42 research outputs found

    Maturation-Induced Cloaking of Neutralization Epitopes on HIV-1 Particles

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    To become infectious, HIV-1 particles undergo a maturation process involving proteolytic cleavage of the Gag and Gag-Pol polyproteins. Immature particles contain a highly stable spherical Gag lattice and are impaired for fusion with target cells. The fusion impairment is relieved by truncation of the gp41 cytoplasmic tail (CT), indicating that an interaction between the immature viral core and gp41 within the particle represses HIV-1 fusion by an unknown mechanism. We hypothesized that the conformation of Env on the viral surface is regulated allosterically by interactions with the HIV-1 core during particle maturation. To test this, we quantified the binding of a panel of monoclonal antibodies to mature and immature HIV-1 particles by immunofluorescence imaging. Surprisingly, immature particles exhibited markedly enhanced binding of several gp41-specific antibodies, including two that recognize the membrane proximal external region (MPER) and neutralize diverse HIV-1 strains. Several of the differences in epitope exposure on mature and immature particles were abolished by truncation of the gp41 CT, thus linking the immature HIV-1 fusion defect with altered Env conformation. Our results suggest that perturbation of fusion-dependent Env conformational changes contributes to the impaired fusion of immature particles. Masking of neutralization-sensitive epitopes during particle maturation may contribute to HIV-1 immune evasion and has practical implications for vaccine strategies targeting the gp41 MPER

    Alternatives and responsibility: an asymmetrical approach

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    En este trabajo defiendo una visiĂłn asimĂ©trica sobre la relaciĂłn entre las posibilidades alternativas y la responsabilidad moral, segĂșn la cual se requiere tener posibilidades alternativas para ser culpable por lo que uno decide o hace, pero no para ser laudable por ello. Defiendo la no necesidad de alternativas para ser laudable a travĂ©s de un examen de lo que yo llamo “ejemplos Lutero”. Mi defensa de la necesidad de alternativas para ser culpable procede en cambio mediante un anĂĄlisis de los llamados “casos Frankfurt”. En ambos casos, mis argumentos se basan en la afirmaciĂłn segĂșn la cual, en las adscripciones de responsabilidad moral, la cuestiĂłn principal no es si el agente podrĂ­a haber hecho algo distinto, sino si deberĂ­a haber hecho lo que hizo, de modo que la primera pregunta solo se vuelve apremiante cuando la respuesta a la segunda es negativa. AsĂ­, pues, en lo que se refiere a la responsabilidad moral, el concepto de obligaciĂłn o deber moral es previo al de posibilidades alternativas.In this paper, I defend an asymmetrical view concerning the relationship between alternative possibilities and moral responsibility, according to which alternative possibilities are required for being blameworthy, but not praiseworthy, for what one decides or does. I defend the non-necessity of alternatives for praiseworthiness through an examination of what I call ‘Luther’ examples. My defence of the necessity of alternatives for blameworthiness proceeds instead through an analysis of so-called ‘Frankfurt’ examples. In both cases, my arguments rest on the contention that, in ascriptions of moral responsibility, the primary question is not whether the agent could have done otherwise, but whether she should have done what she did, so that the former question only becomes pressing when the answer to the latter is negative. Concerning moral responsibility, then, the concept of moral obligation or duty is prior to that of alternative possibilities

    “We ought to eat in order to work, not vice versa”: MacIntyre, practices, and the best work for humankind.

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    This paper draws a distinction between ‘right MacIntyreans’ who are relatively optimistic that MacIntyre’s vision of ethics can be realised in capitalist society, and ‘left MacIntyreans’ who are sceptical about this possibility, and aims to show that the ‘left MacIntyrean’ position is a promising perspective available to business ethicists. It does so by arguing for a distinction between ‘community-focused’ practices and ‘excellence-focused’ practices. The latter concept fulfils the promise of practices to provide us with an understanding of the best work for humankind and highlights the affinities between MacIntyre’s concept of a practice and Marx’s conception of good work as free, creative activity. The paper concludes with a suggestion that we reflect on the best forms of work so that we can strive to ensure the very best activities, those most consonant with our flourishing, one day become available to all

    Moral education at work: on the scope of MacIntyre’s concept of a practice

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    This paper seeks to show how MacIntyre’s concept of a practice can survive a series of ‘scope problems’ which threaten to render the concept inapplicable to business ethics. I begin by outlining MacIntyre’s concept of a practice before arguing that, despite an asymmetry between productive and non-productive practices, the elasticity of the concept of a practice allows us to accommodate productive and profitable activities. This elasticity of practices allows us to sidestep the problem of adjudicating between practitioners and non-practitioners as well as the problem of generic activities. I conclude by suggesting that the contemporary tendency to regard work as an object of consumption, rather than undermining MacIntyre’s account of practices, serves to demonstrate the potential breadth of its applicability

