Verprolin cytokinesis function mediated by the Hof one trap domain

In budding yeast, partitioning of the cytoplasm during cytokinesis can proceed via a pathway dependent on the contractile actomyosin ring, as in other eukaryotes, or alternatively via a septum deposition pathway dependent on an SH3 domain protein, Hof1/Cyk2 (the yeast PSTPIP1 ortholog). In dividing yeast cells, Hof1 forms a ring at the bud neck distinct from the actomyosin ring, and this zone is active in septum deposition. We previously showed the yeast Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP) ortholog, verprolin/Vrp1/End5, interacts with Hof1 and facilitates Hof1 recruitment to the bud neck. A Vrp1 fragment unable to interact with yeast WASP (Las17/Bee1), localize to the actin cytoskeleton or function in polarization of the cortical actin cytoskeleton nevertheless retains function in Hof1 recruitment and cytokinesis. Here, we show the ability of this Vrp1 fragment to bind the Hof1 SH3 domain via its Hof one trap (HOT) domain is critical for cytokinesis. The Vrp1 HOT domain consists of three tandem proline-rich motifs flanked by serines. Unexpectedly, the Hof 1 SH3 domain itself is not required for cytokinesis and indeed appears to negatively regulate cytokinesis. The Vrp1 HOT domain promotes cytokinesis by binding to the Hof 1 SH3 domain and counteracting its inhibitory effect.

Behavioural characterization of Vitamin D receptor knockout mice

Vitamin D (calcitriol) is a nuclear transcription regulator acting via a nuclear hormone receptor (VDR). In addition to its role in the regulation of calcium and phosphate horneostasis and in bone formation, Vitamin D is also thought to be involved in brain function. The aim of this study was to behaviourally phenotype VDR knockout mice. We characterized the behaviour of VDR null mutant mice and wildtype littermate controls by subjecting them to a range of tests including a primary behavioural screen (using the SHIRPA protocol), rotarod, gait analysis, Y-maze, marble burying test, bedding test, holeboard test, elevated plus maze, open field test and prepulse inhibition of the acoustic startle response. There were no effects of genotype on most of the scores from the SHIRPA protocol except that VDR -/- mice had alopecia, were shorter and weighed less than VDR +/+ mice. VDR -/- mice had a shorter gait as well as impairments on the rotarod, in the bedding test and impaired habituation in both the open field and on the acoustic startle response. The VDR -/- mice had normal acoustic startle responses but had impaired PPI at long (256 ms) but not short (64 ms) prepulse to pulse intervals. The VDR -/- mice were less active in the open field and buried fewer marbles in the marble burying test. However, there were no differences in the time spent on the open arms of the elevated plus maze or in working memory as assessed by repeat arm entries on the Y-maze. Therefore, it appears that VDR -/- mice have muscular and motor impairments that significantly affects locomotor behaviour but seemingly no impairments in cognition as indicated by exploration, working memory or anxiety. (C) 2004 Elsevier B.V. All rights reserved.

Purification and partial characterisation of recombinant human hepcidin

Hepcidin is a liver-expressed antimicrobial and iron regulatory peptide. A number of studies have indicated that hepcidin is important for the correct regulation of body iron homeostasis. The aims of this study were to analyse the expression, trafficking and regulation of human hepcidin in an in vitro cell culture system. Human hepcidin was transfected into human embryonic kidney cells. Immunofluorescence and confocal microscopy analysis revealed that recombinant hepcidin localised to the Golgi complex. Recombinant hepcidin is secreted from the cell within 1 h of its synthesis. Recombinant hepcidin was purified from the cell culture medium using ion-exchange and metal-affinity chromatography and was active in antimicrobial assays. Amino-terminal sequence analysis of the secreted peptide revealed that it was the mature 25 amino acid form of hepcidin. Our results show that recombinant myc-His tagged human hepcidin was expressed, processed and secreted correctly and biologically active in antimicrobial assays. (C) 2005 Elsevier SAS. All rights reserved.

