Peptidyl prolyl cis-trans isomerase activity of cyclophilin A in functional homo-oligomeric receptor expression

The functional expression of homo-oligomeric α7 neuronal nicotinic and type 3 serotonin receptors is dependent on the activity of a cyclophilin. In this paper we demonstrate that the mechanism of cyclophilin action during functional homo-oligomeric receptor expression in Xenopus oocytes is distinct from the calcineurin-dependent immunosuppressive mechanism by showing that a nonimmunosuppressive analog of cyclosporin A (CsA), SDZ 211–811, reduces functional receptor expression to the same extent as CsA. The cytoplasmic subtype of cyclophilin, cyclophilin A (CyPA), appears to be required for functional receptor expression. This is because overexpression of CyPA and a CyPA mutant that is deficient in CsA binding activity reverses CsA-induced reduction in functional receptor expression. The mechanism of action of CyPA is likely to involve its prolyl isomerase activity because a mutant CyPA with a single amino acid substitution (arginine 55 to alanine) that is predicted to produce a 1000-fold attenuation in isomerase activity fails to reverse the cyclosporin A effect. Our data also suggest that CyPA does not form a stable complex with receptor subunits.

Vps41p Function in the Alkaline Phosphatase Pathway Requires Homo-oligomerization and Interaction with AP-3 through Two Distinct Domains

Transport of proteins through the ALP (alkaline phosphatase) pathway to the vacuole requires the function of the AP-3 adaptor complex and Vps41p. However, unlike other adaptor protein–dependent pathways, the ALP pathway has not been shown to require additional accessory proteins or coat proteins, such as membrane recruitment factors or clathrin. Two independent genetic approaches have been used to identify new mutants that affect transport through the ALP pathway. These screens yielded new mutants in both VPS41 and the four AP-3 subunit genes. Two new VPS41 alleles exhibited phenotypes distinct from null mutants of VPS41, which are defective in vacuolar morphology and protein transport through both the ALP and CPY sorting pathways. The new alleles displayed severe ALP sorting defects, normal vacuolar morphology, and defects in ALP vesicle formation at the Golgi complex. Sequencing analysis of these VPS41 alleles revealed mutations encoding amino acid changes in two distinct domains of Vps41p: a conserved N-terminal domain and a C-terminal clathrin heavy-chain repeat (CHCR) domain. We demonstrate that the N-terminus of Vps41p is required for binding to AP-3, whereas the C-terminal CHCR domain directs homo-oligomerization of Vps41p. These data indicate that a homo-oligomeric form of Vps41p is required for the formation of ALP containing vesicles at the Golgi complex via interactions with AP-3.

Significance of some previously unrecognized apomorphies in the nasal region of Homo neanderthalensis.

For many years, the Neanderthals have been recognized as a distinctive extinct hominid group that occupied Europe and western Asia between about 200,000 and 30,000 years ago. It is still debated, however, whether these hominids belong in their own species, Homo neanderthalensis, or represent an extinct variant of Homo sapiens. Our ongoing studies indicate that the Neanderthals differ from modern humans in their skeletal anatomy in more ways than have been recognized up to now. The purpose of this contribution is to describe specializations of the Neanderthal internal nasal region that make them unique not only among hominids but possibly among terrestrial mammals in general as well. These features lend additional weight to the suggestion that Neanderthals are specifically distinct from Homo sapiens.

Dated co-occurrence of Homo erectus and Gigantopithecus from Tham Khuyen Cave, Vietnam.

Tham Khuyen Cave (Lang Son Province, northern Vietnam) is one of the more significant sites to yield fossil vertebrates in east Asia. During the mid-1960s, excavation in a suite of deposits produced important hominoid dental remains of middle Pleistocene age. We undertake more rigorous analyses of these sediments to understand the fluvial dynamics of Pleistocene cave infilling as they determine how skeletal elements accumulate within Tham Khuyen and other east Asian sites. Uranium/thorium series analysis of speleothems brackets the Pleistocene chronology for breaching, infilling, and exhuming the regional paleokarst. Clast analysis indicates sedimentary constituents, including hominoid teeth and cranial fragments accumulated from very short distances and under low fluvial energy. Electron spin resonance analysis of vertebrate tooth enamel and sediments shows that the main fossil-bearing suite (S1-S3) was deposited about 475 thousand years ago. Among the hominoid teeth excavated from S1-S3, some represent Homo erectus and Gigantopithecus blacki. Criteria are defined to differentiate these teeth from more numerous Pongo pygmaeus elements. The dated co-occurrence of Homo erectus and Gigantopithecus blacki at Tham Khuyen helps to establish the long co-existence of these two species throughout east Asia during the Early and Middle Pleistocene.

