bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice
Authors: Tanda Koichi , Nishi Akinori , Matsuo Naoki , Nakanishi Kazuo , Yamasaki Nobuyuki , Sugimoto Tohru , Toyama Keiko , Takao Keizo , Miyakawa Tsuyoshi
Published: July 2009

Background

Neuronal nitric oxide synthase (nNOS) is involved in the regulation of a diverse population of intracellular messenger systems in the brain. In humans, abnormal NOS/nitric oxide metabolism is suggested to contribute to the pathogenesis and pathophysiology of some neuropsychiatric disorders, such as schizophrenia and bipolar disorder. Mice with targeted disruption of the nNOS gene exhibit abnormal behaviors. Here, we subjected nNOS knockout (KO) mice to a battery of behavioral tests to further investigate the role of nNOS in neuropsychiatric functions. We also examined the role of nNOS in dopamine/DARPP-32 signaling in striatal slices from nNOS KO mice and the effects of the administration of a dopamine D1 receptor agonist on behavior in nNOS KO mice.

Results

nNOS KO mice showed hyperlocomotor activity in a novel environment, increased social interaction in their home cage, decreased depression-related behavior, and impaired spatial memory retention. In striatal slices from nNOS KO mice, the effects of a dopamine D1 receptor agonist, SKF81297, on the phosphorylation of DARPP-32 and AMPA receptor subunit GluR1 at protein kinase A sites were enhanced. Consistent with the biochemical results, intraperitoneal injection of a low dose of SKF81297 significantly decreased prepulse inhibition in nNOS KO mice, but not in wild-type mice.

Conclusion

These findings indicate that nNOS KO upregulates dopamine D1 receptor signaling, and induces abnormal social behavior, hyperactivity and impaired remote spatial memory. nNOS KO mice may serve as a unique animal model of psychiatric disorders.
Methotrexate therapy associates with reduced prevalence of the metabolic syndrome in rheumatoid arthritis patients over the age of 60- more than just an anti-inflammatory effect? A cross sectional study
Authors: Toms Tracey E , Panoulas Vasileios F , John Holly , Douglas Karen MJ , Kitas George D
Published: July 2009

Introduction

The metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in rheumatoid arthritis (RA). The prevalence and associations of the MetS in RA remain uncertain: systemic inflammation and anti-rheumatic therapy may contribute. Methotrexate (MTX) use has recently been linked to a reduced presence of MetS, via an assumed generic anti-inflammatory mechanism. We aimed to: assess the prevalence of the MetS in RA; identify factors that associate with its presence; and assess their interaction with the potential influence of MTX.

Methods

MetS prevalence was assessed cross-sectionally in 400 RA patients, using five MetS definitions (National Cholesterol Education Programme 2004 and 2001, International Diabetes Federation, World Health Organisation and European Group for Study of Insulin Resistance). Logistic regression was used to identify independent predictors of the MetS. Further analysis established the nature of the association between MTX and the MetS.

Results

MetS prevalence rates varied from 12.1% to 45.3% in RA according to the definition used. Older age and higher HAQ scores associated with the presence of the MetS. MTX use, but not other disease modifying anti-rheumatic drugs (DMARDs) or glucocorticoids, associated with significantly reduced chance of having the MetS in RA (OR = 0.517, CI 0.33–0.81,P= 0.004).

Conclusions

The prevalence of the MetS in RA varies according to the definition used. MTX therapy, unlike other DMARDs or glucocorticoids, independently associates with a reduced propensity to MetS, suggesting a drug-specific mechanism, and makes MTX a good first-line DMARD in RA patients at high risk of developing the MetS, particularly those aged over 60 years.
Inducible expression of EVI1 in human myeloid cells causes phenotypes consistent with its role in myelodysplastic syndromes
Authors: Konrad Torsten A , Karger Anna , Hackl Hubert , Schwarzinger Ilse , Herbacek Irene , Wieser Rotraud
Published: July 2009

EVI1, a gene involved in myelodysplastic syndromes, causes growth arrest and cell death in U937 cells.

The oncogene EVI1 has been implicated in the etiology of AML and MDS. Although AML cells are characterized by accelerated proliferation and differentiation arrest, MDS cells hyperproliferate when immature but fail to differentiate later and die instead. In agreement with its roles in AML and in immature MDS cells, EVI1 was found to stimulate cell proliferation and inhibit differentiation in several experimental systems. In contrast, the variant protein MDS1/EVI1 caused the opposite effect in some of these assays. In the present study, we expressed EVI1 and MDS1/EVI1 in a tetracycline-regulable manner in the human myeloid cell line U937. Induction of either of these proteins caused cells to accumulate in the G0/G1-phase of the cell cycle and moderately increased the rate of spontaneous apoptosis. However, when EVI1- or MDS1/EVI1-expressing cells were induced to differentiate, they massively succumbed to apoptosis, as reflected by the accumulation of phosphatidylserine in the outer leaflet of the plasma membrane and increased rates of DNA fragmentation. In summary, these data show that inducible expression of EVI1 in U937 cells causes phenotypes that may be relevant for its role in MDS and provides a basis for further investigation of its contribution to this fatal disease.
Ca2+ signaling in airway epithelial cells facilitates leukocyte recruitment and transepithelial migration
Authors: Chun Jarin , Prince Alice
Published: July 2009

Review on consequences of TLR2 signaling the activation of Ca2+-dependent proteases (calpains) and link to junctional proteins to facilitate PMN migration into the airway lumen.

