Academic literature on the topic 'Cèl·lules mare'

Abstract Male E. uncula showed a synergistic response to lures containing Z3-10:Ac and Z5-10:Ac in a Z3/Z5 ratio of 1/10. The dodecenyl compounds Z5-12:Ac, Z7-12:Ac and Z7-12:OH, perceived via further types of antennal receptor cells, acted inhibitorily on this binary lure. Two species of Euxoa also responded to Z3-10: Ac as a single compound or lure component, respectively. This is the first report of a Δ3-alkenyl compound being involved in sexual attraction in the Noctuidae.

Abstract The male fruit fly attractants, cue-lure (CL) and raspberry ketone (RK), are important in pest management. These volatile phenylbutanoids occur in daciniphilous Bulbophyllum Thouar (Orchidaceae: Asparagales) orchids, along with zingerone (ZN) and anisyl acetone (AA). While these four compounds attract a similar range of species, their relative attractiveness to multiple species is unknown. We field tested these compounds in two fruit fly speciose locations in north Queensland, Australia (Lockhart and Cairns) for 8 wk. Of 16 species trapped in significant numbers, 14 were trapped with CL and RK, all in significantly greater numbers with CL traps than RK traps (at least in higher population locations). This included the pest species Bactrocera tryoni (Froggatt) (Diptera: Tephritidae) (CL catches ca. 5× > RK), Bactrocera neohumeralis (Hardy) (Diptera: Tephritidae) and Bactrocera bryoniae (Tryon) (Diptera: Tephritidae) (CL catches ca. 3× > RK), and Bactrocera frauenfeldi (Schiner) (Diptera: Tephritidae) (in Cairns—CL catches ca. 1.6× > RK). Seven species were trapped with AA, and all were also caught in CL and RK traps in significantly greater numbers, with the exception of B. frauenfeldi. For this species, catches were not statistically different with CL, RK, and AA in Lockhart, and RK and AA in Cairns. Seven species were trapped with ZN, two at this lure only, and the remainder also with CL or RK but in significantly greater numbers. This is the first quantitative comparison of the relative attractiveness of CL, RK, AA, and ZN against multiple species, and supports the long-held but untested assumption that CL is broadly more attractive lure than RK.

Environmental contextQueensland fruit fly is a major pest of fruits and vegetables in eastern Australia, sometimes causing complete loss of unprotected crops. Odours that attract fruit flies can help control these pests and this study investigated how six fruit fly species smell these chemicals. The strength of fly responses to tested odours gives insight into the way flies smell and provides information for making better attractants, potentially reducing insecticide use. AbstractThe Queensland fruit fly (Bactrocera tryoni, Q-fly) is a major horticultural pest in eastern Australia. The deployment of male lures comprises an important component of several detection and control strategies for this pest. A novel fluorinated analogue of raspberry ketone (RK), raspberry ketone trifluoroacetate (RKTA), has been developed with the aim of further improving Q-fly control. RKTA elicited strong electroantennogram (EAG) responses from Q-flies whereas cuelure (CL) and melolure (ML) responses were not significantly greater than a negative control. Further experimentation showed that RKTA also elicited EAG response from five other fruit fly species, included flies known to be strongly attracted to CL (B. neohumeralis, B. kraussi and B. frauenfeldi), weakly attracted to CL (B. jarvisi), or non-responsive to CL (Zeugodacus cucumis), whereas seven other compounds, RK, CL, ML, raspberry ketone difluoroacetate, raspberry ketone monofluoroacetate, anisyl acetone and trimethylsilyl raspberry ketone, elicited only weak responses comparable with a negative control. However, fly EAG responses to RKTA are likely due at least in part to trifluoroethanoic acid, which is a hydrolysis product of RKTA and elicited strong EAG responses from all six species when tested alone. Furthermore, whereas ethanoic acid, methanoic acid and trifluoroethanoic acid all elicited strong EAG responses in Q-flies, the only corresponding RK ester to elicit an EAG response was RKTA, suggesting that RKTA hydrolyses quickly, whereas CL and ML do not. This is in contrast to the idea that CL readily hydrolyses on contact with atmospheric moisture, an assertion that has been made in the literature repeatedly.

