The subcellular localization of acetyl-CoA carboxylase 2

Animals, including humans, express two isoforms of acetyl-CoA carboxylase (EC 6.4.1.2), ACC1 (Mr = 265 kDa) and ACC2 (Mr = 280 kDa). The predicted amino acid sequence of ACC2 contains an additional 136 aa relative to ACC1, 114 of which constitute the unique N-terminal sequence of ACC2. The hydropathic profiles of the two ACC isoforms generally are comparable, except for the unique N-terminal sequence in ACC2. The sequence of amino acid residues 1–20 of ACC2 is highly hydrophobic, suggesting that it is a leader sequence that targets ACC2 for insertion into membranes. The subcellular localization of ACC2 in mammalian cells was determined by performing immunofluorescence microscopic analysis using affinity-purified anti-ACC2-specific antibodies and transient expression of the green fluorescent protein fused to the C terminus of the N-terminal sequences of ACC1 and ACC2. These analyses demonstrated that ACC1 is a cytosolic protein and that ACC2 was associated with the mitochondria, a finding that was confirmed further by the immunocolocalization of a known human mitochondria-specific protein and the carnitine palmitoyltransferase 1. Based on analyses of the fusion proteins of ACC–green fluorescent protein, we concluded that the N-terminal sequences of ACC2 are responsible for mitochondrial targeting of ACC2. The association of ACC2 with the mitochondria is consistent with the hypothesis that ACC2 is involved in the regulation of mitochondrial fatty acid oxidation through the inhibition of carnitine palmitoyltransferase 1 by its product malonyl-CoA.

NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response

A wealth of evidence supports increased NO (NO⋅) in asthma, but its roles are unknown. To investigate how NO participates in inflammatory airway events in asthma, we measured NO⋅ and NO⋅ chemical reaction products [nitrite, nitrate, S-nitrosothiols (SNO), and nitrotyrosine] before, immediately and 48 h after bronchoscopic antigen (Ag) challenge of the peripheral airways in atopic asthmatic individuals and nonatopic healthy controls. Strikingly, NO\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{3}^{-}}}\end{equation*}\end{document} was the only NO⋅ derivative to increase during the immediate Ag-induced asthmatic response and continued to increase over 2-fold at 48 h after Ag challenge in contrast to controls [P < 0.05]. NO\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{2}^{-}}}\end{equation*}\end{document} was not affected by Ag challenge at 10 min or 48 h after Ag challenge. Although SNO was not detectable in asthmatic airways at baseline or immediately after Ag, SNO increased during the late response to levels found in healthy controls. A model of NO⋅ dynamics derived from the current findings predicts that NO⋅ may have harmful effects through formation of peroxynitrite, but also subserves an antioxidant role by consuming reactive oxygen species during the immediate asthmatic response, whereas nitrosylation during the late asthmatic response generates SNO, safe reservoirs for removal of toxic NO⋅ derivatives.

2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor

Two types of endogenous cannabinoid-receptor agonists have been identified thus far. They are the ethanolamides of polyunsaturated fatty acids—arachidonoyl ethanolamide (anandamide) is the best known compound in the amide series—and 2-arachidonoyl glycerol, the only known endocannabinoid in the ester series. We report now an example of a third, ether-type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether), isolated from porcine brain. The structure of noladin ether was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by comparison with a synthetic sample. It binds to the CB1 cannabinoid receptor (Ki = 21.2 ± 0.5 nM) and causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. It binds weakly to the CB2 receptor (Ki > 3 μM).

Human blood-mobilized hematopoietic precursors differentiate into osteoclasts in the absence of stromal cells.

Osteoclastogenesis is a complex process that is facilitated by bone marrow stromal cells (SCs). To determine if SCs are an absolute requirement for the differentiation of human hematopoietic precursors into fully mature, osteoclasts (OCs), CD34+ cells were mobilized into the peripheral circulation with granulocyte colony-stimulating factor, harvested by leukapheresis, and purified by magnetic-activated cell sorting. This procedure yields a population of CD34+ cells that does not contain SC precursors, as assessed by the lack of expression of the SC antigen Stro-1, and that differentiates only into hematopoietic cells. We found that CD34+, Stro-1- cells cultured with a combination of granulocyte/macrophage colony-stimulating factor, interleukin 1, and interleukin 3 generated cells that fulfill current criteria for the characterization of OCs, including multinucleation, presence of tartrate-resistant acid phosphatase, and expression of the calcitonin and vitronectin receptors and of pp60c-src tyrosine kinase. These OCs also expressed mRNA for the noninserted isoform of the calcitonin receptor and excavated characteristic resorption pits in devitalized bone slices. These data demonstrate that accessory SCs are not essential for human osteoclastogenesis and that granulocyte colony-stimulating factor treatment mobilizes OC precursors into the peripheral circulation.