In airway cells, TLR2 stimulation by bacterial products activates Ca2+ fluxes that signal leukocyte recruitment to the lung and facilitates transepithelial migration into the airway lumen. TLR2 is apically displayed on airway cells, where it senses bacterial stimuli. Biochemical and genetic approaches demonstrate that TLR2 ligands stimulate release of Ca2+ from intracellular stores by activating TLR2 phosphorylation by c-Src and recruiting PI3K and PLCγ to affect Ca2+ release through IP3Rs. This Ca2+ release plays a pivotal role in signaling TLR2-dependent NF-κB activation and chemokine expression to recruit PMNs to the lung. In addition, TLR2-initiated Ca2+ release activates Ca2+-dependent proteases, calpains, which cleave the transmembrane proteins occludin and E-cadherin to promote PMN transmigration. This review highlights recent findings that demonstrate a central role for Ca2+ signaling in airway epithelial cells to induce proinflammatory gene transcription and to initiate junctional changes that accommodate transmigration of recruited PMNs.
Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages
Authors: Stout Robert D , Watkins Stephanie K , Suttles Jill
Published: July 2009

Functionally polarized macrophages in chronic pathologies are highly adaptable cells displaying a functional response to tissue signals, which response can be reprogrammed to therapeutic advantage.

The extent to which the functional heterogeneity of Mφs is dependent on the differentiation of functional sublineages remains unresolved. One alternative hypothesis proposes that Mφs are functionally plastic cells, which are capable of altering their functional activities progressively in response to progressively changing signaling molecules generated in their microenvironment. This “functional plasticity” hypothesis predicts that the functionally polarized Mφs in chronic pathologies do not represent Mφ sublineages but rather, are mutable phenotypes sustained by chronic signaling from the pathological environment. Solid TAMφs are chronically polarized to provide activities that support tumor growth and metastasis and suppress adaptive immune responses. In support of the functional plasticity hypothesis, administration of slow-release microsphere-encapsulated IL-12 successfully reprogrammed TAMφs in situ, reducing Mφ support of tumor growth and metastasis and enhancing Mφ proimmunogenic activities. Increased knowledge of how Mφ function is regulated and how polarized Mφs can be reprogrammed in situ will increase our ability to control Mφ function in a variety of pathological states, including cancer and chronic inflammatory disease.
Up-regulation of alveolar macrophage matrix metalloproteinases in HIV1+ smokers with early emphysema
Authors: Kaner Robert J , Santiago Francisco , Crystal Ronald G
Published: July 2009

Increased production and activation of proteases by alveolar macrophages may contribute to the accelerated destruction of lung tissue in HIV-1+ smokers.

HIV1 + smokers develop emphysema at an earlier age and with a higher incidence than HIV1– smokers. Since human alveolar macrophages (AMs) are capable of producing proteases that degrade extracellular matrix components, we hypothesized that up-regulation of AM matrix metalloproteinases may be associated with the emphysema of HIV1+ smokers. Microarray analysis was used to screen which matrix metalloproteinases (MMPs) genes were expressed by AM of HIV1+ smokers with early emphysema. For each of the MMP genes expressed (MMP-1, −2, −7, −9, −10, −12 and −14), TaqMan PCR was used to quantify the relative expression in AM from four groups of individuals: HIV1– healthy nonsmokers, HIV1– healthy smokers, HIV1– smokers with early emphysema, and HIV1+ smokers with early emphysema. While AM gene expression of MMPs was higher in HIV1– individuals with emphysema in comparison with HIV1– healthy smokers, for the majority of the MMPs (−1, −7, −9, and −12), AM expression from HIV1+ smokers with early emphysema was significantly higher than in HIV1− smokers with early emphysema. HIV1+ individuals with early emphysema also had higher levels of epithelial lining fluid (ELF) MMPs (−2, −7, −9, and −12) than the 3 HIV1− groups. ELF MMP (−2,-7,-9, and −12) levels were similar in HIV1+ nonsmokers compared with HIV1− nonsmokers. Interestingly, the active forms of MMP-2, −9, and −12 were exclusively detected in ELF from HIV1+ individuals with early emphysema. Since the activities of the up-regulated AM MMPs include collagenases, gelatinases, matrilysins, and elastase, these data suggest that up-regulated AM MMP genes and activation of MMP proteins may contribute to the emphysema of HIV1+ individuals who smoke.
The Transformation of Traditional Woodland Management: Commercial Sylviculture in Medieval Champagne
Authors: Keyser Richard
Published: July 2009

This essay argues that high medieval economic growth in Champagne and elsewhere in northern France encouraged a switch in the primary focus of woodland management from extensive silvo-pastoralism to intensive small wood production. For the first time in the thirteenth century, coppicing, short cycles of cutting and regeneration of trees capable of resprouting from stumps or trunks, came to dominate sylviculture as an intensively managed, market-oriented system, one that lasted for centuries. This essay thus provides a wider context for the late medieval and early modern French state's role in shaping forest exploitation. Royal officials did not so much innovate as respond to new market opportunities by appropriating and generalizing practices that had long existed in many regions. Before the sixteenth century few educated experts ventured into the details of woodland management, which remained largely the preserve of nonelite peasants, foresters, and woodmongers, the bearers of a traditional, orally transmitted ecological knowledge.

