A transcriptomics model of estrogen action in the ovine fetal hypothalamus: evidence for estrogenic effects of ICI 182,780

Estradiol plays a critical role in stimulating the fetal hypothalamus?pituitary?adrenal axis at the end of gestation. Estradiol action is mediated through nuclear and membrane receptors that can be modulated by ICI 182,780, a pure antiestrogen compound. The objective of this study was to evaluate the transcriptomic profile of estradiol and ICI 182,780, testing the hypothesis that ICI 182,780 antagonizes the action of estradiol in the fetal hypothalamus. Chronically catheterized ovine fetuses were infused for 48 h with: vehicle (Control, n = 6), 17β‐estradiol 500 μg/kg/day (Estradiol, n = 4), ICI 182,780 5 μg/kg/day (ICI 5 μg, n = 4) and ICI 182,780 5 mg/kg/day (ICI 5 mg, n = 5). Fetal hypothalami were collected afterward, and gene expression was measured through microarray. Statistical analysis of transcriptomic data was performed with Bioconductor‐R and Cytoscape software. Unexpectedly, 35% and 15.5% of the upregulated differentially expressed genes (DEG) by Estradiol significantly overlapped (P < 0.05) with upregulated DEG by ICI 5 mg and ICI 5 μg, respectively. For the downregulated DEG, these percentages were 29.9% and 15.5%, respectively. There was almost no overlap for DEG following opposite directions between Estradiol and ICI ICI 5 mg or ICI 5 μg. Furthermore, most of the genes in the estrogen signaling pathway after activation of the epidermal growth factor receptor followed the same direction in Estradiol, ICI 5 μg or ICI 5 mg compared to Control. In conclusion, estradiol and ICI 182,780 have estrogenic genomic effects in the developing brain, suggesting the possibility that the major action of estradiol on the fetal hypothalamus involves another receptor system rather than estrogen receptors.Fil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Keller Wood, Maureen. University of Florida; Estados UnidosFil: Wood, Charles E.. University of Florida; Estados Unido

Log Roads to Light Rails: The Evolution of Main Street and Transportation in Buffalo, New York

No abstract available at this time

Transcriptomics modeling of the late-gestation fetal pituitary response to transient hypoxia

Background The late-gestation fetal sheep responds to hypoxia with physiological, neuroendocrine, and cellular responses that aid in fetal survival. The response of the fetus to hypoxia represents a coordinated effort to maximize oxygen transfer from the mother and minimize wasteful oxygen consumption by the fetus. While there have been many studies aimed at investigating the coordinated physiological and endocrine responses to hypoxia, and while immunohistochemical or in situ hybridization studies have revealed pathways supporting the endocrine function of the pituitary, there is little known about the coordinated cellular response of the pituitary to the hypoxia. Results Thirty min hypoxia (from 17.0±1.7 to 8.0±0.8 mm Hg, followed by 30 min normoxia) upregulated 595 and downregulated 790 genes in fetal pituitary (123-132 days' gestation; term = 147 days). Network inference of up- and down- regulated genes revealed a high degree of functional relatedness amongst the gene sets. Gene ontology analysis revealed upregulation of cellular metabolic processes (e.g., RNA synthesis, response to estrogens) and downregulation Conclusions The multiple analytical approaches used in this study suggests that the acute response to 30 min of transient hypoxia in the late-gestation fetus results in reduced cellular metabolism and a pattern of gene expression that is consistent with cellular oxygen and ATP starvation. In this early time point, we see a vigorous gene response. But, like the hypothalamus, the transcriptomic response is not consistent with mediation by HIF-1. If HIF-1 is a significant controller of gene expression in the fetal pituitary after hypoxia, it must be at a later time.Fil: Wood, Charles E.. University of Florida; Estados UnidosFil: Chang, Eileen I.. University of Florida; Estados UnidosFil: Richards, Elaine M.. University of Florida; Estados UnidosFil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Keller Wood, Maureen. University of Florida; Estados Unido

Radiostereometric Evaluation of Tendon Elongation After Distal Biceps Repair.