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The present PhD thesis work reports the molecular and genetic dissection for the role of plant steroid hormones Brassinosteroids (BRs) in root growth and development of Arabidopsis thaliana (Arabidopsis). A genetic, physiological and cellular analysis of existing BR mutants, together with the discovery of a novel pathway for the control of BR mediated stem cell divisions. The results presented here provide experimental evidence for a role of BRs in stem cell homeostasis in the primary root of Arabidopsis. Specifically, BRs promote columella stem cell differentiation and the division of a set of low mitotic cells called quiescent center (QC) that maintain the surrounding stem cells. Using a microgenomic approach, a novel BR signaling component, BRAVO (Brassinosteroids at Vascular and Organizing Centre) has been identified that is specifically expressed in the stem cells. BRAVO encodes a R2-R3 MYB transcription factor (MYB56) that acts as a negative regulator of BRmediated QC divisions. This study uncovers a fine example of negative regulation model; BRAVO is directly repressed and interacts with BES1 creating a molecular switch that controls QC divisions. The work carried out during this PhD thesis shed light to a new function of brassinosteroids in the regulation of stem cells. BRAVO provides plasticity to the stem cells to response to DNA damage, and at the same time robustness to ensure QC function upon damage. The control of plant stem cell homeostasis is pivotal to understand plant adaptation to environmental changing conditions and provides a new mechanism to understand plants life span.
Aquesta tesi doctoral té com a objectiu principal investigar els efectes de les hormones vegetals esteroides, Brassinosteroids (BRs), durant el desenvolupament de lʼarrel primària dʼArabidopsis thaliana (Arabidopsis). Per tal dʼassolir aquest objectiu hem realitzat una caracterització genètica, fisiològica i anàlisi cel•lular de mutants de BRs. Així mateix, sʼha descobert una nova ruta de senyalització que controla les divisions de les cèl•lules mare mediades per BRs, Els nostres resultats experimentals mostren com els BRs controlen la homeòstasi de les cèl•lules mare de lʼarrel. En concret, els BRs promouen la diferenciació de les cèl•lules mare de la columel•la i la divisió dʼun grup de cèl•lules mitòticament inactives que actuen en el manteniment de les cèl•lules mare, el centre quiescent (QC). Mitjançant un abordatge microgenòmic hem identificat un nou element de la ruta de senyalització dels BRs específic de les cèl•lules mare, BRAVO (Brassinosteroids at Vascular and Organizing Centre). BRAVO és un factor de transcripció R2R3 de la família MYB (MYB56), que actua com a regulador negatiu de les divisions de QC. Els nostres resultats mostren un model de regulació negativa, on BES1 reprimeix directament i interacciona amb BRAVO, creant un interruptor molecular que controla les divisions del QC. El treball realitzat durant aquesta tesis doctoral permet proposar una nova funció dels BRs en el control de les cèl•lules mare. BRAVO dóna plasticitat a les cèl•lules mare per a poder respondre al dany sobre lADN, així com robustesa per evitar-lo. El control de la homeòstasi de les cèl•lules mare en plantes és vital per entendre lʼadaptació dʼaquests organismes sèssils i la longevitat que presenten algunes espècies.