Cet essai soutient qu'en Champagne et ailleurs dans la France du Nord la croissance économique du Moyen Age classique a encouragé un changement dans l'exploitation forestière du pastoralisme extensif à la production intensive du bois. Pour la première fois au treizième siècle le bois taillis, la coupe rapprochée des arbres capables de rejeter des souches, a dominé la sylviculture en système organisé pour le marché et ce-là persistera pour des siècles. Cet essai donne ainsi un contexte plus large au rôle de l'Etat Français tardo-médiévale et moderne dans le modelage de l'exploitation forestière. Les fonctionnaires royaux ont moins innové que réagi aux nouvelles opportunités commerciales par l'appropriation et la généralisation des pratiques qui existaient depuis longtemps. Jusqu'au seizième siècle, peu de spécialistes formés à l'université ont abordé l'exploitation forestière, qui est restée principalement le domaine des simples paysans, forestiers, et marchands, porteurs d'un savoir écologique populaire.
To Historicize or Naturalize Nature: Hydraulic Communities and Administrative States in Nineteenth-Century Europe
Authors: Ingold Alice
Published: July 2009

This article focuses on the discourses related to the management of water resources occurring in several regions of Europe after the French Revolution. Written by agronomists, engineers, and lawyers, these texts point to hydraulic societies. The writings of two authors are analyzed: those of François-Jacques Jaubert de Passa in France and those of Carlo Cattaneo in Italy. They refer to political and legal institutions and to systems of knowledge that were alternative to those put in place by the administrative states. They presented irrigation systems as edifices created over a long period of time: benefiting from empirical practices and from a technical culture that represented an alternative to that of state engineers, these edifices emerged as the expression of an equilibrium between society and its environment. In contrast to this narrative, state engineers transmitted a naturalized vision of water to support the claims of states on these resources. I argue that the nineteenth century corresponds with a face-to-face vision of nature, the historical one versus the natural one.

Cet article identifie une série de textes sur le gouvernement du territoire et des eaux qui paraissent après la Révolution française dans plusieurs régions d'Europe. Ces textes défendent des institutions politiques et juridiques et des dispositifs de savoirs alternatifs à ceux mis alors en place par les Etats administratifs. L'analyse porte sur deux auteurs qui décrivent des sociétés hydrauliques: François-Jacques Jaubert de Passa en France et Carlo Cattaneo en Italie présentent les systèmes irrigués comme des édifices élaborés dans la très longue durée. Construits à la faveur de pratiques et d'une culture technique alternative à celle des ingénieurs d'Etat, ces édifices apparaissent comme l'expression d'un équilibre entre une société et son environnement. En historicisant ces descriptions ethnographiques, le contexte de leur élaboration et de leur circulation, cet article propose d'identifier les tensions qui s'expriment dans un long dixneuvième siècle entre des définitions alternatives de la nature, une nature historicisée et socialisée et une nature naturalisée, ouvrant chacune à des formes politiques et à des systèmes de droits différents.
The Natures of Nation: Negotiating Modernity in the Landes de Gascogne
Authors: Temple Samuel
Published: July 2009

This article examines the transformation of the Landes de Gascogne in southwestern France. Once dominated by a sparse agropastoral landscape, the region underwent an intense program of pine forestation in the second half of the nineteenth century. The engineered forest, however, quickly escaped the grasp of the administrators, engineers, and local property owners who helped create it. Catastrophic fires plagued the monoculture pine stands, and by the end of the 1940s almost half of the woodlands had been destroyed. By focusing on the complex conflicts and negotiations that marked the origins of the Landais forests, this article presents a case study in the environmental dimensions of state making in modern France. It demonstrates how local and state claims over, first, the pastoral landes and, later, the industrial woodlands, prove difficult to disentangle and suggests the importance of an ambivalent discourse of marginality to the exercise and negotiation of authority in the modern nation-state.

Cet article examine la transformation des Landes de Gascogne, une région qui s'étend sur trois départements du sud-ouest de la France. Jadis couverte de vastes landes qui soutenaient une société agropastorale, la campagne s'était transformée par le boisement des pins après 1850, un grand projet amorcé par le gouvernement du Second Empire. Cependant, la nouvelle forêt a échappé rapidement à l'emprise de ses créateurs: les administrateurs, les ingénieurs et les propriétaires. Frappée par une série d'incendies catastrophiques, presque la moitié de la forêt se trouva détruite à la fin des années 1940. A travers une étude des origines des forêts, cet article offre une analyse du rôle de l'environnement dans l'étatisation en France. L'article montre que les revendications locales et nationales sur, d'abord, les landes pastorales, et plus tard, la forêt industrielle, s'avéraient difficiles à démêler. Un discours de marginalité a été essentiel à la pratique et à la négociation d'autorité dans l'Etat-nation moderne.
A Tasteful Patrimony? Landscape Preservation and Tourism in the Sites and Monuments Campaign, 1900–1935
Authors: Young Patrick
Published: July 2009

This article analyzes the Touring Club de France's Sites and Monuments campaign as a nationwide initiative to define and secure the value of natural landscapes in the face of accelerated economic change in rural France. In its work of inventorying, representation, and associational intervention in Brittany, I argue, the campaign formalized recognition of both a national and tourist interest vis-à-vis the Breton natural landscape; the ethos of bourgeois stewardship (of national resources, regional identity, and taste) that it propagated, though, coexisted uneasily at specific sites with more local usages and dispositions. The effort to reconstitute the Breton (and French) natural environments failed ultimately to secure the value and meaning of landscapes as preservationists had intended. Recast as a patrimony and domain of consumption, that natural environment now played host to multiple and sometimes contradictory appropriations.

