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https://www.readbyqxmd.com/read/28533217/transcriptional-control-of-the-lateral-flagellar-genes-of-bradyrhizobium-diazoefficiens
#1
Elías J Mongiardini, J Ignacio Quelas, Carolina Dardis, M Julia Althabegoiti, Aníbal R Lodeiro
Bradyrhizobium diazoefficiens, the soybean N2-fixing symbiont, possesses a dual flagellar system comprising a constitutive subpolar flagellum and inducible lateral flagella. Here, we analyzed the genomic organization and biosynthetic regulation of the lateral-flagellar genes. We found that those genes are located in a single genomic cluster, organized in two monocistronic transcriptional units and three operons, one possibly containing an internal transcription start site. Among the monocistronic units is blr6846, homologous to the Class-IB master regulators of flagella synthesis in Brucella melitensis and Ensifer meliloti, and required for the expression of all the lateral-flagellar genes except lafA2, which locus encodes a single lateral flagellin...
May 22, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28527578/tr2-and-tr4-orphan-nuclear-receptors-an-overview
#2
Shin-Jen Lin, Dong-Rong Yang, Guosheng Yang, Chang-Yi Lin, Hong-Chiang Chang, Gonghui Li, Chawnshang Chang
Testicular nuclear receptors 2 and 4 (TR2, TR4), also known as NR2C1 and NR2C2, belong to the nuclear receptor superfamily and were first cloned in 1989 and 1994, respectively. Although classified as orphan receptors, several natural molecules, their metabolites, and synthetic compounds including polyunsaturated fatty acids (PUFAs), PUFA metabolites 13-hydroxyoctadecadienoic acid, 15-hydroxyeicosatetraenoic acid, and the antidiabetic drug thiazolidinediones can transactivate TR4. Importantly, many of these ligands/activators can also transactivate peroxisome proliferator-activated receptor gamma (PPARγ), also known as NR1C3 nuclear receptor...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28527573/retinoid-related-orphan-receptor-%C3%AE-and-transcriptional-control-of-neuronal-differentiation
#3
Hong Liu, Michihiko Aramaki, Yulong Fu, Douglas Forrest
The ability to generate neuronal diversity is central to the function of the nervous system. Here we discuss the key neurodevelopmental roles of retinoid-related orphan receptor β (RORβ) encoded by the Rorb (Nr1f2) gene. Recent studies have reported loss of function of the human RORB gene in cases of familial epilepsy and intellectual disability. Principal sites of expression of the Rorb gene in model species include sensory organs, the spinal cord, and brain regions that process sensory and circadian information...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28527252/-characterization-of-clinical-isolates-of-mycobacterium-tuberculosis-from-hiv-positive-individuals-in-colombia-2012
#4
Claudia Castro, Alba Ricardo, Angie Zabaleta, Claudia Llerena, Gloria Puerto
INTRODUCTION: One third of the increase in tuberculosis cases is attributed to the spread of HIV. In 2012, 1,397 HIV-associated tuberculosis cases were reported in Colombia, i.e., 11.8% of the total cases. Molecular epidemiology tools help to understand the transmission of tuberculosis. OBJECTIVE: To characterize clinical isolates of Mycobacterium tuberculosis derived from HIV-infected individuals, received at the Laboratorio Nacional de Referencia in the Instituto Nacional de Salud...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28526554/the-roles-of-orexins-in-sleep-wake-regulation
#5
REVIEW
Michihiro Mieda
Orexin A and orexin B are hypothalamic neuropeptides initially identified as endogenous ligands for two orphan G-protein coupled receptors (GPCRs). A deficiency of orexin signaling results in the sleep disorder narcolepsy-cataplexy in humans, dogs, and rodents, a sleep disorder characterized by excessive daytime sleepiness and cataplexy. Multiple approaches, including molecular genetic, electrophysiological, pharmacological, and neuroanatomical studies have suggested that orexins play critical roles in the maintenance of wakefulness by regulating the function of monoaminergic and cholinergic neurons that are implicated in the regulation of wakefulness...