Human fatty acid synthase: properties and molecular cloning.

Fatty acid synthase (FAS; EC 2.3.1.85) was purified to near homogeneity from a human hepatoma cell line, HepG2. The HepG2 FAS has a specific activity of 600 nmol of NADPH oxidized per min per mg, which is about half that of chicken liver FAS. All the partial activities of human FAS are comparable to those of other animal FASs, except for the beta-ketoacyl synthase, whose significantly lower activity is attributable to the low 4'-phosphopantetheine content of HepG2 FAS. We cloned the human brain FAS cDNA. The cDNA sequence has an open reading frame of 7512 bp that encodes 2504 amino acids (M(r), 272,516). The amino acid sequence of the human FAS has 79% and 63% identity, respectively, with the sequences of the rat and chicken enzymes. Northern analysis revealed that human FAS mRNA was about 9.3 kb in size and that its level varied among human tissues, with brain, lung, and liver tissues showing prominent expression. The nucleotide sequence of a segment of the HepG2 FAS cDNA (bases 2327-3964) was identical to that of the cDNA from normal human liver and brain tissues, except for a 53-bp sequence (bases 3892-3944) that does not alter the reading frame. This altered sequence is also present in HepG2 genomic DNA. The origin and significance of this sequence variance in the HepG2 FAS gene are unclear, but the variance apparently does not contribute to the lower activity of HepG2 FAS.

Synthesis and biological evaluation of superactive agonists of growth hormone-releasing hormone.

Analogs of the 29 amino acid sequence of human growth hormone-releasing hormone (hGH-RH) with agmatine (Agm) in position 29, desaminotyrosine (Dat) in position 1, norleucine (Nle) in position 27, and L-alpha-aminobutyric acid (Abu) in position 15 have been synthesized, and their biological activity was evaluated. Some peptides contained one or two residues of ornithine (Orn) instead of Lys in positions 12 and 21 and additional replacements in positions 8 and 28. All analogs were found to be more potent than hGH-RH-(1-29)-NH2 in the superfused rat pituitary cell system. In tests in vivo in rats after subcutaneous administration, the analogs JI-22, [Dat1, Orn12,21, Abu15, Nle27, Agm29]hGH-RH-(1-29); JI-34, [Dat1, Orn12,21,Abu15,Nle27, Asp28, Agm29]hGH-RH-(1-29); JI-36, [Dat1, Thr8, Orn12,21, Abu15,Nle27,Asp28,Agm29]hGH-RH-(1-29); and JI-38, [Dat1,Gln8, Orn12,21,Abu15,Nle27,Asp28,Agm29]hGH-RH-(1 -29) displayed a potency 44.6,80.9,95.8, and 71.4 times greater, respectively, than that of hGH-RH-(1-29)-NH2 at 15 min and 217.1, 89.7, 87.9, and 116.8 times greater at 30 min. After intravenous administration, JI-22, JI-36, and JI-38 were 3.2-3.8 times more potent than hGH-RH-(1-29)-NH2 at 5 min and 6.1-8.5 times more active at 15 min. All analogs were found to have higher binding affinities for GH-RH receptors on rat pituitary cells than hGH-RH-(1-29)-NH2. Because of high activity and greater stability, these analogs could be considered for therapy of patients with growth hormone deficiency.

Human acetyl-CoA carboxylase: characterization, molecular cloning, and evidence for two isoforms.

We have cloned and sequenced the cDNA coding for human HepG2 acetyl-CoA carboxylase (ACC; EC 6.4.1.2). The sequence has an open reading frame of 7038 bp that encode 2346 amino acids (M(r), 264,737). The C-terminal 2.6-kb sequence is very different from that recently reported for human ACC (Ha, J., Daniel, S., Kong, I.-S., Park, C.-K., Tae, H.-J. & Kim, K.-H. [1994] Eur. J. Biochem. 219, 297-306). Northern blot analysis revealed that the ACC mRNA is approximately 10 kb in size and that its level varies among the tissues tested. Evidence is presented to show that the human ACC gene is 200-480 kbp in size and maps to chromosome 17q12. We also provide evidence for the presence of another ACC-like gene with similarly sized mRNA but tissue-specific expression different from that of the ACC gene reported herein. That this second ACC-like gene encodes the 280-kDa carboxylase is not ruled out.