Does timing and sequencing of transitions to adulthood make a difference? Stress, smoking, and physical activity among young Australian women

The major changes of the transition to adulthood are argued to be stressful, and health-related behaviors such as smoking and physical activity may be adopted, consolidated, or abandoned at this time. On the other hand, research has suggested that the normative transitions of emerging adulthood, although involving considerable change, may be associated with low stress because they are perceived as both positive and normal at this life stage. This article examines relations between the timing and sequencing of life transitions and stress and health-related behaviors, focusing on the transition to young adulthood among Australian women. A total of 853 women aged 22 to 27 provided information about the timing and sequencing of 6 life transitions: moving out of home, stopping full-time education, starting full-time work, having the first live-in relationship, marriage, and motherhood-and stress, smoking, and physical activity. Most had moved out of home, stopped full-time education, and started full-time work, but only 14% had undertaken all 6 transitions. Overall, 70% of participants had made transitions in order Overall, the findings suggest that the relations between timing and sequencing of transitions, and indicators of health, are moderate for smoking, but small for stress and for physical activity. These effects remained after controlling for socioeconomic status of the participants' families of origin. Matching current social norms for the timing and sequencing of life changes may be of less importance for women's well-being than is commonly believed. Although the significant relations between early or out of order transitions and smoking are of concern, the smaller relations with stress and with sedentariness suggest that such transitions may have limited negative consequences, and support the view that individuals are active in choosing the life path that is appropriate for them and their circumstances.

Arthritic disease suppression and cartilage protection with glycosaminoglycan polypeptide complexes (Peptacans) derived from the cartilage extracellular matrix: A novel approach to therapy

Molecular fragments of cartilage are antigenic and can stimulate an autoimmune response. Oral administration of type II collagen prevents disease onset in animal models of arthritis but the effects of other matrix components have not been reported. We evaluated glycosaminoglycan polypeptides (GAG-P) and matrix proteins (CaP) from cartilage for a) mitigating disease activity in rats with collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) and b) stimulating proteoglycan (PG) synthesis by chondrocytes in-vitro. CIA and AIA were established in Wistar rats using standard methods. Agents were administered orally (10–200 mg/kg), either for seven days prior to disease induction (toleragenic protocol), or continuously for 15 days after injecting the arthritigen (prophylactic protocol). Joint swelling and arthritis scores were determined on day 15. Histological sections of joint tissues were assessed post-necropsy. In chondrocyte cultures, CaP + / − interleukin-1 stimulated PG biosynthesis. CaP was also active in preventing arthritis onset at 3.3, 10 or 20 mg/kg in the rat CIA model using the toleragenic protocol. It was only active at 20 and 200 mg/kg in the CIA prophylactic protocol. GAG-P was active in the CIA toleragenic protocol at 20 mg/kg but chondroitin sulfate and glucosamine hydrochloride or glucosamine sulfate were all inactive. The efficacy of CaP in the rat AIA model was less than in the CIA model. These findings lead us to suggest that oral CaP could be used as a disease-modifying anti-arthritic drug.

PERFIL DE EMPREENDEDORAS FEMININAS: ESTUDO DE CASO DO NÚCLEO DAS MULHERES EMPREENDEDORAS DA ASSOCIAÇÃO COMERCIAL E INDUSTRIAL DE SANTO ANDRÉ - SP

