MedWorm: Molecular Biology

Enhanced treatment of articular cartilage defect of the knee by intra-articular injection of Bcl-xL-engineered mesenchymal stem cells in rabbit model

Journal of Tissue Engineering and Regenerative Medicine — Fri, 20 Nov 2009 00:00:00 +0100

We examined whether the transduction of an anti-apoptotic protein, Bcl-xL, into MSCs could prevent cell death and improve the implantation efficiency of MSCs in a rabbit model. Our current findings demonstrate that the group treated with Bcl-xL-engineered MSCs could improve cartilage healing both morphologically and histologically when compared with the controls. These results suggest that intra-articular injection of Bcl-xL-engineered MSCs is a potential non-invasive therapeutic method for effectively treating cartilage defects of the knee. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Journal of Tissue Engineering and Regenerative Medicine)

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The stability of imine-containing dynamic [2]rotaxanes to hydrolysis

RSC - Organic Biomolecular Chemistry — Fri, 20 Nov 2009 00:00:00 +0100

Ken Cham-Fai Leung, Wing-Yan Wong, Fabio Arico, Philip C. Haussmann, J. Fraser Stoddart (Paper from Org. Biomol. Chem.) Ken Cham-Fai Leung, Org. Biomol. Chem., 2010, DOI: 10.1039/b915864b 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)

Conditional gene deletion reveals functional redundancy of GABAB receptors in peripheral nociceptors in vivo

Molecular Pain — Thu, 19 Nov 2009 00:00:00 +0100

Conclusions: This study addressed contribution of GABAB receptors expressed on primary afferent nociceptive fibers to the modulation of pain. We observed that neither the development of acute and chronic pain nor the analgesic effects of a systematically-delivered GABAB agonist was significantly changed upon a specific deletion of GABAB receptors from peripheral nociceptive neurons in vivo. This lets us conclude that GABAB receptors in the peripheral nervous system play a less important role than those in the central nervous system in the regulation of pain. (Source: Molecular Pain)

Cerebrospinal fluid tau and ptau181 increase with cortical amyloid deposition in cognitively normal individuals: Implications for future clinical trials of Alzheimer's disease

EMBO Molecular Medicine — Thu, 19 Nov 2009 00:00:00 +0100

Alzheimer's disease (AD) pathology is estimated to develop many years before detectable cognitive decline. Fluid and imaging biomarkers may identify people in early symptomatic and even preclinical stages, possibly when potential treatments can best preserve cognitive function. We previously reported that cerebrospinal fluid (CSF) levels of amyloid-[beta]42 (A[beta]42) serve as an excellent marker for brain amyloid as detected by the amyloid tracer, Pittsburgh compound B (PIB). Using data from 189 cognitively normal participants, we now report a positive linear relationship between CSF tau/ptau181 (primary constituents of neurofibrillary tangles) with the amount of cortical amyloid. We observe a strong inverse relationship of cortical PIB binding with CSF A[beta]42 but not for plasma A[bet...

Diversification of the cullin family

BMC Evolutionary Biology - Latest articles — Thu, 19 Nov 2009 00:00:00 +0100

Conclusions: Most of the known types of cullin-containing ubiquitin ligase complexes are ancient. The available data suggest that, since the origin of eukaryotes, complex diversity has been mostly generated by combining closely related subunits, while radical innovations, giving rise to novel types of complexes, have been scarce. However, several protist groups not examined so far contain highly divergent cullins, indicating that additional types of complexes may exist. (Source: BMC Evolutionary Biology - Latest articles)

Development of a new microwave-assisted cleavable backbone amide linker (BAL): a comparative study

RSC - Organic Biomolecular Chemistry — Thu, 19 Nov 2009 00:00:00 +0100

Stijn Claerhout, Thibault Duchene, Dirk Tourwe, Erik V. Van der Eycken (Communication from Org. Biomol. Chem.) Stijn Claerhout, Org. Biomol. Chem., 2010, DOI: 10.1039/b919365k 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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Phosphorane intermediate vs. leaving group stabilization by intramolecular hydrogen bonding in the cleavage of trinucleoside monophosphates: implications for understanding catalysis by the large ribozymes

RSC - Organic Biomolecular Chemistry — Thu, 19 Nov 2009 00:00:00 +0100

Tuomas Lonnberg, Maarit Laine (Paper from Org. Biomol. Chem.) Tuomas Lonnberg, Org. Biomol. Chem., 2010, DOI: 10.1039/b912042d 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)

Study on the selectivity in the electrophilic monofluorination of 2,3-allenoates with Selectfluor[trade mark sign]: an efficient synthesis of 4-fluoro-2(5H)-furanones and 3-fluoro-4-oxo-2(E)-alkenoates

RSC - Organic Biomolecular Chemistry — Thu, 19 Nov 2009 00:00:00 +0100

Bo Lu, Chunling Fu, Shengming Ma (Paper from Org. Biomol. Chem.) Bo Lu, Org. Biomol. Chem., 2010, DOI: 10.1039/b917793k 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)

Translational advances and novel therapies for pancreatic ductal adenocarcinoma: hope or hype?

Expert Reviews in Molecular Medicine — Wed, 18 Nov 2009 16:16:31 +0100

Review ArticlesSreenivasa Chandana, Daruka Mahadevan, Expert Reviews in Molecular Medicine, Volume 11 , pp e34AbstractBiological complexity, inaccessible anatomical location, nonspecific symptoms, lack of a screening biomarker, advanced disease at presentation and drug resistance epitomise pancreatic ductal adenocarcinoma (PDA) as a poor-prognosis, lethal disease. Twenty-five years of research (basic, translational and clinical) have barely made strides to improve survival, mainly because of a fundamental lack of knowledge of the biological processes initiating and propagating PDA. However, isolation of pancreas cancer stem cells or progenitors, whole-genome sequencing for driver mutations, advances in functional imaging, mechanistic dissection of the desmoplastic reaction and novel target...

Tissue persistence of fumonisin B1 in ducks and after exposure to a diet containing the maximum European tolerance for fumonisins in avian feeds.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:23:22 +0100

Authors: Tardieu D, Bailly JD, Benlashehr I, Auby A, Jouglar JY, Guerre P Toxicity and persistence of fumonisin B1 (FB1) in liver, kidney and muscle were investigated in ducks fed 5, 10 and 20mg FB1+FB2/kg feed during force-feeding. Mortality and signs of toxicity were only obtained with 20mg/kg, whereas an increased Sa/So ratio was observed from 5mg/kg on. Persistence of FB1 was only found in liver (16 and 20 microg FB1/kg liver in ducks fed 10 and 20 mg FB1+FB2/kg feed, respectively). Toxicokinetic studies were conducted by the intravenous route (IV, single dose: 10mg FB1/kg body weight) and the oral route (single dose: 100mg FB1/kg body weight), in growing ducks and in ducks during force-feeding. After IV administration, serum concentration-time curves were described by a two-compar...

Glucocorticoid and adrenalectomy effects on the rat aryl hydrocarbon receptor pathway depend on the dosing regimen and post-surgical time.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:23:19 +0100

Authors: Mullen Grey AK, Riddick DS The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the effects of aromatic hydrocarbons, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3-methylcholanthrene (MC); the prototypical response is induction of drug-metabolizing enzymes. Factors that regulate AHR levels in vivo are poorly understood and it is also not clear how AHR levels affect aromatic hydrocarbon responsiveness. Our interest in pituitary-dependent regulation of AHR levels was prompted by two findings from our laboratory: (1) hypophysectomized rats have reduced hepatic levels of AHR protein; and (2) glucocorticoids increase AHR expression and aromatic hydrocarbon responsiveness in rodent hepatoma cells. To study whether adrenalectomy and glucoco...

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l-Arginine supplementation induces glutathione synthesis in interscapular brown adipose tissue through activation of glutamate-cysteine ligase expression: The role of nitric oxide.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:23:16 +0100

We examined whether nitric oxide (NO) in vivo could induce interscapular brown adipose tissue (IBAT) glutathione synthesis. Data show that NO induces in vivo IBAT glutathione synthesis through activation of glutamate-cysteine ligase (GCL) mRNA and protein expression. This NO effect appeared to be mediated by nuclear factor-kappaB (NF-kappaB) activation. We have also observed a complex series of in vivo cellular responses during chronic inhibition of NO synthesis, suggesting that regulatory pathways unrelated to GCL alteration underlie glutathione level increase induced by N(omega)-nitro-l-arginine methyl ester (l-NAME). In general, glutathione synthesis in IBAT seemed to be finely tuned by NO to provide glutathione for either mediating the effects of NO, or for preventing potential nitrosa...

(-)-Epigallocatechin gallate prevents carbon tetrachloride-induced rat hepatic fibrosis by inhibiting the expression of the PDGFRbeta and IGF-1R.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:23:14 +0100

Authors: Yasuda Y, Shimizu M, Sakai H, Iwasa J, Kubota M, Adachi S, Osawa Y, Tsurumi H, Hara Y, Moriwaki H Hepatic fibrosis is a major complication of various chronic liver diseases. Activated hepatic stellate cells (HSCs) play a critical role in the development of liver fibrosis and the axis of platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR), a member of receptor tyrosine kinases (RTKs), is closely associated with the activation of HSC. Insulin-like growth factor (IGF)-1 receptor (IGF-1R), which also belongs to RTKs, interacts with the PDGF/PDGFR axis, thereby cooperatively promoting hepatic fibrosis. We herein examined the effects of (-)-epigallocatechin gallate (EGCG), which inhibits the activation of several types of RTKs, on the development of rat liver fibrosis induce...

Antioxidant activity and free radical scavenging reactions of hydroxybenzyl alcohols. Biochemical and pulse radiolysis studies.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:23:11 +0100

Authors: Dhiman SB, Kamat JP, Naik DB Comparative studies on free radical scavenging by isomers of hydroxybenzyl alcohols (HBAs) were carried out to understand the molecular mechanisms involved in the antioxidant action. Using rat liver mitochondria as model systems, we have examined the radioprotective and antioxidant effects of hydroxybenzyl alcohols. Apart from their ability to scavenge free radicals and ferric reducing power, HBAs have shown good protection against radiation and oxidative stress. Using peroxyl radicals as initiator of reactive oxygen species (ROS), studies were carried out to evaluate antioxidant properties of HBAs against rat liver mitochondrial membrane components such as lipid and protein. Our results show that HBAs are potent inhibitor of lipid peroxidation and...

Fetal arsenic exposure appears to facilitate endocrine disruption by postnatal diethylstilbestrol in neonatal mouse adrenal.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:23:09 +0100

Authors: Liu J, Yu L, Coppin JF, Tokar EJ, Diwan BA, Waalkes MP Fetal exposure of mice to arsenic and subsequent postnatal diethylstilbestrol (DES) facilitates production of urogenital system and liver tumors in the offspring when they reach adulthood. The adrenal is a target of endocrine disruption that could influence tumor formation at other sites. Thus, we examined possible fetal arsenic-induced adrenal effects as a potential basis of arsenic enhancement of DES carcinogenesis. Pregnant CD1 mice were given drinking water containing 85 ppm arsenic as sodium arsenite or unaltered water from day 8 to day 18 of gestation and were allowed to deliver normally. Groups of offspring were subsequently injected s.c. on postpartum days 1-5 with DES (2 microg/pup/day) and killed on postnatal day...

Novel nitro-oxy derivatives of celecoxib for the regulation of colon cancer cell growth.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:23:06 +0100

Authors: Bozzo F, Bassignana A, Lazzarato L, Boschi D, Gasco A, Bocca C, Miglietta A Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) developed as a selective inhibitor of cyclooxygenase-2 (COX-2). Despite the associated cardiovascular toxicity risk, celecoxib has been found to be effective in reducing cancer risk in animal and human studies. In the present study the antiproliferative activity of novel nitro-oxy-methyl substituted analogues of celecoxib (NO-cel), potentially less cardiotoxic, has been investigated in vitro on human colon cancer cells and compared with action of the parent drug. Moreover, experiments were performed in order to evaluate whether COX-2 pharmacological inhibition may affect beta-catenin/E-cadherin signalling pathway. All the tested analogues of c...

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Dual action of phenylarsine oxide on the glucose transport activity of GLUT1.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:23:03 +0100

This study investigated the effects of PAO on glucose uptake in L929 fibroblast cells, cells, which express only GLUT1. The data presented here reveal a dual effect of PAO. At low concentrations or short exposure times PAO stimulated glucose uptake reaching a peak activation of about 400% at 3 microM. At higher concentrations (40 microM), PAO clearly inhibited glucose uptake. At intermediate concentrations (10 microM), PAO had no effect under basal conditions but completely inhibited activation of glucose uptake by glucose deprivation and partially inhibited methylene blue-stimulated glucose uptake. PAO increased the specific binding of cytochalasin B to GLUT1 suggesting a direct interaction with the transporter. These data are most consistent with PAO interacting with multiple proteins th...

