Rubrobacter aplysinae sp. nov., isolated from the marine sponge Aplysina aerophoba

A Gram-stain-positive, non-spore-forming bacterium (strain RV113(T)) was isolated from the marine sponge Aplysina aerophoba. 16S rRNA gene sequence analysis showed that strain RV113(T) belongs to the genus Rubrobacter, and is related most closely to Rubrobacter bracarensis VF70612_S1(T) (96.9% similarity) and more distantly related (<93%) to all other species of the genus Rubrobacter. The peptidoglycan diamino acid was lysine. Strain RV113(T) exhibited a quinone system with menaquinone MK-8 as the predominant compound. The polar lipid profile of strain RV113(T) consisted of the major compounds phosphatidylglycerol and two unidentified phosphoglycolipids. The major fatty acid was anteiso-C17 : 0ω9c. These chemotaxonomic traits are in agreement with those of other species of the genus Rubrobacter. The results of physiological and biochemical tests allowed the clear phenotypic differentiation of strain RV113(T) from all recognized Rubrobacter species. Strain RV113(T) is thus considered to represent a novel species, for which the name Rubrobacter aplysinae sp. nov. is proposed. The type strain is RV113(T) ( = DSM 27440(T) = CECT 8425(T))

Actinokineospora spheciospongiae sp. nov., isolated from the marine sponge Spheciospongia vagabunda

A Gram-positive staining, aerobic organism, isolated from the the Red Sea sponge Spheciospongia vagabunda was investigated for its taxonomic position. Based on 16S rRNA gene sequence analysis strain EG49T was most closely related to Actinokineospora cibodasensis and Actinokineospora baliensis (both 97.3%) and Actinokineospora diospyrosas and Actinokineospora auranticolor (both 97.0%). The 16S rRNA gene sequence similarity to all other Actinokineospora species was < 97.0 %. The quinone system of strain EG49T contains the menaqinone MK-9(H4), (47%), MK-9(H6), (27%) and MK-9(H2), (15%) in major amounts. Minor amounts of MK-7(H4), (2%), MK-9(H0), (1%), MK-9(H8) (3%) and MK-10(H4) (3%) were detected as well in addition to MK-8(H4), MK-8(H6), MK-10(H2) and MK-10(H6) (all <1%). The diagnostic diaminoacid of the peptidoglycan is meso-diaminopimelic acid. In the polar lipid profile, diphosphatidylglycerol, phosphatidylethanolamine, and hydroxyl-phosphatidylethanolamine are predominant. Phosphatidylinositol-mannoside, two unidentified phospholipids and two glycoglipids as well as one aminoglycolipid, one aminolipid and one unidentified lipid are found in addition. Fatty acid profile composed of mainly iso-branched fatty acids: iso-C16:0, iso-C14:0, iso-C15:0, and iso-C16:1 H. All these data clearly supported the allocation of the strain to the genus Actinokineospora. In addition, the results of physiological and biochemical tests also allowed phenotypic differentiation of strain EG49T from the most closely related Actinokineospora species. Strain EG49T represents a new species of the genus Actinokineospora, for which we propose the name Actinokineospora spheciospongiae sp. nov., with strain EG49T (= DSM 45935T = CCM 8480T = LMG 27700T) as the type strain

Draft Genome Sequence of the Antitrypanosomally Active Sponge-Associated Bacterium Actinokineospora sp. Strain EG49

The marine sponge-associated bacterium Actinokineospora sp. strain EG49 produces the antitrypanosomal angucycline-like compound actinosporin A. The draft genome of Actinokineospora sp. EG49 has a size of 7.5 megabases and a GC content of 72.8% and contains 6,629 protein-coding sequences (CDS). antiSMASH predicted 996 genes residing in 36 secondary metabolite gene clusters

Metabolic profling of cytotoxic metabolites from five Tabebuia species supported by molecular correlation analysis

Tabebuia is the largest genus among the family Bignoniaceae. Tabebuia species are known for their high ornamental and curative value. Here, the cytotoxic potential of extracts from the leaves and stems of fve Tabebuia species was analyzed. The highest activity was observed for T. rosea (Bertol.) DC. stem extract against HepG2 cell line (IC50 4.7 µg/mL), T. pallida L. stem extract against MCF-7 cell line (IC50 6.3 µg/mL), and T. pulcherrima stem extract against CACO2 cell line (IC50 2.6 µg/mL). Metabolic profiling of the ten extracts using liquid chromatography–high-resolution mass spectrometry for dereplication purposes led to annotation of forty compounds belonging to diferent chemical classes. Among the annotated compounds, irridoids represent the major class. Principle component analysis (PCA) was applied to test the similarity and variability among the tested species and the score plot showed similar chemical profling between the leaves and stems of both T. pulcherrima and T. pallida L. and unique chemical profling among T. rosea (Bertol.) DC., T. argentea Britton, and T. guayacan (Seem.) Hemsl. leaf extracts and the stem extract of T. rosea (Bertol.) DC. Additionally, a molecular correlation analysis was used to annotate the bioactive cytotoxic metabolites in the extracts and correlate between their chemical and biological profles

