The primary purpose of this study was to investigate the effects of aerobic and resistance training on BDNF and IGF-I expression in a 3xTg-AD mouse model of Alzheimer’s disease. Twenty-four 3xTg-AD mice were randomly assigned to either an aerobic (AT, n=8), resistance (RT, n=8), or control (CNT, n=8) group. Intervention groups underwent 9 weeks of exercise training. Motor behavior and grip strength were measured pre- and post- intervention. Our results showed a significant increase in hippocampal BDNF expression in AT mice after a 9-week intervention. Further, AT mice were found to have higher concentrations of IGF-I, and improved motor behavior when compared to RT and CNT. No significant differences were observed in IGF-I concentration between RT and other groups. RT improved grip strength after nine weeks of training. These findings support the use of AT and RT as a tool to improve comorbidities found in Alzheimer’s disease. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

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Neste trabalho foram reativadas 51 linhagens fúngicas isoladas a partir da ascídia Didemnum ligulum. Após a reativação, as linhagens foram cultivadas em meio de cultura líquido (250 mL), a partir dos quais foram obtidos os respectivos extratos brutos. Os extratos foram avaliados em bioensaio de atividade citotóxica, em três linhagens de células tumorais. Observou-se que 14 extratos apresentaram atividade citotóxica. Os extratos foram avaliados por HPLC-UV-MS para determinação do perfil químico. Após esta análise, a linhagem DLM2-12, identificada como Penicillium citrinum, foi selecionada para crescimento em meio de cultura líquido em quantidade suficiente para se realizar o isolamento dos metabólitos secundários do extrato de seu meio de cultura. O extrato de 250 mL do meio de cultura de P. citrinum foi submetido a diferentes métodos de separação cromatográfica. Estas separações permitiram o isolamento e identificação da citrinina (47) como sendo majoritária. Para isolamento de outros compostos presentes no extrato, a linhagem foi cultivada em maior escala (8 L) e obtido o extrato de seu meio de cultura. O novo extrato foi submetido a separações cromatográficas em gel de Sephadex LH-20, sílica gel e sílica gel derivatizada com grupo cianopropila, bem como purificações por HPLC. Estas separações permitiram o isolamento e identificação de três quinolonas, as quinolactacinas C (50) e B (53) e a quinolactacina E (51), inédita na literatura, um ácido tetrâmico, o penicilenol A (54) e duas antraquinonas, a citreoroseína (57) e a emodina (61). As antraquinonas citreoroseína (57) e emodina (61) foram submetidas aos bioensaios de atividade antiviral, antimicrobiana, Leishmanicida e citotóxica. A citreoroseína (57) apresentou atividade contra as linhagens virais BVDV, HSV1 e aMPV e apresentou atividade citotóxica ativa frente à linhagem celular HCT-116 sendo inativa frente às linhagens celulares HL-60, SF295, OVCAR-8, K562, HCT-8, MDA-MB435 e MVF-7. A emodina (61) apresentou atividade contra as linhagens virais BVDV, HSV1, aMPV e hepatite C, atividade antimicrobiana, atividade Leishmanicida, atividade citotóxica frente às linhagens celulares HL-60, HCT-116, SF295, OVCAR-8, K562 e HCT-8 sendo inativa frente às linhagens celulares MDA-MB435 e MVF-7. / The present investigation describes the isolation of secondary metabolites from the culture medium of a marine-derived strain of the fungus Penicillium citrinum. Initially, 51 fungal strains isolated from the ascidian Didemnum ligulum and preserved in stereilized sea water were re-activated in Petri dishes. After reactivation, the strains were grown in 250 mL of liquid culture medium. All media were extracted with EtOAc and, after evaporation, aliquots of the extracts were evaluated in a cytotoxicity assay on three tumor cell lines. It was observed that 14 extracts showed cytotoxic activity. These 14 extracts were analyzed by HPLC-UV-MS in order to investigate their corresponding chemical profile. As a result, the DLM2-12 strain, identified as Penicillium citrinum, was selected for semi-preparative growth in liquid culture medium in sufficient quantity to accomplish the isolation of secondary metabolites. A first growth in 250 mL of culture medium yielded an extract which was subjected to various chromatographic separations, to give citrinin (42) as the major compound. An additional growth of P. citrinum DLM2-12 in a larger volume (8 L) yielded an extract which was subjected to chromatographic separations on Sephadex LH-20, cyanopropyl-bonded silica gel, and by reversed-phase HPLC. These separations gave, after the identification of pure compounds: a) three quinolones, quinolactacins C (51) and B (54) and a new quinolactacin (52), unreported in the literature; b) the tetramic acid penicilenol A (55), and; c) two anthraquinones, citreorosein (57) and emodin (61). The anthraquinones 57 and 61 were evaluated in antiviral, antimicrobial, antileishmanial and cytotoxic assays. Citreorosein (57) displayed activity against the viral strains BVDV, HSV1 and aMPV and showed cytotoxicity against the HCT-116 cell line, being inactive against HL-60, SF295, OVCAR-8, K562, HCT-8, MDA-MB435 and MVF-7 cell lines. Emodin (61) displayed activity against the viral strains BVDV, HSV1, AMPV and hepatitis C, as well as antimicrobial, leishmanicidal, as well as cytotoxic activity against HL-60, HCT-116, SF295, OVCAR-8, K562 and HCT-8 cancer cell lines, being inactive against MDA-MB435 and MVF-7 cell lines.