En traitant du projet de conservation « sites et monuments », cet article analyse l'effet du tourisme sur l'environnement naturel en France, particulièrement en Bretagne pendant l'entre-deux-guerres. Ce projet d'association et d'intervention a rassemblé un grand nombre de bourgeois (notamment dans les associations protectionnistes et touristiques) se donnant pour mission de faire reconnaître et de sauvegarder la valeur des paysages français. L'analyse des rapports d'activités d'organisations de protection et du tourisme, d'ouvrages consacrés au tourisme et des photographies de sites révèle les liens intimes entre l'idée de préservation et l'identité et les aspirations d'une couche sociale en voie de développement sous la Troisième République. Dans leur travail d'inventaire, d'action associative et de représentation des sites et monuments naturels, les partisans de la conservation ont largement assuré la reconnaissance d'un intérêt national et touristique pour le paysage. De plus, ils se sont imposés comme les protecteurs exclusifs du patrimoine régional et national et du bon goût.
A “Watery Desert” in Vichy France: The Environmental History of the Camargue Wetlands, 1940–1944
Authors: Pearson Chris
Published: July 2009

This article traces the environmental history of the Camargue wetlands in southern France during World War II. War, defeat, and occupation ushered in agricultural modernization, the establishment of military training grounds, and German submersion plans, all of which threatened constructions of the region as a pure, wild landscape as well as existing ecological conditions. Throughout the war the Société Nationale d'Acclimatation de France (SNAF) campaigned to save its nature reserve, engaging in actions that lay between resistance and collaboration. The SNAF was aided unwittingly by the Camargue's singular climate. This article supports Bruno Latour's call for a reconceptualization of historical agency that includes the nonhuman. It also exposes wider continuities in French environmental history and contributes to Vichy historiography and the burgeoning literature on war and the environment.

Cet article retrace l'histoire environnementale de la Camargue pendant la Seconde Guerre mondiale. La guerre, la défaite et l'Occupation sont à l'origine de la modernisation agricole, de l'établissement des champs de tir, et du projet allemand de faire submerger la Camargue. Ces événements ont menacé l'image de la région comme paysage pur et sauvage, ainsi que les conditions écologiques existantes. Pendant tout ce temps, la Société nationale d'acclimatation de France (SNAF) tentait de sauver sa réserve naturelle, par des actions qui se situaient entre résistance et collaboration. Le climat particulier de la Camargue a involontairement aidé la SNAF. Cet article soutient l'invitation de Bruno Latour à repenser l'agent historique en y incluant le non-humain tandis qu'il expose les structures plus larges de l'histoire environnementale française et contribue à l'historiographie de la France de Vichy et à la littérature émergente sur les rapports entre la guerre et l'environnement.
Perceptual Objectivity
Authors: Burge Tyler
Published: July 2009

A central preoccupation of philosophy in the twentieth century was to determine constitutive conditions under which accurate (objective) empirical representation of the macrophysical environment is possible. A view that dominated attitudes on this project maintained that an individual cannot empirically represent a physical subject matter as having specific physical characteristics unless the individual can represent some constitutive conditions under which such representation is possible. The version of this view that dominated the century's second half maintained that objective empirical representation of the physical environment requires the individual to be able to supplement this representation with representation of general constitutive features of objectivity. This essay criticizes instances of this version in P. F. Strawson and Quine. It maintains that all versions of the position postulate conditions on objective empirical representation that are more intellectual than are warranted. Such views leave it doubtful that animals and human infants perceptually represent elements in the physical environment. By appeal to common sense and to empirical perceptual psychology, this essay argues that unaided perception yields objective representation of the macrophysical environment. It does so in prelinguistic animals, even in animals that almost surely lack propositional attitudes. The essay concludes with explications of nondeflationary conceptions of representation and perception. It distinguishes nonperceptual sensing from perceptual representation and explicates perceptual representation as a type of objective sensory representation. Objectivity is marked by perceptual constancies. Representation is marked by a nontrivial role for veridicality conditions in explanations of the relevant states.
On Truth-Conditions forIf(but Not Quite OnlyIf)
Authors: Gillies Anthony S.
Published: July 2009

What we want to be true about ordinary indicative conditionals seems to be more than we can possibly get: there just seems to be no good way to assign truth-conditions to ordinary indicative conditionals. Some take this argument as reason to make our wantings more modest. Others take it to show that indicative conditionals don't have truth-conditions in the first place. But we have overlooked two possibilities for assigning truth-conditions to indicatives. What's more, those possibilities deliver what we want and turn out to be equivalent.
Plato's Two Forms of Second-Best Morality
Authors: Wilberding James
Published: July 2009

