1,059 research outputs found
West, by God
No full textMy thesis is a collection of short stories to satisfy the requirements of the MFA program.M.F.A.by Troy J. Graha
Highly efficient small interfering RNA delivery to primary mammalian neurons induces MicroRNA-like effects before mRNA degradation
No full textThe study of protein function in neurons has been hindered by the lack of highly efficient, nontoxic methods of inducing RNA interference in such cells. Here we show that application of synthetic small interfering RNA( siRNA) linked to the vector peptide Penetratin1 results in rapid, highly efficient uptake of siRNA by entire populations of cultured primary mammalian hippocampal and sympathetic neurons. This treatment leads to specific knock-down of targeted proteins within hours without the toxicity associated with transfection. In contrast to current methods, our technique permits study of protein function across entire populations with minimal disturbance of complex cellular networks. Using this technique, we found that protein knock-down ( evident after 6 hr) precedes any decrease in targeted message ( evident after 24 hr), suggesting an early, translational repression by perfectly targeted siRNAs.PT: J; CR: BARTEL DP, 2004, CELL, V116, P281 BERTRAND E, 2001, MOL CELL NEUROSCI, V18, P503 DEROSSI D, 1994, J BIOL CHEM, V269, P10444 DOENCH JG, 2003, GENE DEV, V17, P438 DOSTIE JE, 2003, RNA, V9, P180 ELBASHIR SM, 2001, EMBO J, V20, P6877 FINK CC, 2003, NEURON, V39, P283 FIRE A, 1998, NATURE, V391, P806 GAUDILLIERE B, 2002, J BIOL CHEM, V277, P46442 HANNON GJ, 2002, NATURE, V418, P244 HUTVAGNER G, 2002, SCIENCE, V297, P2056 JOHNSTON RJ, 2003, NATURE, V426, P845 JOLIOT A, 2004, NAT CELL BIOL, V6, P189 KHVOROVA A, 2003, CELL, V115, P209 KIM J, 2004, P NATL ACAD SCI USA, V101, P360 KRICHEVSKY AM, 2002, P NATL ACAD SCI USA, V99, P11926 KRICHEVSKY AM, 2003, RNA, V9, P1274 LAI EC, 2003, CURR BIOL, V13, R925 LLAVE C, 2002, SCIENCE, V297, P2053 MURATOVSKA A, 2004, FEBS LETT, V558, P63 OMI K, 2004, FEBS LETT, V558, P89 RABACCHI SA, 2004, NEUROBIOL AGING, V25, P1057 REYNOLDS A, 2004, NAT BIOTECHNOL, V22, P326 SAXENA S, 2003, J BIOL CHEM, V278, P44312 SCHERER LJ, 2003, NAT BIOTECHNOL, V21, P1457 SCHWARZ DS, 2003, CELL, V115, P199 THEODORE L, 1995, J NEUROSCI, V15, P7158 TOROCSIK B, 2002, J NEUROSCI, V22, P8971 TROY CM, 1994, P NATL ACAD SCI USA, V91, P6384 TROY CM, 1996, J NEUROSCI, V16, P253 TROY CM, 1996, P NATL ACAD SCI USA, V93, P5635 TROY CM, 2001, J NEUROSCI, V21, P5007 TROY CM, 2002, J BIOL CHEM, V277, P34295 VICKERS TA, 2003, J BIOL CHEM, V278, P7108 ZENG Y, 2003, P NATL ACAD SCI USA, V100, P9779; NR: 35; TC: 22; J9: J NEUROSCI; PG: 7; GA: 869ZASource type: Electronic(1
Linoleic acid causes greater weight gain than saturated fat without hypothalamic inflammation in the male mouse
No full textA significant change in the Western diet, concurrent with the obesity epidemic, was a substitution of saturated fatty acids with polyunsaturated, specifically linoleic acid (LA). Despite increasing investigation on type as well as amount of fat, it is unclear which fatty acids are most obesogenic. The objective of this study was to determine the obesogenic potency of LA vs. saturated fatty acids and the involvement of hypothalamic inflammation. Forty-eight mice were divided into four groups: low-fat or three high-fat diets (HFDs, 45% kcals from fat) with LA comprising 1%, 15% and 22.5% of kilocalories, the balance being saturated fatty acids. Over 12 weeks, bodyweight, body composition, food intake, calorimetry, and glycemia assays were performed. Arcuate nucleus and blood were collected for mRNA and protein analysis. All HFD-fed mice were heavier and less glucose tolerant than control. The diet with 22.5% LA caused greater bodyweight gain, decreased activity, and insulin resistance compared to control and 1% LA. All HFDs elevated leptin and decreased ghrelin in plasma. Neuropeptides gene expression was higher in 22.5% HFD. The inflammatory gene Ikk was suppressed in 1% and 22.5% LA. No consistent pattern of inflammatory gene expression was observed, with suppression and augmentation of genes by one or all of the HFDs relative to control. These data indicate that, in male mice, LA induces obesity and insulin resistance and reduces activity more than saturated fat, supporting the hypothesis that increased LA intake may be a contributor to the obesity epidemic.Peer reviewe
Regulation of gene expression by 17β-estradiol in the arcuate nucleus of the mouse through ERE-dependent and ERE-independent mechanisms
