbate-dependent peroxidase activity, and various mutational analyses aiming to convert TL29 into an ascorbate peroxidase failed. Furthermore, in the thylakoid lumen no such activity could be associated with TL29 and, additionally, TL29 knock-out mutants did not show any decreased peroxidase ...