This thesis examines the behaviour of sentential complements in Mohawk within the framework of Government and Binding Theory. Past proposals concerning the syntactic structure of sentential complements in Romance languages (and English) are explored in Mohawk. It is claimed that Mohawk only has full CP complements and no distinct types of embedded clauses (such as a subjunctive or infinitival). This is due to a morphological requirement (specified by the Minimal Word Constraint) on Mohawk verbs which dictates the need for obligatory agreement morphology. Tense/aspect co-occurrence restrictions are given to show what type of CP complements a verb can take. The evidence indicates that selection of complements is due to semantic and not syntactic reasons.

1. The DNA sequence of the human complement C4A gene from a cosmid clone Cos 3A3 was determined and the complete exon-intron structure elucidated. The 5' flanking region of the C4 gene contains three TATA sequences and a transcriptional enhancer core sequence, which are >200 nucleotides (nt) and 60-70 nt upstream from the CAP site, respectively. The gene consists of 42 exons coding for a precursor protein of 1745 residues. The first exon codes for a 51 nt 5' untranslated sequence, a leader peptide of 19 residues, and the N-terminus of the β chain. The β-α and the α-γ chain junctions are encoded by exons 17 and 34, respectively. The anaphylatoxin C4a and the thiolester site are encoded by phase 1-1 symmetrical exons. Most of the amino acids encoded at the splice junctions are polar or charged. Between exons 10 and 11 is a 6-7 kb intron that is flanked by direct long terminal repeats and may be absent in some C4 genes located at the second C4 locus. The last exon codes for the C-terminus of the γ chain and a 140 bp 3' untranslated sequence. The intergenic region between the C4 gene and its neighbouring 21-hydroxylase (210Hase) gene is ~3028 bp. 2. Eighteen polymorphic amino acids on C4 have been identified through genomic DNA, cDNA and protein sequencing. Fourteen of them are located on the* chain (C4a: 2 changes; C4d: 12 changes). The rest are scattered on the β and the γ chains. There are potential size variations by one residue on the β chain, and by a tripeptide that contains a sulphation site on the α chain. 3. Four common and rare C4 alleles have been cloned from individuals whose C4 proteins were chemically and serologically characterised. Analysis of the sequences at the C4d regions has allowed the identification of the C4A/C4B isotypic residues at positions 1101-6: C4A has the sequence PCPVLD, while C4B has the sequence LSPVIH. Presumably these isotypic residues are the cause of the class-specific, differential chemical reactivates. Moreover, the probable locations for the two Eodgers (Kg) and the six Chido (Ch) antigenic determinants were deduced. The C4B isotypic residues may be involved in the expression of the Ch2 and the Ch4 epitopes, while the C4A isotypic residues may not be related to either of the Eg determinants. 4. Definitive restriction fragment length polymorphisms (RFLPs) representing the exact locations responsible for the isotypicity between C4A and C4B, and for their generally associated Rg1 and Ch1 antigenic determinants, have been designed. In combination with the Taq I polymorphic patterns specific for the C4 and for the 210Hase gene loci, it has been shown that the null allele of the HLA haplotype B44 DR6 C4A 3 C4B QO is not a C4B allele, but probably encodes another C4A 3 allotype at the second C4 locus.

Typescript (photocopy) / viii, 102, xxv leaves, [6] leaves of plates : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.) Dept. of Microbiology, University of Adelaide, 1982

Thesis (Ph.D.) Dept. of Microbiology, University of Adelaide, 1982. / Typescript (photocopy).

Thesis (doctoral)--University of Lund, 1981.

Thesis (Ph.D)--Washington State University, August 2006. / Includes bibliographical references (p. 91-93).