Double-stranded-RNA-dependent protein kinase and TAR RNA-binding protein form homo- and heterodimers in vivo.

The yeast two-hybrid system and far-Western protein blot analysis were used to demonstrate dimerization of human double-stranded RNA (dsRNA)-dependent protein kinase (PKR) in vivo and in vitro. A catalytically inactive mutant of PKR with a single amino acid substitution (K296R) was found to dimerize in vivo, and a mutant with a deletion of the catalytic domain of PKR retained the ability to dimerize. In contrast, deletion of the two dsRNA-binding motifs in the N-terminal regulatory domain of PKR abolished dimerization. In vitro dimerization of the dsRNA-binding domain required the presence of dsRNA. These results suggest that the binding of dsRNA by PKR is necessary for dimerization. The mammalian dsRNA-binding protein TRBP, originally identified on the basis of its ability to bind the transactivation region (TAR) of human immunodeficiency virus RNA, also dimerized with itself and with PKR in the yeast assay. Taken together, these results suggest that complexes consisting of different combinations of dsRNA-binding proteins may exist in vivo. Such complexes could mediate differential effects on gene expression and control of cell growth.

A presença do homo academicus na contabilidade: um olhar bourdieusiano sobre o contexto social do desenvolvimento da produção científica contábil brasileira

Esta pesquisa investiga o contexto social do desenvolvimento da produção científica contábil brasileira, defendendo a tese de que os agentes, no decorrer do processo de divulgação de suas investigações, estão priorizando aspectos produtivistas e quantitativos e, consequentemente, deixando em segundo plano a preocupação qualitativa e epistemológica [vigilância crítica] de tal produção. Fundamentado na Teoria de Campos de Pierre Bourdieu, este estudo busca relacionar a socialização acadêmica, o habitus dos agentes imbricados no campo, a distribuição do capital científico na área contábil e as características epistemológicas das publicações científicas da área, para obtenção das evidências sobre a problemática levantada. Trata-se de um levantamento operacionalizado por meio de entrevista semiestruturada, com uma amostra de 9 respondentes e estudo documental, com uma amostra de 43 artigos. Os dados foram analisados com emprego da técnica de análise de conteúdo. Apoiando-se em Bourdieu (2004, 2008, 2009, 2011, 2013) foram encontradas evidências de que as teorias, conceitos, metodologias, técnicas e demais escolhas realizadas pelos pesquisadores da área contábil, na maioria das vezes, não passam de manobras estratégicas que visam conquistar, reforçar, assegurar ou derrubar o monopólio da autoridade científica, visando a obtenção de maior poder simbólico no campo. Com relação ao habitus dos agentes pertencentes ao campo científico contábil, constatou-se uma tendência ao produtivismo em consequência das determinações dos órgãos reguladores da pesquisa em contabilidade (CAPES) e das lutas simbólicas travadas no campo para obtenção da autoridade científica. No tocante à socialização acadêmica, reforçou-se a presença de condutas produtivistas, por meio dos programas de pós-graduação stricto sensu, que repassam aos agentes as regras do jogo científico, doutrinando-os na maneira de publicar grande quantidade de comunicações em pouco tempo e com menos custos. As análises epistemológicas puderam triangular os dois últimos constructos, a fim de lhes dar validade, e evidenciaram uma preferência por temáticas que envolvem a contabilidade destinada aos usuários externos e procedimentos contábeis destinados ao mercado financeiro, privilegiando a utilização de dados secundários, por meio de pesquisas documentais. Em termos metodológicos, constatou-se a presença unânime de estudos positivistas, com alguns aspectos empiristas, mostrando uma ausência de inovação em termos de pesquisas norteadas por abordagens metodológicas alternativas e utilização de modelos econométricos para explicar a realidade observada sem teoria para embasar e explicar esses modelos. Por fim, a distribuição do capital simbólico no campo, mostrou que individualmente nenhum agente desponta com maior capital científico, mas, institucionalmente, a FEA/USP ocupa essa posição de destaque. Por conseguinte, pôde-se concluir que o campo científico contábil permanece estagnado e sem grandes modificações teóricas, pelo fato do produtivismo e das lutas simbólicas no interior do campo; fatos esses que, de certa maneira, motivaram a criação de uma espécie de \"receita mágica para publicar\" ou \"formato ideal\" legitimado, institucionalizado e difícil de ser modificado, a não ser que ocorra uma revolução científica que mude o paradigma existente