A New Bioactive Compound From the Marine Sponge-Derived Streptomyces sp. SBT348 Inhibits Staphylococcal Growth and Biofilm Formation

Staphylococcus epidermidis, the common inhabitant of human skin and mucosal surfaces has emerged as an important pathogen in patients carrying surgical implants and medical devices. Entering the body via surgical sites and colonizing the medical devices through formation of multi-layered biofilms leads to refractory and persistent device-related infections (DRIs). Staphylococci organized in biofilms are more tolerant to antibiotics and immune responses, and thus are difficult-to-treat. The consequent morbidity and mortality, and economic losses in health care systems has strongly necessitated the need for development of new anti-bacterial and anti-biofilm-based therapeutics. In this study, we describe the biological activity of a marine sponge-derived Streptomyces sp. SBT348 extract in restraining staphylococcal growth and biofilm formation on polystyrene, glass, medically relevant titan metal, and silicone surfaces. A bioassay-guided fractionation was performed to isolate the active compound (SKC3) from the crude SBT348 extract. Our results demonstrated that SKC3 effectively inhibits the growth (MIC: 31.25 μg/ml) and biofilm formation (sub-MIC range: 1.95–<31.25 μg/ml) of S. epidermidis RP62A in vitro. Chemical characterization of SKC3 by heat and enzyme treatments, and mass spectrometry (HRMS) revealed its heat-stable and non-proteinaceous nature, and high molecular weight (1258.3 Da). Cytotoxicity profiling of SKC3 in vitro on mouse fibroblast (NIH/3T3) and macrophage (J774.1) cell lines, and in vivo on the greater wax moth larvae Galleria mellonella revealed its non-toxic nature at the effective dose. Transcriptome analysis of SKC3 treated S. epidermidis RP62A has further unmasked its negative effect on central metabolism such as carbon flux as well as, amino acid, lipid, and energy metabolism. Taken together, these findings suggest a potential of SKC3 as a putative drug to prevent staphylococcal DRIs

Cytotoxic Activity and Metabolic Profiling of Fifteen Euphorbia Species

Euphorbia is a large genus of flowering plants with a great diversity in metabolic pattern. Testing the cytotoxic potential of fifteen Euphorbia species revealed highest activity of E. officinarum L. against CACO2 cell line (IC50 7.2 µM) and of E. lactea Haw. against HepG2 and MCF-7 cell lines (IC50 5.2 and 5.1 µM, respectively). Additionally, metabolic profiling of the fifteen tested species, using LC-HRMS, for dereplication purposes, led to the annotation of 44 natural compounds. Among the annotated compounds, diterpenoids represent the major class. Dereplication approach and multivariate data analysis are adopted in order to annotate the compounds responsible for the detected cytotoxic activity. Results of PCA come in a great accordance with results of biological testing, which emphasized the cytotoxic properties of E. lactea Haw. A similarity correlation network showed that the two compounds with the molecular formula C16H18O8 and C20H30O10, are responsible for cytotoxic activity against MCF-7 and HepG2 cell lines. Similarly, the compound with molecular formula C18H35NO correlates with cytotoxic activity against CACO2

The metabolomic analysis of five Mentha species: cytotoxicity, anti-Helicobacter assessment, and the development of polymeric micelles for enhancing the anti-Helicobacter activity