Tot i que es coneix l’involucrament de les cèl·lules pancreàtiques acinars en patologies exocrines (pancreatitis i càncer de pàncrees), la manca de models normals basats en cèl·lules ha limitat l’estudi de les alteracions que succeeixen en el programa de diferenciació pancreàtica. Hem demostrat prèviament que les cèl·lules mare embrionàries murines, que són pluripotents, poden adquirir un fenotip acinar in vitro. Això es va aconseguir, en part, amb una combinació de senyals que provenien del cultiu de pàncrees fetals que no era, però, específic del llinatge pancreàtic. L’objectiu d’aquest treball ha estat el de desenvolupar un protocol selectiu pel llinatge acinar basat en l’activació seqüencial de vies de senyalització que recapitulin el desenvolupament pancreàtic in vivo, a través de la formació definitiva de l’endoderm, l’especificació pancreàtica i acinar i l’expansió/diferenciació de progenitors acinars. El tractament de cossos embrionaris amb Activina A va promoure l’expressió de gens d’endoderm com està prèviament descrit. El tractament subsegüent amb àcid Retinoic, FGF10 i Ciclopamina, un inhibidor de la via de Hedgehog, va resutar en la inducció dels marcadors de progenitors pancreàtics Pdx1, Ptf1a i Cpa1 però també d’aquells expressats en el llinatge pancreàtic, que van ser reduïts amb la inhibició de BMPs. Les cèl·lules van ser a continuació cultivades en Matrigel utilitzant un sistema de cultiu en 3D en presència de fol·listatina, dexametasona i KGF comportant una inducció significativa dels nivells de mRNA i proteïna de marcadors acinars i una disminució de l’expressió dels de marcadors acinars. A més, es va veure que Amyl es secretava en el medi. Aquestes dades indiquen que l’activació selectiva del programa de diferenciació acinar en cèl·lules mare embrionàries es pot dur a terme mitjançant una inducció esgraonada de vies de senyalització involucrades en el desenvolupament pancreàtic exocrí proporcionant una eina potencial per estudiar la diferenciació pancreàtica i malalties relacionades amb el pàncrees.
Despite known involvement of pancreatic acinar cells in exocrine pathologies (pancreatitis and pancreatic cancer), the lack of normal cell-based models has limited the study of the alterations that occur in the acinar differentiation program. We have previously shown that mESC (murine embryonic stem cells), which are pluripotent, can acquire an acinar phenotype in vitro. This was achieved, in part, by a combination of signals provided by the culture of foetal pancreases which was, however, no specific for the acinar lineage. The aim of this work was to develop a protocol selective for the acinar lineage based on the sequential activation of signaling pathways that recapitulate pancreatic development in vivo, through the definitive endoderm formation, the pancreatic and acinar specification and the expansion/differentiation of acinar progenitors. Treatment of embryoid bodies with Activin A enhanced the expression of endodermal genes as previously described. Subsequent treatment with Retinoic acid, FGF10 and Cyclopamine, an inhibitor of the Hedgehog pathway, resulted in the enhancement of pancreatic progenitor markers Pdx1, Ptf1a and Cpa1 but also of those expressed in the hepatic lineage, which were reduced by BMPs inhibition. Cells were further cultured in Matrigel using a 3D culture system in the presence of follistatin, dexamethasone, and KGF leading to a significant enhancement of the mRNA and protein levels of acinar markers while decreasing the expression of endocrine ones. Moreover, active Amyl was released into the medium. These data indicate that the selective activation of the acinar differentiation program in ES cells can be achieved by stepwise induction of signaling pathways involved in pancreatic exocrine development providing a potential tool for studying pancreatic differentiation and pancreas-related diseases.

Parkinson’s disease (PD) is an incurable, chronically progressive neurodegenerative disease leading to premature invalidity and death. The locomotor disability of PD patients is mainly rooted in the gradual and insidious degeneration of dopaminergic neurons (DA) projecting from the midbrain substantia nigra (SN) to the basal ganglia striatum, a pathological process highlighted microscopically by the formation of insoluble cytosolic protein aggregates, known as Lewy bodies and Lewy neurites. The pathogenic mechanisms leading to PD remain poorly understood, arguably owing to the lack of suitable animal and cellular experimental models of the disease. Therefore, there is an urgent need for developing reliable experimental models that recapitulate the key features of PD. The recent development of induced pluripotent stem cell (iPSC) technology has enabled the generation of patient-specific iPSC and their use to model human diseases, although it is currently unclear whether this approach could be useful to successfully model age-related conditions. Importantly, disease modeling using iPSC largely relies on the existence of efficient protocols for the differentiation of disease-relevant cell types. Here, we first developed an efficient protocol for the differentiation of iPSC to authentic midbrain-specific DA neurons with SN properties by forced expression of LMX1A using a lentivirus-mediated gene delivery system. Next, we generated an iPSC-based cellular model of PD that recapitulates key phenotypic features of PD, such as DA neuron loss and α-synuclein accumulation in DA neurons from PD patients. Overall, our results demonstrate that we have developed a valuable tool for elucidating the pathogenic mechanisms leading to PD, as well as an experimental platform for screening new drugs that may prevent or rescue neurodegeneration in PD.