In the Republic Plato presents a hierarchy of five cities, each representing a structural arrangement of the soul. The timocratic soul, characterized by its governance by spirit and its consequent desire for esteem and aversion to shame, is ranked as the second-best kind of soul, though this should strike us as surprising since the timocratic figure would seem to be duplicitous, intellectually passive, and at the mercy of the fortuitous opinions of others. This timocrat's position thus raises problems concerning the intrinsic value of the spirited part of the soul, problems that are best solved by comparing the auxiliary to the timocrat, both of whom represent different forms of second-best morality. A lengthy discussion of the early education's effect on the spirited part shows how the auxiliary represents the best kind of moral agent that the second-best nature (silver-souled individuals) can develop into. This is because the early education ensures that the auxiliary and the philosopher share the same basic structure of soul, with reason being in control of each, though the auxiliary's natural deficiencies create some limitations in terms of his or her moral self-sufficiency. The timocrat by contrast represents the second-best kind of moral agent that the best nature (gold-souled individuals) can develop into. The timocrat is morally inferior to the auxiliary and seems to embody Homeric shame-culture. Plato is critical of this approach to morality, but the timocrat justifiably occupies the second position in the hierarchy on account of his or her concern for the opinions of others.
Regulation of bone formation and remodeling by G-protein-coupled receptor 48
Authors: Luo Jian , Zhou Wei , Zhou Xin , Li Dali , Weng Jinsheng , Yi Zhengfang , Cho Sung Gook , Li Chenghai , Yi Tingfang , Wu Xiushan , Li Xiao-Ying , de Crombrugghe Benoit , Höök Magnus , Liu Mingyao
Published: July 2009

G-protein-coupled receptor (GPCR) 48 (Gpr48; Lgr4), a newly discovered member of the glycoprotein hormone receptor subfamily of GPCRs, is an orphan GPCR of unknown function. Using a knockout mouse model, we have characterized the essential roles of Gpr48 in bone formation and remodeling. Deletion of Gpr48 in mice results in a dramatic delay in osteoblast differentiation and mineralization, but not in chondrocyte proliferation and maturation, during embryonic bone formation. Postnatal bone remodeling is also significantly affected in Gpr48-/- mice, including the kinetic indices of bone formation rate, bone mineral density and osteoid formation, whereas the activity and number of osteoclasts are increased as assessed by tartrate-resistant acid phosphatase staining. Examination of the molecular mechanism of Gpr48 action in bone formation revealed that Gpr48 can activate the cAMP-PKA-CREB signaling pathway to regulate the expression level of Atf4 in osteoblasts. Furthermore, we show that Gpr48 significantly downregulates the expression levels of Atf4 target genes/proteins, such as osteocalcin (Ocn; Bglap2), bone sialoprotein (Bsp; Ibsp) and collagen. Together, our data demonstrate that Gpr48 regulates bone formation and remodeling through the cAMP-PKA-Atf4 signaling pathway.
The Integrator subunits function in hematopoiesis by modulating Smad/BMP signaling
Authors: Tao Shijie , Cai Yu , Sampath Karuna
Published: July 2009

Hematopoiesis, the dynamic process of blood cell development, is regulated by the activity of the bone morphogenetic protein (BMP) signaling pathway and by many transcription factors. However, the molecules and mechanisms that regulate BMP/Smad signaling in hematopoiesis are largely unknown. Here, we show that the Integrator complex, an evolutionarily conserved group of proteins, functions in zebrafish hematopoiesis by modulating Smad/BMP signaling. The Integrator complex proteins are known to directly interact with RNA polymerase II to mediate 3′ end processing of U1 and U2 snRNAs. We have identified several subunits of the Integrator complex in zebrafish. Antisense morpholino-mediated knockdown of the Integrator subunit 5 (Ints5) in zebrafish embryos affects U1 and U2 snRNA processing, leading to aberrant splicing of smad1 and smad5 RNA, and reduced expression of the hematopoietic genes stem cell leukemia (scl, also known as tal1) and gata1. Blood smears from ints5morphant embryos show arrested red blood cell differentiation, similar to scl-deficient embryos. Interestingly, targeting other Integrator subunits also leads to defects in smad5 RNA splicing and arrested hematopoiesis, suggesting that the Ints proteins function as a complex to regulate the BMP pathway during hematopoiesis. Our work establishes a link between the RNA processing machinery and the downstream effectors of BMP signaling, and reveals a new group of proteins that regulates the switch from primitive hematopoietic stem cell identity and blood cell differentiation by modulating Smad function.
TheTbx20homologsmidlineandH15specify ventral fate in theDrosophila melanogasterleg
Authors: Svendsen Pia C. , Formaz-Preston Ann , Leal Sandra M. , Brook William J.
Published: July 2009

Regional fates in the developing limbs of Drosophila melanogasterare controlled by selector gene transcription factors. Ventral fate in the fly leg is specified by the expression of the ligand Wingless. We present evidence that midline and H15, members of the Tbx20 class of T-box transcription factors, are key mediators of the Wingless signal in the formation of the ventral region of the fly leg. midline and H15 are restricted to identical ventral domains of expression through activation by Wingless and repression by the dorsal signal Decapentaplegic. midline and H15 function redundantly and cell autonomously in the formation of ventral-specific structures. Conversely, midlineis sufficient to induce ventral fate. Finally, the induction of ectopic ventral fate by mid is compromised when Wingless signaling is attenuated, suggesting that Wingless acts both upstream and in parallel with midline/H15 to specify ventral fate. Based on these results,we propose that midline and H15 may be considered as the selector genes for ventral leg fate.
The NK-2 class homeodomain factor CEH-51 and the T-box factor TBX-35 have overlapping function inC. elegansmesoderm development
Authors: Broitman-Maduro Gina , Owraghi Melissa , Hung Wendy W. K. , Kuntz Steven , Sternberg Paul W. , Maduro Morris F.
Published: July 2009

