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This page shows you the most recent publications within this specialty of the MedWorm directory. This is page number 18.

Add salt, add sugar: N-glycosylation in Haloferax volcanii.
Abstract Although performed by members of all three domains of life, the archaeal version of N-glycosylation remains the least understood. Studies on Haloferax volcanii have, however, begun to correct this situation. A combination of bioinformatics, molecular biology, biochemical and mass spectrometry approaches have served to delineate the Agl pathway responsible for N-glycosylation of the S-layer glycoprotein, a reporter of this post-translational modification in Hfx. volcanii. More recently, differential N-glycosylation of the S-layer glycoprotein as a function of environmental salinity was demonstrated, showing...
Source: Biochemical Society Transactions - February 1, 2013 Category: Biochemistry Authors: Kaminski L, Naparstek S, Kandiba L, Cohen-Rosenzweig C, Arbiv A, Konrad Z, Eichler J Tags: Biochem Soc Trans Source Type: research

Sulfolobus islandicus: a model system for evolutionary genomics.
We describe how the application of this interdisciplinary approach can lead to novel hypotheses derived from patterns of natural variation that can be tested in the laboratory when combined with a diversity of natural variants and versatile genetic markers. We review how this approach has highlighted the importance of recombination as an evolutionary parameter and provided insight into a molecular mechanism of recombination that may be unique in the archaeal domain. We review the development and improvement of the model system S. islandicus that will enable us to study the mechanism and genomic architecture of recombinatio...
Source: Biochemical Society Transactions - February 1, 2013 Category: Biochemistry Authors: Zhang C, Krause DJ, Whitaker RJ Tags: Biochem Soc Trans Source Type: research

Reflectin genes and development of iridophores pattern in sepia officinalis embryos (Mollusca, Cephalopoda)
Conclusion: These data suggest that several different forms of reflectins are simultaneously used to produce iridescence in S. officinalis and that mRNA production and translation are decoupled in time during iridosome development. Developmental Dynamics, 2013. © 2013 Wiley Periodicals,Inc.
Source: Developmental Dynamics - February 1, 2013 Category: Molecular Biology Authors: Andouche A., Bassaglia Y., Baratte S., Bonnaud L. Tags: Patterns & Phenotypes Source Type: research

Expression of Transcription Factor Satb2 in Adult Mouse Brain
Previous investigations on the expression and function of special AT‐rich sequence binding protein 2 (Satb2) are largely limited to the cerebral cortex. Here, we explore the expression of Satb2 thoroughly by immunohistochemistry in the adult mouse central nervous system (CNS). Besides the cerebral cortex, we found that Satb2 is specifically expressed in the bed nucleus of the stria terminalis, horizontal limb of the diagonal band, lateral hypothalamic area, arcuate nucleus, hypothalamic paraventricular nucleus, ventral tegmental nucleus, laterodorsal tegmental nucleus, dorsal raphe nucleus, rostral periolivary region, an...
Source: The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology - February 1, 2013 Category: Molecular Biology Authors: Ying Huang, Ning‐Ning Song, Wei Lan, Ling Hu, Chang‐Jun Su, Yu‐Qiang Ding, Lei Zhang Tags: Full Length Article Source Type: research

Mesenchymal stem cells from rat olfactory bulbs can differentiate into cells with cardiomyocyte characteristics
In this study, we examined whether olfactory bulb‐derived MSCs could differentiate into myocardial cells in vitro. Fibroblast‐like cells isolated from the olfactory bulb of neonatal rats were grown under four conditions: no treatment; in the presence of growth factors (neuregulin‐1, bFGF and forskolin); co‐cultured with cardiomyocytes; and co‐cultured with cardiomyocytes plus neuregulin‐1, bFGF and forskolin. Cell differentiation into myocardial cells was monitored by RT–PCR, light microscopy immunofluorescence, western blot analysis and contractile response to pharmacological treatments. The isolated olfacto...
Source: Journal of Tissue Engineering and Regenerative Medicine - February 1, 2013 Category: Molecular Biology Authors: Yuahn‐Sieh Huang, I‐Hsun Li, Sheau‐Huei Chueh, Dueng‐Yuan Hueng, Ming‐Cheng Tai, Chang‐Min Liang, Shiu‐Bii Lien, Huey‐Kang Sytwu, Kuo‐Hsing Ma Tags: Research Article Source Type: research

How winner cells cause the demise of loser cells
Abstract Recent results show that, during the process known as cell competition, winner cells identify and kill viable cells from a growing population without requiring engulfment. The engulfment machinery is mainly required in circulating macrophages (hemocytes) after the discrimination between winners and losers is completed and the losers have been killed and extruded from the epithelium. Those new results leave us with the question as to which molecules allow winner cells to recognize and impose cell death on the loser cells during cell competition. During cell competition, winner cells induce apoptosis in loser cells...
Source: BioEssays - February 1, 2013 Category: Molecular Biology Authors: Fidel‐Nicolás Lolo, Sergio Casas Tintó, Eduardo Moreno Tags: Insights & Perspectives Source Type: research

