bluuebunny/crossref_metadata_2025_split huggingface dataset:
Draft Genome Sequence of
Limnobacter
sp. Strain CACIAM 66H1, a Heterotrophic Bacterium Associated with Cyanobacteria
Authors: da Silva Fábio Daniel Florêncio , Lima Alex Ranieri Jerônimo , Moraes Pablo Henrique Gonçalves , Siqueira Andrei Santos , Dall'Agnol Leonardo Teixeira , Baraúna Anna Rafaella Ferreira , Martins Luisa Carício , Oliveira Karol Guimarães , de Lima Clayton Pereira Silva , Nunes Márcio Roberto Teixeira , Vianez-Júnior João Lídio Silva Gonçalves , Gonçalves Evonnildo Costa 
Published: May 2016

ABSTRACT

Ecological interactions between cyanobacteria and heterotrophic prokaryotes are poorly known. To improve the genomic studies of heterotrophic bacterium-cyanobacterium associations, the draft genome sequence (3.2 Mbp) of
Limnobacter
sp. strain CACIAM 66H1, found in a nonaxenic culture of
Synechococcus
sp. (cyanobacteria), is presented here.
Draft Genome Sequence of
Flavobacterium
sp. Strain TAB 87, Able To Inhibit the Growth of Cystic Fibrosis Bacterial Pathogens Belonging to the Burkholderia cepacia Complex
Authors: Presta Luana , Inzucchi Ilaria , Bosi Emanuele , Fondi Marco , Perrin Elena , Miceli Elisangela , Tutino Maria Luisa , Lo Giudice Angelina , de Pascale Donatella , Fani Renato 
Published: May 2016

ABSTRACT

We report here the draft genome sequence of the
Flavobacterium
sp. TAB 87 strain, isolated from Antarctic seawater during a summer campaign near the French Antarctic station Dumont d'Urville (60°40′S, 40°01′E). It will allow for comparative genomics and the fulfillment of both fundamental and application-oriented investigations. It allowed the recognition of genes associated with the production of bioactive compounds and antibiotic resistance.
Complete Nucleotide Sequences and Genome Organization of Two Pepper Mild Mottle Virus Isolates from
Capsicum annuum
in South Korea
Authors: Choi Seung-Kook , Choi Gug-Seoun , Kwon Sun-Jung , Yoon Ju-Yeon 
Published: May 2016

ABSTRACT
The complete genome sequences of pepper mild mottle virus (PMMoV)-P2 and -P3 were determined by the Sanger sequencing method. Although PMMoV-P2 and PMMoV-P3 have different pathogenicity in some pepper cultivars, the complete genome sequences of PMMoV-P2 and -P3 are composed of 6,356 nucleotides (nt). In this study, we report the complete genome sequences and genome organization of PMMoV-P2 and -P3 isolates from pepper species in South Korea.
Venous sinus stenting in patients without idiopathic intracranial hypertension
Authors: Levitt Michael R , Albuquerque Felipe C , Gross Bradley A , Moon Karam , Jadhav Ashutosh P , Ducruet Andrew F , Crowley R Webster 
Published: May 2016

BackgroundVenous sinus stenting is an effective treatment for patients with idiopathic intracranial hypertension (IIH) and venous sinus stenosis.ObjectiveTo determine the usefulness of venous sinus stenting in the treatment of patients with symptomatic venous sinus stenosis without a diagnosis of IIH.MethodsWe performed a retrospective review of a prospective multicenter database of patients undergoing venous sinus stenting between January 2008 and February 2016. Patients with acute dural venous sinus thrombosis, arteriovenous fistula or arteriovenous malformation, or IIH were excluded. Clinical, radiological, and ophthalmological information was recorded.ResultsNine patients met the inclusion criteria and underwent venous sinus stenting for symptomatic dural venous sinus stenosis. Reasons for treatment included isolated unilateral pulsatile tinnitus (n=1), congenital hydrocephalus (n=2), unilateral pulsatile tinnitus following prior venous sinus thrombosis (n=1), acquired hydrocephalus following dural sinus thrombosis (n=2), meningitis (n=2) and tumor invasion into the dural venous sinus (n=1). Six patients underwent lumbar puncture or shunt tap, and all of these patients had elevated intracranial pressure. All stenoses were located in the transverse sinus, transverse–sigmoid junction and/or jugular bulb, and all were treated with self-expanding bare-metal stents. At follow-up, clinical symptoms had resolved in all but two patients, both of whom had congenital hydrocephalus and pre-existing shunts. There was no significant in-stent stenosis, and patients with ophthalmological follow-up demonstrated improvement of papilledema.ConclusionsDural venous sinus stenting may be an effective treatment for patients with symptomatic venous sinus stenosis without IIH in carefully selected cases, but may not be effective in resolving the symptoms of congenital hydrocephalus.
Constraints on the ωπ form factor from analyticity and unitarity
Authors: Ananthanarayan B. , Caprini Irinel , Kubis Bastian 
Published: May 2016

