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https://www.readbyqxmd.com/read/28646017/ror%C3%AE-modulates-semaphorin-3e-transcription-and-neurovascular-interaction-in-pathological-retinal-angiogenesis
#1
Ye Sun, Chi-Hsiu Liu, Zhongxiao Wang, Steven S Meng, Samuel B Burnim, John Paul SanGiovanni, Theodore M Kamenecka, Laura A Solt, Jing Chen
Pathological proliferation of retinal blood vessels commonly causes vision impairment in proliferative retinopathies, including retinopathy of prematurity. Dysregulated crosstalk between the vasculature and retinal neurons is increasingly recognized as a major factor contributing to the pathogenesis of vascular diseases. Class 3 semaphorins (SEMA3s), a group of neuron-secreted axonal and vascular guidance factors, suppress pathological vascular growth in retinopathy. However, the upstream transcriptional regulators that mediate the function of SEMA3s in vascular growth are poorly understood...
June 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28644125/exploiting-crispr-cas-to-manipulate-enterococcus-faecalis-populations
#2
Karthik Hullahalli, Marinelle Rodrigues, Kelli L Palmer
CRISPR-Cas provides a barrier to horizontal gene transfer in prokaryotes. It was previously observed that functional CRISPR-Cas systems are absent from multidrug-resistant (MDR) Enterococcus faecalis, which only possess an orphan CRISPR locus, termed CRISPR2, lacking cas genes. It was of interest to investigate how the interplay between CRISPR-Cas genome defense and antibiotic selection for mobile genetic elements shapes E. faecalis populations. Here, we demonstrate that CRISPR2 can be reactivated for genome defense in MDR strains...
June 23, 2017: ELife
https://www.readbyqxmd.com/read/28642167/mice-lacking-gpr37-exhibit-decreased-expression-of-the-myelin-associated-glycoprotein-mag-and-increased-susceptibility-to-demyelination
#3
Brilee M Smith, Michelle M Giddens, Jessica Neil, Sharon Owino, TrangKimberly T Nguyen, Duc Duong, Fengqiao Li, Randy A Hall
GPR37 is an orphan G protein-coupled receptor that is predominantly expressed in the brain and found at particularly high levels in oligodendrocytes. GPR37 has been shown to exert effects on oligodendrocyte differentiation and myelination during development, but the molecular basis of these actions is incompletely understood and moreover nothing is known about the potential role(s) of this receptor under demyelinating conditions. To shed light on the fundamental biology of GPR37, we performed proteomic studies comparing protein expression levels in the brains of mice lacking GPR37 and its close relative GPR37-like 1 (GPR37L1)...
June 19, 2017: Neuroscience
https://www.readbyqxmd.com/read/28642062/lrh-1-senses-signaling-from-phosphatidylcholine-to-regulate-the-expansion-growth-of-digestive-organs-via-synergy-with-wnt-%C3%AE-catenin-signaling-in-zebrafish
#4
Gang Zhai, Jia Song, Tingting Shu, Junjun Yan, Xia Jin, Jiangyan He, Zhan Yin
Liver receptor homolog-1 (LRH-1) is an orphan nuclear receptor that is critical for the growth and proliferation of cancer cells and other biological processes, including lipid transportation and metabolism, sexual determination and steroidogenesis. However, because homozygous lrh-1(-/-) mice die in utero, the regulatory mechanisms involved in embryonic development mediated by this receptor are poorly understood. In the present study, we performed transcription activator-like effector nuclease (TALEN)-mediated loss-of-function assays, taking advantage of zebrafish external fertilization, to investigate the function of lrh-1...
April 27, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/28639105/towards-efficiency-in-rare-disease-research-what-is-distinctive-and-important
#5
REVIEW
Jinmeng Jia, Tieliu Shi
Characterized by their low prevalence, rare diseases are often chronically debilitating or life threatening. Despite their low prevalence, the aggregate number of individuals suffering from a rare disease is estimated to be nearly 400 million worldwide. Over the past decades, efforts from researchers, clinicians, and pharmaceutical industries have been focused on both the diagnosis and therapy of rare diseases. However, because of the lack of data and medical records for individual rare diseases and the high cost of orphan drug development, only limited progress has been achieved...
