MedWorm: Molecular Biology

Per-channel basis normalization methods for flow cytometry data

Cytometry Part A — Sat, 07 Nov 2009 00:00:00 +0100

Between-sample variation in high-throughput flow cytometry data poses a significant challenge for analysis of large-scale data sets, such as those derived from multicenter clinical trials. It is often hard to match biologically relevant cell populations across samples because of technical variation in sample acquisition and instrumentation differences. Thus, normalization of data is a critical step before analysis, particularly in large-scale data sets from clinical trials, where group-specific differences may be subtle and patient-to-patient variation common. We have developed two normalization methods that remove technical between-sample variation by aligning prominent features (landmarks) in the raw data on a per-channel basis. These algorithms were tested on two independent flow cytome...

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Computational and Systems Biology

RSC - Mol. BioSyst. latest articles — Fri, 06 Nov 2009 00:00:00 +0100

(Editorial from Mol. BioSyst.) Mol. BioSyst., 2009, DOI: 10.1039/b921381n To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

Flow immunocytochemistry of marker expression in cells from body cavity fluids

Cytometry Part A — Fri, 06 Nov 2009 00:00:00 +0100

Diagnostic cytology based on the examination of cells from body cavity fluids misses [sim]50% of patients with a proven malignancy. In an earlier study, we used immunohistochemical detection of epithelial membrane antigen expression with flow cytometric detection of DNA aneuploidy to reduce the number of false negatives. In the present study, we have combined DNA flow cytometry with flow cytometric detection of marker expression to analyze cells from body cavity fluids. Seventy-nine specimens of ascites and pleural fluids were analyzed by diagnostic cytology, DNA flow cytometry, and for the expression of the following markers: Ber-EP4, progesterone (PR), MUC4, and thyroid transcription factor-1 (TTF-1). DNA index of equal to or greater than 1.2 was seen in 33/79 (41.7%) of the samples. Sta...

A quantitative measure for alterations in the actin cytoskeleton investigated with automated high-throughput microscopy

Cytometry Part A — Fri, 06 Nov 2009 00:00:00 +0100

The actin cytoskeleton modulates a large variety of physiological and disease-related processes in the cell. For example, actin has been shown to be a crucial host factor for successful infection by HIV-1, but the underlying mechanistic details are still unknown. Automated approaches open up the perspective to clarify such an issue by processing many samples in a high-throughput manner. To analyze the alterations in the actin cytoskeleton within an automated setting, large-scale image acquisition and analysis were established for JC-53 cells stained for actin. As a quantitative measure in such an automated approach, we suggest a parameter called image coherency. We successfully benchmarked our analysis by calculating coherency for both a biophysical model of the actin cytoskeleton and for ...

BH3-only proteins: The death-puppeteer's wires

Cytometry Part A — Fri, 06 Nov 2009 00:00:00 +0100

Most cell death in vertebrates proceeds through the intrinsic pathway of apoptosis and results from unregulated increase of mitochondrial membrane permeability. Bcl2-associated X protein (Bax) and Bcl2-antagonist/killer protein (Bak), the effector proapoptotic members of the Bcl-2 family, are, in their active state, the principal accomplices for this permeabilization process. How exactly Bax and Bak are activated has been a matter of major investigation in the last decade, and suitable tools offered by quantitative cytometric methodologies have significantly contributed to the understanding of the function of Bcl-2 family members. Here, we review the most relevant findings in this field and highlight one common trait that has emerged from the diverse new theories: a crucial role in the con...

On the Emergence of Biochemical Homochirality: An Elusive Beginning.

Origins of Life and Evolution of the Biosphere — Fri, 06 Nov 2009 00:00:00 +0100

Authors: Pizzarello S, Lahav M PMID: 19890734 [PubMed - as supplied by publisher] (Source: Origins of Life and Evolution of the Biosphere)

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Asymmetric ruthenium-catalyzed 1,4-additions of aryl thiols to enones

RSC - Organic Biomolecular Chemistry — Fri, 06 Nov 2009 00:00:00 +0100

Andrei Badoiu, Gerald Bernardinelli, Celine Besnard, E. Peter Kundig (Paper from Org. Biomol. Chem.) Andrei Badoiu, Org. Biomol. Chem., 2010, DOI: 10.1039/b918877k To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Host-guest complexations of local anaesthetics by cucurbit[7]uril in aqueous solution

RSC - Organic Biomolecular Chemistry — Fri, 06 Nov 2009 00:00:00 +0100

Ian W. Wyman, Donal H. Macartney (Paper from Org. Biomol. Chem.) Ian W. Wyman, Org. Biomol. Chem., 2010, DOI: 10.1039/b915694a To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Ghrelin in gastrointestinal diseases and disorders: a possible role in the pathophysiology and clinical implications (review).

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:43:01 +0100

Authors: El-Salhy M Ghrelin is a peptide hormone, which has been isolated from the stomach. It is localized mostly in endocrine cells in the oxyntic mucosa of the stomach. Ghrelin receptors are expressed equally in all parts of the gastrointestinal tract, with a similar level of expression in the mucosal and muscle layers. This peptide hormone has several functions, the most widely known is its growth hormone (GH)-releasing effect. Ghrelin plays an important role in regulating appetite, feeding and energy metabolism. It also plays a role in mediating immune response and inflammatory processes. Ghrelin stimulates gastric motility and emptying as well as motility in the small and large intestine. Ghrelin has been reported to be affected in several gastrointestinal diseases/disorders such...

Diagnosis of parathyroid carcinoma using immunohistochemical staining against hTERT.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:58 +0100

Authors: Osawa N, Onoda N, Kawajiri H, Tezuka K, Takashima T, Ishikawa T, Miyauchi A, Hirokawa M, Wakasa K, Hirakawa K The differential diagnosis of parathyroid carcinoma from benign adenoma is often difficult when its typical clinicopathological features are absent, even with the aid of various molecular markers. We recently demonstrated that telomerase activation through hTERT expression is a unique characteristic that is limited to parathyroid carcinoma and not seen in benign tumors. In the present study, we investigated hTERT expression in parathyroid tumors using immunohistochemistry in an attempt to determine its clinical utility. There was no evidence of immunoreactivity in the 4 normal parathyroid glands and the 18 typical adenomas. In contrast, one atypical adenoma stained pos...

Neuronal and BBB damage induced by sera from patients with secondary progressive multiple sclerosis.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:56 +0100

Authors: Proia P, Schiera G, Salemi G, Ragonese P, Savettieri G, Di Liegro I An important component of the pathogenic process of multiple sclerosis (MS) is the blood-brain barrier (BBB) damage. We recently set an in vitro model of BBB, based on a three-cell-type co-culture system, in which rat neurons and astrocytes synergistically induce brain capillary endothelial cells to form a monolayer with permeability properties resembling those of the physiological BBB. Herein we report that the serum from patients with secondary progressive multiple sclerosis (SPMS) has a damaging effect on isolated neurons. This finding suggests that neuronal damaging in MS could be a primary event and not only secondary to myelin damage, as generally assumed. SPMS serum affects the permeability of the BBB m...

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Molecular characterization and quantification using state of the art solid-state adiabatic TOBSY NMR in burn trauma.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:53 +0100

We describe a novel solid-state nuclear magnetic resonance (NMR) method that maximizes the advantages of high-resolution magic-angle-spinning (HRMAS), relative conventional liquid-state NMR approaches, when applied to intact biopsies of skeletal muscle specimens collected from burn trauma patients. This novel method, termed optimized adiabatic TOtal through Bond correlation SpectroscopY (TOBSY) solid-state NMR pulse sequence for two-dimensional (2D) 1H-1H homonuclear scalar-coupling longitudinal isotropic mixing, was demonstrated to provide a 40-60% improvement in signal-to-noise ratio (SNR) relative to its liquid-state analogue TOCSY (TOtal Correlation SpectroscopY). Using 1- and 2-dimensional HRMAS NMR experiments, we identified several metabolites in burned tissues. Quantification of me...

Human platelet 12-lipoxygenase: naturally occurring Q261/R261 variants and N544L mutant show altered activity but unaffected substrate binding and membrane association behavior.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:51 +0100

Authors: Aleem AM, Wells L, Jankun J, Walther M, Kühn H, Reinartz J, Skrzypczak-Jankun E The single nucleotide polymorphism (SNP) R261Q in the human platelet 12-lipoxygenase has been correlated with several human diseases. To understand better the biological performance we have compared enzymatic properties of the recombinant enzymes: 'wild-type' as Q261 and R261 variants with a single Q261R mutation at the enzyme periphery and N544L mutant with an altered active site. The R261 variant does not follow the same kinetics such as WT-Q261 showing a lag phase, a slower accumulation of product, following a different time-course without reaching plateau characteristic for the Q261 variant. The N544L substitution in the active site almost eradicates enzymatic activity proving that asparag...

Evaluation of annexin II as a potential serum marker for hepatocellular carcinoma using a developed sandwich ELISA method.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:48 +0100

Authors: Ji NY, Park MY, Kang YH, Lee CI, Kim DG, Yeom YI, Jang YJ, Myung PK, Kim JW, Lee HG, Kim JW, Lee K, Song EY Annexin II (Annexin A2, ANXA2) is a 36 kDa calcium-dependent phospholipid-binding protein that is located on the surface of most eukaryotic cells. ANXA2 is involved in several biological processes, including anti-inflammatory effects, Ca27+-dependent exocytosis, immune responses, Ca2+ transport and phospholipase A2 regulation. In our previous study, ANXA2 was identified as an up-regulated gene in hepatocellular carcinoma (HCC) tissue by cDNA microarray. In the present study, we have evaluated ANXA2 as a tumor-associated marker of HCC. We determined the ANXA2 levels in human liver tissues with HCC using real-time RT-PCR and Western blot analysis. For quantitative analysis...

Experimental study of the anti-cancer mechanism of tanshinone IIA against human breast cancer.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:45 +0100

This study was performed to determine the anti-cancer activity of tanshinone IIA on human breast cancer cells in vitro and in vivo and to elucidate the underlying mechanism of this activity. Human breast cancer cell lines (estrogen receptor-positive and -negative) were treated with tanshinone IIA and tamoxifen. The inhibitory effects of tanshinone IIA and tamoxifen on breast cancer cell proliferation were examined using MTT assays, BrdU incorporation, immunohistochemistry and flow cytometry. Upon treatment with tanshinone IIA, breast cancer cell proliferation was significantly inhibited in a dose- and time-dependent manner (IC50 = 0.25 microg/ml) and apoptotic cell populations increased, while tamoxifen inhibited only ER-positive breast cancer cells prominently and had no effect on ER-nega...

Neuropeptide B (NPB) and neuropeptide W (NPW) system in cultured rat calvarial osteoblast-like (ROB) cells: NPW and NPB inhibit proliferative activity of ROB cells.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:42 +0100

Authors: Ziolkowska A, Rucinski M, Tyczewska M, Malendowicz LK Neuropeptides B (NPB) and W (NPW) have been identified as endogenous ligands of two G-protein-coupled receptors, neuropeptides B/W receptor 1 (NPBWR1, formerly known as GPR7) and neuropeptides B/W receptor 2 (NPBWR2, formerly known as GPR8). In rodents where NPBWR2 is absent, its counterpart is named the similar to neuropeptides B/W receptor 2 (similar to NPBWR2, formerly GPR8-like). Both NPB and NPW play a role in the control of feeding, neuroendocrine axis functions, memory and learning processes as well as in pain regulation. The present study aimed to investigate the expression of NPB, NPW, NPBWR1 and the similar to NPBWR2 genes in cultured rat calvarial osteoblast-like (ROB) cells and the effects of both peptides on pr...

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REIC/Dkk-3 stable transfection reduces the malignant phenotype of mouse prostate cancer RM9 cells.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:40 +0100

Authors: Chen J, Watanabe M, Huang P, Sakaguchi M, Ochiai K, Nasu Y, Ouchida M, Huh NH, Shimizu K, Kashiwakura Y, Kaku H, Kumon H The reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3, a member of the Dkk gene family, is a tumor suppressor in a broad range of cancers. REIC/Dkk-3 transfected stable clones of mouse prostate cancer RM9 cells (RM9-REIC) and the empty vector-transfected control clone cells (RM9-EV) were established. Clones were used to evaluate the anti-cancer effects and a proteomics analysis of REIC/Dkk-3 continuous expression was performed. The RM9-REIC cells show a feeble appearance and the cell membrane shows irregular buds known as blebs. In vitro cell proliferation was significantly suppressed in RM9-REIC clones in comparison to the control. The apopto...

Dysfunction of Ca2+/CaM kinase IIalpha cascades in the amygdala in post-traumatic stress disorder.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:36 +0100

In this study, we investigated changes in Ca2+-CaM-CaMKIIalpha in the basolateral amygdala of rats after SPS which may reveal part of the pathogenesis of PTSD. The intracellular free calcium level in the basolateral amygdala was examined by fluorescence spectrophotometry. CaM and CaMKIIalpha expression in basolateral amygdala was examined using immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction. The intracellular free calcium level in the basolateral amygdala was increased when compared to that in the control group 1 day after SPS exposure (P<0.05). CaM expression significantly increased, and CaMKIIalpha expression significantly decreased (P<0.05) in the basolateral amygdala after SPS. These findings suggest dysfunction of Ca2+-CaM-CaMKIIalpha ...

Lambda-carrageenan oligosaccharides elicit reactive oxygen species production resulting in mitochondrial-dependent apoptosis in human umbilical vein endothelial cells.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:34 +0100

Authors: Chen HM, Yan XJ, Mai TY, Wang F, Xu WF Previous studies have shown that highly sulfated lambda-carrageenan oligosaccharides (lambda-CO) possess an anti-angiogenetic effect, while high concentrations of lambda-CO present a cytotoxic effect towards human umbilical vein endothelial cells (HUVECs). The aim of this study was to explore the underlying mechanism of lambda-CO on inhibiting cell proliferation. lambda-CO elicited reactive oxygen species (ROS) production with concentrations at 0.8 and 1 mg/ml, and this event was accompanied by the increase of early apoptotic cells, nuclear morphology changes and cell cycle arrest at the S and G2/M phases. However, prevention of oxidative stress by N-acetyl-L-cysteine (NAC) could abolish the effect of lambda-CO on these events. Yet, lambd...

Neurotrophic receptor tyrosine kinase B induces c-fos-associated cell survival.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:31 +0100

In this study, we established 293T cells stably expressing human TrkB to elucidate its intracellular functions. Using this cell system, we examined the biological roles of TrkB and its downstream target molecules. The TrkB expressing cells showed an increased survival rate through increased c-fos mRNA expression by BDNF, which were completely suppressed by TrkB inhibitor. Moreover, the combination of inhibitors of mitogen-activated protein kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) partially reduced both the cell survival rate and c-fos mRNA expression, whereas monotreatment of these reagents could not affect cell survival nor c-fos mRNA expression. These results suggested that TrkB could play a role in c-fos-associated cell survival through both MEK and PI3K pathway. It is conc...