May 16, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28525844/the-discovery-of-novel-potent-err-alpha-inverse-agonists-for-the-treatment-of-triple-negative-breast-cancer
#6
Yongli Du, Lianhua Song, Liudi Zhang, Hao Ling, Yanhui Zhang, Haifei Chen, Huijie Qi, Xiaojin Shi, Qunyi Li
The estrogen-related receptor α (ERRα) is an orphan receptor and a novel target for solid tumor therapy, conceivably through effects on the regulation of tumor cell energy metabolism associated with energy stress within solid tumor micro environments. Here we describe the discovery of novel potent inverse agonists of ERRα. In vitro, compound 11 potently inhibits ERRα's transcriptional activity by preventing endogenous PGC-1α and ERRα binding and suppresses the proliferation of different human cancer cell lines and the migration of breast cancer cells (MDA-MB-231)...
April 22, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28524870/autotrophic-and-heterotrophic-acquisition-of-carbon-and-nitrogen-by-a-mixotrophic-chrysophyte-established-through-stable-isotope-analysis
#7
Ramon Terrado, Alexis L Pasulka, Alle A-Y Lie, Victoria J Orphan, Karla B Heidelberg, David A Caron
Collectively, phagotrophic algae (mixotrophs) form a functional continuum of nutritional modes between autotrophy and heterotrophy, but the specific physiological benefits of mixotrophic nutrition differ among taxa. Ochromonas spp. are ubiquitous chrysophytes that exhibit high nutritional flexibility, although most species generally fall towards the heterotrophic end of the mixotrophy spectrum. We assessed the sources of carbon and nitrogen in Ochromonas sp. strain BG-1 growing mixotrophically via short-term stable isotope probing...
May 19, 2017: ISME Journal
https://www.readbyqxmd.com/read/28524673/detecting-gravitational-wave-memory-without-parent-signals
#8
Lucy O McNeill, Eric Thrane, Paul D Lasky
Gravitational-wave memory manifests as a permanent distortion of an idealized gravitational-wave detector and arises generically from energetic astrophysical events. For example, binary black hole mergers are expected to emit memory bursts a little more than an order of magnitude smaller in strain than the oscillatory parent waves. We introduce the concept of "orphan memory": gravitational-wave memory for which there is no detectable parent signal. In particular, high-frequency gravitational-wave bursts (≳kHz) produce orphan memory in the LIGO/Virgo band...
May 5, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28521378/-studies-in-rare-diseases-a-descriptive-analysis-of-completed-orphan-drug-benefit-assessments-at-the-federal-joint-committee
#9
Sandra Schulz, Anna Passon, Michael Kulig, Matthias Perleth, Katja Matthias
No abstract text is available yet for this article.
May 18, 2017: Das Gesundheitswesen
https://www.readbyqxmd.com/read/28520915/ovary-specific-depletion-of-the-nuclear-receptor-nr5a2-compromises-expansion-of-the-cumulus-oophorus-but-not-fertilization-by-icsi
#10
Kalyne Bertolin, Marie-Charlotte Meinsohn, João Suzuki, Jan Gossen, Kristina Schoonjans, Rajesha Duggavathi, Bruce D Murphy
The orphan nuclear receptor, liver receptor homolog-1 (Nr5a2) is widely expressed in mammalian tissues, its ovarian expression is restricted to granulosa cells of activated follicles. We employed the floxed Nr5a2 (Nr5a2f/f) mutant mouse line and two granulosa-specific Cre lines, Amhr2Cre and tgCyp19Cre, to develop two tissue- and time-specific Nr5a2 depletion models, Nr5a2Amhr2-/- and Nr5a2Cyp19-/-. In the Nr5a2Cyp19-/- ovaries, Nr5a2 was depleted in mural granulosa, but not cumulus cells. We induced follicular development in mutant and wild type (control, CON) mice with equine chorionic gonadotropin (eCG) followed 44h later treatment with human chorionic gonadotropin (hCG) to induce ovulation...
