Changes in Proopiomelanocortin Primary Transcript Levels in the Anterior Pituitary Accompany Increased Adrenocorticotropin Secretion During the Diurnal Surge

Proopiomelanocortin (POMC) gene transcription in the anterior pituitary varies during stress and glucocorticoid feedback. These changes appear to parallel alterations in peptide release. The diurnal rhythm of the hypothalamo-pituitary-adrenal axis also involves the periodic excursion of adrenocorticotropin (ACTH) levels in plasma, but it is not clear whether the diurnal release is accompanied by changes at the transcriptional level. In the present study, we have initially characterized the heteronuclear species of POMC (hnPOMC) RNA found in the anterior pituitary by a Northern blot analysis and subsequently used this method to quantitate relative changes in the levels of heteronuclear transcript during diurnal stimulation. Two species of RNA migrating at 6.0 kb and 4.1 kb were found in the nuclear fraction of the anterior pituitary. Successive probing by various POMC cRNAs indicated that the 6.0 kb fragment was the primary transcript and the 4.1 kb fragment corresponded to the intron A-containing processing intermediate of POMC. The nuclear species were quantitated after acute swim stress and during the diurnal ACTH secretion. Acute swim increased plasma ACTH levels by 243% after 30 min. This was paralleled by a 214% increase in the primary transcript RNA levels. Endogenous circadian stimulation in the evening produced a smaller rise of plasma ACTH (79%), and was accompanied by a 34% increase in POMC hnRNA levels. Nuclear processing intermediate (4.1 kb) and the mRNA levels did not vary during the evening. These results suggest that the diurnal mechanism transiently increases ACTH release as well as POMC gene transcription in the anterior pituitary. Release and transcription appear to be tightly coupled during circadian activation as well as during stress.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75121/1/j.1365-2826.1992.tb00340.x.pd

hVH-5: A Protein Tyrosine Phosphatase Abundant in Brain that Inactivates Mitogen-Activated Protein Kinase

A novel protein tyrosine phosphatase [ h omologue of v accinia virus H 1 phosphatase gene clone 5 (hVH-5)] was cloned; it shared sequence similarity with a subset of protein tyrosine phosphatases that regulate mitogen-activated protein kinase. The catalytic region of hVH-5 was expressed as a fusion protein and was shown to hydrolyze p -nitrophenylphosphate and inactivate mitogen-activated protein kinase, thus proving that hVH-5 possessed phosphatase activity. A unique proline-rich region distinguished hVH-5 from other closely related protein tyrosine phosphatases. Another feature that distinguished hVH-5 from related phosphatases was that hVH-5 was expressed predominantly in the adult brain, heart, and skeletal muscle. In addition, in situ hybridization histochemistry of mouse embryo revealed high levels of expression and a wide distribution in the central and peripheral nervous system. Some specific areas of abundant hVH-5 expression included the olfactory bulb, retina, layers of the cerebral cortex, and cranial and spinal ganglia. hVH-5 was induced in PC12 cells upon nerve growth factor and insulin treatment in a manner characteristic of an immediate-early gene, suggesting a possible role in the signal transduction cascade.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65883/1/j.1471-4159.1995.65041823.x.pd

Pro-opiomelanocortin mRNA and peptide co-expression in the developing rat pituitary

Pro-opiomelanocortin (POMC) is synthesized in both the pituitary gland and the brain. Various peptide products of this precursor, namely beta-endorphin, ACTH and alpha-MSH are co-localized in the anterior lobe corticotrophs, all intermediate lobe cells and in hypothalamic neurons. Messenger RNA (mRNA) for POMC has further been shown to exist in these tissues. In this study, we have shown that POMC mRNA, and peptide accumulation as detected by in situ hybridization and immunocytochemistry, respectively, occur simultaneously within the rat pituitary gland during ontogeny and that their maturation occurs in parallel during prenatal and early postnatal development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29476/1/0000562.pd

Frame-like Geometry of Double Field Theory

We relate two formulations of the recently constructed double field theory to a frame-like geometrical formalism developed by Siegel. A self-contained presentation of this formalism is given, including a discussion of the constraints and its solutions, and of the resulting Riemann tensor, Ricci tensor and curvature scalar. This curvature scalar can be used to define an action, and it is shown that this action is equivalent to that of double field theory.Comment: 35 pages, v2: minor corrections, to appear in J. Phys.

Double Field Theory Formulation of Heterotic Strings

We extend the recently constructed double field theory formulation of the low-energy theory of the closed bosonic string to the heterotic string. The action can be written in terms of a generalized metric that is a covariant tensor under O(D,D+n), where n denotes the number of gauge vectors, and n additional coordinates are introduced together with a covariant constraint that locally removes these new coordinates. For the abelian subsector, the action takes the same structural form as for the bosonic string, but based on the enlarged generalized metric, thereby featuring a global O(D,D+n) symmetry. After turning on non-abelian gauge couplings, this global symmetry is broken, but the action can still be written in a fully O(D,D+n) covariant fashion, in analogy to similar constructions in gauged supergravities.Comment: 28 pages, v2: minor changes, version published in JHE

Massive Type II in Double Field Theory

We provide an extension of the recently constructed double field theory formulation of the low-energy limits of type II strings, in which the RR fields can depend simultaneously on the 10-dimensional space-time coordinates and linearly on the dual winding coordinates. For the special case that only the RR one-form of type IIA carries such a dependence, we obtain the massive deformation of type IIA supergravity due to Romans. For T-dual configurations we obtain a `massive' but non-covariant formulation of type IIB, in which the 10-dimensional diffeomorphism symmetry is deformed by the mass parameter.Comment: 21 page

Future Climate Data from RCP 4.5 and Occurrence of Malaria in Korea

Since its reappearance at the Military Demarcation Line in 1993, malaria has been occurring annually in Korea. Malaria is regarded as a third grade nationally notifiable disease susceptible to climate change. The objective of this study is to quantify the effect of climatic factors on the occurrence of malaria in Korea and construct a malaria occurrence model for predicting the future trend of malaria under the influence of climate change. Using data from 2001–2011, the effect of time lag between malaria occurrence and mean temperature, relative humidity and total precipitation was investigated using spectral analysis. Also, a principal component regression model was constructed, considering multicollinearity. Future climate data, generated from RCP 4.5 climate change scenario and CNCM3 climate model, was applied to the constructed regression model to simulate future malaria occurrence and analyze the trend of occurrence. Results show an increase in the occurrence of malaria and the shortening of annual time of occurrence in the future

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

N=1 Supersymmetric Double Field Theory

We construct the N=1 supersymmetric extension of double field theory for D=10, including the coupling to an arbitrary number n of abelian vector multiplets. This theory features a local O(1,9+n) x O(1,9) tangent space symmetry under which the fermions transform. It is shown that the supersymmetry transformations close into the generalized diffeomorphisms of double field theory.Comment: 22 pages, v2: minor corrections, ref. added, to appear in JHE