Chronic myelogenous leukemia and benzene exposure: a systematic review and meta-analysis of the case-control literature.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:23:01 +0100

Authors: Lamm SH, Engel A, Joshi KP, Byrd DM, Chen R Benzene exposure is well demonstrated as a cause of acute myelogenous leukemia, but not of chronic myelogenous leukemia. Previous literature reviews based on case series and cohort studies have not shown an association. We have now conducted a literature search for case-control studies that examine the association between benzene exposure and chronic myelogenous leukemia. Six case-control studies have been found. These derive from occupational groups, cancer registries, and a clinical laboratory. Their exposure ascertainments are all based on job histories, job-exposure matricies, or industrial hygiene data. The odds ratios (ORs) for individual studies range from 0.73 to 1.2. The pooled OR is 1.003 with 95% confidence interval (CI) o...

Modulatory role of lipoic acid on lipopolysaccharide-induced oxidative stress in adult rat Sertoli cells in vitro.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:22:58 +0100

Authors: Aly HA, Lightfoot DA, El-Shemy HA Inflammatory reactions to microbial infections may cause male infertility. The mechanisms of inhibition of spermatogenesis can be studied in vitro using rat Sertoli cells. Bacterial lipopolysaccharides (LPS) induce acute inflammations. So LPS treated Sertoli cells can be used to test for new therapeutic compounds. The present study aimed to investigate the protective efficacy of dl-alpha-lipoic acid (LA) on lipopolysaccharide (LPS)-induced oxidative stress in adult rat Sertoli cells. Sertoli cells were divided into 4 groups. Group I served as a control incubated with water (vehicle). Groups II and IV were incubated with 100 microM LA for 24h before incubating Groups III and IV with 50 microg/ml lipopolysaccharide (LPS) for 12h. In Group III ce...

Superoxide anion mediated mitochondrial dysfunction leads to hepatocyte apoptosis preferentially in the periportal region during copper toxicity in rats.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:22:56 +0100

Authors: Roy DN, Mandal S, Sen G, Biswas T Chronic exposure to copper induces hepatocellular apoptosis with greater injury in the periportal region compared to the perivenous region. Here we have identified the factors responsible for the development of regional damage in the liver under in vivo conditions. Enhanced production of reactive oxygen species (ROS) with predominance of superoxide radical (O(2)(-)) indicates the contribution of redox imbalance in the process. This may be linked with copper catalyzed oxidation of GSH to GSSG resulting in the generation of O(2)(-). Downregulation of Cu-Zn SOD in consequence of the degradation of this enzyme, causes decreased dismutation of O(2)(-), that further contributes to the enhanced level of O(2)(-) in the periportal region. Decreased fun...

Oxaliplatin-induced gamma-H2AX activation via both p53-dependent and -independent pathways but is not associated with cell cycle arrest in human colorectal cancer cells.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:22:53 +0100

In this study, we investigated the roles of p53 and gamma-H2AX following oxaliplatin treatment, as they are important effector proteins for apoptosis and DSB repair, respectively. Both phosphorylated-p53 (Ser-15) and gamma-H2AX were up-regulated and accumulated in the nuclei of p53-wild type human colorectal cancer HCT116 cells after exposure to oxaliplatin. Concomitantly, oxaliplatin-induced G2/M arrest was associated with a reduction in both cyclin B1 expression and phosphorylated-CDC2 (Thr-161). Release of G2/M arrest by caffeine was accompanied by a decrease in the levels of p53/p21; however, gamma-H2AX levels were unchanged. Furthermore, inhibition of p53 phosphorylation by pifithrin-alpha was sufficient to reduce the oxaliplatin-induced up-regulation of gamma-H2AX and apoptosis. Oxal...

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Synergistic increases of metabolism and oxidation-reduction genes on their expression after combined treatment with a CYP1A inducer and andrographolide.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:22:51 +0100

Authors: Chatuphonprasert W, Jarukamjorn K, Kondo S, Nemoto N We previously reported that andrographolide greatly enhanced the expression of CYP1A1. Since andrographolide is a major constituent of Andrographis paniculata, which has been employed for centuries in Asia and Europe as a folk remedy, we further analyzed genes whose expression was modified by andrographolide using primary-cultured mouse hepatocytes in a microarray assay. With the threshold for modification set at 2-fold, andrographolide up-regulated 18 genes among 28,853 genes, most of them related to metabolism/oxidation/reduction. Meanwhile, 5 genes, related to protein binding or calcium ion binding, were down-regulated. A combination of beta-naphthoflavone (beta-NF), a CYP1A inducer, and andrographolide modified the expre...

Inhibition of proliferation of a hepatoma cell line by fucoxanthin in relation to cell cycle arrest and enhanced gap junctional intercellular communication.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:22:48 +0100

In this study, we hypothesized that fucoxanthin may cause cell cycle arrest and enhance gap junctional intercellular communication (GJIC) in SK-Hep-1 human hepatoma cells. Data revealed that fucoxanthin (1-20microM) strongly and concentration-dependently inhibited the proliferation of SK-Hep-1 cells at 24h of incubation, whereas fucoxanthin facilitated the growth of a murine embryonic hepatic (BNL CL.2) cells at 24h of incubation and only slightly slowed the cell proliferation at 48h. In SK-Hep-1 cells, fucoxanthin caused cell cycle arrest at G0/G1 phase and induced cell apoptosis, as evidenced by increased subG1 cells and induction of DNA strand breaks. Using scrape loading-dye-transfer assay, fucoxanthin was found to significantly enhance GJIC of SK-Hep-1 cells without affecting that of ...

Altered pH homeostasis modulates the glutathione peroxidase mimics and other antioxidant properties of diphenyl diselenide.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:22:46 +0100

Authors: Ogunmoyole T, Rocha JB, Okoronkwo AE, Kade IJ Recent evidences have shown that the in vivo antioxidant chemistry of organoselenium compounds such as diphenyl diselenide (DPDS) is complex and it is not completely understood. The complexity is partly due to the fact that DPDS is generally thought to exert its antioxidant action by mimicking glutathione peroxidase (GPx) with concomitant utilization of glutathione (GSH) in vitro. In contrast to in vitro data, we recently observed that DPDS increases rather than diminish GSH levels in diabetic models. The present study therefore sought to investigate a possible change in the antioxidant mechanisms of DPDS in changing physiological pH that may be associated with hyperglycaemia. The results show that in all the pHs tested (acidic, ne...

Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:22:43 +0100

Authors: Elingold I, Taboas MI, Casanova MB, Galleano M, Silva RS, Menna-Barreto RF, Ventura Pinto A, de Castro SL, Costa LE, Dubin M In order to elucidate the effect on mammal systems of new derivatives from 2-hydroxy-3-allyl-naphthoquinone, alpha-iodinated naphthofuranquinone (NPPN-3223), beta-iodinated naphthofuranquinone (NPPN-3222) and beta-methyl naphthofuranquinone (NPPN-3226) synthesized as possible trypanocidal agents, their effect on rat liver microsomal lipid peroxidation was investigated. They (a) inhibited NADPH-dependent, iron-catalyzed microsomal rat liver lipid peroxidation; (b) did not inhibit the tert-butyl hydroperoxide-dependent lipid peroxidation; (c) did not inhibit ascorbate-lipid peroxidation with the exception of NPPN-3226 which did inhibit it; (d) stimulated N...

Cytotoxic, cytoprotective and antioxidant activities of resveratrol and analogues in C6 astroglioma cells in vitro.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:22:40 +0100

Authors: Rüweler M, Gülden M, Maser E, Murias M, Seibert H Resveratrol (3,4',5-trans-trihydroxystilbene) and other hydroxystilbenes exhibit in vitro antioxidant as well as prooxidant effects. The antioxidant properties are assumed to enable these compounds to protect cells from oxidative damage. The prooxidant effects are held likely to be responsible for their cytotoxic, anti-proliferative or pro-apoptotic effects observed in vitro. Regarding antioxidant/prooxidant activities in the past various studies were performed aiming at defining structure-activity relationships for hydroxystilbenes using cell-free systems. In the present study cultured C6 glioma cells were used in order to investigate the relationship between the antioxidant, cytoprotective and cytotoxic activities o...

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Non-dioxin-like-PCBs phosphorylate Mdm2 at Ser166 and attenuate the p53 response in HepG2 cells.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:22:38 +0100

In this study we investigated the effects of 20 NDL-PCBs (concentration range 0.01-10microM) on pMdm2 Ser166, pErk Tyr204 and p53 on HepG2 cells. Six of the NDL-PCBs induced pErk Tyr204 and pMdm3 Ser166. This effect correlated with lowered basal levels of p53, as well as with an attenuated p53 response induced by etoposide and leptomycin B. Similar effects were induced by TCDD and the DL-PCB 126. We conclude that both DL-PCBs and NDL-PCBs in low concentrations can induce alterations in p53 signaling and that these effects can be correlated to rat liver carcinogenesis. PMID: 19751709 [PubMed - indexed for MEDLINE] (Source: Chemico-Biological Interactions)

Herb-drug interaction of silymarin or silibinin on the pharmacokinetics of trazodone in rats.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:22:35 +0100

In conclusion, the present study finds no marked effects of silymarin and silibinin on the pharmacokinetics of trazodone under normal daily doses and the relative safety of taking the herb with trazodone. PMID: 19765569 [PubMed - indexed for MEDLINE] (Source: Chemico-Biological Interactions)

Hyper- and hypo-induction of cytochrome P450 activities with Aroclor 1254 and 3-methylcholanthrene in Cyp1a2(-/-) mice.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:22:32 +0100

Authors: Barker ML, Hathaway LB, Arch DD, Westbroek ML, Kushner JP, Phillips JD, Franklin MR The response of hepatic mono-oxygenase activities to Aroclor 1254 or 3-methylcholanthrene was investigated in wild-type and Cyp1a2(-/-) mice. Cytochrome P450 concentrations were similar in naïve Cyp1a2(-/-) and wild-type mice. There was no difference between naïve wild-type and Cyp1a2(-/-) animals in 7-ethoxyresorufin and 7-ethoxy-4-trifluoromethylcoumarin dealkylase activities, nor was the induction response after 3-methylcholanthrene any different between the two genotypes. However, both activities were induced to a higher extent in Cyp1a2(-/-) mice after Aroclor 1254. In contrast, 7-pentoxyresorufin dealkylation activity was lower in Cyp1a2(-/-) mice and this differential was maint...

Effect of permethrin insecticide on rat polymorphonuclear neutrophils.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:22:27 +0100

In conclusion, immunotoxicity of permethrin measured in rats could prompt future studies on the consequences of chronic insecticide exposure. PMID: 19772857 [PubMed - indexed for MEDLINE] (Source: Chemico-Biological Interactions)

Effect of alpha tocopherol acetate in Walker 256/B cells-induced oxidative damage in a rat model of breast cancer skeletal metastases.

Chemico-Biological Interactions — Wed, 18 Nov 2009 10:22:24 +0100

Authors: Badraoui R, Blouin S, Moreau MF, Gallois Y, Rebai T, Sahnoun Z, Baslé M, Chappard D The pathophysiological changes and the oxidative-antioxidative status were evaluated in the bone microenvironment of rat inoculated with Walker 256/B mammary gland carcinoma cells, and used alpha-tocopherol acetate (ATA) as a countermeasure. Walker 256/B cells were injected into the right femora of aged male rats. Animals were randomized into three groups: 12 rats were injected with saline (control group); 14 rats were injected with Walker 256/B cells (5x10(4)) in the medullar cavity (W256 group); 14 rats were inoculated with Walker 256/B cells and treated with ATA (45mg/kg BW) (W256+ATA group). After 20 days, rats were euthanized and the femurs were radiographed. Micro architectural param...

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Fragment C of tetanus toxin, more than a carrier. Novel perspectives in non-viral ALS gene therapy

Journal of Molecular Medicine — Wed, 18 Nov 2009 09:30:18 +0100

Abstract The non-toxic carboxy-terminal fragment of tetanus toxin heavy chain (TTC) has been implicated in the activation of cascades responsible for trophic actions and neuroprotection by inhibition of apoptosis. Previous in vitro studies have described signalling pathways that underlie the administration of TTC to neurons. We investigated whether these properties were maintained in a mouse model of neurodegenerative disease. Naked DNA encoding for TTC was injected intramuscularly and neuromuscular function and clinical behaviour were monitored until endstage in the transgenic SOD1G93A mouse model that expresses a mutant variant of human superoxide dismutase 1 (SOD1). Our results indicate that TTC treatment ameliorated the decline of hindlimb muscle innervation, significan...

A novel porcine gene, MAPKAPK3, is differentially expressed in the pituitary gland from mini-type Diannan small-ear pigs and large-type Diannan small-ear pigs.

Molecular Biology Reports — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Yonggang L The mRNA differential display technique was performed to investigate the differences of gene expression in the pituitary gland from mini-type Diannan small-ear pigs and large-type Diannan small-ear pigs. One novel gene differentially expressed was identified through semi-quantitative RT-PCR and its cDNA complete sequence was then obtained using the rapid amplification of cDNA ends (RACE) method. Nucleotide sequence of the gene is not homologous to any of the known porcine genes. The sequence analysis revealed that the open reading frame of this gene encodes a protein of 384 amino acids has high homology with the mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3) of eight species-cattle (96%), horse (96%), rhesus monkey (93%), rabbit (77%), human ...

