Metabolic regulation of ApoB mRNA editing is associated with phosphorylation of APOBEC-1 complementation factor

Apolipoprotein B (apoB) mRNA editing is a nuclear event that minimally requires the RNA substrate, APOBEC-1 and APOBEC-1 Complementation Factor (ACF). The co-localization of these macro-molecules within the nucleus and the modulation of hepatic apoB mRNA editing activity have been described following a variety of metabolic perturbations, but the mechanism that regulates editosome assembly is unknown. APOBEC-1 was effectively co-immunoprecipitated with ACF from nuclear, but not cytoplasmic extracts. Moreover, alkaline phosphatase treatment of nuclear extracts reduced the amount of APOBEC-1 co-immunoprecipitated with ACF and inhibited in vitro editing activity. Ethanol stimulated apoB mRNA editing was associated with a 2- to 3-fold increase in ACF phosphorylation relative to that in control primary hepatocytes. Significantly, phosphorylated ACF was restricted to nuclear extracts where it co-sedimented with 27S editing competent complexes. Two-dimensional phosphoamino acid analysis of ACF immunopurified from hepatocyte nuclear extracts demonstrated phosphorylation of serine residues that was increased by ethanol treatment. Inhibition of protein phosphatase I, but not PPIIA or IIB, stimulated apoB mRNA editing activity coincident with enhanced ACF phosphorylation in vivo. These data demonstrate that ACF is a metabolically regulated phosphoprotein and suggest that this post-translational modification increases hepatic apoB mRNA editing activity by enhancing ACF nuclear localization/retention, facilitating the interaction of ACF with APOBEC-1 and thereby increasing the probability of editosome assembly and activity

The Enjoyment and Acquisition of Resources in Outer Space

In their interactions in the larger arena, states and their surrogates may be observed to employ many different types of resources as bases of power and to make claims of many varying degrees in comprehensiveness of authority and in scope and duration of control over such resources. The more important resources so employed and subjected to claim include, apart from manpower, not only the land masses, in all their protean forms, but also the oceans, air space, outer space, polar areas, rivers and so on. Some of these resources, such as the oceans, air space over the oceans, and international rivers, which experience has demonstrated to admit of a high degree of shared use by reasonable mutual accommodation, have been generally regarded as not being subject to exclusive appropriation by particular states, and the only claims which states have reciprocally honored in traditional international law have been those asserting shared access and requiring reasonable accommodation among users. Other resources, such as the land masses and closely proximate waters and air space, have commonly been regarded as admitting only in modest degree of shared use and competence, and states have reciprocally honored each other\u27s claims to a most comprehensive and continuing, exclusive competence over such resources; indeed the very conception of the contemporary state embodies, as is well known, this high degree of exclusivity in the competence of a territorially organized group. The policies followed by the general community in this allocation of resources between inclusive and exclusive authoritative control have, building upon the experience that inclusive use and competence most often achieve the greatest production and widest distribution of goods and services for the benefit of all, established a very strong presumption in favor of the inclusive control of sharable resources, with exclusive control being protected only when it can be shown to contribute most to common interest

Frost-Free Record Reconstruction for Eastern Massachusetts, 1733-1980

A reconstruction methodology utilizing such varied documents as diaries, agricultural journals, U.S. Weather Bureau killing frost records and instrumental records is discussed. A resultant 248-year frost record for eastern Massachusetts exhibits marked variations in the length of the growing season, that occur on a time scale of approximately 70 years. There is an apparent systematic long-term relationship between the timing of spring and fall killing frosts and the last 100 years of record reveals a decline in year-to-year variability

Reactive Attachment Disorder: Challenges for Early Identification and Intervention within the Schools

Attachment is of key importance in childhood development. The quality of attachment relationship between the child and parent/primary caregiver may have an effect on the child and future relationships and social success (Rubin, Bukowski, & Parker, 1998). When a child fails to bond with a caring adult, attachment becomes disordered and children may not be able to bond appropriately or at all with other people. This inability to relate and connect with others may disrupt or arrest not only children\u27s social development, but also their overall development. The purpose of this review is to synthesize information and research on characteristics, diagnosis, and interventions currently in practice in working with young children with Reactive Attachment Disorder (RAD). A discussion will highlight the themes found during this review and conclude with implications for intervention and practice

Metabolic regulation of APOBEC-1 Complementation Factor trafficking in mouse models of obesity and its positive correlation with the expression of ApoB protein in hepatocytes

