This SuperSeries is composed of the SubSeries listed below.
Knockout of G protein β5 impairs brain development and causes multiple neurologic abnormalities in mice.
Specimen part
View SamplesGb5 is a divergent, evolutionarily-conserved, member of the heterotrimeric G protein b subunit family that is expressed principally in brain and neuronal tissue. Among Gb isoforms, Gb5 is unique in its ability to heterodimerize with members of the R7 subfamily of the regulator of G protein signaling (RGS) proteins that contain G protein-g like (GGL) domains. Previous studies employing Gb5 knockout mice have shown that Gb5 is an essential stabilizer of GGL domain-containing RGS proteins and regulates the deactivation of retinal phototransduction and the proper functioning of retinal bipolar cells. The purpose of this study is to better understand the functions of Gb5 in the brain outside the visual system by employing molecular biology, immunohistochemistry and confocal imaging technologies. We show here that mice lacking Gb5 have a markedly abnormal neurologic phenotype that includes neurobehavioral developmental delay, wide-based gait, motor learning and coordination deficiencies, and hyperactivity. Using immunohistochemical analysis and a green fluorescent reporter of Purkinje cell maturation we show that the phenotype of Gb5-deficient mice includes, in part, delayed development of the cerebellar cortex, an abnormality that likely contributes to the neurobehavioral phenotype. Multiple neuronally-expressed genes are dysregulated in non-cerebellar portion of Gb5 KO mice.
Knockout of G protein β5 impairs brain development and causes multiple neurologic abnormalities in mice.
Specimen part
View SamplesGb5 is a divergent, evolutionarily-conserved, member of the heterotrimeric G protein b subunit family that is expressed principally in brain and neuronal tissue. Among Gb isoforms, Gb5 is unique in its ability to heterodimerize with members of the R7 subfamily of the regulator of G protein signaling (RGS) proteins that contain G protein-g like (GGL) domains. Previous studies employing Gb5 knockout mice have shown that Gb5 is an essential stabilizer of GGL domain-containing RGS proteins and regulates the deactivation of retinal phototransduction and the proper functioning of retinal bipolar cells. The purpose of this study is to better understand the functions of Gb5 in the brain outside the visual system by employing molecular biology, immunohistochemistry and confocal imaging technologies. We show here that mice lacking Gb5 have a markedly abnormal neurologic phenotype that includes neurobehavioral developmental delay, wide-based gait, motor learning and coordination deficiencies, and hyperactivity. Using immunohistochemical analysis and a green fluorescent reporter of Purkinje cell maturation we show that the phenotype of Gb5-deficient mice includes, in part, delayed development of the cerebellar cortex, an abnormality that likely contributes to the neurobehavioral phenotype. Multiple neuronally-expressed genes are dysregulated in cerebellum of Gb5 KO mice.
Knockout of G protein β5 impairs brain development and causes multiple neurologic abnormalities in mice.
Specimen part
View SamplesStore operated calcium entry (SOCE) downstream of T cell receptor (TCR) activation in T lymphocytes has been shown to be mediated mainly through the Calcium Release Activated Calcium (CRAC) channel. Here, we compared the effects of a novel, potent and selective CRAC inhibitor, 2,6-Difluoro-N-{5-[4-methyl-1-(5-methyl-thiazol-2-yl)-1,2,5,6-tetrahydro-pyridin-3-yl]-pyrazin-2-yl}-benzamide (RO2959), on T cell effector functions with that of a previously reported CRAC channel inhibitor, YM-58483, and a calcineurin inhibitor Cyclosporin A (CsA). Using both electrophysiological and calcium-based fluorescence measurements, we showed that RO2959 is a potent SOCE inhibitor that blocked an IP3-dependent current in CRAC-expressing RBL-2H3 cells and CHO cells stably expressing human Orai1 and Stim1, as well as SOCE in human primary CD4+ T cells triggered by either TCR stimulation or thapsigargin treatment. Furthermore, we demonstrated that RO2959 completely inhibited cytokine production as well as T cell proliferation mediated by TCR stimulation or MLR (Mixed Lymphocyte Reaction). Lastly, we showed by gene expression array analysis that RO2959 potently blocked TCR triggered gene expression and T cell functional pathways similar to CsA and FK506. Thus, both from a functional and transcriptional level, our data provide evidence that RO2959 is a novel and selective CRAC inhibitor that potently inhibits human T cell functions.