A obesidade comum, determinada por mecanismo de herança multifatorial, é atualmente um dos problemas mais importantes de saúde publica no mundo. Estudos de associação entre polimorfismos em genes candidatos e a predisposição à obesidade têm sido realizados em diferentes populações a fim de tentar esclarecer as bases genéticas que controlam o acúmulo de gordura corporal. Esse trabalho teve por objetivo principal estudar a associação dos polimorfismos LEP A19G, LEPR Gln223Arg, ADRB2 Arg16Gly, PPARG Pro12Ala, PLIN 6209T>C, RETN -420C>G e INSIG2 rs7566605 a medidas antropométricas relacionadas ao fenótipo de obesidade, tais como Índice de Massa Corporal (IMC), Circunferência da Cintura (Cc) e Razão Cintura/Quadril (RCQ) em populações afrodescendentes de remanescentes de quilombos, localizadas no Vale do Ribeira-SP. Além disso, procuramos identificar os principais fatores ambientais que influenciam o acúmulo de gordura corporal nessas populações. Nossa amostra constituiu-se de cerca de 790 indivíduos genotipados em relação a esses sete polimorfismos dos quais foram coletadas medidas de peso, altura, circunferências da cintura e do quadril, pregas cutâneas tricipital e subescapular e informações sobre o seu Grau de Atividade Física (GAF), tabagismo e consumo de álcool. Para os estudos de associação, os indivíduos foram analisados de duas formas distintas: como indivíduos independentes e agrupados em 53 genealogias. As metodologias de estudo casocontrole, comparação entre os valores das medianas entre indivíduos com diferentes genótipos e análises de regressão linear e logística foram empregadas quando estudamos os indivíduos de forma independente. Testes de estratificação populacional, associação total e associação dentro das famílias, utilizando pares de irmãos, foram realizados por meio do pacote computacional QTDT (Quantitative Transmission Disequilibrium Test). Nossos resultados indicaram uma maior freqüência de indivíduos com sobrepeso (IMC>=25 Kg/m2) e obesos (IMC>=30 Kg/m2) entre as mulheres (52% e 17,5%, respectivamente) do que entre os homens (17,5% e 2,75%, respectivamente), devido provavelmente à diferença em relação ao GAF, que é maior no grupo dos homens. Apesar de o GAF estar relacionado às diferenças observadas entre homens e mulheres em relação ao IMC, ele não explica as diferenças encontradas em relação ao IMC, Cc e RCQ entre indivíduos do mesmo sexo. Análises de regressão indicaram que os parâmetros não-genéticos que parecem melhor explicar as variações do IMC são o sexo e o tabagismo; da Cc são o sexo, a idade e o tabagismo e da RCQ, a idade e o sexo. Análises de regressão logística indicaram que entre as mulheres, o aumento do risco de apresentar fenótipos de sobrepeso, medidos por meio do IMC, Cc e RCQ, está relacionado ao fato de não fumar, consumir bebida alcoólica e ter maior idade. As análises de associação indicaram que nessas populações o alelo Gln do polimorfismo LEPR Gln23Arg está associado a valores maiores de IMC nas mulheres e RCQ nos homens, conforme apontaram as análises caso-controle, de comparação entre medianas e regressões linear e logística. O alelo Arg do polimorfismo ADRB2 Arg16Gly está associado a valores maiores de Cc e RCQ apenas entre os homens, conforme indicaram as análises de comparação entre as medianas e regressão linear. O alelo Ala do polimorfismo PPARG Pro12Ala está associado a valores maiores de IMC, Cc e RCQ nas mulheres, conforme apontaram as análises caso-controle, de comparação entre medianas e regressão linear. O alelo A do polimorfismo PLIN 6209T>C está associado a valores maiores de IMC e Cc entre as mulheres e a valores maiores de IMC, Cc e RCQ entre os homens, conforme indicaram os resultados obtidos com a análise de comparação entre medianas, regressão linear e regressão logística. Apenas entre as mulheres o alelo G do polimorfismo RETN -420C>G mostrou-se associado a valores mais altos de IMC e Cc de acordo com os resultados obtidos com a comparação entre medianas e com a regressão logística. Os resultados obtidos com as análises caso-controle e de comparação entre medianas indicaram que o alelo C do polimorfismo INSIG2 rs7566605 está associado a valores maiores de Cc nas mulheres e IMC nos homens. O único resultado positivo de associação detectado por meio da análise de pares de irmãos refere-se ao polimorfismo LEP A19G e o IMC, sendo o alelo G o que está