    Puhtaan suomenlampaan menestyminen EtelÀ-Afrikassa

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    Reproduction, survival, growth and wool parameters were calculated for an experimental flock of Finnsheep from 1969 until 1986 under semi-intensive conditions. The total number of lambs bom were 1774. Litter size, survival rate at birth and from birth to weaning differed significantly (PLammastalouden taloudellista ja biologista tehoa parannettaessa on kiinnitetty huomio lisÀÀntymiskykyyn ja sikiÀviin rotuihin. SikiÀvyysgeenien tuonti muista roduista on tÀssÀ osoittautunut nopeaksi menetelmÀksi. TÀhÀn on kÀytetty paljon suomenlammasta. SiitÀ haluttiin kokemuksia EtelÀ- Afrikassakin, jonne koe-elÀinainesta tuotiin 1968 sekÀ lisÀksi neljÀn pÀssin spermaa 1981. NÀmÀ pidettiin sisÀmaassa (22 et.lev., 1523 m kork.), jossa kesÀpÀivÀt ovat kuumia ja yöt viileitÀ, talvipÀivÀt lauhkeita ja yöt kylmiÀ. Sadetta tulee keskimÀÀrin 580 mm/v, pÀÀosa kesÀllÀ. Karitsointi-%:ssa, vuonuekoossa ja eloonjÀÀnti-%:ssa oli merkitseviÀ vuosien vÀlisiÀ eroja. Karitsointi-% vaihteli 56.0 -90.6 % ja vuonuekoko 1.97 - 3.1. EloonjÀÀnti-% syntyessÀ ja syntymÀstÀ vieroitukseen aleni vuonuekoon noustessa. SyntymÀvuosien ja -tyyppien vÀlillÀ oli merkitseviÀ eroja syntymÀ-, vieroitus- ja 12 kk:n painossa. Ykkösten vastaavat painot olivat 47, 16 ja 13 % suuremmat kuin viitosten, mutta 3-, 4-ja 5-karitsoiden vÀliset erot vieroitus- ja 12 kk:n painoissa eivÀt olleet merkitseviÀ, koska 4- ja 5-karitsat saivat lisÀhoitoa syntymÀstÀ alkaen. Uuhen iÀllÀ oli hyvin merkitsevÀ vaikutus syntymÀ- ja 12 kk:n painoon, mutta ei vieroituspainoon, koska heikkojen karitsoiden saama lisÀmaito syntymÀstÀ vieroitukseen eliminoi maidontuotannon vaikutuksen. Uuhen vanhetessa syntymÀpaino nousi 9 vuoden ikÀÀn asti. 1-vuorisista uuhista syntyneet karitsat painoivat 12 kk:n iÀssÀ merkitsevÀsti vÀhemmÀn kuin aikuisten uuhien karitsat, vaikka vieroituspainossa ei ollut merkitseviÀ eroja. Karitsoiden sukupuoli vaikutti merkitsevÀsti kaikkiin painoihin: uuhet olivat kevyempiÀ kuin pÀssit. SekÀ pÀssien ettÀ uuhien villamÀÀrÀt olivat pienet (2.6,2.2 kg). Villan laadussa ei ollut merkitseviÀ sukupuolieroja. Se poikkesi suuresti merinotyypin villasta, mutta villakuitujen hienous ja kiharatiheys tÀyttivÀt maan laatuvaatimukset. Tulosten perusteella ei puhtaalle suomenlampaalle ole nÀhtÀvissÀ merkittÀvÀÀ roolia EtelÀ-Afrikan lammastaloudessa. Risteytyskokeiden mukaan voidaan sen hyvÀstÀ hedelmÀllisyydestÀ silti saada arvokas apu lammastalouden lisÀÀntymistehoon maan erilaisissa voimaperÀisyysolosuhteissa. Maassa on vastustettu monisynnytysten edistÀmistÀ, koska elÀinyksilöiden vÀhÀarvoisuus ei ole innostanut hoitotyön lisÀÀmiseen. KÀsitys on kuitenkin muuttunut viime vuosina, laitumien parantuessa sekÀ lampaanlihan hintojen noustessa. Maan villamarkkinat eivÀt myöskÀÀn ole olleet kovin innostuneita suomenlampaan villasta, mutta suomenlammas x merinoristeytysten villan kÀsittelyominaisuudet ovat lÀhempÀnÀ merinovillaa kuin minkÀÀn muun rodun merino-risteytysten. Koska villa on maan lammastalouden pÀÀtuote, voisi suomenlammas nÀytellÀ tÀrkeÀtÀ osaa valkovilla- lihaemÀlinjan perustamisessa teollisuutta varten, erityisesti siellÀ, missÀ ruokintaolosuhteet suosivat voimaperÀistÀ karitsantuotantoa
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