La malaltia de Parkinson (MP) és una malaltia neurodegenerativa incurable que causa invalidesa i mort prematura. Els pacients de la malaltia de Parkinson presenten alteracions motores degudes a una degeneració gradual de les neurones dopaminèrgiques que projecten des de la substància nigra fins a l’estriat. A nivell microscòpic s’observa la presència d’agregats proteics insolubles en el citosol de les neurones coneguts com cossos o neurites de Lewy. Els mecanismes patològics responsables de la MP no es coneixen bé, possiblement a causa de la manca de models animals i cel•lulars adequats. Per tant, existeix una gran necessitat de desenvolupar models experimentals fiables que recapitulin les característiques bàsiques de la MP. El recent desenvolupament de les cèl•lules mare pluripotents induïdes (iPSC) ha permès la generació de iPSC específiques de pacient i el seu ús per modelar malalties humanes, ara bé, no és clar si aquesta estratègia es pot utilitzar per modelar exitosament malalties d’origen tardà, com ara la MP. És important destacar que el modelatge de malalties utilitzant iPSC, es basa, en gran mesura en l'existència de protocols eficients per a la diferenciació de les iPSC cap al tipus cel•lular rellevant per a la malaltia. Durant aquest període, per primera vegada, s’ha desenvolupat un protocol per a l’eficient diferenciació de les iPSC cap a neurones dopaminèrgiques amb les propietats característiques de neurones dopaminèrgiques nigrostriatals, mitjançant l’expressió forçada de LMX1A utilitzant vectors lentivirals. A continuació, s’ha generat un model cel•lular usant iPSC derivades de pacients de MP que recapitula les principals característiques fenotípiques de la malaltia, com ara la pèrdua de neurones dopaminèrgiques i l'acumulació de α-sinucleïna en les neurones dopaminèrgiques. En general, els nostres resultats demostren que hem desenvolupat una eina valuosa per a l’estudi dels mecanismes patològics que condueixen a la MP, així com una nova plataforma pel descobriment de nous fàrmacs encaminats a prevenir o evitar la neurodegeneració.

P63 is a transcription factor of the p53 family with key roles in embryonic development, stem cells and cancer. P63-deficient mice fail to form stratified and glandular epithelia, including the prostate, demonstrating a critical function for this protein in prostate development. The P63 gene encodes two different isoform groups, TA and N, which can act as tumor suppressors or oncogenes respectively in different tumors. In the prostate gland, Np63 is the main isoform expressed specifically in basal stem cells. There is evidence that p63+ basal stem cells are the cells-of-origin in prostate cancer. However the mature tumor has a luminal phenotype and loss of p63 expression is used as a diagnostic marker for carcinoma. To date, there have been few studies investigating the role of p63 in prostate stem cells and cancer. First, we confirmed the expression of Np63 in basal prostate stem cells of wild type mice. Surprisingly we also detected Np63 in a subpopulation of cells with cancer stem cell characteristics in the PC3 human prostate metastatic cell line, which is derived from metastasis to the bone. We then performed in vitro and in vivo gain and loss of function studies in non-transformed and bone metastatic human prostate cells. We identified a role for Np63 in stem cell proliferation and self-renewal. Interestingly we discovered a new function for this isoform in favoring bone metastatic colonization through the regulation of cell adhesion and signaling to the surrounding microenvironment. Our results uncover Np63 as a critical new mediator of prostate stem cells maintenance and prostate cancer metastatic colonization to the bone.