Effective relief of neuropathic pain by adeno-associated virus-mediated expression of a small hairpin RNA against GTP cyclohydrolase 1

Molecular Pain — Wed, 18 Nov 2009 00:00:00 +0100

Conclusions: Therefore, the data suggests that GCH1 levels can be reduced by introducing rAAV-shGCH1, leading to pain relief. Based on the results, we propose that GCH1 modulation may be developed as a clinically applicable gene therapy strategy to treat neuropathic pain. (Source: Molecular Pain)

Different forms of glycine- and GABAA-receptor mediated inhibitory synaptic transmission in mouse superficial and deep dorsal horn neurons

Molecular Pain — Wed, 18 Nov 2009 00:00:00 +0100

Conclusions: Together these data show that Gly- and GABAARs with clearly differing physiological properties and cannabinoid-sensitivity contribute to fast synaptic inhibition in mouse SDH and DDH. (Source: Molecular Pain)

Oxaliplatin-induced loss of phosphorylated heavy neurofilament subunit neuronal immunoreactivity in rat DRG tissue

Molecular Pain — Wed, 18 Nov 2009 00:00:00 +0100

Background: Oxaliplatin and related chemotherapeutic drugs cause painful chronic peripheral neuropathies in cancer patients. We investigated changes in neuronal size profiles and neurofilament immunoreactivity in L5 dorsal root ganglion (DRG) tissue of adult female Wistar rats after multiple-dose treatment with oxaliplatin, cisplatin, carboplatin or paclitaxel. Results: After treatment with oxaliplatin, phosphorylated neurofilament heavy subunit (pNF-H) immunoreactivity was reduced in neuronal cell bodies, but unchanged in nerve fibres, of the L5 DRG. Morphometric analysis confirmed significant changes in the number (-75%; P (Source: Molecular Pain)

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Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes

BMC Evolutionary Biology - Latest articles — Wed, 18 Nov 2009 00:00:00 +0100

Conclusions: This study challenges the current view on the classification, origin and evolution of the cystatin superfamily and provides valuable insights into their functional diversification. The findings of this comprehensive study provide guides for future structural and evolutionary studies of the cystatin superfamily as well as of other protease inhibitors and proteases. (Source: BMC Evolutionary Biology - Latest articles)

Direct fixation of [11C]-CO2 by amines: formation of [11C-carbonyl]-methylcarbamates

RSC - Organic Biomolecular Chemistry — Wed, 18 Nov 2009 00:00:00 +0100

Alan A. Wilson, Armando Garcia, Sylvain Houle, Neil Vasdev (Paper from Org. Biomol. Chem.) Alan A. Wilson, Org. Biomol. Chem., 2010, DOI: 10.1039/b916419g 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)

Imaging of Gadolinium Spatial Distribution in Tumor Tissue by Laser Ablation Inductively Coupled Plasma Mass Spectrometry

Molecular Imaging and Biology — Tue, 17 Nov 2009 23:39:55 +0100

Conclusions We have demonstrated, in a novel manner, the use of LA–ICP–MS for the spatial detection of Gd in tumor tissue. LA–ICP–MS is valuable in providing spatio-specific information of MRI contrast agents and more importantly Gd in tumor tissue. Content Type Journal ArticleCategory Brief ArticleDOI 10.1007/s11307-009-0282-4Authors Nazila Kamaly, Hammersmith Hospital, Imperial College London Imaging Sciences Department, Metabolic and Molecular Imaging Group, MRC Clinical Sciences Center London W12 0NN UKJohn A. Pugh, University of Sheffield Department of Chemistry, Center for Analytical Sciences Sheffield UKTammy L. Kalber, Hammersmith Hospital, Imperial College London Imaging Sciences Department, Metabolic and Molecular Imaging Group, MRC Clinical Sciences ...

High Impact of 18F-FDG-PET on Management and Prognostic Stratification of Newly Diagnosed Small Cell Lung Cancer

Molecular Imaging and Biology — Tue, 17 Nov 2009 23:39:54 +0100

Conclusion PET had a major impact on stage classification, management, and prognostic stratification of newly diagnosed SCLC. Content Type Journal ArticleCategory Research ArticleDOI 10.1007/s11307-009-0295-zAuthors Arun Azad, Ludwig Institute Oncology Unit, Austin Health Heidelberg AustraliaFiona Chionh, Ludwig Institute Oncology Unit, Austin Health Heidelberg AustraliaAndrew M. Scott, Centre for Positron Emission Tomography, Austin Health Melbourne AustraliaSzeting T. Lee, Centre for Positron Emission Tomography, Austin Health Melbourne AustraliaSam U. Berlangieri, Centre for Positron Emission Tomography, Austin Health Melbourne AustraliaShane White, Ludwig Institute Oncology Unit, Austin Health Heidelberg AustraliaPaul L. Mitchell, Ludwig Institute Oncology Unit, Aus...

Fetal microchimerism: the cellular and immunological legacy of pregnancy

Expert Reviews in Molecular Medicine — Tue, 17 Nov 2009 16:15:21 +0100

Review ArticlesDavid M. Lissauer, Karen P. Piper, Paul A.H. Moss, Mark D. Kilby, Expert Reviews in Molecular Medicine, Volume 11 , pp e33AbstractDuring pregnancy there is transplacental traffic of fetal cells into the maternal circulation. Remarkably, cells of fetal origin can then persist for decades in the mother and are detectable in the circulation and in a wide range of tissues. Maternal CD8 T cell responses directed against fetal antigens can also be detected following pregnancy. However, the impact that the persistence of allogenic cells of fetal origin and the maternal immune response towards them has on the mother's health remains unclear and is the subject of considerable investigation. The potentially harmful effects of fetal microchimerism include an association with autoimmune...

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BioEssays 12/2009

BioEssays — Tue, 17 Nov 2009 16:14:35 +0100

Cover Photograph: 3D computer graphics of DNA transcription in eukaryotes. Previously determined molecular structures were placed in this scene according to available experimental data and rendered using the Blender software (). Please see article by Wong, Winn and Mozziconacci . (Source: BioEssays)

Identification of an exonic splicing silencer in exon 6A of the human VEGF gene

BMC Molecular Biology - Latest articles — Tue, 17 Nov 2009 00:00:00 +0100

Conclusion: This work establishes the identity of cis sequences that regulate alternative VEGFsplicing and dictate the relative expression levels of VEGF isoforms. (Source: BMC Molecular Biology - Latest articles)

DASMiner: discovering and integrating data from DAS sources

BMC Systems Biology - Latest articles — Tue, 17 Nov 2009 00:00:00 +0100

Conclusions: The support of the DAS protocol allows that hundreds of molecular biology databases to be treated as a federated, online collection of resources. DASMiner enables full exploration of these resources, and can be used to deploy applications and create integrated views of biological systems using the information deposited in DAS repositories. (Source: BMC Systems Biology - Latest articles)

1,1[prime or minute]-Binaphthyl-based imidazolium chemosensors for highly selective recognition of tryptophan in aqueous solutions

RSC - Organic Biomolecular Chemistry — Tue, 17 Nov 2009 00:00:00 +0100

Li Yang, Song Qin, Xiaoyu Su, Fei Yang, Jingsong You, Changwei Hu, Rugang Xie, Jingbo Lan (Paper from Org. Biomol. Chem.) Li Yang, Org. Biomol. Chem., 2010, DOI: 10.1039/b908540h 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)

Abstracts from the Proceedings of the XXVII National Conference of Cytometry

Cytometry Part A — Tue, 17 Nov 2009 00:00:00 +0100

No abstract. (Source: Cytometry Part A)

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Coming next month:

BioEssays — Tue, 17 Nov 2009 00:00:00 +0100

No Abstract. (Source: BioEssays)

Nature of methods in science: technology driven science versus science driven technology

BioEssays — Tue, 17 Nov 2009 00:00:00 +0100

No Abstract. (Source: BioEssays)

The Dictionary of Genomics, Transcriptomics, and Proteomics

BioEssays — Tue, 17 Nov 2009 00:00:00 +0100

No Abstract. (Source: BioEssays)

Transcription-blocking DNA damage in aging: a mechanism for hormesis

BioEssays — Tue, 17 Nov 2009 00:00:00 +0100

Recent evidence from studies on DNA repair systems that are implicated in accelerated aging syndromes, have revealed a mechanism through which low levels of persistent damage might exert beneficial effects for both cancer prevention and longevity assurance. Beneficial effects of adaptive responses to low doses of insults that in higher concentrations show adverse effects are generally referred to as hormesis. There are numerous examples of hormetic effects ranging from mild stresses of irradiation to heat stress, hypergravity, pro-oxidants, or food restriction. Although the notion of hormesis is supported by many observations in various organisms, at least two major caveats have thus far prevented the application of hormesis for disease prevention in humans. First, the very nature of horme...

Thinking in continua: beyond the "adaptive radiation" metaphor

BioEssays — Tue, 17 Nov 2009 00:00:00 +0100

"Adaptive radiation" is an evocative metaphor for explosive evolutionary divergence, which for over 100 years has given a powerful heuristic to countless scientists working on all types of organisms at all phylogenetic levels. However, success has come at the price of making "adaptive radiation" so vague that it can no longer reflect the detailed results yielded by powerful new phylogeny-based techniques that quantify continuous adaptive radiation variables such as speciation rate, phylogenetic tree shape, and morphological diversity. Attempts to shoehorn the results of these techniques into categorical "adaptive radiation: yes/no" schemes lead to reification, in which arbitrary quantitative thresholds are regarded as real. Our account of the life cycle of metaphors in science suggests tha...

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Thalidomide-induced limb defects: resolving a 50-year-old puzzle

BioEssays — Tue, 17 Nov 2009 00:00:00 +0100

Despite the recent discovery that thalidomide causes limb defects by targeting highly angiogenic, immature blood vessels, several challenges still remain and new ones have arisen. These include understanding the drug's species specificity, determining molecular target(s) in the endothelial cell, shedding light on the molecular basis of phocomelia and producing a form of the drug that is clinically effective without having side effects. Now that the trigger of thalidomide-induced teratogenesis has been uncovered, a framework is proposed, incorporating and uniting previous models of thalidomide action, explaining how thalidomide causes not just limb defects, but also all the other defects it induces. (Source: BioEssays)

Monoallelic gene expression and mammalian evolution

BioEssays — Tue, 17 Nov 2009 00:00:00 +0100

Monoallelic gene expression has played a significant role in the evolution of mammals enabling the expansion of a vast repertoire of olfactory receptor types and providing increased sensitivity and diversity. Monoallelic expression of immune receptor genes has also increased diversity for antigen recognition, while the same mechanism that marks a single allele for preferential rearrangement also provides a distinguishing feature for directing hypermutations. Random monoallelic expression of the X chromosome is necessary to balance gene dosage across sexes. In marsupials only the maternal X chromosome is expressed, while in eutherian mammals the paternal X genes are silenced in the developing placenta and early blastocyst. These examples of epigenetic gene regulation commonly employ asynchr...

Growth plasticity of the embryonic and fetal heart

BioEssays — Tue, 17 Nov 2009 00:00:00 +0100

The developing mammalian heart responds to a variety of conditions, including changes in nutrient availability, blood oxygenation, hemodynamics, or tissue homeostasis, with impressive growth plasticity. This ensures the formation of a functional and normal sized organ by birth. During embryonic and fetal development the heart is exposed to various physiological and potentially pathological changes in the intrauterine environment which dramatically impact on normal cardiac function, tissue composition, and morphology. This paper summarizes the mechanisms employed by the embryonic and fetal heart to adapt to various intrauterine challenges to prevent or minimize postnatal consequences of impaired cardiac development. Future investigations of this growth plasticity might lead to new therapeut...

RNAi in X inactivation: contrasting findings on the role of interference

BioEssays — Tue, 17 Nov 2009 00:00:00 +0100

X inactivation is the process that brings about the dosage equivalence of X-linked genes in females to that of males. This complex process initiated at a very early stage of female embryonic development is orchestrated by long non-coding RNAs transcribed in both sense and antisense orientation. Recent studies present contradicting evidence for the role of small RNAs and RNase III enzyme Dicer in the X inactivation process. In this review, I discuss these results in the overall perspective of X inactivation and gene silencing. (Source: BioEssays)

Sizing up the genomic footprint of endosymbiosis

BioEssays — Tue, 17 Nov 2009 00:00:00 +0100

A flurry of recent publications have challenged consensus views on the tempo and mode of plastid (chloroplast) evolution in eukaryotes and, more generally, the impact of endosymbiosis in the evolution of the nuclear genome. Endosymbiont-to-nucleus gene transfer is an essential component of the transition from endosymbiont to organelle, but the sheer diversity of algal-derived genes in photosynthetic organisms such as diatoms, as well as the existence of genes of putative plastid ancestry in the nuclear genomes of plastid-lacking eukaryotes such as ciliates and choanoflagellates, defy simple explanation. Collectively, these papers underscore the power of comparative genomics and, at the same time, reveal how little we know with certainty about the earliest stages of the evolution of photosy...

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More than mentoring: the importance of group culture for scientific integrity

BioEssays — Tue, 17 Nov 2009 00:00:00 +0100

No Abstract. (Source: BioEssays)

Highlights from this Issue

BioEssays — Tue, 17 Nov 2009 00:00:00 +0100

No Abstract. (Source: BioEssays)

BioEssays 12/2009

BioEssays — Tue, 17 Nov 2009 00:00:00 +0100

No Abstract. (Source: BioEssays)

Linear model for fast background subtraction in oligonucleotide microarrays.