Uzbekistán: la configuración de un nuevo estado. Especial referencia al estatus de la mujer

Uzbekistan has a long and interesting heritage of ancient civilization linked to the historic “Silk Road”, through which transited people, goods, ideas and cultures. The major cities of the Silk Road - Samarkand, Bukhara, and Khiva are testimonies of the past and leave a deep impression on any visitor. As time goes by, Uzbekistan has become a key country in the whole Central Asian region, because it possesses mineral, agricultural and natural resources and has a huge potential for development. It is rich in energy resources such as oil and gas, but it is very difficult to commercialize them due to its landlocked position. The historical legacy of the Republic of Uzbekistan is a valuable heritage. The above mentioned ancient cities used to be centers of science and art, where important architects created palaces, mosques, madrassas, minarets, and mausoleums of the Islamic style, that still exist today. This cultural wealth is an element of internal cohesion and external outreach towards Islamic heritage, related to such Muslim countries as Turkey and the Gulf States. Moreover, this historical and architectural heritage has enormous economic potential for tourism, which can contribute to strengthen the relations of cooperation and friendship between Uzbekistan and the International Society. The influence of tradition and culture has still a huge impact on the society. This can be felt for example, in the traditional gender roles distribution. As a result of which, meńs presence in the areas of decision making is still slightly higher than womeńs one...

State-building y entorno de seguridad en los países de Oriente Medio. Especial referencia al subcomplejo de seguridad regional del Golfo

El objetivo principal de esta investigación es contribuir al debate académico sobre la problemática de seguridad/inseguridad que afecta a los Estados árabes de Oriente Medio, indagando sobre sus causas y reflexionando sobre sus consecuencias desde el enfoque de los estudios de seguridad y, más concretamente, desde la corriente que aborda la cuestión de la seguridad en el Tercer Mundo. Una perspectiva novedosa tanto desde el punto de vista de las investigaciones llevadas a cabo en nuestro país sobre la región de Oriente Medio, como de las investigaciones existentes en lengua árabe. El punto de partida de nuestra investigación consiste en cuestionar la capacidad explicativa de las teorías tradicionales y dominantes de seguridad al ser aplicadas al análisis de la seguridad nacional en el contexto particular del Tercer Mundo y, como parte de este, al mundo árabe en general. En nuestra opinión, este enfoque tradicional no permite entender las causas de la inestabilidad permanente que azota el Oriente Medio, al no conseguir captar la naturaleza esencial de dicha problemática. La razón fundamental es que los estudios de seguridad surgieron para explicar y dar respuesta a los problemas de la seguridad occidental. Aplicar indiscriminadamente los postulados de la definición de seguridad dominante a cualquier escenario no sólo limita enormemente el alcance del análisis, sino que distorsiona la realidad objeto de estudio. Esta limitación es aplicable también al explicar el escenario de inestabilidad e inseguridad del Oriente Medio. Con el propósito de abordar el vacío existente dentro de los estudios de seguridad relativos a la problemática de la seguridad en el Tercer Mundo, y de poder llegar a entender lo que no alcanzan a explicar las teorías clásicas sobre seguridad surge la corriente del Realismo Subalterno. Dentro del marco de la teoría realista, el Realismo Subalterno no se ha limitado únicamente a ser una manifestación más de contestación del concepto de seguridad tradicional, sino que se presenta como un instrumento analítico alternativo a los paradigmas y teorías dominantes sobre seguridad –tanto de la concepción realista tradicional como de los nuevos intentos de revisión del concepto-. Una perspectiva útil para explicar problemas contemporáneos de seguridad frente a la insuficiente capacidad de las teorías de seguridad clásicas, especialmente frente a los nuevos desafíos surgidos tras el final de la Guerra Fría...

The Affective Dimensions of Social Controversy

Social controversy is a sustained, mediated debate between at least two oppositional parties which is more than just a difference of opinion; rather it is a persistent conflict over the political and cultural implications that dominant forms of communicative reasoning, practices, and norms have for a public. Simply put, during social controversies the norms guiding public life can be negotiated, reaffirmed, negated, and/or transformed. This can lead to progressive political, cultural, and/or social change in some instances, while establishing or reifying conservative and even oppressive norms, practices, and laws in others. Building upon Olson and Goodnight's (1994) theoretical and methodological framework of social controversy, this dissertation argues that scholars should analyze the role affect plays in this type of conflict as a means to address the regulation of public conduct as well as public discourse. The rhetorical and argumentative significance of the affective dimensions of social controversy have been conceptualized and analyzed via an examination of emotion-based claims and affective states that have become salient, discernable and/or apprehendable during specific public disagreements. Such a conceptualization demonstrates that critical insights regarding the norms that guide public conduct, the role risk and vulnerability play in the regulation of individuals' public behavior, and the relationship between affect and citizenship can be gained by focusing on a controversy's affective dimensions. To highlight the importance of the study of affect in social controversy as well as better understand the larger critical significance affect theory has for rhetorical and argumentation studies, this dissertation has analyzed the affective dimensions of three conflicts. They are: the Abu Ghraib prisoner abuse social controversy, the International Freedom Center social controversy, and the controversy over the 2004 French ban on conspicuous religious attire in public schools. The findings from this dissertation that have specific and general implications for future work in the field of controversy as well as rhetoric and argumentation, respectively.