Ao longo do tempo, diversos estudos foram realizados com a intenção de compreender as diferenças entre pessoas empreendedoras e não empreendedoras e, especialmente, o que leva tais pessoas a terem atitudes. No entanto tais estudos geralmente focam características isoladas, que podem ser compreendidas por meio de construtos, sem a capacidade efetiva de construir perfis empreendedores. Outro aspecto importante é que a maioria dos estudos sobre o empreendedorismo, por características sociais e históricas, tem como foco o empreendedor masculino. Neste último aspecto, por mais que haja muitos estudos já realizados e em curso com o objetivo de corrigir esta distorção no estudo do empreendedorismo, ao incluir e evidenciar a parte feminina do empreendedorismo, ainda há muito a fazer. Este estudo, portanto, tem vários objetivos e cursos de ação: enfocar o empreendedorismo feminino, selecionar os construtos de empreendedorismo mais importantes sob a ótica feminina e, finalmente, construir um perfil empreendedor. Isto é, construir um perfil em que os diversos construtos se relacionam entre si e se organizam hierarquicamente em termos de importância. Para tanto, este estudo contou com o apoio do Núcleo de Mulheres Empreendedoras (NME) da Associação Comercial e Industrial de Santo André, onde o estudo foi realizado, sendo este um grupo de mulheres inovadoras e pioneiras na organização do empreendedorismo feminino no Estado de São Paulo e atuantes no ABC Paulista. Para conseguir os objetivos definidos, este estudo contou com várias fases como a entrevista inicial, onde foram identificados construtos relevantes e o contraste com a literatura - pesquisa bibliométrica com o objetivo de amalgamar a visão do NME com o que já foi previamente publicado. De forma inovadora, buscou-se utilizar uma técnica da família da Análise de Decisão Multicritério, a PAPRIKA (sigla inglesa para Ranqueamento Pareado Potencial de todas as Alternativas Possíveis), como parte das entrevistas e questionários, de modo a ser possível organizar as relações hierárquicas entre os construtos, que se mostrou adequado e compatível com o propósito original. Finalmente, utilizando-se da PAPRIKA e das entrevistas, foi possível construir um perfil final relacionado hierarquicamente de quais construtos são mais importantes no sucesso empreendedor feminino, de acordo com a visão de um grupo de mulheres empreendedoras.

Retrotransposon expression profiling: Unveiling the hidden SINE transcriptome through Next-Generation Sequencing data analysis

Of the ~1.7 million SINE elements in the human genome, only a tiny number are estimated to be active in transcription by RNA polymerase (Pol) III. Tracing the individual loci from which SINE transcripts originate is complicated by their highly repetitive nature. By exploiting RNA-Seq datasets and unique SINE DNA sequences, we devised a bioinformatic pipeline allowing us to identify Pol III-dependent transcripts of individual SINE elements. When applied to ENCODE transcriptomes of seven human cell lines, this search strategy identified ~1300 Alu loci and ~1100 MIR loci corresponding to detectable transcripts, with ~120 and ~60 respectively Alu and MIR loci expressed in at least three cell lines. In vitro transcription of selected SINEs did not reflect their in vivo expression properties, and required the native 5’-flanking region in addition to internal promoter. We also identified a cluster of expressed AluYa5-derived transcription units, juxtaposed to snaR genes on chromosome 19, formed by a promoter-containing left monomer fused to an Alu-unrelated downstream moiety. Autonomous Pol III transcription was also revealed for SINEs nested within Pol II-transcribed genes raising the possibility of an underlying mechanism for Pol II gene regulation by SINE transcriptional units. Moreover the application of our bioinformatic pipeline to both RNA-seq data of cells subjected to an in vitro pro-oncogenic stimulus and of in vivo matched tumor and non-tumor samples allowed us to detect increased Alu RNA expression as well as the source loci of such deregulation. The ability to investigate SINE transcriptomes at single-locus resolution will facilitate both the identification of novel biologically relevant SINE RNAs and the assessment of SINE expression alteration under pathological conditions.