Distribution of Collagen Fiber Orientation in the Human Lung
Collagen fiber, a major component of the extracellular matrix in the human lung, is crucial in maintaining the lung structure mechanically. It is necessary to study the collagen fiber orientation which the mechanical function is closely related to. In the present study the collagen fiber orientation in the lung was quantitatively measured by Osaki's microwave method. We succeeded in preparing sheet samples cut in a coronal direction from the lung for the measurements. It was found that the collagen fibers were, on average, orientated parallel to the longitudinal axis of the spine. The void spaces in the lung sample observe...
Source: The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology - February 1, 2013 Category: Molecular Biology Authors: Koichi Tomoda, Hiroshi Kimura, Shigeyoshi Osaki Tags: Full Length Article Source Type: research

Molecular mapping of stomatal‐conductance‐related traits in durum wheat (Triticum turgidum ssp. durum)
Abstract The most promising traits identified in wheat to raise yield potential via an increase in biomass accumulation are stomatal conductance and stomatal‐conductance‐related traits, such as carbon isotope discrimination (CID) and photosynthetic rate. The evaluation of the extent of genetic variation and the mapping of chromosomal regions controlling these traits are essential for the development of effective breeding strategies in durum wheat. A population of 161 F2‐derived, F8–F9 recombinant inbred lines obtained from a cross between durum wheat (Triticum turgidum ssp. durum) cultivars Ofanto and Cappelli was ...
Source: Annals of Applied Biology - February 1, 2013 Category: Biology Authors: G. Panio, R. Motzo, A.M. Mastrangelo, D. Marone, L. Cattivelli, F. Giunta, P. Vita Tags: RESEARCH ARTICLE Source Type: research

EMA opens consultation on draft guideline on biosimilars containing low-molecular-weight heparins
Source: European Medicines Agency (EMA) Area: News The European Medicines Agency has launched a six-month public consultation on the revised guideline on non-clinical and clinical development of similar biological medicinal products containing low-molecular-weight heparins (LMWHs). This guideline describes the non-clinical and clinical requirements for a LMWH-containing medicinal product claiming to be similar to another one already on the market. The non-clinical section addresses the pharmacotoxicological requirements and the clinical section describes the requirements for pharmacokinetic, pharmacodynamic, ef...
Source: NeLM - News - February 1, 2013 Category: Drugs & Pharmacology Source Type: news

"Atypical rearrangement involving 3[prime]-IGH@ and a breakpoint at least 400 Kb upstream of an intact MYC in a CLL patient with an apparently balanced t(8;14)(q24.1;q32) and negative MYC expression"
The t(8;14)(q24.1;q32), the cytogenetic hallmark of Burkitt's lymphoma, is also found, but rarely, in cases of chronic lymphocytic leukemia (CLL). Such translocation typically results in a MYC-IGH@ fusion subsequently deregulating and overexpressing MYC on der 14q32. In CLL, atypical rearrangements resulting in its gain or loss, within or outside of IGH@ or MYC locus, have been reported, but their clinical significance remains uncertain. Herein, we report a 67 year-old male with complex cytogenetic findings of apparently balanced t(8;14) and unreported complex rearrangements of IGH@ and MYC loci. His clinical, morphologica...
Source: Molecular Cytogenetics - February 1, 2013 Category: Molecular Biology Authors: Ina AmarilloPeter BuiSibel KantarciNagesh RaoBrit ShackleyRolando GarcíaCarlos Tirado Source Type: research

Indo-Pacific bottlenose dolphin (Tursiops aduncus) habitat preference in a heterogeneous, urban, coastal environment
Conclusions: It is anticipated that these results will benefit the further development of management and conservation strategies.
Source: Saline Systems - February 1, 2013 Category: Molecular Biology Authors: Nardi CribbCara MillerLaurent Seuront Source Type: research

Bacterial diversity of the rock-water interface in an East Antarctic freshwater ecosystem, Lake Tawani(P)
In this study, we describe the bacterial diversity of the rock-water interface in Lake Tawani(P) using culture-independent Bacterial Tag Encoded FLX Amplicon Pyrosequencing (bTEFAP), clone library construction, and culture-based analysis targeting the eubacterial 16S rRNA gene. Lake Tawani(P)was formed in a fossil valley by the accumulation of snow and glacial melt through surface channels into a low-catchment depression. Overall this lake exhibited thirteen bacterial phyla and one-hundred and twelve genera. The Qiime bioinformatics analysis on the bTEFAP alone exhibited higher coverage of the bacterial composition in Lake...
Source: Saline Systems - February 1, 2013 Category: Molecular Biology Authors: Jonathan HuangAshit SwainRobert ThackerRasik RavindraDale AndersenAsim Bej Source Type: research

Activity Cliffs: Facts or Artifacts?
Abstract The fact that similar compounds may have very different properties has a large impact in several areas of chemistry. In drug discovery, almost every medicinal chemist working on lead optimization has faced unexpected large ‘jumps’ in activity due to small changes in structure, i.e., activity cliffs. A number of computational approaches have been developed to detect and quantify activity cliffs and help to understand, and eventually predict, structure‐activity relationships in compound data sets. Although activity cliffs do exist, the identification and quantification of cliffs have to proceed with caution si...
Source: Chemical Biology and Drug Design - February 1, 2013 Category: Biology Authors: José L. Medina‐Franco Tags: Commentary Source Type: research