BACKGROUND: Operative repair of distal biceps tendon ruptures has shown successful outcomes. However, little is known about the amount of tendon or repair site lengthening after repair. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate distal biceps tendon repair via intratendinous radiostereometric analysis to analyze tendon lengthening at different time intervals of healing. The hypothesis was that there is significant lengthening after repair. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Eleven patients with distal biceps ruptures requiring operative repair were recruited. During repair, two 2-mm tantalum beads with laser-etched holes were sutured to the distal biceps tendon. Beads were evaluated via computed tomography scans immediately postoperatively and at 16 weeks. Radiographs were obtained at time 0 and then at 4, 8, and 16 weeks postoperatively. Measurements were made using the button-to-bead and bead-to-bead distances to assess repair site elongation as well as tendon elongation over time. After final follow-up, patients filled out the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and underwent ultrasound to confirm the integrity of the tendon. RESULTS: Ten patients had complete ruptures, with 1 having a partial rupture that underwent completion of the tear and subsequent repair. All patients showed statistically significant lengthening after surgery. The mean amount of tendon lengthening after surgery was 22.8 mm (range, 11.2-30.9 mm; P \u3c .05), and the repair site lengthened a mean 17.0 mm (range, 9.6-30.6 mm; P \u3c .05) from surgery to final follow-up. The greatest change in lengthening was noted between time 0 and week 4 (mean, 11.3 mm; P \u3c .05), with the least amount of lengthening between weeks 8 and 16 (mean, 2.6 mm; P \u3c .05). The mean DASH score was 11.2. Final ultrasound evaluations found all tendons to be in continuity. CONCLUSION: All patients undergoing distal biceps tendon repair have significant elongation after surgery, with the greatest amount of lengthening seen in the early postoperative period

Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex

Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain. We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the cerebral cortex and that ketamine, an antagonist of NMDA receptors and a known anti-inflammatory agent, reduces the damage. Late gestation, chronically catheterized fetal sheep were subjected to a 30-min period of ventilatory hypoxia that decreased fetal PaO2 from 17 ± 1 to 10 ± 1 mmHg, or normoxia (PaO2 17 ± 1 mmHg), with or without pretreatment (10 min before hypoxia/normoxia) with ketamine (3 mg/kg, i.v.). One day (24 h) after hypoxia/normoxia, fetal cerebral cortex was removed and mRNA extracted for transcriptomics and systems biology analysis (n = 3-5 per group). Hypoxia stimulated a transcriptomic response consistent with a reduction in cellular metabolism and an increase in inflammation. Ketamine pretreatment reduced both of these responses. The inflammation response modeled with transcriptomic systems biology was validated by immunohistochemistry and showed increased abundance of microglia/macrophages after hypoxia in the cerebral cortical tissue that ketamine significantly reduced. We conclude that transient hypoxia produces inflammation of the fetal cerebral cortex and that ketamine, in a standard clinical dose, reduces the inflammation response.Fil: Chang, Eileen I.. University of Florida; Estados UnidosFil: Zárate, Miguel A.. University of Florida; Estados UnidosFil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Richards, Elaine M.. University of Florida; Estados UnidosFil: Arndt, Thomas J.. University of Florida; Estados UnidosFil: Keller Wood, Maureen. University of Florida; Estados UnidosFil: Wood, Charles E.. University of Florida; Estados Unido

Ketamine reduces inflammation pathways in the hypothalamus and hippocampus following transient hypoxia in the late-gestation fetal sheep