Digitizing the Historical Periodical Collection at the Al-Aqsa Mosque Library in East Jerusalem

The Arab Press in Palestine developed at the turn of the twentieth century and proliferated for several decades despite restrictions imposed under the Ottoman Empire and during the British Mandate Period (1917-1948). Hardcopies of the early newspapers and periodicals are rare and access to them at a few Palestinian municipal or private libraries is limited. The Al-Aqsa Mosque Library holds one of the largest collections of Palestinian historical newspapers and periodicals. The collection provides a unique and rich source of information about the history of Palestine in the first half of the twentieth century. Access to the collection is limited and brittle paper copies have been rapidly deteriorating. This paper provides an overview of the digitization project aimed at preserving the historical periodical collection located at the AlAqsa Mosque Library

Las perspectivas de los refugiados sobre el regreso a Somalia

MSF preguntó hace poco a los refugiados somalíes en el campo de Dagahaley en Dadaab acerca de sus condiciones de vida y de lo que piensan sobre su posible regreso a Somalia en un futuro próximo. Las respuestas sugieren que las malas condiciones de vida en el campo no les llevan a querer regresar a pesar de lo extendida que está la creencia contraria.

Transport across two interacting quantum dots: Bulk Kondo, Kondo box, and molecular regimes

We analyze the transport properties of a double quantum dot device with both dots coupled to perfect conducting leads and to a finite chain of N noninteracting sites connecting both of them. The interdot chain strongly influences the transport across the system and the local density of states of the dots. We study the case of a small number of sites, so that Kondo box effects are present, varying the coupling between the dots and the chain. For odd N and small coupling between the interdot chain and the dots, a state with two coexisting Kondo regimes develops: the bulk Kondo due to the quantum dots connected to leads and the one produced by the screening of the quantum dot spins by the spin in the finite chain at the Fermi level. As the coupling to the interdot chain increases, there is a crossover to a molecular Kondo effect, due to the screening of the molecule (formed by the finite chain and the quantum dots) spin by the leads. For even N the two Kondo temperatures regime does not develop and the physics is dominated by the usual competition between Kondo and antiferromagnetism between the quantum dots. We finally study how the transport properties are affected as N is increased. For the study we used exact multiconfigurational Lanczos calculations and finite-U slave-boson mean-field theory at T=0. The results obtained with both methods describe qualitatively and also quantitatively the same physics.

Yemen, 1774 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Terrae Yemen maxima Pars. seu Imperii Imami, Principatus Kaukebân, nec non ditionum Haschid U Bekîl, Nehhm, Chaulân, Abu Arîsch Et Aden Tabula : ex observationibus astronomicis et hodometricis jussu et suntibus Potentissimor: Daniae Regnum Friderici V et Christiani VII institutis, delineata Auctore C. Niebuhr ; Gustav Conrad Lotter Sculps. It was published by Tob. Conr. Lotter in 1774. Scale [ca. 1,250,000]. Covers a portion of Yemen and Saudi Arabia. Map in Latin. The image inside the map neatline is georeferenced to the surface of the earth and fit to the World Miller Cylindrical projection. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial boundaries, shoreline features, and more. Relief shown by hachures. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection as part of the Open Collections Program at Harvard University project: Islamic Heritage Project. Maps selected for the project represent a range of regions, originators, ground condition dates, scales, and purposes. The Islamic Heritage Project consists of over 100,000 digitized pages from Harvard's collections of Islamic manuscripts and published materials. Supported by Prince Alwaleed Bin Talal and developed in association with the Prince Alwaleed Bin Talal Islamic Studies Program at Harvard University.

Majmūʻah : manuscript, 1401-1402

1. Tarih-i Al-i Osman bin Ertuğrul (dates of Ottoman Sultans) (f. 1r) -- 2. Suret-i arzname (ff. 1v--2v) -- 3. Arabic poem, awāʼil Muḥarram 804 [August 11-20, 1401] (copied by Ḥājjī Aḥmad ibn ... al-B.f.l.ghānī) (ff. 3r-11r) -- 4. Taʻrīfāt ʻilm usūl fiqh, Shawwāl 804 [May 1402] (ff. 11v-16v) -- 5. Arabic glossary (explanations in Arabic and Persian), 804 [1402] (copied by Idrīs b. Ḥasan b. Bayram) (ff. 17r-52r) -- 6. Sharḥ al-Farāʼiḍ al-Sirājīyah / ʻAbd al-Karīm b. Muḥammad b. al-Ḥasan al-Hamadānī al-Tabrīzī, awāsiṭ Dhī al-Ḥijja 804 [July 1402] (copied by Idrīs b. Ḥasan b. Bayram) (ff. 52v-94r) -- 7. Lughat-i ḥurūf (ff. 94v-95r) -- 8. Mufradāt-i Pārsī (A list of Persian verbs) (ff. 95v-97v).