{beta}1-Subunit Regulates TP-MaxiK Function [Molecular Biophysics]
The large conductance voltage- and Ca2+-activated K+ channel (MaxiK, BKCa, BK) is composed of four pore-forming α-subunits and can be associated with regulatory β-subunits. One of the functional roles of MaxiK is to regulate vascular tone. We recently found that the MaxiK channel from coronary smooth muscle is trans-inhibited by activation of the vasoconstricting thromboxane A2 prostanoid receptor (TP), a mechanism supported by MaxiK α-subunit (MaxiKα)-TP physical interaction. Here, we examined the role of the MaxiK β1-subunit in TP-MaxiK association. We found that the β1-subunit can by itself interact with TP and th...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Li, M., Zhang, Z., Koh, H., Lu, R., Jiang, Z., Alioua, A., Garcia-Valdes, J., Stefani, E., Toro, L. Tags: Membrane Biology Source Type: research

The Sur1-Trpm4 Channel [Molecular Bases of Disease]
The sulfonylurea receptor 1 (Sur1)-NCCa-ATP channel plays a central role in necrotic cell death in central nervous system (CNS) injury, including ischemic stroke, and traumatic brain and spinal cord injury. Here, we show that Sur1-NCCa-ATP channels are formed by co-assembly of Sur1 and transient receptor potential melastatin 4 (Trpm4). Co-expression of Sur1 and Trpm4 yielded Sur1-Trpm4 heteromers, as shown in experiments with Förster resonance energy transfer (FRET) and co-immunoprecipitation. Co-expression of Sur1 and Trpm4 also yielded functional Sur1-Trpm4 channels with biophysical properties of Trpm4 and pharmacologic...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Woo, S. K., Kwon, M. S., Ivanov, A., Gerzanich, V., Simard, J. M. Tags: Membrane Biology Source Type: research

Accelerated ALS Disease Onset with Stable TDP-43 Mutations [Neurobiology]
Abnormal protein accumulation is a pathological hallmark of neurodegenerative diseases, including accumulation of TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis (ALS). Dominant mutations in the TDP-43 gene are causative for familial ALS; however, the relationship between mutant protein biochemical phenotypes and disease course and their significance to disease pathomechanism are not known. Here, we found that longer half-lives of mutant proteins correlated with accelerated disease onset. Based on our findings, we established a cell model in which chronic stabilization of wild-type TDP-43 protein provo...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Watanabe, S., Kaneko, K., Yamanaka, K. Tags: Molecular Bases of Disease Source Type: research

Requirement for Charged Residue at Position 75 in Cx32 [Molecular Biophysics]
Charcot Marie Tooth disease (CMT) is a group of inherited disorders characterized clinically by exclusively or predominantly peripheral nerve dysfunction. CMT1X, the most common form of X-linked CMT is caused by mutations in connexin 32 (Cx32). In this work, we used dual whole cell patch clamp recording to examine the functional effects of mutations at the Arg75 position. This residue is highly conserved among members of the connexin family, and disease-causing mutations have been identified at this (or the corresponding) position in Cx26, Cx43, and Cx46. Thus, a better understanding of the effects of mutations of this pos...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Abrams, C. K., Islam, M., Mahmoud, R., Kwon, T., Bargiello, T. A., Freidin, M. M. Tags: Molecular Bases of Disease Source Type: research

TOPK in Chemoresistance to Doxorubicin-mediated Apoptosis [Cell Biology]
T-lymphokine-activated killer cell-originated protein kinase (TOPK) is known to be up-regulated in cancer cells and appears to contribute to cancer cell proliferation and survival. However, the molecular mechanism by which TOPK regulates cancer cell survival still remains elusive. Here we show that TOPK directly interacted with and phosphorylated IκBα at Ser-32, leading to p65 nuclear translocation and NF-κB activation. We also revealed that doxorubicin promoted the interaction between nonphosphorylated or phosphorylated TOPK and IκBα and that TOPK-mediated IκBα phosphorylation was enhanced in response to doxorubici...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Park, J.-H., Yoon, D.-S., Choi, H.-J., Hahm, D.-H., Oh, S.-M. Tags: Signal Transduction Source Type: research

MMP-9 and Islet Amyloid [Cell Biology]
Deposition of islet amyloid polypeptide (IAPP) as amyloid is a pathological hallmark of the islet in type 2 diabetes, which is toxic to β-cells. We previously showed that the enzyme neprilysin reduces islet amyloid deposition and thereby reduces β-cell apoptosis, by inhibiting fibril formation. Two other enzymes, matrix metalloproteinase (MMP)-2 and MMP-9, are extracellular gelatinases capable of degrading another amyloidogenic peptide, Aβ, the constituent of amyloid deposits in Alzheimer disease. We therefore investigated whether MMP-2 and MMP-9 play a role in reducing islet amyloid deposition. MMP-2 and MMP-9 mRNA wer...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Aston-Mourney, K., Zraika, S., Udayasankar, J., Subramanian, S. L., Green, P. S., Kahn, S. E., Hull, R. L. Tags: Molecular Bases of Disease Source Type: research

