A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis

Multiple sclerosis (MS) is a chronic relapsing-remitting inflammatory disease of the central nervous system characterized by oligodendrocyte damage, demyelination and neuronal death. Genetic association studies have shown a 2-fold or greater prevalence of the HLA-DRB1*1501 allele in the MS population compared with normal Caucasians. In discovery cohorts of Australasian patients with MS (total 2941 patients and 3008 controls), we examined the associations of 12 functional polymorphisms of P2X7, a microglial/macrophage receptor with proinflammatory effects when activated by extracellular adenosine triphosphate (ATP). In discovery cohorts, rs28360457, coding for Arg307Gln was associated with MS and combined analysis showed a 2-fold lower minor allele frequency compared with controls (1.11% for MS and 2.15% for controls, P = 0.0000071). Replication analysis of four independent European MS case–control cohorts (total 2140 cases and 2634 controls) confirmed this association [odds ratio (OR) = 0.69, P = 0.026]. A meta-analysis of all Australasian and European cohorts indicated that Arg307Gln confers a 1.8-fold protective effect on MS risk (OR = 0.57, P = 0.0000024). Fresh human monocytes heterozygous for Arg307Gln have >85% loss of ‘pore’ function of the P2X7 receptor measured by ATP-induced ethidium uptake. Analysis shows Arg307Gln always occurred with 270His suggesting a single 307Gln–270His haplotype that confers dominant negative effects on P2X7 function and protection against MS. Modeling based on the homologous zP2X4 receptor showed Arg307 is located in a region rich in basic residues located only 12 Å from the ligand binding site. Our data show the protective effect against MS of a rare genetic variant of P2RX7 with heterozygotes showing near absent proinflammatory ‘pore’ function.

Ukrainan vuosien 1932-33 nälänhädän historiapolitiikka

Ukrainan presidentiksi nousi ns. oranssin vallankumouksen nosteessa Viktor Justsenko. Hänen presidenttikaudellaan (2005-2010) vuosien 1932-33 nälänhätä (holodomor) nousi keskeiseksi sekä sisä-, että ulkopolitiikan teemaksi. Holodomor, joka viittaa nälällä aiheutettuun tuhoon, pyrittiin tuomaan osaksi ukrainalaista kollektiivista muistia. Justsenkon aloitteesta säädettiin laki, jonka mukaan holodomor oli ukrainalaisten kansanmurha. Vuosina 1932-33 ympäri Neuvostoliittoa vallitsi nälänhätä. Ukrainalainen maaseutu kärsi pahoin nälänhädän seurauksista, sillä eri arvioiden mukaan 3,5-10 miljoonaa ukrainalaista menehtyi joko suoranaisesti tai välillisesti nälänhädän seurauksena. Ukrainan itsenäistyttyä nälänhätä, jota oli diasporassa alettu kutsua holodomoriksi (nälkätuho), nousi kansallisen historian keskeiseksi teemaksi. Ukrainalainen historioitsija Georgi Kasjanov on nimittänyt tätä uutta vaihetta historian kansallistamiseksi. Tässä työssä pohditaan sitä, miksi holodomor nostettiin keskeiseen asemaan presidentti Viktor Justsenkon valtakaudella. Keskeinen vastakkainasettelun lähtökohta on ollut itsenäisen Ukrainan ja Neuvostoliiton seuraajavaltion Venäjän suhtautuminen nälänhätään 1932-33. Ukrainalaisissa näkökulmissa on painottunut stalinistisen järjestelmän kritiikki, mikä toisaalta on saatettu tulkita myös koko kommunistisen aikakauden tuomitsemiseksi. Venäjällä taas nälänhätä on tulkittu useimmiten yleisneuvostoliittolaiseksi tragediaksi, joka ei kohdistunut erityisesti mitään tiettyä kansallisuutta vastaan. Tutkimuksen keskeinen lähtökohta on tarkastella ukrainalaisten ja venäläisten tulkintojen eroja ja sitä, millä tavoin holodomorilla on tehty politiikkaa. Tutkimusaineistona on käytetty ukrainalaisten osalta presidentti Justsenkon puheita, lakialoitteita ja muita julkilausumia, sekä eräiden yhteiskunnallisten toimijoiden ja historioitsijoiden kannanottoja. Venäläisen osapuolen tulkintoja on pyritty luomaan muutamien tutkimusten ja yhteiskunnallisten toimijoiden, sekä poliitikkojen lausumien pohjalta. Suurin osa aineistosta on kerätty venäjänkielisistä verkkolehdistä. Presidentti Justsenkolle vuosien 1932-1933 historiasta muodostui ase, jolla hän kävi omaa poliittista taisteluaan lännen puolesta itää vastaan. Välit Venäjään olivat viileät koko hänen presidenttikautensa ajan. Lähimmäksi presidentin kantaa holodomor-kysymyksessä tulivat diasporaukrainalaiset. Venäjällä kritisoitiin ankarasti Justsenkon tanssia haudoilla eli hänen tapaansa käyttää nälänhädän uhreja oman politiikkansa välineenä. Venäläiset korostivat nälänhädän tragediaa kaikkien Neuvostoliiton kansojen tragediana. Holodomor oli osa kansallisen historian uudelleenkirjoitusta ja kansakunnan rakentamisen prosessia. Justsenkon päämääränä oli lähentää Ukrainaa länteen, jolloin ukrainalaisen kansakunnan uhriasema antoi oikeutuksen sanoutua irti neuvostoajasta. Tietyssä mielessä holodomor-projekti oli venäläisvastainen, sillä se implisiittisesti tuki käsitystä venäläisistä rikollisina, kansanmurhan toimeenpanijoina.