associado aos valores maiores em ambos os sexos. Em resumo, nossos resultados sugerem a participação dos genótipos nos genes LEP, LEPR, ADRB2, PPARG, PLIN, RETN e INSIG2 na predisposição à obesidade nas populações de remanescentes de quilombos do Vale do Ribeira. / Obesity, which is determined by multifactorial inheritance, is currently one of the most important issues concerning public health all over the world. Studies on the association of polymorphisms in genes with a possible role in the susceptibility to obesity have been conducted in different populations in the world, in order to elucidate the genetic basis that control the accumulation of body fat. This work had as the main goal to study the association of the polymorphisms LEP A19G, LEPR Gln223Arg, ADRB2 Arg16Gly, PPARG Pro12Ala, PLIN 6209T>C, RETN -420C>G and INSIG2 rs7566605 to the anthropometrical measurements related to the phenotype of obesity, such as Body Mass Index (BMI), Waist Circumference (WC) and Waist to Hip Ratio (WHR) in african-derived populations from remnants of quilombos, located in Ribeira Valley, in State of São Paulo, Brazil. Furthermore, we sought to identify the main environmental factors that influenced the accumulation of body fat in these populations. Our sample comprises about 790 individuals genotyped in relation to these seven polymorphisms, from which measurements of weight, height, hip and waist circumferences, tricipital and subscapular skinfolds, and information about the Physical Activity Level (PAL), alcohol and tobacco consumption were obtained. For the association studies, the individuals were analyzed in two distinct ways: as independent individuals or grouped in 53 genealogies. The methodologies of case-control study, comparison between the medians among individuals with different genotypes, linear and logistic regression analysis were applied when we studied the individuals in the independent approach. Tests of population stratification, total association and association within the families, using pairs of siblings, were conducted by the computational pack QTDT (Quantitative Transmission Disequilibrium Test). Our results indicated a higher incidence of overweighed (BMI>=25 Kg/m2) and obese individuals (BMI>=30 Kg/m2) among women (52% and 17,5%, respectively) than among men (17,5% and 2,75%, respectively), probably due to the difference in the PAL, which is higher among men. Although the PAL is related to the differences in BMI observed between men and women, it does not explain the differences in relation to the BMI, WC and WHR found among individuals of the same sex. Regression analyses indicated that the non-genetic parameters that better explain the variations of BMI are sex and tobacco consumption; for WC are sex, age and tobacco consumption and for the WHR are age and sex. Logistic regression analyses indicated that among women, the increase in risk of presenting overweight, measured by the BMI, WC and WHR is related to not smoking (BMI, WC), consuming alcohol (BMI) and being elder (WC, WHR). The association analyses indicated that in these populations, the allele Gln of the polymorphism LEPR Gln23Arg is associated to higher values of BMI in women and WHR in men, as the case-control, median comparisons and linear regressions analyses indicated. The allele Ala of the polymorphism PPARG Pro12Ala is associated to higher values of BMI and WC among women and higher values of BMI, WC and WHR among men, according to the results obtained with the median comparison, and linear and logistic regressions analyses. Only among women, the allele G of the polymorphism RETN -420C>G was associated to higher BMI and WC values, as from the analysis of comparison of medians, and logistic regression indicated. The results obtained with the case-control analyses and median comparisons, suggested that the allele C of the polymorphism INSIG2 rs7566605 is associated to higher values of WC in women and BMI in men. The only positive result of association detected by the analysis of pairs of siblings is related to the polymorphism LEP A19G and the BMI. The allele G is associated to higher values of BMI in both sexes. As a summary, our results indicate the participation of the genotypes in genes LEP, LEPR, ADRB2, PPARG, PLIN, RETN and INSIG2 in the susceptibility to obesity in african-derived populations from quilombos in Ribeira River Valley.