Coronary artery disease and depression: possible role of brain-derived neurotrophic factor and serotonin transporter gene polymorphisms.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:29 +0100

Authors: Bozzini S, Gambelli P, Boiocchi C, Schirinzi S, Falcone R, Buzzi P, Storti C, Falcone C Cardiovascular disease (CVD) and depression are two of the most common human health problems. Patients with depression have an increased risk of developing cardiovascular disease and mortality after experiencing a cardiac event. Both diseases are complex disorders that are influenced by genetic and environmental factors. Brain-derived neuro-trophic factor (BDNF) plays a critical role in regulating both vascular development and response to injury, and promotes survival, differentiation, and maintenance of neurons in the peripheral and nervous system. Evidence suggests that BDNF can enhance serotoninergic transmission. Serotonin modulates different brain functions and is known to regulate sle...

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Glycoprotein extraction from Laminaria japonica promotes IEC-6 cell proliferation.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:26 +0100

In this study, we isolated a novel glycoprotein from L. japonica that stimulates the growth of the IEC-6 normal murine intestinal epithelial cells. We also identified the mechanism by which this glycoprotein, referred to as LJGP, stimulates cell growth. After 24 h of exposure to LJGP, cell proliferation increased in a dose-dependent manner. To further explore the mechanism associated with LJGP-induced cell proliferation, we treated cells for various times with LJGP. We focused on the epidermal growth factor receptor (EGFR) signaling pathway, which is involved in the regulation of cellular proliferation and differentiation, during LJGP-induced cell growth. The results showed that LJGP induced EGFR and Akt activation. Furthermore, LJGP stimulated Shc/Grb2 binding and ERK activation, but inhi...

Changes in the expression of cholesterol metabolism-associated genes in HCV-infected liver: a novel target for therapy?

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:24 +0100

In this study, we evaluated the expression of lipid metabolism-associated genes in patients with HCV infection by real-time PCR. Sterol regulatory element-binding protein (SREBP)-2 expression was unchanged and low density lipoprotein receptor expression was markedly reduced by 90% in HCV-infected liver. The expression of apolipoprotein B100, microsomal triglyceride transfer protein and ATP-binding cassette G5 was significantly increased. Up-regulation of cholesterol synthesis-associated genes, including HMG-CoA reductase, HMG-CoA synthase, farnesyl-diphosphate synthase and squalene synthase, confirmed enhanced de novo cholesterol synthesis. The expression of cholesterol 7alpha-hydroxylase and farnesoid X receptor was enhanced, while bile salt export pump expression was unchanged. Fatty aci...

Dislocation of Rab13 and vasodilator-stimulated phosphoprotein in inactive colon epithelium in patients with Crohn's disease.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:20 +0100

Authors: Ohira M, Oshitani N, Hosomi S, Watanabe K, Yamagami H, Tominaga K, Watanabe T, Fujiwara Y, Maeda K, Hirakawa K, Arakawa T Crohn's disease is associated with increased permeability of the intestine even in quiescent patients. Increased intestinal permeability may cause dysregulated immunological responses in the intestinal mucosa that leads to chronic intestinal inflammation. Tight junction proteins contribute to intestinal permeability, and functional abnormality and dislocation of such proteins may cause increased intestinal permeability. We studied the expression of tight junction proteins Rab13, vasodilator-stimulated phosphoprotein (VASP), zonula occludin-1 (ZO-1), and F-actin in the intestinal epithelium of patients with inactive inflammatory bowel disease. Surgical sampl...

Middle-term expansion of hematopoietic cord blood cells with new human stromal cell line feeder-layers and different cytokine cocktails.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:17 +0100

Authors: De Angeli S, Baiguera S, Del Pup L, Pavan E, Gajo GB, Di Liddo R, Conconi MT, Grandi C, Schiavon O, Parnigotto PP Cord blood (CB) is a source of hematopoietic stem cells (HSCs) and is an alternative to bone marrow for allogenic transplantation in patients with hematological disorders. The improvement of HSC in vitro expansion is one of the main challenges in cell therapy. Stromal components and soluble factors, such as cytokines, can be useful to induce in vitro cell expansion. Hence, we investigated whether feeder-layers from new stromal cell lines and different exogenous cytokine cocktails induce HSC expansion in middle-term cultures. CB HSC middle-term expansion was carried out in co-cultures on different feeder-layers exposed to three different cytokine cocktails. CB HSC e...

The effects of adiponectin on interleukin-6 and MCP-1 secretion in lipopolysaccharide-treated 3T3-L1 adipocytes: role of the NF-kappaB pathway.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:15 +0100

Authors: Zoico E, Garbin U, Olioso D, Mazzali G, Fratta Pasini AM, Di Francesco V, Sepe A, Cominacini L, Zamboni M It was recently suggested that the transcription nuclear factor-kappaB (NF-kappaB) plays an important role in controlling the inflammation and metabolic alterations associated with obesity. In endothelial and monocytic cells, adiponectin acts as a modulator of the inflammatory response, suppressing NF-kappaB activation. The aim of this study was to assess the ability of different forms of adiponectin to modulate the inflammatory response in adipocytes. 3T3-L1 preadipocytes were cultured according to standard conditions. Fully differentiated adipocytes were stimulated with 1 microg/ml lipopolysaccharides (LPS) for 16 h, with or without pre-treatment with 10 microg/ml of glo...

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Effects of protein kinase Cdelta and phospholipase C-gamma1 on monocyte chemoattractant protein-1 expression in taxol-induced breast cancer cell death.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:12 +0100

Authors: Kim YS, An HT, Kim J, Ko J Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that plays an important role in immune cell migration. It has been reported that chemokines, including MCP-1, are involved in angiogenesis and metastasis. However, the exact role of chemokines in cancer development is still obscure. We investigated the involvement of MCP-1 in taxol-induced breast cancer cell death. The anti-cancer drug taxol induced MCF-7 breast cancer cell death. Treatment with taxol increased the mRNA expression level of MCP-1 in a dose- and time-dependent manner. Up-regulation of MCP-1 by taxol was augmented in cells treated with rottlerin, a specific inhibitor of protein kinase Cdelta (PKCdelta). In addition, taxol-induced MCP-1 expression was reduced by the ectopic exp...

The metabolic syndrome of omega3-depleted rats. IV. Intestinal phospholipid omega3 fatty acids.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:10 +0100

Authors: Hacquebard M, Portois L, Malaisse WJ, Carpentier YA A dietary deprivation in long-chain polyunsaturated omega3 fatty acids initiated in 7-week old normal rats provokes within 3 to 7 months the appearance of several features of the metabolic syndrome. Likewise, within 2 to 4-5 weeks exposure to a flaxseed oil-enriched diet, these anomalies are rapidly corrected. The present study deals with the omega3 fatty acid content of intestinal phospholipids under the same experimental conditions. For the sake of comparison, the control rats were given access during the last 4-5 weeks to either a soybean or flaxseed oil-enriched diet. In control rats, the relative weight content of omega3 fatty acids as well as their product/precursor ratio differed in distinct segments of the intestinal ...

The metabolic syndrome of omega3-depleted rats. V. Intestinal phospholipid omega6 fatty acids.

International Journal of Molecular Medicine — Thu, 05 Nov 2009 12:42:07 +0100

This study aims mainly at investigating the effects of a dietary deprivation and replenishment of omega3 PUFA upon the phospholipid pattern of omega6 PUFA in the duodenum, jejunum, caecum and colon of rats exposed for 3-7 months to an omega3-depleted diet and then eventually exposed for 2-4 weeks to an omega3-rich diet. In control rats, the relative weight content of all omega6 fatty acids differed in the proximal and distal intestinal segments. In the omega3-depleted rats the C18:2omega6, C20:2omega6 and C20:3omega6 content was decreased whilst that of C20:4omega6 and C22:4omega6 was increased. Significant correlations were found in the caecum or colon between the C18:2omega6 or C20:4omega6 content of intestinal phospholipids and their C22:6omega3 content, an increase in the latter conten...

Using the ratio of means as the effect size measure in combining results of microarray experiments

BMC Systems Biology - Latest articles — Thu, 05 Nov 2009 00:00:00 +0100

Conclusions: Our results show that the proposed effect size measure (log ratio of means) has better power to identify differentially expressed genes, and that the detected genes have better performance in predicting cancer outcomes than the commonly used effect size measure, the standardized mean difference (SMD), under both quality-weighted and quality-unweighted data integration frameworks. The new effect size measure and the quality-weighted microarray data integration framework provide efficient ways to combine microarray results. (Source: BMC Systems Biology - Latest articles)

Glycosidase inhibition: assessing mimicry of the transition state

RSC - Organic Biomolecular Chemistry — Thu, 05 Nov 2009 00:00:00 +0100

Tracey M. Gloster, Gideon J. Davies (Perspective from Org. Biomol. Chem.) Tracey M. Gloster, Org. Biomol. Chem., 2010, DOI: 10.1039/b915870g To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

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A novel bimodal lipidic contrast agent for cellular labelling and tumour MRI

RSC - Organic Biomolecular Chemistry — Thu, 05 Nov 2009 00:00:00 +0100

Nazila Kamaly, Tammy Kalber, Gavin Kenny, Jimmy Bell, Michael Jorgensen, Andrew Miller (Paper from Org. Biomol. Chem.) Nazila Kamaly, Org. Biomol. Chem., 2010, DOI: 10.1039/b910561a To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Facile P,N-heterocycle synthesis via tandem aminomethylation-cyclization of H-phosphinate building blocks

RSC - Organic Biomolecular Chemistry — Thu, 05 Nov 2009 00:00:00 +0100

Clemence Queffelec, Jean-Luc Montchamp (Paper from Org. Biomol. Chem.) Clemence Queffelec, Org. Biomol. Chem., 2010, DOI: 10.1039/b917428a To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Total synthesis of asperlicin C, circumdatin F, demethylbenzomalvin A, demethoxycircumdatin H, sclerotigenin, and other fused quinazolinones

RSC - Organic Biomolecular Chemistry — Thu, 05 Nov 2009 00:00:00 +0100

Ming-Chung Tseng, Huei-Yun Yang, Yen-Ho Chu (Paper from Org. Biomol. Chem.) Ming-Chung Tseng, Org. Biomol. Chem., 2010, DOI: 10.1039/b910545j To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Dual functions of Mdt1 in genome maintenance and cell integrity pathways in Saccharomyces cerevisiae

Yeast — Thu, 05 Nov 2009 00:00:00 +0100

Recent evidence indicates considerable cross-talk between genome maintenance and cell integrity control pathways. The RNA recognition motif (RRM)- and SQ/TQ cluster domain (SCD)-containing protein Mdt1 is required for repair of 3[prime]-blocked DNA double-strand breaks (DSBs) and efficient recombinational maintenance of telomeres in budding yeast. Here we show that deletion of MDT1 (PIN4/YBL051C) leads to severe synthetic sickness in the absence of the genes for the central cell integrity MAP kinases Bck1 and Slt2/Mpk1. Consistent with a cell integrity function, mdt1[Delta] cells are hypersensitive to the cell wall toxin calcofluor white and the Bck1-Slt2 pathway activator caffeine. An RRM-deficient mdt1-RRM0 allele shares the severe bleomycin hypersensitivity, inefficient recombinational ...

Normal table of postembryonic zebrafish development: Staging by externally visible anatomy of the living fish

Developmental Dynamics — Thu, 05 Nov 2009 00:00:00 +0100

The zebrafish is a premier model organism yet lacks a system for assigning postembryonic fish to developmental stages. To provide such a staging series, we describe postembryonic changes in several traits that are visible under brightfield illumination or through vital staining and epiflourescent illumination. These include the swim bladder, median and pelvic fins, pigment pattern, scale formation, larval fin fold, and skeleton. We further identify milestones for placing postembryonic fish into discrete stages. We relate these milestones to changes in size and age and show that size is a better indicator of developmental progress than is age. We also examine how relationships between size and developmental progress vary with temperature and density, and we document the effects of histologi...

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The role of mass spectrometry-based metabolomics in medical countermeasures against radiation.

Mass Spectrometry Reviews — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Patterson AD, Lanz C, Gonzalez FJ, Idle JR Radiation metabolomics can be defined as the global profiling of biological fluids to uncover latent, endogenous small molecules whose concentrations change in a dose-response manner following exposure to ionizing radiation. In response to the potential threat of nuclear or radiological terrorism, the Center for High-Throughput Minimally Invasive Radiation Biodosimetry was established to develop field-deployable biodosimeters based, in part, on rapid analysis by mass spectrometry of readily and easily obtainable biofluids. In this review, we briefly summarize radiation biology and key events related to actual and potential nuclear disasters, discuss the important contributions the field of mass spectrometry has made to the field of ra...

The study of ribonucleoproteomics with mass spectrometry (MS)-based technology.

Mass Spectrometry Reviews — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Takahashi N PMID: 19890945 [PubMed - as supplied by publisher] (Source: Mass Spectrometry Reviews)

Controlled band dispersion for quantitative binding determination and analysis with electrospray ionization-mass spectrometry.

Mass Spectrometry Reviews — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Schug KA, Serrano C, Fryčák P This review discusses recent emerging techniques that have been used to couple flow-injection analysis (FIA) and electrospray ionization-mass spectrometry (ESI-MS) for the quantitation of noncovalent binding interactions. Focus is placed predominantly on two such methods. Diffusion-based measurements, developed by Konermann and co-workers, uses controlled-band dispersion prior to ESI-MS to determine diffusion constants and binding constants based on the temporal variation of ligand signal measured in the mass spectrum (an indirect technique). Dynamic titration, developed by Schug and co-workers, is a direct method, where a temporal compositional gradient of a guest molecule is induced in the presence of host in solution to monitor the c...

Mass spectrometry of the photolysis of sulfonylurea herbicides in prairie waters.

Mass Spectrometry Reviews — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Headley JV, Du JL, Peru KM, McMartin DW This review of mass spectrometry of sulfonylurea herbicides includes a focus on studies relevant to Canadian Prairie waters. Emphasis is given to data gaps in the literature for the rates of photolysis of selected sulfonylurea herbicides in different water matrices. Specifically, results are evaluated for positive ion electrospray tandem mass spectrometry with liquid chromatography separation for the study of the photolysis of chlorsulfuron, tribenuron-methyl, thifensulfuron-methyl, metsulfuron-methyl, and ethametsulfuron-methyl. LC-MS/MS is shown to be the method of choice for the quantification of sulfonylurea herbicides with instrumental detection limits ranging from 1.3 to 7.2 pg (on-column). Tandem mass spectrometry coupled with the...