PENTECOSTAIS, POLÍTICAS PÚBLICAS E MEIO AMBIENTE: Estudo Socioambiental em Rio Grande da Serra, periferia urbana no Grande ABC Paulista

O tema central de nossa pesquisa são as interações dos pentecostais com as questões socioambientais. Portanto, trata-se do estudo do grau de envolvimento dos pentecostais com as políticas públicas ambientais e o meio ambiente em periferia urbana - Rio Grande da Serra - Grande ABC Paulista. A intensa presença dos pentecostais nos bairros mais periféricos da cidade permitiu-nos indagar sobre as relações que esses mantêm com a expansão urbana nas áreas a serem protegidas, com os impactos ambientais, com consumo e pós-consumo na região, na participação de políticas públicas, bem como, os discursos e práticas religiosas interferem no comportamento dos religiosos frente a todas essas questões, uma vez que, a cidade está inserida em Área de Proteção e Recuperação de Mananciais, imbricada em um dos biomas terrestres mais ameaçados de extinção - o Bioma da Mata Atlântica. Como procedimentos metodológicos servimo-nos das observações empíricas, registro dos aspectos e impactos ambientais, aplicação de formulários e entrevistas com roteiro semiestruturado, elementos que constituíram uma tríade instrumental analítica. Concluímos que os pentecostais embora sejam atuantes em questões sociais, todavia, não o são quanto às questões ambientais na cidade, pois, não participam de maneira mais efetiva nas políticas públicas ambientais. Entretanto, os pentecostais demonstram uma potencialidade em participar do planejamento urbano participativo e dos processos de gestão urbana a médio e longos prazos, desde que sejam estimulados, primando dessa maneira, pela proteção, defesa e justiça ambiental nessas áreas de vulnerabilidade socioambiental.

Rastros e rostos do protestantismo brasileiro: uma historiografia de mulheres

Esta pesquisa abrange mulheres atuantes no chamado protestantismo histórico, principalmente vinculadas à Igreja Metodista do Brasil. O trabalho pretende visibilizar especialmente mulheres leigas e suas redes, geralmente informais, de articulação e chamar a atenção para seu papel na constituição destas comunidades de fé. Trata-se de um aspecto pouco explorado nas investigações sobre o protestantismo no Brasil que, quando abordado, se restringe a alguns ícones femininos. O foco principal do trabalho se restringe ao período de 1930, ano em que a Igreja Metodista do Brasil se constituiu como instituição autônoma, desvinculando-se formalmente de sua congênere nos EUA, até 1970/71, quando mulheres metodistas passam a ser admitidas no presbiterato, ou seja, podem solicitar a ordenação ao pastorado. Além de discutir a produção bibliográfica principalmente no âmbito da história do protestantismo, a pesquisa se baseia em fontes primárias, como boletins e jornais denominacionais, relatórios de eventos, correspondências e informações dispersas em diferentes materiais. Como referencial teórico a pesquisa se valeu da micro-história, procurando assim dar vida a personagens esquecidos e desvelar enredos ocultados pela história oficial. Portanto, além de demonstrar aspectos da atuação de mulheres no protestantismo brasileiro, silenciados tanto na memória institucional como na historiografia em suas diferentes matizes, a pesquisa pretende contribuir para uma avaliação crítica da mentalidade de mulheres sobre sua atuação no campo religioso, entre a adequação aos padrões culturais dominantes e os indícios de autonomia de pensamento diante de demandas específicas.(AU)

CONFIGURAÇÕES E TENDÊNCIAS DAS RÁDIOS COMUNITÁRIAS DO INTERIOR PAULISTA DA REGIÃO DE BAURU

Esta pesquisa oferece um mapeamento das principais tendências e características das rádios comunitárias legalizadas na Região Administrativa de Bauru, interior paulista, o que totaliza 23 emissoras. Objetivou-se entender qual a relação dessas emissoras com a população local, o modo como operam, os modelos de gestão adotados, as circunstâncias em que foram outorgadas, se e como têm viabilizado a participação popular e contribuído para a ampliação da cidadania. A partir da discussão de conceitos como comunidade , local e região , buscou-se enumerar as características usualmente encontradas e aquelas que idealmente deveriam estar presentes nas mídias comunitária, local e regional, especialmente sob o aspecto da participação popular e da cidadania, para empregá-los como parâmetros norteadores de análise das rádios estudadas. O trabalho se utilizou do estudo de casos múltiplos como tipo de pesquisa, além da pesquisa bibliográfica. As técnicas utilizadas foram entrevistas com os gestores das emissoras, estudo de documentos e observação da programação. Considera-se que tais emissoras são fenômenos comunicacionais complexos, flexíveis e contingentes, contexto esperado por lidar com o estudo de objetos díspares e em circunstâncias variadas. Contribuem para a ampliação da cidadania e promovem a participação, quando e na proporção em que sua equipe de gestão possui esse foco de trabalho. Apesar de seus limites, representam avanço para a democratização das comunicações no Brasil, proporcionando acesso da população a um meio de comunicação local.(AU)