May 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28520909/large-scale-data-driven-integrative-framework-for-extracting-essential-targets-and-processes-from-disease-associated-gene-data-sets
#11
Gaston K Mazandu, Emile R Chimusa, Kayleigh Rutherford, Elsa-Gayle Zekeng, Zoe Z Gebremariam, Maryam Y Onifade, Nicola J Mulder
Populations worldwide currently face several public health challenges, including growing prevalence of infections and the emergence of new pathogenic organisms. The cost and risk associated with drug development make the development of new drugs for several diseases, especially orphan or rare diseases, unappealing to the pharmaceutical industry. Proof of drug safety and efficacy is required before market approval, and rigorous testing makes the drug development process slow, expensive and frequently result in failure...
May 18, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28511375/impact-of-nutritional-status-on-cognition-in-institutionalized-orphans-a-pilot-study
#12
Sanjana M Kamath, Kavana G Venkatappa, Ergod Manjunath Sparshadeep
INTRODUCTION: Proper nutrition is critical for maximizing brain function and enhancing learning. There is accumulating evidence that early malnutrition, marked by stunting, is associated with long-term deficits in cognitive and academic performance, even when social and psychological differences are controlled. All over the world, children living without permanent parental care are at a heightened risk for under-nutrition, putting their health and development in great jeopardy. AIM: To assess the nutritional and cognitive status in institutionalized orphans which might help to formulate effective interventions for improving the nutritional status of vulnerable children in future...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28510298/drugs-for-children
#13
S Ito
The "Therapeutic Orphan" status of children is gradually improving, but our efforts to eliminate off-label/off-evidence use must be sustained for safer and more effective pediatric drug therapy. This is even more important in resource-scarce settings, because of the increasing child population in those regions. The juncture of pediatric pharmacology and global child health represents an emerging field of clinical pharmacology illuminating a crucial societal need on a global scale.
June 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28508305/recent-advances-in-targeting-dna-repair-pathways-for-the-treatment-of-ovarian-cancer-and-their-clinical-relevance
#14
REVIEW
Katsutoshi Oda, Michihiro Tanikawa, Kenbun Sone, Mayuyo Mori-Uchino, Yutaka Osuga, Tomoyuki Fujii
Poly (ADP-ribose) polymerase (PARP) inhibitors have attracted much attention as one of the major molecular-targeted therapeutics for inhibiting DNA damage response. The PARP inhibitor, olaparib, has been clinically applied for treating certain recurrent ovarian cancer patients with BRCA1/2 mutations in Europe and the United States. It was also designated on 24 March 2017 as an orphan drug in Japan for similar clinical indications. In this review, we discuss (i) the prevalence of BRCA1/2 mutations in ovarian cancer, (ii) clinical trials of PARP inhibitors in ovarian cancer, (iii) genetic counseling for hereditary breast and ovarian cancer patients, and (iv) non-BRCA genes that may be associated with homologous recombination deficiency...
May 15, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28506594/fingolimod-and-teriflunomide-attenuate-neurodegeneration-in-mouse-models-of-neuronal-ceroid-lipofuscinosis
#15
Janos Groh, Kristina Berve, Rudolf Martini
CLN diseases are rare lysosomal storage diseases characterized by progressive axonal degeneration and neuron loss in the CNS, manifesting in disability, blindness, and premature death. We have previously demonstrated that, in animal models of infantile and juvenile forms of CLN disease (CLN1 and CLN3, respectively), secondary neuroinflammation in the CNS substantially amplifies neural damage, opening the possibility that immunomodulatory treatment might improve disease outcome. First, we recapitulated the inflammatory phenotype, originally seen in mice in autopsies of CLN patients...
May 13, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28503187/worker-reproduction-of-the-invasive-yellow-crazy-ant-anoplolepis-gracilipes
#16
Ching-Chen Lee, Hirotaka Nakao, Shu-Ping Tseng, Hung-Wei Hsu, Gwo-Li Lin, Jia-Wei Tay, Johan Billen, Fuminori Ito, Chow-Yang Lee, Chung-Chi Lin, Chin-Cheng Scotty Yang
BACKGROUND: Reproductive division of labor is one of the key features of social insects. Queens are adapted for reproduction while workers are adapted for foraging and colony maintenance. In many species, however, workers retain functional ovaries and can lay unfertilized male eggs or trophic eggs. Here we report for the first time on the occurrence of physogastric workers and apparent worker reproduction in the invasive yellow crazy ant Anoplolepis gracilipes (Fr. Smith). We further examined the reproductive potential and nutritional role of physogastric workers through multidisciplinary approaches including morphological characterization, laboratory manipulation, genetic analysis and behavioral observation...