Effect of the membrane permeable cAMP analog, dibutyryl cAMP, on caspase-dependent apoptosis, inflammatory gene expression, and graft survival in acute cardiac allograft rejection.

exp Mol Med — Wed, 04 Nov 2009 00:00:00 +0100

This study was designed to investigate the effects of cAMP on immune regulation and apoptosis during acute rat cardiac allograft rejection. We found that the production of immune markers such as inflammatory cytokines (interlukin-1b, interlukin-6, and tumor necrosis factor-a), inducible nitric oxide synthase (iNOS) expression, and nitric oxide (NO) production, was significantly increased in the blood and transplanted hearts of allograft recipients, but not of isograft controls. These increases were effectively suppressed by the administration of the membrane permeable cAMP analog dibutyryl cAMP (db-cAMP). Administration of db-cAMP reduced allograft-induced elevation of several biochemical markers, such as adhesion molecule expression, iron-nitrosyl complex formation, caspase-3 activation, ...

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Further understanding of fat biology: Lessons from a fat fly.

exp Mol Med — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Hong JW, Park KW Obesity is a leading risk factor for insulin resistance, hypertension, hyperlipidemia, and cardiovascular complications, collectively referred to as metabolic diseases. Given the prevalence of obesity and its associated medical problems, new strategies are required to prevent or treat obesity and obesity-related metabolic effects. Here we summarize contributors of obesity, and molecular mechanisms controlling adipogenesis from studies in mammalian systems. We also discuss the possibilities of using Drosophila as a genetic model system to advance our understanding of players in fat biology. PMID: 19887892 [PubMed - as supplied by publisher] (Source: exp Mol Med)

PTH accelerates decompensation following left ventricular hypertrophy.

exp Mol Med — Wed, 04 Nov 2009 00:00:00 +0100

In this study, pressure overload-induced left ventricular hypertrophy (LVH) was induced in mice by transverse aortic banding (TAB) for 2 weeks. We subsequently evaluated the effects of a 2-week treatment with PTH or saline on compensated LVH. After another 4 weeks, the hearts of the mice were analyzed by echocardiography, histology, and molecular biology. Echocardiography showed that hearts of the PTH-treated mice have more severe failing phenotypes than the saline-treated mice following TAB with a greater reduction in fractional shortening and left ventricular posterior wall thickness and with a greater increase in left ventricular internal dimension. Increases in the heart weight to body weight ratio and lung weight to body weight ratio following TAB were significantly exacerbated in PTH...

Aspirin attenuates the anti-inflammatory effects of theophylline via inhibition of cAMP production in mice with non-eosinophilic asthma.

exp Mol Med — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Moon HG, Kim YS, Choi JP, Choi DS, Yoon CM, Jeon SG, Gho YS, Kim YK Theophylline is commonly used to treat severe asthma and chronic obstructive pulmonary disease (COPD) characterized by non-eosinophilic inflammation. Acetyl salicylic acid (ASA) is one of the most widely used medications worldwide, but up to 20% of patients with asthma experience aggravated respiratory symptoms after taking ASA. Here we evaluated the adverse effect of ASA on the therapeutic effect of theophylline in mice with non-eosinophilic asthma. A non-eosinophilic asthma mouse model was induced by airway sensitization with lipopolysaccharide (LPS)-containing allergen and then challenged with allergen alone. Therapeutic intervention was performed during allergen challenge. Theophylline inhibited lung infla...

Induction of TIMP-2 by cholesterol depletion leads to the conversion of pro MMP-2 into active-MMP-2 in human dermal fibroblasts.

exp Mol Med — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Kim S, Oh JH, Lee Y, Lee J, Cho KH, Chung JH Cholesterol is one of major components of cell membrane and plays a role in vesicular trafficking and cellular signaling. We investigated the effects of cholesterol on MMP-2 activation in human dermal fibroblasts. We found that TIMP-2 expression and active form MMP-2 (64 kD) were dose-dependently increased by methyl-b-cyclodextrin (MbCD), a cholesterol depletion agent. In contrast, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation were suppressed by cholesterol repletion. Then we investigated the regulatory mechanism of TIMP-2 expression by cholesterol depletion. We found that the phosphorylation of JNK as well as ERK was significantly increased by cholesterol depletion. Moreover, cholesterol depletion-induced TIM...

Neuronal RNA granule contains ApCPEB1, a novel Aplysia CPEB, in Aplysia sensory neuron.

exp Mol Med — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Chae YS, Lee SH, Cheang YH, Lee N, Rim YS, Jang DJ, Kaang BK The cytoplasmic polyadenylation element (CPE)-binding protein (CPEB) binds to CPE containing mRNAs on their 3' untranslated regions (3'UTRs). This RNA binding protein comes out many important tasks, especially in learning and memory, by modifying the translational efficiency of target mRNAs via poly (A) tailing. Overexpressed CPEB has been reported to induce the formation of stress granules (SGs), a sort of RNA granule in mammalian cell lines. In these days, RNA granule is considered to be a potentially important factor in learning and memory. However, there is no study about RNA granule in Aplysia. To examine whether an Aplysia CPEB, ApCPEB1, forms RNA granules, we overexpressed ApCPEB1-EGFP in Aplysia sensory neuro...

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Orphan nuclear receptor small heterodimer partner inhibits angiotensin II- stimulated PAI-1 expression in vascular smooth muscle cells.

exp Mol Med — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Lee KM, Seo HY, Kim MK, Min AK, Ryu SY, Kim YN, Park YJ, Choi HS, Lee KU, Park WJ, Park KG, Lee IK Angiotensin II is a major effector molecule in the development of cardiovascular disease. In vascular smooth muscle cells (VSMCs), angiotensin II promotes cellular proliferation and extracellular matrix accumulation through the upregulation of plasminogen activator inhibitor-1 (PAI-1) expression. Previously, we demonstrated that small heterodimer partner (SHP) represses PAI-1 expression in the liver through the inhibition of Transforming growth factor-b (TGF-b) signaling pathways. Here, we investigated whether SHP inhibited angiotensin II-stimulated PAI-1 expression in VSMCs. Adenovirus-mediated overexpression of SHP (Ad-SHP) in VSMCs inhibited angiotensin II- and TGF-beta-stimul...

Mass spectrometry based cellular phosphoinositides profiling and phospholipid analysis: a brief review.

exp Mol Med — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Kim Y, Shanta SR, Zhou LH, Kim KP Phospholipids are key components of cellular membrane and signaling. Among cellular phospholipids, phosphoinositides, phosphorylated derivatives of phosphatidylinositol are important as a participant in essential metabolic processes in animals. However, due to its low abundance in cells and tissues, it is difficult to identify the composition of phosphoinositides. Recent advances in mass spectrometric techniques, combined with established separation methods, have allowed the rapid and sensitive detection and quantification of a variety of lipid species including phosphoinositides. In this mini review, we briefly introduce progress in profiling of cellular phosphoinositides using mass spectrometry. We, also summarize current progress of matrice...

The function of p27(KIP1) during tumor development.

exp Mol Med — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Lee J, Kim SS Timely cell cycle regulation is conducted by sequential activation of a family of serine-threonine kinases called cycle dependent kinases (CDKs). Tight CDK regulation involves cyclin dependent kinase inhibitors (CKIs) which ensure the correct timing of CDK activation in different phases of the cell cycle. One CKI of importance is p27(KIP1). The regulation and cellular localization of p27(KIP1) can result in biologically contradicting roles when found in the nucleus or cytoplasm of both normal and tumor cells. The p27(KIP1) protein is mainly regulated by proteasomal degradation and its downregulation is often correlated with poor prognosis in several types of human cancers. The protein can also be functionally inactivated by cytoplasmic localization or by phosphor...

Age-dependent Preferential Dense-core Vesicle Exocytosis in Neuroendocrine Cells Revealed by Newly Developed Monomeric Fluorescent Timer Protein.

Mol Biol Cell — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Tsuboi T, Kitaguchi T, Karasawa S, Fukuda M, Miyawaki A Monitoring Editor: Akihiko Nakano Although it is evident that only a few secretory vesicles accumulating in neuroendocrine cells are qualified to fuse with the plasma membrane and release their contents to the extracellular space, the molecular mechanisms that regulate their exocytosis are poorly understood. For example, it has been controversial whether secretory vesicles are exocytosed randomly or preferentially according to their age. Using a newly developed protein-based fluorescent timer, mK-GO, which changes color with a predictable time course, here we show that small GTPase Rab27A effectors regulate age-dependent exocytosis of secretory vesicles in PC12 cells. When the vesicles were labeled with mK-GO-tagged neuro...

Growth-limiting Intracellular Metabolites in Yeast Growing Under Diverse Nutrient Limitations.

Mol Biol Cell — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Boer VM, Crutchfield CA, Bradley PH, Botstein D, Rabinowitz JD Monitoring Editor: Charles Boone Microbes tailor their growth rate to nutrient availability. Here we measured, using liquid chromatography-mass spectrometry, more than 100 intracellular metabolites in steady-state cultures of S. cerevisiae growing at five different rates and in each of five different limiting nutrients. In contrast to gene transcripts, where approximately 25% correlated with growth rate irrespective of the nature of the limiting nutrient, metabolite concentrations were highly sensitive to the limiting nutrient's identity. Nitrogen (ammonium) and carbon (glucose) limitation were characterized by low intracellular amino acid and high nucleotide levels, whereas phosphorus (phosphate) limitation result...

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Molecular Architecture of Synaptic Actin Cytoskeleton in Hippocampal Neurons Reveals a Mechanism of Dendritic Spine Morphogenesis.

Mol Biol Cell — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Korobova F, Svitkina T Monitoring Editor: Paul Forscher Excitatory synapses in the brain play key roles in learning and memory. The formation and functions of postsynaptic mushroom-shaped structures, dendritic spines, and possibly of presynaptic terminals, rely on actin cytoskeleton remodeling. However, the cytoskeletal architecture of synapses remains unknown hindering the understanding of synapse morphogenesis. Using platinum replica electron microscopy, we characterized the cytoskeletal organization and molecular composition of dendritic spines, their precursors, dendritic filopodia, and presynaptic boutons. A branched actin filament network containing Arp2/3 complex and capping protein was a dominant feature of spine heads and presynaptic boutons. Surprisingly, the spine n...

Novel Role of ATPase Subunit C Targeting Peptides Beyond Mitochondrial Protein Import.

Mol Biol Cell — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Vives-Bauza C, Magrané J, Andreu AL, Manfredi G Monitoring Editor: Thomas D. Fox In mammals, subunit c of the F1F0-ATP synthase has three isoforms (P1, P2, P3). These isoforms differ by their cleavable mitochondrial targeting peptides, while the mature peptides are identical. To investigate this apparent genetic redundancy we knocked down each of the three subunit c isoform by RNA interference in HeLa cells. Silencing any of the subunit c isoforms individually resulted in an ATP synthesis defect, indicating that these isoforms are not functionally redundant. We found that subunit c knock down impaired the structure and function of the mitochondrial respiratory chain. In particular, P2 silencing caused defective cytochrome oxidase assembly and function. Because the express...

Sec3-containing Exocyst Complex Is Required for Desmosome Assembly in Mammalian Epithelial Cells.

Mol Biol Cell — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Andersen NJ, Yeaman C Monitoring Editor: Patrick J. Brennwald The Exocyst is a conserved multi-subunit complex involved in the docking of post-Golgi transport vesicles to sites of membrane remodeling during cellular processes such as polarization, migration and division. In mammalian epithelial cells, Exocyst complexes are recruited to nascent sites of cell-cell contact in response to E-cadherin-mediated adhesive interactions, and this event is an important early step in the assembly of intercellular junctions. Sec3 has been hypothesized to function as a spatial landmark for the development of polarity in budding yeast, but its role in epithelial cells has not been investigated. Here we provide evidence in support of a function for a Sec3-containing Exocyst complex in the asse...

Hsp90 Nuclear Accumulation in Quiescence Is Linked to Chaperone Function and Spore Development in Yeast.

Mol Biol Cell — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Tapia H, Morano KA Monitoring Editor: Benjamin S. Glick Hsp90 operates in the context of a multichaperone complex to promote maturation of nuclear and cytoplasmic clients. We have discovered that Hsp90 and the cochaperone Sba1/p23 accumulate in the nucleus of quiescent S. cerevisiae cells. Hsp90 nuclear accumulation was unaffected in sba1Delta cells, demonstrating that Hsp82 translocates independently of Sba1. Translocation of both chaperones was dependent on the alpha/beta importin SRP1/KAP95. Hsp90 nuclear retention was coincident with glucose exhaustion and appears to be a starvation-specific response, as heat shock or 10% ethanol stress failed to elicit translocation. We generated nuclear accumulation-defective HSP82 mutants to probe the nature of this targeting event and ...

Rad4 Regulates Protein Turnover at a Postubiquitylation Step.

Mol Biol Cell — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Li Y, Yan J, Kim I, Liu C, Huo K, Rao H Monitoring Editor: Jeffrey L. Brodsky The Ub-binding protein Rad23 plays an important role in facilitating the transfer of substrates to the proteasome. However, the mechanism underlying Rad23's function in proteolysis remains unknown. Here, we demonstrate that Rad4, a Rad23-binding protein, also regulates ubiquitylated substrate turnover. Rad4 was previously known only as a key repair factor which directly recognizes DNA damage and initiates DNA repair. Our results, however, reveal a novel function of Rad4. We found that Rad4 and Rad23 share several common substrates. Substrates in rad4Delta cells are ubiquitylated, indicating that Rad4 regulates a postubiquitylation event. Moreover, we found that Rad4 participates in the Rad23-Ufd2 pat...

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Hydrogen Sulfide Increases HIF-1 Activity Independent of VHL-1 in C. elegans.

Mol Biol Cell — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Budde MW, Roth MB Monitoring Editor: William P. Tansey Rapid alteration of gene expression in response to environmental changes is essential for normal development and behavior. The transcription factor HIF-1 is well known to respond to alterations in oxygen availability. In nature, low oxygen environments are often found to contain high levels of hydrogen sulfide (H2S). Here we show that C. elegans can have mutually exclusive responses to H2S and hypoxia, both involving HIF-1. Specifically, H2S results in HIF-1 activity throughout the hypodermis while hypoxia causes HIF-1 activity in the gut as judged by a reporter for HIF-1 activity. C. elegans require hif-1 to survive in room air containing trace amounts of H2S. Exposure to H2S results in HIF-1 nuclear localization and tran...

NHERF1 Overexpression-dependent Increase of Cytoskeleton Organization Is Fundamental in the Rescue of F508del CFTR in Human Airway CFBE41o- Cells.