Role of Calcineurin in Metabolic Complications [Signal Transduction]
Insulin resistance, hyperlipidemia, and cardiovascular complications are common dysregulations of metabolic syndrome. Transplant patients treated with immunosuppressant drugs such as cyclosporine A (CsA), an inhibitor of calcineurin phosphatase, frequently develop similar metabolic complications. Although calcineurin is known to mediate insulin sensitivity by regulating β-cell growth and adipokine gene transcription, its role in lipid homeostasis is poorly understood. Here, we examined lipid homeostasis in mice lacking calcineurin Aβ (CnAβ−/−). We show that mice lacking calcineurin Aβ are hyperlipidemic and develop...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Suk, H. Y., Zhou, C., Yang, T. T. C., Zhu, H., Yu, R. Y. L., Olabisi, O., Yang, X., Brancho, D., Kim, J.-Y., Scherer, P. E., Frank, P. G., Lisanti, M. P., Calvert, J. W., Lefer, D. J., Molkentin, J. D., Ghigo, A., Hirsch, E., Jin, J., Chow, C.-W. Tags: Molecular Bases of Disease Source Type: research

Oncogenic Role of Nuclear {Delta}EGFR [Signal Transduction]
ΔEGFR is a potent glioblastoma oncogene which has been studied primarily as a plasma membrane kinase. Using intracranial xenograft studies in mice, we show that blocking ΔEGFR access to the nucleus attenuates its tumorigenicity and, conversely, that promoting nuclear accumulation enhances this, providing the first in vivo evidence that the nuclear actions of ΔEGFR contribute strongly to its oncogenic function. Nuclear actions of ΔEGFR include regulation of gene expression by participation in chromatin-bound complexes, and genome-wide mapping of these sequences by chromatin immunoprecipitation and massively parallel seq...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Gururaj, A. E., Gibson, L., Panchabhai, S., Bai, M., Manyam, G., Lu, Y., Latha, K., Rojas, M. L., Hwang, Y., Liang, S., Bogler, O. Tags: Molecular Bases of Disease Source Type: research

Characterization of an Anti-parallel Coiled-coil Complex [Protein Structure and Folding]
The methyl-cytosine binding domain 2 (MBD2)-nucleosome remodeling and deacetylase (NuRD) complex recognizes methylated DNA and silences expression of associated genes through histone deacetylase and nucleosome remodeling functions. Our previous structural work demonstrated that a coiled-coil interaction between MBD2 and GATA zinc finger domain containing 2A (GATAD2A/p66α) proteins recruits the chromodomain helicase DNA-binding protein (CHD4/Mi2β) to the NuRD complex and is necessary for MBD2-mediated DNA methylation-dependent gene silencing in vivo (Gnanapragasam, M. N., Scarsdale, J. N., Amaya, M. L., Webb, H. D., Desai...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Walavalkar, N. M., Gordon, N., Williams, D. C. Tags: Molecular Biophysics Source Type: research

Autoregulation of BMI1 [Gene Regulation]
Polycomb group protein BMI1 plays an important role in cellular homeostasis by maintaining a balance between proliferation and senescence. It is often overexpressed in cancer cells and is required for self-renewal of stem cells. At present, very little is known about the signaling pathways that regulate the expression of BMI1. Here, we report that BMI1 autoactivates its own promoter via an E-box present in its promoter. We show that BMI1 acts as an activator of the WNT pathway by repressing Dickkopf (DKK) family of WNT inhibitors. BMI1 mediated repression of DKK proteins; in particular, DKK1 led to up-regulation of WNT tar...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Cho, J.-H., Dimri, M., Dimri, G. P. Tags: Molecular Bases of Disease Source Type: research

Visual Arrestin-1 with Special Functional Characteristics [Protein Structure and Folding]
Arrestin-1 preferentially binds active phosphorylated rhodopsin. Previously, a mutant with enhanced binding to unphosphorylated active rhodopsin (Rh*) was shown to partially compensate for lack of rhodopsin phosphorylation in vivo. Here we showed that reengineering of the receptor binding surface of arrestin-1 further improves the binding to Rh* while preserving protein stability. In mammals, arrestin-1 readily self-associates at physiological concentrations. The biological role of this phenomenon can only be elucidated by replacing wild type arrestin-1 in living animals with a non-oligomerizing mutant retaining all other ...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Vishnivetskiy, S. A., Chen, Q., Palazzo, M. C., Brooks, E. K., Altenbach, C., Iverson, T. M., Hubbell, W. L., Gurevich, V. V. Tags: Signal Transduction Source Type: research