The physiological response to hypoxia in the fetus has been extensively studied with regard to redistribution of fetal combined ventricular output and sparing of oxygen delivery to fetal brain and heart. Previously, we have shown that the fetal brain is capable of mounting changes in gene expression that are consistent with tissue inflammation. The present study was designed to use transcriptomics and systems biology modeling to test the hypothesis that ketamine reduces or prevents the upregulation of inflammation-related pathways in hypothalamus and hippocampus after transient hypoxic hypoxia. Chronically catheterized fetal sheep (122 ± 5 days gestation) were subjected to 30 min hypoxia (relative reduction in PaO2∼50%) caused by infusion of nitrogen into the inspired gas of the pregnant ewe. RNA was isolated from fetal hypothalamus and hippocampus collected 24 h after hypoxia, and was analyzed for gene expression using the Agilent 15.5 k ovine microarray. Ketamine, injected 10 min prior to hypoxia, reduced the cerebral immune response activation to the hypoxia in both brain regions. Genes both upregulated by hypoxia and downregulated by ketamine after hypoxia were significantly associated with gene ontology terms and KEGG pathways that are, themselves, associated with the tissue response to exposure to bacteria. We conclude that the results are consistent with interruption of the cellular response to bacteria by ketamine.Fil: Chang, Eileen I.. University of Florida; Estados UnidosFil: Zarate, Miguel A.. University of Florida; Estados UnidosFil: Arndt, Thomas J.. University of Florida; Estados UnidosFil: Richards, Elaine M.. University of Florida; Estados UnidosFil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Keller Wood, Maureen. University of Florida; Estados UnidosFil: Wood, Charles E.. University of Florida; Estados Unido

First Science Observations with SOFIA/FORCAST: Properties of Intermediate-Luminosity Protostars and Circumstellar Disks in OMC-2

We examine eight young stellar objects in the OMC-2 star forming region based on observations from the SOFIA/FORCAST early science phase, the Spitzer Space Telescope, the Herschel Space Observatory, 2MASS, APEX, and other results in the literature. We show the spectral energy distributions of these objects from near-infrared to millimeter wavelengths, and compare the SEDs with those of sheet collapse models of protostars and circumstellar disks. Four of the objects can be modelled as protostars with infalling envelopes, two as young stars surrounded by disks, and the remaining two objects have double-peaked SEDs. We model the double-peaked sources as binaries containing a young star with a disk and a protostar. The six most luminous sources are found in a dense group within a 0.15 x 0.25 pc region; these sources have luminosities ranging from 300 L_sun to 20 L_sun. The most embedded source (OMC-2 FIR 4) can be fit by a class 0 protostar model having a luminosity of ~50 L_sun and mass infall rate of ~10^-4 solar masses per year.Comment: Accepted by ApJ Letter

SOFIA/FORCAST and Spitzer/IRAC Imaging of the Ultra Compact H II Region W3(OH) and Associated Protostars in W3

We present infrared observations of the ultra-compact H II region W3(OH) made by the FORCAST instrument aboard SOFIA and by Spitzer/IRAC. We contribute new wavelength data to the spectral energy distribution, which constrains the optical depth, grain size distribution, and temperature gradient of the dusty shell surrounding the H II region. We model the dust component as a spherical shell containing an inner cavity with radius ~ 600 AU, irradiated by a central star of type O9 and temperature ~ 31,000 K. The total luminosity of this system is 71,000 L_solar. An observed excess of 2.2 - 4.5 microns emission in the SED can be explained by our viewing a cavity opening or clumpiness in the shell structure whereby radiation from the warm interior of the shell can escape. We claim to detect the nearby water maser source W3 (H2O) at 31.4 and 37.1 microns using beam deconvolution of the FORCAST images. We constrain the flux densities of this object at 19.7 - 37.1 microns. Additionally, we present in situ observations of four young stellar and protostellar objects in the SOFIA field, presumably associated with the W3 molecular cloud. Results from the model SED fitting tool of Robitaille et al. (2006, 2007} suggest that two objects (2MASS J02270352+6152357 and 2MASS J02270824+6152281) are intermediate-luminosity (~ 236 - 432 L_solar) protostars; one object (2MASS J02270887+6152344) is either a high-mass protostar with luminosity 3000 L_solar or a less massive young star with a substantial circumstellar disk but depleted envelope; and one object (2MASS J02270743+6152281) is an intermediate-luminosity (~ 768 L_solar) protostar nearing the end of its envelope accretion phase or a young star surrounded by a circumstellar disk with no appreciable circumstellar envelope.Comment: 12 pages, 8 figures, 2 tables, accepted by Ap