The C. elegans MS blastomere, born at the 7-cell stage of embryogenesis, generates primarily mesodermal cell types, including pharynx cells, body muscles and coelomocytes. A presumptive null mutation in the T-box factor gene tbx-35, a target of the MED-1 and MED-2 divergent GATA factors, was previously found to result in a profound decrease in the production of MS-derived tissues, although the tbx-35(-) embryonic arrest phenotype was variable. We report here that the NK-2 class homeobox gene ceh-51 is a direct target of TBX-35 and at least one other factor, and that CEH-51 and TBX-35 share functions. Embryos homozygous for a ceh-51 null mutation arrest as larvae with pharynx and muscle defects, although these tissues appear to be specified correctly. Loss of tbx-35 and ceh-51 together results in a synergistic phenotype resembling loss of med-1 and med-2. Overexpression of ceh-51 causes embryonic arrest and generation of ectopic body muscle and coelomocytes. Our data show that TBX-35 and CEH-51 have overlapping function in MS lineage development. As T-box regulators and NK-2 homeodomain factors are both important for heart development in Drosophila and vertebrates, our results suggest that these regulators function in a similar manner in C. elegans to specify a major precursor of mesoderm.
UNC-83 is a nuclear-specific cargo adaptor for kinesin-1-mediated nuclear migration
Authors: Meyerzon Marina , Fridolfsson Heidi N. , Ly Nina , McNally Francis J. , Starr Daniel A.
Published: July 2009

Intracellular nuclear migration is essential for many cellular events including fertilization, establishment of polarity, division and differentiation. How nuclei migrate is not understood at the molecular level. The C. elegans KASH protein UNC-83 is required for nuclear migration and localizes to the outer nuclear membrane. UNC-83 interacts with the inner nuclear membrane SUN protein UNC-84 and is proposed to connect the cytoskeleton to the nuclear lamina. Here, we show that UNC-83 also interacts with the kinesin-1 light chain KLC-2, as identified in a yeast two-hybrid screen and confirmed by in vitro assays. UNC-83 interacts with and recruits KLC-2 to the nuclear envelope in a heterologous tissue culture system. Additionally, analysis of mutant phenotypes demonstrated that both KLC-2 and the kinesin-1 heavy chain UNC-116 are required for nuclear migration. Finally,the requirement for UNC-83 in nuclear migration could be partially bypassed by expressing a synthetic outer nuclear membrane KLC-2::KASH fusion protein. Our data support a model in which UNC-83 plays a central role in nuclear migration by acting to bridge the nuclear envelope and as a kinesin-1 cargo-specific adaptor so that motor-generated forces specifically move the nucleus as a single unit.
Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis
Authors: Driskell Ryan R. , Giangreco Adam , Jensen Kim B. , Mulder Klaas W. , Watt Fiona M.
Published: July 2009

The dermal papilla comprises the specialised mesenchymal cells at the base of the hair follicle. Communication between dermal papilla cells and the overlying epithelium is essential for differentiation of the hair follicle lineages. We report that Sox2 is expressed in all dermal papillae at E16.5,but from E18.5 onwards expression is confined to a subset of dermal papillae. In postnatal skin, Sox2 is only expressed in the dermal papillae of guard/awl/auchene follicles, whereas CD133 is expressed both in guard/awl/auchene and in zigzag dermal papillae. Using transgenic mice that express GFP under the control of the Sox2 promoter, we isolated Sox2+ (GFP+) CD133+ cells and compared them with Sox2- (GFP-) CD133+ dermal papilla cells. In addition to the `core' dermal papilla gene signature, each subpopulation expressed distinct sets of genes. GFP+CD133+ cells had upregulated Wnt, FGF and BMP pathways and expressed neural crest markers. In GFP- CD133+ cells,the hedgehog, IGF, Notch and integrin pathways were prominent. In skin reconstitution assays, hair follicles failed to form when dermis was depleted of both GFP+ CD133+ and GFP-CD133+ cells. In the absence of GFP+ CD133+cells, awl/auchene hairs failed to form and only zigzag hairs were found. We have thus demonstrated a previously unrecognised heterogeneity in dermal papilla cells and shown that Sox2-positive cells specify particular hair follicle types.
Distinct roles for sequences upstream of and downstream from Physarum editing sites
Authors: Rhee Amy C. , Somerlot Benjamin H. , Parimi Neeta , Gott Jonatha M.
Published: July 2009

RNAs in the mitochondria of Physarum polycephalum contain nonencoded nucleotides that are added during RNA synthesis. Essentially all steady-state RNAs are accurately and fully edited, yet the signals guiding these precise nucleotide insertions are presently unknown. To localize the regions of the template that are required for editing, we constructed a series of chimeric templates that substitute varying amounts of DNA either upstream of or downstream from C insertion sites. Remarkably, all sequences necessary for C addition are contained within ∼9 base pairs on either side of the insertion site. In addition, our data strongly suggest that sequences within this critical region affect different steps in the editing reaction. Template alterations upstream of an editing site influence nucleotide selection and/or insertion, while downstream changes affect editing site recognition and templated extension from the added, unpaired nucleotide. The data presented here provide the first evidence that individual regions of the DNA template play discrete mechanistic roles and represent a crucial initial step toward defining the source of the editing specificity in Physarum mitochondria. In addition, these findings have mechanistic implications regarding the potential involvement of the mitochondrial RNA polymerase in the editing reaction.
Structural tuning and self-association of (arylimido)vanadium(V) compounds
Authors: Moriuchi Toshiyuki , Hirao Toshikazu
Published: July 2009