June 16, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28638936/nuclear-receptors-in-neural-stem-progenitor-cell-homeostasis
#6
REVIEW
Dimitrios Gkikas, Matina Tsampoula, Panagiotis K Politis
In the central nervous system, embryonic and adult neural stem/progenitor cells (NSCs) generate the enormous variety and huge numbers of neuronal and glial cells that provide structural and functional support in the brain and spinal cord. Over the last decades, nuclear receptors and their natural ligands have emerged as critical regulators of NSC homeostasis during embryonic development and adult life. Furthermore, substantial progress has been achieved towards elucidating the molecular mechanisms of nuclear receptors action in proliferative and differentiation capacities of NSCs...
June 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28637666/nr4a-orphan-nuclear-receptor-family-members-nr4a2-and-nr4a3-regulate-neutrophil-number-and-survival
#7
Lynne R Prince, Svenja Dannewitz Prosseda, Kathryn Higgins, Jennifer Carlring, Elizabeth C Prestwich, Nikolay V Ogryzko, Atiqur Rahman, Alexander Basran, Francesco Falciani, Philip Taylor, Stephen A Renshaw, Moira K B Whyte, Ian Sabroe
Neutrophil lifespan is plastic and highly responsive to factors that regulate cellular survival. Defects in neutrophil number and survival are common to both hematologic disorders and chronic inflammatory diseases. At sites of inflammation, neutrophils respond to multiple signals that activate protein kinase A (PKA) signaling, which positively regulates neutrophil survival. The aim of this study was to define transcriptional responses to PKA activation and to delineate the roles of these factors in neutrophil function and survival...
June 21, 2017: Blood
https://www.readbyqxmd.com/read/28636277/esrrb-plays-a-crucial-role-in-the-promotion-of-porcine-cell-reprogramming
#8
Fan Yang, Yahui Ren, Huan Li Huayan Wang
The estrogen-related receptor b (ESRRB) is an orphan nuclear receptor and targets many genes involved in self-renewal and pluripotency. In mouse ES cells, overexpression of ESRRB can maintain LIF-independent self-renewal in the absence of Nanog. However, the fundamental features of porcine ESRRB remain elusive. In this study, we revealed the expression profiles of ESRRB in both porcine pluripotent stem cells and early stage embryos and dissected the functional domains of ESRRB protein to prove that ESRRB is a key transcription factor that enhanced porcine pluripotent gene activation...
June 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28630384/modulation-of-cd4-t-cell-subsets-by-euphorbia-microciadia-and-euphorbia-osyridea-plant-extracts
#9
Haideh Namdari, Maryam Izad, Zahra Amirghofran
BACKGROUND: Euphorbia plants are traditionally used in folk medicine for infections, inflammation, and cancer. OBJECTIVES: To investigate the effects of the butanolic extracts of Euphorbia micorociadia and Euphorbia osyridea on specific transcription factors and cytokines expression of T cell subsets. METHODS: Activated mouse splenocytes were cultured in the presence of non-cytotoxic concentrations of the extracts. Cells were evaluated for the gene expressions of T cell transcription factors and cytokines of T helper (Th)1 [T-bet and interferon gamma (IFNγ)], Th17 [retinoic acid receptor related orphan receptor (RORγt) and interleukin (IL)-17], and T regulatory (Treg) cells [forkhead box P3(Foxp3), IL-10, and Transforming growth factor (TGF)-β] using real-time PCR...
June 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28629392/do-investors-value-the-fda-orphan-drug-designation
#10
Kathleen L Miller
BACKGROUND: The Orphan Drug Act is an important piece of legislation that uses financial incentives to encourage the development of drugs that treat rare diseases. This analysis studies the effects of a portion of the Orphan Drug Act, the orphan drug designation. Specifically, it studies the value that investors place on the orphan drug designation, by investigating how investors react to companies' announcing that their product has received the designation. RESULTS: The results, on average, show that the stock price of a company increases by 3...
June 19, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28628775/developing-new-pet-tracers-to-image-the-growth-hormone-secretagogue-receptor-1a-ghs-r1a
#11
Kazunori Kawamura, Masayuki Fujinaga, Yoko Shimoda, Tomoteru Yamasaki, Yiding Zhang, Akiko Hatori, Lin Xie, Hidekatsu Wakizaka, Katsushi Kumata, Takayuki Ohkubo, Yusuke Kurihara, Masanao Ogawa, Nobuki Nengaki, Ming-Rong Zhang
INTRODUCTION: `The growth hormone secretagogue receptor 1a (GHS-R1a) is the orphan G-protein-coupled receptor, and its endogenous ligand is ghrelin. GHS-R1a contributes to regulation of glucose homeostasis, memory and learning, food addiction, and neuroprotection. Several PET tracers for GHS-R1a have been developed, but none have been reported to be clinically applicable to GHS-R1a imaging. In this study, we developed three new PET tracers for GHS-R1a: (18)F-labeled 6-(4-chlorophenyl)-3-((1-(2-fluoroethyl)piperidin-3-yl)methyl)-2-(o-tolyl)quinazolin-4(3H)-one (1), (11)C-labeled 6-(4-chlorophenyl)-3-((1-(2-methoxyethyl)piperidin-3-yl)methyl)-2-(o-tolyl)quinazolin-4(3H)-one (2), and (11)C-labeled (S)-(4-(1H-indole-6-carbonyl)-3-methylpiperazin-1-yl)(4'-methoxy-[1,1'-biphenyl]-4-yl)methanone (3)...