Algorithms for Molecular Biology : AMB — Mon, 16 Nov 2009 00:00:00 +0100

CONCLUSIONS: The algorithm has been tested on 360 GeneChips from publicly available data of recent expression experiments. The algorithm is fast and accurate. Strong correlations between the fitted values for different experiments as well as between the free-energy parameters and their counterparts in aqueous solution indicate that our model captures a significant part of the underlying physical chemistry. PMID: 19917117 [PubMed - as supplied by publisher] (Source: Algorithms for Molecular Biology : AMB)

p53-based Anti-cancer Therapies: an Empty Promise?

Current Issues in Molecular Biology — Mon, 16 Nov 2009 00:00:00 +0100

Authors: Desilet N, Campbell TN, Choy FY Since its discovery in 1979, p53 has become the focus of intensive cancer-based research in laboratories around the world. The p53 protein mediates critical cellular functions including the response to genotoxic stress, differentiation, senescence, and apoptosis, and has been shown to be mutated in a large proportion of human cancers. These observations led many to speculate that targeting the p53 pathway would result in the development of successful anti-cancer treatments. In spite of this, 30 years later, p53 has yet to fulfill this promise. However, new insights into small molecule combination therapies, microRNA regulation, structuring of clinical trials, and potential involvement in stem cell regulation may help p53 reach its potential. ...

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Network analysis of the transcriptional pattern of young and old cells of Escherichia coli during lag phase

BMC Systems Biology - Latest articles — Mon, 16 Nov 2009 00:00:00 +0100

Conclusion: Network analysis revealed very different transcriptional activities during the lag period in old and young cells. Rejuvenation seems to take place during exponential growth by replicative dilution of old cellular components. (Source: BMC Systems Biology - Latest articles)

Splitting statistical potentials into meaningful scoring functions: Testing the prediction of near-native structures from decoy conformations.

BMC Structural Biology - Latest articles — Mon, 16 Nov 2009 00:00:00 +0100

Conclusions: We have introduced a method to split knowledge-based potentials and to solve the problem of defining a reference state. The new scores have detected near-native structures as accurately as state-of-art methods and have been successful to identify wrongly modeled regions of many near-native conformations. (Source: BMC Structural Biology - Latest articles)

Ribosomal protein L10 is encoded in the mitochondrial genome of many land plants and green algae

BMC Evolutionary Biology - Latest articles — Mon, 16 Nov 2009 00:00:00 +0100

Conclusions: Despite the fact that there are now over 20 mitochondrial genome sequences for land plants and green algae, this gene has remained unidentified and largely undetected until now because of the unlikely coincidence that most of the earlier sequences were from the few lineages that lack the intact gene. These results illustrate the power of comparative sequencing to identify novel genomic features. (Source: BMC Evolutionary Biology - Latest articles)

Impregnated copper on magnetite: an efficient and green catalyst for the multicomponent preparation of propargylamines under solvent free conditions

RSC - Organic Biomolecular Chemistry — Mon, 16 Nov 2009 00:00:00 +0100

Maria J. Aliaga, Diego J. Ramon, Miguel Yus (Communication from Org. Biomol. Chem.) Maria J. Aliaga, Org. Biomol. Chem., 2010, DOI: 10.1039/b917923b 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)

Water-solubilised BF2-chelated tetraarylazadipyrromethenes

RSC - Organic Biomolecular Chemistry — Mon, 16 Nov 2009 00:00:00 +0100

Mariusz Tasior, Julie Murtagh, Daniel O. Frimannsson, Shane O. McDonnell, Donal F. O'Shea (Communication from Org. Biomol. Chem.) Mariusz Tasior, Org. Biomol. Chem., 2010, DOI: 10.1039/b919546g 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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Epimeric and amino disaccharide analogs as probes of an [small alpha]-(1[rightward arrow]6)-mannosyltransferase involved in mycobacterial lipoarabinomannan biosynthesis

RSC - Organic Biomolecular Chemistry — Mon, 16 Nov 2009 00:00:00 +0100

Pui Hang Tam, Todd L. Lowary (Paper from Org. Biomol. Chem.) Pui Hang Tam, Org. Biomol. Chem., 2010, DOI: 10.1039/b916580k 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)

Synthesis and room temperature photo-induced electron transfer in biologically active bis(terpyridine)ruthenium(ii)-cytochrome c bioconjugates and the effect of solvents on the bioconjugation of cytochrome c

RSC - Organic Biomolecular Chemistry — Mon, 16 Nov 2009 00:00:00 +0100

Joshua R. Peterson, Trevor A. Smith, Pall Thordarson (Paper from Org. Biomol. Chem.) Joshua R. Peterson, Org. Biomol. Chem., 2010, DOI: 10.1039/b919289a 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)

Expansion of the mycobacterial "PUPylome"

RSC - Mol. BioSyst. latest articles — Mon, 16 Nov 2009 00:00:00 +0100

Jeramie Watrous, Kristin Burns, Wei-Ting Liu, Anand Patel, Vivian Hook, Vineet Bafna, Clifton E. Barry 3rd, Steve Bark, Pieter C. Dorrestein (Paper from Mol. BioSyst.) Jeramie Watrous, Mol. BioSyst., 2010, DOI: 10.1039/b916104j 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)

Random network behaviour of protein structures

RSC - Mol. BioSyst. latest articles — Mon, 16 Nov 2009 00:00:00 +0100

K. V. Brinda, Saraswathi Vishveshwara, Smitha Vishveshwara (Paper from Mol. BioSyst.) K. V. Brinda, Mol. BioSyst., 2010, DOI: 10.1039/b903019k 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)

Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

Yeast — Mon, 16 Nov 2009 00:00:00 +0100

We describe a synthetic growth defect of an mph1 deletion if combined with an srs2 deletion that can result - depending on the genetic background - in synthetic lethality. The lethality is suppressed by mutations in homologous recombination (rad51, rad52, rad55, rad57) and in the DNA damage checkpoint (rad9, rad24, rad17). Importantly, rad54 and mph1, epistatic for damage sensitivity, are subadditive for spontaneous mutator phenotype. Therefore, Mph1 could be placed at the Rad51-mediated strand invasion process, with a function distinct from Rad54. Moreover, siz1 mutation is viable with mph1 and additive for DNA damage sensitivity. mph1 srs2 double mutants, isolated in a background where they are viable, are synergistically sensitive to DNA damage. Moderate overexpression of SGS1 partially...

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Linear model for fast background subtraction in oligonucleotide microarrays

Algorithms for Molecular Biology — Mon, 16 Nov 2009 00:00:00 +0100

Conclusions: The algorithm has been tested on 360 GeneChips from publicly available data of recent expression experiments. The algorithm is fast and accurate. Strong correlations between the fitted values for different experiments as well as between the free-energy parameters and their counterparts in aqueous solution indicate that our model captures a significant part of the underlying physical chemistry. (Source: Algorithms for Molecular Biology)

Connective tissue growth factor is induced in bleomycin-induced skin scleroderma.

Journal of Cell Communication and Signaling — Sun, 15 Nov 2009 00:00:00 +0100

In this report, we use an antibody recognizing CCN2 to assess the cell types in mouse dermis which express CCN2 in the bleomycin model of skin scleroderma. Control (PBS injected) and fibrotic (bleomycin-injected) dermis was examined for CCN2, alpha-smooth muscle actin (alpha-SMA) (to detect myofibroblasts), and NG2 (to detect pericytes) expression. Consistent with previously published data, CCN2 expression was largely absent in the dermis of control mice. However, upon exposure to bleomycin, CCN2 was observed in the dermis. Cells that expressed CCN2 were alpha-SMA-expressing myofibroblasts. Approximately 85% of myofibroblasts were NG2-positive, CCN2-expressing pericytes, indicating that pericytes significantly contributed to the presence of myofibroblasts in sclerotic dermis. Thus CCN2 is ...

WNT5A mutations in patients with autosomal dominant Robinow syndrome

Developmental Dynamics — Sat, 14 Nov 2009 00:00:00 +0100

Robinow syndrome is a skeletal dysplasia with both autosomal dominant and autosomal recessive inheritance patterns. It is characterized by short stature, limb shortening, genital hypoplasia, and craniofacial abnormalities. The etiology of dominant Robinow syndrome is unknown; however, the phenotypically more severe autosomal recessive form of Robinow syndrome has been associated with mutations in the orphan tyrosine kinase receptor, ROR2, which has recently been identified as a putative WNT5A receptor. Here, we show that two different missense mutations in WNT5A, which result in amino acid substitutions of highly conserved cysteines, are associated with autosomal dominant Robinow syndrome. One mutation has been found in all living affected members of the original family described by Meinha...

Statins enhance peroxisome proliferator-activated receptor γ coactivator-1α activity to regulate energy metabolism

Journal of Molecular Medicine — Fri, 13 Nov 2009 18:21:04 +0100

In this study, we found that statins reduced the active form of Akt and enhanced PGC-1α activity. Specifically, statins failed to activate an S571A mutant of PGC-1α. The activation of PGC-1α by statins selectively enhanced the expression of energy metabolizing enzymes and regulators including peroxisome proliferator-activated receptor α, acyl-CoA oxidase, carnitine palmitoyl transferase-1A, and pyruvate dehydrogenase kinase 4. Importantly, a constitutively active form of Akt partially reduced the statin-enhanced gene expression. Our study thus provides a plausible mechanistic explanation for the hypolipidemic effect of statin through elevating the rate of β-oxidation and mitochondrial Kreb’s cycle capacity to enhance fatty acid utilization while reducing the rate of glycolysis...

Structural and functional studies on Ycf12 (Psb30) and PsbZ deletion mutants from a thermophilic cyanobacterium.

Mol Biol Cell — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Takasaka K, Iwai M, Umena Y, Kawakami K, Ohmori Y, Ikeuchi M, Takahashi Y, Kamiya N, Shen JR Ycf12 (Psb30) and PsbZ are two low-molecular weight subunits of photosystem II (PSII), with one and two trans-membrane helices, respectively. In order to study the functions of these two subunits from a structural point of view, we constructed deletion mutants lacking either Ycf12 or PsbZ from Thermosynechococcus elongatus, and purified, crystallized and analyzed the structure of PSII dimer from the two mutants. Our results showed that Ycf12 is located in the periphery of PSII, close to PsbK, PsbZ and PsbJ, and corresponded to the unassigned helix X1 reported previously, in agreement with the recent structure at 2.9 A resolution (A. Guskov, J. Kern, A. Gabdulkhakov, M. Broser, A. Zouni...

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Functionalized self-assembling peptide hydrogel enhance maintenance of hepatocyte activity in vitro.

J Cell Mol Med — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Genové E, Schmitmeier S, Sala A, Borrós S, Bader A, Griffith LG, Semino CE ABSTRACT There is a major challenge in maintaining functional hepatocytes in vivo as these cells rapidly lose their metabolic properties in culture. In this work we have developed a bioengineered platform that replaces the use of the collagen I -in the traditional culture sandwich technique- by a defined extracellular matrix analog, the self-assembling peptide hydrogel RAD16-I functionalized with biologically active motifs. Thus, after examining side by side the two culture systems we have found that in both cases hepatocytes acquired similar parenchymal morphology, presence of functional bile canaliculi structures, CYP3A2 induction by dexamethasone, urea production, secretion of proteins such...

Human ribosomal protein S13 promotes gastric cancer growth through downregulating p27(Kip1).

J Cell Mol Med — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Guo X, Shi Y, Gou Y, Li J, Han S, Zhang Y, Huo J, Ning X, Sun L, Chen Y, Sun S, Fan D Abstract Our previous works revealed that human ribosomal protein S13 (RPS13) was upregulated in multidrug-resistant gastric cancer cells and overexpression of RPS13 could protect gastric cancer cells from drug-induced apoptosis. The present study was designed to explore the role of RPS13 in tumorigenesis and development of gastric cancer. The expression of RPS13 in gastric cancer tissues and normal gastric mucosa was evaluated by immunohistochemical staining and Western blot analysis. It was found RPS13 was expressed at a higher level in gastric cancer tissues than that in normal gastric mucosa. RPS13 was then genetically overexpressed in gastric cancer cells or knocked down by RNA interfere...

Bone marrow-derived cells can acquire cardiac stem cells properties in damaged heart.

J Cell Mol Med — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Barile L, Cerisoli F, Frati G, Gaetani R, Chimenti I, Forte E, Cassinelli L, Spinardi L, Altomare C, Kizana E, Giacomello A, Messina E, Ottolenghi S, Magli MC ABSTRACT Experimental data suggest that cell-based therapies may be useful for cardiac regeneration following ischaemic heart disease. Bone marrow (BM) cells have been reported to contribute to tissue repair after myocardial infarction (MI) by a variety of humoral and cellular mechanisms. However, there is no direct evidence, so far, that BM cells can generate Cardiac Stem Cells (CSCs). To investigate whether BM cells contribute to repopulate the Kit+ CSCs pool, we transplanted BM cells from transgenic mice, expressing Green Fluorescent Protein (GFP) under the control of Kit regulatory elements, into wild type irradiated...

The CMT4B disease-causing proteins MTMR2 and MTMR13/SBF2 regulate AKT signaling.