Mol Biol Cell — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Favia M, Guerra L, Fanelli T, Cardone RA, Monterisi S, Di Sole F, Castellani S, Chen M, Seidler U, Reshkin SJ, Conese M, Casavola V Monitoring Editor: Keith E. Mostov We have demonstrated that NHERF1 overexpression in CFBE41o- cells induces a significant redistribution of F508del CFTR from the cytoplasm to the apical membrane and rescues CFTR-dependent chloride secretion. Here, we observe that CFBE41o- monolayers displayed substantial disassembly of actin filaments and that overexpression of wt NHERF1 but not NHERF1-DeltaERM increased F-actin assembly and organization. Further, the dominant negative FERM domain of ezrin reversed the wt NHERF1 overexpression-induced increase in both F-actin and CFTR-dependent chloride secretion. wt NHERF1 overexpression enhanced the interaction...

Analyzing the Effects of Delaying Aster Separation on Furrow Formation during Cytokinesis in the C. elegans Embryo.

Mol Biol Cell — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Lewellyn L, Dumont J, Desai A, Oegema K Monitoring Editor: Yu-Li Wang Signaling by the centrosomal asters and spindle midzone coordinately directs formation of the cytokinetic furrow. Here, we explore the contribution of the asters by analyzing the consequences of altering interaster distance during the first cytokinesis of the C. elegans embryo. Delaying aster separation, using TPXL-1 depletion to shorten the metaphase spindle, leads to a corresponding delay in furrow formation, but results in a single furrow that ingresses at a normal rate. Preventing aster separation, by simultaneously inhibiting TPXL-1 and Galpha signaling-based cortical forces pulling on the asters, delays furrow formation and leads to the formation of multiple furrows that ingress toward the midzone. Dis...

Molecular characterization and expression analysis of lipopolysaccharide and beta-1,3-glucan-binding protein (LGBP) from pearl oyster Pinctada fucata.

Molecular Biology Reports — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Zhang D, Ma J, Jiang J, Qiu L, Zhu C, Su T, Li Y, Wu K, Jiang S The lipopolysaccharide and beta-1,3-glucan-binding protein (LGBP) plays an important function in the innate immune response of invertebrates as a pattern recognition receptor (PRR). Herein, we described the isolation and characterization of pearl oyster Pinctada fucata LGBP (designated as poLGBP). The poLGBP cDNA was 2,075 bp long and consisted of a 5'-untranslated region (UTR) of 18 bp, a 3'-UTR of 299 bp with one cytokine RNA instability motifs (ATTTA), and an open reading frame (ORF) of 1,758 bp encoding a polypeptide of 585 amino acids with an estimated molecular mass of 65.1 kDa and a theoretical isoelectric point of 5.80. Homology analysis of the deduced amino acid sequence of the poLGBP with other known LGB...

Gene expression profiling during gland morphogenesis of a mutant and a glandless upland cotton.

Molecular Biology Reports — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Sun Q, Cai Y, Xie Y, Mo J, Yuan Y, Shi Y, Li S, Jiang H, Pan Z, Gao Y, Chen M, He X To identify genes involved in pigment gland morphogenesis in cotton, gene expression was profiled using genechip (Affymetrix) during pigment gland morphogenesis in cotton variety Xiangmian-18, which has glandless seeds but glanded plants, and a glandless line, N5. The results showed that 303 genes were differentially expressed by a factor greater than two during gland morphogenesis; 59% (180) of these genes shared similarity with known genes in GenBank. These genes play roles in defense response, response to oxidative stress, peroxidase activity, and other metabolic pathways. KOBAS (KEGG Orthology-Based Annotation System) indicate that these genes are involved in 68 biochemical pathways. These ...

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Cloning and characterization of a functional flavanone-3ss-hydroxylase gene from Medicago truncatula.

Molecular Biology Reports — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Shen X, Martens S, Chen M, Li D, Dong J, Wang T As a key enzyme in the biosynthesis of flavonols, anthocyanidins and proanthocyanidins, flavanone-3ss-hydroxylase (F3H) plays very important roles in plant stress response. A putative flavanone-3ss-hydroxylase gene from Medicago truncatula (MtF3H), a model legume species, was identified from a bio-data analysis platform. It was speculated to be induced by salt stress based on the outcomes of the analysis platform. The complementary DNA (cDNA) consists of 1499 bp with an open reading frame (ORF) of 1098 bp, which encodes a putative protein of 365 amino acids with a molecular weight of about 41.36 kDa and an isoelectric point of 5.60. To measure the catalytic activity of the protein, the MtF3H gene was ligated to pYES2 vector and h...

Overexpression of CsNMAPK in tobacco enhanced seed germination under salt and osmotic stresses.

Molecular Biology Reports — Wed, 04 Nov 2009 00:00:00 +0100

Authors: Xu H, Li K, Yang F, Shi Q, Wang X In this research, biological function of CsNMAPK, encoding a mitogen-activated protein kinase of cucumber, was investigated under salt and osmotic stresses. Northern blot analysis showed that the expression of CsNMAPK was induced by salt and osmotic stresses in the cucumber root. In order to determine whether CsNMAPK was involved in plant tolerance to salt and osmotic stresses, transgenic tobacco plants constitutively overexpressing CsNMAPK were generated. Northern and Western blot analysis showed that strong signals were detected in the RNA and protein samples extracted from transgenic lines, whereas no signal was detected in the wild type tobacco, indicating that CsNMAPK was successfully transferred into tobacco genome and overexpressed. The...

Computational approaches for the genetic and phenotypic characterization of a Saccharomyces cerevisiae wine yeast collection

Yeast — Wed, 04 Nov 2009 00:00:00 +0100

Within this study, we have used a set of computational techniques to relate the genotypes and phenotypes of natural populations of Saccharomyces cerevisiae, using allelic information from 11 microsatellite loci and results from 24 phenotypic tests. A group of 103 strains was obtained from a larger S. cerevisiae winemaking strain collection by clustering with self-organizing maps. These strains were further characterized regarding their allelic combinations for 11 microsatellites and analysed in phenotypic screens that included taxonomic criteria (carbon and nitrogen assimilation tests, growth at different temperatures) and tests with biotechnological relevance (ethanol resistance, H2S or aromatic precursors formation). Phenotypic variability was rather high and each strain showed a unique ...

Random and targeted gene integrations through the control of non-homologous end joining in the yeast Kluyveromyces marxianus

Yeast — Wed, 04 Nov 2009 00:00:00 +0100

Kluyveromyces marxianus DMKU3-1042 is a thermotolerant yeast strain suitable for high-temperature ethanol fermentation and genetic engineering with linear DNA. We have developed a highly efficient random gene integration method with a frequency that exceeds 2.5 × 106 transformants/µg linear DNA, a figure comparable to what is observed with autonomously replicating plasmid transformation in Saccharomyces cerevisiae. To establish the mechanism of random integration in DMKU3-1042, we identified and deleted the K. marxianus KU70 gene, which is known to be involved in the non-homologous end-joining (NHEJ) pathway. In yeast lacking KU70, high-frequency non-homologous gene integration was abolished and the Kmku70 mutants showed 82-95% homologous gene targeting efficiencies using homologous sequ...

Collagen type IV and Perlecan exhibit dynamic localization in the Allantoic Core Domain, a putative stem cell niche in the murine allantois

Developmental Dynamics — Wed, 04 Nov 2009 00:00:00 +0100

A body of evidence suggests that the murine allantois contains a stem cell niche, the Allantoic Core Domain (ACD), that may contribute to a variety of allantoic and embryonic cell types. Given that extracellular matrix (ECM) regulates cell fate and function in niches, the allantois was systematically examined for Collagen type IV (ColIV) and Perlecan, both of which are associated with stem cell proliferation and differentiation. Not only was localization of ColIV and Perlecan more widespread during gastrulation than previously reported, but protein localization profiles were particularly robust and dynamic within the allantois and associated visceral endoderm as the ACD formed and matured. We propose that these data provide further evidence that the ACD is a stem cell niche whose activity ...

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Oxidative spirocyclisation routes towards the sawaranospirolides. Synthesis of ent-sawaranospirolides C and D

RSC - Organic Biomolecular Chemistry — Wed, 04 Nov 2009 00:00:00 +0100

Jeremy Robertson, Praful T. Chovatia, Thomas G. Fowler, Jonathan M. Withey, Daniel J. Woollaston (Paper from Org. Biomol. Chem.) Jeremy Robertson, Org. Biomol. Chem., 2010, DOI: 10.1039/b918091e To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Release of nitrite from the antitubercular nitroimidazole drug PA-824 and analogues upon one-electron reduction in protic, non-aqueous solvent

RSC - Organic Biomolecular Chemistry — Wed, 04 Nov 2009 00:00:00 +0100

Andrej Maroz, Sujata S. Shinde, Scott G. Franzblau, Zhenkun Ma, William A. Denny, Brian D. Palmer, Robert F. Anderson (Paper from Org. Biomol. Chem.) Andrej Maroz, Org. Biomol. Chem., 2010, DOI: 10.1039/b915877d To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Bis-cation salt complexation by meso-octamethylcalix[4]pyrrole: linking complexes in solution and in the solid state

RSC - Organic Biomolecular Chemistry — Wed, 04 Nov 2009 00:00:00 +0100

Claudia Caltagirone, Nathan L. Bill, Dustin E. Gross, Mark E. Light, Jonathan L. Sessler, Philip A. Gale (Paper from Org. Biomol. Chem.) Claudia Caltagirone, Org. Biomol. Chem., 2010, DOI: 10.1039/b916113a To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Muscleblind-like 1 is a negative regulator of TGF-[beta]-dependent epithelial-mesenchymal transition of atrioventricular canal endocardial cells

Developmental Dynamics — Wed, 04 Nov 2009 00:00:00 +0100

The development of the valves and septa of the heart depends on the formation and remodeling of endocardial cushions. Here, we report that the alternative splicing regulator muscleblind-like 1 (MBNL1) exhibits a regionally restricted pattern of expression in canal region endocardium and ventricular myocardium during endocardial cushion development in chicken. Knockdown of MBNL1 in atrioventricular explants leads to a transforming growth factor [beta]-dependent increase in epithelial-mesenchymal transition (EMT) of endocardial cells. This reveals a novel role for MBNL1 during embryonic development, and represents the first evidence that an alternative splicing regulator is a key player in endocardial cushion development. Developmental Dynamics, 2009. © 2009 Wiley-Liss, Inc. (Source: Develo...

Introduction to the Proceedings of the 2nd World Molecular Imaging Congress

Molecular Imaging and Biology — Tue, 03 Nov 2009 14:01:46 +0100

Content Type Journal ArticleDOI 10.1007/s11307-009-0253-9 Journal Molecular Imaging and BiologyOnline ISSN 1860-2002Print ISSN 1536-1632 (Source: Molecular Imaging and Biology)

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Proceedings of the 2009 World Molecular Imaging Congress Montreal, Canada, September 23–26

Molecular Imaging and Biology — Tue, 03 Nov 2009 14:01:46 +0100

Content Type Journal ArticleDOI 10.1007/s11307-009-0251-y Journal Molecular Imaging and BiologyOnline ISSN 1860-2002Print ISSN 1536-1632 (Source: Molecular Imaging and Biology)

Author Index

Molecular Imaging and Biology — Tue, 03 Nov 2009 14:01:44 +0100

Content Type Journal ArticleDOI 10.1007/s11307-009-0252-x Journal Molecular Imaging and BiologyOnline ISSN 1860-2002Print ISSN 1536-1632 (Source: Molecular Imaging and Biology)

Molecular cloning and localization of a novel cotton annexin gene expressed preferentially during fiber development.

Molecular Biology Reports — Tue, 03 Nov 2009 00:00:00 +0100

In this study, a novel cotton annexin gene (designated as GhFAnnx) was isolated from a fiber cDNA library of cotton (Gossypium hirsutum). The full-length cDNA of GhFAnnx comprises an open reading frame of 945 bp that encodes a 314-amino acid protein with a calculated molecular mass of 35.7 kDa and an isoelectric point of 6.49. Genomic GhFAnnx sequences from different cotton species, TM-1, Hai7124 and two diploid progenitor cottons, G. herbaceum (A-genome) and G. raimondii (D-genome) showed that at least two copies of the GhFAnnx gene, each with six exons and five introns in the coding region, were identified in the allotetraploid cotton genome. The GhFAnnx gene cloned from the cDNA library in this study was mapped to the chromosome 10 of the A-subgenome of the tetraploid cotton. Sequence a...

Temporal and spatial expression analysis of PRGL in Gerbera hybrida.

Molecular Biology Reports — Tue, 03 Nov 2009 00:00:00 +0100

Authors: Peng J, Lai L, Wang X GASA-like genes form multigene families in diverse plant species and encode the proteins with a unique cysteine-rich domain (GASA domain). In our previously work, we cloned a GASA-like gene PRGL (Proline-rich GASA-like) from gerbera. Here we report the expression profiles of PRGL and the subcellular localization of PRGL protein. Multiple sequence alignment of the GASA domains indicates that PRGL shows the highest homology to AtPRGL (73.3% of amino acid identity) from Arabidopsis. Phylogenic analysis based on the full amino acid sequences indicates that PRGL and AtPRGL belong to a novel subfamily of GASA proteins. Northern blot assay showed that PRGL is highly expressed in young flower, young leaf and young root, whereas hardly detected when these organs b...

Identification of Elymus (Triticeae, Poaceae) and its related genera genomes by RFLP analysis of PCR-amplified Adh genes.

Molecular Biology Reports — Tue, 03 Nov 2009 00:00:00 +0100

Authors: Liu Q, Zhang N, Li L, Liu J Elymus L. is the largest genus in Triticeae, containing about 150 species with four recognized genome donors (St, H, P, and W). Traditionally, the genome compound of this genus is identified based on cytological data. Recently, molecular phylogenetic analysis was used to investigate its genomic combination. Here we describe a restriction fragment length polymorphism (RFLP) assay based on digesting alcohol dehydrogenase (Adh) amplicons with two restriction enzyme combinations, EcoRI-HindIII and EcoRI-PstI, which easily can be used to distinguish Elymus and its closely related genera genomes. The method includes only four steps: (1) amplifying nuclear Adh genes with universal primers; (2) purifying and cloning PCR products; (3) digesting plasmids with...

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Acid-sensing ion channels 3: a potential therapeutic target for pain treatment in arthritis.

Molecular Biology Reports — Tue, 03 Nov 2009 00:00:00 +0100

Authors: Yuan FL, Chen FH, Lu WG, Li X Acid-sensing ion channels 3 (ASIC3) is the most sensitive to such a pH change, predominantly distributed in the sensory peripheral nervous system, and strongly correlated with pain. Recently, there is increasing evidence that ASIC3 may contribute to the pathogenesis of chronic inflammatory pain diseases due to it is predominantly expressed in dorsal root ganglia (DRG) neurons making it a good candidate for a pain sensor. Elevated expression of ASIC3 was found in DRG of rodents with inflamed hind paws. In addition, it has been shown that ASIC3 gene knock-out mice (ASIC3-/-) exhibited no enhanced hyperalgesia in inflamed joint. All theses findings suggest that ASIC3 have important biological effects in inflammation that might be a promising therapeu...

