The M17 leucine aminopeptidase of the malaria parasite Plasmodium falciparum:importance of active site metal ions in the binding of substrates and inhibitors

The M17 leucine aminopeptidase of the intraerythrocytic stages of the malaria parasite Plasmodium falciparum (PfLAP) plays a role in releasing amino acids from host hemoglobin that are used for parasite protein synthesis, growth, and development. This enzyme represents a target at which new antimalarials could be designed since metalloaminopeptidase inhibitors prevent the growth of the parasites in vitro and in vivo. A study on the metal ion binding characteristics of recombinant P. falciparum M17 leucine aminopeptidase (rPfLAP) shows that the active site of this exopeptidase contains two metal-binding sites, a readily exchangeable site (site 1) and a tight binding site (site 2). The enzyme retains activity when the metal ion is removed from site 1, while removal of metal ions from both sites results in an inactive apoenzyme that cannot be reactivated by the addition of divalent metal cations. The metal ion at site 1 is readily exchangeable with several divalent metal ions and displays a preference in the order of preference Zn(2+) > Mn(2+) > Co(2+) > Mg(2+). While it is likely that native PfLAP contains a Zn(2+) in site 2, the metal ion located in site 1 may be dependent on the type and concentration of metal ions in the cytosolic compartment of the parasite. Importantly, the type of metal ion present at site 1 influences not only the catalytic efficiency of the enzyme for peptide substrates but also the mode of binding by bestatin, a metal-chelating inhibitor of M17 aminopeptidases with antimalarial activity.

Oppositional Political Identity in the Song Culture of the Vormärz and the 1848 Revolution in Germany

Historically political song has often been perceived negatively, as a disturbance of the peace, summed up by the legendary line from Goethe’s Faust: “Politisches Lied – ein garstiges Lied”. In the period in Germany of the Vormärz (from 1815 up to the revolution of March 1848), however, we see how this perception may be changing as it increasingly becomes a means of self-expression in public life. This was the era of restauration, in which broader sections of German society are striving for political emancipation from the princes and kings. A whole host of political themes emerge in the songs (Freiheitslieder) of that period in which a new oppositional political consciousness is reflected. The themes range from freedom of speech, freedom from censorship, and the need for democratic and national self-determination to critiques of injustice and hunger, and parodies of political convention and opportunism. Sources of reception give indications about the social and political milieus in which these songs circulated. Such sources include broadsheets, handwritten manuscripts, song collections, commemoration events, advertisements in political press, memoires, police reports and general literature of the time. In many cases we see how these songs reflect the emerging social and political identities of those who sing them. One also sees the use of well known melodies in the popular dissemination of these songs. An intertextual function of music often becomes apparent in the practice of contrefacture whereby melodies with particular semantic associations are used to either underline the message or parody the subject of the song.

The limits of democracy: Ireland 1778-1848

A survey of the use of the term democracy in Irish politics in the late eighteenth and early ninetenth centuries

John Rich as Opera Patron

This article traces the sustained support that theatre manager John Rich offered to operatic endeavours in 18th-century London. Rich effectively entered the contemporary discourse regarding the valid definition of opera through the kinds of works he supported, and also through the prefatory comments to two works staged at his theatre.

Chiton phylogeny (Mollusca Polyplacophora) and the placement of the enigmatic species Choriplax grayi (H. Adams & Angas)

Shallow marine chitons (Mollusca:Polyplacophora:Chitonida) are widespread and well described from established morphoanatomical characters, yet key aspects of polyplacophoran phylogeny have remained unresolved. Several species, including Hemiarthrum setulosum Carpenter in Dall, 1876, and especially the rare and enigmatic Choriplax grayi (Adams & Angas, 1864), defy systematic placement. Choriplax is known from only a handful of specimens and its morphology is a mosaic of key taxonomic features from two different clades. Here, new molecular evidence provides robust support for its correct association with a third different clade: Choriplax is placed in the superfamily Mopalioidea. Hemiarthrum is included in Cryptoplacoidea, as predicted from morphological evidence. Our multigene analysis of standard nuclear and mitochondrial markers demonstrates that the topology of the order Chitonida is divided into four clades, which have also been recovered in previous studies: Mopalioidea is sister to Cryptoplacoidea, forming a clade Acanthochitonina. The family Callochitonidae is sister to Acanthochitonina. Chitonoidea is resolved as the earliest diverging group within Chitonida. Consideration of this unexpected result for Choriplax and our well-supported phylogeny has revealed differing patterns of shell reduction separating the two superfamilies within Acanthochitonina. As in many molluscs, shell reduction as well as the de novo development of key shell features has occurred using different mechanisms, in multiple lineages of chitons.

A test for mucus removal in the chiton Lepidochitona cinerea (Linnaeus, 1767) (Polyplacophora: Chitonida: Ischnochitonidae)

Several methods have been proposed to ‘clean’ the soft tissues of molluscs of mucus, so that the surface cilia can be examined microscopically. We report the first empirical test of the effectiveness of methods for removing mucus in the pallial cavity surface of chitons. Three methods were compared, at several time intervals: the enzyme hyaluronidase, the mucolytic agent N-acetyl cysteine (NAC), and seawater washing via the natural action of cilia in excised tissue. Treatment in NAC for 10 min produced the best results, and we recommend this protocol as a starting point for further investigation on mucus removal in a broader suite of taxa. We present the first description of the pallial surface cilia in the chiton Lepidochitona cinerea. During the course of this study, we also determined that these chitons were frequently infested with a ciliate protozoan parasite, Trichodina sp., which have been historically reported from chitons but never studied in detail. The parasites were absent where antimucus treatments were effective, but their abundance and large size (about 30-mm diameter) in less successful treatments obscured the view of the pallial cavity surface.

Race, space and politics in Mid-Victorian Ireland: the ethnologies of Abraham Hume and John McElheran

There has been much scholarly debate about the significance and influence of racialist thinking in the political and cultural history of nineteenth-century Ireland. With reference to that ongoing historiographical discussion, this paper considers the racial geographies and opposing political motivations of two Irish ethnologists, Abraham Hume and John McElheran, using their racialist regimes to query some of the common assumptions that have informed disagreements over the role and reach of racial typecasting in mid-nineteenth-century Ireland. As well as examining in detail the racial imaginaries promulgated by Hume and McElheran, the paper also argues for the importance of situating racialist discourse in the spaces in which it was communicated and contested. Further, in highlighting the ways in which Hume and McElheran collapsed together race, class and religion, the paper troubles the utility of a crisp analytical distinction between those disputed categories.