J Cell Mol Med — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Berger P, Tersar K, Ballmer-Hofer K, Suter U Abstract Charcot-Marie-Tooth disease type 4B is caused by mutations in the genes encoding either the lipid phosphatase Myotubularin-Related-Protein-2 (MTMR2) or its regulatory binding partner MTMR13/SBF2. Mtmr2 dephosphorylates PI-3-P and PI-3,5-P2 to form phosphatidylinositol and PI-5-P, respectively, while Mtmr13/Sbf2 is an enzymatically inactive member of the myotubularin protein family. We have found altered levels of the critical signaling protein AKT in mouse mutants for Mtmr2 and Mtmr13/Sbf2. Thus, we analyzed the influence of Mtmr2 and Mtmr13/Sbf2 on signaling processes. We found that overexpression of Mtmr2 prevents the degradation of the epidermal growth factor receptor (EGFR) and leads to sustained Akt activation whereas ...

PPARgamma ligands inhibit telomerase activity and hTERT expression through modulation of the Myc/Mad/Max network, in colon cancer cells.

J Cell Mol Med — Fri, 13 Nov 2009 00:00:00 +0100

In this study, we demonstrated that 15d-PG J2 and rosiglitazone (an endogenous and synthetic PPARgamma ligand, respectively) inhibited hTERT expression and telomerase activity in CaCo-2 colon cancer cells. Moreover, both ligands inhibited c-Myc protein expression and its E-box DNA binding activity. Additionally, Mad1 protein expression and its E-box DNA binding activity were strongly increased by 15d-PG J2 and, to a lesser extent, by rosiglitazone. Sp1 transcription factor expression and its GC-box DNA binding activity were not affected by both PPARgamma ligands. Results obtained by transient transfection of CaCo-2 cells with pmaxFP-Green-PRL plasmid constructs containing the functional hTERT core promoter (including one E-box and five GC-boxes) and its E-box deleted sequences, cloned upst...

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Dual Role of Hydrophobic Racemic Thioesters of alpha-Amino Acids in the Generation of Isotactic Peptides and Co-peptides in Water; Implications for the Origin of Homochirality.

Origins of Life and Evolution of the Biosphere — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Illos RA, Clodic G, Bolbach G, Weissbuch I, Lahav M Thioesters of alpha-amino acids are considered as plausible monomers for the generation of the primeval peptides. DL-Leucine-thioethyl esters (LeuSEt), where the L-enantiomer was tagged with deuterium atoms, undergo polycondensation in water or in bicarbonate or imidazole buffer solutions to yield mainly heterochiral (atactic) peptides and diketopiperazine, as analyzed by MALDI-TOF and ESI mass-spectrometry. In variance, when polymerization of DL(d(10))-Leu, first activated with N,N'-carbonyldiimidazole, then initiated with ethanethiol or with DL(d(3))-LeuSEt yielded a library of peptides up to 30 detectable residues where those of homochiral sequence (isotactic) are the dominant diastereoisomers. At these conditions, racemic...

Amplification of Chirality at Solid Surfaces.

Origins of Life and Evolution of the Biosphere — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Ernst KH Symmetry-breaking phenomena in two-dimensional crystallization at surfaces are reviewed and the potential impact to chiral amplification in three-dimensional systems in connection with the origin of homochirality in the biomolecular world is discussed. Adsorption of prochiral molecules leads to two-dimensional conglomerates, i.e., on a local scale spontaneously to homochiral crystal structures. Small enantiomeric excess or chiral impurities in this environment install homochirality on a global scale, that is, on the entire surface. PMID: 19911299 [PubMed - as supplied by publisher] (Source: Origins of Life and Evolution of the Biosphere)

Asymmetric Autocatalysis Induced by Chiral Crystals of Achiral Tetraphenylethylenes.

Origins of Life and Evolution of the Biosphere — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Kawasaki T, Nakaoda M, Kaito N, Sasagawa T, Soai K The achiral hydrocarbon tetraphenylethylene crystallizes in enantiomorphous forms (chiral space group: P2(1)) to afford right- and left-handed hemihedral crystals, which can be recognized by solid-state circular dichroism spectroscopic analysis. Chiral organic crystals of tetraphenylethylene mediated enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde to give, in conjunction with asymmetric autocatalysis with amplification of chirality, almost enantiomerically pure (S)- and (R)-5-pyrimidyl alkanols whose absolute configurations were controlled efficiently by the crystalline chirality of the tetraphenylethylene substrate. Tetrakis(p-chlorophenyl)ethylene and tetrakis(p-bromophenyl)ethylene also show chiral...

Homochirality and the Need for Energy.

Origins of Life and Evolution of the Biosphere — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Plasson R, Brandenburg A The mechanisms for explaining how a stable asymmetric chemical system can be formed from a symmetric chemical system, in the absence of any asymmetric influence other than statistical fluctuations, have been developed during the last decades, focusing on the non-linear kinetic aspects. Besides the absolute necessity of self-amplification processes, the importance of energetic aspects is often underestimated. Going down to the most fundamental aspects, the distinction between a single object-that can be intrinsically asymmetric-and a collection of objects-whose racemic state is the more stable one-must be emphasized. A system of strongly interacting objects can be described as one single object retaining its individuality and a single asymmetry; weakly ...

Homochirality in Life: Two Equal Runners, One Tripped.

Origins of Life and Evolution of the Biosphere — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Green MM, Jain V Strong arguments can be found in the literature addressed to the question of the origin of homochirality in life, supporting the hypothesis that primordial life could have evolved in both homochiral forms and that early on when life was still rarely found, random events led to the survival of only one of these living mirror images. This proposal is an alternative to the generally accepted view that small enantiomeric excesses of biologically important molecules were amplified to homochirality prior to life's origin. Acceptance of the possibility of "two equal runners" leads to the importance of research investigations on routes to formation of ensembles of racemic mixtures of isotactic biologically interesting polymers, supramolecular entities and aggregates. ...

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Imitating Prebiotic Homochirality on Earth.

Origins of Life and Evolution of the Biosphere — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Breslow R, Levine M, Cheng ZL We show how the amino acids needed on prebiotic earth in their homochiral L form can be produced by a reaction of L-alpha-methyl amino acids-that have been identified in the Murchison meteorite-with alpha-keto acids under credible prebiotic conditions. When they are simply heated together they perform a process of decarboxylative transamination but with almost no chiral transfer, and that in the wrong direction, producing D-amino acids from the L-alpha-methyl amino acids. With copper ion a square planar complex with two of the reaction intermediates is formed, and now there is the desired L to L transformation, producing small enantioexcesses of the normal L-amino acids. We also show how these can be amplified, not by making more of the L form but...

Spontaneous Mirror Symmetry Breaking in the Aldol Reaction and its Potential Relevance in Prebiotic Chemistry.

Origins of Life and Evolution of the Biosphere — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Mauksch M, Wei S, Freund M, Zamfir A, Tsogoeva SB The origin of the single chirality of most biomolecules is still a great puzzle. Carbohydrates could form in the formose reaction, which is proposed to be autocatalytic and contains aldol reaction steps. Based on our earlier observation of organoautocatalysis and spontaneous enantioenrichment in absence of deliberate chiral influences in the aldol reaction of acetone and p-nitrobenzaldehyde we suggest that a similar effect might be present also in the aldol reactions involved in gluconeogenesis. Herein we show that reactant precipitation observed in our earlier reported experiments does not affect the asymmetric autocatalysis in the aldol reaction we studied. We explain the phenomenon of spontaneous mirror symmetry breaking in ...

Dynamic regulation of glutamate decarboxylase 67 gene expression by alternative promoters and splicing during rat testis maturation.

Molecular Biology Reports — Fri, 13 Nov 2009 00:00:00 +0100

Authors: Liu H, Zhang Y, Li S, Yan Y, Li Y Glutamate decarboxylase produces GABA, the main inhibitory neurotransmitter in adult mammalian brain. Two homologous forms of GAD encoded by separate genes have been identified in mammalian brain, with molecular weight of 67 kDa (GAD67) and 65 kDa (GAD65). Here, we studied the transcriptional regulation of GAD67. Three transcript variants (GAD67A, GAD67B, and GAD67C) transcribed from distinct categories of transcriptional start sites were identified. RT-PCR revealed these transcripts have distinct tissues distributions. Though GAD67A and GAD67B were co-expressed in brain and many nonneural tissues, in heart, only GAD67A was expressed. GAD67C was specifically expressed in testis. These transcripts also showed distinct developmental expression p...

Fusion of uniluminal vascular spheroids: A model for assembly of blood vessels

Developmental Dynamics — Fri, 13 Nov 2009 00:00:00 +0100

We evaluated the self-assembly properties of uniluminal vascular spheroids having outer layers of vascular smooth muscle cells and a contiguous inner layer of endothelial cells lining a central lumen. We showed that while pairs of uniluminal vascular spheroids suspended in culture medium fused to form a larger diameter spheroidal structure, spheroids in collagen hydrogels formed elongated structures. These findings highlight the potential use of uniluminal vascular spheroids as modules to engineer blood vessels. We also demonstrate that uniluminal vascular spheroid fusion conforms to models describing the coalescence of liquid drops. Furthermore, the fusion of uniluminal vascular spheroids in vitro closely resembled the in vivo process by which the descending aorta forms from the fusion of...

Sinusoid development and morphogenesis may be stimulated by VEGF-Flk-1 signaling during fetal mouse liver development

Developmental Dynamics — Fri, 13 Nov 2009 00:00:00 +0100

Early morphogenesis of hepatic sinusoids was histochemically and experimentally analyzed, and the importance of VEGF-Flk-1 signaling in the vascular development was examined during murine liver organogenesis. FITC-gelatin injection experiments into young murine fetuses demonstrated that all primitive sinusoidal structures were confluent with portal and central veins, suggesting that hepatic vessel development may occur via angiogenesis. At 12.5-14.5 days of gestation, VEGF receptors designated Flk-1, especially their mature form, were highly expressed in endothelial cells of primitive sinusoidal structures and highly phosphorylated on their tyrosine residues. At the same time, VEGF was also detected in hepatoblasts/hepatocytes, hemopoietic cells, and megakaryocytes of the whole liver paren...

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A migratory role for EphrinB ligands in avian epicardial mesothelial cells

Developmental Dynamics — Fri, 13 Nov 2009 00:00:00 +0100

Little is known about the molecules that mediate the attachment of proepicardial cells to the heart. Ephrins are cell surface ligands for Eph tyrosine kinase receptors, molecules known to play a role in cell adhesion and migration. Here, we detected EphrinB ligands in proepicardial and epicardial mesothelial cells (EMCs) using reverse transcriptase-polymerase chain reaction, immunoblotting, immunolocalization, and EphB-Fc binding. Aggregated EphB-Fc fragments clustered ephrinB1 ligands on living EMCs indicating that they are cell surface expressed. In vitro assays demonstrated that ephrinB ligands participate in EMC migration but not cell adhesion. Localization studies in hearts at Hamburger and Hamilton stage 30 and older revealed that ephrinB1 is expressed in the epicardium and subepicar...

Visualization of myelination in GFP-transgenic zebrafish

Developmental Dynamics — Fri, 13 Nov 2009 00:00:00 +0100

The insulation of axons in the vertebrate nervous system by myelin is essential for efficient axonal conduction. Myelination disruption and remyelination failure can cause human diseases, such as multiple sclerosis and hereditary myelin diseases. However, despite progress in understanding myelination regulation, many important questions remain unanswered. To investigate the mechanisms underlying myelination in vivo, we generated transgenic zebrafish expressing enhanced green fluorescent protein (EGFP) under the control of the mbp promoter. This transgenic fish displayed faithful EGFP expression in oligodendrocytes and Schwann cells in embryonic and adult zebrafish. Interestingly, although myelination progressed continuously in the postembryonic central nervous system, some of the spinal co...

Pachymic acid inhibits cell growth and modulates arachidonic acid metabolism in nonsmall cell lung cancer A549 cells

Molecular Carcinogenesis — Fri, 13 Nov 2009 00:00:00 +0100

In this study, we examined the effect of PA on the proliferation of human nonsmall cell lung cancer A549 cells. Furthermore, we investigated the influences of nontoxic levels of PA on AA metabolism. Additionally, the cellular events and signal transduction pathways influenced by PA were also examined. Our results showed that PA (1) inhibited anchorage-dependent and -independent A549 growth in a concentration-dependent manner, (2) induced apoptosis and disrupted mitochondrial membrane potential in A549 cells, and at nonlethal levels, (3) decreased IL-1[beta]-induced activation of cPLA2 and COX-2, (4) suppressed IL-1[beta]-induced activation of mitogen-activated protein kinases (MAPKs), and (5) inhibited IL-1[beta]-stimulated nuclear factor kappa B (NF-[kappa]B) signaling pathways. We specul...

The sterol carrier protein 2/3-oxoacyl-CoA thiolase (SCPx) is involved in cholesterol uptake in the midgut of Spodoptera litura: gene cloning, expression, localization and functional analyses

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

Conclusion: Spatial and temporal expression pattern of this SlSCPx gene during the larval developmental stages of S. litura showed its specific association with the midgut at the feeding stage. Over-expression of this gene increased cholesterol uptake and interference of its transcript decreased cholesterol uptake and delayed the larval to pupal metamorphosis. All of these results taken together suggest that this midgut-specific SlSCPx gene is important for cholesterol uptake and normal development in S. litura. (Source: BMC Molecular Biology - Latest articles)

DG-AMMOS: A New tool to generate 3D conformation of small molecules using Distance Geometry and Automated Molecular Mechanics Optimization for in silico Screening.