Thioredoxin and Thioredoxin Reductase Regulate Tissue Factor [Enzymology]
Abnormally enhanced tissue factor (TF) activity is related to increased thrombosis risk in which oxidative stress plays a critical role. Human cytosolic thioredoxin (hTrx1) and thioredoxin reductase (TrxR), also secreted into circulation, have the power to protect against oxidative stress. However, the relationship between hTrx1/TrxR and TF remains unknown. Here we show reversible association of hTrx1 with TF in human serum and plasma samples. The association is dependent on hTrx1-Cys-73 that bridges TF-Cys-209 via a disulfide bond. hTrx1-Cys-73 is absolutely required for hTrx1 to interfere with FVIIa binding to purified a...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Wang, P., Wu, Y., Li, X., Ma, X., Zhong, L. Tags: Molecular Bases of Disease Source Type: research

ATP Binding Plays Multiple Roles in Proteasome Function [Cell Biology]
We examined the role of ATP binding by six different ATPase subunits (Rpt1–6) in the cellular assembly and molecular functions of mammalian 26 S proteasome. Four Rpt subunits (Rpt1–4) with ATP binding mutations were incompetent for cellular assembly into 26 S proteasome. In contrast, analogous mutants of Rpt5 and Rpt6 were incorporated normally into 26 S proteasomes in both intact cells and an in vitro assembly assay. Surprisingly, purified 26 S proteasomes containing either mutant Rpt5 or Rpt6 had normal basal ATPase activity and substrate gate opening for hydrolysis of short peptides. However, these mutant 26 S prote...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Kim, Y.-C., Li, X., Thompson, D., DeMartino, G. N. Tags: Protein Synthesis and Degradation Source Type: research

FAK Scaffolding Function in Breast Cancer [Signal Transduction]
Tyrosine kinases have been shown to play critical roles in cancer development and progression, and their inhibitors hold the potential as effective targeted therapies for breast and other cancers. However, some of these kinases like focal adhesion kinase (FAK) also possess scaffolding functions in intracellular signaling, but such kinase-independent functions of FAK or other kinases have not been examined in cancer directly in vivo. Here, we report that disruption of the function of FAK scaffolding through its Pro-878/881 motif suppressed mammary tumor growth and metastasis in a well characterized murine model of human bre...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Fan, H., Zhao, X., Sun, S., Luo, M., Guan, J.-L. Tags: Molecular Bases of Disease Source Type: research

Structure-based Kinetics of Transcript Initiation [Enzymology]
The challenge for structural biology is to understand atomic-level macromolecular motions during enzymatic reaction. X-ray crystallography can reveal high resolution structures; however, one perceived limitation is that it reveals only static views. Here we use time-dependent soak-trigger-freeze X-ray crystallography, namely, soaking nucleotide and divalent metal into the bacteriophage RNA polymerase (RNAP)-promoter DNA complex crystals to trigger the nucleotidyl transfer reaction and freezing crystals at different time points, to capture real-time intermediates in the pathway of transcription. In each crystal structure, d...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Basu, R. S., Murakami, K. S. Tags: Molecular Biophysics Source Type: research

Mast Cells Produce Novel Shorter Forms of Perlecan [Cell Biology]
This study demonstrated that primary human mast cells as well as the rat and human mast cell lines, RBL-2H3 and HMC-1, produce the heparan sulfate proteoglycan, perlecan, with a molecular mass of 640 kDa as well as smaller molecular mass species of 300 and 130 kDa. Utilizing domain-specific antibodies coupled with N-terminal sequencing, it was confirmed that both forms contained the C-terminal module of the protein core known as endorepellin, which were generated by mast cell-derived proteases. Domain-specific RT-PCR experiments demonstrated that transcripts corresponding to domains I and V, including endorepellin, were pr...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Jung, M., Lord, M. S., Cheng, B., Lyons, J. G., Alkhouri, H., Hughes, J. M., McCarthy, S. J., Iozzo, R. V., Whitelock, J. M. Tags: Glycobiology and Extracellular Matrices Source Type: research

{Delta}Np63{alpha} Regulates miR-205 Expression [Cell Biology]
Epithelial-mesenchymal transition (EMT) is a physiological process that plays important roles in tumor metastasis, “stemness,” and drug resistance. EMT is typically characterized by the loss of the epithelial marker E-cadherin and increased expression of EMT-associated transcriptional repressors, including ZEB1 and ZEB2. The miR-200 family and miR-205 prevent EMT through suppression of ZEB1/2. p53 has been implicated in the regulation of miR-200c, but the mechanisms controlling miR-205 expression remain elusive. Here we report that the p53 family member and p63 isoform, ΔNp63α, promotes miR-205 transcription and cont...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Tran, M. N., Choi, W., Wszolek, M. F., Navai, N., Lee, I.-L. C., Nitti, G., Wen, S., Flores, E. R., Siefker-Radtke, A., Czerniak, B., Dinney, C., Barton, M., McConkey, D. J. Tags: Molecular Bases of Disease Source Type: research

Sp1 Drives SYN1 Promoter Activation [Neurobiology]
The development and function of the nervous system are directly dependent on a well defined pattern of gene expression. Indeed, perturbation of transcriptional activity or epigenetic modifications of chromatin can dramatically influence neuronal phenotypes. The phosphoprotein synapsin I (Syn I) plays a crucial role during axonogenesis and synaptogenesis as well as in synaptic transmission and plasticity of mature neurons. Abnormalities in SYN1 gene expression have been linked to important neuropsychiatric disorders, such as epilepsy and autism. SYN1 gene transcription is suppressed in non-neural tissues by the RE1-silencin...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Paonessa, F., Latifi, S., Scarongella, H., Cesca, F., Benfenati, F. Tags: Gene Regulation Source Type: research