Complement system includes a conglomeration of a set of soluble factors and membrane anchored receptors, which has been designed to recognise and clear non self (pathogens) and altered self (apoptotic cells, necrotic cells and transformed cells). In a general theme, the recognition subcomponents bind to target, which is followed by limited proteolytic cleavage of downstream complement components. Three pathways namely classical, alternative and lectin converge on the generation of C3 convertase. The alternative pathway is activated by spontaneous cleavage of C3, generating C3a, an anaphylatoxin, and C3b, which binds to the surface of pathogens. A C3 convertase is formed, which has a half-life of about 90 seconds, is stabilised by properdin, and in an amplification loop a C5 convertase is formed leading to lytic pathway and cell lysis. This puts properdin at the heart of up regulator of alternative pathway. Properdin is structurally organised into seven thrombospondin repeats (TSR), whose functions have been delineated via deletion mutagenesis studies. In the chapter 3, we have expressed TSR4 and TSR5 in tandem in E. coli and shown that the two-module recombinant protein binds to C3b, sulfatides, and glycosaminoglycans similarly to native properdin. The recombinant module also seems to be an efficient inhibitor of properdin’s ability to stabilise C3bBb complex, thus offering a therapeutic possibility to dampen alternative pathway. Although properdin’s definite role in perpetuating the alternative pathway is well established, its structural organisation also appears to suggest its potential as an independent innate immune soluble factor that would not require engagement with complement system. In chapter 4, we report the ability of properdin to interact with mycobacterium (BCG) via TSR4+5 module, down regulate the microbial uptake by macrophages, and up regulate pro-inflammatory cytokine response via enhancing anti-mycobacterial TNF-α production. In chapter 5, we demonstrate that properdin as well as TSR4+5 interacts directly with a range of influenza A virus strains leading to inhibition of infection and dampening of pro-inflammatory response. The ability of properdin to interact with non-self is further reaffirmed by its ability to interact with nanoparticles and modulate subsequent immune cell response as presented under discussion chapter. Thus, this thesis reports a set of novel observations highlighting non-complement properties of properdin, which may be crucial in host pathogen interaction.

Uma criança brasileira (LAS) vítima de infecções recidivantes e vasculite, cujos pais são consangüíneos em segundo grau apresentou 0,15 µg/mL de C3 plasmático e atividades hemolíticas nulas pelas vias clássica e alternativa, já outras proteínas do complemento e Igs estavam normais (exceto IgG4, que foi indetectável). Diferentemente de sua mãe os fibroblastos da criança não foram capazes de sintetizar as cadeias a e b de C3, como observado por SDS-PAGE. O probando possui dois alelos C3S, assim como seu irmão mais novo e saudável, enquanto a mãe é FS. A migração de leucócitos, em resposta ao soro do probando ativado com LPS foi menor que a obtida com soro normal e estatisticamente semelhante àquela gerada por SHN inativado a 56oC (SHNi). A ingestão e a morte de C. albicans, opsonizadas por soro do probando, por fagócitos normais foram semelhantes às dos fungos opsonizados por SHNi. Nós concluimos que, em conseqüência da incapacidade de sintetizar C3, o probando não é capaz de exercer as funções imunológicas dependentes do complemento, resultando em uma maior susceptibilidade a infecções. / A brasilian child (LAS) victim of recurrent infections whose parents have second degree consanguinity presented 0.15 µg/mL of serum C3 and no hemolytic activities either after activation of the classical or alternative pathways. His mother presented C3 alpha and beta chains of normal sizes, while LAS's fibroblasts did not secrete any C3 as observed by SDS-PAGE. The proband possesses two C3S alleles, like his younger and healthy brother whereas his mother is FS. Leukocyte migration across nitrocellulose membrane in response to the proband's LPS-activated serum was less intense than that obtained in response to normal serum. Phagocytosis and killing of C. albicans opsonized with the proband's serum was comparable to fungi opsonized with inactivated serum, incdicating that chemotactic and opsonic activities of the proband's serum are greatly diminished. We colclude that as a consequence of C3 deficiency the proband's complement system is uncapable of performing it's normal effector functions resulting in greater susceptibility to infections.

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(工学) / 甲第16406号 / 工博第3487号 / 新制||工||1527(附属図書館) / 29037 / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 岩田 博夫, 教授 田畑 泰彦, 教授 秋吉 一成 / 学位規則第4条第1項該当

This thesis describes an attempt to increase the life span of mice after injection of a leukemic tumor. Fatty acids were used as a protecting agent against the leukemic tumor.