Form factors are important low-energy quantities and an accurate knowledge of these sheds light on the strong interactions. A variety of methods based on general principles have been developed to use information known in different energy regimes to constrain them in regions where experimental information needs to be tested precisely. Here we review our recent work on the electromagnetic [Formula: see text] form factor in a model-independent framework known as the method of unitarity bounds, partly motivated by the discrepancies noted recently between the theoretical calculations of the form factor based on dispersion relations and certain experimental data measured from the decay [Formula: see text]. We have applied a modified dispersive formalism, which uses as input the discontinuity of the [Formula: see text] form factor calculated by unitarity below the [Formula: see text] threshold and an integral constraint on the square of its modulus above this threshold. The latter constraint was obtained by exploiting unitarity and the positivity of the spectral function of a QCD correlator, computed on the spacelike axis by operator product expansion and perturbative QCD. An alternative constraint is obtained by using data available at higher energies for evaluating an integral of the modulus squared with a suitable weight function. From these conditions we derived upper and lower bounds on the modulus of the [Formula: see text] form factor in the region below the [Formula: see text] threshold. The results confirm the existence of a disagreement between dispersion theory and experimental data on the [Formula: see text] form factor around 0.6 GeV, including those from NA60 published in 2016.
Abstract A124: Amino acid availability modulates vacuolar-ATPase activity and assembly
Authors: Stransky Laura A. , Forgac Michael 
Published: May 2016

Abstract
Mechanistic target of rapamycin complex 1 (mTORC1) activity is frequently deregulated in cancers of many etiologies. The mechanisms governing its activity in normal and pathological settings are incompletely understood, particularly with respect to amino acid sensing, an important contributor to its activation. Characterization of the processes controlling mTORC1 activation by amino acids may identify novel targets with broad application to cancer treatment.
Amino acid sensing requires the Vacuolar H+-ATPase (V-ATPase), an ATP-dependent proton pump primarily responsible for the pH control of intracellular compartments. While it is known that the intact V-ATPase is necessary for mTORC1 activation by amino acids, the mechanism of its involvement unknown. We thus sought to determine if amino acids affect activity of the V-ATPase by assessing V-ATPase-dependent fluorescence quenching in lysosomes loaded with FITC-Dextran (a pH sensitive dye). Our data demonstrate that amino acid starvation increases V-ATPase activity, and that readdition of amino acids reverses this effect. We then demonstrated that amino acid starvation increases V-ATPase assembly, a main mode of regulation of the enzyme whereby association of the two functional domains, V1 and V0, is altered to increase or decrease the amount of active V-ATPase. Similarly to the change observed in activity, the change in V-ATPase assembly is reversed by amino acid readdition. These changes do not depend on PI3K or mTORC1 activity, both of which have been linked to changes in V-ATPase activity and assembly in response to other stimuli, such as glucose and growth factor stimulation. Further, we sought to determine if specific amino acids recapitulate the effect of total amino acid starvation, and preliminary data suggest that leucine and lysine both play important roles in controlling V-ATPase activity. These studies demonstrate that amino acid sensing controls V-ATPase activity and assembly, which may be important in subsequent signaling to mTORC1.
Citation Format: Laura A. Stransky, Michael Forgac. Amino acid availability modulates vacuolar-ATPase activity and assembly. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A124.
Abstract A147: MI130004, a new ADC with a payload of marine origin shows outstanding activity against HER2-expressing tumors
Authors: Aviles Pablo , Guillen Maria Jose , Dominguez Juan Manuel , Galmarini Carlos M. , Cuevas Carmen 
Published: May 2016