L'espace des lacets lisses C(S^1,M) associé à une variété symplectique M se voit doté d'une structure (quasi-)symplectique induite par celle de M.Nous traiterons dans cette thèse d'un analogue algébrique de cet énoncé.Dans leur article, Kapranov et Vasserot ont introduit l'espace des lacets formels associé à un schéma. Il s'agit d'un analogue algébrique à l'espace des lacets lisses.Nous generalisons ici leur construction à des lacets de dimension supérieure. Nous associons à tout schéma X -- pas forcément lisse -- l'espace L^d(X) de ses lacets formels de dimension d.Nous démontrerons que ce dernier admet une structure de schéma (dérivé) de Tate : son espace tangent est de Tate, c'est-à-dire de dimension infinie mais suffisamment structuré pour se soumettre à la dualité.Nous définirons également l'espace B^d(X) des bulles de X, une variante de l'espace des lacets, et nous montrerons que le cas échéant, il hérite de la structure symplectique de X. Notons que ces résultats sont toujours valides dans des cas plus généraux : X peut être un champs d'Artin dérivé.Pour démontrer nos résultats, nous définirons ce que sont les objets de Tate dans une infinie-catégorie C stable et complète par idempotence.Nous prouverons au passage que le spectre de K-théorie non-connective de Tate(C) est équivalent à la suspension de celui de C, donnant une version infini-catégorique d'un résultat de Saito.Dans le dernier chapitre, nous traiterons d'un problème différent. Nous démontrerons l'existence d'une structure d'algèbre de Lie sur le tangent décalé de n'importe quel champ d'Artin dérivé X. Qui plus est, ce tangent agit sur tout quasi-cohérent E, l'action étant donnée par la classe d'Atiyah de E.Ces résultats sont par exemple valides dans le cas d'un schéma X sans hypothèse de lissité. / If M is a symplectic manifold then the space of smooth loops C(S^1,M) inherits of a quasi-symplectic form. We will focus in this thesis on an algebraic analogue of that result.In their article, Kapranov and Vasserot introduced and studied the formal loop space of a scheme X. It is an algebraic version of the space of smooth loops in a differentiable manifold.We generalize their construction to higher dimensional loops. To any scheme X -- not necessarily smooth -- we associate L^d(X), the space of loops of dimension d. We prove it has a structure of (derived) Tate scheme -- ie its tangent is a Tate module: it is infinite dimensional but behaves nicely enough regarding duality.We also define the bubble space B^d(X), a variation of the loop space.We prove that B^d(X) is endowed with a natural symplectic form as soon as X has one.To prove our results, we develop a theory of Tate objects in a stable infinity category C. We also prove that the non-connective K-theory of Tate(C) is the suspension of that of C, giving an infinity categorical version of a result of Saito.The last chapter is aimed at a different problem: we prove there the existence of a Lie structure on the tangent of a derived Artin stack X. Moreover, any quasi-coherent module E on X is endowed with an action of this tangent Lie algebra through the Atiyah class of E. This in particular applies to not necessarily smooth schemes X.

This thesis constructs tilting bundles obtained from full strong exceptional collections of line bundles on all smooth toric Fano fourfolds. The tilting bundles lead to a large class of explicit Calabi-Yau-5 algebras, obtained as the corresponding rolled-up helix algebra. We provide two different methods to show that a collection of line bundles is full, whilst the strong exceptional condition is checked using the package QuiversToricVarieties for the computer algebra system Macaulay2, written by the author. A database of the full strong exceptional collections can also be found in this package.