TRADIÇÃO & INOVAÇÃO COMPETÊNCIAS TECNOLÓGICAS NECESSÁRIAS À PRÁTICA EDUCACIONAL

No presente trabalho realizamos uma análise sobre os novos paradigmas educacionais diante do fenômeno da expansão das tecnologias, as recomendações oficiais sobre a incorporação da tecnologia no contexto educacional e nas práticas docentes. Teve como objetivos pesquisar sobre as discussões acerca das contribuições da tecnologia no contexto educacional; analisar as competências necessárias para uma ação docente significativa utilizando as ferramentas que a tecnologia educacional disponibiliza para o professor; identificar como as inovações tecnológicas podem agregar valores às ações pedagógicas já existentes e suas múltiplas possibilidades de enriquecer a prática docente; analisar as razões pelas quais professores não conseguem agregar em sua rotina pedagógica a tecnologia. Realizamos uma pesquisa de campo que teve como sujeitos cinco professores do Fundamental 1ª fase, de Instituições Públicas(s) e Privadas(s) da cidade de Juiz de Fora/MG, atuantes na sala de aula. Para a coleta de dados aplicamos um questionário para a identificação do perfil dos sujeitos e entrevistas de aprofundamento. Para a análise dos dados das entrevistas utilizamos a metodologia de análise de conteúdo , proposta por Bardin (1979) e Franco (2003). Os resultados obtidos apontam para a necessidade de mudança no sistema educacional, um repensar da formação docente, pois hoje é fundamental que tenhamos professores capazes de incorporarem as tecnologias na prática cotidiana.

From national innovation systems to national innovation capacity:internationalisation and technology transfer perspectives