Abstract
PM050489 is a tubulin-binding agent originally isolated from the marine sponge Lithoplocamia lithistoides. This compound binds with very high affinity to β-tubulin at a new site, disrupting the microtubule network and impairing its function during divison, which leads to mitotic aberrations. MI130004 (a novel antibody-drug conjugate formed by PM050489, a non-hydrolysable linker and trastuzumab) was tested for its in vitro and in vivo activity against selected tumor cell lines with different levels of HER2 expression. In vitro MI130004 showed very high potency and good selectivity for tumor cells that overexpressed HER2, namely HCC-1954 (IC50, 0.036 μg/mL), SK-BR-3 (IC50, 0.017 μg/mL) and BT-474 (IC50, 0.156 μg/mL). At the cellular level, MI130004 impaired tubulin polymerization, causing disorganization and disintegration of the microtubule network which ultimately led to mitotic failure. Expressing HER2 cells of breast (BT-474 and JIMT-1), gastric (Gastric-008 and N87) and ovarian (SK-OV-3 and A2780cis) as well as negative HER2 breast (MDA-MB-231) and gastric (Hs748t) were subcutaneously implanted into immunosuppressed (SCID or athymic) mice. Tumor (ca. 115 mm3) bearing animals (N = 10/group) were randomly allocated to receive the ADC treatments (at different doses) or the appropriate control (placebo included). Treatments were administered weekly for 5
consecutive weeks. Tumor growth (as median/group) was calculated 2-3 times per week. Twenty-four hours after the first dose, representative tumors were dissected free and processed for HER2 expression (erb2) and chromatin organization (Hoescht 33258). The treatment with MI130004 induced a long lasting antitumor effect with statistically significant increases (P&lt;0.05) in median survival time compared to placebo. The highest dose of MI130004 induced complete tumor remissions in mice bearing BT-474, JIMT-1, Gastric-008, N87, SK-OV-3 and A2780cis xenografts lasting up to 120, 60, 165, 63, 237 and 231 days, respectively. Also 24-h post-dosing, MI130004 induced a dose-dependent disappearance of HER2-expressing cells as well as mitotic aberrations, this last being consistent with the mechanism of action of PM050489. These results demonstrate that PM050489, a marine derived compound, is a novel and remarkable payload for the design of new ADCs with potential therapeutic anti-cancer properties.
Citation Format: Pablo Aviles, Maria Jose Guillen, Juan Manuel Dominguez, Carlos M. Galmarini, Carmen Cuevas. MI130004, a new ADC with a payload of marine origin shows outstanding activity against HER2-expressing tumors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A147.
Abstract A201: UCHL1 promotes distant tumor metastasis through its deubiquitinating effect on HIF-1α
Authors: Harada Hiroshi 
Published: May 2016

Abstract
A Hypoxia-inducible transcription factor, HIF-1, has been associated with distant tumor metastases; however, genes that activate HIF-1 and promote metastases remain largely unknown. Here we identified Ubiquitin C-terminal hydrolase-L1 (UCHL1) as an novel activator of HIF-1 and revealed that it directly bound to HIF-1α, the regulatory subunit of HIF-1, abrogated the von Hippel-Lindau-mediated ubiquitination of HIF-1α, upregulated HIF-1 activity, and consequently promoted metastasis in murine models of pulmonary metastasis. Blockade of the UCHL1-HIF-1 axis by silencing UCHL1 or a pharmacological UCHL1 inhibitor, LDN57444, suppressed the formation of metastatic tumors. The expression levels of UCHL1 correlated with those of HIF-1α and were strongly associated with the poor prognosis of breast and lung cancer patients. These results indicate that UCHL1 promotes metastases as a deubiquitinating enzyme for HIF-1α, which justifies exploiting it as a prognostic marker and therapeutic target of cancers.
Citation Format: Hiroshi Harada. UCHL1 promotes distant tumor metastasis through its deubiquitinating effect on HIF-1α. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A201.
Abstract A202: Lipocalin2 stabilizes hypoxia inducible factor-1α through the iron delivery into normoxic cancer cells
Authors: Hama Susumu , Nakamura Ibuki , Nishimoto Akinori , Nishi Takayuki , Itakura Shoko , Kogure Kentaro 
Published: May 2016