Cathepsin D and U18666A-treated Hippocampal Cultured Neurons [Molecular Bases of Disease]
Cathepsin D is an aspartyl protease that plays a crucial role in normal cellular functions and in a variety of neurodegenerative disorders, including Niemann-Pick type C (NPC) disease, which is characterized by intracellular accumulation of cholesterol and glycosphingolipids in many tissues, including the brain. There is evidence that the level and activity of cathepsin D increased markedly in vulnerable neurons in NPC pathology, but its involvement in neurodegeneration remains unclear. In the present study, using mouse hippocampal cultured neurons, we evaluated the significance of cathepsin D in toxicity induced by U18666...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Amritraj, A., Wang, Y., Revett, T. J., Vergote, D., Westaway, D., Kar, S. Tags: Neurobiology Source Type: research

Type 10 Adenylyl Cyclase Controls Proliferation [Signal Transduction]
In conclusion, this study suggests a novel sAC-dependent signaling pathway that controls the proliferation of prostate carcinoma cells.
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Flacke, J.-P., Flacke, H., Appukuttan, A., Palisaar, R., Noldus, J., Robinson, B. D., Reusch, H. P., Zippin, J. H., Ladilov, Y. Tags: Molecular Bases of Disease Source Type: research

Osteopontin Cleavage Affects Glioma Cell Behavior [Molecular Bases of Disease]
Osteopontin (OPN), which is highly expressed in malignant glioblastoma (GBM), possesses inflammatory activity modulated by proteolytic cleavage by thrombin and plasma carboxypeptidase B2 (CPB2) at a highly conserved cleavage site. Full-length OPN (OPN-FL) was elevated in cerebrospinal fluid (CSF) samples from all cancer patients compared with noncancer patients. However, thrombin-cleaved OPN (OPN-R) and thrombin/CPB2-double-cleaved OPN (OPN-L) levels were markedly increased in GBM and non-GBM gliomas compared with systemic cancer and noncancer patients. Cleaved OPN constituted ∼23 and ∼31% of the total OPN in the GBM a...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Yamaguchi, Y., Shao, Z., Sharif, S., Du, X.-Y., Myles, T., Merchant, M., Harsh, G., Glantz, M., Recht, L., Morser, J., Leung, L. L. K. Tags: Cell Biology Source Type: research

Mitochondrial DNA Damage in Huntington Disease [Cell Biology]
This study provides strong evidence to support a new causal link between dysregulated mitochondrial Ca2+ signaling, elevated mitochondrial oxidant stress, and mtDNA damage in HD. Our results also indicate that reducing mitochondrial Ca2+ uptake could be a therapeutic strategy for HD.
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Wang, J.-Q., Chen, Q., Wang, X., Wang, Q.-C., Wang, Y., Cheng, H.-P., Guo, C., Sun, Q., , Tang, T.-S. Tags: Molecular Bases of Disease Source Type: research

Pak1 in Prostate Cancer [Molecular Bases of Disease]
We report here that highly invasive prostate cancer cells express significantly higher levels of Pak1 protein compared with non-invasive prostate cancer cells. Furthermore, prostate tumor tissues and prostate cancer metastasized to lungs showed a higher expression of Pak1 compared with normal tissues. Interestingly, Pak6 protein expression levels did not change with the invasive/metastatic potential of the cancer cells or tumors. Although inhibition of Pak1, and not Pak6, resulted in impaired PC3 cell migration, the effects of Pak1 knockdown on transendothelial migration (microinvasion), tumor growth, and tumor angiogenesi...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Goc, A., Al-Azayzih, A., Abdalla, M., Al-Husein, B., Kavuri, S., Lee, J., Moses, K., Somanath, P. R. Tags: Signal Transduction Source Type: research

Trapping the Actin-binding Cleft of Myosin II [Molecular Biophysics]
We have trapped the catalytic domain of Dictyostelium (Dicty) myosin II in a weak actin-binding conformation by chemically crosslinking two engineered cysteines across the actin-binding cleft, using a bifunctional spin label (BSL). By connecting the lower and upper 50 kDa domains of myosin, the crosslink restricts the conformation of the actin-binding cleft. Crosslinking has no effect on the basal ATPase activity of isolated myosin, but it impairs rigor actin binding and actin-activation of myosin ATPase. EPR spectra of BSL provide insight into actomyosin structural dynamics. BSL is highly immobilized within the actin-bind...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Moen, R. J., Thomas, D. D., Klein, J. C. Tags: Molecular Biophysics Source Type: research