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

Conclusions: DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods. (Source: BMC Chemical Biology - Latest articles)

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Total synthesis of LeA-LacNAc pentasaccharide as a ligand for Clostridium difficile toxin A

RSC - Organic Biomolecular Chemistry — Fri, 13 Nov 2009 00:00:00 +0100

Ping Zhang, Kenneth Ng, Chang-Chun Ling (Paper from Org. Biomol. Chem.) Ping Zhang, Org. Biomol. Chem., 2010, DOI: 10.1039/b914193f 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)

Ankyrin regulates K(ATP) channel membrane trafficking and gating in excitable cells.

Channels — Thu, 12 Nov 2009 18:38:07 +0100

Authors: Kline CF, Hund TJ, Mohler PJ K(ATP) channels play critical roles in many cellular functions by coupling cell metabolic status to electrical activity. First discovered in cardiomyocytes,(1) K(ATP) channels (comprised of Kir6.x and SUR subunits) have since been found in many other tissues, including pancreatic beta cells, skeletal muscle, smooth muscle, brain, pituitary and kidney. By linking cellular metabolic state with membrane potential, K(ATP) channels are able to regulate a number of cellular functions such as hormone secretion, vascular tone and excitability. Specifically, a reduction in metabolism causes a decrease in the ATP:ADP ratio, opening of K(ATP) channels, K(+) efflux, membrane hyperpolarization, and suppression of electrical activity. Conversely, increased cellu...

A novel N-terminal motif of dipeptidyl peptidase-like proteins produces rapid inactivation of K(V)4.2 channels by a pore-blocking mechanism.

Channels — Thu, 12 Nov 2009 18:38:04 +0100

Authors: Jerng HH, Dougherty K, Covarrubias M, Pfaffinger PJ The somatodendritic subthreshold A-type K(+) current in neurons (I(SA)) depends on its kinetic and voltage-dependent properties to regulate membrane excitability, action potential repetitive firing, and signal integration. Key functional properties of the K(V)4 channel complex underlying I(SA) are determined by dipeptidyl peptidase-like proteins known as dipeptidyl peptidase 6 (DPP6) and dipeptidyl peptidase 10 (DPP10). Among the multiple known DPP10 isoforms with alternative N-terminal sequences, DPP10a confers exceptionally fast inactivation to K(V)4.2 channels. To elucidate the molecular basis of this fast inactivation, we investigated the structure-function relationship of the DPP10a N-terminal region and its interaction ...

2009 Meetings Calendar

Journal of Biomolecular Screening — Thu, 12 Nov 2009 16:41:25 +0100

(Source: Journal of Biomolecular Screening)

Product Focus: Analytical and Preparative Instrumentation

Journal of Biomolecular Screening — Thu, 12 Nov 2009 16:41:25 +0100

(Source: Journal of Biomolecular Screening)

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Utilization of the TangoTM {beta}-Arrestin Recruitment Technology for Cell-Based EDG Receptor Assay Development and Interrogation

Journal of Biomolecular Screening — Thu, 12 Nov 2009 16:41:25 +0100

Cellular assay development for the endothelial differentiation gene (EDG) family of G-protein-coupled receptors (GPCRs) and related lysophospholipid (LP) receptors is complicated by endogenous receptor expression and divergent receptor signaling. Endogenously expressed LP receptors exist in most tissue culture cell lines. these LP receptors, along with other endogenously expressed GPCRs, contribute to off-target signaling that can complicate interpretation of second-messenger-based cellular assay results. these receptors also activate a diverse and divergent set of cellular signaling pathways, necessitating the use of a variety of assay formats with mismatched procedures and functional readouts. this complicates examination and comparison of these receptors across the entire family. the ta...

A Continuous Protein Methyltransferase (G9a) Assay for Enzyme Activity Measurement and Inhibitor Screening

Journal of Biomolecular Screening — Thu, 12 Nov 2009 16:41:25 +0100

The authors describe a continuous protein methylation assay using the G9a protein lysine methyltransferase and its substrate protein WIZ (widely interspaced zinc finger motifs). The assay is based on the coupling of the biotinylated substrate protein to streptavidin-coated FlashPlates and the transfer of radioactive methyl groups from the S-adenosyl-L-methionine to the substrate. The reaction progress is monitored continuously by proximity scintillation counting. The assay is very accurate, convenient, well suited for automation, and highly reproducible with standard errors in the range of 5%. Because of few pipetting steps and continuous data readout, it is ideal for high-throughput applications such as screening of inhibitors, testing many enzyme variants, or analyzing differences in met...

A Novel High-Throughput Screening Assay for HCN Channel Blocker Using Membrane Potential-Sensitive Dye and FLIPR

Journal of Biomolecular Screening — Thu, 12 Nov 2009 16:41:25 +0100

In this study, the authors report the development of a novel membrane potential-sensitive dye (MPSD) assay for HCN channel modulators that has been miniaturized into 384-well fluorescent imaging plate reader (FLIPR) high-throughput screening (HTS) format. When optimized (by cell plating density, plate type, cell recovery from cryopreservation), the wellto-well signal variability was low, with a Z' = 0.73 and coefficient of variation = 6.4%, whereas the MPSD fluorescence signal amplitude was -23,700 ± 1500 FLIPR3 relative fluorescence units (a linear relationship was found between HCN1 MPSD fluorescence signal and the cell plating density) and was completely blocked by 30 µM ZD7288. The assay tolerated up to 1% DMSO, inclusion of which did not significantly change the signal ki...

Virtual Screening Against {alpha}-Cobratoxin

Journal of Biomolecular Screening — Thu, 12 Nov 2009 16:41:25 +0100

-Cobratoxin (Cbtx), the neurotoxin isolated from the venom of the Thai cobra Naja kaouthia , causes paralysis by preventing acetylcholine (ACh) binding to nicotinic acetylcholine receptors (nAChRs). In the current study, the region of the Cbtx molecule that is directly involved in binding to nAChRs is used as the target for anticobratoxin drug design. The crystal structure (1YI5) of Cbtx in complex with the acetylcholine binding protein (AChBP), a soluble homolog of the extracellular binding domain of nAChRs, was selected to prepare an -cobratoxin active binding site for docking. The amino acid residues (Ser182-Tyr192) of the AChBP structure, the binding site of Cbtx, were used as the positive control to validate the prepared Cbtx active binding site (root mean square deviation < 1.2 &A...

Optimization of Assay Conditions fo r Dengue Virus Protease: Effect of Various Polyols and Nonionic Detergents

Journal of Biomolecular Screening — Thu, 12 Nov 2009 16:41:25 +0100

The aim of this work was to perform a systematic study of the effect of nonionic detergents on the activity of the dengue virus NS2B-NS3 protease. To ensure a high activity of the protease, the assay procedures for the dengue virus and other flaviviral proteases published to date are performed in the presence of up to 35% glycerol, which does not represent the cellular physicochemical environment. In addition, the high viscosity of glycerol-containing solutions leads to various experimental problems in miniaturized assays. Using an internally quenched peptide substrate, the authors show that glycerol is not essential for enzymatic activity if certain nonionic detergents are added to the assay buffer. In addition, nonionic detergents may help to avoid false-positive screening results caused...

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Inhibitors of RecA Activity Discovered by High-Throughput Screening: Cell-Permeable Small Molecules Attenuate the SOS Response in Escherichia coli

Journal of Biomolecular Screening — Thu, 12 Nov 2009 16:41:25 +0100

The phenomenon of antibiotic resistance has created a need for the development of novel antibiotic classes with nonclassical cellular targets. Unfortunately, target-based drug discovery against proteins considered essential for in vitro bacterial viability has yielded few new therapeutic classes of antibiotics. Targeting the large proportion of genes considered nonessential that have yet to be explored by high-throughput screening, for example, RecA, can complement these efforts. Recent evidence suggests that RecA-controlled processes are responsible for tolerance to antibiotic chemotherapy and are involved in pathways that ultimately lead to full-fledged antibiotic resistance. Therefore inhibitors of RecA may serve as therapeutic adjuvants in combination chemotherapy of bacterial infectio...

CXCR2 Inverse Agonism Detected by Arrestin Redistribution

Journal of Biomolecular Screening — Thu, 12 Nov 2009 16:41:25 +0100

To study CXCR2 modulated arrestin redistribution, the authors employed arrestin as a fusion protein containing either the Aequorea victoria—derived enhanced green fluorescent protein (EGFP) or a recently developed mutant of eqFP611, a red fluorescent protein derived from Entacmaea quadricolor. This mutant, referred to as RFP611, had earlier been found to assume a dimeric quarternary structure. It was therefore employed in this work as a "tandem" (td) construct for pseudo monomeric fusion protein labeling. Both arrestin fusion proteins, containing either td RFP611 (Arr td RFP611) or enhanced green fluorescent protein (EGFP; Arr EGFP), were found to colocalize with internalized fluorescently labeled Gro a few minutes after Gro addition. Intriguingly, however, Arr td RFP611 and Arr EGFP...

C5a-Stimulated Recruitment of {beta}-Arrestin2 to the Nonsignaling 7-Transmembrane Decoy Receptor C5L2

Journal of Biomolecular Screening — Thu, 12 Nov 2009 16:41:25 +0100

C5L2 (or GPR77) is a high-affinity receptor for the complement fragment C5a and its desarginated product, C5a-desArg. Unlike the classical C5a receptor CD88, C5L2 does not couple to intracellular G-protein-signaling pathways but is thought to function as a decoy receptor. The authors show that stimulation of C5L2 with C5a and C5a-desArg induces redistribution of green fluorescent protein—labeled β-arrestin2 to cytoplasmic vesicles. C3a and C3a-desArg were inactive in the β-arrestin translocation assay. Direct interaction of ligand-stimulated C5L2 with β-arrestin was confirmed using a novel β-galactosidase fragment complementation assay. In this assay, C5L2 was labeled with a mutationally altered peptide fragment of β-galactosidase, whereas β-arrestin2 wa...

Profiling Bioactivity of the ToxCast Chemical Library Using BioMAP Primary Human Cell Systems

Journal of Biomolecular Screening — Thu, 12 Nov 2009 16:41:25 +0100

The complexity of human biology has made prediction of health effects as a consequence of exposure to environmental chemicals especially challenging. Complex cell systems, such as the Biologically Multiplexed Activity Profiling (BioMAP) primary, human, cell-based disease models, leverage cellular regulatory networks to detect and distinguish chemicals with a broad range of target mechanisms and biological processes relevant to human toxicity. Here the authors use the BioMAP human cell systems to characterize effects relevant to human tissue and inflammatory disease biology following exposure to the 320 environmental chemicals in the Environmental Protection Agency’s (EPA’s) ToxCast phase I library. The ToxCast chemicals were assayed at 4 concentrations in 8 BioMAP cell systems,...

Automated High-Content Screening for Compounds That Disassemble the Perinucleolar Compartment

Journal of Biomolecular Screening — Thu, 12 Nov 2009 16:41:25 +0100

All solid malignancies share characteristic traits, including unlimited cellular proliferation, evasion of immune regulation, and the propensity to metastasize. The authors have previously described that a subnuclear structure, the perinucleolar compartment (PNC), is associated with the metastatic phenotype in solid tumor cancer cells. The percentage of cancer cells that contain PNCs (PNC prevalence) is indicative of the malignancy of a tumor both in vitro and in vivo, and thus PNC prevalence is a marker that reflects metastatic capability in a population of tumor cells. Although the function of the PNC remains to be determined, the PNC is highly enriched with small RNAs and RNA binding proteins. The initial chemical biology studies using a set of anticancer drugs that disassemble PNCs rev...

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In Memoriam: Tony J. Beugelsdijk (1949--2009)

Journal of Biomolecular Screening — Thu, 12 Nov 2009 16:41:25 +0100

(Source: Journal of Biomolecular Screening)

Anticancer activities of artemisinin and its bioactive derivatives

Expert Reviews in Molecular Medicine — Thu, 12 Nov 2009 16:09:54 +0100

Review ArticlesGary L. Firestone, Shyam N. Sundar, Expert Reviews in Molecular Medicine, Volume 11 , pp e32AbstractArtemisinin, a sesquiterpene lactone derived from the sweet wormwood plant Artemisia annua, and its bioactive derivatives exhibit potent anticancer effects in a variety of human cancer cell model systems. The pleiotropic response in cancer cells includes growth inhibition by cell cycle arrest, apoptosis, inhibition of angiogenesis, disruption of cell migration, and modulation of nuclear receptor responsiveness. These effects of artemisinin and its derivatives result from perturbations of many cellular signalling pathways. This review provides a comprehensive discussion of these cellular responses, and considers the ramifications for the potential development of artemisinin-bas...

Paracrine support of ovarian stimulation

Molecular Human Reproduction — Thu, 12 Nov 2009 15:49:49 +0100

Assisted reproductive technology has evolved on the back of blunderbuss ovarian stimulation regimes designed to maximize the number of oocytes recoverable for treatment purposes. However, oocyte ‘quality’ is finely programmed by local paracrine and autocrine signalling events during folliculogenesis and can be adversely affected by inappropriate gonadotrophic stimulation. This brief review traces the full follicular lifespan—from initiation to ovulation—to identify gonadotrophin-responsive checkpoints likely to impact oocyte quality. It is argued that these might be targeted during controlled ovarian stimulation therapy to (i) increase responsiveness to FSH through follicular priming with LH or hCG, (ii) improve follicular synchrony and oocyte quality through condit...