Abstract
The level of lipocalin 2 (LCN2), a secreted protein of the lipocalin superfamily, increases in various tumors. Moreover, LCN2 is known to promote tumor progression with the hypoxia inducible factor-1α (HIF-1α)-mediated epithelial mesenchymal transition and angiogenesis. However, the mechanism of LCN2-induced HIF-1α activation is not fully understood. In the present study, we examined the effect of LCN2 on HIF-1α activation in the normoxic cancer cells that HIF-1α is immediately degraded. A mouse melanoma cell line, B16-F1, was treated with recomninant LCN2 protein under normoxic condition. After the treatment, the protein level and nuclear translocation of HIF-1α were examined by western blot and immunohistochemical staining, respectively. Moreover, the activation of HIF-1α was evaluated by reporter gene assay in the cells transfected with the plasmid DNA containing HIF-1α response element. The intracellular iron was quantified by iron colorimetric assay kit. In the B16-F1 cells treated with LCN2, HIF-1α protein was not degraded and its nuclear translocation was observed even under normoxic condition, suggesting that LCN2 stabilizes HIF-1α in normoxic cancer cells. Moreover, the HIF-1α-mediated transcriptional activity in the B16-F1 cells treated with LCN2 was significantly higher than those with non-treatment, suggesting that LCN2 activates HIF-1α in normoxic cancer cells. Next, to clarify the mechanism of LCN2-mediated HIF-1α activation, we hypothesized that LCN2, which is an Fe3+ transport protein, stabilizes HIF-1α by preventing the activity of proline hydroxylase (PHD) as a primary enzyme of HIF-1α degradation, because the increase of intracellular Fe3+ is known to inhibit PHD activity. As a result, the intracellular iron increased in the cells treated with LCN2 protein. Moreover, the level of HIF-1α by co-treatment of LCN2 with FeCl3 was higher than that only by LCN2 treatment. Collectively, LCN2-mediated Fe3+ influx stabilizes HIF-1α in normoxic cancer cells.
Citation Format: Susumu Hama, Ibuki Nakamura, Akinori Nishimoto, Takayuki Nishi, Shoko Itakura, Kentaro Kogure. Lipocalin2 stabilizes hypoxia inducible factor-1α through the iron delivery into normoxic cancer cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A202.
Abstract A4: CXCR3-B-mediated signaling suppresses c-MET-mediated angiogenic signals through the down-regulation of HO-1 and VEGF expression
Authors: Balan Murugabaskar , Pal Soumitro 
Published: May 2016

Abstract
Chemokine receptor CXCR3 gene encodes two splice variants with opposite functions; CXCR3-A promotes cell growth whereas CXCR3-B is growth inhibitory. Down-regulation of CXCR3-B promotes survival of many cancer cell types including Renal Cell Carcinoma (RCC) cells. However, the molecular signaling events that mediate down-regulation of CXCR3-B are not fully understood. Growth factors mediated signaling events govern Alternative Splicing (AS) of genes. The receptor tyrosine kinase c-MET is over-expressed in RCC cells and signaling through its ligand Hepatocyte Growth Factor (HGF) can play a major role in the growth and survival of tumor. In this study, we investigated the role of c-MET-mediated signaling in the modulation of AS of CXCR3 gene and analyzed the impact of CXCR3-B-mediated growth inhibitory signals on c-MET-mediated angiogenic pathway in RCC cells. We found that HGF treatment down-regulated CXCR3-B expression in both primary renal epithelial (RPTEC) and RCC (786-O and ACHN) cells. We found that c-MET-mediated signaling increased the expression of gene AS regulating protein SAM68 (also a prognostic marker for RCC) and modulated the association of SAM68 with CXCR3 gene. Utilizing gene over expression approach, we found that CXCR3-B-mediated signaling down-regulated the expression of cytoprotective molecule Hemeoxygenease-1 (HO-1) and angiogenic factor VEGF at both transcription and protein levels. We also found that CXCR3-B-mediated signaling down-regulated c-MET-induced secretion of angiogenic factors from RCC cells, as observed by the decrease in the tube formation ability of endothelial (HUVEC) cells grown with supernatant obtained from CXCR3-B over-expressing RCC cells culture.
Together, we suggest that CXCR3-B-mediated signaling acts as a checkpoint for c-MET-mediated angiogenic signals in RCC. We propose a novel function for c-MET-mediated signaling in promoting angiogenesis in renal cancer cells through the down-regulation of CXCR3-B expression.
Citation Format: Murugabaskar Balan, Soumitro Pal. CXCR3-B-mediated signaling suppresses c-MET-mediated angiogenic signals through the down-regulation of HO-1 and VEGF expression. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A4.
Abstract A41: Targeting the ARK5/MYC axis to develop second generation CDK4/6 inhibitors
Authors: Parekh Samir , Perumal Deepal , Kuo Pei Yu , Leshchenko Violetta , Jiang Zewei , Chari Ajai , Cho Hearn Jay , Jagannath Sundar , Reddy E. Premkumar 
Published: May 2016