Plant chemical defence: a partner control mechanism stabilising plant - seed-eating pollinator mutualisms.

BMC Evolutionary Biology - Latest articles — Tue, 03 Nov 2009 00:00:00 +0100

Conclusions: Adonivernith accumulation and larval predation intensity appear to be both the reciprocal cause and effect. Adonivernith not only constitutes an effective chemical means of partner control, but may also play a role in the sympatric diversification of the Chiastocheta genus. (Source: BMC Evolutionary Biology - Latest articles)

Loss of Wnt8b has no overt effect on hippocampus development but leads to altered Wnt gene expression levels in dorsomedial telencephalon

Developmental Dynamics — Tue, 03 Nov 2009 00:00:00 +0100

Wnt signalling proteins regulate many aspects of animal development. We have investigated the function of mouse Wnt8b during forebrain development. Wnt8b is expressed in a highly restricted pattern including the prospective hippocampus and hypothalamus. Mutant mice lacking Wnt8b are viable and healthy. The size and morphology of the hippocampus appeared normal in mutant embryos and adults, and we found no evidence of hypothalamic defects in mutants. Wnt8b is also expressed in the neurogenic region of the adult dentate gyrus, however, cell proliferation was unchanged in Wnt8b-/- mutants. Mutant embryos did, however, display altered levels of expression of other Wnt genes normally expressed in forebrain. The spatial expression patterns of other Wnt genes and the overall level of canonical Wn...

A rapid and efficient method of genotyping zebrafish mutants

Developmental Dynamics — Tue, 03 Nov 2009 00:00:00 +0100

In order to facilitate high throughput genotyping of zebrafish, we have developed a novel technique that uses High Resolution Melting Analysis (HRMA) to distinguish wild-type, heterozygous mutants and homogyzous mutants. This one hour technique removes the need for restriction enzymes and agarose gels. The generated melting curve profiles are sensitive enough to detect non-specific PCR products. We have been able to reliably genotype three classes of mutations in zebrafish, including point mutants, apchu745 (apcmcr), and p53zy7 (p53I166T), a small deletion mutant (bap28y75) and a retroviral insertion mutant (wdr43hi821a). This technique can genotype individual zebrafish embryos and adults (by tail-clip) and is applicable to other model organisms. Developmental Dynamics, 2009. © 2009 Wiley...

Characterization of molecular markers to assess cardiac cushions formation in Xenopus

Developmental Dynamics — Tue, 03 Nov 2009 00:00:00 +0100

The valves and septa of the mature heart are derived from the cardiac cushions, which develop from discrete swellings in two regions of developing heart tube: the atrioventricular (AV) canal and the ventricular outflow tract (OFT). In higher vertebrates, three distinct lineages contribute to the heart valves and septa, the endocardium, the myocardium, and the cardiac neural crest that will populate the cardiac jelly of the OFT. Very little is known about cardiac cushions development in amphibians. Here, we describe the expression of eight genes during key stages of cardiac cushion development in Xenopus. Among these genes, the Wnt antagonist Frzb1 and the transcription factors Xl-Fli, Sox8, Sox9, and Sox10 are differentially expressed in the mesenchyme of the OFT and AV cushions. These gen...

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Asator, a tau-tubulin kinase homolog in Drosophila localizes to the mitotic spindle

Developmental Dynamics — Tue, 03 Nov 2009 00:00:00 +0100

We have used a yeast two-hybrid interaction assay to identify Asator, a tau-tubulin kinase homolog in Drosophila that interacts directly with the spindle matrix protein Megator. Using immunocytochemical labeling by an Asator-specific mAb as well as by transgenic expression of a GFP-labeled Asator construct, we show that Asator is localized to the cytoplasm during interphase but redistributes to the spindle region during mitosis. Determination of transcript levels using qRT-PCR suggested that Asator is expressed throughout development but at relatively low levels. By P-element excision, we generated a null or strong hypomorphic Asatorexc allele that resulted in complete adult lethality when homozygous, indicating that Asator is an essential gene. That the observed lethality was caused by im...

Chondroitin sulfate expression is required for cardiac atrioventricular canal formation

Developmental Dynamics — Tue, 03 Nov 2009 00:00:00 +0100

Defects in cardiac valvulogenesis are a common cause of congenital heart disease, and the study of this process promises to provide mechanistic insights and lead to novel therapeutics. Normal valve development involves multiple signaling pathways, and recently roles have been identified for extracellular matrix components, including glycosaminoglycans. We, therefore, explored the role of the glycosaminoglycan chondroitin sulfate during zebrafish cardiac development. Beginning at 33 hr, there is a distinct zone of chondroitin sulfate expression in the atrioventricular (AV) boundary, in the cardiac jelly between the endocardium and myocardium. This expression is both spatially and temporally restricted, and is undetectable after 48 hr. Chemical as well as genetic inhibition of chondroitin sy...

Differential role of the menthol-binding residue Y745 in the antagonism of thermally gated TRPM8 channels

Molecular Pain — Tue, 03 Nov 2009 00:00:00 +0100

Conclusions: In summary, we identify structural elements on the TRPM8 channel that are critical for the action of channel antagonists, providing valuable information for the future design of new, specific modulator compounds. (Source: Molecular Pain)

Functional characterization of two CITED3 homologs (gcCITED3a and gcCITED3b) in the hypoxia-tolerant grass carp, Ctenopharyngodon idella

BMC Molecular Biology - Latest articles — Tue, 03 Nov 2009 00:00:00 +0100

Conclusion: The grass carp gcCITED3a and gcCITED3b genes are differentially expressed and regulated in different fish organs in response to hypoxic stress. This is the first report demonstrating in vivo regulation of two closely-related CITED3 isogenes by HIF-1, as well as CITED3 regulation of HIF-1 transcriptional activity in fish. Overall, our findings suggest that unique molecular mechanisms operate through these two gcCITED3 isoforms that likely play an important regulatory role in the hypoxic response in the grass carp. (Source: BMC Molecular Biology - Latest articles)

Protein intrinsic disorder and oligomericity in cell signaling

RSC - Mol. BioSyst. latest articles — Tue, 03 Nov 2009 00:00:00 +0100

Alexander B. Sigalov (Review from Mol. BioSyst.) Alexander B. Sigalov, Mol. BioSyst., 2010, DOI: 10.1039/b916030m To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Mol. BioSyst. latest articles)

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A novel strategy to inhibit FAK and IGF-1R decreases growth of pancreatic cancer xenografts

Molecular Carcinogenesis — Tue, 03 Nov 2009 00:00:00 +0100

Deregulation of insulin-like growth factor-1 receptor (IGF-1R) and focal adhesion kinase (FAK) signaling pathways plays an important role in cancer cell proliferation and metastasis. In pancreatic cancer cells, the crosstalk and compensatory mechanisms between these two pathways reduce the efficacy of the treatments that target only one of the pathways. Ablation of IGF-1R signaling by siRNA showed minimal effects on the survival and growth of pancreatic cancer cells. An increased activity of FAK pathway was seen in these cells after IGF-1R knockdown. Further inhibition of FAK pathway using Y15 significantly decreased cell survival, adhesion, and promoted apoptosis. The combination of Y15 treatment and IGF-1R knockdown also showed significant antitumor effect in vivo. The current study demo...

Inhibitory role of cAMP on doxorubicin-induced apoptosis in pre-B ALL cells through dephosphorylation of p53 serine residues

Apoptosis — Mon, 02 Nov 2009 18:11:34 +0100

In conclusion, our results suggest that activation of cAMP-signaling system may repress p53-dependent apoptosis in malignant cells exposed to doxorubicin. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s10495-009-0417-8Authors Majid Safa, Iran University of Medical Sciences Department of Hematology, Faculty of Allied Medicine P.O. Box # 14155-6183 Tehran IranAhmad Kazemi, Iran University of Medical Sciences Department of Hematology, Faculty of Allied Medicine P.O. Box # 14155-6183 Tehran IranHamid Zand, Shahid Beheshti University M. C. Department of Basic Medical Sciences, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology Tehran IranAzita Azarkeivan, Iranian Blood Transfusion Organization Research Center Tehran...

Histone H1 subtype preferences of DFF40 and possible nuclear localization of DFF40/45 in normal and trichostatin A-treated NB4 leukemic cells

Apoptosis — Mon, 02 Nov 2009 18:11:33 +0100

Abstract A major hallmark of the terminal stages of apoptosis is the internucleosomal DNA fragmentation. The endonuclease responsible for this type of DNA degradation is the DNA fragmentation factor (DFF). DFF is a complex of the endonuclease DFF40 and its chaperone/inhibitor, DFF45. In vitro work has shown that histone H1 and HMGB1/2 recruit/target DFF40 to the internucleosomal linker regions of chromatin and that histone H1 directly interacts with DFF40 conferring DNA binding ability and enhancing its nuclease activity. The histone H1 family is comprised of many subtypes, which recent work has shown may have distinct roles in chromatin function. Thus we studied the binding association of DFF40 with specific H1 subtypes and whether these binding associations are altered a...

Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling

Apoptosis — Mon, 02 Nov 2009 18:11:32 +0100

Abstract Thymoquinone (TQ), a component of black seed essential oil, is known to induce apoptotic cell death and oxidative stress, however, the direct involvement of oxidants in TQ-induced cell death has not been established yet. Here, we show that TQ inhibited the proliferation of a panel of human colon cancer cells (Caco-2, HCT-116, LoVo, DLD-1 and HT-29), without exhibiting cytotoxicity to normal human intestinal FHs74Int cells. Further investigation in DLD-1 revealed that apoptotic cell death is the mechanism for TQ-induced growth inhibition as confirmed by flow cytometry, M30 cytodeath and caspase-3/7 activation. Apoptosis was induced via the generation of reactive oxygen species (ROS) as evidenced by the abrogation of TQ apoptotic effect in cells preincubated with th...

Impaired IL-7 signaling may explain a case of atypical JAK3-SCID.

Cytokine — Mon, 02 Nov 2009 00:00:00 +0100

We report here that the JAK3-E481G mutant transduced IL-2-, IL-4-, IL-15-, and IL-21-induced signals as efficiently as wild-type JAK3. However, this mutant failed to respond to IL-7 by phosphorylating JAK1, JAK3, or STAT5. The other mutant JAK3, JAK3-del482-596, was non-functional. Thus, an impaired IL-7 signal may cause SCID and compromise T-cell differentiation, even if the IL-15 signal is preserved and supports NK-cell development, as in this patient. PMID: 19889552 [PubMed - as supplied by publisher] (Source: Cytokine)

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Brain cancer propagating cells: biology, genetics and targeted therapies.

Trends in Molecular Medicine — Mon, 02 Nov 2009 00:00:00 +0100

Authors: Hadjipanayis CG, Van Meir EG Cancer propagating cells (CPCs) within primary central nervous system (CNS) tumors (glioblastoma multiforme (GBM), medulloblastoma (MB) and ependymoma) might be integral to tumor development and perpetuation. These cells, also known as brain cancer propagating cells (BCPCs), have the ability to self-renew and proliferate. BCPCs can initiate new tumors in mice with high efficiency and these exhibit many features that are characteristic of patient's brain tumors. Accumulating evidence suggests that BCPCs might originate from the transformation of neural stem cells (NSCs) and their progenitors. Furthermore, recent studies have shown that NSC surface markers also define BCPCs. Ultimately, treatments that include specific targeting of BCPCs might potent...

Application of proteomic marker ensembles to subcellular organelle identification.

Molecular and Cellular Proteomics : MCP — Mon, 02 Nov 2009 00:00:00 +0100

Authors: Andreyev AY, Shen Z, Guan Z, Ryan A, Fahy E, Subramaniam S, Raetz CR, Briggs S, Dennis EA Compartmentalization of biological processes and the associated cellular components is crucial for cell function. Typically, the location of a component is revealed through a co-localization and/or co-purification with an organelle marker. Therefore, the identification of reliable markers is critical for a thorough understanding of cellular function and dysfunction. We fractionated macrophage-like RAW264.7 cells, both in the resting and in the endotoxin-activated state, into six fractions representing the major organelles/ compartments: nuclei, mitochondria, cytoplasm, endoplasmic reticulum and plasma membrane, as well as an additional dense microsomal fraction. The identity of the first ...

HPLC-method for determination of permethrin enantiomers using chiral beta-cyclodextrin-based stationary phase.

Chirality — Mon, 02 Nov 2009 00:00:00 +0100

Authors: Shishovska M, Trajkovska V The liquid chromatographic separation of permethrin enantiomers on chiral beta-cyclodextrin-based stationary phase has been investigated. All four enantiomers are obtained by using simple methanol and water mobile phase, under gradient mode. The method was optimized and validated. The relationship between temperature and chromatographic parameters: k' (capacity factor), alpha (separation factor) and Rs (resolution factor) was studied. Van't Hoff's curves for each enantiomer were plotted for temperature range 288-318 K. It was noticed that the response factor ratio of permethrin isomers differ and calculated value is found to be 1.66 (cis/trans, for n = 5). This method has been used for determining permethrin enantiomer ratio for a few samples of work...

New applications and challenges for computational ROA spectroscopy.

Chirality — Mon, 02 Nov 2009 00:00:00 +0100

Authors: Pecul M In this article, applications of quantum chemical methods in calculations of the vibrational Raman optical activity (ROA) spectra are reviewed and new developements are discussed. Modeling of ROA spectra of amino acids and peptides and applications for establishing absolute configuration are briefly outlined. Particular attention is paid to the modeling of solvent effects on ROA spectra, anharmonicity in ROA, resonance and pre-resonance ROA spectra, and ROA spectra of molecules adsorbed on metal surfaces or metal nanoparticles (surface-enhanced Raman optical activity, SEROA). Remaining challenges in computational ROA spectroscopy are also pointed out. Chirality 2010. (c) 2009 Wiley-Liss, Inc. PMID: 19885819 [PubMed - as supplied by publisher] (Source: Chirality)

Channel-like crystal structure of cinchoninium L-O-phosphoserine salt dihydrate.

Chirality — Mon, 02 Nov 2009 00:00:00 +0100

Authors: Wesełucha-Birczyńska A, Oleksyn BJ, Wątroba J Studies on the interactions between L-O- phosphoserine, as one of the simplest fragments of membrane components, and the Cinchona alkaloid cinchonine, in the crystalline state were performed. Cinchoninium L-O-phosposerine salt dihydrate (PhSerCin) crystallizes in a monoclinic crystal system, space group P2(1), with unit cell parameters: a = 8.45400(10) A, b = 7.17100(10) A, c = 20.7760(4) A, alpha = 90 degrees , beta = 98.7830(10) degrees , gamma = 90 degrees , Z = 2. The asymmetric unit consists of the cinchoninium cation linked by hydrogen bonds to a phosphoserine anion and two water molecules. Intermolecular hydrogen bonds connecting phosphoserine anions via water molecules form chains extended along the b axis...