No full text17β-Estradiol (E2) modulates gene expression in the hypothalamic arcuate nucleus (ARC) to control homeostatic functions. In the ARC, estrogen receptor (ER) α is highly expressed and is an important contributor to E2's actions, controlling gene expression through estrogen response element (ERE)-dependent and -independent mechanisms. The objective of this study was to determine if known E2-regulated genes are regulated through these mechanisms. The selected genes have been shown to regulate homeostasis and have been separated into three subsections: channels, receptors, and neuropeptides. To determine if ERE-dependent or ERE-independent mechanisms regulate gene expression, two transgenic mouse models, an ERα knock-out (ERKO) and an ERα knock-in/knock-out (KIKO), which lacks a functional ERE binding domain, were used in addition to their wild-type littermates. Females of all genotypes were ovariectomized and injected with oil or estradiol benzoate (E2B). Our results suggest that E2B regulates multiple genes through these mechanisms. Of note, Cacna1g and Kcnmb1 channel expression was increased by E2B in WT females only, suggesting an ERE-dependent regulation. Furthermore, the NKB receptor, Tac3r, was suppressed by E2B in WT and KIKO females but not ERKO females, suggesting that ERα-dependent, ERE-independent signaling is necessary for Tac3r regulation. The adrenergic receptor Adra1b was suppressed by E2B in all genotypes indicating that ERα is not the primary receptor for E2B's actions. The neuropeptide Tac2 was suppressed by E2B through ERE-dependent mechanisms. These results indicate that E2B activates both ERα-dependent and independent signaling in the ARC through ERE-dependent and ERE-independent mechanisms to control gene expression.Peer reviewe
Estrogen response element-independent signaling partially restores post-ovariectomy body weight gain but is not sufficient for 17β-estradiol's control of energy homeostasis
No full textThe steroid 17β-estradiol (E2) modulates energy homeostasis by reducing feeding behavior and increasing energy expenditure primarily through estrogen receptor α (ERα)-mediated mechanisms. Intact ERαKO female mice develop obesity as adults exhibiting decreased energy expenditure and increased fat deposition. However, intact transgenic female mice expressing a DNA-binding-deficient ERα (KIKO) are not obese and have similar energy expenditure, activity and fat deposition as to wild type (WT) females, suggesting that non-estrogen response element (ERE)-mediated signaling is important in E2 regulation of energy homeostasis. Initial reports did not examine the effects of ovariectomy on energy homeostasis or E2's attenuation of post-ovariectomy body weight gain. Therefore, we sought to determine if low physiological doses of E2 (250 ng QOD) known to suppress post-ovariectomy body weight gain in WT females would suppress body weight gain in ovariectomized KIKO females. We observed that the post-ovariectomy increase in body weight was significantly greater in WT females than in KIKO females. Furthermore, E2 did not significantly attenuate the body weight gain in KIKO females as it did in WT females. E2 replacement suppressed food intake and fat accumulation while increasing nighttime oxygen consumption and activity only in WT females. E2 replacement also increased arcuate POMC gene expression in WT females only. These data suggest that in the intact female, ERE-independent mechanisms are sufficient to maintain normal energy homeostasis and to partially restore the normal response to ovariectomy. However, they are not sufficient for E2's suppression of post-ovariectomy body weight gain and its effects on metabolism and activity.Peer reviewe
Regulation of arcuate genes by developmental exposures to endocrine-disrupting compounds in female rats
No full textDevelopmental exposure to endocrine-disrupting compounds (EDCs) alters reproduction and energy homeostasis, both of which are regulated by the arcuate nucleus (ARC). Little is known about the effects of EDC on ARC gene expression. In Experiment #1, pregnant dams were treated with either two doses of bisphenol A (BPA) or oil from embryonic day (E)18-21. Neonates were injected from postnatal day (PND)0-7. Vaginal opening, body weights, and ARC gene expression were measured. Chrm3 (muscarinic receptor 3) and Adipor1 (adiponectin receptor 1) were decreased by BPA. Bdnf (brain-derived neurotropic factor), Igf1 (insulin-like growth factor 1), Htr2c (5-hydroxytryptamine receptor), and Cck2r (cholescystokinin 2 receptor) were impacted. In Experiment #2, females were exposed to BPA, diethylstilbestrol (DES), di(2-ethylhexyl)phthalate, or methoxychlor (MXC) during E11-PND7. MXC and DES advanced the age of vaginal opening and ARC gene expression was impacted. These data indicate that EDCs alter ARC genes involved in reproduction and energy homeostasis in females.Peer reviewe
Joint stewardship of the Barents Sea: Russian and Norwegian policy expectations for preventing offshore oil spills