Mentha species are medicinally used worldwide and remain attractive for research due to the diversity of their phytoconstituents and large therapeutic indices for various ailments. This study used the metabolomics examination of five Mentha species (M. suaveolens, M. sylvestris, M. piperita, M. longifolia, and M. viridis) to justify their cytotoxicity and their anti-Helicobacter effects. The activities of species were correlated with their phytochemical profiles by orthogonal partial least square discriminant analysis (OPLS-DA). Tentatively characterized phytoconstituents using liquid chromatography high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) included 49 compounds: 14 flavonoids, 10 caffeic acid esters, 7 phenolic acids, and other constituents. M. piperita showed the highest cytotoxicity to HepG2 (human hepatoma), MCF-7 (human breast adenocarcinoma), and CACO2 (human colon adenocarcinoma) cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. OPLS-DA and dereplication studies predicted that the cytotoxic activity was related to benzyl glucopyranoside-sulfate, a lignin glycoside. Furthermore, M. viridis was effective in suppressing the growth of Helicobacter pylori at a concentration of 50 mg mL−1. OPLS-DA predicted that this activity was related to a dihydroxytrimethoxyflavone. M. viridis extract was formulated with Pluronic® F127 to develop polymeric micelles as a nanocarrier that enhanced the anti-Helicobacter activity of the extract and provided minimum inhibitory concentrations and minimum bactericidal concentrations of 6.5 and 50 mg mL−1, respectively. This activity was also correlated to tentatively identified constituents, including rosmarinic acid, catechins, carvone, and piperitone oxide

The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer

<p>Abstract</p> <p>Background</p> <p>The discordance between steady-state levels of mRNAs and protein has been attributed to posttranscriptional control mechanisms affecting mRNA stability and translation. Traditional methods of genome wide microarray analysis, profiling steady-state levels of mRNA, may miss important mRNA targets owing to significant posttranscriptional gene regulation by RNA binding proteins (RBPs).</p> <p>Methods</p> <p>The ribonomic approach, utilizing RNA immunoprecipitation hybridized to microarray (RIP-Chip), provides global identification of putative endogenous mRNA targets of different RBPs. HuR is an RBP that binds to the AU-rich elements (ARE) of labile mRNAs, such as proto-oncogenes, facilitating their translation into protein. HuR has been shown to play a role in cancer progression and elevated levels of cytoplasmic HuR directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. HuR has been described to control genes in several of the acquired capabilities of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established.</p> <p>Results</p> <p>We used HuR RIP-Chip as a comprehensive and systematic method to survey breast cancer target genes in both MCF-7 (estrogen receptor positive, ER+) and MDA-MB-231 (estrogen receptor negative, ER-) breast cancer cell lines. We identified unique subsets of HuR-associated mRNAs found individually or in both cell types. Two novel HuR targets, <it>CD9 </it>and <it>CALM2 </it>mRNAs, were identified and validated by quantitative RT-PCR and biotin pull-down analysis.</p> <p>Conclusion</p> <p>This is the first report of a side-by-side genome-wide comparison of HuR-associated targets in wild type ER+ and ER- breast cancer. We found distinct, differentially expressed subsets of cancer related genes in ER+ and ER- breast cancer cell lines, and noted that the differential regulation of two cancer-related genes by HuR was contingent upon the cellular environment.</p

Computational analysis of expression of human embryonic stem cell-associated signatures in tumors

<p>Abstract</p> <p>Background</p> <p>The cancer stem cell model has been proposed based on the linkage between human embryonic stem cells and human cancer cells. However, the evidences supporting the cancer stem cell model remain to be collected. In this study, we extensively examined the expression of human embryonic stem cell-associated signatures including core genes, transcription factors, pathways and microRNAs in various cancers using the computational biology approach.</p> <p>Results</p> <p>We used the class comparison analysis and survival analysis algorithms to identify differentially expressed genes and their associated transcription factors, pathways and microRNAs among normal vs. tumor or good prognosis vs. poor prognosis phenotypes classes based on numerous human cancer gene expression data. We found that most of the human embryonic stem cell- associated signatures were frequently identified in the analysis, suggesting a strong linkage between human embryonic stem cells and cancer cells.</p> <p>Conclusions</p> <p>The present study revealed the close linkage between the human embryonic stem cell associated gene expression profiles and cancer-associated gene expression profiles, and therefore offered an indirect support for the cancer stem cell theory. However, many interest issues remain to be addressed further.</p

MicroRNA networks direct neuronal development and plasticity

MicroRNAs (miRNAs) constitute a class of small, non-coding RNAs that act as post-transcriptional regulators of gene expression. In neurons, the functions of individual miRNAs are just beginning to emerge, and recent studies have elucidated roles for neural miRNAs at various stages of neuronal development and maturation, including neurite outgrowth, dendritogenesis, and spine formation. Notably, miRNAs regulate mRNA translation locally in the axosomal and synaptodendritic compartments, and thereby contribute to the dynamic spatial organization of axonal and dendritic structures and their function. Given the critical role for miRNAs in regulating early brain development and in mediating synaptic plasticity later in life, it is tempting to speculate that the pathology of neurological disorders is affected by altered expression or functioning of miRNAs. Here we provide an overview of recently identified mechanisms of neuronal development and plasticity involving miRNAs, and the consequences of miRNA dysregulation