"Recent data show that 7.6 million Americans have survived a myocardial infarction (MI), and 5.1 million Americans suffer from severe heart failure. Stem cell therapy has the potential to improve cardiac function after MI. Two promising cells for cardiovascular regeneration therapies include human mesenchymal stem cells (hMSCs) and pluripotent stem cell derived cardiomyocytes (hPS-CM) each with their own unique method for improving cardiac function post-infarct. However, a limiting factor to cell therapies is that the methods currently used to deliver cells to the myocardium, including intramyocardial injection (considered the gold standard), suffer from low retention rates. To promote localization of delivered cells to the infarct and increase retention rates, our lab has developed a fibrin biological suture that can deliver human mesenchymal stem cells (hMSCs) with an efficiency of 64% compared to just 11% with intramyocardial injection in the normal rat heart. In this dissertation we sought to examine the functionality of hMSC and hPS-CM seeded sutures and their impact on cardiovascular regeneration applications. We began by delivering hMSC seeded fibrin sutures to an infarcted rat heart and found that the sutures are an effective method to deliver cells to the infarcted myocardium and demonstrated a trend towards improved regional mechanical function in the infarct region over infarct alone. Next, we transitioned to using hPS-CM and developed methods to seed the sutures, as well as a method to measure hPS-CM contractility with high spatial and temporal resolution, while concurrently capturing calcium transients. This technique allowed us to examine the contractile behavior in terms of contractile strain and conduction velocity of hPS-CM seeded on fibrin microthreads over 21 days in culture. We found that the fibrin microthread is a suitable scaffold for hPS-CM attachment and contraction and that extended culture promotes cell alignment along the length of the suture as well as improvements in contractile function in terms of increases in contractile strain and conduction velocity. Finally, we delivered the hPS-CM seeded microthreads to an uninjured rat heart and found a delivery efficiency of 67%. Overall, we further demonstrated the technology of the fibrin suture to deliver cells to an infarct as well as the ability to support the attachment, contraction and delivery of hPS-CM to cardiac tissue. "

Every year, 400,000 coronary artery bypasses (CABG) are performed in the United States. However, one third of all patients who need a CABG cannot undergo the procedure because of the lack of suitable autologous blood vessels. Both synthetic and tissue engineered vascular grafts have been used clinically for vascular grafts or other surgical applications, but no small- diameter engineered vessels have yet been successfully used for CABG. The success of vascular tissue engineering is strongly dependent on being able to control tissue contractility and extracellular matrix (ECM) production to achieve balance between tissue strength and physiological function. Smooth muscle cells (SMCs), the main contributor of contractility in blood vessels, retain phenotypic plasticity, meaning they possess the ability to switch between a contractile and synthetic phenotype. In 2D culture, a number of biochemical and mechanical cues have been shown to promote the switch to a contractile phenotype in SMCs. However, achieving a stable contractile phenotype in 3D tissue has proven difficult. The work in this dissertation describes an investigation of how passive and dynamic environmental cues influence the smooth muscle phenotype. We studied the effects of substrate modulus in conjunction with changes in cell culture media composition on SMC phenotype in 2D and 3D cultures. Culturing SMCs in a low-serum culture medium resulted in an increase in SMC contractility in 2D cell culture but not in 3D cell-derived tissue. We found that, in SMCs cultured on soft substrates, the ability to modulate SMC phenotype in response to changes in media was diminished. Passively crosslinking the ECM of our cell-derived tissues with genipin resulted in modest increases in elastic modulus, though not enough to observe changes in SMC phenotype. Additionally, we investigated how dynamic cyclic mechanical stretch, in conjunction with cell culture medium, modified SMC contractility in cell and tissue cultures. SMCs increased contractile protein expression when exposed to dynamic stretch in 2D culture, even on soft substrates, which have previously been shown to inhibit phenotypic modulation. In 3D tissue rings, after mechanical stimulation, SMCs became more aligned, the tissue became tougher, and SMCs exhibited a measurable increase in contractile protein expression. In summary, we found that increasing substrate modulus, culturing in low serum cell culture medium, and imparting cyclic mechanical stretch can promote SMC differentiation and cellular alignment, and improve tissue mechanical properties. This information can be used to more accurately recapitulate vascular tissue for use in modeling or in the creation of tissue engineered blood vessels.