Structural tuning and self-association of (arylimido)vanadium(V) compounds are demonstrated to be controlled through π-conjugation by the para-substituents of the aryl moieties.
[ONNO]-type amine bis(phenolate)-based vanadium catalysts for ethylene homo- and copolymerization
Authors: Lorber Christian
Published: July 2009

The synthesis and solution and solid-state structural characterization of a family of amine bis(phenolate) [ONNO]-vanadium complexes is reviewed. These compounds have oxidation states ranging from vanadium(II) to vanadium(V), and were evaluated as olefin polymerization catalysts. In association with EtAlCl2 cocatalyst, we studied the homopolymerization of ethylene, propene, and 1-hexene, as well as the copolymerization of ethylene with α-olefins (1-hexene, 1-octene) and cycloolefins (norbornene, cyclopentene). Some of these catalysts were shown to produce copolymers with a good activity and comonomer content.
NMR characterization and dynamics of vanadium(V) complexes with tripod (hydroquinonate/phenolate) iminodiacetate ligands in aqueous solution
Authors: Drouza Chryssoula , Stylianou Marios , Keramidas Anastasios D.
Published: July 2009

Reaction of NH4VO3 with (phenolate/hydroquinonate) iminodiacetate tripod ligands in aqueous solution in the pH range 7–8 results in the isolation of three new dioxido vanadium(V) complexes, one dinuclear (NH4)4{(VVO)2[μ-bicah(6-)-N,O,O,O]}·8H2O, (H6bicah, 2,5-bis[N,N'-bis(carboxymethyl)aminomethyl]-hydroquinone), and two mononuclear (NH4)2{(VVO)2[Hcah(3-)-N,O,O,O]·2H2O, (H4cah, 2-[N,N'-bis(carboxymethyl)aminomethyl]-hydroquinone) and (NH4)2{(VVO)[Hcacp(3-)-N,O,O,O]}·4H2O, (H4cacp, 2-[N,N'-bis(carboxymethyl)aminomethyl]-4-carboxyphenol). The 51V, 1H, and 13C NMR spectra in D2O show the coordination environment of vanadium in the above complexes to be octahedral, with four out of six positions to be occupied by the two carboxylate oxygen, one hydroquinonate oxygen, and one amine nitrogen atoms of the tripod ligand. The two acetate arms are in cis position to each other. Variable-temperature 1H and 13C NMR measurements show that the complexes are kinetically labile. An intramolecular exchange that proceeds through the opening of the phenolate/hydroquinonate chelate ring has been revealed by 2D{1H} NMR EXSY (exchange spectroscopy).
Electron transfer in non-oxovanadium(IV) and (V) complexes: Kinetic studies of an amavadin model
Authors: Lenhardt Jeremy M. , Baruah Bharat , Crans Debbie C. , Johnson Michael D.
Published: July 2009

Electron-transfer reactions of the eight-coordinate vanadium complex, bis-(N-hydroxyiminodiacetate)vanadium(IV) [V(HIDA)2]2–, a synthetic analog of amavadin with ascorbic acid and hexachloroiridate(IV), have been studied. The self-exchange rate constant for this analog has been calculated from oxidation and reduction cross-reactions using Marcus theory and directly measured using 51V NMR paramagnetic line-broadening techniques. The average self-exchange rate constant for the bis-HIDA vanadium(IV/V) couple equals 1.5 × 105 M–1 s–1. The observed rate enhancements are proposed to be due to the small structural differences between the oxidized and reduced forms of the HIDA complex and inner-sphere reorganizational energies. The electron-transfer reaction of this synthetic analog is experimentally indistinguishable from amavadin itself, although significant differences exist in the reduction potential of these compounds. This suggests that ligand modification effects the thermodynamic driving force and not the self-exchange process.
Synthesis of a bowl-type dodecavanadate by the coupling reaction of alkoxohexavanadate and discovery of a chiral octadecavanadate
Authors: Domae Kyosuke , Uchimura Daisuke , Koyama Yuuki , Inami Shinnosuke , Hayashi Yoshihito , Isobe Kiyoshi , Kameda Hiroyuki , Shimoda Tatsuya
Published: July 2009

A new route to an alkoxohexavanadate species leads to the isolation of a bowl-type dodecavanadate without a guest molecule in the cavity. The 1D tetravanadate, [V4O11]2-, is a good precursor for the alkoxohexavanadate, [V6O13(OCH3)6]2-, which is then utilized for the [V6 + V6] coupling reaction to form the dodecavanadate, [V12O42]4-, with a capped dichloromethane molecule at the cavity entrance. We also obtained structural information on a newly discovered octadecavanadate,  [V18O46(NO3)]5-,in both the solid and solution states through extended X-ray absorption fine structure (EXAFS) studies. The existence of a chiral inorganic species in acetonitrile with double-stranded V8 chains was confirmed through EXAFS oscillations.
From vanadium(V) to vanadium(IV) - and backwards
Authors: Rosenthal Esther C. E.
Published: July 2009