M129V Polymorphism in Prion Amyloid Fibrils [Molecular Bases of Disease]
Misfolding of the natively α-helical prion protein into a β-sheet rich isoform is related to various human diseases such as Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker syndrome. In humans, the disease phenotype is modified by a methionine/valine polymorphism at codon 129 of the prion protein gene. Using a combination of hydrogen/deuterium exchange coupled to NMR spectroscopy, hydroxyl radical probing detected by mass spectrometry, and site-directed mutagenesis, we demonstrate that stop mutants of the human prion protein have a conserved amyloid core. The 129 residue is deeply buried in the amyloid core ...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Skora, L., Fonseca-Ornelas, L., Hofele, R. V., Riedel, D., Giller, K., Watzlawik, J., Schulz-Schaeffer, W. J., Urlaub, H., Becker, S., Zweckstetter, M. Tags: Protein Structure and Folding Source Type: research

The Role of rpS3 and TRAF2 in Radioresistance of NSCLC Cells [Cell Biology]
In this study, to elucidate radioresistance mechanism in lung cancer, we compared radiation responses in two types of non-small cell lung cancer (NSCLC) cells with different radiosensitivity and identified key molecules conferring radioresistance. In radioresistant NSCLC cells, ionizing radiation (IR) led to casein kinase 2α (CK2α)- and PKC-mediated phosphorylation of rpS3 and TRAF2, respectively, which induced dissociation of rpS3-TRAF2 complex and NF-κB activation, resulting in significant up-regulation of prosurvival genes (cIAP1, cIAP2, and survivin). Also, dissociated phospho-rpS3 translocated into nucleus and boun...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Yang, H. J., Youn, H., Seong, K. M., Jin, Y.-W., Kim, J., Youn, B. Tags: Signal Transduction Source Type: research

MDEG Hyperactivation Induces Caspase-8 Activation [Molecular Bases of Disease]
Intracellular calcium overload plays a critical role in numerous pathological syndromes such as heart failure, brain ischemia, and stroke. Hyperactivation of the acid-sensing ion channels including degenerin/epithelial amiloride-sensitive sodium (DEG/ENaC) channels has been shown to elevate intracellular calcium and cause subsequent neuronal cell death that is independent of the canonical Egl-1/Ced-9/Ced-4/Ced-3 apoptotic pathway in Caenorhabditis elegans. In mammalian cells, hyperactivation of the DEG/ENaC channels can also lead to cell death, although the underlying mechanism remains largely unknown. Here, we use a tetra...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Pan, J.-A., Fan, Y., Gandhirajan, R. K., Madesh, M., Zong, W.-X. Tags: Cell Biology Source Type: research

{Delta}Np63, a Novel Target of Arsenic [Protein Synthesis and Degradation]
Transcription factor p63, a member of the p53 family, shares a high degree of sequence similarity with p53. Because of transcription from two distinct promoters, the p63 gene encodes two isoforms, TAp63 and ΔNp63. Although TAp63 acts as a tumor suppressor, ΔNp63 functions as an oncogene and is often overexpressed in squamous cell carcinomas. Thus, therapeutic agents targeting ΔNp63 might be used to manage tumors that overexpress ΔNp63. Here we found that arsenic trioxide, a frontline agent for acute promyelocytic leukemia, inhibits ΔNp63 but not TAp63 expression in time- and dose-dependent manners. In addition, we fou...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Yan, W., Chen, X., Zhang, Y., Zhang, J., Jung, Y.-S., Tags: Molecular Bases of Disease Source Type: research

Use of digital gene expression to discriminate gene expression differences in early generations of resynthesized Brassica napus and its diploid progenitors
Conclusions: The systematic deep sequencing analysis provided a comprehensive understanding of the transcriptome complexity of early generations of synthesized B. napus. This information broadens our understanding of the mechanisms of B. napus polyploidization and contributes to molecular and genetic research by enriching the Brassica database.
Source: BMC Genomics - Latest articles - February 1, 2013 Category: Genetics & Stem Cells Authors: Jinjin JiangYanlin ShaoKun DuLiping RanXiaoping FangYouping Wang Source Type: research

[Clinico-pathological and molecular aspects of diagnostic and prognostic value in gliomas].
CONCLUSIONS. The study of proteomics and molecular biomarkers should complement the histopathological analysis and sometimes allows to determine direct or indirect predictive factors as well as the study of affected pathways which may become selective therapeutic targets. PMID: 23359078 [PubMed - in process]
Source: Revista de Neurologia - February 1, 2013 Category: Neurology Authors: Ortega-Aznar A, Jimenez-Leon P, Martinez E, Romero-Vidal FJ Tags: Rev Neurol Source Type: research

Replication of a carcinogenic nitropyrene DNA lesion by human Y-family DNA polymerase
Nitrated polycyclic aromatic hydrocarbons are common environmental pollutants, of which many are mutagenic and carcinogenic. 1-Nitropyrene is the most abundant nitrated polycyclic aromatic hydrocarbon, which causes DNA damage and is carcinogenic in experimental animals. Error-prone translesion synthesis of 1-nitropyrene–derived DNA lesions generates mutations that likely play a role in the etiology of cancer. Here, we report two crystal structures of the human Y-family DNA polymerase iota complexed with the major 1-nitropyrene DNA lesion at the insertion stage, incorporating either dCTP or dATP nucleotide opposite th...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Kirouac, K. N., Basu, A. K., Ling, H. Tags: Structural Biology Source Type: research