Kansan raittiudeksi ja kotien onneksi : Naisten kieltolakimielipiteet ja toiminta kieltolain puolesta ja sitä vastaan 1919 - 1932

It is often maintained that the Prohibition Act (in force from 1 June 1919 to 5 April 1932) still influences both the Finnish alcohol policy and notions about alcohol. This study focuses on the development of women s opinions concerning Prohibition in Finland. What role did the formulation and expression of women s opinions and women's actions play in the final outcome of the Prohibition Act? What do the debate on Prohibition and women s activities for and against the legislation tell us about the status and possibilities of women to exert influence in the Finnish society of the Prohibition era? Women s opinions are particularly interesting since they deviated radically from what has generally been assumed. It was expected that the referendum of 1931 would result in a resounding vote of 100% in favour of Prohibition, but the outcome was a majority vote against it. Over 65% of the women who cast their vote in the referendum wanted a full repeal of Prohibition. The study approaches the history of Prohibition by combining methods and theories of the history of mentalities and social history with gender history. Women are examined as a heterogeneous group with dissimilar objectives and differing ways of acting and thinking. The research material consists of press materials, archival materials from organisations, personal materials and statistics from the Prohibition period. Both discourses and practices are examined; the object of the research is best described by Michel Foucault's concept of dispositif. When participating in the public debate on Prohibition, women based their right to express their opinions and take part in action on an ideological continuum spanning a hundred years, according to which home and family were central areas of women s interest. This idea was linked to questions of morality and social policy. On the other hand, women presented themselves as working taxpayers, voters and equal citizens. The most crucial issue in women's discussions was whether Prohibition improved or worsened the temperance of fathers, husbands and sons. The dichotomies town dweller - countryside dweller, Swedish-speaking Finnish-speaking, and middle class - working class were highly significant backgrounds both as factors dividing women and in public discussions regarding Prohibition. The 1931 referendum showed that the lines of demarcation drawn during the preceding debate did not materialise in political action in line with these dichotomies: the dispositif did not correspond to the discourse. Contrary to what was expressed in public, a great number of women among the labour and rural classes, among inland inhabitants and among Finnish-speakers were also against Prohibition. The media and organisations defended temperance and Prohibition almost until the end of the Prohibition era. This discourse was in conflict with the discourse of everyday conversations and practices in which alcohol was present.

Characterization of Birkhoff-James orthogonality

The Birkhoff-James orthogonality is a generalization of Hilbert space orthogonality to Banach spaces. We investigate this notion of orthogonality when the Banach space has more structures. We start by doing so for the Banach space of square matrices moving gradually to all bounded operators on any Hilbert space, then to an arbitrary C*-algebra and finally a Hilbert C*-module.

The first teresomatan caecilian (Amphibia: Gymnophiona) from the Eastern Ghats of India-a new species of Gegeneophis Peters, 1880

A new species of caecilian amphibian, Gegeneophis orientalis sp. nov., is described based on a series of nine specimens from high elevation (ca. 1,200 m) habitats in the Eastern Ghats in the states of Andhra Pradesh and Odisha, India. This species differs from all other congeners in having only bicuspid teeth in the outer as well as inner rows. The new species is the first caecilian reported from the state of Odisha, the first teresomatan caecilian from the Eastern Ghats, and is the only Indian indotyphlid known from outside the Western Ghats region.

Libertad y democracia en el discurso de Monseñor de Andrea : (1932-1946)

Resumen: Los conceptos de “libertad” y “democracia” que se presentan en los discursos de Monseñor Miguel de Andrea durante los años 1932 y 1946 fueron fundamentales para elaborar una estrategia comunicacional orientada a combatir el comunismo y defender los valores republicanos. Se parte de la premisa de que el discurso es una herramienta primordial para difundir ideas y pensamientos, formar opinión y movilizar a la acción. El carácter excepcional de Miguel de Andrea en el mundo eclesiástico e intelectual de su tiempo lo convierten en una figura clave en la defensa de la Constitución y la democracia del período de entreguerras.

Entre gauchos y gringos. Costumbres nacionales y extranjeras en Santa Fe (1880-1900)

La política de fomento inmigratorio impulsada en la Argentina a partir de mediados del siglo XIX incluyó, entre sus objetivos, el de generar un cambio de costumbres en la población nativa. En este artículo, además de describirse la realidad resultante como consecuencia de la incorporación de pautas culturales foráneas, se analizan –desde un recorte espacial santafesino centrado en las dos últimas décadas del siglo XIX– comportamientos puestos de manifiesto por las élites políticas e intelectuales de la provincia con respecto a las costumbres nacionales y extranjeras. Lo que se busca es evaluar si dichos comportamientos pudieron encontrarse condicionados por las diferentes adscripciones político-ideológicas y/o por las variantes circunstancias históricas.