Homo Jihadicus. Islam in the former USSR and the phenomenon of the post-Soviet militants in Syria and Iraq. OSW REPORT 2015-09-21

The post-Soviet area, along with the countries of the Middle East, North Africa and Western Europe, have become one of the main global exporters of Islamic militants. Currently on the territory of Syria, and to a lesser extent of Iraq, there are several thousands of foreign fighters from the post-Soviet states. The causes of the war migration from the former USSR states to the Middle East have their roots in the dynamic changes taking place inside Islam in the post-Soviet area: primarily the growth of Salafism and militant Islam, as well as the internationalisation and globalisation of the local Islam. The deep political, economic, social and ideological changes which Muslims underwent after the collapse of the USSR, led to the creation of a specific group within them, for which Islam in its radical form became the main element of their identity. Homo sovieticus, without fully eradicating his Soviet part, became Homo jihadicus who not only identifies himself with the global Ummah, but is also ready to leave his country and join jihad beyond its borders in the name of the professed ideas.

Chiral, Three-Dimensional Supramolecular Compounds: Homo- and Bimetallic Oxalate- and 1,2-Dithiooxalate-Bridged Networks. A Structural and Photophysical Study.

In analogy to the [M(II)(bpy)(3)](2+) cations, where M(II) is a divalent transition-metal and bpy is 2,2'-bipyridine, the tris-chelated [M(III)(bpy)(3)](3+) cations, where M(III) is Cr(III) or Co(III), induce the crystallization of chiral, anionic three-dimensional (3D) coordination polymers of oxalate-bridged (&mgr;-ox) metal complexes with stoichiometries [M(II)(2)(ox)(3)](n)()(2)(n)()(-) or [M(I)M(III)(ox)(3)](n)()(2)(n)()(-). The tripositive charge is partially compensated by inclusion of additional complex anions like ClO(4)(-), BF(4)(-), or PF(6)(-) which are encapsulated in cubic shaped cavities formed by the bipyridine ligands of the cations. Thus, an elaborate structure of cationic and anionic species within a polymeric anionic network is realized. The compounds isolated and structurally characterized include [Cr(III)(bpy)(3)][ClO(4)] [NaCr(III)(ox)(3)] (1), [Cr(III)(bpy)(3)][ClO(4)][Mn(II)(2)(ox)(3)] (2), [Cr(III)(bpy)(3)][BF(4)] [Mn(II)(2)(ox)(3)] (3), [Co(III)(bpy)(3)][PF(6)][NaCr(III)(ox)(3)] (4). Crystal data: 1, cubic, P2(1)3, a = 15.523(4) Å, Z = 4; 2, cubic, P4(1)32, a = 15.564(3) Å, Z = 4; 3, cubic, P4(1)32, a = 15.553(3) Å, Z = 4; 4, cubic, P2(1)3, a = 15.515(3) Å, Z = 4. Furthermore, it seemed likely that 1,2-dithiooxalate (dto) could act as an alternative to the oxalate bridging ligand, and as a result the compound [Ni(II)(phen)(3)][NaCo(III)(dto)(3)].C(3)H(6)O (5) has successfully been isolated and structurally characterized. Crystal data: 5, orthorhombic, P2(1)2(1)2(1), a = 16.238(4) Å, b = 16.225(4) Å, c = 18.371(5) Å, Z = 4. In addition, the photophysical properties of compound 1 have been investigated in detail. In single crystal absorption spectra of [Cr(III)(bpy)(3)][ClO(4)][NaCr(III)(ox)(3)] (1), the spin-flip transitions of both the [Cr(bpy)(3)](3+) and the [Cr(ox)(3)](3)(-) chromophores are observed and can be clearly distinguished. Irradiating into the spin-allowed (4)A(2) --> (4)T(2) absorption band of [Cr(ox)(3)](3)(-) results in intense luminescence from the (2)E state of [Cr(bpy)(3)](3+) as a result of rapid energy transfer processes.

Theologia naturalis siue liber creatura[rum] specialiter de homine [et] de natura eius in qua[n]tum homo ...

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Homo christianus in sua lege institutus siue Discursus morales quibus totum hominis christiani officium explicatur ... /

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De machina et anima humana prorsus a se inuicem distinctis commentatio, libello latere amantis auctoris Gallico Homo machina inscripto opposita et ad illustrissimum virum Albertum Haller ... /

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Quotidiana christiani militis tessera : qua homo fugiens mala è servitute manu mittitur, faciens bona ad libertatem manu ducitur /

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