Guanine base stacking in G-quadruplex nucleic acids
In this study, we investigate how guanine base stacking influences the stability of G-quadruplexes and their stacked higher-order structures. A structural survey of the Protein Data Bank is conducted to characterize experimentally observed guanine base stacking geometries within the core of G-quadruplexes and at the interface between stacked G-quadruplex structures. We couple this survey with a systematic computational examination of stacked G-tetrad energy landscapes using quantum mechanical computations. Energy calculations of stacked G-tetrads reveal large energy differences of up to 12 kcal/mol between experimentally o...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Lech, C. J., Heddi, B., Phan, A. T. Tags: Structural Biology Source Type: research

Sleeping Beauty transposon-based system for cellular reprogramming and targeted gene insertion in induced pluripotent stem cells
The discovery of direct cell reprogramming and induced pluripotent stem (iPS) cell technology opened up new avenues for the application of non-viral, transposon-based gene delivery systems. The Sleeping Beauty (SB) transposon is highly advanced for versatile genetic manipulations in mammalian cells. We established iPS cell reprogramming of mouse embryonic fibroblasts and human foreskin fibroblasts by transposition of OSKM (Oct4, Sox2, Klf4 and c-Myc) and OSKML (OSKM + Lin28) expression cassettes mobilized by the SB100X hyperactive transposase. The efficiency of iPS cell derivation with SB transposon system was in the range...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Grabundzija, I., Wang, J., Sebe, A., Erdei, Z., Kajdi, R., Devaraj, A., Steinemann, D., Szuhai, K., Stein, U., Cantz, T., Schambach, A., Baum, C., Izsvak, Z., Sarkadi, B., Ivics, Z. Tags: Molecular Biology Source Type: research

Transcription blockage by homopurine DNA sequences: role of sequence composition and single-strand breaks
The ability of DNA to adopt non-canonical structures can affect transcription and has broad implications for genome functioning. We have recently reported that guanine-rich (G-rich) homopurine-homopyrimidine sequences cause significant blockage of transcription in vitro in a strictly orientation-dependent manner: when the G-rich strand serves as the non-template strand [Belotserkovskii et al. (2010) Mechanisms and implications of transcription blockage by guanine-rich DNA sequences., Proc. Natl Acad. Sci. USA, 107, 12816–12821]. We have now systematically studied the effect of the sequence composition and single-stra...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Belotserkovskii, B. P., Neil, A. J., Saleh, S. S., Shin, J. H. S., Mirkin, S. M., Hanawalt, P. C. Tags: Molecular Biology Source Type: research

A novel mechanism of eukaryotic translation initiation that is neither m7G-cap-, nor IRES-dependent
Resistance of translation of some eukaryotic messenger RNAs (mRNAs) to inactivation of the cap-binding factor eIF4E under unfavorable conditions is well documented. To date, it is the mechanism of internal ribosome entry that is predominantly thought to underlay this stress tolerance. However, many cellular mRNAs that had been considered to contain internal ribosome entry sites (IRESs) failed to pass stringent control tests for internal initiation, thus raising the question of how they are translated under stress conditions. Here, we show that inserting an eIF4G-binding element from a virus IRES into 5'-UTRs of strongly ca...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Terenin, I. M., Andreev, D. E., Dmitriev, S. E., Shatsky, I. N. Tags: Molecular Biology Source Type: research

AT-rich sequence elements promote nascent transcript cleavage leading to RNA polymerase II termination
RNA Polymerase II (Pol II) termination is dependent on RNA processing signals as well as specific terminator elements located downstream of the poly(A) site. One of the two major terminator classes described so far is the Co-Transcriptional Cleavage (CoTC) element. We show that homopolymer A/T tracts within the human β-globin CoTC-mediated terminator element play a critical role in Pol II termination. These short A/T tracts, dispersed within seemingly random sequences, are strong terminator elements, and bioinformatics analysis confirms the presence of such sequences in 70% of the putative terminator regions (PTRs) genome-wide.
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: White, E., Kamieniarz-Gdula, K., Dye, M. J., Proudfoot, N. J. Tags: Molecular Biology Source Type: research

Identification of RNA targets for the nuclear multidomain cyclophilin atCyp59 and their effect on PPIase activity
AtCyp59 is a multidomain cyclophilin containing a peptidyl-prolyl cis/trans isomerase (PPIase) domain and an evolutionarily highly conserved RRM domain. Deregulation of this class of cyclophilins has been shown to affect transcription and to influence phosphorylation of the C-terminal repeat domain of the largest subunit of the RNA polymerase II. We used a genomic SELEX method for identifying RNA targets of AtCyp59. Analysis of the selected RNAs revealed an RNA-binding motif (G[U/C]N[G/A]CC[A/G]) and we show that it is evolutionarily conserved. Binding to this motif was verified by gel shift assays in vitro and by RNA immu...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Bannikova, O., Zywicki, M., Marquez, Y., Skrahina, T., Kalyna, M., Barta, A. Tags: Molecular Biology Source Type: research