Abstract
Inhibition of cyclin dependent kinases CDK4/6 is an emerging therapeutic approach in myeloma and other cancers. A direct link between MYC and the cell cycle machinery exists through its ability to directly transactivate the CCND1 and CCNE genes. Deregulated MYC expression is linked to increased cyclin A, cyclin E expression and activation of CDK4 via its direct target gene CDC25. We describe a novel mechanism of MYC silencing that is therapeutically targeted by small molecule inhibitors. ARK5 (AMPK-related protein kinase 5), a novel member of the human AMPK family, represses MYC and MYC-driven gene expression, leading to rapid induction of apoptosis and cell cycle arrest. RNAi loss of function studies confirm that ARK5 decreases MYC expression via post-translational de-acetylation by NAD-dependent deacetylase sirtuin 1 (SIRT1). In ARK5 over-expressing primary myeloma cells and cell lines, treatment with dual ARK5 and CDK4/6 inhibitor ON123300 resulted in down-regulation of pS6K, Rb and MYC, resulting in cell cycle arrest followed by apoptosis in vitro. Treatment of MM tumor-bearing mice with ON123300 significantly decreased the growth of tumors as opposed to control treated mice and was well tolerated, with no significant weight loss. The CDK4/6 selective inhibitor PD0332991 in contrast does not inhibit the ARK5 or mTOR/pS6K pathways. We hypothesized that the modest activity for the current class of CDK4/6 inhibitors could be the result of a narrow kinase inhibition profile and incomplete targeting of critical onco-kinases, resulting in cytostatic rather than cytotoxic effects. This is the first report showing that dual CDK4/6 and ARK5 inhibitor ON123300 has significant effects on mTOR and MYC. In summary, our results demonstrate a novel mechanistic connection between ARK5 and SIRT1 in the regulation of MYC in MM cells. Our data showing potent cytotoxicity of ARK5 inhibition along with inhibition of MYC and mTOR signaling provides the foundation for further development of ARK5 inhibitors and second generation CDK inhibitors such as ON123300 for MM and potentially other MYC over expressing cancers.
Citation Format: Samir Parekh, Deepal Perumal, Pei Yu Kuo, Violetta Leshchenko, Zewei Jiang, Ajai Chari, Hearn Jay Cho, Sundar Jagannath, E. Premkumar Reddy. Targeting the ARK5/MYC axis to develop second generation CDK4/6 inhibitors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A41.
Abstract A46: Exposure of quercetin, kaempferol and exogenous glutathione on the expression levels of phospho- and total-Akt in 3T3-L1 preadipocytes
Authors: Boadi William Y. 
Published: May 2016

Abstract
Obesity has been reported to be a risk factor for several types of cancer. The Akt pathway or PI3K-Akt pathway is a signal transduction pathway that promotes survival and growth in response to extracellular signals. Key proteins involved are phosphatidylinositol 3-kinase (PI3K) and Akt, or Protein Kinase B. Activated Akt mediates downstream responses, including cell survival, growth, proliferation, cell migration and angiogenesis, by phosphorylating a range of intracellular proteins. The effects of the exposure of several doses each of the flavonoids quercetin and kaempferol and that of exogenous glutathione (GSH) (at 0, 5 10, 15, 20 and 25 μM doses) for 24 hr on the expression levels of phospho- and total-Akt levels in 3T3-L1 preadipocytes were investigated. Phospho-, total-Akt and the expression levels of glyceraldehyde 3-phosphate dehydrogenase (GAPDH, which was used as an internal standard) were assayed by the MILLIPLEX® MAP mates protocol, based on the Luminex® xMAP® technology (Millipore Corp. St. Charles, MI). There were no significant differences in the expression levels of GAPDH for the tested compounds and at the different concentrations. Significant (p&lt;0.05) decreases however, in the espression levels of phospho-Akt in cells for the quercetin, kaempferol and GSH treated samples were observed. Total-Akt levels remained the same and, were not significantly different from each other for the tested compounds and at the various concentrations. The results may indicate that exposure of 3T3-L1 preadipocytes to quercetin, kaempferol and GSH did not result in the activation of Akt suggesting the role of such compounds in blocking cell differentiation in 3T3-L1 cells. Thus, quercetin, kaempferol and GSH may significantly cause a decrease in the proliferation of 3T3-L1 preadipocytes, suggesting an association with the low phosphorylation of the Akt protein.
Citation Format: William Y. Boadi. Exposure of quercetin, kaempferol and exogenous glutathione on the expression levels of phospho- and total-Akt in 3T3-L1 preadipocytes. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A46.