June 10, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28627642/effect-of-retinoid-x-receptor-%C3%AE-nuclear-export-inhibition-on-apoptosis-of-neurons-in%C3%A2-vivo-and-in%C3%A2-vitro
#12
Yingchun Liu, Jiangguo Tang, Xiaoxiao Gao, Min Wang, Jie Shen, Xiaoqing You
Alzheimer's disease (AD), which is characte-rized by excessive apoptosis of neurons, is considered to be a global public health crisis. Retinoid-induced apoptosis is dependent on the orphan nuclear receptor Nur77, a transcription factor that is expressed predominantly in brain tissues. Nur77 nuclear export requires retinoid X receptor‑α (RXRα) as a carrier. However, the involvement of Nur77 in mediating β‑amyloid (Aβ)‑induced neuronal apoptosis has not yet been elucidated. The primary aim of the present study was to investigate the potential of Nur77 in Aβ‑induced neuron apoptosis, and to evaluate the effect of RXRα nuclear export inhibition on neuronal apoptosis...
June 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627588/il%C3%A2-22-expression-is-increased-variedly-in-the-initial-phase-onset-and-chronic-phase-of-a-pristane%C3%A2-induced-arthritis-rat-model
#13
Weikun Hou, Bo Wang, Yan Zhou, Ke Xu, Liesu Meng, Wenhua Zhu, Congshan Jiang, Peng Xu, Shemin Lu
The aim of the present study was to investigate the expression pattern of T helper (Th) 17 and Th22 cell-related factors in a pristane‑induced arthritis (PIA) rat model. PIA rats were divided into the initial phase group [day (D) 6 post‑pristane injection], the onset of clinical arthritis group (D12), the acute arthritis group (D26) and the chronic arthritis group (D70). Rats injected with saline alone were used as the control group. The mRNA expression levels of interleukin (IL)‑17A, IL‑17F, interferon (IFN)‑γ, IL‑22, IL‑22 receptor (R) 1, IL‑22 binding protein (BP) and RAR‑related orphan receptor α were examined in the spleen and/or synovium of the various phases of PIA rats by reverse transcription‑quantitative polymerase chain reaction analysis...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626275/phylogeny-of-saprobic-microfungi-from-southern-europe
#14
M Hernández-Restrepo, J Gené, R F Castañeda-Ruiz, J Mena-Portales, P W Crous, J Guarro
During a survey of saprophytic microfungi on decomposing woody, herbaceous debris and soil from different regions in Southern Europe, a wide range of interesting species of asexual ascomycetes were found. Phylogenetic analyses based on partial gene sequences of SSU, LSU and ITS proved that most of these fungi were related to Sordariomycetes and Dothideomycetes and to lesser extent to Leotiomycetes and Eurotiomycetes. Four new monotypic orders with their respective families are proposed here, i.e. Lauriomycetales, Lauriomycetaceae; Parasympodiellales, Parasympodiellaceae; Vermiculariopsiellales, Vermiculariopsiellaceae and Xenospadicoidales, Xenospadicoidaceae...
March 2017: Studies in Mycology
https://www.readbyqxmd.com/read/28623849/population-pharmacokinetics-pharmacodynamics-of-3-4-diaminopyridine-free-base-in-patients-with-lambert-eaton-myasthenia
#15
Nilay Thakkar, Jeffrey T Guptill, Kathy Aleš, David Jacobus, Laura Jacobus, Charles Peloquin, Michael Cohen-Wolkowiez, Daniel Gonzalez
Lambert-Eaton Myasthenia (LEM) is a rare autoimmune disorder associated with debilitating muscle weakness. There are limited treatment options and 3,4-diaminopyridine free base (3,4-DAP) is an investigational orphan drug used to treat LEM-related weakness. We performed a population PK/PD analysis using 3,4-DAP and metabolite concentrations collected from a phase 2 study in LEM patients. The Triple Timed Up & Go (3TUG) assessment, which measures lower extremity weakness, was the primary outcome measure. A total of 1270 PK samples (49 patients) and 1091 3TUG data points (32 randomized patients) were included in the PK/PD analysis...