Full text linkThesis (M.A.) University of Alaska Fairbanks, 2016As Arctic environmental conditions fluctuate, ongoing economic-related agreements established for the Barents Region continue to support and attract Norwegian and Russian oil-producing expeditions within the shared maritime zone. Increased industrial activity throughout the Circumpolar North heightens the need to understand the factors that influence policies responsible for protecting the environment – in particular, preventive measures. Agency theory provides the framework for an analysis of various dynamics that influence the Norwegian and Russian governments (principals) as they develop and enforce rules that regulate petroleum industries (agents). The research question asks about differences between the prevention policies of the two nations even though both acknowledge a very similar need to protect the Barents. Since the regulatory and governance structures cannot fully explain the differences between the two countries’ prevention policies, the hypothesis presents an argument that the strategic goals of Norway and Russia in the global political economy provide sufficient conditions for policy divergence. This research presents case studies of economic and environmental factors that influence how Russia and Norway develop energy-related prevention policies in the Barents Sea. The findings suggest that differing strategic goals between the two countries influence their oil spill prevention policies. Russia’s oil spill prevention policy enables it to maintain high production levels that it can leverage to further its geopolitical aims. Norway’s more cautious prevention policies promote domestic economic stability. In a progressively interdependent world, this study contributes insight into contemporary international relations regarding aspects of partnerships, energy economics, and geostrategic policy
Correction to: The “Risser+” grade: a new grading system to classify skeletal maturity in idiopathic scoliosis (European Spine Journal, (2019), 28, 3, (559-566), 10.1007/s00586-018-5821-8)
No full textUnfortunately, the affiliation of the author Negrini S has been incorrectly published in the original version. The complete correct affiliation of this author should read as follows
Genetic analysis of synaptogyrin function in the synaptic vesicle cycle
No full textThesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2012.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references.Neuronal communication relies on the continual replenishment of synaptic vesicles that are primed for neurotransmitter release in response to action potentials. A vast array of proteins is required to mediate synaptic vesicle biogenesis, trafficking, docking, exocytosis, and endocytosis. Synaptogyrin and synaptophysin are abundant and evolutionarily conserved synaptic vesicles proteins that were identified over twenty years ago, yet their exact function in the synaptic vesicle cycle remains unknown. To further elucidate the role of these proteins, we have generated and characterized a synaptogyrin null mutant in Drosophila, whose genome encodes a single synaptogyrin isoform and lacks a synaptophysin homolog. Here we demonstrate that Drosophila synaptogyrin is abundantly expressed in neurons, where it localizes to the presynaptic terminal of the larval neuromuscular junction (NMJ). Drosophila lacking synaptogyrin are viable and fertile and have no overt deficits in motor function or courtship behavior. Ultrastructural analysis of mutant larvae revealed an increase in average synaptic vesicle diameter as well as enhanced variability in the size of synaptic vesicles. In addition, the resolution of endocytic cisternae into synaptic vesicles in response to robust exocytosis is defective in synaptogyrin mutants. While basal synaptic transmission at the larval NMJ is unaffected, synaptogyrin mutants do display increased facilitation during high-frequency stimulation, indicating that synaptic vesicle exocytosis is abnormally regulated during strong stimulation conditions. These results suggest that, while not required for neurotransmission, Drosophila synaptogyrin nevertheless modulates synaptic vesicle exo-endocytosis, especially during elevated rates of synaptic vesicle fusion.by Robin J. Stevens.Ph.D
The Days When the Animals Talked.
No full textI learned more from this book than its good fables. I learned that the great American author is William Harrison Faulkner. The book has a clear ethnic agenda, signalled in the cover's giving black hands to Brer Rabbit and white hands to Brer Wolf. Fable motifs and material play frequently through the twenty-two folktales in Part II of the book. Brer Possum and Brer Snake (99) is a combination of the Aesopic Frozen Snake and The Brahmin and the Caged Tiger. It has a great moral: Don't you ever trouble trouble, until trouble troubles you! Brer Rabbit and Brer Cooter Race (132) is the Aesopic TH but with the hedgehog twist, namely, that all those in one species look alike to those of other species. Brer Rabbit Rescues His Children (168) has the motif of tracks going in but not coming out. There are three planting tales with strong fable elements (102, 106, 110). The respective tricks in the three are eating the peanuts (like the monkey with the cat) instead of planting them, agreeing to give the tops, and agreeing to give tops and bottoms. How the Cow Went Under the Ground (152) is not only a good fable; it illustrates well the motif of repression that Faulkner, himself a Black, finds frequent in these stories. Other good stories, though not fables, in this section include Brer Tiger and the Big Wind (89) and Brer Rabbit Keeps His Word (95).This is a hardbound book (hard cover)This book has a dust jacket (book cover)Signed by the authorWilliam J. Faulkne
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