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Factors influencing the interconversion of a new class of dibenzodiazepine sulfonamide atropisomers.

Chirality — Mon, 02 Nov 2009 00:00:00 +0100

Authors: Welch CJ, Gong X, Schafer W, Chobanian H, Lin L, Biba M, Liu P, Guo Y, Beard A A novel family of atropisomers based on a conformationally constrained seven membered ring system is investigated using a combination of preparative chiral chromatography, circular dichroism, and other analytical techniques. The influence of structure on the rate of atropisomer interconversion was explored with a series of analogs showing a range of interconversion rates ranging from very fast (undetectable on the HPLC timescale) to very slow (half life of many days). Chirality 2010. (c) 2009 Wiley-Liss, Inc. PMID: 19885821 [PubMed - as supplied by publisher] (Source: Chirality)

Molecular tweezers for enantiodiscrimination in NMR: Di-(R,R)-1-[10-(1-hydroxy-2,2,2-trifluoroethyl)-9-anthryl]-2,2,2-trifluoroethyl benzenedicarboxylates.

Chirality — Mon, 02 Nov 2009 00:00:00 +0100

Authors: Gil S, Palomino-Schätzlein M, Burusco KK, Jaime C, Virgili A A series of new chiral molecular tweezers, di-(R,R)-1-[10-(1-hydroxy-2,2,2-trifluoroethyl)-9-anthryl]-2,2,2-trifluoroethyl phthalate (2), isophthalate (3) and terephthalate (4), were synthesized and their structure studied by NMR and molecular mechanics. Their effectiveness as chiral solvating agents for the determination of the enantiomeric purity of chiral compounds using NMR was demonstrated. Chirality 2010. (c) 2009 Wiley-Liss, Inc. PMID: 19885822 [PubMed - as supplied by publisher] (Source: Chirality)

Experimental and computational studies of enantioseparation of structurally similar chiral compounds on amylose tris(3,5-dimethylphenylcarbamate).

Chirality — Mon, 02 Nov 2009 00:00:00 +0100

Authors: Kasat RB, Franses EI, Wang NH The enantioseparation of 14 structurally similar chiral solutes, with one or two chiral centers, are studied for a commercially important polysaccharide-based chiral stationary phase, amylose tris(3,5-dimethylphenylcarbamate) (ADMPC). Among these solutes, only two solutes show significant enantioresolutions of 2 to 2.5 in n-hexane/2-propanol (90/10, v/v) at 298 K. The retention factors of the chiral solutes vary significantly from 0.7 to 7.0, and they are compared with those of simpler nonchiral solutes having similar but fewer functional groups. The sorbent-solute H-bonding interactions between the solute functional groups and the polymer C==O and NH functional groups are probed with attenuated total reflection infrared spectroscopy (ATR-IR). The...

Inhibition of focal adhesion kinase and src increases detachment and apoptosis in human neuroblastoma cell lines

Molecular Carcinogenesis — Mon, 02 Nov 2009 00:00:00 +0100

Neuroblastoma is the most common extracranial solid tumor of childhood. Focal adhesion kinase (FAK) is an intracellular kinase that is overexpressed in a number of human tumors including neuroblastoma, and regulates both cellular adhesion and survival. We have studied the effects of FAK inhibition upon neuroblastoma using adenovirus-containing FAK-CD (AdFAK-CD). Utilizing an isogenic MYCN+/MYCN- neuroblastoma cell line, we found that the MYCN+ cells are more sensitive to FAK inhibition with AdFAK-CD than their MYCN negative counterparts. In addition, we have shown that phosphorylation of Src is increased in the untreated isogenic MYCN- neuroblastoma cells, and that the decreased sensitivity of the MYCN- neuroblastoma cells to FAK inhibition with AdFAK-CD is abrogated by the addition of the...

Matrix mechanics and receptor-ligand interactions in cell adhesion

RSC - Organic Biomolecular Chemistry — Mon, 02 Nov 2009 00:00:00 +0100

Dewi Harjanto, Muhammad H. Zaman (Emerging Area from Org. Biomol. Chem.) Dewi Harjanto, Org. Biomol. Chem., 2010, DOI: 10.1039/b913064k To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

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Synthesis and conformational analysis of d-2[prime or minute]-deoxy-2[prime or minute],2[prime or minute]-difluoro-4[prime or minute]-dihydro-4[prime or minute]-thionucleosides

RSC - Organic Biomolecular Chemistry — Mon, 02 Nov 2009 00:00:00 +0100

Feng Zheng, Lin Fu, Renxiao Wang, Feng-Ling Qing (Paper from Org. Biomol. Chem.) Feng Zheng, Org. Biomol. Chem., 2010, DOI: 10.1039/b914679b To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

TGFBR1*6A/9A polymorphism and cancer risk: a meta-analysis of 13,662 cases and 14,147 controls.

Molecular Biology Reports — Sun, 01 Nov 2009 00:00:00 +0100

Authors: Liao RY, Mao C, Qiu LX, Ding H, Chen Q, Pan HF Published data on the association between TGFBR1*6A/9A polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 32 studies including 13,662 cases and 14,147 controls were involved in this meta-analysis. Overall, significantly elevated cancer risks were associated with TGFBR1*6A in all genetic models (for allelic effect: OR = 1.11; 95% CI = 1.03-1.21; for 6A/6A vs. 9A/9A: OR = 1.30; 95% CI = 1.01-1.69; for 9A/6A vs. 9A/9A: OR = 1.08; 95% CI = 1.01-1.15; for dominant model: OR = 1.08; 95% CI = 1.02-1.15; for recessive model: OR = 1.29; 95% CI = 1.00-1.68). In the subgroup analysis by cancer types, significant associations were found in breast ca...

Autoimmunity against type VII collagen in inflammatory bowel disease.

J Cell Mol Med — Sat, 31 Oct 2009 00:00:00 +0100

Authors: Hundorfean G, Neurath MF, Sitaru C Abstract Autoimmunity against type VII collagen, an adhesion molecule of the extracellular matrix in epithelial basement membranes, is causing the rare organ-specific epidermolysis bullosa acquisita (EBA). An intriguing association between EBA and inflammatory bowel disease (IBD) has been extensively documented over the last decades, but, due to the very low incidence of EBA, received little attention from physicians involved in the care of patients with IBD. More recently, autoantibodies against type VII collagen have been detected in up to 68% of IBD patients. While these findings suggest that chronic intestinal inflammation in IBD predisposes for autoimmunity against type VII collagen, their relevance for the pathogenesis of both IBD and E...

Prediction and validation of conservative microRNAs of Solanum tuberosum L.

Molecular Biology Reports — Sat, 31 Oct 2009 00:00:00 +0100

Authors: Yang W, Liu X, Zhang J, Feng J, Li C, Chen J Potato (Solanum tuberosum) is an important crop around the world, and accounts for a significant amount of the food consumed by humans. However, little information is available about potato miRNAs which play important regulatory roles in plant growth and development. In the present study, computational prediction of potential miRNAs from potato revealed 71 miRNAs belonging to 48 families. Amongst these 71 mRNAs, 65 were predicted for the first time. Most potato miRNA families have one to three members, and sequence analysis showed that the candidate pre-miRNA sequences varied from 48 to 224 bp in length. To verify the predicted miRNAs, specific stem-loop RT primers were designed and real-time PCR assays were used to profile the expr...

Phylogenetic analysis of mitochondrial substitution rate variation in the angiosperm tribe Sileneae

BMC Evolutionary Biology - Latest articles — Sat, 31 Oct 2009 00:00:00 +0100

Conclusions: The patterns of phylogenetic divergence within Sileneae suggest enormous variability in plant mitochondrial mutation rates and reveal a complex interaction of gene and species effects. The variation in rates across genomic and phylogenetic scales raises questions about the mechanisms responsible for the evolution of mutation rates in plant mitochondrial genomes. (Source: BMC Evolutionary Biology - Latest articles)

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Probing events with single molecule sensitivity in zebrafish and Drosophila embryos by fluorescence correlation spectroscopy

Developmental Dynamics — Sat, 31 Oct 2009 00:00:00 +0100

Zebrafish and Drosophila are animal models widely used in developmental biology. High-resolution microscopy and live imaging techniques have allowed the investigation of biological processes down to the cellular level in these models. Here, using fluorescence correlation spectroscopy (FCS), we show that even processes on a molecular level can be studied in these embryos. The two animal models provide different advantages and challenges. We first characterize their autofluorescence pattern and determine usable penetration depth for FCS especially in the case of zebrafish, where tissue thickness is an issue. Next, the applicability of FCS to study molecular processes is shown by the determination of blood flow velocities with high spatial resolution and the determination of diffusion coeffic...

Interaction of porphyrins with human organic anion transporting polypeptide 1B1.

Chemico-Biological Interactions — Fri, 30 Oct 2009 21:54:34 +0100

Authors: Campbell SD, Lau WF, Xu JJ The existence of a porphyrin uptake transporter in hepatocytes has been hypothesized in recent years, but to date it has not been identified. While the linear tetrapyrrole bilirubin has been shown to be a substrate for the organic anion transporting polypeptide 1B1 (OATP1B1), similar studies have not been conducted for the cyclic tetrapyrroles (porphyrins). The aim of this study was to determine the structural features of linear and cyclic tetrapyroles necessary for interaction with OATP1B1. The interaction was quantified using HEK cells stably expressing OATP1B1 and measuring the inhibition of OATP1B1-mediated uptake of estradiol 17beta-d-glucuronide in the presence or absence of various linear and cyclic tetrapyrroles. Ditaurine-conjugated bilirubi...

Towards the mechanism and comparative effect of diphenyl diselenide, diphenyl ditelluride and ebselen under various pathophysiological conditions in rat's kidney preparation.

Chemico-Biological Interactions — Fri, 30 Oct 2009 21:54:31 +0100

This study provides evidence for acidosis catalyzed oxidative stress in kidney homogenate and for the first time anti-oxidant potential of diphenyl diselenide and diphenyl ditelluride not only at physiological pH but also at a range of acidic values. PMID: 19589335 [PubMed - indexed for MEDLINE] (Source: Chemico-Biological Interactions)

Alteration of Toll-like receptor 4 activation by 4-hydroxy-2-nonenal mediated by the suppression of receptor homodimerization.

Chemico-Biological Interactions — Fri, 30 Oct 2009 21:54:29 +0100

Authors: Kim YS, Park ZY, Kim SY, Jeong E, Lee JY Toll-like receptors (TLRs) detect invading microbial pathogens and initiate immune responses as part of host defense mechanisms. They also respond to host-derived substances released from injured cells and tissues to ensure wound healing and tissue homeostasis. Dysregulation of TLRs increases the risk of chronic inflammatory diseases and immune disorders. Inflammatory events are often accompanied by oxidative stress, which generates lipid peroxidation products such as 4-hydroxy-2-nonenal (4-HNE). Therefore, we investigated if 4-HNE affects TLR activation. We found that 4-HNE blocked LPS (a TLR4 agonist)-induced activation of NFkappaB and IRF3 as well as expression of IFNbeta, IP-10, RANTES, and TNFalpha. To investigate the mechanism of ...

Apigenin-induced apoptosis is mediated by reactive oxygen species and activation of ERK1/2 in rheumatoid fibroblast-like synoviocytes.

Chemico-Biological Interactions — Fri, 30 Oct 2009 21:54:25 +0100

In this study, we investigated the roles of apigenin in RA-FLSs. The survival rate decreased, and apoptotic cell death was induced by apigenin treatment in RA-FLSs. Apigenin treatment resulted in activation of the mitogen-activated protein kinase (MAPK) ERK1/2, and pretreatment with an ERK inhibitor PD98059 dramatically reduced apigenin-induced apoptosis. We found that apigenin-mediated production of a large amount of intracellular reactive oxygen species (ROS) caused activation of ERK1/2 and apoptosis; treatment with the antioxidant Tiron strongly inhibited the apigenin-induced generation of ROS, phosphorylation of ERK1/2, and apoptotic cell death. Apigenin-induced apoptotic cell death was mediated through activation of the effectors caspase-3 and caspase-7, and was blocked by pretreatmen...

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Responses of PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) in MCF-7 cells are culture condition dependent.

Chemico-Biological Interactions — Fri, 30 Oct 2009 21:54:23 +0100

In conclusion, the effects of PhIP and estradiol in MCF-7 cells are dependent on culture conditions. The detected PhIP-induced changes are weaker compared to those induced by estradiol. PMID: 19647730 [PubMed - indexed for MEDLINE] (Source: Chemico-Biological Interactions)

Crystalline silica Min-U-Sil 5 induces oxidative stress in human bronchial epithelial cells BEAS-2B by reducing the efficiency of antiglycation and antioxidant enzymatic defenses.

Chemico-Biological Interactions — Fri, 30 Oct 2009 21:54:20 +0100

In this study we investigated the hypothesis that crystalline silica Min-U-Sil 5 can induce elevations in intracellular ROS in human bronchial epithelial cells BEAS-2B, via an indirect mechanism that involves ROS-inducing intracellular factors, through a reduction of antiglycation (glyoxalase enzymes) and antioxidant (paraoxonase 1 and glutathione-S-transferases) enzymatic defenses. The results show that crystalline silica Min-U-Sil 5 causes a significant reduction in the efficiency of antiglycation and antioxidant enzymatic defenses, paralleled by an early and extensive ROS generation, thus preventing the cells from an efficient scavenging action, and eliciting oxidative damage. These results confirm the importance of ROS in development of crystalline silica-induced oxidative stress and e...

A novel phenotype-based approach for systematically screening antiproliferation metallodrugs.

Chemico-Biological Interactions — Fri, 30 Oct 2009 21:54:17 +0100

In this study, zebrafish were employed as a whole-organism model to screen new Ru compounds for anti-cell proliferation activity. After soaking fish embryos in cisplatin and five Ru derivatives, [Ru(terpy)(bpy)Cl]Cl, [Ru(terpy)(dppz)OH(2)](ClO(4))(2), [Ru(terpy)(tMen)OH(2)](ClO(4))(2), [Ru(terpy)(Me(4)Phen)OH(2)](ClO(4))(2), and Ru(bpy)(2)Cl(2), only cisplatin and [Ru(terpy)(bpy)Cl]Cl-treated embryos displayed obvious phenotypic effects, such as fin-reduction. After further modification of [Ru(terpy)(bpy)Cl]Cl's main structure and the synthesis of two structurally related compounds, [Ru(terpy)(dcbpyH(2))Cl]Cl and [Ru(terpy)(dmbpy)Cl]Cl, only [Ru(terpy)(dmbpy)Cl]Cl exhibited fin-reduction phenotypes. TUNEL assays combined with immunostaining techniques revealed that treatment with cisplatin...

Antidiabetic and antilipidemic effect of eremanthin from Costus speciosus (Koen.)Sm., in STZ-induced diabetic rats.