AbstractAPOBEC-1 Complementation Factor (ACF) is an RNA-binding protein that interacts with apoB mRNA to support RNA editing. ACF traffics between the cytoplasm and nucleus. It is retained in the nucleus in response to elevated serum insulin levels where it supports enhanced apoB mRNA editing. In this report we tested whether ACF may have the ability to regulate nuclear export of apoB mRNA to the sites of translation in the cytoplasm. Using mouse models of obesity-induced insulin resistance and primary hepatocyte cultures we demonstrated that both nuclear retention of ACF and apoB mRNA editing were reduced in the livers of hyperinsulinemic obese mice relative to lean controls. Coincident with an increase in the recovery of ACF in the cytoplasm was an increase in the proportion of total cellular apoB mRNA recovered in cytoplasmic extracts. Cytoplasmic ACF from both lean controls and obese mouse livers was enriched in endosomal fractions associated with apoB mRNA translation and ApoB lipoprotein assembly. Inhibition of ACF export to the cytoplasm resulted in nuclear retention of apoB mRNA and reduced both intracellular and secreted ApoB protein in primary hepatocytes. The importance of ACF for modulating ApoB was supported by the finding that RNAi knockdown of ACF reduced ApoB secretion. An additional discovery from this study was the finding that leptin is a suppressor ACF expression. Dyslipidemia is a common pathology associated with insulin resistance that is in part due to the loss of insulin controlled secretion of lipid in ApoB-containing very low density lipoproteins. The data from animal models suggested that loss of insulin regulated ACF trafficking and leptin regulated ACF expression may make an early contribution to the overall pathology associated with very low density lipoprotein secretion from the liver in obese individuals

Slopes To Prevent Trapping of Bubbles in Microfluidic Channels

The idea of designing a microfluidic channel to slope upward along the direction of flow of the liquid in the channel has been conceived to help prevent trapping of gas bubbles in the channel. In the original application that gave rise to this idea, the microfluidic channels are parts of micro-capillary electrophoresis (microCE) devices undergoing development for use on Mars in detecting compounds indicative of life. It is necessary to prevent trapping of gas bubbles in these devices because uninterrupted liquid pathways are essential for sustaining the electrical conduction and flows that are essential for CE. The idea is also applicable to microfluidic devices that may be developed for similar terrestrial microCE biotechnological applications or other terrestrial applications in which trapping of bubbles in microfluidic channels cannot be tolerated. A typical microCE device in the original application includes, among other things, multiple layers of borosilicate float glass wafers. Microfluidic channels are formed in the wafers, typically by use of wet chemical etching. The figure presents a simplified cross section of part of such a device in which the CE channel is formed in the lowermost wafer (denoted the channel wafer) and, according to the present innovation, slopes upward into a via hole in another wafer (denoted the manifold wafer) lying immediately above the channel wafer. Another feature of the present innovation is that the via hole in the manifold wafer is made to taper to a wider opening at the top to further reduce the tendency to trap bubbles. At the time of reporting the information for this article, an effort to identify an optimum technique for forming the slope and the taper was in progress. Of the techniques considered thus far, the one considered to be most promising is precision milling by use of femtosecond laser pulses. Other similar techniques that may work equally well are precision milling using a focused ion beam, or a small diamond-tipped drill bit

B771: Long-Time Series Temperature and Precipitation Records for Maine, 1808-1978

The purpose of this Bulletin is to reconstruct a series of long run temperature and precipitation instrumental records for Maine (monthly means and accumulations). We hope that the data tables and graphs produced here will be of use to climatologists and other researchers and to Maine residents who are interested in the climatic history of the state. To aid in reconstruction, regional records were formed by grouping records from several geographical locations. Much of the data reproduced here have been published elsewhere in a wide variety of publications. Some are found easily in libraries while others are not readily available. A small number of records are published here for the first time. A bibliography of source materials, organized by region and then location is provided for those wishing to consult the original records.https://digitalcommons.library.umaine.edu/aes_bulletin/1132/thumbnail.jp

Climate Fluctuation and Agricultural Change in Southern and Central New England, 1765-1880

This article discusses the theory that previous discussions of the decline of Maine population in the period 1765-1880 failed the address the impact of weather fluctuations on the society of Maine

The Meteoritical Bulletin, No. 92, 2007 September

Abstract— In this edition of The Meteoritical Bulletin, 1394 recognized meteorites are reported, 27 from specific locations within Africa, 133 from Northwest Africa, 1227 from Antarctica (from ANSMET, PNRA, and PRIC expeditions), and 7 from Asia. The Meteoritical Bulletin announces the approval of four new names series by the Nomenclature Committee of the Meteoritical Society, two from Africa and one from Asia, including Al Haggounia, from Al Haggounia, Morocco, which is projected to be on the order of 3 metric tons of material related to enstatite chondrites and aubrites. Approved are two falls from Africa, Bassikounou (Mauritania) and Gashua (Nigeria). Approved from areas other than Antarctica are one lunar, two Martian, 32 other achondrites, three mesosiderites, two pallasites, one CM, two CK, one CR2, two CV3, one CR2, and four R chondrites. The Nomenclature Committee of the Meteoritical Society announces 48 newly approved relict meteorites from two new name series, Österplana and Gullhögen (both from Sweden)