With bidentate alkoxy alkoxide and alkoxy alcohol ligands, respectively, a series of oxovanadium complexes in the oxidation state +4 is synthesized starting from oxovanadium(V) compounds. The reaction of two or more equivalents of 2-methoxyethanol with VOCl3 in n-hexane yields a mixture of the monomeric oxovanadium(IV) complex cis-[VOCl2(HOCH2CH2OMe-κ2O)(HOCH2CH2OMe-κO1)] and the alkoxide-bridged oxovanadium(IV) dimer syn-[VOCl(µ-OCH2CH2OMe-κ2O)]2, which are separated by fractionated crystallization. The same reaction with 2-ethoxy- and 2-iso-propoxyethanol gives only the alkoxide-bridged oxovanadium(IV) dimers anti-[VOCl(µ-OCH2CH2OR-κ2O)]2 (R = Et, iPr). All alkoxide bridged oxovanadium(IV) dimers are furthermore obtained as decomposition products of the chloride-bridged oxovanadium(V) complexes [VO(µ-Cl)Cl(OCH2CH2OR-κ2O)]2 (R = Me, Et, iPr) by Cl2 elimination and react inversely with Cl2 to the vanadium(V) compounds.
On the reactivity of bromoperoxidase I (Ascophyllum nodosum) in buffered organic media: Formation of carbon bromine bonds
Authors: Hartung Jens , Dumont Yvonne , Greb Marco , Hach Diana , Köhler Franz , Schulz Heiko , Časný Marian , Rehder Dieter , Vilter Hans
Published: July 2009

Peroxidase (PO) activity of vanadate(V)-dependent bromoperoxidase (BPO) I (Ascophyllum nodosum) [VBrPO(AnI)] was retained with a half-life time of ~60 days, if stored in H2O2-incubated, morpholin-4-ethane sulfonic acid (MES)-buffered aqueous alcoholic solutions. These conditions were applied for converting bromide and, e.g., methyl pyrrole-2-carboxylate into bromopyrroles with an almost quantitative peroxide yield. δ,ε-unsaturated alcohols furnished β-bromohydrins and products of bromocyclization, i.e., tetrahydrofurans and tetrahydropyrans (70–84 % mass balance), if treated with H2O2, KBr, and VBrPO(AnI) in phosphate-buffered, CH3CN-diluted media.
Influence of polydentate ligands in the structure of dinuclear vanadium compounds
Authors: Avecilla Fernando , Adão Pedro , Correia Isabel , Costa Pessoa João
Published: July 2009

A review discussing general structural features of oxygen-bridged dinuclear vanadium(IV and/or V) complexes is presented, covering those that have been characterized by single-crystal X-ray diffraction. Many of these compounds contain functional Schiff bases or amines as ligands, this work illustrating the high propensity of the V center to increase its coordination number via dimerization of two tetra- or penta-coordinate monomers, if the steric and electronic control exerted by the ligands allows it. We also report the synthesis and characterization by single-crystal X-ray diffraction of two new dinuclear complexes: [{VVO[sal(R,R-chen)]}2(μ2-O)2] and [{VVO[mvan(S,S-chen)]}2(μ2-O)2]. The complexes contain tridentate ligands with O-phenolate, N-imine, and N-amine coordination to the VV center. The molecular structures of these compounds demonstrate that they form dinuclear species in the solid state with a {OVV(μ2-O)2VVO} core.
Vanadium-catalyzed, microwave-assisted oxidations with H2O2 in ionic liquids
Authors: Conte Valeria , Fabbianesi Francesca , Floris Barbara , Galloni Pierluca , Sordi Daniela , Arends Isabel W. C. E. , Bonchio Marcella , Rehder Dieter , Bogdal Dariusz
Published: July 2009

The application of vanadium(V) catalysts in selective oxidation with peroxides offers an efficient procedure that is compatible with different functional groups and leads to good yields and selectivities. However, the search for more efficient and sustainable procedures that employ H2O2 as oxidant remains an important topic. In the last few years, striking results have been obtained by applying microwave (MW) activation in metal-catalyzed reactions carried out in ionic liquids (ILs). In the present study, results achieved with vanadium-based catalysts in oxidations of various substrates with H2O2 are presented; in particular, epoxidation of alkenes and sulfoxidation of thioethers have been investigated. Notably, in the latter oxidation, a significant improvement in the rate of reaction and an increase in selectivity have been observed in the case of hydrophobic ILs in combination with MW activation.
Vanadium haloperoxidases as supramolecular hosts: Synthetic and computational models
Authors: Plass Winfried
Published: July 2009

In the active-site cavity of vanadium haloperoxidases vanadate as the prosthetic group is solely fixed by one covalent bond to a histidine residue and embedded in a supramolecular environment of extensive hydrogen bonds. Structural aspects of relevant vanadium complexes with supramolecular interactions, including assemblies with chiral hosts, are presented. The importance of hydrogen-bonding relays is presented together with relevant examples. The reactivity of related functional mimics containing vanadium and molybdenum toward the oxidation of thioethers is described. Computational modeling based on density functional theory (DFT) is used for the investigation of model systems. The resulting implications for structure and function of vanadium haloperoxidases, including their substrate and cofactor specificity, are discussed.
Cardiac Valvular and Vascular Disease in Bull Terriers
Authors: O'Leary C. A. , Wilkie I.
Published: July 2009

The hearts of 27 Bull Terriers and 6 control dogs were evaluated. Heart murmurs were auscultated in 14 (52%) Bull Terriers. At necropsy, 25 Bull Terriers (93%) had myxomatous degeneration of the mitral valve or abnormalities of the left ventricular outflow tract. Small vessel arteriosclerosis in the myocardium and fibrosis of cardiac conduction tissue were common histologic findings in Bull Terriers with clinical cardiac disease. These lesions were also detected in dogs without clinical evidence of cardiac disease and only mild murmurs or structural valvular disease.