Genetic and gene expression analyses of the polycystic ovary syndrome candidate gene fibrillin-3 and other fibrillin family members in human ovaries

Molecular Human Reproduction — Thu, 12 Nov 2009 15:49:49 +0100

Several studies have demonstrated an association between polycystic ovary syndrome (PCOS) and the dinucleotide repeat microsatellite marker D19S884, which is located in intron 55 of the fibrillin-3 (FBN3) gene. Fibrillins, including FBN1 and 2, interact with latent transforming growth factor (TGF)-β-binding proteins (LTBP) and thereby control the bioactivity of TGFβs. TGFβs stimulate fibroblast replication and collagen production. The PCOS ovarian phenotype includes increased stromal collagen and expansion of the ovarian cortex, features feasibly influenced by abnormal fibrillin expression. To examine a possible role of fibrillins in PCOS, particularly FBN3, we undertook tagging and functional single nucleotide polymorphism (SNP) analysis (32 SNPs including 10 that generate ...

Control of ovulation in mice by progesterone receptor-regulated gene networks

Molecular Human Reproduction — Thu, 12 Nov 2009 15:49:49 +0100

The mid-cycle surge of luteinizing hormone (LH) induces ovulation, a process during which a fertilizable oocyte is released from a mature ovarian follicle. Although ovulation is a physiologically well-characterized event, the underlying molecular pathways remain poorly understood. Progesterone receptor (PGR), which mediates the biological effects of the steroid hormone progesterone, has emerged as a key regulator of ovulation in mice. The development of a progesterone-receptor-null (Pgr-null) mouse model confirmed a critical role of this hormone in ovulation because in these mutant mice, mature pre-ovulatory follicles fail to release the oocytes. This animal model has thus presented a unique opportunity to study the molecular pathways underlying ovulation. Gene-expression profiling experim...

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Oogenesis and cell death in human prenatal ovaries: what are the criteria for oocyte selection?

Molecular Human Reproduction — Thu, 12 Nov 2009 15:49:49 +0100

Prenatal oogenesis produces hundreds of thousands of oocytes, most of which are discarded through apoptosis before birth. Despite this large-scale selection, the survivors do not constitute a perfect population, and the factors at the cellular level that result in apoptosis or survival of any individual oocyte are largely unknown. What then are the selection criteria that determine the size and quality of the ovarian reserve in women? This review focuses on new data at the cellular level, on human prenatal oogenesis, offering clues about the importance of the timing of entry to meiotic prophase I by linking the stages and progress through MPI with the presence or absence of apoptotic markers. The characteristics and responsiveness of cultured human fetal ovarian tissue at different gestati...

The primordial pool of follicles and nest breakdown in mammalian ovaries

Molecular Human Reproduction — Thu, 12 Nov 2009 15:49:49 +0100

The creation of the pool of follicles available for selection and ovulation is a multi-faceted, tightly regulated process that spans the period from embryonic development through to the first reproductive cycle of the organism. In mice, this development can occur in mere weeks, but in humans, it is sustained for years. Embryonic germ cell development involves the migration of primordial germs cells to the genital ridge, and the mitotic division of germ cell nuclei without complete cytokinesis to form a multi-nucleated syncytia, or germ cell nest. Through combined actions of germ cell apoptosis and somatic cell migration, the germ cell nuclei are packaged, with surrounding granulosa cells, into primordial follicles to form the initial follicle pool. Though often dismissed as quiescent and p...

Oocyte peptides as paracrine tools for ovarian stimulation and oocyte maturation

Molecular Human Reproduction — Thu, 12 Nov 2009 15:49:49 +0100

Recent studies report the production and isolation of a stable bioactive recombinant human bone morphogenetic protein 15 (rhBMP15) that is appropriately processed in HEK-293 cells and activates the SMAD 1/5/8 pathway in mouse granulosa cell cultures. Further, the purified rhBMP15 induces the expression of genes associated with cumulus expansion. Thanks to recent research, we have a greater understanding of the importance of the dialogue that occurs between the oocyte and the granulosa cell layer with regard to regulating folliculogenesis and the acquisition of oocyte developmental competence and maturation. BMP15 is one of the critical components of these intra-follicular communication pathways. The production of recombinant human BMP15 is important for understanding the biochemistry of th...

Stable expression and characterization of N-terminal tagged recombinant human bone morphogenetic protein 15

Molecular Human Reproduction — Thu, 12 Nov 2009 15:49:49 +0100

Oocyte-derived growth factors are critically involved in multiple ovarian processes via paracrine actions. Although recombinant proteins have been applied to dissect the physiological functions of these factors, variation of activities among different protein preparations remains an issue. To further elucidate the roles of one of these growth factors, bone morphogenetic protein 15 (BMP15), in mediating oocyte-regulated molecular and cellular events and to explore its potential clinical application, we engineered the human BMP15 sequence to efficiently produce bioactive recombinant human BMP15 (rhBMP15). The proteolytic cleavage site of the hBMP15 precursor was optimized to facilitate the production of the mature protein, and a FLAG-tag was placed at the N-terminus of the mature region to e...

The forkhead transcription factor FOXL2 is expressed in somatic cells of the human ovary prior to follicle formation

Molecular Human Reproduction — Thu, 12 Nov 2009 15:49:49 +0100

Interactions between germ cells and surrounding somatic cells are central to ovarian development as well as later function. Disruption of these interactions arising from abnormalities in either cell type can lead to premature ovarian failure (POF). The forkhead transcription factor FOXL2 is a candidate POF factor, and mutations in the FOXL2 gene are associated with syndromic and non-syndromic ovarian failure. Foxl2-deficient mice display major defects in primordial follicle activation with consequent follicle loss, and earlier roles in gonadal development and sex determination have also been suggested. However, despite its importance no data presently exist on its expression in the developing human ovary. Expression of FOXL2 mRNA was demonstrated in the human fetal ovary between 8 and 19 w...

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Disruption of Tsc2 in oocytes leads to overactivation of the entire pool of primordial follicles

Molecular Human Reproduction — Thu, 12 Nov 2009 15:49:49 +0100

In this study, we provide some genetic evidence to show that the tumor suppressor tuberous sclerosis complex 2 (Tsc2), which negatively regulates mammalian target of rapamycin complex 1 (mTORC1), functions in oocytes to maintain the dormancy of primordial follicles. In mutant mice lacking the Tsc2 gene in oocytes, the pool of primordial follicles is activated prematurely due to elevated mTORC1 activity in oocytes. This results in depletion of follicles in early adulthood, causing premature ovarian failure (POF). Our results suggest that the Tsc1–Tsc2 complex mediated suppression of mTORC1 activity is indispensable for maintenance of the dormancy of primordial follicles, thus preserving the follicular pool, and that mTORC1 activity in oocytes promotes follicular activation. Our result...

The ovary: from basic research to clinic

Molecular Human Reproduction — Thu, 12 Nov 2009 15:49:48 +0100

(Source: Molecular Human Reproduction)

Blockade of multiple but not single cytokines abrogates downregulation of angiotensin II type-I receptors and anticipates septic shock.

Cytokine — Thu, 12 Nov 2009 00:00:00 +0100

Authors: Schmidt C, Höcherl K, Kurt B, Moritz S, Kurtz A, Bucher M In this prospective, randomized animal study, the role of proinflammatory cytokines in the pathogenesis sepsis-induced circulatory failure with downregulation of angiotensin-II-type-I-(AT(1))-receptors was investigated. Sepsis in wild-type mice and in mice with deficiencies for TNF-alpha, IL-1beta, IFN-gamma or IL-6 was induced by cecal ligation and puncture (CLP) and wild-type mice were injected with cytokines. Animals were treated with glucocorticoids or small interfering RNA (siRNA) targeting single or multiple cytokines or NF-kappaB. Vascular smooth muscle cells (VSMCs) were incubated with cytokines. CLP resulted in circulatory failure and a significant downregulation of AT(1)-receptors. Injection of single pro...

A Novel JNK Binding Protein WDR62 Is Recruited to Stress Granules and Mediates a Non-classical JNK Activation.

Mol Biol Cell — Thu, 12 Nov 2009 00:00:00 +0100

Authors: Wasserman T, Katsenelson K, Daniliuc S, Hasin T, Choder M, Aronheim A Monitoring Editor: Jonathan Chernoff The c-Jun N-terminal kinase (JNK) is part of a Mitogen-activated protein kinase (MAPK) signaling cascade. Scaffold proteins simultaneously associate with various components of the MAPK signaling pathway and play a role in signal transmission and regulation. Here we describe the identification of a novel scaffold JNK binding protein, WDR62, with no sequence homology to any of the known scaffold proteins. WDR62 is a ubiquitously expressed heat-sensitive 175 kDa protein that specifically associates with JNK but not with ERK and p38. Association between WDR62 and JNKs occurs in the absence and following either transient or persistent stimuli. WDR62 potentiates JNK kinase acti...

Mobility, Microtubule Nucleation and Structure of MTOCs in Multinucleated Hyphae of Ashbya gossypii.

Mol Biol Cell — Thu, 12 Nov 2009 00:00:00 +0100

Authors: Lang C, Grava S, van den Hoorn T, Trimble R, Philippsen P, Jaspersen SL Monitoring Editor: Kerry S. Bloom We investigated the migration of multiple nuclei in hyphae of the filamentous fungus Ashbya gossypii. Three types of cytoplasmic microtubule (cMT)-dependent nuclear movements were characterized using live cell imaging: short range oscillations (up to 4.5 mum/min), rotations (up to 180 degrees in 30 s) and long-range nuclear bypassing (up to 9 mum/min). These movements were superimposed on a cMT-independent mode of nuclear migration, cotransport with the cytoplasmic stream. This latter mode is sufficient to support wild-type-like hyphal growth speeds. cMT-dependent nuclear movements were led by a nuclear-associated MTOC, the spindle pole body (SPB), which is the sole site o...

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Centromeric Localization of Dispersed Pol III Genes in Fission Yeast.

Mol Biol Cell — Thu, 12 Nov 2009 00:00:00 +0100

We present evidence that Pol III transcribed genes such as tRNA and 5S rRNA genes can localize to centromeres and contribute to a global genome organization. Furthermore, we find that ectopic insertion of Pol III genes into a nonPol III gene locus results in the centromeric localization of the locus. We show that the centromeric localization of Pol III genes is mediated by condensin, which interacts with the Pol III transcription machinery, and that transcription levels of the Pol III genes are negatively correlated with the centromeric localization of Pol III genes. This centromeric localization of Pol III genes initially observed in interphase becomes prominent during mitosis, when chromosomes are condensed. Remarkably, defective mitotic chromosome condensation by a condensin mutation, c...

Mechanisms of Self-organization of Cortical Microtubules in Plants Revealed by Computational Simulations.

Mol Biol Cell — Thu, 12 Nov 2009 00:00:00 +0100

Authors: Allard JF, Wasteneys GO, Cytrynbaum EN Monitoring Editor: David G. Drubin Microtubules confined to the two-dimensional cortex of elongating plant cells must form a parallel yet dispersed array transverse to the elongation axis for proper cell wall expansion. Some of these microtubules exhibit free minus-ends, leading to migration at the cortex by hybrid treadmilling. Collisions between microtubules can result in plus-end entrainment ("zippering") or rapid depolymerization. Here, we present a computational model of cortical microtubule organization. We find that plus-end entrainment leads to self-organization of microtubules into parallel arrays, while catastrophe-inducing collisions do not. Catastrophe-inducing boundaries (e.g., upper and lower cross-walls) can tune the orient...

Actin Binding Protein-1 Interacts with WIP to Regulate Growth Factor-induced Dorsal Ruffle Formation.

Mol Biol Cell — Thu, 12 Nov 2009 00:00:00 +0100

Authors: Cortesio CL, Perrin BJ, Bennin DA, Huttenlocher A Monitoring Editor: Josephine C. Adams Growth factor stimulation induces the formation of dynamic actin structures known as dorsal ruffles. Mammalian actin binding protein-1 (mAbp1) is an actin binding protein that has been implicated in regulating clathrin-mediated endocytosis; however, a role for mAbp1 in regulating the dynamics of growth factor-induced actin-based structures has not been defined. Here we show that mAbp1 localizes to dorsal ruffles and is necessary for platelet-derived growth factor (PDGF)-mediated dorsal ruffle formation. Despite their structural similarity, we find that mAbp1 and cortactin have nonredundant functions in the regulation of dorsal ruffle formation. mAbp1, like cortactin, is a calpain 2 substrat...

Expression of hepatic antioxidant genes in L-thyroxine-induced hyperthyroid rats: Regulation by vitamin E and curcumin.