P63 es un factor de transcripción de la familia de p53 con un papel clave en el desarrollo embrionario, células madre y cáncer. Ratones deficientes para P63 presentan un defecto en la formación de epitelios estratificados y glandulares, incluyendo la próstata, lo que establece una función crítica para p63 en el desarrollo de la próstata. El gen de P63 codifica para dos grupos de isoformas diferentes, TA y ΔN, que pueden actuar como supresores de tumores u oncogenes, respectivamente, en diferentes tipos tumorales. En la próstata, ΔNp63α es la isoforma principal expresada específicamente en las células madre basales. Hay pruebas de que las células madre basales p63+ son las células de origen del cáncer de próstata. Sin embargo, el carcinoma tiene un fenotipo luminal y la pérdida de expresión de p63 se utiliza como un marcador de diagnóstico. Hasta aquí no existen muchos estudios que investiguen el papel de p63 en las células madre y en el cáncer de próstata. En primer lugar, confirmamos la expresión de ΔNp63α en las células madre basales de próstata de ratones wild type. Sorprendentemente también detectamos ΔNp63α en una subpoblación de células con características de células madre de cáncer en la línea celular metastásica de próstata humana PC3, que deriva de metástasis en el hueso. A continuación realizamos estudios de sobre-expresión y pérdida de expresión in vitro e in vivo en células de próstata humana no transformadas y en células de metástasis al hueso. Identificamos así un papel de ΔNp63α en la proliferación y en el mantenimiento de las células madre. Sorprendentemente descubrimos una nueva función para esta isoforma en favorecer la colonización metastásica al hueso a través de la regulación de la adhesión celular y la señalización extracelular. Nuestros resultados establecen ΔNp63α como un nuevo mediador crítico para el mantenimiento de las células madre de la próstata y la colonización metastásica del cáncer de próstata al hueso.

ABSTRACT Background and Objective: Stem cells offer an interesting tool for tissue engineering, but the clinical applications are limited by donor site morbidity and low cell number upon harvest. Recent studies have identified an abundant source of stem cells in subcutaneous adipose tissue. These adipose stem cells (ASC), are able to differentiate to several lineages and express multiple growth factors, which makes them suitable for clinical application. Buccal fat pad (BFP), an adipose encapsulated mass in the oral cavity, could represent an easy access source for dentists and oral surgeons. Biosynthetic substitutes such as β-tricalcium phosphate (β-TCP), hydroxyapatite (HA), and mixtures of HA/β-TCP (biphasic calcium phosphate; BCP) have been successfully used as bone graft biomaterials. Growth factors stimulating osteogenic differentiation are also interesting for bone tissue engineering applications. We aimed to investigate whether BFP is a rich source of ASC, and whether ASC triggered for only 15 min with bone morphogenetic protein-2 (BMP-2), and seeded onto different calcium phosphate scaffolds composed of β-TCP alone or mixtures of HA/β-TCP, could stimulate bone formation. Materials & Methods: ASC obtained from subcutaneous abdominal adipose tissue and BFP were counted and analyzed by flow cytometry, to determine ASC cell number, phenotype and percentage. At two weeks of culture, the multipotent differentiation potential of ASC from BFP was analyzed. Furthermore, fresh ASC either or not stimulated with 10ng/ml BMP-2 for 15min were seeded on different calcium phosphate scaffolds. ASC attachment, proliferation and osteogenic differentiation was analyzed and compared. Results: BFP contained ~30% of ASC. The ASC number obtained per gram of adipose tissue from BFP at one week of culture was 2-fold higher than in subcutaneous abdominal adipose tissue. Angiogenic marker expression was also higher, and ASC showed multipotent differentiation potential as well. Fifteen min BMP-2 treatment increased ASC cell proliferation and osteogenic differentiation on BCP composed of 60% HA and 40% β-TCP, but not on other scaffolds containing less percentage of HA. Conclusions: Buccal fat pad is a rich alternative source of ASC suitable for bone tissue engineering. Short stimulation of only 15 minutes with BMP-2 is enough to stimulate ASC proliferation and osteogenic differentiation. Therefore ASC could be treated shortly with BMP-2 and seeded on BCP with 60% HA to improve bone regeneration.