Chemico-Biological Interactions — Fri, 30 Oct 2009 21:54:15 +0100

Authors: Eliza J, Daisy P, Ignacimuthu S, Duraipandiyan V The increasing prevalence of diabetes mellitus worldwide is an issue of major socio-economic concern. Diabetes mellitus is a complex and a multifarious group of disorders that disturbs the metabolism of carbohydrates, fat and protein. Medicinal plants play an important role in the management of diabetes mellitus especially in developing countries. Costus speciosus is widely used in Indian medicine to treat various diseases. Eremanthin was isolated from C. speciosus. The structure was identified using gas chromatography-mass spectrometry (GC-MS) analysis. Eremanthin was administered to streptozotocin (STZ) (50mg/kg bw) induced diabetic male Wistar rats at different doses (5, 10, 20mg/kg bw) for 60 days. Plasma glucose level was s...

Induced expression of drug metabolizing enzymes by preventive agents: role of the antioxidant response element.

Chemico-Biological Interactions — Fri, 30 Oct 2009 21:54:12 +0100

Authors: Lubet RA, Yao R, Grubbs CJ, You M, Wang Y Identifying agents that block tumor initiation is a goal of cancer prevention. The ability of a chemically varied group of agents to induce various drug metabolizing genes in livers of rats was examined. Sprague-Dawley rats were treated for 7 days with various agents in the diet or by gavage. The agents examined, which might be expected to respond via specific nuclear receptors (CAR, AhR) as well as antioxidant response elements (AREs), included Phase I/II inducers [5,6-benzoflavone (BF, 5000mg/kg diet), diallyl sulfide (DAS, 500mg/kg BW/day), ethoxyquin (EXO, 300mg/kg BW/day) and phenobarbital (PB, 500mg/kg diet)] or pure Phase II inducers [1,2-dithiol-3-thione (DTT, 500mg/kg diet), and cyclopentadithiolthione (CPDTT, 175mg/kg BW/day)...

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Modulation of arsenic trioxide-induced apoptosis by genistein and functionally related agents in U937 human leukaemia cells. Regulation by ROS and mitogen-activated protein kinases.

Chemico-Biological Interactions — Fri, 30 Oct 2009 21:54:09 +0100

Authors: Sánchez Y, Calle C, de Blas E, Aller P The proved radio- and chemo-sensitizing capacity of genistein supports the potential use of this isoflavone in antitumour therapies. In this regard, we recently reported that genistein potentiates apoptosis induction by the anti-leukaemic agent arsenic trioxide (ATO) via reactive oxygen species (ROS) generation and p38-MAPK activation. In the present study we analyze the action of agents sharing functional similarities with the isoflavone, namely 17-beta-estradiol, the DNA topoisomerase II poison etoposide, and the tyrosine kinase (PTK) inhibitors herbimycin A, epigallocatechin-3-gallate (EGCG) and adaphostin, in U937 and other human acute myeloid leukaemia cell lines. Co-treatment with 17-beta-estradiol or etoposide failed to stimul...

Effect of acute and chronic administration of progesterone, estrogen, FSH and LH on oxidant and antioxidant parameters in rat gastric tissue.

Chemico-Biological Interactions — Fri, 30 Oct 2009 21:54:05 +0100

This study was conducted to investigate whether gastro-protective and gastro-toxic effects of acute and chronic administration of progesterone, estrogen, FSH and LH were related to oxidant and antioxidant parameters. Chronic administration of progesterone at a low dose (1mg/kg), which probably could not stimulate progesterone receptors (PRs), inhibited oxidative stress of FSH in gastric tissue by suppressing FSH. Progesterone (5mg/kg) may have been caused oxidative stress as reflected by PR stimulation. FSH may have decreased antioxidant parameters and increased oxidant parameters via PRs. Chronic administration of low dose of estrogen (1mg/kg) inhibited LH and but could not stimulate alpha-2 adrenergic receptors, which resulted in oxidative stress in gastric tissue. The higher dose of est...

Anti-angiogenic actions of pyrrolidine dithiocarbamate, a nuclear factor kappa B inhibitor

Angiogenesis — Fri, 30 Oct 2009 18:32:00 +0100

In this study, we tested the anti-angiogenic properties of pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor, using established in vitro and ex vivo assays in human umbilical vein endothelial cells (HUVEC) and human metastatic RCC cell lines (ACHN and SN12K1). In vitro, PDTC inhibited proliferation, capillary tube formation, invasion and trans-differentiation of HUVEC. Ex vivo, PDTC blocked vessel sprouting from aortic explants and disrupted the integrity of pre-formed vessels. PDTC also inhibited the adhesion of HUVEC and RCC cells to substratum and inhibited their invasion. PDTC inhibited RCC-induced proliferation of HUVEC. Protein microarray demonstrated heterogenic actions in each cell line: in HUVEC, epidermal growth factor was significantly decreased; in ACHN, basic fibrob...

Trypanocidal drugs: mechanisms, resistance and new targets

Expert Reviews in Molecular Medicine — Fri, 30 Oct 2009 15:56:33 +0100

Review ArticlesShane R. Wilkinson, John M. Kelly, Expert Reviews in Molecular Medicine, Volume 11 , pp e31AbstractThe protozoan parasites Trypanosoma brucei and Trypanosoma cruzi are the causative agents of African trypanosomiasis and Chagas disease, respectively. These are debilitating infections that exert a considerable health burden on some of the poorest people on the planet. Treatment of trypanosome infections is dependent on a small number of drugs that have limited efficacy and can cause severe side effects. Here, we review the properties of these drugs and describe new findings on their modes of action and the mechanisms by which resistance can arise. We further outline how a greater understanding of parasite biology is being exploited in the search for novel chemotherapeutic agen...

Suppressing IL-32 in monocytes impairs the induction of the proinflammatory cytokines TNFalpha and IL-1beta.

Cytokine — Fri, 30 Oct 2009 00:00:00 +0100

Authors: Hong J, Bae S, Kang Y, Yoon D, Bai X, Chan ED, Azam T, Dinarello CA, Lee S, Her E, Rho G, Kim S Targeting major proinflammatory cytokines such as IL-1beta and TNFalpha is of great interest in patients with chronic inflammatory diseases, including rheumatoid arthritis, colitis, and psoriasis. The cytokine Interleukin (IL)-32 induces proinflammatory cytokines such as TNFalpha, IL-1beta, IL-6, and chemokines. We previously used an IL-32 ligand-affinity column to purify proteinase 3, which is abundantly expressed in neutrophil and monocytic leukocytes but not in other cell types, and found that IL-32 is mainly produced by monocytic leukocytes. This evidence suggested that silencing endogenous IL-32 by short hairpin RNA (shRNA) in monocytic cells might reveal the precise function o...

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Cloning and expression analysis of a pollen preferential rapid alkalinization factor gene, BoRALF1, from broccoli flowers.

Molecular Biology Reports — Fri, 30 Oct 2009 00:00:00 +0100

Authors: Zhang GY, Wu J, Wang XW Rapid alkalinization factors (RALFs) are recently reported active peptide hormones and are considered to play important roles in plant development. We previously identified a differentially expressed cDNA fragment between cabbage flower buds of sterility lines and its maintainer line, which showed significant homology to Arabidopsis RALFL9. The novel RALF cDNA (BoRALF1) was isolated from broccoli flower buds by EST assembly. The open reading frame (ORF) comprises 240 bp, encoding a small putative preprotein of 79 amino acids (molecular weight of 8.72 kDa and a pI of 7.8), which contains the mature polypeptide at its C terminus. BoRALF1 shares 70.3% identity with Arabidopsis RALFL9, but has only moderate similarity with functionally characterized RALFs (...

Leptin plays a catabolic role on articular cartilage.

Molecular Biology Reports — Fri, 30 Oct 2009 00:00:00 +0100

Authors: Bao JP, Chen WP, Feng J, Hu PF, Shi ZL, Wu LD Leptin has been shown to play a crucial role in the regulation of body weight. There is also evidence that this adipokine plays a key role in the process of osteoarthritis. However, the precise role of leptin on articular cartilage metabolism is not clear. We investigate the role of leptin on articular cartilage in vivo in this study. Recombinant rat leptin (100 mug) was injected into the knee joints of rats, 48 h later, messenger RNA (mRNA) expression and protein levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), cathepsin D, and collagen II from articular cartilage were analyzed by real-time quantitative polymerase chain reaction (PCR) and ...

In silico cloning, expression of Rieske-like apoprotein gene and protein subcellular localization in the Pacific oyster, Crassostrea gigas.

Molecular Biology Reports — Fri, 30 Oct 2009 00:00:00 +0100

Authors: He X, Zhang Y, Yu Z Rieske protein gene in the Pacific oyster Crassostrea gigas was obtained by in silico cloning for the first time, and its expression profiles and subcellular localization were determined, respectively. The full-length cDNA of Cgisp is 985 bp in length and contains a 5'- and 3'-untranslated regions of 35 and 161 bp, respectively, with an open reading frame of 786 bp encoding a protein of 262 amino acids. The predicted molecular weight of 30 kDa of Cgisp protein was verified by prokaryotic expression. Conserved Rieske [2Fe-2S] cluster binding sites and highly matched-pair tertiary structure with 3CWB_E (Gallus gallus) were revealed by homologous analysis and molecular modeling. Eleven putative SNP sites and two conserved hexapeptide sequences, box I (THLGC) a...

Targeted antitumor effect induced by hTERT promoter mediated ODC antisense adenovirus.

Molecular Biology Reports — Fri, 30 Oct 2009 00:00:00 +0100

Authors: Wang W, Jin B, Li W, Xu CX, Cui FA, Liu B, Yan YF, Liu XX, Wang XL The expression of Ornithine decarboxylase (ODC) which is the first key enzyme of polyamine biosynthesis is increased in cancer cells. We had blocked the polyamine synthesis pathway using the adenoviral-mediated antisense ODC in some cancer cells such as prostate cancers and colorectal cancers. These researches demonstrated that ODC antisense expression could inhibit tumor cell growth. In order to reach the goal of applying the targeting gene therapy in clinical practice, we cloned the antisense ODC RNA which was driven by cancer specific promoter (hTERT promoter; telomerase reverse transcriptase promoter) into the adenovirus vector (rAd-CMV-GFP-hTERTp-ODC). Human cancer cell lines (HepG2, Bel-7402, A549) and no...

Robust marking of photoreceptor cells and pinealocytes with several reporters under control of the Crx gene

Developmental Dynamics — Fri, 30 Oct 2009 00:00:00 +0100

Crx is a member of the Otx family of homeobox genes with expression restricted to vertebrate retinal photoreceptor and bipolar cells as well as the pinealocytes of the pineal organ. To facilitate the visualization of Crx-expressing cells, we generated transgenic mice expressing several reporters under the control of the Crx regulatory sequences present within a bacterial artificial chromosome (BAC). These mice expand the transgenic mouse collection, which uses photoreceptor regulatory elements for reporter gene expression by providing a broader repertoire of reporter genes. In addition, because Crx is expressed very soon after a cell fated to be a photoreceptor cell becomes postmitotic, they provide a means for early identification of immature photoreceptor cells. Developmental Dynamics, 2...

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Cyclic Nrarp mRNA expression is regulated by the somitic oscillator but Nrarp protein levels do not oscillate

Developmental Dynamics — Fri, 30 Oct 2009 00:00:00 +0100

Somites are formed progressively from the presomitic mesoderm (PSM) in a highly regulated process according to a strict periodicity driven by an oscillatory mechanism. The Notch and Wnt pathways are key components in the regulation of this somitic oscillator and data from Xenopus and zebrafish embryos indicate that the Notch-downstream target Nrarp participates in the regulation of both activities. We have analyzed Nrarp/nrarp-a expression in the PSM of chick, mouse and zebrafish embryos, and we show that it cycles in synchrony with other Notch regulated cyclic genes. In the mouse its transcription is both Wnt- and Notch-dependent, whereas in the chick and fish embryo it is simply Notch-dependent. Despite oscillating mRNA levels, Nrarp protein does not oscillate in the PSM. Finally, neithe...

Dorsal closure in Drosophila: cells cannot get out of the tight spot

BioEssays — Fri, 30 Oct 2009 00:00:00 +0100

Dorsal closure (DC), the closure of a hole in the dorsal epidermis of Drosophila embryos by the joining of opposing epithelial cell sheets, has been used as a model process to study the molecular and cellular mechanisms underlying epithelial spreading and wound healing. Recent studies have provided novel insights into how different tissues function cooperatively in this process. Specifically, they demonstrate a critical function of the epidermis surrounding the hole in modulating the behavior of the amnioserosa cells inside. These findings shed light not only on the mechanisms by which the behavior of different tissues is coordinated during DC, but also on the general mechanisms by which tissues interact to trigger global morphogenesis, an essential but yet poorly explored aspect of embryo...

Validation of reference genes for quantitative expression analysis by real-time RT-PCR in Saccharomyces cerevisiae

BMC Molecular Biology - Latest articles — Fri, 30 Oct 2009 00:00:00 +0100

Conclusions: In this work, we provided a set of genes that are suitable reference genes for quantitative gene expression analysis by real-time RT-PCR in yeast biological samples covering a large panel of physiological states. In contrast, we invalidated and discourage the use of ACT1 as well as other commonly used reference genes (PDA1, TDH3, RDN18, etc) as internal controls for quantitative gene expression analysis in yeast. (Source: BMC Molecular Biology - Latest articles)

Neutral push-pull chromophores for nonlinear optical imaging of cell membranes

RSC - Organic Biomolecular Chemistry — Fri, 30 Oct 2009 00:00:00 +0100

Cyril Barsu, Rouba Cheaib, Stephane Chambert, Yves Queneau, Olivier Maury, Davy Cottet, Hartmut Wege, Julien Douady, Yann Bretonniere, Chantal Andraud (Paper from Org. Biomol. Chem.) Cyril Barsu, Org. Biomol. Chem., 2010, DOI: 10.1039/b915654b To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

Mirabilins revisited: polyketide alkaloids from a southern Australian marine sponge, Clathria sp.

RSC - Organic Biomolecular Chemistry — Fri, 30 Oct 2009 00:00:00 +0100

Mohamed El-Naggar, Melissa Conte, Robert J. Capon (Paper from Org. Biomol. Chem.) Mohamed El-Naggar, Org. Biomol. Chem., 2010, DOI: 10.1039/b915624k To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)

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The metalloendopeptidase gene Pitrm1 is regulated by hedgehog signaling in the developing mouse limb and is expressed in muscle progenitors

Developmental Dynamics — Fri, 30 Oct 2009 00:00:00 +0100

Pitrm1 is a zinc metalloendopeptidase that has been implicated in Alzheimer's disease and mitochondrial peptide degradation, but to date no major role in embryonic development has been documented. In a screen for genes regulated by hedgehog signaling in the mouse limb, we showed that expression of Pitrm1 is upregulated in response to loss of the Gli3 transcription factor. Here we confirm spatial changes in Pitrm1 expression in the Gli3 mutant mouse limb and examine Pitrm1 expression in Shh null and Ptch1 conditional deletion mouse mutants. In wild-type mice, Pitrm1 is expressed in a number of developing tissues known to be patterned by Sonic hedgehog, including the limbs, face, cortex, hippocampus, cerebellum, tectum, sub-mandibular gland, lung, genital tubercle, hair follicles, and the en...