June 17, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28621663/ionotropic-receptor-dependent-moist-and-dry-cells-control-hygrosensation-in-drosophila
#16
Zachary A Knecht, Ana F Silbering, Joyner Cruz, Ludi Yang, Vincent Croset, Richard Benton, Paul A Garrity
Insects use hygrosensation (humidity sensing) to avoid desiccation and, in vectors such as mosquitoes, to locate vertebrate hosts. Sensory neurons activated by either dry or moist air ('dry cells' and 'moist cells') have been described in many insects, but their behavioral roles and the molecular basis of their hygrosensitivity remain unclear. We recently reported that Drosophila hygrosensation relies on three Ionotropic Receptors (IRs) required for dry cell function: IR25a, IR93a and IR40a (Knecht et al., 2016)...
June 16, 2017: ELife
https://www.readbyqxmd.com/read/28620457/early-fruiting-in-synsepalum-dulcificum-schumach-thonn-daniell-juveniles-induced-by-water-and-inorganic-nutrient-management
#17
Dèdéou Apocalypse Tchokponhoué, Sognigbé N'Danikou, Iago Hale, Allen Van Deynze, Enoch Gbènato Achigan-Dako
Background. The miracle plant, Synsepalum dulcificum (Schumach. & Thonn.) Daniell is a native African orphan crop species that has recently received increased attention due to its promise as a sweetener and source of antioxidants in both the food and pharmaceutical industries. However, a major obstacle to the species' widespread utilization is its relatively slow growth rate and prolonged juvenile period. Method. In this study, we tested twelve treatments made up of various watering regimes and exogenous nutrient application (nitrogen, phosphorus and potassium, at varying dosages) on the relative survival, growth, and reproductive development of 15-months-old S...
2017: F1000Research
https://www.readbyqxmd.com/read/28618961/microrna-208b-inhibits-human-osteosarcoma-progression-by-targeting-ror2
#18
Zhe Jiang, Chunshan Jiang, Chonglong Yu, Jinnv Fang
MicroRNAs are widely involved in cancer progression by inhibiting the expression levels of oncogenes or tumor suppressor genes, and dysregulation of microRNAs may contribute to tumorigenesis. Here, we found that overexpressed miR-208b can reduce the proliferation of human osteosarcoma cell lines U-2OS and Saos-2 by arresting cell cycle progression. The in vivo xenograft tumors induced by Saos-2 cells overexpressing miR-208b had smaller size and grew more slowly than those induced by the control cells. The mobility of U-2OS or Saos-2 cells was also downregulated by miR-208b...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28617945/microrna-cluster-106a-363-is-involved-in-t-helper-17-th17-cell-differentiation
#19
Marc Kaestle, Sabine Bartel, Kerstin Geillinger-Kästle, Martin Irmler, Johannes Beckers, Bernhard Ryffel, Oliver Eickelberg, Susanne Krauss-Etschmann
T-helper cell 17 (Th17) mediated inflammation is associated with various diseases including autoimmune encephalitis, inflammatory bowel disease and lung diseases such as chronic obstructive pulmonary disease and asthma. Differentiation into distinct Th subtypes needs to be tightly regulated to ensure an immunological balance. As microRNAs (miRNAs) are critical regulators of signaling pathways, we aimed to identify specific miRNAs implicated in controlling Th17 differentiation. We were able to create a regulatory network model of murine Th cell differentiation by combining Affymetrix mRNA and miRNA arrays and in-silico analysis...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28616476/proteobacteria-from-the-human-skin-microbiota-species-level-diversity-and-hypotheses
#20
C Cosseau, S Romano-Bertrand, H Duplan, O Lucas, I Ingrassia, C Pigasse, C Roques, E Jumas-Bilak
The human skin microbiota is quantitatively dominated by Gram-positive bacteria, detected by both culture and metagenomics. However, metagenomics revealed a huge variety of Gram-negative taxa generally considered from environmental origin. For species affiliation of bacteria in skin microbiota, clones of 16S rRNA gene and colonies growing on diverse culture media were analyzed. Species-level identification was achieved for 81% of both clones and colonies. Fifty species distributed in 26 genera were identified by culture, mostly belonging to Actinobacteria and Firmicutes, while 45 species-level operational taxonomic units distributed in 30 genera were detected by sequencing, with a high diversity of Proteobacteria...
December 2016: One Health
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