2017: Frontiers in Zoology
https://www.readbyqxmd.com/read/28502923/g-protein-coupled-receptor-signaling-through-gpr176-gz-and-rgs16-tunes-time-in-the-center-of-the-circadian-clock-review
#17
Kaoru Goto, Masao Doi, Tianyu Wang, Sumihiro Kunisue, Iori Murai, Hitoshi Okamura
G-protein-coupled receptors (GPCRs) constitute an immensely important class of drug targets with diverse clinical applications. There are still more than 120 orphan GPCRs whose cognate ligands and physiological functions are not known. A set of circadian pacemaker neurons that governs daily rhythms in behavior and physiology resides in the suprachiasmatic nucleus (SCN) in the brain. Malfunction of the circadian clock has been linked to a multitude of diseases, such as sleeping disorders, obesity, diabetes, cardiovascular diseases, and cancer, which makes the clock an attractive target for drug development...
May 13, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28501860/single-center-experience-with-intimal-sarcoma-an-ultra-orphan-commonly-fatal-mesenchymal-malignancy
#18
Julie Van Dievel, Raf Sciot, Marion Delcroix, Raf O Vandeweyer, Maria Debiec-Rychter, Barbara Dewaele, Jasmien Cornillie, Thomas Van Cann, Bart Meyns, Patrick Schöffski
No abstract text is available yet for this article.
May 12, 2017: Oncology Research and Treatment
https://www.readbyqxmd.com/read/28500250/characterization-of-nmb-grp-and-their-receptors-brs3-nmbr-and-grpr-in-chickens
#19
Chunheng Mo, Long Huang, Lin Cui, Can Lv, Dongliang Lin, Liang Song, Guoqiang Zhu, Juan Li, Yajun Wang
The two structurally and functionally related peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) play critical roles in many physiological/pathological processes in mammals. However, the information regarding the expression and functionality of avian NMB, GRP, and their receptors is limited. Here, we characterized cNMB, cGRP and their receptors (cNMBR, cGRPR, cBRS3) in chickens. Our results showed that: 1) cNMBR and cGRPR expressed in CHO cells could be potently activated by cNMB and cGRP respectively, as monitored by cell-based luciferase reporter assays, indicating that cNMBR and cGRPR are cNMB- and cGRP-specific receptors; Strikingly, BRS3 of chickens (/spotted gars), which is orthologous to mouse bombesin receptor subtype-3 (BRS3), could be potently activated by GRP and NMB, demonstrating that both peptides are the endogenous ligands for chicken(/spotted gar) BRS3; 2) Quantitative real-time PCR revealed that cGRPR is widely expressed in chicken tissues with abundant expression in the ovary, pancreas, proventriculus, spinal cord and brain, whereas cNMB, cNMBR and cBRS3 are mainly expressed in the brain and testes; 3) Interestingly, qPCR, Western blot, and immuno-staining revealed that cGRP is predominantly expressed in the anterior pituitary and mainly localized to LH-cells, suggesting that cGRP is likely a novel pituitary hormone in chickens...
May 12, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28498099/synthekines-are-surrogate-cytokine-and-growth-factor-agonists-that-compel-signaling-through-non-natural-receptor-dimers
#20
Ignacio Moraga, Jamie B Spangler, Juan L Mendoza, Milica Gakovic, Tom S Wehrman, Peter Krutzik, K Christopher Garcia
Cytokine and growth-factor ligands typically signal through homo- or hetero-dimeric cell surface receptors via Janus Kinase (JAK/TYK), or Receptor Tyrosine Kinase (RTK)-mediated trans-phosphorylation. However, the number of receptor dimer pairings occurring in nature is limited to those driven by natural ligands encoded within our genome. We have engineered synthethic cytokines (synthekines) that drive formation of cytokine receptor dimer pairings that are not formed by endogenous cytokines and that are not found in nature, and which activate distinct signaling programs...
May 12, 2017: ELife
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