Submitted by Maicon Juliano Schmidt (maicons) on 2015-06-30T18:16:48Z No. of bitstreams: 1 Vinícius Cunha dos Santos.pdf: 554014 bytes, checksum: 4a4b4c9093db3071a57b6bb0ba7a6e56 (MD5) / Made available in DSpace on 2015-06-30T18:16:48Z (GMT). No. of bitstreams: 1 Vinícius Cunha dos Santos.pdf: 554014 bytes, checksum: 4a4b4c9093db3071a57b6bb0ba7a6e56 (MD5) Previous issue date: 2013-01-31 / Nenhuma / O objetivo da presente dissertação é analisar a presença dos modos originário e derivado nas reflexões heideggerianas sobre queda, impessoal, objetivação e tempo. Para isso, nos utilizaremos de Ser e Tempo como obra central. A conferência O Conceito de Tempo, de 1924, a análise das epístolas paulinas e das Confissões de Agostinho, presentes no livro Fenomenologia da Vida Religiosa, e a resenha crítica feita por Heidegger sobre o texto A psicologia das visões de mundo de Karl Jaspers, também aparecem como constituintes importantes de nosso estudo. Para levarmos a cabo nosso objetivo de pesquisa, começamos apresentando, nos primeiros capítulos, a analítica existencial e alguns elementos que compõem sua estrutura, como o Dasein, a queda, o impessoal e a objetivação. Em seguida, entramos nos modos como os entes vêm ao encontro do Dasein no mundo, ou seja, o modo manual do lidar nas ocupações e o modo objetivado como "coisa". Por fim, entraremos nos temas da falação, curiosidade, ambiguidade, que compõem a queda no impessoal e no tema do tempo. / The aim of the present dissertation is to analyze the presence of originating and derived modes on Heidegger’s reflection on fall, impersonal, objectification and time. To do so, we will use Being and Time as a core reference. The conference The Concept of Time in 1924, the analysis of the Pauline epistles and the Confessions of St. Augustine within the book Phenomenology of Religious Life, despite Heidegger’s review and critique on the text Psychology of Worldviews by Karl Jaspers, also appear as important constituents of our study. In order to fulfill our research goal, we begin by presenting in the early chapters, the existential analytic and some elements that compose its structure as the Dasein, the fall, the impersonal and the objetification. Then, we get into the ways in which beings come to meet Dasein in the world, i.e., the manual mode to handle occupations and the objectified way as “thing”. Finally, we will go into themes like talk-talk, curiosity and ambiguity that compose the fall in impersonal and the theme of time.

The mammalian target of rapamycin (mTOR) signalling pathway takes part in both extracellular and intracellular signals. It is a major regulator of cell metabolism, growth, proliferation and survival. mTOR also regulates critical processes such as cytoskeletal organization, ribosomal biogenesis, transcription and protein synthesis. The mTOR pathway has been implicated in many diseases such as cancer, neurodegeneration and diabetes, which impact homeostasis and cellular functions. Moreover, mTOR has also been shown to play a critical role in immune cell regulation of T and B cells together with neutrophils and antigen presenting cells, as it integrates signals between them extending to the entire immune microenvironment. The aim of my study was to investigate the role of a component of the mTOR complex 1, Raptor, in myeloid cells. My findings show that the absence of Raptor knock out (KO) does not affect bone marrow derived macrophage (BMDM) differentiation and maturation. However, the absence of Raptor influences BMDM polarisation towards an inflammatory phenotype, at least at the level of transcription as observed by increases in mRNA expression of inflammatory cytokines such as TNFα, IL-12β, and IL-6. This finding was consolidated by an increase in NFκΒ pathway signalling in Raptor KO BMDMs. Downstream intracellular signalling in myeloid cells was affected by deletion of Raptor as I found reduced S6K phosphorylation in Raptor KO BMDMs compared to wild type (WT) BMDMs. As a consequence of Raptor absence in BMDMs, STAT3 phosphorylation was also reduced. Raptor deletion did not impact the PI3K/Akt signalling pathway, but decreased phosphorylation of ERK. BMDMs lacking Raptor had reduced phagocytic activity as they were also observed to migrate less towards a pancreatic cancer cell line. However preliminary experiments in pancreatic cancer models did not indicate a major role for Raptor in the activity of tumour associated myeloid cells. My results demonstrate that Raptor and by implication mTORC1, is involved in macrophage polarisation and function.