Chemico-Biological Interactions — Thu, 12 Nov 2009 00:00:00 +0100

Authors: Subudhi U, Chainy GB Earlier we have demonstrated that oral supplementation of vitamin E and curcumin alleviates hyperthyroidism-induced oxidative stress and distorted histoarchitecture in rat liver (Chem. Biol. Interact. 173:105-114, 2008). To delineate the underlying mechanism of protection, the present study was undertaken to investigate the regulatory role of vitamin E and curcumin on antioxidant gene (AOG) expression in hyperthyroid rat liver. Adult male rats were rendered hyperthyroid by administration of 0.0012% L-thyroxine in their drinking water, while vitamin E (200mg/Kg body weight) and curcumin (30mg/Kg body weight) were supplemented orally for 30 days. L-thyroxine-induced hyperthyroidism decreased the transcript levels of superoxide dismutase (SOD), catalase (CAT)...

How much does benzene contribute to the overall burden of cancer due to occupation?

Chemico-Biological Interactions — Thu, 12 Nov 2009 00:00:00 +0100

Authors: Rushton L, Brown TP, Cherrie J, Fortunato L, Van Tongeren M, Hutchings SJ PMID: 19914225 [PubMed - as supplied by publisher] (Source: Chemico-Biological Interactions)

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Dietary flavonoids suppress azoxymethane-induced colonic preneoplastic lesions in male C57BL/KsJ-db/db mice.

Chemico-Biological Interactions — Thu, 12 Nov 2009 00:00:00 +0100

Authors: Miyamoto S, Yasui Y, Ohigashi H, Tanaka T, Murakami A Obesity is known to be a risk factor for colon carcinogenesis. Although there are several reports on the chemopreventive abilities of dietary flavonoids in chemically induced colon carcinogenesis, those have not been addressed in an obesity-associated carcinogenesis model. In the present study, the effects of 3 flavonoids (chrysin, quercetin and nobiletin) on modulation of the occurrence of putative preneoplastic lesions, aberrant crypt foci (ACF), and beta-catenin accumulated crypts (BCACs) in the development of colon cancer were determined in male db/db mice with obesity and diabetic phenotypes. Male db/db mice were given 3 weekly intraperitoneal injections of azoxymethane (AOM) to induce the ACF and BCAC. Each flavonoid ...

Ensuring comparability of benzene exposure estimates across three nested case-control studies in the petroleum industry in support of a pooled epidemiological analysis.

Chemico-Biological Interactions — Thu, 12 Nov 2009 00:00:00 +0100

CONCLUSIONS: The revised exposure estimates will be used in the pooled analysis to examine the risk of haematopoietic cancers and benzene exposure. This exercise provided an important quality control check on the exposure estimates and identified similarly exposed Job Categories that could be grouped for risk assessment analyses. PMID: 19914227 [PubMed - as supplied by publisher] (Source: Chemico-Biological Interactions)

Identification and expression of an elastase homologue in Branchiostoma belcheri with implications to the origin of vertebrate pancreas.

Molecular Biology Reports — Thu, 12 Nov 2009 00:00:00 +0100

In this study we demonstrate the presence of an elastase homologue, named BbElas, in Branchiostoma belcheri. The recombinant BbElas hydrolyses the elastase specific substrate N-succinyl-Ala-Ala-Ala p-nitroanilide, which can be inhibited by the serine proteinase inhibitor PMSF, the elastase-specific inhibitor elastatinal and the cysteine proteinase inhibitor PCMB. Phylogenetic analysis shows that BbElas represents the archetype of vertebrate elastases, hinting at the clues that the different isoforms of vertebrate elastases are originated from an ancestral gene like BbElas. Our results also suggest that the mid-gut in amphioxus is to homologous vertebrate pancreas, a novel proposal which deserves further study. PMID: 19908163 [PubMed - as supplied by publisher] (Source: Molecular Biolog...

Inhibition of MAPK signaling by eNOS gene transfer improves ventricular remodeling after myocardial infarction through reduction of inflammation.

Molecular Biology Reports — Thu, 12 Nov 2009 00:00:00 +0100

Authors: Chen LL, Zhu TB, Yin H, Huang J, Wang LS, Cao KJ, Yang ZJ Endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) may play an important role in attenuating cardiac remodeling and apoptosis after myocardial infarction. However, the anti-inflammation effects of eNOS in infarcted myocardium and the role of MAPK signaling in eNOS/NO mediated cardiac remodeling have not yet been elucidated. Adenovirus carrying Human eNOS gene was delivered locally into heart 4 days prior to induction of myocardial infarction (MI) by left anterior descending coronary artery ligation. Monocyte/macrophage infiltration was detected by ED-1 immunohistochemistry. Western blot was employed to examine the activation of MAPK. eNOS gene transfer significantly reduced myocardial infarct size and improv...

Antinociceptive action of oxytocin involves inhibition of potassium channel currents in lamina II neurons of the rat spinal cord

Molecular Pain — Thu, 12 Nov 2009 00:00:00 +0100

Conclusions: This effect of OT on the firing profile of lamina II neurons is in good agreement with the antinociceptive and analgesic properties of OT described in vivo. (Source: Molecular Pain)

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A small supernumerary marker chromosome present in a Turner syndrome patient not derived from X- or Y-chromosome: a case report

Molecular Cytogenetics — Thu, 12 Nov 2009 00:00:00 +0100

Conclusion: More comprehensive characterization of such sSMCT might identify them to be more frequent than only ~0.6% in Turner syndrome cases according to available data. (Source: Molecular Cytogenetics)

The structural and functional determinants of the Axin and Dishevelled DIX domains

BMC Structural Biology - Latest articles — Thu, 12 Nov 2009 00:00:00 +0100

Conclusions: This report provides the first explanation of the mutant phenotypes caused by non-synonymous substitutions in the Dishevelled and Axin DIX domain by correlating their presumed functional significance with molecular structure. (Source: BMC Structural Biology - Latest articles)

DIBAL-H mediated triple and quadruple debenzylations of perbenzylated cyclodextrins

RSC - Organic Biomolecular Chemistry — Thu, 12 Nov 2009 00:00:00 +0100

Girish K. Rawal, Shikha Rani, Sandra Ward, Chang-Chun Ling (Paper from Org. Biomol. Chem.) Girish K. Rawal, Org. Biomol. Chem., 2010, DOI: 10.1039/b915450g 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)

Mechanism of chemical O-glycosylation: from early studies to recent discoveries

RSC - Organic Biomolecular Chemistry — Thu, 12 Nov 2009 00:00:00 +0100

Laurel K. Mydock, Alexei V. Demchenko (Perspective from Org. Biomol. Chem.) Laurel K. Mydock, Org. Biomol. Chem., 2010, DOI: 10.1039/b916088d 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)

Stereoselective synthesis and structure-affinity relationships of bicyclic [small kappa] receptor agonists

RSC - Organic Biomolecular Chemistry — Thu, 12 Nov 2009 00:00:00 +0100

Daniel Kracht, Elisabeth Rack, Dirk Schepmann, Roland Frohlich, Bernhard Wunsch (Paper from Org. Biomol. Chem.) Daniel Kracht, Org. Biomol. Chem., 2010, DOI: 10.1039/b915180j 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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Identification and biosynthesis of tropone derivatives and sulfur volatiles produced by bacteria of the marine Roseobacter clade

RSC - Organic Biomolecular Chemistry — Thu, 12 Nov 2009 00:00:00 +0100

Verena Thiel, Thorsten Brinkhoff, Jeroen S. Dickschat, Susanne Wickel, Jorg Grunenberg, Irene Wagner-Dobler, Meinhard Simon, Stefan Schulz (Paper from Org. Biomol. Chem.) Verena Thiel, Org. Biomol. Chem., 2010, DOI: 10.1039/b909133e 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)

Combining nanotechnology with current biomedical knowledge for the vascular imaging and treatment of atherosclerosis

RSC - Mol. BioSyst. latest articles — Thu, 12 Nov 2009 00:00:00 +0100

M. Slevin, L. Badimon, M. Grau-Olivares, M. Ramis, J. Sendra, M. Morrison, J. Krupinski (Review from Mol. BioSyst.) M. Slevin, Mol. BioSyst., 2010, DOI: 10.1039/b916175a 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)

Therapeutic applications of hyaluronan

RSC - Mol. BioSyst. latest articles — Thu, 12 Nov 2009 00:00:00 +0100

John Gaffney, Sabine Matou-Nasri, Marta Grau-Olivares, Mark Slevin (Review from Mol. BioSyst.) John Gaffney, Mol. BioSyst., 2010, DOI: 10.1039/b910552m 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)

Three-dimensional polar representation for multispectral fluorescence lifetime imaging microscopy

Cytometry Part A — Thu, 12 Nov 2009 00:00:00 +0100

We present here a new approach that considerably simplifies this analysis avoiding complex fitting algorithm strategies and permitting a fast and visual graphical representation of the fluorescence lifetimes. By transforming the experimental data from time domain to frequency domain for each spectral channel, we calculate the multispectral polar representation and demonstrate its interest on multiply fluorescent labeled sample. We further apply it on Förster resonance energy transfer (FRET) experiments and demonstrate that FRET measurements with a high level of precision can be performed. With addition of emission wavelength as third dimension in the polar representation, autofluorescence emitted by the sample is thus clearly identified. Analysis artifacts induced by the sample or by fitt...

Up regulation of GW112 Gene by NF[kappa]B promotes an antiapoptotic property in gastric cancer cells

Molecular Carcinogenesis — Thu, 12 Nov 2009 00:00:00 +0100

To clarify the regulatory mechanism of GW112 gene expression, 5[prime]-flanking region of the human GW112 gene was isolated and characterized in the present study. 5[prime]-RACE analysis showed a single transcription start site, which is located 142 nucleotides upstream of the translation initiation site. Transient transfection studies with serial deletion constructs and close examination of the sequences identified a putative NF[kappa]B binding sequence between -442 and -430, which could be responsible for efficient expression of the GW112 gene. Indeed, GW112 gene was found to be regulated by NF[kappa]B signals including overexpressed p65 and I[kappa]B[alpha], IKK inhibitor, and proteasome inhibitor. Binding of NF[kappa]B to its putative site was confirmed by EMSA and ChIP assays. These r...

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Pigment epithelium–derived factor down regulates hyperglycemia-induced apoptosis via PI3K/Akt activation in goat retinal pericytes

Angiogenesis — Wed, 11 Nov 2009 07:18:31 +0100

Abstract Pigment epithelium–derived factor (PEDF) is a well-known protease inhibitor for angiogenesis in the eye, suggesting that loss of PEDF in eye is implicated in the pathogenesis of proliferative diabetic retinopathy. Since the role of PEDF in diabetic retinopathy is unclear, the effect of PEDF on different types of cells constituting the blood vessel has to be checked. Here, we have investigated the effects of PEDF under hyperglycemic conditions in retinal pericytes, isolated from goat’s eye and used to analyze the signaling pathway involved. High glucose increased the apoptotic cell death and intracellular reactive oxygen species generation, which was blocked on the addition of PEDF. PEDF was found to inhibit the apoptotic cell death and protect the cells via ac...

The human alpha11 integrin promoter drives fibroblast-restricted expression in vivo and is regulated by TGF-beta1 in a Smad- and Sp1-dependent manner.

Matrix Biology — Wed, 11 Nov 2009 00:00:00 +0100

Authors: Lu N, Ranta J, Heuchel R, Soininen R, Gullberg D Integrin alpha11beta1 is expressed by ectomesenchymally- and mesodermally- derived fibroblasts and is the major collagen receptor on embryonic fibroblasts. We have previously characterized a 3kb human alpha11 promoter region in vitro. In the current study we generated promoter-LacZ reporter transgenic mice to examine the ability of the 3kb alpha11 promoter to drive tissue-specific expression also in vivo. Our data show that the alpha11 promoter region that we have characterized contains most of the regulatory elements that direct ectomesenchymal and mesodermal fibroblast-specific expression. Not much is known about integrin alpha11 regulation by TGF-beta family members and the potential role of alpha11 in TGF-beta1 driven proces...

Hyaluronan oligosaccharides promote excisional wound healing through enhanced angiogenesis.

Matrix Biology — Wed, 11 Nov 2009 00:00:00 +0100

In this study, we prepared a special slow-releasing gel that contains a mixture of defined size of o-HA and studied the healing effects of o-HA by topical application to an acute wound model. We report that o-HA complex promotes the repair of tissue injury of a murine excisional dermal wound. The therapy by o-HA was compared with high molecular weight HA (HMW-HA) and the known angiogenesis stimulator, VEGF. At days 6 to 8 after treatment, significant differences were seen in wound closure rates between o-HA and control or HMW-HA groups, in which o-HA showed an increased wound recovery. Histological analysis revealed that increased neo-blood and lymph vessels were formed in wounded tissues treated by o-HA. In addition, treatments of wounds with o-HA resulted in more granulation productionco...

The cardiovascular unit as a dynamic player in disease and regeneration.

Trends in Molecular Medicine — Wed, 11 Nov 2009 00:00:00 +0100

Authors: Ausoni S, Sartore S Cell-mediated cardiac regeneration remains a challenge as a therapeutic option in heart failure, but modest success using experimental models suggests that a better understanding of normal histogenesis will be needed to make progress towards cardiac regeneration. Recent studies of the heart show that the interstitium informs organogenesis and responsiveness to pathological stimuli through continuous bidirectional cross-talk between cardiomyocytes and non-cardiac cells. Here, we introduce the concept of the "cardiovascular unit" (CVU) as a building block of the heart, which includes cardiomyocytes and adjacent capillaries and fibroblasts. We discuss how the CVU might be used as a tool for re-interpreting degenerative changes of the myocardium during aging an...