The last decade or so has witnessed the emergence of the national innovation system (NIS) phenomenon. Since then, many scholars have investigated NIS and its implementation in different countries. However, there are very few investigations into the relationship between the NIS of a country and its national innovation capacity. This paper aims to make a contribution in this area by examining the link that currently exists between these two topics. Whilst examining this relationship, we also explore internationalisation and technology transfer, being cognate areas that have been investigated during the same period. This follows our assertion that the link between NIS and national innovation capacity is the mechanism of internationalisation and technology transfer. The NIS approach was introduced in the late 1980s (see Freeman, 1987; Dosi et al., 1988) and further elaborated later (see Lundvall, 1992; Nelson, 1993; Edquist, 1997). In essence, a country?s NIS is a historically grown subsystem of the entire national economy consisting of organisations and institutions which play a major role in the innovative activity in the country. In the NIS approach, interactions within organisations as well as the interplay between organisations and institutions are of central importance. The NIS approach has been used to reveal the structure of the innovation processes and the main actors involved in them in industrialised and emerging countries. Although the national focus remains strong, it has been accompanied by studies seeking to analyse the notion of systems of innovation at an international level and at a sub-national scale (Archibugi et al., 1999). Dosi in the edition of Archibugi et al. (1999) argues that the general background of the discussion of national systems is the observation of non-random distributions across countries of: corporate capabilities; organisational forms; strategies; and ultimately revealed performances, in terms of production efficiency and inputs productivities, rates of innovation, rates of adoption/diffusion of innovation themselves, dynamics of market shares on the world markets, growth of income and employment. They also mention that there are several approaches to NIS. Nelson (1993) focuses upon the specificities of national institutions and policies supporting directly or indirectly innovation, diffusion and skills accumulation. Patel and Pavitt (1991) have stressed the links between the national patterns of technological accumulation and the competencies and innovative strategies of a few major national companies. Amable et al (1997) and Soskice (1993) and Zysman (1994) focus on the specifics of national institutions including, for example, the forms of organization, financial and labour markets, training institutions, forms of state intervention in the economy etc. However, the most common reference is by Lundvall (1992) who argues that the focus on the national level is associated with the fact that national economies vary according to their production system and their institutional framework and these differences are in turn strengthened by different historical experiences, language and culture. On the other hand, the national innovation capability consists of abilities to create and carry new technological possibilities through to economic practice. The term covers a wide range of activities from capability to invent to capability to innovate and to capability to improve existing technology beyond the original design parameters (Kim, 1997). The term innovation is often associated by many with technological change at international frontiers. However, technological capability is not the same as innovation capability. Technological capability refers to assimilation, use, adaptation, and change to existing technologies. It also enables the creation of new technologies and development of new products and processes in response to changing economic environments. It denotes operational command over knowledge (Kim, 1997). It is manifested not merely by the knowledge possessed, but, more important, by the uses to which that knowledge can be put and by the proficiency with which it is applied in the activities of investment and production and in the creation of new knowledge (Westphal et al., 1985). Therefore, the analytical framework that is used in this paper is based on the way a country derives from its NIS a national innovation capacity. There are two perspectives that are identified on this way. These are internationalisation and technology transfer. Even though NIS is not directly related to national innovation capacity, to achieve national innovation capacity from NIS, the country should have the ability for technology transfer. Technology transfer is a link between these two phenomena. On the other hand, internationalisation can be either the input or the output of the relationship between NIS and national innovation capability. If a company is investing in a country because of its national innovation capacity, this can be regarded as an input to the relationship between NIS and national innovation capacity. If this company is investigating the national innovation capacity of a country then, for its internationalisation, the national innovation capacity should be important, which in turn means this company is active in innovation and innovation is also an important success factor. The interrelationship between the investment of the company and the NIS of the country (assuming that the country is competent and competitive in technology transfer) will generate and improve that country?s national innovation capacity. This is the output of internationalisation from the relationship between NIS and national innovation capacity. When companies are evaluating whether to internationalise, they investigate certain factors in the countries in which they are considering to invest. The ability to transfer technology is dependent on ability to adopt a new technology and also on the learning derived from this technology. If countries wish to attract innovation related investment they need to show their ability to have a NIS and also the capability to transfer technology. Without the technology transfer capability, the NIS is not functioning. Therefore, companies that internationalise will investigate the factors common to NIS, technology transfer, and their business needs. Through this paper we will demonstrate this link though its mechanisms. Our research will be through extensive literature review and identifying relevant aspects of previous research carried out by the authors. It will investigate certain factors of different countries that are successful in attracting innovation related foreign direct investment. Through these, we will point out the factors that are important for the link and mechanisms of NIS and national innovation capability.

An ideal ocular nutritional supplement?