Characterization of a novel CRAC inhibitor that potently blocks human T cell activation and effector functions.
Specimen part, Treatment, Subject
View SamplesWe report the cloning and sequencing of both endogenous small RNAs and virus-derived siRNAs produced by the antiviral RNAi pathway in Drosophila. We find that a diverse panel of viruses are targeted by the RNAi pathway in Drosophila to produce abundant virus-derived siRNAs, and these siRNAs map to various locations within the viral genomes. Knockdown of various RNAi and miRNA pathway components alters the levels of these viral small RNAs. Overall design: Drosophila DL1 cells were treated with dsRNA for 3 days to deplete factors involved in the antiviral RNAi pathway and miRNA pathway, then were challenged with one of four viruses for 4 days. Total RNA was collected, and the small RNA populations from 15-29 nt were cloned and sequenced.
RNase III nucleases from diverse kingdoms serve as antiviral effectors.
Cell line, Subject
View SamplesSenescence is a developmental process and chlorophyll is an indicator of leaf senescene. In plants cytokinin plays a role in delaying leaf senescence. Chlorophyll degradation is tightly regulated during senescence and cytokinin might interplay in the chrorophyll degradation pathway to regulate leaf greening.
Cytokinin delays dark-induced senescence in rice by maintaining the chlorophyll cycle and photosynthetic complexes.
Specimen part
View SamplesWe identify regulatory mechanisms that influence inflammation and metabolism during metabolic disease development. In addition to the other data represented in our paper, we performed RNA-seq to demonstrate a role for miR-146a, an anti-inflammatory miRNA, in regulating both inflammation and cellular metabolism during obesity. Overall design: Each sample represents pooled cells from three mice of the same genotype and treatment group. Samples were pooled before FACS to ensure sufficient cell numbers for sorting and RNA collection. WT or miR-146a-/- mice were treated with either high fat diet or normal chow diet for 14 weeks starting from 6 weeks of age. Mice were sacrificed and live, singlet CD45+ CD11b+ F4/80+ cells were sorted from the stromal vascular fraction of adipose tissue using FACS Aria. RNA was collected from the sorted cells via Qiazol/RNeasy Kit (Qiagen) and library preparation used Illumina TruSeq Stranded RNA Kit with Ribo-Zero Gold. RNA-seq was performed using Illumina HiSeq 50 cycle single-read sequencing version 4. Sequence alignment was performed through the University of Utah Bioinformatics Core Facility.
Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease.
Specimen part, Subject
View SamplesMammalian nephrons are the physiological subunits of mammalian kidneys which consist of different highly apicobasally polarized epithelial cell types. In epithelial cells polarization is controlled by evolutionary conserved CRB, PAR, or SRIB complexes. Here, we focused on the role of Pals1/Mpp5 in the nephron. Pals1, a core component of the apical membrane determining CRB complex, is highly expressed in renal tubular epithelial and glomerular epithelial cells (podocytes). Surprisingly, haplo-deficient mice, lacking one Pals1/Mpp5 allele in the nephron developed a strong phenotype, accompanied by cyst formation and severe renal filtration barrier defects, which subsequently lead to death after 6-8 weeks. Supporting studies in Drosophila nephrocytes, and epithelial cell culture models elucidated the role of Pals1 as a dose dependent upstream regulator of the crosstalk between Hippo- and TGF-signaling during nephrogenesis.
Pals1 Haploinsufficiency Results in Proteinuria and Cyst Formation.
Specimen part
View SamplesHypersensitivity reactions are rare, but potentially severe adverse effects of sulfonamide antibiotics. Increased in vitro toxicity of lymphocytes, primarily CD8+ T cells, to sulfonamide drug metabolites as been proposed as a marker for sulfonamide hypersensitivity, but the mechanisms underlying this marker are unknown.
RNA expression profiling in sulfamethoxazole-treated patients with a range of in vitro lymphocyte cytotoxicity phenotypes.
Specimen part
View SamplesNotch signaling is widely implicated in mouse mammary gland development and tumorigenesis. To investigate the effects of acute activation of Notch signaling in the mammary epithelial compartment, we generated bi-transgenic MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice that conditionally express a constitutively active NOTCH1 intracellular domain (NICD1) construct in the mammary epithelium upon doxycycline administration.
Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy.
Sex, Age, Specimen part, Treatment, Time
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