Synthetic cells and organelles: compartmentalization strategies

BioEssays — Fri, 30 Oct 2009 00:00:00 +0100

The recent development of RNA replicating protocells and capsules that enclose complex biosynthetic cascade reactions are encouraging signs that we are gradually getting better at mastering the complexity of biological systems. The road to truly cellular compartments is still very long, but concrete progress is being made. Compartmentalization is a crucial natural methodology to enable control over biological processes occurring within the living cell. In fact, compartmentalization has been considered by some theories to be instrumental in the creation of life. With the advancement of chemical biology, artificial compartments that can mimic the cell as a whole, or that can be regarded as cell organelles, have recently received much attention. The membrane between the inner and outer enviro...

Apoptosis: focus on sea urchin development

Apoptosis — Thu, 29 Oct 2009 19:51:28 +0100

Abstract It has been proposed that the apoptosis is an essential requirement for the evolution of all animals, in fact the apoptotic program is highly conserved from nematodes to mammals. Throughout development, apoptosis is employed by multicellular organisms to eliminate damaged or unnecessary cells. Here, we will discuss both developmental programmed cell death (PCD) under normal conditions and stress induced apoptosis, in sea urchin embryos. Sea urchin represent an excellent model system for studying embryogenesis and cellular processes involved in metamorphosis. PCD plays an essential role in sculpting and remodelling the embryos and larvae undergoing metamorphosis. Moreover, this marine organism directly interacts with its environment, and is susceptible to effects o...

Malignant peripheral nerve sheath tumour (MPNST): the clinical implications of cellular signalling pathways

Expert Reviews in Molecular Medicine — Thu, 29 Oct 2009 15:57:05 +0100

Review ArticlesDaniela Katz, Alexander Lazar, Dina Lev, Expert Reviews in Molecular Medicine, Volume 11 , pp e30AbstractMalignant peripheral nerve sheath tumour (MPNST) is a rare malignancy accounting for 3 13% of NF1 patients develop MPNSTs, which are the leading cause of NF1-related mortality. Surgical resection is the mainstay of MPNST clinical management. However, because of invasive growth, propensity to metastasise, and limited sensitivity to chemotherapy and radiation, MPNST has a guarded to poor prognosis. Five-year survival rates of only 20 50% indicate an urgent need for improved therapeutic approaches. Recent work in this field has identified several altered intracellular signal transduction cascades and deregulated tyrosine kinase receptors, posing the possibility of personalis...

Regulation of memory T cells by gammac cytokines.

Cytokine — Thu, 29 Oct 2009 00:00:00 +0100

Authors: Osborne LC, Abraham N T cells rely on a duality of TCR and gammac cytokine signals for development, activation and peripheral T cell homeostasis. Previous data had suggested that the requirements for CD4 and CD8 memory T cell regulation were qualitatively distinct, but emerging data has shown that the requirements for true antigen specific memory T cells are very similar between these two cell types. This review will focus on contributions made by members of the gammac cytokine family (IL-2, IL-4, IL-7, IL-15 and IL-21) to homeostasis of naïve, memory phenotype and antigen experienced memory T cells. PMID: 19879771 [PubMed - as supplied by publisher] (Source: Cytokine)

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TNFalpha and TGF-beta1 influence IL-18-induced IFNgamma production through regulation of IL-18 receptor and T-bet expression.

Cytokine — Thu, 29 Oct 2009 00:00:00 +0100

In this study, we demonstrate that in the dendritic precursor-like cell line KG-1, IFNgamma production induced by IL-18 is potentiated (>5-fold) by TNFalpha and completely suppressed by TGF-beta1. IL-18 stimulation rapidly activates different MAPK signalling pathways but only blocking of p38 activation alleviates IFNgamma production. The mechanism through which TNFalpha enhances IL-18 induced IFNgamma production is by promoting IL-18 receptor alpha-chain expression which results in higher levels of p38 activation and induces expression of T-bet, a transcriptional regulator of the IFNG gene. In contrast, TGF-beta1 rapidly suppresses IFNgamma production by limiting IL-18 receptor numbers at the cell surface and preventing induction of T-bet expression. TGF-beta1 experience by cells leads ...

Serum evaluation of soluble interferon-alpha/beta receptor and high-sensitivity C-reactive protein for diagnosis of the patients with gastrointestinal and hepatobiliary-pancreatic cancer.

Cytokine — Thu, 29 Oct 2009 00:00:00 +0100

Authors: Miyake K, Imura S, Nishioka M, Batmunkh E, Sugimoto K, Ohmoto Y, Shimada M Serum soluble interferon-alpha/beta receptor (sIFN-alpha/betaR) and high-sensitivity C-reactive protein (hs-CRP) levels were evaluated in the patients with gastrointestinal and hepatobiliary-pancreatic cancer. We compared the sensitivity and specificity of serum sIFN-alpha/betaR with that of serum hs-CRP and evaluated the two diagnostic parameters in combination. Serum sIFN-alpha/betaR levels were measured in 92 patients and 25 healthy individuals by enzyme-linked immunosorbent assay. The diagnoses were 37 cases of hepatocellular carcinoma, 17 cases of pancreatic cancer, 15 cases of colon cancer, 13 cases of biliary tract cancer, and 10 cases of gastric cancer. Serum levels of sIFN-alpha/betaR and hs-CR...

Nuclear applications of inorganic mass spectrometry.

Mass Spectrometry Reviews — Thu, 29 Oct 2009 00:00:00 +0100

Authors: De Laeter J There are several basic characteristics of mass spectrometry that are not always fully appreciated by the science community. These characteristics include the distinction between relative and absolute isotope abundances, and the influence of isotope fractionation on the accuracy of isotopic measurements. These characteristics can be illustrated in the field of nuclear physics with reference to the measurement of nuclear parameters, which involve the use of enriched isotopes, and to test models of s-, r-, and p-process nucleosynthesis. The power of isotope-dilution mass spectrometry (IDMS) to measure trace elements in primitive meteorites to produce accurate Solar System abundances has been essential to the development of nuclear astrophysics. The variety of mass sp...

Isthmin is a novel secreted angiogenesis inhibitor that inhibits tumor growth in mice.

J Cell Mol Med — Thu, 29 Oct 2009 00:00:00 +0100

Authors: Xiang W, Ke Z, Zhang Y, Cheng GH, Irwan ID, Sulochana KN, Potturi P, Wang Z, Yang H, Wang J, Zhuo L, Kini RM, Ge R Abstract Antiangiogenesis represents a promising therapeutic strategy for the treatment of various malignances. Isthmin is a gene highly expressed in the isthmus of the midbrain-hindbrain organizer in Xenopus with no known functions. It encodes a secreted 60 kDa protein containing a Thrombospondin Type 1 Repeat (TSR) domain in the central region and an Adhesion-associated domain in MUC4 and Other Proteins (AMOP) domain at the C-terminal. In this work, we demonstrate that isthmin is a novel angiogenesis inhibitor. Recombinant mouse isthmin inhibited endothelial cell (EC) capillary network formation on Matrigel through its C-terminal AMOP domain. It also suppressed ...

Phosphatidylinositol 3-kinase interacts with the glucocorticoid receptor upon TLR2 activation.

J Cell Mol Med — Thu, 29 Oct 2009 00:00:00 +0100

Authors: Arancibia S, Benítez D, Núñez LE, Jewell CM, Langjhar P, Candia E, Zapata-Torres G, Cidlowski JA, González MJ, Hermoso MA ABSTRACT Airway inflammation is a common condition where glucocorticoids (GC) are a well-established therapy. It has been demonstrated that GC stimulate components of innate immunity. Specifically, glucocorticoids up-regulate TLR2 expression and activation upon inflammatory stimuli; however, little is known about the signaling involved in this process. To determine the mechanism by which dexamethasone modulates TLR2-induced cytokine production this signaling pathway was monitored in a lung epithelial cell line exposed to the TLR2 synthetic agonist, Pam(3)-Cys-Ser-Lys(4). These experiments demonstrate that phosphatidylinositol 3-kinase (P...

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Serially heterotransplanted human prostate tumors as an experimental model.

J Cell Mol Med — Thu, 29 Oct 2009 00:00:00 +0100

Authors: Lopez-Barcons LA Abstract Preclinical research on prostate cancer (PC) therapies uses several models to represent the human disease accurately. A common model uses patient prostate tumor biopsies to develop a cell line by serially passaging and subsequent implantation, in immunodeficient mice. An alternative model is direct implantation of patient prostate tumor biopsies into immunodeficient mice, followed by serial passage in vivo. The purpose of this review is to compile data from the more than 30 years of human PC serial heterotransplantation research. Serially heterotransplanted tumors are characterized by evaluating the histopathology of the resulting heterotransplants, including cellular differentiation, karyotype, marker expression, hormone-sensitivity, cellular prolife...

Involvement of neuropeptide Y and its Y1 and Y5 receptors in maintaining self-renewal and proliferation of human embryonic stem cells.

J Cell Mol Med — Thu, 29 Oct 2009 00:00:00 +0100

Authors: Son MY, Kim MJ, Yu K, Koo DB, Cho YS Abstract Neuropeptide Y (NPY) and NPY receptors are widely expressed in various organs and cell types and have been shown to have pleiotropic functions. However, their presence or role in human embryonic stem cells (hESCs) remains unknown. We now show that undifferentiated hESCs primarily express NPY and its Y1 and Y5 receptors. Inhibition of NPY signaling using either the selective NPY Y1 or Y5 receptor antagonist reduces the maintenance of self-renewal and proliferation of undifferentiated hESCs. We also provide compelling evidence that exogenous NPY supports the long-term growth of undifferentiated hESCs in the absence of feeder cell factors using only knockout serum replacement media. In further, NPY facilitates the use of chemically-de...

Exendin-4 regulates pancreatic ABCA1 transcription via CaMKK/CaMKIV pathway.

J Cell Mol Med — Thu, 29 Oct 2009 00:00:00 +0100

CONCLUSIONS: Activation of the CaMKK/CaMKIV cascade by exendin-4 stimulated ABCA1 gene transcription, indicating that exendin-4 plays an important role in insulin secretion and cholesterol ester content in pancreatic beta cells. PMID: 19874424 [PubMed - as supplied by publisher] (Source: J Cell Mol Med)

Metformin attenuates ovarian cancer cell growth in an AMP- kinase dispensable manner.

J Cell Mol Med — Thu, 29 Oct 2009 00:00:00 +0100

Authors: Rattan R, Giri S, Hartmann L, Shridhar V ABSTRACT Metformin, the most widely used drug for type 2 diabetes activates AMP-activated protein kinase (AMPK), which regulates cellular energy metabolism. Here, we report that ovarian cell lines VOSE, A2780, CP70, C200, OV202, OVCAR3, SKOV3ip, PE01 and PE04 predominantly express -alpha1, -beta1, -gamma1 and -gamma2 isoforms of AMPK subunits. Our studies show that metformin treatment (1) significantly inhibited proliferation of diverse chemo-responsive and -resistant ovarian cancer cell lines (A2780, CP70, C200, OV202, OVCAR3, SKVO3ip, PE01 and PE04), (2) caused cell cycle arrest accompanied by decreased cyclin D1 and increased p21 protein expression, (3) activated AMPK in various ovarian cancer cell lines as evident from increased pho...

iTriplet, a rule-based nucleic acid sequence motif finder.

Algorithms for Molecular Biology : AMB — Thu, 29 Oct 2009 00:00:00 +0100

CONCLUSION: iTriplet is a novel rule-based combinatorial or enumerative motif finding method that is able to process highly degenerate and long motifs that have resisted analysis by other methods. In addition, iTriplet is distinguished from other methods of the same family by its parallelizability, which allows it to leverage the power of today's readily available high-performance computing systems. PMID: 19874606 [PubMed - as supplied by publisher] (Source: Algorithms for Molecular Biology : AMB)

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Proteomic-based refinement of Deinococcus deserti genome annotation reveals an unwonted use of non-canonical translation initiation codons.

Molecular and Cellular Proteomics : MCP — Thu, 29 Oct 2009 00:00:00 +0100

Authors: Baudet M, Ortet P, Gaillard JC, Fernandez B, Guérin P, Enjalbal C, Subra G, de Groot A, Barakat M, Dedieu A, Armengaud J Deinococcaceae are a family of extremely radiation tolerant bacteria that are currently subjected to numerous studies aimed at understanding the molecular mechanisms for such radiotolerance. To achieve a comprehensive and accurate annotation of the Deinococcus deserti genome, we performed an N-terminal-oriented characterization of its proteome. For this, we used a labeling reagent, N-Tris(2,4,6-trimethoxyphenyl)phosphonium acetyl succinimide (TMPP), to selectively derivatize protein N-termini. The large scale identification of TMPP-modified N-terminal-most peptides by shotgun liquid chromatography-tandem mass spectrometry analysis led to the validation ...

Inferring branching pathways in genome-scale metabolic networks

BMC Systems Biology - Latest articles — Thu, 29 Oct 2009 00:00:00 +0100

Conclusions: ReTrace is a useful method in metabolic path finding tasks, combining some of the best aspects in constraint-based and graph-theoretic methods. It finds use in a multitude of tasks ranging from metabolic engineering to metabolic reconstruction of recently sequenced organisms. (Source: BMC Systems Biology - Latest articles)

13C-metabolic flux ratio and novel carbon path analyses confirmed that Trichoderma reesei uses primarily the respirative pathway also on the preferred carbon source glucose

BMC Systems Biology - Latest articles — Thu, 29 Oct 2009 00:00:00 +0100

Conclusions: High similarity between the biosynthetic pathways of amino acids in T. reesei and yeast S. cerevisiae was concluded. In vivo flux distributions confirmed that T. reesei uses primarily the respirative pathway also when growing on the repressive carbon source glucose in contrast to Saccharomyces cerevisiae, which substantially diminishes the respirative pathway flux under glucose repression. (Source: BMC Systems Biology - Latest articles)

The crystal structure of an lll-configured depsipeptide substrate analogue bound to isopenicillin N synthase

RSC - Organic Biomolecular Chemistry — Thu, 29 Oct 2009 00:00:00 +0100

Wei Ge, Ian J. Clifton, Jeanette E. Stok, Robert M. Adlington, Jack E. Baldwin, Peter J. Rutledge (Paper from Org. Biomol. Chem.) Wei Ge, Org. Biomol. Chem., 2010, DOI: 10.1039/b910170e To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Organic Biomolecular Chemistry)