The role of nutritional supplementation in prevention of onset or progression of ocular disease is of interest to health care professionals and patients. The aim of this review is to identify those antioxidants most appropriate for inclusion in an ideal ocular nutritional supplement, suitable for those with a family history of glaucoma, cataract, or age-related macular disease, or lifestyle factors predisposing onset of these conditions, such as smoking, poor nutritional status, or high levels of sunlight exposure. It would also be suitable for those with early stages of age-related ocular disease. Literature searches were carried out on Web of Science and PubMed for articles relating to the use of nutrients in ocular disease. Those highlighted for possible inclusion were vitamins A, B, C and E, carotenoids beta-carotene, lutein, and zeaxanthin, minerals selenium and zinc, and the herb, Ginkgo biloba. Conflicting evidence is presented for vitamins A and E in prevention of ocular disease; these vitamins have roles in the production of rhodopsin and prevention of lipid peroxidation respectively. B vitamins have been linked with a reduced risk of cataract and studies have provided evidence supporting a protective role of vitamin C in cataract prevention. Beta-carotene is active in the prevention of free radical formation, but has been linked with an increased risk of lung cancer in smokers. Improvements in visual function in patients with age-related macular disease have been noted with lutein and zeaxanthin supplementation. Selenium has been linked with a reduced risk of cataract and activates the antioxidant enzyme glutathione peroxidase, protecting cell membranes from oxidative damage while zinc, although an essential component of antioxidant enzymes, has been highlighted for risk of adverse effects. As well as reducing platelet aggregation and increasing vasodilation, Gingko biloba has been linked with improvements in pre-existing field damage in some patients with normal tension glaucoma. We advocate that vitamins C and E, and lutein/zeaxanthin should be included in our theoretically ideal ocular nutritional supplement.

Visual word recognition:The first half second

We used magnetoencephalography (MEG) to map the spatiotemporal evolution of cortical activity for visual word recognition. We show that for five-letter words, activity in the left hemisphere (LH) fusiform gyrus expands systematically in both the posterior-anterior and medial-lateral directions over the course of the first 500 ms after stimulus presentation. Contrary to what would be expected from cognitive models and hemodynamic studies, the component of this activity that spatially coincides with the visual word form area (VWFA) is not active until around 200 ms post-stimulus, and critically, this activity is preceded by and co-active with activity in parts of the inferior frontal gyrus (IFG, BA44/6). The spread of activity in the VWFA for words does not appear in isolation but is co-active in parallel with spread of activity in anterior middle temporal gyrus (aMTG, BA 21 and 38), posterior middle temporal gyrus (pMTG, BA37/39), and IFG. © 2004 Elsevier Inc. All rights reserved.

Automated synthesis and evaluation of potential new anti-microbial agents

A series of N1-benzylideneheteroarylcarboxamidrazones was prepared in an automated fashion, and tested against Mycobacterium fortuitum in a rapid screen for antimycobacterial activity. Many of the compounds from this series were also tested against Mycobacterium tuberculosis, and the usefulness as M.fortuitum as a rapid, initial screen for anti-tubercular activity evaluated. Various deletions were made to the N1-benzylideneheteroarylcarboxamidrazone structure in order to establish the minimum structural requirements for activity. The N1-benzylideneheteroarylcarbox-amidrazones were then subjected to molecular modelling studies and their activities against M.fortuitum and M.tuberculosis were analysed using quantitative structure-analysis relationship (QSAR) techniques in the computational package TSAR (Oxford Molecular Ltd.). A set of equations predictive of antimycobacterial activity was hereby obtained. The series of N1-benzylidenehetero-arylcarboxamidrazones was also tested against a multidrug-resistant strain of Staphylococcus aureus (MRSA), followed by a panel of Gram-positive and Gram-negative bacteria, if activity was observed for MRSA. A set of antimycobacterial N1-benzylideneheteroarylcarboxamidrazones was hereby discovered, the best of which had MICs against m. fortuitum in the range 4-8μgml-1 and displayed 94% inhibition of M.tuberculosis at a concentration of 6.25μgml-1. The antimycobacterial activity of these compounds appeared to be specific, since the same compounds were shown to be inactive against other classes of organisms. Compounds which were found to be sufficiently active in any screen were also tested for their toxicity against human mononuclear leucocytes. Polyethylene glycol (PEG) was used as a soluble polymeric support for the synthesis of some fatty acid derivatives, containing an isoxazoline group, which may inhibit mycolic acid synthesis in mycobacteria. Both the PEG-bound products and the cleaved, isolated products themselves were tested against M.fortuitum and some low levels of antimycobacterial activity were observed, which may serve as lead compounds for further studies.