A difícil inserção : voto feminino e as condições sociais de acesso ao campo político no Brasil (1932-2012)

Consultoria Legislativa - Área XIX - Ciência Política, Sociologia Política e História.

Collecção das Leis do Imperio do Brazil de 1880

Parte 1 - Atos do Poder Legislativo

Coleção das Leis da Republica dos Estados Unidos do Brasil de 1932

Atos do Governo Provisório

Automated, objective texture segmentation of multibeam echosounder data - Seafloor survey and substrate maps from James Island to Ozette Lake, Washington Outer Coast

Without knowledge of basic seafloor characteristics, the ability to address any number of critical marine and/or coastal management issues is diminished. For example, management and conservation of essential fish habitat (EFH), a requirement mandated by federally guided fishery management plans (FMPs), requires among other things a description of habitats for federally managed species. Although the list of attributes important to habitat are numerous, the ability to efficiently and effectively describe many, and especially at the scales required, does not exist with the tools currently available. However, several characteristics of seafloor morphology are readily obtainable at multiple scales and can serve as useful descriptors of habitat. Recent advancements in acoustic technology, such as multibeam echosounding (MBES), can provide remote indication of surficial sediment properties such as texture, hardness, or roughness, and further permit highly detailed renderings of seafloor morphology. With acoustic-based surveys providing a relatively efficient method for data acquisition, there exists a need for efficient and reproducible automated segmentation routines to process the data. Using MBES data collected by the Olympic Coast National Marine Sanctuary (OCNMS), and through a contracted seafloor survey, we expanded on the techniques of Cutter et al. (2003) to describe an objective repeatable process that uses parameterized local Fourier histogram (LFH) texture features to automate segmentation of surficial sediments from acoustic imagery using a maximum likelihood decision rule. Sonar signatures and classification performance were evaluated using video imagery obtained from a towed camera sled. Segmented raster images were converted to polygon features and attributed using a hierarchical deep-water marine benthic classification scheme (Greene et al. 1999) for use in a geographical information system (GIS). (PDF contains 41 pages.)

Let sleeping doggerel lie?: James Joyce's "The Death of Parnell" and the challenges of addressing 'bad' verse in translation

Eterio Pajares, Raquel Merino y José Miguel Santamaría (eds.)

Development of kelp rockfish, Sebastes atrovirens (Jordan and Gilbert 1880), and brown rockfish, S. auriculatus (Girard 1854), from birth to pelagic juvenile stage, with notes on early larval development of black-and-yellow rockfish, S. chrysomelas (Jordan and Gilbert 1880), reared in the laboratory (Pisces: Sebastidae).

Larval kelp (Sebastes atrovirens), brown (S. auriculatus), and blackand-yellow (S. chrysomelas) rockfish were reared from known adults, to preflexion stage, nine days after birth for S. chrysomelas, to late postflexion stage for S. atrovirens, and to pelagic juvenile stage for S. auriculatus. Larval S. atrovirens and S. chrysomelas were about 4.6 mm body length (BL) and S. auriculatus about 5.2 mm BL at birth. Both S. atrovirens and S. auriculatus underwent notochord flexion at about 6–9 mm BL. Sebastes atrovirens transform to the pelagic juvenile stage at about 14–16 mm BL and S. auriculatus transformed at ca. 25 mm BL. Early larvae of all three species were characterized by melanistic pigment dorsally on the head, on the gut, on most of the ventral margin of the tail, and in a long series on the dorsal margin of the tail. Larval S. atrovirens and S. auriculatus developed a posterior bar on the tail during the flexion or postflexion stage. In S. atrovirens xanthic pigment resembled the melanistic pattern throughout larval development. Larval S. auriculatus lacked xanthophores except on the head until late preflexion stage, when a pattern much like the melanophore pattern gradually developed. Larval S. chrysomelas had extensive xanthic pigmentation dorsally, but none ventrally, in preflexion stage. All members of the Sebastes subgenus Pteropodus (S. atrovirens, S. auriculatus, S. carnatus, S. caurinus, S. chrysomelas, S. dalli, S. maliger, S. nebulosus, S. rastrelliger) are morphologically similar and all share the basic melanistic pigment pattern described here. Although the three species reared in this study can be distinguished on the basis of xanthic pigmentation, it seems unlikely that it will be possible to reliably identify field-collected larvae to species using traditional morphological and melanistic pigmentation characters. (PDF file contains 36 pages.)

Scientific fisheries work in Maryland

Presentation to elected officials [and American Fisheries Society] on the wealth of research to be done in the Chesapeake Bay. Citing drop in oyster production from a high of 17,000,000 bushels in 1885 to 2,000,000 bushels in 1925 or one-eighth of its one-time abundance. Citing water studies through the late 1880's-90's. Report of experiments with the Japanese Oyster O. gigas. Also addresses Crab, Callinectes sapidus and classes held. (PDF contains 7 pages)